NOAEL Studies
Emollient
Tea Tree Oil (Melaleuca Alternifolia Leaf Oil) NOAEL Studies
INCI: MELALEUCA ALTERNIFOLIA LEAF OIL
CAS: 68647-73-4
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
NTP_ICE_skin_sensitization 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_skin_sensitization | Incidence of positive responses | 0 | % | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Maximization Test | sheet=Data_invivo; excel_row=9586; Record_ID=skin_sensitization_invivo_2126; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID60100611; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=0; Response_Unit=%; Species=Human; Route=Dermal; Reference=Epstein 1981: report to RIFM|Anonymous 1988; Not available; 10.1016/0278-6915(88)90204-9; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID60100611 |
| NTP_ICE_skin_sensitization | Induction dose per skin area | 675 | ug/cm2 | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Maximization Test | sheet=Data_invivo; excel_row=9584; Record_ID=skin_sensitization_invivo_2126; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID60100611; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=675; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Epstein 1981: report to RIFM|Anonymous 1988; Not available; 10.1016/0278-6915(88)90204-9; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID60100611 |
| NTP_ICE_skin_sensitization | Relative reliability score | 3 | unitless | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Maximization Test | sheet=Data_invivo; excel_row=9588; Record_ID=skin_sensitization_invivo_2126; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID60100611; Assay=Human Maximization Test; Endpoint=Relative reliability score; Response=3; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=Epstein 1981: report to RIFM|Anonymous 1988; Not available; 10.1016/0278-6915(88)90204-9; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID60100611 |
SCCS_vision_codex 152 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 28-days | repeated dose toxicity | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided. In the dossier the repeated dose toxicity studies of some constituents of Tea Tree Oil were discussed. For the constituents with a maximum content of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_001"} |
| SCCS_vision_codex | NOAEL | =15 | % | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"t of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_002"} |
| SCCS_vision_codex | NOAEL | =300 | mg/kg bw/day | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the al","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"verage constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a minimum lethal dose of 60 mg/kg bw/day for children applying a safety factor of 300 (Council of Europe, 2000). Ref.: 85","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_003"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 86 p-Cymene (max","dose":"13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats.","effect":"SCCP/1155/08 Opinion on tea tree oil 29 a-Terpinene (max. 13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats. No maternal toxicity was observed at 60 mg/kg bw/day, and a NOAEL of 60 mg/kg bw/day for systemic effects following repeated exposure to α-terpinene is suggested. Ref.: 86 p-Cymene (max. 8 %) Cumene is a chemical similar to cymene: cumene is only lacking the methyl-group residing in the para-position on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dos","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_004"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"citation":"Ref.: 87 α-Terpineol (max","dose":"A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene.","effect":"on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene. A LOAEL of 769 mg/kg bw/day based on kidney effects in a study with oral exposure was identified. Based on the oral study and using an uncertainty factor of 10, a NOAEL for cumene/p-cymene of 75 mg/kg bw/day was suggested. p-Cymene Cumene Ref.: 87 α-Terpineol (max. 8%) 10 male and 10 female weanling Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_005"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"dose":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm.","effect":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and female animals in the high dose and control groups. No statistically significant adverse effects were reported. Based on this study a NOAEL of 500 mg/kg bw/day for α-terpineol can be suggested. α-Pinene (max. 6 %) α-and β-pinene are bicyclic terpene hydrocarbons and the major components of turpentine. With the structurally related bicyclic terpene hydrocarbon camphene a 28-day repeat dose study has been performed according to OECD Guideline 407 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_006"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days.","effect":"7 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | % | rat | - | 28-day | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels.","effect":"increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_009"} |
| SCCS_vision_codex | NOAEL | =40 | % | - | - | - | NOAEL study | {"dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","effect":"-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal t","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_011"} |
| SCCS_vision_codex | NOAEL | =4.5 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 5","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_015"} |
| SCCS_vision_codex | NOAEL | =6 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_016"} |
| SCCS_vision_codex | NOAEL | =100 | % | - | - | - | NOAEL study | {"dose":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% B","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_020"} |
| SCCS_vision_codex | NOAEL | =510 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_021"} |
| SCCS_vision_codex | NOAEL | =49.5 | % | - | - | - | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","effect":"ea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects woul","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_022"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/day | - | oral | 28 days | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day.","effect":"remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_026"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy.","effect":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxico","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_028"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/day | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights.","effect":"e also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_029"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/d | human | oral | 10 years | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day.","effect":"g/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil containing products. It was shown that both essential oils exert oestrogen-like activity in vitro by inducing growth in MCF-7 cells. Ref.:","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_031"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/d | mouse | - | - | repeated dose toxicity | {"dose":"General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"e bacterial reverse mutation assay using S. typhimurium tester strain TA102 with and without S9-mix. In a mouse micronucleus test Tea Tree Oil was considered to be non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalitie","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_032"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/d | - | - | - | repeated dose toxicity | {"dose":"Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_034"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg | - | - | - | reproductive toxicity | {"dose":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_036"} |
| SCCS_vision_codex | NOAEL | =3 | - | - | - | - | NOAEL study | {"effect":"Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_039"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"dose":"Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","effect":"Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_041"} |
| SCCS_vision_codex | NOAEL | =400 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Terpinen-4-ol | 48 | 400","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_042"} |
| SCCS_vision_codex | NOAEL | =300 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: 1,8-Cineole (eucalyptol) | 15 | 300","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_043"} |
| SCCS_vision_codex | NOAEL | =60 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpinene | 13 | 60","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_044"} |
| SCCS_vision_codex | NOAEL | =500 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpineol | 8 | 500","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_046"} |
| SCCS_vision_codex | NOAEL | =250 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Pinene | 6 | 250","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_047"} |
| SCCS_vision_codex | NOAEL | =10000 | μg/cm2 | human | - | 442D | sensitisation | {"effect":"SCCS-rejected applicant NOAEL: ers all available data. A WoE NESIL is an exposure to a skin sensitizer which should not result in the induction of sensitization in humans. TTO is negative in the KeratinoSens assay according to OECD TG 442D. There are two clearly negative GMPT available and four positive LLNA. Data from 2 HRIPT and 1 HMT are available which gave negative results in tested volunteers. The EC3 values from the 4 studies with TTO ranged from 4.4% (1100 μg/cm2) to 25.5% (6375 μg/cm2). No sensitisation was induced in the HRIPT, with a NOEL of 10000 μg/cm2. The NOEL from the HMT conducted with petrolatum was 675 µg/cm2. However, the composition of TTO was not reported in the HRIPT and HMT studies and adjuvant tests like GPMT cannot be used as primary data sources for defining NESILs (SCCS/1666/24). RAC indicates that Human data confirm that TTO induces skin sensitisation but with an incidence not very high and the concentrations that induced","page":47,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_001"} |
| SCCS_vision_codex | NOAEL | =45 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Reference: ECHA disseminated Dossier EC 285-377-1","dose":"5/sex/dose Test substance:","effect":"ontrol. Study Design: Guidelines/Methods: OECD TG407 Report year: 2017 Species/strain: rat/Sprague-Dawley (m/f) Exposure route:oral gavage Vehicle: corn oil Group size: 5/sex/dose Test substance: Tea Tree Oil (Essential oil obtained from the leaves and terminal branchlets of Melaleuca alternifolia, by steam distillation) Concentrations: 0, 5, 15, 45 mg/kg bw/day Exposure duration: 28 days GLP: Yes Reference: ECHA disseminated Dossier EC 285-377-1. No test-item related toxicological effects have been reported. The NOAEL was determined to be 45 mg/kg bw/day for male and female rats. Based on the new available data it can be concluded that TTO, where the composition meets ISO Standard 4730-2004, induced no local or systemic effects up to 45 mg/kg bw/day after repeated oral exposure. Further data on repeated dose toxicity are available in the Combined Draft Renewal Assessment Report prepared according to Regulation (EC) No 1107/2009: In an OECD TG 407 (non-GLP) study Wistar rats were administered TTO by oral gavage with 0, 62.5, 125","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_003"} |
| SCCS_vision_codex | NOAEL | =62.5 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group).","effect":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group). Control animals received the vehicle groundnut oil. The test item TTO which was used followed ISO 4730:2004 specifications. In the highest dose group decreased weights of testes and epididymides, degenerative changes in both organs and aspermia were observed. Liver and adrenal were increased in the highest dose. At 125 mg/kg bw/day degenerative changes in tested and epididymides and oligospermia were observed. Liver weight was increased also in the mid dose. The NOEL from this study was 62.5 mg/kg bw/day. Minimal/mild liver vacuolation was reported starting from the lowest dose of 62.5 mg/kg bw/day.","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_004"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 8 weeks | NOAEL study | {"dose":"Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day.","effect":"and GLP was performed in male and female Wistar rats (report year 2011). Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day. Control animals received the vehicle groundnut oil. The test item TTO was in compliance with ISO 4730:2004 specifications. Effects on sperm were reported for mid and high dose. At the high dose histopathological changes were found in testes and epididymides. Further effects noted were spleen vacuolation (minimal degree) and tubular dilation in kidneys (minimal degree). The NOAEL for males is 30 mg/kg bw/day and for females 60 mg/kg bw/day. In another study according to OECD TG 408 and GLP Wistar rats (males and females) were dosed by gavage with 0 or 60 mg/kg bw/day (report year 2016). The test item TTO was in compliance with ISO 4730:2004 specifications. At 60 mg/kg bw/day effects on sperm were reported and degeneration and atrophy of seminiferous tubules were noted. All effects recovered after 8 weeks without dosing. A NOAEL could not be derived. The LOAEL was 60 mg/kg bw/d. In a furthe","page":54,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_005"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | - | 28 days | repeated dose toxicity | {"dose":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group.","effect":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group. In the F1 generation, the number of pregnancies was still affected, but not as much at the highest (lowered compared to F0- generation) dose of 38 mg/kg bw/d (100, 96, 96, 87 % respectively). At the highest dose, cauda sperm counts (number of sperms per cauda epididymis and number of sperms per gram of cauda epididymis) were lower. However, mean number of corpora lutea, number of implantations and mean litter size were not different from control.” The NOAEL for reproductive toxicity is considered to be 25 mg/kg bw/day. In the available 28 days and 90 days repeated dose toxicity studies (see section above for further details), similar effects are reported at testes organ weight and spermatogenesis supporting the effects noted in the 2-generation study. A detailed discussion on the effects observed on sperm and tested/epididymis is presented in the section 3.9 below. Conclusion from Applicant: The reproductive toxicity of TTO has been assessed in a study according to","page":55,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_009"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/d | rat | - | Developmental | reproductive toxicity | {"dose":"However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier.","effect":"of sperms per gram of cauda epididymis) were lower and the number of pregnancies was affected. However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier. Excluding this outlier from the statistical analysis, and keeping in view the historic control values, the SCCS considers that a NOAEL of 25 mg/kg bw/d could be derived for fertility and reproductive toxicity from this study. 3.5.5.2 Developmental Toxicity In the previous SCCP Opinion for TTO (SCCP/1155/08), no data on developmental toxicity were provided for TTO. A new study according to OECD TG 414 performed under GLP conditions is available from the REACH Dossier for Melaleuca alternifolia, ext. (EC 285-377-1/CAS 85085-48-9) The full report for this study is attached in Appendix 9 [Study Report OECD TG 414, rats, STUDY CODE: 09/016-105P, 08","page":56,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_010"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only).","effect":"scapula, humerus or femur. All formulations proved to be homogeneous, as similar results were obtained at analysis of the top/middle/bottom samples, and the measured concentrations were found to be in the acceptable range of 100±10% (94 to 108%) of the nominal concentrations. No peak was detected in the control samples at the retention time of (+/-) Terpinen-4-ol. Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only). The NOAEL for maternal toxicity was 20 mg/kg bw/day. Reductions in fetal body weight were seen in the mid and high dose groups. Increases in external and skeletal malformations were also seen in fetuses from the high dose group. All effects were secondary to maternal toxicity. The NOAEL for fetuses for TTO for developmental toxicity (secondary to severe maternal toxicity) was 20 mg/kg bw/day. The NOAEL of 20 mg/kg/day for maternal toxicity was used as Point of Departure for MoS calculations because it was the lowest NOAEL f","page":59,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_011"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations.","effect":"SCCS/1681/25 Finaly version Scientific Opinion on Tea Tree Oil (CAS/EC No. 68647-73-4 /285-377-1) ___________________________________________________________________________________________ ___________________________________________________________________________________________ 71 were secondary to maternal toxicity. Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations. SCCS overall assessment on fertility, reproduction and developmental toxicity SCCS, while agreeing with the Applicant regarding the kinetic differences depending on the different exposure routes (gavage and diet), believes that no clear species differences emerge since following repeated administration for 90 days in the rat study (OECD TG 408) and in the dog study (OECD TG 409), the viability an","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_026"} |
| SCCS_vision_codex | NOAEL | =0.117 | mg/kg bw/day | rat | oral | - | NOAEL study | {"dose":"As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD.","effect":"2th revision, 2023). As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_030"} |
| SCCS_vision_codex | NOAEL | =70 | % | rat | oral | - | NOAEL study | {"dose":"Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day.","effect":"D. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_032"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 28-days | repeated dose toxicity | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided. In the dossier the repeated dose toxicity studies of some constituents of Tea Tree Oil were discussed. For the constituents with a maximum content of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_001"} |
| SCCS_vision_codex | NOAEL | =15 | % | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"t of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_002"} |
| SCCS_vision_codex | NOAEL | =300 | mg/kg bw/day | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the al","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"verage constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a minimum lethal dose of 60 mg/kg bw/day for children applying a safety factor of 300 (Council of Europe, 2000). Ref.: 85","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_003"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 86 p-Cymene (max","dose":"13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats.","effect":"SCCP/1155/08 Opinion on tea tree oil 29 a-Terpinene (max. 13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats. No maternal toxicity was observed at 60 mg/kg bw/day, and a NOAEL of 60 mg/kg bw/day for systemic effects following repeated exposure to α-terpinene is suggested. Ref.: 86 p-Cymene (max. 8 %) Cumene is a chemical similar to cymene: cumene is only lacking the methyl-group residing in the para-position on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dos","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_004"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"citation":"Ref.: 87 α-Terpineol (max","dose":"A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene.","effect":"on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene. A LOAEL of 769 mg/kg bw/day based on kidney effects in a study with oral exposure was identified. Based on the oral study and using an uncertainty factor of 10, a NOAEL for cumene/p-cymene of 75 mg/kg bw/day was suggested. p-Cymene Cumene Ref.: 87 α-Terpineol (max. 8%) 10 male and 10 female weanling Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_005"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"dose":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm.","effect":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and female animals in the high dose and control groups. No statistically significant adverse effects were reported. Based on this study a NOAEL of 500 mg/kg bw/day for α-terpineol can be suggested. α-Pinene (max. 6 %) α-and β-pinene are bicyclic terpene hydrocarbons and the major components of turpentine. With the structurally related bicyclic terpene hydrocarbon camphene a 28-day repeat dose study has been performed according to OECD Guideline 407 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_006"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days.","effect":"7 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | % | rat | - | 28-day | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels.","effect":"increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_009"} |
| SCCS_vision_codex | NOAEL | =40 | % | - | - | - | NOAEL study | {"dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","effect":"-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal t","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_011"} |
| SCCS_vision_codex | NOAEL | =4.5 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 5","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_015"} |
| SCCS_vision_codex | NOAEL | =6 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_016"} |
| SCCS_vision_codex | NOAEL | =100 | % | - | - | - | NOAEL study | {"dose":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% B","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_020"} |
| SCCS_vision_codex | NOAEL | =510 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_021"} |
| SCCS_vision_codex | NOAEL | =49.5 | % | - | - | - | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","effect":"ea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects woul","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_022"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/day | - | oral | 28 days | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day.","effect":"remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_026"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy.","effect":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxico","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_028"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/day | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights.","effect":"e also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_029"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/d | human | oral | 10 years | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day.","effect":"g/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil containing products. It was shown that both essential oils exert oestrogen-like activity in vitro by inducing growth in MCF-7 cells. Ref.:","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_031"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/d | mouse | - | - | repeated dose toxicity | {"dose":"General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"e bacterial reverse mutation assay using S. typhimurium tester strain TA102 with and without S9-mix. In a mouse micronucleus test Tea Tree Oil was considered to be non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalitie","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_032"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/d | - | - | - | repeated dose toxicity | {"dose":"Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_034"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg | - | - | - | reproductive toxicity | {"dose":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_036"} |
| SCCS_vision_codex | NOAEL | =3 | - | - | - | - | NOAEL study | {"effect":"Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_039"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"dose":"Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","effect":"Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_041"} |
| SCCS_vision_codex | NOAEL | =400 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Terpinen-4-ol | 48 | 400","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_042"} |
| SCCS_vision_codex | NOAEL | =300 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: 1,8-Cineole (eucalyptol) | 15 | 300","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_043"} |
| SCCS_vision_codex | NOAEL | =60 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpinene | 13 | 60","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_044"} |
| SCCS_vision_codex | NOAEL | =500 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpineol | 8 | 500","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_046"} |
| SCCS_vision_codex | NOAEL | =250 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Pinene | 6 | 250","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_047"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 28-days | repeated dose toxicity | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided. In the dossier the repeated dose toxicity studies of some constituents of Tea Tree Oil were discussed. For the constituents with a maximum content of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_001"} |
| SCCS_vision_codex | NOAEL | =15 | % | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"t of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_002"} |
| SCCS_vision_codex | NOAEL | =300 | mg/kg bw/day | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the al","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"verage constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a minimum lethal dose of 60 mg/kg bw/day for children applying a safety factor of 300 (Council of Europe, 2000). Ref.: 85","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_003"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 86 p-Cymene (max","dose":"13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats.","effect":"SCCP/1155/08 Opinion on tea tree oil 29 a-Terpinene (max. 13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats. No maternal toxicity was observed at 60 mg/kg bw/day, and a NOAEL of 60 mg/kg bw/day for systemic effects following repeated exposure to α-terpinene is suggested. Ref.: 86 p-Cymene (max. 8 %) Cumene is a chemical similar to cymene: cumene is only lacking the methyl-group residing in the para-position on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dos","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_004"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"citation":"Ref.: 87 α-Terpineol (max","dose":"A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene.","effect":"on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene. A LOAEL of 769 mg/kg bw/day based on kidney effects in a study with oral exposure was identified. Based on the oral study and using an uncertainty factor of 10, a NOAEL for cumene/p-cymene of 75 mg/kg bw/day was suggested. p-Cymene Cumene Ref.: 87 α-Terpineol (max. 8%) 10 male and 10 female weanling Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_005"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"dose":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm.","effect":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and female animals in the high dose and control groups. No statistically significant adverse effects were reported. Based on this study a NOAEL of 500 mg/kg bw/day for α-terpineol can be suggested. α-Pinene (max. 6 %) α-and β-pinene are bicyclic terpene hydrocarbons and the major components of turpentine. With the structurally related bicyclic terpene hydrocarbon camphene a 28-day repeat dose study has been performed according to OECD Guideline 407 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_006"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days.","effect":"7 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | % | rat | - | 28-day | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels.","effect":"increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_009"} |
| SCCS_vision_codex | NOAEL | =40 | % | - | - | - | NOAEL study | {"dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","effect":"-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal t","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_011"} |
| SCCS_vision_codex | NOAEL | =4.5 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 5","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_015"} |
| SCCS_vision_codex | NOAEL | =6 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_016"} |
| SCCS_vision_codex | NOAEL | =100 | % | - | - | - | NOAEL study | {"dose":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% B","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_020"} |
| SCCS_vision_codex | NOAEL | =510 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_021"} |
| SCCS_vision_codex | NOAEL | =49.5 | % | - | - | - | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","effect":"ea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects woul","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_022"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/day | - | oral | 28 days | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day.","effect":"remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_026"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy.","effect":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxico","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_028"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/day | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights.","effect":"e also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_029"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/d | human | oral | 10 years | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day.","effect":"g/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil containing products. It was shown that both essential oils exert oestrogen-like activity in vitro by inducing growth in MCF-7 cells. Ref.:","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_031"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/d | mouse | - | - | repeated dose toxicity | {"dose":"General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"e bacterial reverse mutation assay using S. typhimurium tester strain TA102 with and without S9-mix. In a mouse micronucleus test Tea Tree Oil was considered to be non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalitie","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_032"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/d | - | - | - | repeated dose toxicity | {"dose":"Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_034"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg | - | - | - | reproductive toxicity | {"dose":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_036"} |
| SCCS_vision_codex | NOAEL | =3 | - | - | - | - | NOAEL study | {"effect":"Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_039"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"dose":"Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","effect":"Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_041"} |
| SCCS_vision_codex | NOAEL | =400 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Terpinen-4-ol | 48 | 400","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_042"} |
| SCCS_vision_codex | NOAEL | =300 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: 1,8-Cineole (eucalyptol) | 15 | 300","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_043"} |
| SCCS_vision_codex | NOAEL | =60 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpinene | 13 | 60","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_044"} |
| SCCS_vision_codex | NOAEL | =500 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpineol | 8 | 500","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_046"} |
| SCCS_vision_codex | NOAEL | =250 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Pinene | 6 | 250","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_047"} |
| SCCS_vision_codex | NOAEL | =10000 | μg/cm2 | human | - | 442D | sensitisation | {"effect":"SCCS-rejected applicant NOAEL: ers all available data. A WoE NESIL is an exposure to a skin sensitizer which should not result in the induction of sensitization in humans. TTO is negative in the KeratinoSens assay according to OECD TG 442D. There are two clearly negative GMPT available and four positive LLNA. Data from 2 HRIPT and 1 HMT are available which gave negative results in tested volunteers. The EC3 values from the 4 studies with TTO ranged from 4.4% (1100 μg/cm2) to 25.5% (6375 μg/cm2). No sensitisation was induced in the HRIPT, with a NOEL of 10000 μg/cm2. The NOEL from the HMT conducted with petrolatum was 675 µg/cm2. However, the composition of TTO was not reported in the HRIPT and HMT studies and adjuvant tests like GPMT cannot be used as primary data sources for defining NESILs (SCCS/1666/24). RAC indicates that Human data confirm that TTO induces skin sensitisation but with an incidence not very high and the concentrations that induced","page":47,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_001"} |
| SCCS_vision_codex | NOAEL | =45 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Reference: ECHA disseminated Dossier EC 285-377-1","dose":"5/sex/dose Test substance:","effect":"ontrol. Study Design: Guidelines/Methods: OECD TG407 Report year: 2017 Species/strain: rat/Sprague-Dawley (m/f) Exposure route:oral gavage Vehicle: corn oil Group size: 5/sex/dose Test substance: Tea Tree Oil (Essential oil obtained from the leaves and terminal branchlets of Melaleuca alternifolia, by steam distillation) Concentrations: 0, 5, 15, 45 mg/kg bw/day Exposure duration: 28 days GLP: Yes Reference: ECHA disseminated Dossier EC 285-377-1. No test-item related toxicological effects have been reported. The NOAEL was determined to be 45 mg/kg bw/day for male and female rats. Based on the new available data it can be concluded that TTO, where the composition meets ISO Standard 4730-2004, induced no local or systemic effects up to 45 mg/kg bw/day after repeated oral exposure. Further data on repeated dose toxicity are available in the Combined Draft Renewal Assessment Report prepared according to Regulation (EC) No 1107/2009: In an OECD TG 407 (non-GLP) study Wistar rats were administered TTO by oral gavage with 0, 62.5, 125","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_003"} |
| SCCS_vision_codex | NOAEL | =62.5 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group).","effect":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group). Control animals received the vehicle groundnut oil. The test item TTO which was used followed ISO 4730:2004 specifications. In the highest dose group decreased weights of testes and epididymides, degenerative changes in both organs and aspermia were observed. Liver and adrenal were increased in the highest dose. At 125 mg/kg bw/day degenerative changes in tested and epididymides and oligospermia were observed. Liver weight was increased also in the mid dose. The NOEL from this study was 62.5 mg/kg bw/day. Minimal/mild liver vacuolation was reported starting from the lowest dose of 62.5 mg/kg bw/day.","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_004"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 8 weeks | NOAEL study | {"dose":"Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day.","effect":"and GLP was performed in male and female Wistar rats (report year 2011). Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day. Control animals received the vehicle groundnut oil. The test item TTO was in compliance with ISO 4730:2004 specifications. Effects on sperm were reported for mid and high dose. At the high dose histopathological changes were found in testes and epididymides. Further effects noted were spleen vacuolation (minimal degree) and tubular dilation in kidneys (minimal degree). The NOAEL for males is 30 mg/kg bw/day and for females 60 mg/kg bw/day. In another study according to OECD TG 408 and GLP Wistar rats (males and females) were dosed by gavage with 0 or 60 mg/kg bw/day (report year 2016). The test item TTO was in compliance with ISO 4730:2004 specifications. At 60 mg/kg bw/day effects on sperm were reported and degeneration and atrophy of seminiferous tubules were noted. All effects recovered after 8 weeks without dosing. A NOAEL could not be derived. The LOAEL was 60 mg/kg bw/d. In a furthe","page":54,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_005"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | - | 28 days | repeated dose toxicity | {"dose":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group.","effect":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group. In the F1 generation, the number of pregnancies was still affected, but not as much at the highest (lowered compared to F0- generation) dose of 38 mg/kg bw/d (100, 96, 96, 87 % respectively). At the highest dose, cauda sperm counts (number of sperms per cauda epididymis and number of sperms per gram of cauda epididymis) were lower. However, mean number of corpora lutea, number of implantations and mean litter size were not different from control.” The NOAEL for reproductive toxicity is considered to be 25 mg/kg bw/day. In the available 28 days and 90 days repeated dose toxicity studies (see section above for further details), similar effects are reported at testes organ weight and spermatogenesis supporting the effects noted in the 2-generation study. A detailed discussion on the effects observed on sperm and tested/epididymis is presented in the section 3.9 below. Conclusion from Applicant: The reproductive toxicity of TTO has been assessed in a study according to","page":55,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_009"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/d | rat | - | Developmental | reproductive toxicity | {"dose":"However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier.","effect":"of sperms per gram of cauda epididymis) were lower and the number of pregnancies was affected. However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier. Excluding this outlier from the statistical analysis, and keeping in view the historic control values, the SCCS considers that a NOAEL of 25 mg/kg bw/d could be derived for fertility and reproductive toxicity from this study. 3.5.5.2 Developmental Toxicity In the previous SCCP Opinion for TTO (SCCP/1155/08), no data on developmental toxicity were provided for TTO. A new study according to OECD TG 414 performed under GLP conditions is available from the REACH Dossier for Melaleuca alternifolia, ext. (EC 285-377-1/CAS 85085-48-9) The full report for this study is attached in Appendix 9 [Study Report OECD TG 414, rats, STUDY CODE: 09/016-105P, 08","page":56,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_010"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only).","effect":"scapula, humerus or femur. All formulations proved to be homogeneous, as similar results were obtained at analysis of the top/middle/bottom samples, and the measured concentrations were found to be in the acceptable range of 100±10% (94 to 108%) of the nominal concentrations. No peak was detected in the control samples at the retention time of (+/-) Terpinen-4-ol. Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only). The NOAEL for maternal toxicity was 20 mg/kg bw/day. Reductions in fetal body weight were seen in the mid and high dose groups. Increases in external and skeletal malformations were also seen in fetuses from the high dose group. All effects were secondary to maternal toxicity. The NOAEL for fetuses for TTO for developmental toxicity (secondary to severe maternal toxicity) was 20 mg/kg bw/day. The NOAEL of 20 mg/kg/day for maternal toxicity was used as Point of Departure for MoS calculations because it was the lowest NOAEL f","page":59,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_011"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations.","effect":"SCCS/1681/25 Finaly version Scientific Opinion on Tea Tree Oil (CAS/EC No. 68647-73-4 /285-377-1) ___________________________________________________________________________________________ ___________________________________________________________________________________________ 71 were secondary to maternal toxicity. Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations. SCCS overall assessment on fertility, reproduction and developmental toxicity SCCS, while agreeing with the Applicant regarding the kinetic differences depending on the different exposure routes (gavage and diet), believes that no clear species differences emerge since following repeated administration for 90 days in the rat study (OECD TG 408) and in the dog study (OECD TG 409), the viability an","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_026"} |
| SCCS_vision_codex | NOAEL | =0.117 | mg/kg bw/day | rat | oral | - | NOAEL study | {"dose":"As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD.","effect":"2th revision, 2023). As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_030"} |
| SCCS_vision_codex | NOAEL | =70 | % | rat | oral | - | NOAEL study | {"dose":"Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day.","effect":"D. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_032"} |
| SCCS_vision_codex | NOAEL | =10000 | μg/cm2 | human | - | 442D | sensitisation | {"effect":"SCCS-rejected applicant NOAEL: ers all available data. A WoE NESIL is an exposure to a skin sensitizer which should not result in the induction of sensitization in humans. TTO is negative in the KeratinoSens assay according to OECD TG 442D. There are two clearly negative GMPT available and four positive LLNA. Data from 2 HRIPT and 1 HMT are available which gave negative results in tested volunteers. The EC3 values from the 4 studies with TTO ranged from 4.4% (1100 μg/cm2) to 25.5% (6375 μg/cm2). No sensitisation was induced in the HRIPT, with a NOEL of 10000 μg/cm2. The NOEL from the HMT conducted with petrolatum was 675 µg/cm2. However, the composition of TTO was not reported in the HRIPT and HMT studies and adjuvant tests like GPMT cannot be used as primary data sources for defining NESILs (SCCS/1666/24). RAC indicates that Human data confirm that TTO induces skin sensitisation but with an incidence not very high and the concentrations that induced","page":47,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_001"} |
| SCCS_vision_codex | NOAEL | =45 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Reference: ECHA disseminated Dossier EC 285-377-1","dose":"5/sex/dose Test substance:","effect":"ontrol. Study Design: Guidelines/Methods: OECD TG407 Report year: 2017 Species/strain: rat/Sprague-Dawley (m/f) Exposure route:oral gavage Vehicle: corn oil Group size: 5/sex/dose Test substance: Tea Tree Oil (Essential oil obtained from the leaves and terminal branchlets of Melaleuca alternifolia, by steam distillation) Concentrations: 0, 5, 15, 45 mg/kg bw/day Exposure duration: 28 days GLP: Yes Reference: ECHA disseminated Dossier EC 285-377-1. No test-item related toxicological effects have been reported. The NOAEL was determined to be 45 mg/kg bw/day for male and female rats. Based on the new available data it can be concluded that TTO, where the composition meets ISO Standard 4730-2004, induced no local or systemic effects up to 45 mg/kg bw/day after repeated oral exposure. Further data on repeated dose toxicity are available in the Combined Draft Renewal Assessment Report prepared according to Regulation (EC) No 1107/2009: In an OECD TG 407 (non-GLP) study Wistar rats were administered TTO by oral gavage with 0, 62.5, 125","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_003"} |
| SCCS_vision_codex | NOAEL | =62.5 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group).","effect":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group). Control animals received the vehicle groundnut oil. The test item TTO which was used followed ISO 4730:2004 specifications. In the highest dose group decreased weights of testes and epididymides, degenerative changes in both organs and aspermia were observed. Liver and adrenal were increased in the highest dose. At 125 mg/kg bw/day degenerative changes in tested and epididymides and oligospermia were observed. Liver weight was increased also in the mid dose. The NOEL from this study was 62.5 mg/kg bw/day. Minimal/mild liver vacuolation was reported starting from the lowest dose of 62.5 mg/kg bw/day.","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_004"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 8 weeks | NOAEL study | {"dose":"Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day.","effect":"and GLP was performed in male and female Wistar rats (report year 2011). Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day. Control animals received the vehicle groundnut oil. The test item TTO was in compliance with ISO 4730:2004 specifications. Effects on sperm were reported for mid and high dose. At the high dose histopathological changes were found in testes and epididymides. Further effects noted were spleen vacuolation (minimal degree) and tubular dilation in kidneys (minimal degree). The NOAEL for males is 30 mg/kg bw/day and for females 60 mg/kg bw/day. In another study according to OECD TG 408 and GLP Wistar rats (males and females) were dosed by gavage with 0 or 60 mg/kg bw/day (report year 2016). The test item TTO was in compliance with ISO 4730:2004 specifications. At 60 mg/kg bw/day effects on sperm were reported and degeneration and atrophy of seminiferous tubules were noted. All effects recovered after 8 weeks without dosing. A NOAEL could not be derived. The LOAEL was 60 mg/kg bw/d. In a furthe","page":54,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_005"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | - | 28 days | repeated dose toxicity | {"dose":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group.","effect":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group. In the F1 generation, the number of pregnancies was still affected, but not as much at the highest (lowered compared to F0- generation) dose of 38 mg/kg bw/d (100, 96, 96, 87 % respectively). At the highest dose, cauda sperm counts (number of sperms per cauda epididymis and number of sperms per gram of cauda epididymis) were lower. However, mean number of corpora lutea, number of implantations and mean litter size were not different from control.” The NOAEL for reproductive toxicity is considered to be 25 mg/kg bw/day. In the available 28 days and 90 days repeated dose toxicity studies (see section above for further details), similar effects are reported at testes organ weight and spermatogenesis supporting the effects noted in the 2-generation study. A detailed discussion on the effects observed on sperm and tested/epididymis is presented in the section 3.9 below. Conclusion from Applicant: The reproductive toxicity of TTO has been assessed in a study according to","page":55,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_009"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/d | rat | - | Developmental | reproductive toxicity | {"dose":"However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier.","effect":"of sperms per gram of cauda epididymis) were lower and the number of pregnancies was affected. However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier. Excluding this outlier from the statistical analysis, and keeping in view the historic control values, the SCCS considers that a NOAEL of 25 mg/kg bw/d could be derived for fertility and reproductive toxicity from this study. 3.5.5.2 Developmental Toxicity In the previous SCCP Opinion for TTO (SCCP/1155/08), no data on developmental toxicity were provided for TTO. A new study according to OECD TG 414 performed under GLP conditions is available from the REACH Dossier for Melaleuca alternifolia, ext. (EC 285-377-1/CAS 85085-48-9) The full report for this study is attached in Appendix 9 [Study Report OECD TG 414, rats, STUDY CODE: 09/016-105P, 08","page":56,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_010"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only).","effect":"scapula, humerus or femur. All formulations proved to be homogeneous, as similar results were obtained at analysis of the top/middle/bottom samples, and the measured concentrations were found to be in the acceptable range of 100±10% (94 to 108%) of the nominal concentrations. No peak was detected in the control samples at the retention time of (+/-) Terpinen-4-ol. Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only). The NOAEL for maternal toxicity was 20 mg/kg bw/day. Reductions in fetal body weight were seen in the mid and high dose groups. Increases in external and skeletal malformations were also seen in fetuses from the high dose group. All effects were secondary to maternal toxicity. The NOAEL for fetuses for TTO for developmental toxicity (secondary to severe maternal toxicity) was 20 mg/kg bw/day. The NOAEL of 20 mg/kg/day for maternal toxicity was used as Point of Departure for MoS calculations because it was the lowest NOAEL f","page":59,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_011"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations.","effect":"SCCS/1681/25 Finaly version Scientific Opinion on Tea Tree Oil (CAS/EC No. 68647-73-4 /285-377-1) ___________________________________________________________________________________________ ___________________________________________________________________________________________ 71 were secondary to maternal toxicity. Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations. SCCS overall assessment on fertility, reproduction and developmental toxicity SCCS, while agreeing with the Applicant regarding the kinetic differences depending on the different exposure routes (gavage and diet), believes that no clear species differences emerge since following repeated administration for 90 days in the rat study (OECD TG 408) and in the dog study (OECD TG 409), the viability an","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_026"} |
| SCCS_vision_codex | NOAEL | =0.117 | mg/kg bw/day | rat | oral | - | NOAEL study | {"dose":"As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD.","effect":"2th revision, 2023). As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_030"} |
| SCCS_vision_codex | NOAEL | =70 | % | rat | oral | - | NOAEL study | {"dose":"Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day.","effect":"D. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_032"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 28-days | repeated dose toxicity | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided. In the dossier the repeated dose toxicity studies of some constituents of Tea Tree Oil were discussed. For the constituents with a maximum content of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_001"} |
| SCCS_vision_codex | NOAEL | =15 | % | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 35 Terpinen-4-ol (max","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"t of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_002"} |
| SCCS_vision_codex | NOAEL | =300 | mg/kg bw/day | rat | oral | 28-days | NOAEL study | {"citation":"Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the al","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","effect":"verage constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a minimum lethal dose of 60 mg/kg bw/day for children applying a safety factor of 300 (Council of Europe, 2000). Ref.: 85","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_003"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 86 p-Cymene (max","dose":"13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats.","effect":"SCCP/1155/08 Opinion on tea tree oil 29 a-Terpinene (max. 13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats. No maternal toxicity was observed at 60 mg/kg bw/day, and a NOAEL of 60 mg/kg bw/day for systemic effects following repeated exposure to α-terpinene is suggested. Ref.: 86 p-Cymene (max. 8 %) Cumene is a chemical similar to cymene: cumene is only lacking the methyl-group residing in the para-position on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dos","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_004"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"citation":"Ref.: 87 α-Terpineol (max","dose":"A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene.","effect":"on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene. A LOAEL of 769 mg/kg bw/day based on kidney effects in a study with oral exposure was identified. Based on the oral study and using an uncertainty factor of 10, a NOAEL for cumene/p-cymene of 75 mg/kg bw/day was suggested. p-Cymene Cumene Ref.: 87 α-Terpineol (max. 8%) 10 male and 10 female weanling Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_005"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw/day | rat | oral | 20 weeks | NOAEL study | {"dose":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm.","effect":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and female animals in the high dose and control groups. No statistically significant adverse effects were reported. Based on this study a NOAEL of 500 mg/kg bw/day for α-terpineol can be suggested. α-Pinene (max. 6 %) α-and β-pinene are bicyclic terpene hydrocarbons and the major components of turpentine. With the structurally related bicyclic terpene hydrocarbon camphene a 28-day repeat dose study has been performed according to OECD Guideline 407 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_006"} |
| SCCS_vision_codex | NOAEL | =250 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days.","effect":"7 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | % | rat | - | 28-day | repeated dose toxicity | {"citation":"Ref.: 88 Terpinolene (max","dose":"Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels.","effect":"increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","page":29,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_009"} |
| SCCS_vision_codex | NOAEL | =40 | % | - | - | - | NOAEL study | {"dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","effect":"-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal t","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_011"} |
| SCCS_vision_codex | NOAEL | =4.5 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 5","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_015"} |
| SCCS_vision_codex | NOAEL | =6 | % | - | - | - | NOAEL study | {"dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_016"} |
| SCCS_vision_codex | NOAEL | =100 | % | - | - | - | NOAEL study | {"dose":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% B","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_020"} |
| SCCS_vision_codex | NOAEL | =510 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","effect":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_021"} |
| SCCS_vision_codex | NOAEL | =49.5 | % | - | - | - | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","effect":"ea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects woul","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_022"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/day | - | oral | 28 days | repeated dose toxicity | {"dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day.","effect":"remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_026"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy.","effect":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxico","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_028"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/day | rat | oral | - | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights.","effect":"e also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_029"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/d | human | oral | 10 years | reproductive toxicity | {"citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day.","effect":"g/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil containing products. It was shown that both essential oils exert oestrogen-like activity in vitro by inducing growth in MCF-7 cells. Ref.:","page":33,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_031"} |
| SCCS_vision_codex | NOAEL | =117 | mg/kg bw/d | mouse | - | - | repeated dose toxicity | {"dose":"General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","effect":"e bacterial reverse mutation assay using S. typhimurium tester strain TA102 with and without S9-mix. In a mouse micronucleus test Tea Tree Oil was considered to be non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalitie","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_032"} |
| SCCS_vision_codex | NOAEL | =60 | mg/kg bw/d | - | - | - | repeated dose toxicity | {"dose":"Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_034"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg | - | - | - | reproductive toxicity | {"dose":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","effect":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.","page":35,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_036"} |
| SCCS_vision_codex | NOAEL | =3 | - | - | - | - | NOAEL study | {"effect":"Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg","page":28,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_039"} |
| SCCS_vision_codex | NOAEL | =30 | - | - | - | - | NOAEL study | {"dose":"Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","effect":"Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_041"} |
| SCCS_vision_codex | NOAEL | =400 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: Terpinen-4-ol | 48 | 400","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_042"} |
| SCCS_vision_codex | NOAEL | =300 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: 1,8-Cineole (eucalyptol) | 15 | 300","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_043"} |
| SCCS_vision_codex | NOAEL | =60 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpinene | 13 | 60","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_044"} |
| SCCS_vision_codex | NOAEL | =500 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Terpineol | 8 | 500","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_046"} |
| SCCS_vision_codex | NOAEL | =250 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 30: α-Pinene | 6 | 250","page":30,"pdf":"sccp_o_160.pdf","row_type":"noael_study","study_id":"sccp_o_160_noael_047"} |
| SCCS_vision_codex | NOAEL | =10000 | μg/cm2 | human | - | 442D | sensitisation | {"effect":"SCCS-rejected applicant NOAEL: ers all available data. A WoE NESIL is an exposure to a skin sensitizer which should not result in the induction of sensitization in humans. TTO is negative in the KeratinoSens assay according to OECD TG 442D. There are two clearly negative GMPT available and four positive LLNA. Data from 2 HRIPT and 1 HMT are available which gave negative results in tested volunteers. The EC3 values from the 4 studies with TTO ranged from 4.4% (1100 μg/cm2) to 25.5% (6375 μg/cm2). No sensitisation was induced in the HRIPT, with a NOEL of 10000 μg/cm2. The NOEL from the HMT conducted with petrolatum was 675 µg/cm2. However, the composition of TTO was not reported in the HRIPT and HMT studies and adjuvant tests like GPMT cannot be used as primary data sources for defining NESILs (SCCS/1666/24). RAC indicates that Human data confirm that TTO induces skin sensitisation but with an incidence not very high and the concentrations that induced","page":47,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_001"} |
| SCCS_vision_codex | NOAEL | =45 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | {"citation":"Reference: ECHA disseminated Dossier EC 285-377-1","dose":"5/sex/dose Test substance:","effect":"ontrol. Study Design: Guidelines/Methods: OECD TG407 Report year: 2017 Species/strain: rat/Sprague-Dawley (m/f) Exposure route:oral gavage Vehicle: corn oil Group size: 5/sex/dose Test substance: Tea Tree Oil (Essential oil obtained from the leaves and terminal branchlets of Melaleuca alternifolia, by steam distillation) Concentrations: 0, 5, 15, 45 mg/kg bw/day Exposure duration: 28 days GLP: Yes Reference: ECHA disseminated Dossier EC 285-377-1. No test-item related toxicological effects have been reported. The NOAEL was determined to be 45 mg/kg bw/day for male and female rats. Based on the new available data it can be concluded that TTO, where the composition meets ISO Standard 4730-2004, induced no local or systemic effects up to 45 mg/kg bw/day after repeated oral exposure. Further data on repeated dose toxicity are available in the Combined Draft Renewal Assessment Report prepared according to Regulation (EC) No 1107/2009: In an OECD TG 407 (non-GLP) study Wistar rats were administered TTO by oral gavage with 0, 62.5, 125","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_003"} |
| SCCS_vision_codex | NOAEL | =62.5 | mg/kg bw/day | - | - | - | NOAEL study | {"dose":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group).","effect":"62.5, 125 and 250 mg/kg bw/day (n=6 m/f per group). Control animals received the vehicle groundnut oil. The test item TTO which was used followed ISO 4730:2004 specifications. In the highest dose group decreased weights of testes and epididymides, degenerative changes in both organs and aspermia were observed. Liver and adrenal were increased in the highest dose. At 125 mg/kg bw/day degenerative changes in tested and epididymides and oligospermia were observed. Liver weight was increased also in the mid dose. The NOEL from this study was 62.5 mg/kg bw/day. Minimal/mild liver vacuolation was reported starting from the lowest dose of 62.5 mg/kg bw/day.","page":53,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_004"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 8 weeks | NOAEL study | {"dose":"Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day.","effect":"and GLP was performed in male and female Wistar rats (report year 2011). Animals were dosed by oral gavage with 0, 30, 60, or 120 mg/kg bw/day. Control animals received the vehicle groundnut oil. The test item TTO was in compliance with ISO 4730:2004 specifications. Effects on sperm were reported for mid and high dose. At the high dose histopathological changes were found in testes and epididymides. Further effects noted were spleen vacuolation (minimal degree) and tubular dilation in kidneys (minimal degree). The NOAEL for males is 30 mg/kg bw/day and for females 60 mg/kg bw/day. In another study according to OECD TG 408 and GLP Wistar rats (males and females) were dosed by gavage with 0 or 60 mg/kg bw/day (report year 2016). The test item TTO was in compliance with ISO 4730:2004 specifications. At 60 mg/kg bw/day effects on sperm were reported and degeneration and atrophy of seminiferous tubules were noted. All effects recovered after 8 weeks without dosing. A NOAEL could not be derived. The LOAEL was 60 mg/kg bw/d. In a furthe","page":54,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_005"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | - | 28 days | repeated dose toxicity | {"dose":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group.","effect":"8.7,9.0 and 7.0 in the control, 10, 25 and 50 mg/kg bw/d group. In the F1 generation, the number of pregnancies was still affected, but not as much at the highest (lowered compared to F0- generation) dose of 38 mg/kg bw/d (100, 96, 96, 87 % respectively). At the highest dose, cauda sperm counts (number of sperms per cauda epididymis and number of sperms per gram of cauda epididymis) were lower. However, mean number of corpora lutea, number of implantations and mean litter size were not different from control.” The NOAEL for reproductive toxicity is considered to be 25 mg/kg bw/day. In the available 28 days and 90 days repeated dose toxicity studies (see section above for further details), similar effects are reported at testes organ weight and spermatogenesis supporting the effects noted in the 2-generation study. A detailed discussion on the effects observed on sperm and tested/epididymis is presented in the section 3.9 below. Conclusion from Applicant: The reproductive toxicity of TTO has been assessed in a study according to","page":55,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_009"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/d | rat | - | Developmental | reproductive toxicity | {"dose":"However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier.","effect":"of sperms per gram of cauda epididymis) were lower and the number of pregnancies was affected. However, the effect at 25 mg/kg bw/d on the number of sperms per cauda epididymis (x106) and number of sperms per gram of cauda epididymis (x106) is due to one rat (1831), whose value is 100 times lower than the average of the other 24 rats in the same group and is therefore clearly an outlier. Excluding this outlier from the statistical analysis, and keeping in view the historic control values, the SCCS considers that a NOAEL of 25 mg/kg bw/d could be derived for fertility and reproductive toxicity from this study. 3.5.5.2 Developmental Toxicity In the previous SCCP Opinion for TTO (SCCP/1155/08), no data on developmental toxicity were provided for TTO. A new study according to OECD TG 414 performed under GLP conditions is available from the REACH Dossier for Melaleuca alternifolia, ext. (EC 285-377-1/CAS 85085-48-9) The full report for this study is attached in Appendix 9 [Study Report OECD TG 414, rats, STUDY CODE: 09/016-105P, 08","page":56,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_010"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only).","effect":"scapula, humerus or femur. All formulations proved to be homogeneous, as similar results were obtained at analysis of the top/middle/bottom samples, and the measured concentrations were found to be in the acceptable range of 100±10% (94 to 108%) of the nominal concentrations. No peak was detected in the control samples at the retention time of (+/-) Terpinen-4-ol. Severe maternal toxicity was seen in mid and high dose dams (reduced food consumption and weight loss gains, and mortality in high dose group only). The NOAEL for maternal toxicity was 20 mg/kg bw/day. Reductions in fetal body weight were seen in the mid and high dose groups. Increases in external and skeletal malformations were also seen in fetuses from the high dose group. All effects were secondary to maternal toxicity. The NOAEL for fetuses for TTO for developmental toxicity (secondary to severe maternal toxicity) was 20 mg/kg bw/day. The NOAEL of 20 mg/kg/day for maternal toxicity was used as Point of Departure for MoS calculations because it was the lowest NOAEL f","page":59,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_011"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations.","effect":"SCCS/1681/25 Finaly version Scientific Opinion on Tea Tree Oil (CAS/EC No. 68647-73-4 /285-377-1) ___________________________________________________________________________________________ ___________________________________________________________________________________________ 71 were secondary to maternal toxicity. Using a conservative approach, the NOAEL of 20 mg/kg bw/d for maternal, systemic toxicity from this OECD TG 414 study was used as PoD for all MoS calculations. SCCS overall assessment on fertility, reproduction and developmental toxicity SCCS, while agreeing with the Applicant regarding the kinetic differences depending on the different exposure routes (gavage and diet), believes that no clear species differences emerge since following repeated administration for 90 days in the rat study (OECD TG 408) and in the dog study (OECD TG 409), the viability an","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_026"} |
| SCCS_vision_codex | NOAEL | =0.117 | mg/kg bw/day | rat | oral | - | NOAEL study | {"dose":"As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD.","effect":"2th revision, 2023). As indicated above the NOAEL of 20 mg/kg bw/day, derived from the OECD TG 414 study in rats was used as PoD. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_030"} |
| SCCS_vision_codex | NOAEL | =70 | % | rat | oral | - | NOAEL study | {"dose":"Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day.","effect":"D. Considering an oral bioavailability of 70%, the resulting systemic Point of Departure (PoDsys) is 14 mg/kg bw/day. The MoS for aggregated exposure for adults is 120 based on the SED of 0.117 mg/kg bw/day, which was obtained by aggregating the cosmetic and non-cosmetics exposure values for TTO. MoS calculation (adults) Systemic exposure dose (aggregated SED) sum SED 0.117 mg/kg bw/day No observed adverse effect level (OECD 414, rat) NOAEL 20 mg/kg bw/day Oral absorption (source: REACH dossier) 70% Adjusted NOAEL considering oral absorption of 70% PoDsys 14 mg/kg bw/day Margin of Safety MoS PoDsys/SED 120 Applicant’s Overall Conclusions Based on the safety profile of TTO and the MoS calculations presented here, it is concluded that TTO as an ingredient at 2% in shampoo, 1% in shower gel, 0.1% in face cream and 1%","page":71,"pdf":"sccs_o_303.pdf","row_type":"noael_study","study_id":"sccs_o_303_noael_032"} |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 47 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 15 | % | rat | oral | 28-days | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=15; DOSE=Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.; EFFECT=t of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a; CITATION=Ref.: 35 Terpinen-4-ol (max; CITATION_NUMBERS=[35,4]; REFERENCE=Ref.: 35 Terpinen-4-ol (max; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 35 Terpinen-4-ol (max","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","duration":"28-days","effect":"t of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"15","page":28,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 300 | mg/kg bw/day | rat | oral | 28-days | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=300; DOSE=Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.; EFFECT=verage constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a minimum lethal dose of 60 mg/kg bw/day for children applying a safety factor of 300 (Council of Europe, 2000). Ref.: 85; CITATION=Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the al; CITATION_NUMBERS=[84]; REFERENCE=Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the al; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the al","dose":"Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max.","duration":"28-days","effect":"verage constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol was evaluated as component of natural sources of flavourings by the Committee of Experts on Flavouring Substances of the Council of Europe (CEFS), resulting in the allocation of a provisional TDI of 0.2 mg/kg bw. This TDI was derived from a minimum lethal dose of 60 mg/kg bw/day for children applying a safety factor of 300 (Council of Europe, 2000). Ref.: 85","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":28,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 60 | mg/kg bw/day | rat | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=60; DOSE=13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats.; EFFECT=SCCP/1155/08 Opinion on tea tree oil 29 a-Terpinene (max. 13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats. No maternal toxicity was observed at 60 mg/kg bw/day, and a NOAEL of 60 mg/kg bw/day for systemic effects following repeated exposure to α-terpinene is suggested. Ref.: 86 p-Cymene (max. 8 %) Cumene is a chemical similar to cymene: cumene is only lacking the methyl-group residing in the para-position on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dos; CITATION=Ref.: 86 p-Cymene (max; CITATION_NUMBERS=[86]; REFERENCE=Ref.: 86 p-Cymene (max; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 86 p-Cymene (max","dose":"13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats.","duration":"","effect":"SCCP/1155/08 Opinion on tea tree oil 29 a-Terpinene (max. 13%) Exposure to α-terpinene (125 or 250 mg/kg bw) for nine consecutive days caused decreased body weight gain in pregnant Wistar rats. No maternal toxicity was observed at 60 mg/kg bw/day, and a NOAEL of 60 mg/kg bw/day for systemic effects following repeated exposure to α-terpinene is suggested. Ref.: 86 p-Cymene (max. 8 %) Cumene is a chemical similar to cymene: cumene is only lacking the methyl-group residing in the para-position on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dos","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"60","page":29,"route":"","species":"rat","study_id":"sccp_o_160_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 75 | mg/kg bw/day | rat | oral | 20 weeks | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=75; DOSE=A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene.; LOAEL_VALUE=769 mg/kg bw/day; EFFECT=on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene. A LOAEL of 769 mg/kg bw/day based on kidney effects in a study with oral exposure was identified. Based on the oral study and using an uncertainty factor of 10, a NOAEL for cumene/p-cymene of 75 mg/kg bw/day was suggested. p-Cymene Cumene Ref.: 87 α-Terpineol (max. 8%) 10 male and 10 female weanling Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and; CITATION=Ref.: 87 α-Terpineol (max; CITATION_NUMBERS=[87]; REFERENCE=Ref.: 87 α-Terpineol (max; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 87 α-Terpineol (max","dose":"A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene.","duration":"20 weeks","effect":"on p-cymene. Studies on the metabolism of cumene and cymene demonstrate considerable similarities and they are expected to have comparable toxicological profiles. A review on the toxicity of cymene and cumene has been submitted to the US EPA. A limited number of relevant repeat-dose studies are available and the inhalation route is often used for cumene. A LOAEL of 769 mg/kg bw/day based on kidney effects in a study with oral exposure was identified. Based on the oral study and using an uncertainty factor of 10, a NOAEL for cumene/p-cymene of 75 mg/kg bw/day was suggested. p-Cymene Cumene Ref.: 87 α-Terpineol (max. 8%) 10 male and 10 female weanling Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"769 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"75","page":29,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 500 | mg/kg bw/day | rat | oral | 20 weeks | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=500; DOSE=Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm.; EFFECT=Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and female animals in the high dose and control groups. No statistically significant adverse effects were reported. Based on this study a NOAEL of 500 mg/kg bw/day for α-terpineol can be suggested. α-Pinene (max. 6 %) α-and β-pinene are bicyclic terpene hydrocarbons and the major components of turpentine. With the structurally related bicyclic terpene hydrocarbon camphene a 28-day repeat dose study has been performed according to OECD Guideline 407 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm.","duration":"20 weeks","effect":"Osborne-Mendel rats were fed α-terpineol acetate in the diet for 20 weeks at concentrations of 0, 1000, 2500 or 10,000 ppm. These dietary levels were calculated to result in daily intakes of 0, 50, 125 and 500 mg/kg bw/day, respectively. All animals were examined for growth, haematology, and macroscopic changes in the tissues. Microscopic examination was performed on 6 - 8 male and female animals in the high dose and control groups. No statistically significant adverse effects were reported. Based on this study a NOAEL of 500 mg/kg bw/day for α-terpineol can be suggested. α-Pinene (max. 6 %) α-and β-pinene are bicyclic terpene hydrocarbons and the major components of turpentine. With the structurally related bicyclic terpene hydrocarbon camphene a 28-day repeat dose study has been performed according to OECD Guideline 407 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"500","page":29,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 5 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=5; DOSE=Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...; EFFECT=ions were provided regarding the systemic toxicity of some constituents or related compounds. There are 8 major constituents of Tea Tree Oil with a maximum content of 5% and more are: terpinen-4-ol (max. 48%), γ-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","duration":"","effect":"ions were provided regarding the systemic toxicity of some constituents or related compounds. There are 8 major constituents of Tea Tree Oil with a maximum content of 5% and more are: terpinen-4-ol (max. 48%), γ-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"5","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=40; DOSE=Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...; EFFECT=-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","duration":"","effect":"-terpinene (max. 28%), 1,8-cineole (eucalyptol, max. 15%), α-terpinene (max. 13%), p-cymene (max. 8 %), α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal t","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"40","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=40; DOSE=Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...; EFFECT=, α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","duration":"","effect":", α-terpineol (max. 8%), α-pinene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"40","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=40; DOSE=Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...; EFFECT=nene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be cons; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation...","duration":"","effect":"nene (max. 6%) and terpinolene (max. 5%). For these constituents, the following NOAELS were established or estimated: Compound Max. Content in TTO (%) Established or Estimated NOAEL (mg/kg bw/day) Terpinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be cons","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"40","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=40; DOSE=Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=pinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This fo; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"pinen-4-ol 48 400 1,8-Cineole (eucalyptol) 15 300 α-Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This fo","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"40","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 4.5 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=4.5; DOSE=Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 5; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"Terpinene 13 60 Cumene / p-Cymene 8 75 α-Terpineol 8 500 α-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 5","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"4.5","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 6 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=6; DOSE=Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"-Pinene 6 250 Terpinolene 5 no data γ-Terpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"6","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 75 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=75; DOSE=Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=erpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decreas; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"erpinene 28 no data Derivation of a NOAEL for Tea Tree Oil based on systemic toxicity of its constituents The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decreas","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 75 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=75; DOSE=Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"The direct extrapolation from a NOAEL for a constituent to a NOAEL for Tea Tree Oil might be only acceptable when no other constituent is reported to affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=40; DOSE=Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity f; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"affect the same target. Three constituents have been reported to affect the kidneys: terpinen-4-ol (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity f","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"40","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =100 | % | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT== 100; DOSE=l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% B; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"l (content 40%, NOAEL 400 mg/kg bw/day), 1,8-cineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% B","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"= 100","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 510 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=510; DOSE=ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).; EFFECT=ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day).","duration":"","effect":"ineole (content 4.5%, NOAEL 300 mg/kg bw/day) and cumene/p- cymene (content 6%, NOAEL 75 mg/kg bw/day). To estimate a NOAEL for Tea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"510","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 3 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=unclear:Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg; EFFECT=Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"unclear:Table 3: Overview on: conclusions on chroni | c toxicity o | r estimate a | NOAEL. | The d | ermal LD value 50 | above 5 g/kg","page":28,"route":"","species":"","study_id":"sccp_o_160_noael_039"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 3 | - | rat | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=unclear:Table 3: Overview on: 1,8-Cineole (eucalypt | ol) has be | en studied s | ubchroni | cally i | n rats and mice: | a NOAEL of; EFFECT=Table 3: Overview on: 1,8-Cineole (eucalypt | ol) has be | en studied s | ubchroni | cally i | n rats and mice: | a NOAEL of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Table 3: Overview on: 1,8-Cineole (eucalypt | ol) has be | en studied s | ubchroni | cally i | n rats and mice: | a NOAEL of","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"unclear:Table 3: Overview on: 1,8-Cineole (eucalypt | ol) has be | en studied s | ubchroni | cally i | n rats and mice: | a NOAEL of","page":28,"route":"","species":"rat","study_id":"sccp_o_160_noael_040"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 30 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=unclear:Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day); DOSE=Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day); EFFECT=Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","duration":"","effect":"Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 30: Compound | Max. Content in TTO (%) | Established or Estimated NOAEL (mg/kg bw/day)","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_041"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 400 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=400; EFFECT=Unlabeled table on page 30: Terpinen-4-ol | 48 | 400; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 30: Terpinen-4-ol | 48 | 400","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"400","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_042"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 300 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=300; EFFECT=Unlabeled table on page 30: 1,8-Cineole (eucalyptol) | 15 | 300; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 30: 1,8-Cineole (eucalyptol) | 15 | 300","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"300","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_043"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 60 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=60; EFFECT=Unlabeled table on page 30: α-Terpinene | 13 | 60; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 30: α-Terpinene | 13 | 60","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"60","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_044"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 75 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=75; EFFECT=Unlabeled table on page 30: Cumene / p-Cymene | 8 | 75; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 30: Cumene / p-Cymene | 8 | 75","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"75","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_045"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 500 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=500; EFFECT=Unlabeled table on page 30: α-Terpineol | 8 | 500; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 30: α-Terpineol | 8 | 500","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"500","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_046"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 250 | - | - | - | - | - | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=250; EFFECT=Unlabeled table on page 30: α-Pinene | 6 | 250; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 30: α-Pinene | 6 | 250","endpoint":"","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"","noael_value":"250","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_047"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 400 | mg/kg bw/day | rat | oral | 28-days | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=400; DOSE=3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided.; EFFECT=3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided. In the dossier the repeated dose toxicity studies of some constituents of Tea Tree Oil were discussed. For the constituents with a maximum content of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol; CITATION=Ref.: 35 Terpinen-4-ol (max; CITATION_NUMBERS=[35,4]; REFERENCE=Ref.: 35 Terpinen-4-ol (max; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 35 Terpinen-4-ol (max","dose":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","duration":"28-days","effect":"3.3.5 Repeated dose toxicity No repeated dose toxicity study with Tea Tree Oil was provided. In the dossier the repeated dose toxicity studies of some constituents of Tea Tree Oil were discussed. For the constituents with a maximum content of 5% and more they are briefly summarized in the following. The order is according to the maximum content in Tea Tree Oil. Ref.: 35 Terpinen-4-ol (max. 48%) Terpinen-4-ol on average constitutes 40% of Tea Tree Oil. Based on the 28-days study on kidney toxicity in rats, the NOAEL for terpinen-4-ol after oral exposure may be estimated to be 400 mg/kg bw/day. γ-Terpinene (max. 28%) The available literature on systemic effects of γ-terpinene is not sufficient to reach conclusions on chronic toxicity or estimate a NOAEL. The dermal LD50 value above 5 g/kg indicates low toxicity. 1,8-Cineole (eucalyptol, max. 15%) 1,8-Cineole (eucalyptol) has been studied subchronically in rats and mice: a NOAEL of 300 mg/kg bw/day has been established based on hepatic and renal toxicity. Ref.: 84 Eucalyptol","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":28,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 250 | mg/kg bw/day | rat | oral | 28 days | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=250; DOSE=Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days.; EFFECT=7 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.; CITATION=Ref.: 88 Terpinolene (max; CITATION_NUMBERS=[88]; REFERENCE=Ref.: 88 Terpinolene (max; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 88 Terpinolene (max","dose":"Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days.","duration":"28 days","effect":"7 in both sexes of Wistar rats. Groups of animals (5/sex/group) were given daily oral doses of 0, 62.5, 250, or 1000 mg/kg bw by gavage for 28 days. Weekly measurement of body weight and food intake revealed no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":29,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 250 | mg/kg bw/day | rat | - | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=250; DOSE=Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights.; EFFECT=no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.; CITATION=Ref.: 88 Terpinolene (max; CITATION_NUMBERS=[88]; REFERENCE=Ref.: 88 Terpinolene (max; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 88 Terpinolene (max","dose":"Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights.","duration":"28-day","effect":"no significant differences between test and control animals. Animals of both sexes at the 1000 mg/kg bw/day dose exhibited vacuolization of hepatocytes and increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":29,"route":"","species":"rat","study_id":"sccp_o_160_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 5 | % | rat | - | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=5; DOSE=Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels.; EFFECT=increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.; CITATION=Ref.: 88 Terpinolene (max; CITATION_NUMBERS=[88]; REFERENCE=Ref.: 88 Terpinolene (max; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 88 Terpinolene (max","dose":"Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels.","duration":"28-day","effect":"increase in liver weights. Male rats also exhibited α2u-microglobulin-type nephrotoxicity at all dose levels. The repeat-dose study for camphene provides a NOAEL of 250 mg/kg bw/day. It is expected that α-pinene, if subjected to a 28-day study at similar dose levels would exhibit α2u- microglobulin nephrotoxicity in male rats and would be expected to exhibit a NOAEL of at least 250 mg/kg bw/day. Ref.: 88 Terpinolene (max. 5%) No subchronic, chronic, or foeto-toxicity studies were identified for terpinolene, and a NOAEL for systemic toxicity can not be estimated.","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"5","page":29,"route":"","species":"rat","study_id":"sccp_o_160_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 49.5 | % | - | - | - | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=49.5; DOSE=(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.; EFFECT=ea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects woul; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","duration":"","effect":"ea Tree Oil based on the renal toxicity data, information on the estimated constituent-specific NOAEL as well as relative presence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects woul","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"49.5","page":30,"route":"","species":"","study_id":"sccp_o_160_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 49.5 | % | - | oral | 28 days | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=49.5; DOSE=(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.; EFFECT=resence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","duration":"28 days","effect":"resence in Tea Tree Oil needs to be considered. When available data from terpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"49.5","page":30,"route":"oral","species":"","study_id":"sccp_o_160_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 40 | % | - | oral | 28 days | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=40; DOSE=(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.; EFFECT=rpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","duration":"28 days","effect":"rpinen-4-ol, 1,8-cineole, and cumene is used, a NOAEL may be estimated using the formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"40","page":30,"route":"oral","species":"","study_id":"sccp_o_160_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | =100 | % | - | oral | 28 days | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT== 100; DOSE=mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.; EFFECT=mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further.","duration":"28 days","effect":"mg/kg) x NOAEL = 100% This formula gives an estimated NOAEL for Tea Tree Oil of 510 mg/kg bw/day Lack of data on possible renal effects of the remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"%","noael_value":"= 100","page":30,"route":"oral","species":"","study_id":"sccp_o_160_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 117 | mg/kg bw/day | - | oral | 28 days | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=117; DOSE=(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day.; EFFECT=remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"(40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day.","duration":"28 days","effect":"remaining constituents may decrease the NOAEL further. As a possible scenario one could assume that the remaining 49.5% of Tea Tree Oil had a constituent-specific NOAEL equal to cumene. Incorporating this estimate in the calculation of a NOAEL for Tea Tree Oil gives an adjusted additivity formula: (40% / 400 mg/kg + 4.5% / 300 mg/kg + 6% / 75 mg/kg + 49.5% / 75 mg/kg) x NOAEL = 100% Based on the available information on repeated dose toxicity, using these assumptions and following this approach an estimate for a NOAEL for Tea Tree Oil for renal effects would be 117 mg/kg bw/day. 3.3.5.1. Repeated Dose (28 days) oral / dermal / inhalation toxicity No data submitted","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"117","page":30,"route":"oral","species":"","study_id":"sccp_o_160_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 117 | mg/kg bw/d | mouse | - | - | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=117; DOSE=General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.; EFFECT=e bacterial reverse mutation assay using S. typhimurium tester strain TA102 with and without S9-mix. In a mouse micronucleus test Tea Tree Oil was considered to be non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalitie; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","duration":"","effect":"e bacterial reverse mutation assay using S. typhimurium tester strain TA102 with and without S9-mix. In a mouse micronucleus test Tea Tree Oil was considered to be non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalitie","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"117","page":35,"route":"","species":"mouse","study_id":"sccp_o_160_noael_032"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 117 | mg/kg bw/d | - | - | - | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=117; DOSE=General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.; EFFECT=non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"General toxicity No repeated dose toxicity study with Tea Tree Oil was provided.","duration":"","effect":"non-clastogenic under the conditions of the study. No data on carcinogenicity are available. General toxicity No repeated dose toxicity study with Tea Tree Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"117","page":35,"route":"","species":"","study_id":"sccp_o_160_noael_033"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 60 | mg/kg bw/d | - | - | - | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=60; DOSE=Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.; EFFECT=Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","duration":"","effect":"Oil was provided. However, for some of the constituents of Tea Tree Oil and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":35,"route":"","species":"","study_id":"sccp_o_160_noael_034"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 60 | mg/kg bw/d | - | - | - | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=60; DOSE=Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.; EFFECT=il and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","duration":"","effect":"il and related compounds a range of toxic effects has been reported after repeated exposure to them and could be used to estimate NOAEL values. Based on the available information on renal effects in the repeated dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of","endpoint":"repeated dose toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":35,"route":"","species":"","study_id":"sccp_o_160_noael_035"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 60 | mg/kg bw/day | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=60; DOSE=250 and 365 mg/kg bw/d.; EFFECT=250 and 365 mg/kg bw/d. Ref.: cited in 35 α-Terpinene was given to female Wistar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d; CITATION=Ref.: cited in 35 α-Terpinene was given to female Wistar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy; CITATION_NUMBERS=[35,30,60,125,250,15]; REFERENCE=Ref.: cited in 35 α-Terpinene was given to female Wistar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: cited in 35 α-Terpinene was given to female Wistar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy","dose":"250 and 365 mg/kg bw/d.","duration":"","effect":"250 and 365 mg/kg bw/d. Ref.: cited in 35 α-Terpinene was given to female Wistar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"60","page":33,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_027"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 30 | mg/kg | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=30; DOSE=ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy.; EFFECT=ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxico; CITATION=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; CITATION_NUMBERS=[86]; REFERENCE=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy.","duration":"","effect":"ar rats at 30, 60, 125 and 250 mg/kg bw on days six to 15 of pregnancy. The two highest doses were maternally toxic, and the highest dose also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxico","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg","noael_value":"30","page":33,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 333 | mg/kg bw/day | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=333; DOSE=Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights.; EFFECT=e also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations; CITATION=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; CITATION_NUMBERS=[86]; REFERENCE=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights.","duration":"","effect":"e also caused a reduction in the proportion of pregnant females. Foetuses from rats given 250 mg/kg bw/day had reduced body weights and increased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"333","page":33,"route":"oral","species":"rat","study_id":"sccp_o_160_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 333 | mg/kg bw/day | human | oral | 10 years | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=333; DOSE=Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more.; EFFECT=reased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil cont; CITATION=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; CITATION_NUMBERS=[86]; REFERENCE=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more.","duration":"10 years","effect":"reased kidney weights. Abnormal ossification of bones and minor skeletal abnormalities were evident in foetuses from females given 60 mg/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil cont","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"333","page":33,"route":"oral","species":"human","study_id":"sccp_o_160_noael_030"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 30 | mg/kg bw/d | human | oral | 10 years | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=30; DOSE=Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day.; EFFECT=g/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil containing products. It was shown that both essential oils exert oestrogen-like activity in vitro by inducing growth in MCF-7 cells. Ref.:; CITATION=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; CITATION_NUMBERS=[86]; REFERENCE=Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed; DETAILS_JSON={"cas_number":"68647-73-4","citation":"Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed","dose":"Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day.","duration":"10 years","effect":"g/kg bw/day or more. Thus the NOAEL for embryo-foetotoxicity was set at 30 mg/kg body weight (oral route).The NOAEL of maternal toxicity was 60 mg/kg bw/day. It was argued that α-terpinene is typically present at 9% in tea tree oil and that this NOEL would equate to 333 mg/kg bw/day of Tea Tree Oil. Ref.: 86 Comment of the SCCP It is obvious that from the data available a definite NOAEL for reproductive toxicity cannot be assessed. However, from the data from other terpenoids it can be deduced that the use of the NOAEL of α-terpinene (30 mg/kg bw/d) as a representative of Tea Tree Oil is a conservative approach. 3.3.9. Toxicokinetics No data provided. 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data / 3.3.12. Special investigations Gynecomastia in 3 prepubertal boys (4, 7, and 10 years old) was reported and related to the topical use of lavender and/or Tea Tree Oil containing products. It was shown that both essential oils exert oestrogen-like activity in vitro by inducing growth in MCF-7 cells. Ref.:","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"30","page":33,"route":"oral","species":"human","study_id":"sccp_o_160_noael_031"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 333 | mg/kg | - | - | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=333; DOSE=dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.; EFFECT=dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d.","duration":"","effect":"dose toxicity studies an estimate based on assumed additivity would result in an NOAEL for Tea Tree Oil of 117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg","noael_value":"333","page":35,"route":"","species":"","study_id":"sccp_o_160_noael_036"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 333 | mg/kg | - | - | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=333; DOSE=In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d.; EFFECT=117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d.","duration":"","effect":"117 mg/kg bw/d. No reproductive toxicity study with Tea Tree Oil was provided. In a reproductive toxicity study of α-terpinene the NOAEL of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg","noael_value":"333","page":35,"route":"","species":"","study_id":"sccp_o_160_noael_037"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 30 | mg/kg bw/d | - | - | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_160; REPORT_TITLE=OPINION ON Tea tree oil; OPINION_NUMBER=SCCP/1155/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=30; DOSE=of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d.; EFFECT=of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"68647-73-4","citation":"","dose":"of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d.","duration":"","effect":"of maternal toxicity of α-terpinene was 60 mg/kg bw/d while the NOAEL of embryo-/foetotoxicity was 30 mg/kg bw/d. The latter is based on abnormal ossification of bones and minor skeletal abnormalities. Given the presence of 9% α-terpinene in Tea Tree Oil, this would equal a NOAEL for Tea Tree Oil of 333 mg/kg according to the applicant. However, from the data available a definite NOAEL for reproductive toxicity of Tea Tree Oil cannot be assessed. From data of other terpenoids it can be deduced that the use of the NOAEL for reproductive toxicity of α-terpinene as a representative of Tea Tree Oil (30 mg/kg bw/d) would be a conservative approach.","endpoint":"reproductive toxicity","ingredient":"Tea Tree Oil","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"30","page":35,"route":"","species":"","study_id":"sccp_o_160_noael_038"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | VIF565UC2G | UNII | - | - | - | structurallyDiverse | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"structurallyDiverse","unii_code":"VIF565UC2G"} |
| openFDA substances | FDA UNII substance identifier | VIF565UC2G | UNII | - | - | - | structurallyDiverse | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"structurallyDiverse","unii_code":"VIF565UC2G"} |
| openFDA substances | FDA UNII substance identifier | VIF565UC2G | UNII | - | - | - | structurallyDiverse | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"structurallyDiverse","unii_code":"VIF565UC2G"} |
| openFDA substances | FDA UNII substance identifier | VIF565UC2G | UNII | - | - | - | structurallyDiverse | {"approval_status":null,"molecular_formula":null,"source_table":"substance_identifiers_fda","substance_class":"structurallyDiverse","unii_code":"VIF565UC2G"} |