NOAEL Studies Cosmetic Ingredient

P-AMINOPHENOL NOAEL Studies

CAS: 123-30-8

Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.

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COSMOS_DB 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB LOAEL 133 mg/kg bw/day rat oral 6 month Subchronic REACH; Food Chem. Toxicol. Vol. 27, No. 10, pp. 691-698.
COSMOS_DB LOAEL 30 mg/kg bw/day rat oral 90 day Subchronic REACH; study report
COSMOS_DB NOAEL 47 mg/kg bw/day rat oral 6 month Subchronic REACH; Food Chem. Toxicol. Vol. 27, No. 10, pp. 691-698.
COSMOS_DB NOAEL 10 mg/kg bw/day rat oral 90 day Subchronic REACH; study report
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =3.2 mg/kg bw/day Rat - 730 days chronic/long term toxicity EFSA - 2018 - OutputID 3028 - haematology - hemopoietic - Peer review of the pesticide risk assessment of the active substance desmedipham - doi:10.2903/j.efsa.2018.5150
EFSA_OpenFoodTox_EFSA_ReferencePoints.xlsx NOAEL =5.2 mg/kg bw/day Rat oral: unspecified 90 days subchronic EFSA - 2018 - OutputID 3028 - haematology - hemopoietic - Peer review of the pesticide risk assessment of the active substance desmedipham - doi:10.2903/j.efsa.2018.5150
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI =0.016 mg/kg bw/day Consumers - - ADI EFSA - 2018 - OutputID 3028 - Consumers - Peer review of the pesticide risk assessment of the active substance desmedipham - doi:10.2903/j.efsa.2018.5150
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ADI =0.016 mg/kg bw/day Consumers - - ADI EFSA - 2018 - OutputID 3028 - Consumers - Peer review of the pesticide risk assessment of the active substance desmedipham - doi:10.2903/j.efsa.2018.5150
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ARfD =0.05 mg/kg bw/day Consumers - - ARfD EFSA - 2018 - OutputID 3028 - Consumers - Peer review of the pesticide risk assessment of the active substance desmedipham - doi:10.2903/j.efsa.2018.5150
EFSA_OpenFoodTox_EFSA_ReferenceValues.xlsx ARfD =0.05 mg/kg bw/day Consumers - - ARfD EFSA - 2018 - OutputID 3028 - Consumers - Peer review of the pesticide risk assessment of the active substance desmedipham - doi:10.2903/j.efsa.2018.5150
NTP_ICE_acute_inhalation 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_inhalation LC50 >0.005 mg/L - Inhalation Duration=1 hr In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity sheet=Data; excel_row=2035; Record_ID=acute_inhalation_3058; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID3024499; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response_Modifier=>; Response=0.005; Response_Unit=mg/L; Reference=ChemIDplus; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3024499; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID3024499
SCCS_vision_codex 36 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =24 - human - - NOAEL study {"citation":"Ref.: Col","dose":"98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose;","effect":"e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff","page":31,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_001"}
SCCS_vision_codex NOAEL =10 mg/kg rat oral subchronic repeated dose toxicity {"dose":"An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"also refers to references from previous submissions I, II and III. Regarding the possible recent classification of PAP within CMR categories in class 3 it was necessary to repeat older studies or to perform entirely new ones; these were reported in submissions IV and V and especially laid down in an appendix, covering references Col. 69-96. PAP showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses;","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_002"}
SCCS_vision_codex NOAEL =25 mg/kg rat oral 90 day genotoxicity {"dose":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses; the respective NOAEL is 25 mg/kg/bw/day. p-Aminophenol is genotoxic in vitro and in vivo. It induces clastogenic effects under standard test conditions. These effects occur at high dose in the presence of toxic effects. The biological significance of these effects and their relevance for exposed humans has to be discussed. There is evidence that p-aminophenol is metabolized in the skin to acetaminophen (Paracetamol). Paracetamol has also been shown to be clastogenic in vitro and in vivo in standard genotoxicity tests. However, the po","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_003"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rabbit dermal 13 weeks NOAEL study {"citation":"Ref.: Col","dose":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only.","effect":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations i","page":17,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_001"}
SCCS_vision_codex NOAEL =1409 - human - - NOAEL study {"citation":"Ref.: KM4)","dose":"Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_003"}
SCCS_vision_codex NOAEL =3 - rat oral - NOAEL study {"citation":"(Ref. KM9)","dose":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref.","effect":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_004"}
SCCS_vision_codex NOAEL =6.9 µg/cm human dermal - dermal absorption {"dose":"exposed at a dose level close to the NOAEL/LOAEL.","effect":"exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_006"}
SCCS_vision_codex NOAEL =0.067 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human follow","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_007"}
SCCS_vision_codex NOAEL =10 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following ha","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_008"}
SCCS_vision_codex NOAEL =24 - human - - NOAEL study {"citation":"Ref.: Col","dose":"98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose;","effect":"e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff","page":31,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_001"}
SCCS_vision_codex NOAEL =10 mg/kg rat oral subchronic repeated dose toxicity {"dose":"An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"also refers to references from previous submissions I, II and III. Regarding the possible recent classification of PAP within CMR categories in class 3 it was necessary to repeat older studies or to perform entirely new ones; these were reported in submissions IV and V and especially laid down in an appendix, covering references Col. 69-96. PAP showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses;","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_002"}
SCCS_vision_codex NOAEL =25 mg/kg rat oral 90 day genotoxicity {"dose":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses; the respective NOAEL is 25 mg/kg/bw/day. p-Aminophenol is genotoxic in vitro and in vivo. It induces clastogenic effects under standard test conditions. These effects occur at high dose in the presence of toxic effects. The biological significance of these effects and their relevance for exposed humans has to be discussed. There is evidence that p-aminophenol is metabolized in the skin to acetaminophen (Paracetamol). Paracetamol has also been shown to be clastogenic in vitro and in vivo in standard genotoxicity tests. However, the po","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_003"}
SCCS_vision_codex NOAEL =24 - human - - NOAEL study {"citation":"Ref.: Col","dose":"98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose;","effect":"e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff","page":31,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_001"}
SCCS_vision_codex NOAEL =10 mg/kg rat oral subchronic repeated dose toxicity {"dose":"An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"also refers to references from previous submissions I, II and III. Regarding the possible recent classification of PAP within CMR categories in class 3 it was necessary to repeat older studies or to perform entirely new ones; these were reported in submissions IV and V and especially laid down in an appendix, covering references Col. 69-96. PAP showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses;","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_002"}
SCCS_vision_codex NOAEL =25 mg/kg rat oral 90 day genotoxicity {"dose":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses; the respective NOAEL is 25 mg/kg/bw/day. p-Aminophenol is genotoxic in vitro and in vivo. It induces clastogenic effects under standard test conditions. These effects occur at high dose in the presence of toxic effects. The biological significance of these effects and their relevance for exposed humans has to be discussed. There is evidence that p-aminophenol is metabolized in the skin to acetaminophen (Paracetamol). Paracetamol has also been shown to be clastogenic in vitro and in vivo in standard genotoxicity tests. However, the po","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_003"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rabbit dermal 13 weeks NOAEL study {"citation":"Ref.: Col","dose":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only.","effect":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations i","page":17,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_001"}
SCCS_vision_codex NOAEL =1409 - human - - NOAEL study {"citation":"Ref.: KM4)","dose":"Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_003"}
SCCS_vision_codex NOAEL =3 - rat oral - NOAEL study {"citation":"(Ref. KM9)","dose":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref.","effect":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_004"}
SCCS_vision_codex NOAEL =6.9 µg/cm human dermal - dermal absorption {"dose":"exposed at a dose level close to the NOAEL/LOAEL.","effect":"exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_006"}
SCCS_vision_codex NOAEL =0.067 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human follow","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_007"}
SCCS_vision_codex NOAEL =10 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following ha","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_008"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rabbit dermal 13 weeks NOAEL study {"citation":"Ref.: Col","dose":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only.","effect":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations i","page":17,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_001"}
SCCS_vision_codex NOAEL =1409 - human - - NOAEL study {"citation":"Ref.: KM4)","dose":"Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_003"}
SCCS_vision_codex NOAEL =3 - rat oral - NOAEL study {"citation":"(Ref. KM9)","dose":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref.","effect":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_004"}
SCCS_vision_codex NOAEL =6.9 µg/cm human dermal - dermal absorption {"dose":"exposed at a dose level close to the NOAEL/LOAEL.","effect":"exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_006"}
SCCS_vision_codex NOAEL =0.067 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human follow","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_007"}
SCCS_vision_codex NOAEL =10 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following ha","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_008"}
SCCS_vision_codex NOAEL =24 - human - - NOAEL study {"citation":"Ref.: Col","dose":"98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose;","effect":"e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff","page":31,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_001"}
SCCS_vision_codex NOAEL =10 mg/kg rat oral subchronic repeated dose toxicity {"dose":"An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"also refers to references from previous submissions I, II and III. Regarding the possible recent classification of PAP within CMR categories in class 3 it was necessary to repeat older studies or to perform entirely new ones; these were reported in submissions IV and V and especially laid down in an appendix, covering references Col. 69-96. PAP showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses;","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_002"}
SCCS_vision_codex NOAEL =25 mg/kg rat oral 90 day genotoxicity {"dose":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","effect":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses; the respective NOAEL is 25 mg/kg/bw/day. p-Aminophenol is genotoxic in vitro and in vivo. It induces clastogenic effects under standard test conditions. These effects occur at high dose in the presence of toxic effects. The biological significance of these effects and their relevance for exposed humans has to be discussed. There is evidence that p-aminophenol is metabolized in the skin to acetaminophen (Paracetamol). Paracetamol has also been shown to be clastogenic in vitro and in vivo in standard genotoxicity tests. However, the po","page":39,"pdf":"sccp_o_00e.pdf","row_type":"noael_study","study_id":"sccp_o_00e_noael_003"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day rabbit dermal 13 weeks NOAEL study {"citation":"Ref.: Col","dose":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only.","effect":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations i","page":17,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_001"}
SCCS_vision_codex NOAEL =1409 - human - - NOAEL study {"citation":"Ref.: KM4)","dose":"Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_003"}
SCCS_vision_codex NOAEL =3 - rat oral - NOAEL study {"citation":"(Ref. KM9)","dose":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref.","effect":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).","page":47,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_004"}
SCCS_vision_codex NOAEL =6.9 µg/cm human dermal - dermal absorption {"dose":"exposed at a dose level close to the NOAEL/LOAEL.","effect":"exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_006"}
SCCS_vision_codex NOAEL =0.067 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human follow","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_007"}
SCCS_vision_codex NOAEL =10 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","effect":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following ha","page":48,"pdf":"sccs_o_078.pdf","row_type":"noael_study","study_id":"sccs_o_078_noael_008"}
ToxValDB_ECHA_IUCLID 9 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECHA_IUCLID LEL =467 mg/kg bw/day Rat oral subchronic; 13 weeks subchronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead1be4b0a7c65d1c2849; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/6/2?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; STUDY_GROUP=ECHA IUCLID:15835473:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_9f86127d67abff16a24b676e8deab829
ToxValDB_ECHA_IUCLID LEL =667 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa7ee4b0a7c65d1b61ae; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/9/2?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15855362_15856190:F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_c08ba1e5129f7802ca638c5910fe56bd
ToxValDB_ECHA_IUCLID LOAEL =133 mg/kg bw/day Rat oral subchronic; 13 weeks subchronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead1be4b0a7c65d1c2849; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/6/2?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; STUDY_GROUP=ECHA IUCLID:15835472:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_1ef388f455862e3402b8d9eff45f1a57
ToxValDB_ECHA_IUCLID LOEL =30 mg/kg bw/day Rat oral subchronic; 13 weeks subchronic QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead1be4b0a7c65d1c2845; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/6/2?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15832158_15832159:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_379fca27e5ee6549287d10cb9e6b9b1f
ToxValDB_ECHA_IUCLID NOAEL =100 mg/kg bw/day Rat oral - developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabd2e4b0a7c65d1bbeac; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/9/3?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; TOXICOLOGICAL_EFFECT=fetus: fetal/pup body weight changes; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ECHA IUCLID:15820636:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_eafda469e3437ee27b5e6fc4f02f9b30
ToxValDB_ECHA_IUCLID NOAEL =10 mg/kg bw/day Rat oral subchronic; 13 weeks subchronic QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead1be4b0a7c65d1c2845; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/6/2?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15832158_15832159:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_02d63c891a48a90f950476c08c3d1e33
ToxValDB_ECHA_IUCLID NOAEL =20 mg/kg bw/day Rat oral short-term; 28 days short-term QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead1be4b0a7c65d1c284b; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/6/2?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; STUDY_GROUP=ECHA IUCLID:15846162:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_f799ef65e12a4fe523120f582af318c0
ToxValDB_ECHA_IUCLID NOAEL =333 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa7ee4b0a7c65d1b61ae; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/9/2?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; TOXICOLOGICAL_EFFECT=P0: body weight and weight gain; TOXICOLOGICAL_EFFECT_CATEGORY=body weight; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15855362_15856190:F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_5a29408b5f0d11995f57a2a74f2e234d
ToxValDB_ECHA_IUCLID NOEC =30 mg/kg bw/day Rat oral - chronic QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ea9d8e4b0a7c65d1b30a9; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/6216/7/8?documentUUID=f29f0e2c-59c9-4496-b308-258a6ac468f8; YEAR=1997; ORIGINAL_YEAR=1997; STUDY_GROUP=ECHA IUCLID:15817677:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_f9ca255f06e9259a9fe8645963061f63
ToxValDB_EFSA 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_EFSA NOAEL =3.2 mg/kg bw/day Rat oral chronic; 2 years chronic LONG_REF=EFSA (2018). Peer review of the pesticide risk assessment of the active substance desmedipham. doi:10.2903/j.efsa.2018.5150.; TITLE=Peer review of the pesticide risk assessment of the active substance desmedipham; AUTHOR=EFSA; DOI=doi:10.2903/j.efsa.2018.5150; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65201d30e4b0f0a60ddd1165; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://zenodo.org/record/5076033#.Y9fEoXbMI2z; YEAR=2018; ORIGINAL_YEAR=2018; TOXICOLOGICAL_EFFECT=hematological; TOXICOLOGICAL_EFFECT_CATEGORY=hematology; STUDY_GROUP=EFSA:15625317:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d287fb5fcc1cd4c8ad5ca5fdd2f22372
ToxValDB_EFSA NOAEL =5.2 mg/kg bw/day Rat oral subchronic; 90 days subchronic LONG_REF=EFSA (2018). Peer review of the pesticide risk assessment of the active substance desmedipham. doi:10.2903/j.efsa.2018.5150.; TITLE=Peer review of the pesticide risk assessment of the active substance desmedipham; AUTHOR=EFSA; DOI=doi:10.2903/j.efsa.2018.5150; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65201d30e4b0f0a60ddd1165; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://zenodo.org/record/5076033#.Y9fEoXbMI2z; YEAR=2018; ORIGINAL_YEAR=2018; TOXICOLOGICAL_EFFECT=hematological; TOXICOLOGICAL_EFFECT_CATEGORY=hematology; STUDY_GROUP=EFSA:15625318:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_523fe79c0a3611e2be0482cac15064bb
ToxValDB_GESTIS_DNEL 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL systemic =2.1 mg/m3 Human inhalation - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL:15629767:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_f5e9a5e748d1ebfd1add381b4b1c068f
ToxValDB_PPRTV_(CPHEA) 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_PPRTV_(CPHEA) NOAEL =50 mg/kg bw/day Rat oral subchronic; 13 weeks subchronic LONG_REF=Burnett el al 1989; AUTHOR=Burnett el al; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/640754fce4b08a6b3934bd0a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/pprtv/basic-information-about-provisional-peer-reviewed-toxicity-values-pprtvs; SUBSOURCE_URL=https://cfpub.epa.gov/ncea/pprtv/chemicalLanding.cfm?pprtv_sub_id=1567; TOXICOLOGICAL_EFFECT=tubular necrosis, increased levels of enzymes indicative of renal failure, measures of impaired renal function; TOXICOLOGICAL_EFFECT_CATEGORY=multiple; STUDY_GROUP=PPRTV (CPHEA):15654005:M/F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_0fddf03c9b259d923e1b041337c4b2e6
ToxValDB_PPRTV_(CPHEA) RfD (provisional) =0.02 mg/kg bw/day Human oral - Toxicity Value LONG_REF=Burnett el al 1989; AUTHOR=Burnett el al; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/640754fce4b08a6b3934bd0a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/pprtv/basic-information-about-provisional-peer-reviewed-toxicity-values-pprtvs; SUBSOURCE_URL=https://cfpub.epa.gov/ncea/pprtv/chemicalLanding.cfm?pprtv_sub_id=1567; TOXICOLOGICAL_EFFECT=Tubular necrosis, increased levels of enzymes indicative of renal failure, measures of impaired renal function in male/female rats; STUDY_GROUP=PPRTV (CPHEA)_dup_PPRTV Summary_15653504_15653664:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_a224ff6c7be5515616e16f191d9635a7
ToxValDB_PPRTV_(CPHEA) RfD (provisional) =0.2 mg/kg bw/day Human oral - Toxicity Value LONG_REF=Burnett el al 1989; AUTHOR=Burnett el al; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/640754fce4b08a6b3934bd0a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/pprtv/basic-information-about-provisional-peer-reviewed-toxicity-values-pprtvs; SUBSOURCE_URL=https://cfpub.epa.gov/ncea/pprtv/chemicalLanding.cfm?pprtv_sub_id=1567; TOXICOLOGICAL_EFFECT=Tubular necrosis, increased levels of enzymes indicative of renal failure, measures of impaired renal function in male/female rats; STUDY_GROUP=PPRTV (CPHEA)_dup_PPRTV Summary_15653504_15653664:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_c595d9b945ad997b27dbd5611bc524f3
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 13 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 24 - human - - - SOURCE_SUBDIR=sccp_o_00e; REPORT_TITLE=Opinion on para-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCP/0867/05; COMMITTEE=SCCP; REPORT_DATE=15 March 2005; VALUE_TEXT=unclear:e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff; DOSE=98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose;; EFFECT=e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff; CITATION=Ref.: Col; CITATION_NUMBERS=[]; REFERENCE=Ref.: Col; DETAILS_JSON={"cas_number":"123-30-8","citation":"Ref.: Col","dose":"98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose;","duration":"","effect":"e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff","endpoint":"","ingredient":"para-Aminophenol (INCI name)","loael_value":"","noael_unit":"","noael_value":"unclear:e peak that was observed upon analysis for metabolites in the plasma was identified as APAP. The parent compound, PAP, was undetectable in the plasma. From these results, it was concluded that PAP was not present in the plasma of the pig during 24 hours of continuous exposure. Only its metabolite, APAP could be detected. Ref.: Col. 98 Conclusion The safety of a topically applied substance may be assessed by two principal methods: comparison of the calculated penetrated amount (systemic exposure dose; SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). comparison of toxicokinetic, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies with respective human data (Ref. KM5). Although the first approach permits an approximate estimation of a potential risk of a topically applied substance, it includes a number of uncertainty factors, such as statistical uncertainty of no-eff","page":31,"route":"","species":"human","study_id":"sccp_o_00e_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 10 mg/kg bw/day rabbit dermal 13 weeks - SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT=10; DOSE=induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only.; EFFECT=induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations i; CITATION=Ref.: Col; CITATION_NUMBERS=[]; REFERENCE=Ref.: Col; DETAILS_JSON={"cas_number":"123-30-8","citation":"Ref.: Col","dose":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only.","duration":"13 weeks","effect":"induced at all doses a not dose-related lower body weight gain and ptyalism at 100 mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations i","endpoint":"","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":17,"route":"dermal","species":"rabbit","study_id":"sccs_o_078_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 10 mg/kg bw/day rabbit dermal 13 weeks - SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT=10; DOSE=mg/kg bw/d, in females only.; EFFECT=mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations in clinical pathology parameters were observed, but none were considered to be of tox; CITATION=Ref.: Col; CITATION_NUMBERS=[]; REFERENCE=Ref.: Col; DETAILS_JSON={"cas_number":"123-30-8","citation":"Ref.: Col","dose":"mg/kg bw/d, in females only.","duration":"13 weeks","effect":"mg/kg bw/d, in females only. The major finding consisted of the tubular nephrosis observed with a dose-related incidence at the two-highest doses in both sexes (in 5/10 males and 2/10 females given 30 mg/kg bw/d and in 9/10 males and 10/10 females given 100 mg/kg bw/d). As the dose of 10 mg/kg bw/d induced only a lower body weight gain (-16% as compared to the control) in females, this dose level was considered to be close to the NOEL. Ref.: Col. 69 Comment The SCCS considers the dose of 10 mg/kg bw/day as the NOAEL since the decrease in body weight gain was not dose related. Dermal Three hair dye formulations containing 0.04%, 0.2% or 1.0% p-aminophenol and mixed with 6% hydrogen peroxide were applied topically to the clipped skin of rabbits twice weekly for 13 weeks. Rabbits in three independent control groups were clipped as were treated animals, but no dyes were applied. No compound-related findings were observed. Scattered variations in clinical pathology parameters were observed, but none were considered to be of tox","endpoint":"","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":17,"route":"dermal","species":"rabbit","study_id":"sccs_o_078_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1409 - human - - - SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT=unclear:SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM; DOSE=Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.; EFFECT=SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM; CITATION=Ref.: KM4); CITATION_NUMBERS=[4]; REFERENCE=Ref.: KM4); DETAILS_JSON={"cas_number":"123-30-8","citation":"Ref.: KM4)","dose":"Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","duration":"","effect":"SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM","endpoint":"","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 47 3.3.13. Safety evaluation (including calculation of the MoS) In most cases, the safety evaluation of cosmetic ingredients is based on a comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold (Ref.: KM4). In the submitted dossier, the applicant, in addition to the conventional MoS approach, proposes for p-aminophenol to base the assessment on the comparison of toxicokinetics, quantitative exposure data (plasma levels, area under curve) from animal toxicology studies (p-aminophenol applied topically) with respective human data (APAP administered orally) (Ref. KM","page":47,"route":"","species":"human","study_id":"sccs_o_078_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 3 - rat oral - - SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT=unclear:e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).; DOSE=e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref.; EFFECT=e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).; CITATION=(Ref. KM9); CITATION_NUMBERS=[9]; REFERENCE=(Ref. KM9); DETAILS_JSON={"cas_number":"123-30-8","citation":"(Ref. KM9)","dose":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref.","duration":"","effect":"e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).","endpoint":"","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"","noael_value":"unclear:e maximum therapeutic dose of 3x1000 mg over 8 hours (Ref. KM9). Given that topically applied p- aminophenol results in systemic exposure to APAP and/or its metabolites only, in both humans and animals, the systemic exposure seen in animal studies after topical application may be compared to the systemic human exposure after a single oral dose of the drug APAP (= AUCman). The proposal from the applicant is to compare the AUC in rats (n = 12) or pig (n = 1), from 0 to 12 hours, at a high dose levels not related to NOAEL/LOAEL (p-aminophenol applied topically) to the AUC in humans following administration of therapeutic dose of APAP considered as safe (500 mg/day). However, the scientific rationale behind this approach is not completely convincing. Assessment by the SCCS The safety of a topically applied substance may be assessed by two principal methods: MoS calculation and the toxicokinetics based approach (cf SCCS Notes of Guidance).","page":47,"route":"oral","species":"rat","study_id":"sccs_o_078_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1409 - human - - - SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT=unclear:SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 48 The SCCS is of the opinion that for a toxicokinetic-based risk assessment, the AUC from 0 to the infinite in humans exposed at realistic doses of the hair dye should be compared to the AUC of the compound (or its active metabolite) in a sensitive animal species exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity; DOSE=SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 48 The SCCS is of the opinion that for a toxicokinetic-based risk assessment, the AUC from 0 to the infinite in humans exposed at realistic doses of the hair dye should be compared to the AUC of the compound (or its a...; EFFECT=SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 48 The SCCS is of the opinion that for a toxicokinetic-based risk assessment, the AUC from 0 to the infinite in humans exposed at realistic doses of the hair dye should be compared to the AUC of the compound (or its active metabolite) in a sensitive animal species exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 48 The SCCS is of the opinion that for a toxicokinetic-based risk assessment, the AUC from 0 to the infinite in humans exposed at realistic doses of the hair dye should be compared to the AUC of the compound (or its a...","duration":"","effect":"SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 48 The SCCS is of the opinion that for a toxicokinetic-based risk assessment, the AUC from 0 to the infinite in humans exposed at realistic doses of the hair dye should be compared to the AUC of the compound (or its active metabolite) in a sensitive animal species exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity","endpoint":"","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1409/11 Opinion on p-aminophenol ___________________________________________________________________________________________ 48 The SCCS is of the opinion that for a toxicokinetic-based risk assessment, the AUC from 0 to the infinite in humans exposed at realistic doses of the hair dye should be compared to the AUC of the compound (or its active metabolite) in a sensitive animal species exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity","page":48,"route":"","species":"human","study_id":"sccs_o_078_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =6.9 µg/cm human dermal - dermal absorption SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT== 6.9; DOSE=exposed at a dose level close to the NOAEL/LOAEL.; EFFECT=exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"exposed at a dose level close to the NOAEL/LOAEL.","duration":"","effect":"exposed at a dose level close to the NOAEL/LOAEL. If the ratio between both of the AUCs (AUCrat/ AUChuman) is more than 25, then the safety of the compound may be demonstrated (KM06). In the case of p-aminophenol, in addition to the conventional MoS calculation, a different approach is used based on comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use. A) Usual MoS calculation: Comparison of the calculated penetrated amount (systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10","endpoint":"dermal absorption","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"µg/cm","noael_value":"= 6.9","page":48,"route":"dermal","species":"human","study_id":"sccs_o_078_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =0.067 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT== 0.067; DOSE=(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.; EFFECT=(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human follow; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","duration":"90-day","effect":"(systemic exposure dose, SED) with a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human follow","endpoint":"dermal absorption","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.067","page":48,"route":"oral","species":"rat","study_id":"sccs_o_078_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =10 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT== 10; DOSE=th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.; EFFECT=th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following ha; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”.","duration":"90-day","effect":"th a NOAEL from a repeated-dose animal toxicity study yielding a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following ha","endpoint":"dermal absorption","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 10","page":48,"route":"oral","species":"rat","study_id":"sccs_o_078_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =10 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT== 10; DOSE=CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse eff...; EFFECT=ng a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following hair dyeing with p- aminophenol, to the systemic dose of APAP; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse eff...","duration":"90-day","effect":"ng a nominal “margin of safety”. The accepted empirical margin of safety is generally 100-fold. CALCULATION OF THE MARGIN OF SAFETY p-Aminophenol (oxidative conditions) Absorption through the skin A (mean + 2 SD) = 6.9 µg/cm² Skin Area surface SAS = 580 cm² Dermal absorption per treatment SAS x A x 0.001 = 4.00 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.067 mg/kg bw/d No observed adverse effect level NOAEL = 10 mg/kg bw/d (90-day, oral, rat) Margin of Safety NOAEL / SED = 150 B) Comparison of systemic exposures of APAP from hair dyeing to the systemic exposure from therapeutic use: Since topically applied p-aminophenol results in systemic exposure only to APAP and/or its metabolites in both humans and animals (cf above), the toxicity of p-aminophenol is considered to be mainly related to the toxicity of APAP. Therefore, the SCCS considers it appropriate to compare the systemic dose of APAP in human following hair dyeing with p- aminophenol, to the systemic dose of APAP","endpoint":"dermal absorption","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 10","page":48,"route":"oral","species":"rat","study_id":"sccs_o_078_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies genotoxicity 25 mg/kg rat oral 90 day genotoxicity SOURCE_SUBDIR=sccp_o_00e; REPORT_TITLE=Opinion on para-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCP/0867/05; COMMITTEE=SCCP; REPORT_DATE=15 March 2005; VALUE_TEXT=25; DOSE=90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.; EFFECT=90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses; the respective NOAEL is 25 mg/kg/bw/day. p-Aminophenol is genotoxic in vitro and in vivo. It induces clastogenic effects under standard test conditions. These effects occur at high dose in the presence of toxic effects. The biological significance of these effects and their relevance for exposed humans has to be discussed. There is evidence that p-aminophenol is metabolized in the skin to acetaminophen (Paracetamol). Paracetamol has also been shown to be clastogenic in vitro and in vivo in standard genotoxicity tests. However, the po; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","duration":"90 day","effect":"90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses; the respective NOAEL is 25 mg/kg/bw/day. p-Aminophenol is genotoxic in vitro and in vivo. It induces clastogenic effects under standard test conditions. These effects occur at high dose in the presence of toxic effects. The biological significance of these effects and their relevance for exposed humans has to be discussed. There is evidence that p-aminophenol is metabolized in the skin to acetaminophen (Paracetamol). Paracetamol has also been shown to be clastogenic in vitro and in vivo in standard genotoxicity tests. However, the po","endpoint":"genotoxicity","ingredient":"para-Aminophenol (INCI name)","loael_value":"","noael_unit":"mg/kg","noael_value":"25","page":39,"route":"oral","species":"rat","study_id":"sccp_o_00e_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 10 mg/kg rat oral subchronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_00e; REPORT_TITLE=Opinion on para-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCP/0867/05; COMMITTEE=SCCP; REPORT_DATE=15 March 2005; VALUE_TEXT=10; DOSE=An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.; EFFECT=also refers to references from previous submissions I, II and III. Regarding the possible recent classification of PAP within CMR categories in class 3 it was necessary to repeat older studies or to perform entirely new ones; these were reported in submissions IV and V and especially laid down in an appendix, covering references Col. 69-96. PAP showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses;; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects.","duration":"subchronic","effect":"also refers to references from previous submissions I, II and III. Regarding the possible recent classification of PAP within CMR categories in class 3 it was necessary to repeat older studies or to perform entirely new ones; these were reported in submissions IV and V and especially laid down in an appendix, covering references Col. 69-96. PAP showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. An NOAEL was found in a 90 day oral study in the rat at 10 mg/kg/bw/day and 30 mg/kg/bw/day were administered in a long term (110 d) study without harmful effects. No irritancy was seen on the skin following OECD/AFOR methodology up to a concentration of 2.5 % PAP aqueous solution. On mucous membranes PAP was classified as slightly irritant. Tests for sensitization revealed such a potential; no photosensitization. Within the teratologic sector no signs of embryo – or foeto-toxicity were seen at non-maternal toxic doses;","endpoint":"repeated dose toxicity","ingredient":"para-Aminophenol (INCI name)","loael_value":"","noael_unit":"mg/kg","noael_value":"10","page":39,"route":"oral","species":"rat","study_id":"sccp_o_00e_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 10 mg/kg bw/day rabbit dermal subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_078; REPORT_TITLE=OPINION ON p-Aminophenol COLIPA n° A16; OPINION_NUMBER=SCCS/1409/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=14 December 2011; VALUE_TEXT=10; DOSE=Dose-related nephrosis at 30 and 100 mg/kg bw/day were observed in both sexes.; EFFECT=pigs. As a consequence, the safety of p-aminophenol has been assessed via the comparison of systemic exposure of APAP from hair dyeing to systemic exposure of APAP from the therapeutic use. General toxicity p-Aminophenol showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. Dose-related nephrosis at 30 and 100 mg/kg bw/day were observed in both sexes. The dose of 10 mg/kg bw/day was considered as the NOAEL. Irritation, sensitisation p-Aminophenol showed irritancy on rabbit skin at 2.5% aqueous solution and when applied neat under semi-occlusion. It was also irritant on mucous membranes at 2.5% aqueous solution and when applied neat to rabbit eye. p-Aminophenol was shown to be a strong sensitiser. Dermal absorption Complete original data is not available. The concentration of p-aminophenol used was 0.42% when the intended maximum on-head concentration is 0.9% in oxidative dyes. Accordingly, the amount considered; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"123-30-8","citation":"","dose":"Dose-related nephrosis at 30 and 100 mg/kg bw/day were observed in both sexes.","duration":"subchronic","effect":"pigs. As a consequence, the safety of p-aminophenol has been assessed via the comparison of systemic exposure of APAP from hair dyeing to systemic exposure of APAP from the therapeutic use. General toxicity p-Aminophenol showed a low acute toxicity in several species and different application sites. In subchronic and chronic experiments the target organs were the kidneys and the liver. Dose-related nephrosis at 30 and 100 mg/kg bw/day were observed in both sexes. The dose of 10 mg/kg bw/day was considered as the NOAEL. Irritation, sensitisation p-Aminophenol showed irritancy on rabbit skin at 2.5% aqueous solution and when applied neat under semi-occlusion. It was also irritant on mucous membranes at 2.5% aqueous solution and when applied neat to rabbit eye. p-Aminophenol was shown to be a strong sensitiser. Dermal absorption Complete original data is not available. The concentration of p-aminophenol used was 0.42% when the intended maximum on-head concentration is 0.9% in oxidative dyes. Accordingly, the amount considered","endpoint":"repeated dose toxicity","ingredient":"was submitted in June 1985 by COLIPA².","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":50,"route":"dermal","species":"rabbit","study_id":"sccs_o_078_noael_010"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier R7P8FRP05V UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H7NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R7P8FRP05V"}
openFDA substances FDA UNII substance identifier R7P8FRP05V UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H7NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R7P8FRP05V"}
openFDA substances FDA UNII substance identifier R7P8FRP05V UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H7NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R7P8FRP05V"}
openFDA substances FDA UNII substance identifier R7P8FRP05V UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H7NO","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"R7P8FRP05V"}