NOAEL Studies
Fragrance
Methyl Salicylate NOAEL Studies
INCI: METHYL SALICYLATE
CAS: 119-36-8
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
COSMOS DB 7 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| COSMOS DB | LOAEL | 150 | mg/kg bw/day | dog | oral | 225 day | Subchronic | PAFA;REACH; FAP |
| COSMOS DB | LOAEL | 250 | mg/kg bw/day | rat | oral | 2 year | Chronic | REACH; Toxicology and Applied Pharmacology 5: 576-687 |
| COSMOS DB | NOAEL | 50 | mg/kg bw/day | dog | oral | 2 day | Chronic | REACH; Toxicology and Applied Pharmacology 5: 576-687 |
| COSMOS DB | NOAEL | 100 | mg/kg bw/day | mouse | oral | NA | Multigeneration Reproductive | US FDA CFSAN PAFA; US FDA CFSAN PAFA Study |
| COSMOS DB | NOAEL | 150 | mg/kg bw/day | dog | oral | 225 day | Chronic | US FDA CFSAN PAFA; US FDA CFSAN PAFA Study |
| COSMOS DB | NOAEL | 167 | mg/kg bw/day | dog | oral | 180 day | Chronic | US FDA CFSAN PAFA; US FDA CFSAN PAFA Study |
| COSMOS DB | NOAEL | 250 | mg/kg bw/day | rat | oral | NA | Multigeneration Reproductive | US FDA CFSAN PAFA; US FDA CFSAN PAFA Study |
EFSA 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| EFSA | NOAEL | =50 | mg/kg bw/day | Dog | - | 730 days | chronic/long term toxicity | EFSA AFC - 2008 - OutputID 2243 - Flavouring Group Evaluation 52 (FGE.52): Consideration of hydroxy- and alkoxy substituted benzyl derivatives evaluated by JECFA (57th meeting) structurally related to benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters evaluated by EFSA in FGE.20 (2005) (Commission Regulation (EC) No 1565/2000 of 18 July 2000) - doi:10.2903/j.efsa.2008.637 |
| EFSA | NOAEL | =50 | mg/kg bw/day | Dog | - | 730 days | chronic/long term toxicity | EFSA AFC - 2008 - OutputID 2243 - Flavouring Group Evaluation 52 (FGE.52): Consideration of hydroxy- and alkoxy substituted benzyl derivatives evaluated by JECFA (57th meeting) structurally related to benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters evaluated by EFSA in FGE.20 (2005) (Commission Regulation (EC) No 1565/2000 of 18 July 2000) - doi:10.2903/j.efsa.2008.637 |
NTP ICE acute oral 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE acute oral | LD50 | =887 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | NLM Hazardous Substances Data Bank (undated); record_id=acute_oral_1579; row=8909; data_type=In Vivo; mixture=Chemical; chemical_name=Methyl salicylate; preferred_name=Methyl salicylate; dtxsid=DTXSID5025659; url=https://pubchem.ncbi.nlm.nih.gov/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID5025659; source_file=acute_oral.xlsx |
| NTP ICE acute oral | LD50 | =2820 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | ECHA ChemProp (undated); record_id=acute_oral_1582; row=8910; data_type=In Vivo; mixture=Chemical; chemical_name=Methyl salicylate; preferred_name=Methyl salicylate; dtxsid=DTXSID5025659; url=https://echa.europa.eu/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID5025659; source_file=acute_oral.xlsx |
NTP ICE adme parameters 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE adme parameters | Clint | 817 | uL/min/10^6 cells | Human | - | - | Measured; httk, Human Hepatic Intrinsic Clearance | sheet=Data; excel_row=2090; Record_ID=adme_parameters_1047; Data_Type=Measured; DTXSID=DTXSID5025659; Assay=httk, Human Hepatic Intrinsic Clearance; Endpoint=Clint; Response=817.0; Response_Unit=ul/min/10^6 cells; Species=Human; Reference=httk2.3.1, Wambaugh 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE adme parameters | Fu | 0.107 | fraction | Human | - | - | Measured; httk, Human Plasma Fraction Unbound | sheet=Data; excel_row=2089; Record_ID=adme_parameters_1047; Data_Type=Measured; DTXSID=DTXSID5025659; Assay=httk, Human Plasma Fraction Unbound; Endpoint=Fu; Response=0.107; Response_Unit=Unitless Fraction; Species=Human; Reference=httk2.3.1, Wambaugh 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
NTP ICE endocrine 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE endocrine | Model Score | 0 | unitless | - | - | - | ARPathway2016; AR Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=11526; RecordID=ARPathway2016_657; DatasetName=ARPathway2016; DTXSID=DTXSID5025659; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
NTP ICE skin sensitization 77 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE skin sensitization | CD86, EC150 | >200 | ug/mL | - | Dermal | - | In Vitro; CE_USENSE2018; U-SENS | sheet=Data_invitro; excel_row=8735; Record_ID=skin_sensitization_invitro_2421; Data_Type=In Vitro; Internal_Data_Source=CE_USENSE2018; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=U-SENS; Endpoint=CD86, EC150; Response_Modifier=>; Reported_Response_Modifier=>; Reported_Response=200; Reported_Response_Unit=ug/mL; Response=200; Response_Unit=ug/mL; Reference=Piroird et al. 2015; 25820135; 10.1016/j.tiv.2015.03.009; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | CD86, EC150 | >1065.043 | ug/mL | - | Dermal | - | In Vitro; Urbisch_SkinSensitization2020; U-SENS | sheet=Data_invitro; excel_row=8190; Record_ID=skin_sensitization_invitro_2213; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=U-SENS; Endpoint=CD86, EC150; Response_Modifier=>; Reported_Response_Modifier=>; Reported_Response=7000; Reported_Response_Unit=uM; Conversion_Factor_Value=152.149; Conversion_Factor_Source=EPA Dashboard; Converted_Response_Modifier=>; Converted_Response=1065.043; Converted_Response_Unit=ug/mL; Response=1065.043; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | CV75 | 95 | ug/mL | - | Dermal | - | In Vitro; hCLAT2015; h-CLAT | sheet=Data_invitro; excel_row=3018; Record_ID=skin_sensitization_invitro_696; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=h-CLAT; Endpoint=CV75; Reported_Response=95; Reported_Response_Unit=ug/mL; Response=95; Response_Unit=ug/mL; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | CV75 | 542.4 | ug/mL | - | Dermal | - | In Vitro; CE_hCLAT2018; h-CLAT | sheet=Data_invitro; excel_row=2259; Record_ID=skin_sensitization_invitro_554; Data_Type=In Vitro; Internal_Data_Source=CE_hCLAT2018; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=h-CLAT; Endpoint=CV75; Reported_Response=542.4; Reported_Response_Unit=ug/mL; Response=542.4; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | -2.4 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=834; Record_ID=skin_sensitization_invitro_232; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=-2.4; Reported_Response_Unit=%; Response=-2.4; Response_Unit=%; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | 0 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=826; Record_ID=skin_sensitization_invitro_230; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=0; Reported_Response_Unit=%; Response=0; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | 0.2 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=854; Record_ID=skin_sensitization_invitro_237; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=0.2; Reported_Response_Unit=%; Response=0.2; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | 0.3 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=822; Record_ID=skin_sensitization_invitro_229; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=0.3; Reported_Response_Unit=%; Response=0.3; Response_Unit=%; Reference=Gerberick et al. 2004; 15254333; 10.1093/toxsci/kfh213|Natsch et al. 2013; 23576290; 10.1002/jat.2868; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | 0.4 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=830; Record_ID=skin_sensitization_invitro_231; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=0.4; Reported_Response_Unit=%; Response=0.4; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | 3.4 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=842; Record_ID=skin_sensitization_invitro_234; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=3.4; Reported_Response_Unit=%; Response=3.4; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | 9.1 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=838; Record_ID=skin_sensitization_invitro_233; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=9.1; Reported_Response_Unit=%; Response=9.1; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Cys | 11.3 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=846; Record_ID=skin_sensitization_invitro_235; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=11.3; Reported_Response_Unit=%; Response=11.3; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | -0.2 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=833; Record_ID=skin_sensitization_invitro_232; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=-0.2; Reported_Response_Unit=%; Response=-0.2; Response_Unit=%; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 1 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=837; Record_ID=skin_sensitization_invitro_233; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=1; Reported_Response_Unit=%; Response=1; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 1.3 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=849; Record_ID=skin_sensitization_invitro_236; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=1.3; Reported_Response_Unit=%; Response=1.3; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 1.6 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=821; Record_ID=skin_sensitization_invitro_229; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=1.6; Reported_Response_Unit=%; Response=1.6; Response_Unit=%; Reference=Gerberick et al. 2004; 15254333; 10.1093/toxsci/kfh213|Natsch et al. 2013; 23576290; 10.1002/jat.2868; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 2.9 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=841; Record_ID=skin_sensitization_invitro_234; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=2.9; Reported_Response_Unit=%; Response=2.9; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 3 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=845; Record_ID=skin_sensitization_invitro_235; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=3; Reported_Response_Unit=%; Response=3; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 22.9 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=829; Record_ID=skin_sensitization_invitro_231; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=22.9; Reported_Response_Unit=%; Response=22.9; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 24.4 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=825; Record_ID=skin_sensitization_invitro_230; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=24.4; Reported_Response_Unit=%; Response=24.4; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys | 24.6 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=865; Record_ID=skin_sensitization_invitro_240; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=24.6; Reported_Response_Unit=%; Response=24.6; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 0.7 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=859; Record_ID=skin_sensitization_invitro_238; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=0.7; Reported_Response_Unit=%; Response=0.7; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 0.8 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=851; Record_ID=skin_sensitization_invitro_236; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=0.8; Reported_Response_Unit=%; Response=0.8; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 0.9 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=855; Record_ID=skin_sensitization_invitro_237; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=0.9; Reported_Response_Unit=%; Response=0.9; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 0.95 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=823; Record_ID=skin_sensitization_invitro_229; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=0.95; Reported_Response_Unit=%; Response=0.95; Response_Unit=%; Reference=Gerberick et al. 2004; 15254333; 10.1093/toxsci/kfh213|Natsch et al. 2013; 23576290; 10.1002/jat.2868; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 3.15 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=843; Record_ID=skin_sensitization_invitro_234; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=3.15; Reported_Response_Unit=%; Response=3.15; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 5.05 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=839; Record_ID=skin_sensitization_invitro_233; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=5.05; Reported_Response_Unit=%; Response=5.05; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 7.15 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=847; Record_ID=skin_sensitization_invitro_235; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=7.15; Reported_Response_Unit=%; Response=7.15; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 11.65 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=831; Record_ID=skin_sensitization_invitro_231; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=11.65; Reported_Response_Unit=%; Response=11.65; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 12.2 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=827; Record_ID=skin_sensitization_invitro_230; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=12.2; Reported_Response_Unit=%; Response=12.2; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Depletion Lys + Cys | 12.8 | % | - | Dermal | - | In Vitro; DPRA2015; DPRA | sheet=Data_invitro; excel_row=867; Record_ID=skin_sensitization_invitro_240; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=12.8; Reported_Response_Unit=%; Response=12.8; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC1.5 | 80.98 | uM | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4827; Record_ID=skin_sensitization_invitro_1112; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=80.98; Reported_Response_Unit=uM; Response=80.98; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC1.5 | 228.87 | uM | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4824; Record_ID=skin_sensitization_invitro_1121; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=228.87; Reported_Response_Unit=uM; Response=228.87; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC1.5 | 508.18 | uM | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4825; Record_ID=skin_sensitization_invitro_1122; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=508.18; Reported_Response_Unit=uM; Response=508.18; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC1.5 | <803.76 | uM | - | Dermal | - | In Vitro; Urbisch_SkinSensitization2020; LuSens | sheet=Data_invitro; excel_row=7990; Record_ID=skin_sensitization_invitro_1806; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LuSens; Endpoint=EC1.5; Response_Modifier=<; Reported_Response_Modifier=<; Reported_Response=803.76; Reported_Response_Unit=uM; Response=803.76; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC1.5 | 1076 | uM | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4818; Record_ID=skin_sensitization_invitro_1111; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=1075.8699999999999; Reported_Response_Unit=uM; Response=1076; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC1.5 | 1612 | uM | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4820; Record_ID=skin_sensitization_invitro_1118; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=1612; Reported_Response_Unit=uM; Response=1612; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC1.5 | >2000 | uM | - | Dermal | - | In Vitro; CE_KeratinoSense2018; KeratinoSens | sheet=Data_invitro; excel_row=4822; Record_ID=skin_sensitization_invitro_1116; Data_Type=In Vitro; Internal_Data_Source=CE_KeratinoSense2018; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=EC1.5; Response_Modifier=>; Reported_Response_Modifier=>; Reported_Response=2000; Reported_Response_Unit=uM; Response=2000; Response_Unit=uM; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009|Natsch et al. 2013; 23576290; 10.1002/jat.2868|Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 11.5 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13464; Record_ID=skin_sensitization_invivo_3630; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=11.5; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 11.5 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13464; Record_ID=skin_sensitization_invivo_3630; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=11.5; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 11.5 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13464; Record_ID=skin_sensitization_invivo_3630; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=11.5; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 11.5 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13464; Record_ID=skin_sensitization_invivo_3630; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=11.5; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 25 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13462; Record_ID=skin_sensitization_invivo_3627; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=25; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 25 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13462; Record_ID=skin_sensitization_invivo_3627; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=25; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 25 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13462; Record_ID=skin_sensitization_invivo_3627; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=25; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | EC3 | 25 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13462; Record_ID=skin_sensitization_invivo_3627; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=EC3; Response=25; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | IC50 | >2000 | uM | - | Dermal | - | In Vitro; Urbisch_SkinSensitization2020; LuSens | sheet=Data_invitro; excel_row=7638; Record_ID=skin_sensitization_invitro_1806; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LuSens; Endpoint=IC50; Response_Modifier=>; Reported_Response_Modifier=>; Reported_Response=2000; Reported_Response_Unit=uM; Response=2000; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.198 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4879; Record_ID=skin_sensitization_invitro_1120; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.198; Reported_Response_Unit=Unitless; Response=1.198; Response_Unit=Ratio; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009|Natsch et al. 2013; 23576290; 10.1002/jat.2868; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.2 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4881; Record_ID=skin_sensitization_invitro_1131; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.2; Reported_Response_Unit=Unitless; Response=1.2; Response_Unit=Ratio; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009|Natsch et al. 2013; 23576290; 10.1002/jat.2868; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.202 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4883; Record_ID=skin_sensitization_invitro_1124; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.202; Reported_Response_Unit=Unitless; Response=1.202; Response_Unit=Ratio; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009|Natsch et al. 2013; 23576290; 10.1002/jat.2868; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.22 | ratio | - | Dermal | - | In Vitro; CE_KeratinoSense2018; KeratinoSens | sheet=Data_invitro; excel_row=4885; Record_ID=skin_sensitization_invitro_1116; Data_Type=In Vitro; Internal_Data_Source=CE_KeratinoSense2018; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.22; Reported_Response_Unit=Unitless; Response=1.22; Response_Unit=Ratio; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009|Natsch et al. 2013; 23576290; 10.1002/jat.2868|Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.237 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4887; Record_ID=skin_sensitization_invitro_1123; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.2370000000000001; Reported_Response_Unit=Unitless; Response=1.237; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.344 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4888; Record_ID=skin_sensitization_invitro_1125; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.3440000000000001; Reported_Response_Unit=Unitless; Response=1.344; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.351 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4890; Record_ID=skin_sensitization_invitro_1126; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.351; Reported_Response_Unit=Unitless; Response=1.351; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.365 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4892; Record_ID=skin_sensitization_invitro_1129; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.365; Reported_Response_Unit=Unitless; Response=1.365; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.4 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4894; Record_ID=skin_sensitization_invitro_1132; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.4; Reported_Response_Unit=Unitless; Response=1.4; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.419 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4896; Record_ID=skin_sensitization_invitro_1127; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.419; Reported_Response_Unit=Unitless; Response=1.419; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.473 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4898; Record_ID=skin_sensitization_invitro_1130; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.4730000000000001; Reported_Response_Unit=Unitless; Response=1.473; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.475 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4899; Record_ID=skin_sensitization_invitro_1128; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.4750000000000001; Reported_Response_Unit=Unitless; Response=1.475; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.478 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4900; Record_ID=skin_sensitization_invitro_1115; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.478; Reported_Response_Unit=Unitless; Response=1.478; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.5 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4901; Record_ID=skin_sensitization_invitro_1134; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.5; Reported_Response_Unit=Unitless; Response=1.5; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.54 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4907; Record_ID=skin_sensitization_invitro_1119; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.54; Reported_Response_Unit=Unitless; Response=1.54; Response_Unit=Ratio; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.586 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4908; Record_ID=skin_sensitization_invitro_1122; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.5860000000000001; Reported_Response_Unit=Unitless; Response=1.586; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.615 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4910; Record_ID=skin_sensitization_invitro_1117; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.615; Reported_Response_Unit=Unitless; Response=1.615; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.623 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4912; Record_ID=skin_sensitization_invitro_1112; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.623; Reported_Response_Unit=Unitless; Response=1.623; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.705 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4914; Record_ID=skin_sensitization_invitro_1118; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.7050000000000001; Reported_Response_Unit=Unitless; Response=1.705; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 1.748 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4916; Record_ID=skin_sensitization_invitro_1121; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.748; Reported_Response_Unit=Unitless; Response=1.748; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 2.219 | ratio | - | Dermal | - | In Vitro; Urbisch_SkinSensitization2020; LuSens | sheet=Data_invitro; excel_row=7540; Record_ID=skin_sensitization_invitro_1806; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LuSens; Endpoint=Imax; Reported_Response=2.218990032; Reported_Response_Unit=Unitless; Response=2.219; Response_Unit=Ratio; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 2.7 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4919; Record_ID=skin_sensitization_invitro_1133; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=2.7; Reported_Response_Unit=Unitless; Response=2.7; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 3.049 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4921; Record_ID=skin_sensitization_invitro_1114; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=3.0489999999999999; Reported_Response_Unit=Unitless; Response=3.049; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Imax | 3.548 | ratio | - | Dermal | - | In Vitro; KeratinoSens2015; KeratinoSens | sheet=Data_invitro; excel_row=4923; Record_ID=skin_sensitization_invitro_1111; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=3.548; Reported_Response_Unit=Unitless; Response=3.548; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Incidence of positive responses | 0 | % | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Maximization Test | sheet=Data_invivo; excel_row=4179; Record_ID=skin_sensitization_invivo_1013; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=8.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=0; Response_Unit=%; Species=Human; Route=Dermal; Reference=Epstein 1973: report to RIFM|RIFM 1973; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Anonymous 1978; Not available; 10.1016/S0015-6264(78)80132-1; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Induction dose per skin area | 968.8 | ug/cm2 | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test | sheet=Data_invivo; excel_row=4184; Record_ID=skin_sensitization_invivo_1015; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.25; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=968.8; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=RIFM 1964; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Belsito et al. 2007; 18022746; 10.1016/j.fct.2007.09.066|Lapczynski et al. 2007; 18031908; 10.1016/j.fct.2007.09.053; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Induction dose per skin area | 5184 | ug/cm2 | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Maximization Test | sheet=Data_invivo; excel_row=4176; Record_ID=skin_sensitization_invivo_1013; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=8.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=5184; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Epstein 1973: report to RIFM|RIFM 1973; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Anonymous 1978; Not available; 10.1016/S0015-6264(78)80132-1; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Max stimulation index | 2.7 | ratio | Mouse | Dermal | - | In Vivo; LLNA2013; LLNA | sheet=Data_invivo; excel_row=12853; Record_ID=skin_sensitization_invivo_485; Data_Type=In Vivo; Internal_Data_Source=LLNA2013; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=LLNA; Endpoint=Max stimulation index; Response=2.7; Response_Unit=Ratio; Species=Mouse; Route=Dermal; Reference=ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Relative reliability score | 3 | unitless | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Maximization Test | sheet=Data_invivo; excel_row=4183; Record_ID=skin_sensitization_invivo_1013; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=8.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=Human Maximization Test; Endpoint=Relative reliability score; Response=3; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=Epstein 1973: report to RIFM|RIFM 1973; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Anonymous 1978; Not available; 10.1016/S0015-6264(78)80132-1; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
| NTP ICE skin sensitization | Relative reliability score | 4 | unitless | Human | Dermal | - | In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test | sheet=Data_invivo; excel_row=4190; Record_ID=skin_sensitization_invivo_1015; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.25; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID5025659; Assay=Human Repeat Insult Patch Test; Endpoint=Relative reliability score; Response=4; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=RIFM 1964; https://www.rifm.org/rifm-science-database.php#gsc.tab=0|Belsito et al. 2007; 18022746; 10.1016/j.fct.2007.09.066|Lapczynski et al. 2007; 18031908; 10.1016/j.fct.2007.09.053; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5025659; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5025659 |
SCCS Opinion 100 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"as also been conducted by the applicant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by th","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_001"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"as also been conducted by the applicant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by th","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_001"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"as also been conducted by the applicant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by th","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_001"} |
| SCCS Opinion | NOAEL | =0.5 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"as also been conducted by the applicant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by th","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_001"} |
| SCCS Opinion | NOAEL | =0.9 | % | rat | oral | 12 weeks | NOAEL study | {"dose":"In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations.","effect":"in bones (femur, humerus, tibia, and radius). The effects of methyl salicylate administration on bones have been reproduced in rats in a series of short-term experiments conducted by Abbott and Harrisson (1978). In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations. At the highest level, there were observations of increased density in the femur, humerus, tibia and radius. The NOAEL for bone effects was determined to be 0.9%, which was equivalent to approximately 863 mg/kg bw/day. The authors noted that the effects on bone appeared to be species-specific as they were only observed in rats and not in other experimental animals. Webb and Hansen (1963) also investigated the effects of chronic exposure in beagle dogs (n=2/sex/group), whereby methyl salicylate was administered as oral capsules containing 0, 50, 150, 350 mg/kg/day, 6 days a week for 2 years. The animals were weighed weekly and hema","page":40,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_003"} |
| SCCS Opinion | NOAEL | =0.9 | % | rat | oral | 12 weeks | NOAEL study | {"dose":"In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations.","effect":"in bones (femur, humerus, tibia, and radius). The effects of methyl salicylate administration on bones have been reproduced in rats in a series of short-term experiments conducted by Abbott and Harrisson (1978). In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations. At the highest level, there were observations of increased density in the femur, humerus, tibia and radius. The NOAEL for bone effects was determined to be 0.9%, which was equivalent to approximately 863 mg/kg bw/day. The authors noted that the effects on bone appeared to be species-specific as they were only observed in rats and not in other experimental animals. Webb and Hansen (1963) also investigated the effects of chronic exposure in beagle dogs (n=2/sex/group), whereby methyl salicylate was administered as oral capsules containing 0, 50, 150, 350 mg/kg/day, 6 days a week for 2 years. The animals were weighed weekly and hema","page":40,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_003"} |
| SCCS Opinion | NOAEL | =0.9 | % | rat | oral | 12 weeks | NOAEL study | {"dose":"In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations.","effect":"in bones (femur, humerus, tibia, and radius). The effects of methyl salicylate administration on bones have been reproduced in rats in a series of short-term experiments conducted by Abbott and Harrisson (1978). In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations. At the highest level, there were observations of increased density in the femur, humerus, tibia and radius. The NOAEL for bone effects was determined to be 0.9%, which was equivalent to approximately 863 mg/kg bw/day. The authors noted that the effects on bone appeared to be species-specific as they were only observed in rats and not in other experimental animals. Webb and Hansen (1963) also investigated the effects of chronic exposure in beagle dogs (n=2/sex/group), whereby methyl salicylate was administered as oral capsules containing 0, 50, 150, 350 mg/kg/day, 6 days a week for 2 years. The animals were weighed weekly and hema","page":40,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_003"} |
| SCCS Opinion | NOAEL | =0.9 | % | rat | oral | 12 weeks | NOAEL study | {"dose":"In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations.","effect":"in bones (femur, humerus, tibia, and radius). The effects of methyl salicylate administration on bones have been reproduced in rats in a series of short-term experiments conducted by Abbott and Harrisson (1978). In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations. At the highest level, there were observations of increased density in the femur, humerus, tibia and radius. The NOAEL for bone effects was determined to be 0.9%, which was equivalent to approximately 863 mg/kg bw/day. The authors noted that the effects on bone appeared to be species-specific as they were only observed in rats and not in other experimental animals. Webb and Hansen (1963) also investigated the effects of chronic exposure in beagle dogs (n=2/sex/group), whereby methyl salicylate was administered as oral capsules containing 0, 50, 150, 350 mg/kg/day, 6 days a week for 2 years. The animals were weighed weekly and hema","page":40,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_003"} |
| SCCS Opinion | NOAEL | =2 | % | - | dermal | 3 years | dermal absorption | {"dose":"MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot,...","effect":"CCS/1654/23 ___________________________________________________________________________________________ _________________________________________________________________________ 19 • Dermally applied products Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,56 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,49 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,24 9,37 0,02% 50,00% 0,94 75000 80043 HAND SOAP Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,90 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,78 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,52 9,37 0,02% 50,00% 0,94 75000 80043 SHAMPOO Ficheux et Roudot, 2017, shampoing Infan","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_007"} |
| SCCS Opinion | NOAEL | =2 | % | - | dermal | 3 years | dermal absorption | {"dose":"MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot,...","effect":"CCS/1654/23 ___________________________________________________________________________________________ _________________________________________________________________________ 19 • Dermally applied products Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,56 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,49 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,24 9,37 0,02% 50,00% 0,94 75000 80043 HAND SOAP Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,90 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,78 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,52 9,37 0,02% 50,00% 0,94 75000 80043 SHAMPOO Ficheux et Roudot, 2017, shampoing Infan","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_007"} |
| SCCS Opinion | NOAEL | =2 | % | - | dermal | 3 years | dermal absorption | {"dose":"MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot,...","effect":"CCS/1654/23 ___________________________________________________________________________________________ _________________________________________________________________________ 19 • Dermally applied products Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,56 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,49 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,24 9,37 0,02% 50,00% 0,94 75000 80043 HAND SOAP Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,90 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,78 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,52 9,37 0,02% 50,00% 0,94 75000 80043 SHAMPOO Ficheux et Roudot, 2017, shampoing Infan","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_007"} |
| SCCS Opinion | NOAEL | =2 | % | - | dermal | 3 years | dermal absorption | {"dose":"MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot,...","effect":"CCS/1654/23 ___________________________________________________________________________________________ _________________________________________________________________________ 19 • Dermally applied products Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children up to 3 years old Product type Data source used for SED derivation Applicant SSA approach (mg/kg bw/d) Daily exposure F&R, 2017 (mg/kg bw/d) substance concentration (%) Dermal absorption DAp (%) SED (µg/kg/d) NOAEL (µg/kg/bw/d MOS SHOWER GEL Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,56 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,49 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,24 9,37 0,02% 50,00% 0,94 75000 80043 HAND SOAP Ficheux et Roudot, 2017, gel douche Infants 0 - 0.5 yrs 6,90 7,40 0,02% 50,00% 0,74 75000 101351 Infants 0.5 - 1 yrs 5,78 7,40 0,02% 50,00% 0,74 75000 101351 Toddlers 1 - 3 yrs 5,52 9,37 0,02% 50,00% 0,94 75000 80043 SHAMPOO Ficheux et Roudot, 2017, shampoing Infan","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_007"} |
| SCCS Opinion | NOAEL | =2.52 | % | - | oral | 6 years | NOAEL study | {"effect":"SCCS/1654/23 Final version Scientific Advice on methyl salicylate (methyl 2-hydroxybenzoate) - children exposure ___________________________________________________________________________________________ _________________________________________________________________________ 21 rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. For systemic effects, considering all dermally applied products include in the table 2 above and oral exposure via toothpastes, the MOS is above 100 for individual exposure as well as for aggregated exposure. 4. CONCLUSION In the SCCS/1633/21 Opinion, the Committee concluded that Methyl Salicylate in toothpaste is safe for children under 6 years of age when used up to the maximum concentration of 2.52%. 1. In light of the data provided and taking under consideration the conclusions of SCCS/1633/21 and th","page":21,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_009"} |
| SCCS Opinion | NOAEL | =2.52 | % | - | oral | 6 years | NOAEL study | {"effect":"SCCS/1654/23 Final version Scientific Advice on methyl salicylate (methyl 2-hydroxybenzoate) - children exposure ___________________________________________________________________________________________ _________________________________________________________________________ 21 rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. For systemic effects, considering all dermally applied products include in the table 2 above and oral exposure via toothpastes, the MOS is above 100 for individual exposure as well as for aggregated exposure. 4. CONCLUSION In the SCCS/1633/21 Opinion, the Committee concluded that Methyl Salicylate in toothpaste is safe for children under 6 years of age when used up to the maximum concentration of 2.52%. 1. In light of the data provided and taking under consideration the conclusions of SCCS/1633/21 and th","page":21,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_009"} |
| SCCS Opinion | NOAEL | =2.52 | % | - | oral | 6 years | NOAEL study | {"effect":"SCCS/1654/23 Final version Scientific Advice on methyl salicylate (methyl 2-hydroxybenzoate) - children exposure ___________________________________________________________________________________________ _________________________________________________________________________ 21 rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. For systemic effects, considering all dermally applied products include in the table 2 above and oral exposure via toothpastes, the MOS is above 100 for individual exposure as well as for aggregated exposure. 4. CONCLUSION In the SCCS/1633/21 Opinion, the Committee concluded that Methyl Salicylate in toothpaste is safe for children under 6 years of age when used up to the maximum concentration of 2.52%. 1. In light of the data provided and taking under consideration the conclusions of SCCS/1633/21 and th","page":21,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_009"} |
| SCCS Opinion | NOAEL | =2.52 | % | - | oral | 6 years | NOAEL study | {"effect":"SCCS/1654/23 Final version Scientific Advice on methyl salicylate (methyl 2-hydroxybenzoate) - children exposure ___________________________________________________________________________________________ _________________________________________________________________________ 21 rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. For systemic effects, considering all dermally applied products include in the table 2 above and oral exposure via toothpastes, the MOS is above 100 for individual exposure as well as for aggregated exposure. 4. CONCLUSION In the SCCS/1633/21 Opinion, the Committee concluded that Methyl Salicylate in toothpaste is safe for children under 6 years of age when used up to the maximum concentration of 2.52%. 1. In light of the data provided and taking under consideration the conclusions of SCCS/1633/21 and th","page":21,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_009"} |
| SCCS Opinion | NOAEL | =6 | - | - | dermal | - | dermal absorption | {"dose":"Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","effect":"Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children: Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_009"} |
| SCCS Opinion | NOAEL | =6 | - | - | dermal | - | dermal absorption | {"dose":"Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","effect":"Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children: Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_009"} |
| SCCS Opinion | NOAEL | =6 | - | - | dermal | - | dermal absorption | {"dose":"Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","effect":"Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children: Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_009"} |
| SCCS Opinion | NOAEL | =6 | - | - | dermal | - | dermal absorption | {"dose":"Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","effect":"Table 6: MoS calculation for dermally applied products containing Methyl Salicylate in children: Product type | Data source used for SED derivation | Applicant SSA approach (mg/kg bw/d) | Daily exposure F&R, 2017 (mg/kg bw/d) | substance concentration (%) | Dermal absorption DAp (%) | SED (µg/kg/d) | NOAEL (µg/kg/bw/d | MOS","page":19,"pdf":"sccs_o_298.pdf","row_type":"noael_study","study_id":"sccs_o_298_noael_009"} |
| SCCS Opinion | NOAEL | =8 | - | - | oral | 6 years | NOAEL study | {"effect":"able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_007"} |
| SCCS Opinion | NOAEL | =8 | - | - | oral | 6 years | NOAEL study | {"effect":"able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_007"} |
| SCCS Opinion | NOAEL | =8 | - | - | oral | 6 years | NOAEL study | {"effect":"able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_007"} |
| SCCS Opinion | NOAEL | =8 | - | - | oral | 6 years | NOAEL study | {"effect":"able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_007"} |
| SCCS Opinion | NOAEL | =31 | - | - | inhalation | - | NOAEL study | {"dose":"L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","effect":"Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_023"} |
| SCCS Opinion | NOAEL | =31 | - | - | inhalation | - | NOAEL study | {"dose":"L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","effect":"Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_023"} |
| SCCS Opinion | NOAEL | =31 | - | - | inhalation | - | NOAEL study | {"dose":"L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","effect":"Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_023"} |
| SCCS Opinion | NOAEL | =31 | - | - | inhalation | - | NOAEL study | {"dose":"L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","effect":"Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_023"} |
| SCCS Opinion | NOAEL | =34 | - | - | oral | developmental | reproductive toxicity | {"effect":"Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_022"} |
| SCCS Opinion | NOAEL | =34 | - | - | oral | developmental | reproductive toxicity | {"effect":"Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_022"} |
| SCCS Opinion | NOAEL | =34 | - | - | oral | developmental | reproductive toxicity | {"effect":"Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_022"} |
| SCCS Opinion | NOAEL | =34 | - | - | oral | developmental | reproductive toxicity | {"effect":"Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_022"} |
| SCCS Opinion | NOAEL | =50 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"icant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by the Frenc","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_002"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers.","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 41 ovary/uterus. The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers. Microscopically, these livers had larger hepatic cells than those in control. The NOAEL was determined to be 50 mg/kg bw/day on the basis of reduced body weight and liver effects observed at the next dose level (150 mg/kg bw/day). No treatment-related, adverse effects were observed when weanling albino rats were administered methyl salicylate derived from the oil of sweet birch, which can comprise up to 90.4% of the extract (Tisserand and Young, 2014). In a two-year chronic study, the experimental animals (n=25/sex/group, unknown strain) were administered 700 and 2100 ppm of oil of sweet birch throu","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_004"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | - | dermal absorption | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"t the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For lipstick and oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product ty","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_014"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"re, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_001"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | 6 years | dermal absorption | {"dose":"The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"essed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product types are given","page":17,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_006"} |
| SCCS Opinion | NOAEL | =50 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"icant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by the Frenc","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_002"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers.","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 41 ovary/uterus. The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers. Microscopically, these livers had larger hepatic cells than those in control. The NOAEL was determined to be 50 mg/kg bw/day on the basis of reduced body weight and liver effects observed at the next dose level (150 mg/kg bw/day). No treatment-related, adverse effects were observed when weanling albino rats were administered methyl salicylate derived from the oil of sweet birch, which can comprise up to 90.4% of the extract (Tisserand and Young, 2014). In a two-year chronic study, the experimental animals (n=25/sex/group, unknown strain) were administered 700 and 2100 ppm of oil of sweet birch throu","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_004"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | - | dermal absorption | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"t the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For lipstick and oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product ty","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_014"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"re, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_001"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | 6 years | dermal absorption | {"dose":"The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"essed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product types are given","page":17,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_006"} |
| SCCS Opinion | NOAEL | =50 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"icant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by the Frenc","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_002"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers.","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 41 ovary/uterus. The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers. Microscopically, these livers had larger hepatic cells than those in control. The NOAEL was determined to be 50 mg/kg bw/day on the basis of reduced body weight and liver effects observed at the next dose level (150 mg/kg bw/day). No treatment-related, adverse effects were observed when weanling albino rats were administered methyl salicylate derived from the oil of sweet birch, which can comprise up to 90.4% of the extract (Tisserand and Young, 2014). In a two-year chronic study, the experimental animals (n=25/sex/group, unknown strain) were administered 700 and 2100 ppm of oil of sweet birch throu","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_004"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | - | dermal absorption | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"t the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For lipstick and oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product ty","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_014"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"re, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_001"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | 6 years | dermal absorption | {"dose":"The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"essed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product types are given","page":17,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_006"} |
| SCCS Opinion | NOAEL | =50 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | {"dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","effect":"icant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by the Frenc","page":29,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_002"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers.","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 41 ovary/uterus. The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers. Microscopically, these livers had larger hepatic cells than those in control. The NOAEL was determined to be 50 mg/kg bw/day on the basis of reduced body weight and liver effects observed at the next dose level (150 mg/kg bw/day). No treatment-related, adverse effects were observed when weanling albino rats were administered methyl salicylate derived from the oil of sweet birch, which can comprise up to 90.4% of the extract (Tisserand and Young, 2014). In a two-year chronic study, the experimental animals (n=25/sex/group, unknown strain) were administered 700 and 2100 ppm of oil of sweet birch throu","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_004"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | - | dermal absorption | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"t the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For lipstick and oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product ty","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_014"} |
| SCCS Opinion | NOAEL | =50 | mg/kg bw/day | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"re, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_001"} |
| SCCS Opinion | NOAEL | =50 | % | rat | oral | 6 years | dermal absorption | {"dose":"The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"essed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product types are given","page":17,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_006"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"rved in the top-dose group.","effect":"rved in the top-dose group. There are also several studies with some shortcomings and unusual routes of administration, such as dermal application or intraperitoneal injection, where the effects varied from severe toxicity and 100 % resorption (Infurna et al., 1990 – only abstract available) to neural tube defects (Overman & White, 1983) and lethality, external malformations, visceral and skeletal anomalies and effects on differentiation indices (Kavlock et al., 1982; Daston et al., 1988). The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3- generation study in rats by oral route (Collins et al., 1971). This value will be used for the margin of Safety (MoS) calculation. With respect to developmental toxicity, RAC was of the opinion that MeS should be classified in Cat. 2, mainly due to the weight of evidence put on the human data with ASA which do not indicate that ASA is a human teratogen. Among the salicylates, the vast majority of human data d","page":49,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_012"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"tion and fertility. Concerning effects on development, a CMR category 2 classification was agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_003"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"rved in the top-dose group.","effect":"rved in the top-dose group. There are also several studies with some shortcomings and unusual routes of administration, such as dermal application or intraperitoneal injection, where the effects varied from severe toxicity and 100 % resorption (Infurna et al., 1990 – only abstract available) to neural tube defects (Overman & White, 1983) and lethality, external malformations, visceral and skeletal anomalies and effects on differentiation indices (Kavlock et al., 1982; Daston et al., 1988). The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3- generation study in rats by oral route (Collins et al., 1971). This value will be used for the margin of Safety (MoS) calculation. With respect to developmental toxicity, RAC was of the opinion that MeS should be classified in Cat. 2, mainly due to the weight of evidence put on the human data with ASA which do not indicate that ASA is a human teratogen. Among the salicylates, the vast majority of human data d","page":49,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_012"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"tion and fertility. Concerning effects on development, a CMR category 2 classification was agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_003"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"rved in the top-dose group.","effect":"rved in the top-dose group. There are also several studies with some shortcomings and unusual routes of administration, such as dermal application or intraperitoneal injection, where the effects varied from severe toxicity and 100 % resorption (Infurna et al., 1990 – only abstract available) to neural tube defects (Overman & White, 1983) and lethality, external malformations, visceral and skeletal anomalies and effects on differentiation indices (Kavlock et al., 1982; Daston et al., 1988). The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3- generation study in rats by oral route (Collins et al., 1971). This value will be used for the margin of Safety (MoS) calculation. With respect to developmental toxicity, RAC was of the opinion that MeS should be classified in Cat. 2, mainly due to the weight of evidence put on the human data with ASA which do not indicate that ASA is a human teratogen. Among the salicylates, the vast majority of human data d","page":49,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_012"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"tion and fertility. Concerning effects on development, a CMR category 2 classification was agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_003"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"rved in the top-dose group.","effect":"rved in the top-dose group. There are also several studies with some shortcomings and unusual routes of administration, such as dermal application or intraperitoneal injection, where the effects varied from severe toxicity and 100 % resorption (Infurna et al., 1990 – only abstract available) to neural tube defects (Overman & White, 1983) and lethality, external malformations, visceral and skeletal anomalies and effects on differentiation indices (Kavlock et al., 1982; Daston et al., 1988). The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3- generation study in rats by oral route (Collins et al., 1971). This value will be used for the margin of Safety (MoS) calculation. With respect to developmental toxicity, RAC was of the opinion that MeS should be classified in Cat. 2, mainly due to the weight of evidence put on the human data with ASA which do not indicate that ASA is a human teratogen. Among the salicylates, the vast majority of human data d","page":49,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_012"} |
| SCCS Opinion | NOAEL | <60 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"tion and fertility. Concerning effects on development, a CMR category 2 classification was agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_003"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only).","effect":"ls: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertility and reproductive function A number of studies have been conducted to investigate adverse effects on s","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_011"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | 3 years | NOAEL study | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"dermal, oral and by inhalation – therefore, aggregated exposure has to be taken into consideration. These products could be used by adults but also by children below 3 years old and above. The SED have been calculated for adults and for children, taking into account the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calcula","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_013"} |
| SCCS Opinion | NOAEL | =75 | mg/kg | - | - | 6 years | NOAEL study | {"dose":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 be...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 below). Table 32: MoS calculation for children SED (mg/kg bw/d) (P95) NOAEL MoS Toothpaste, 1-6 years 0,579 75 130 Toothpaste, 6-10 years 0,248 75 302 Toothpaste, 10-14 years 0,118 75 636 Toothpaste, 14-18 years 0,077 75 974 mouthwash, 6-10 years [MeS = 0.1%] 0,155 75 484 mouthwash, 10-14 years [MeS = 0.6%] 0,442 75 170 mouthwash, 14-18 years [MeS = 0.6%] 0,289 75 260 mouthwash + toothpaste, 6-10 years 0,403 75 186 all other skin products (Total from Ficheux, et al.","page":58,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_017"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result was provided. Based on the results, methyl salicylate can be considered to pose no genotoxic hazard. Carcinogenicity The overall totality of evidence, even if limited, indicate","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_004"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only).","effect":"ls: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertility and reproductive function A number of studies have been conducted to investigate adverse effects on s","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_011"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | 3 years | NOAEL study | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"dermal, oral and by inhalation – therefore, aggregated exposure has to be taken into consideration. These products could be used by adults but also by children below 3 years old and above. The SED have been calculated for adults and for children, taking into account the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calcula","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_013"} |
| SCCS Opinion | NOAEL | =75 | mg/kg | - | - | 6 years | NOAEL study | {"dose":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 be...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 below). Table 32: MoS calculation for children SED (mg/kg bw/d) (P95) NOAEL MoS Toothpaste, 1-6 years 0,579 75 130 Toothpaste, 6-10 years 0,248 75 302 Toothpaste, 10-14 years 0,118 75 636 Toothpaste, 14-18 years 0,077 75 974 mouthwash, 6-10 years [MeS = 0.1%] 0,155 75 484 mouthwash, 10-14 years [MeS = 0.6%] 0,442 75 170 mouthwash, 14-18 years [MeS = 0.6%] 0,289 75 260 mouthwash + toothpaste, 6-10 years 0,403 75 186 all other skin products (Total from Ficheux, et al.","page":58,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_017"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result was provided. Based on the results, methyl salicylate can be considered to pose no genotoxic hazard. Carcinogenicity The overall totality of evidence, even if limited, indicate","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_004"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only).","effect":"ls: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertility and reproductive function A number of studies have been conducted to investigate adverse effects on s","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_011"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | 3 years | NOAEL study | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"dermal, oral and by inhalation – therefore, aggregated exposure has to be taken into consideration. These products could be used by adults but also by children below 3 years old and above. The SED have been calculated for adults and for children, taking into account the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calcula","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_013"} |
| SCCS Opinion | NOAEL | =75 | mg/kg | - | - | 6 years | NOAEL study | {"dose":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 be...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 below). Table 32: MoS calculation for children SED (mg/kg bw/d) (P95) NOAEL MoS Toothpaste, 1-6 years 0,579 75 130 Toothpaste, 6-10 years 0,248 75 302 Toothpaste, 10-14 years 0,118 75 636 Toothpaste, 14-18 years 0,077 75 974 mouthwash, 6-10 years [MeS = 0.1%] 0,155 75 484 mouthwash, 10-14 years [MeS = 0.6%] 0,442 75 170 mouthwash, 14-18 years [MeS = 0.6%] 0,289 75 260 mouthwash + toothpaste, 6-10 years 0,403 75 186 all other skin products (Total from Ficheux, et al.","page":58,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_017"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result was provided. Based on the results, methyl salicylate can be considered to pose no genotoxic hazard. Carcinogenicity The overall totality of evidence, even if limited, indicate","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_004"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only).","effect":"ls: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertility and reproductive function A number of studies have been conducted to investigate adverse effects on s","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_011"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | 3 years | NOAEL study | {"dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","effect":"dermal, oral and by inhalation – therefore, aggregated exposure has to be taken into consideration. These products could be used by adults but also by children below 3 years old and above. The SED have been calculated for adults and for children, taking into account the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calcula","page":56,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_013"} |
| SCCS Opinion | NOAEL | =75 | mg/kg | - | - | 6 years | NOAEL study | {"dose":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 be...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 below). Table 32: MoS calculation for children SED (mg/kg bw/d) (P95) NOAEL MoS Toothpaste, 1-6 years 0,579 75 130 Toothpaste, 6-10 years 0,248 75 302 Toothpaste, 10-14 years 0,118 75 636 Toothpaste, 14-18 years 0,077 75 974 mouthwash, 6-10 years [MeS = 0.1%] 0,155 75 484 mouthwash, 10-14 years [MeS = 0.6%] 0,442 75 170 mouthwash, 14-18 years [MeS = 0.6%] 0,289 75 260 mouthwash + toothpaste, 6-10 years 0,403 75 186 all other skin products (Total from Ficheux, et al.","page":58,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_017"} |
| SCCS Opinion | NOAEL | =75 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | {"dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","effect":"ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result was provided. Based on the results, methyl salicylate can be considered to pose no genotoxic hazard. Carcinogenicity The overall totality of evidence, even if limited, indicate","page":16,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_004"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/day | rat | oral | developmental | reproductive toxicity | {"dose":"Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data.","effect":"determine which sex was affected by the treatment. Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_008"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/day | rat | oral | developmental | reproductive toxicity | {"dose":"Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data.","effect":"determine which sex was affected by the treatment. Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_008"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/day | rat | oral | developmental | reproductive toxicity | {"dose":"Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data.","effect":"determine which sex was affected by the treatment. Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_008"} |
| SCCS Opinion | NOAEL | =100 | mg/kg/day | rat | oral | developmental | reproductive toxicity | {"dose":"Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data.","effect":"determine which sex was affected by the treatment. Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP","page":47,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_008"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | - | - | NOAEL study | {"dose":"A NOAEL of 700 mg/m3 (120 ppm) was determined.","effect":"ondition and behaviour recorded throughout the exposure period. Urine and blood were collected for further analyses. After gross examination of the organs, the following organs were also taken for microscopic examination: lungs, liver, kidneys, spleen, adrenals, occasionally heart, jejunum, ileum, and thymus. The authors reported “no toxic signs” (i.e., the animals remained in good condition) and “organs normal” (i.e., histopathological examinations revealed no changes that could be attributed to the treatment). A NOAEL of 700 mg/m3 (120 ppm) was determined.","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_005"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"gans that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_002"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | - | - | NOAEL study | {"dose":"A NOAEL of 700 mg/m3 (120 ppm) was determined.","effect":"ondition and behaviour recorded throughout the exposure period. Urine and blood were collected for further analyses. After gross examination of the organs, the following organs were also taken for microscopic examination: lungs, liver, kidneys, spleen, adrenals, occasionally heart, jejunum, ileum, and thymus. The authors reported “no toxic signs” (i.e., the animals remained in good condition) and “organs normal” (i.e., histopathological examinations revealed no changes that could be attributed to the treatment). A NOAEL of 700 mg/m3 (120 ppm) was determined.","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_005"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"gans that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_002"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | - | - | NOAEL study | {"dose":"A NOAEL of 700 mg/m3 (120 ppm) was determined.","effect":"ondition and behaviour recorded throughout the exposure period. Urine and blood were collected for further analyses. After gross examination of the organs, the following organs were also taken for microscopic examination: lungs, liver, kidneys, spleen, adrenals, occasionally heart, jejunum, ileum, and thymus. The authors reported “no toxic signs” (i.e., the animals remained in good condition) and “organs normal” (i.e., histopathological examinations revealed no changes that could be attributed to the treatment). A NOAEL of 700 mg/m3 (120 ppm) was determined.","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_005"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"gans that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_002"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | - | - | NOAEL study | {"dose":"A NOAEL of 700 mg/m3 (120 ppm) was determined.","effect":"ondition and behaviour recorded throughout the exposure period. Urine and blood were collected for further analyses. After gross examination of the organs, the following organs were also taken for microscopic examination: lungs, liver, kidneys, spleen, adrenals, occasionally heart, jejunum, ileum, and thymus. The authors reported “no toxic signs” (i.e., the animals remained in good condition) and “organs normal” (i.e., histopathological examinations revealed no changes that could be attributed to the treatment). A NOAEL of 700 mg/m3 (120 ppm) was determined.","page":41,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_005"} |
| SCCS Opinion | NOAEL | =120 | ppm | - | oral | - | reproductive toxicity | {"dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","effect":"gans that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","page":15,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_002"} |
| SCCS Opinion | NOAEL | =250 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals:","effect":"oses: 0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertil","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_010"} |
| SCCS Opinion | NOAEL | =250 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals:","effect":"oses: 0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertil","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_010"} |
| SCCS Opinion | NOAEL | =250 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals:","effect":"oses: 0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertil","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_010"} |
| SCCS Opinion | NOAEL | =250 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"dose":"0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals:","effect":"oses: 0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertil","page":48,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_010"} |
| SCCS Opinion | NOAEL | =1633 | - | - | oral | - | NOAEL study | {"dose":"MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_015"} |
| SCCS Opinion | NOAEL | =1633 | - | - | oral | - | NOAEL study | {"dose":"MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_015"} |
| SCCS Opinion | NOAEL | =1633 | - | - | oral | - | NOAEL study | {"dose":"MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_015"} |
| SCCS Opinion | NOAEL | =1633 | - | - | oral | - | NOAEL study | {"dose":"MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002...","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin","page":57,"pdf":"sccs_o_255.pdf","row_type":"noael_study","study_id":"sccs_o_255_noael_015"} |
| SCCS Opinion | NOAEL | =75000 | - | - | oral | - | NOAEL study | {"effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Infants | 0.5 -1 | 34.7 | 0 | 35 | 75000 | 2161","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_011"} |
| SCCS Opinion | NOAEL | =75000 | - | - | oral | - | NOAEL study | {"effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Infants | 0.5 -1 | 34.7 | 0 | 35 | 75000 | 2161","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_011"} |
| SCCS Opinion | NOAEL | =75000 | - | - | oral | - | NOAEL study | {"effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Infants | 0.5 -1 | 34.7 | 0 | 35 | 75000 | 2161","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_011"} |
| SCCS Opinion | NOAEL | =75000 | - | - | oral | - | NOAEL study | {"effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Infants | 0.5 -1 | 34.7 | 0 | 35 | 75000 | 2161","page":19,"pdf":"sccs_o_274.pdf","row_type":"noael_study","study_id":"sccs_o_274_noael_011"} |
ECHA 21 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ECHA | LEL | =1440 | mg/kg bw/day | Mouse | oral | short-term; 14 days | short-term | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca26e4b0a7c65d2208c8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID:15850469:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_fd542456f634aa274c22a48f9494c703 |
| ECHA | LOAEL | =150 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa64e4b0a7c65d1b5ab5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/9/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15855154_15856670_15863175:M/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_f6833eb1ae97026fb27ca5d6c1a39051 |
| ECHA | LOAEL | <=390 | mg/kg bw/day | Rat | oral | chronic; 2 years | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eae65e4b0a7c65d1c8f62; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/13593/7/6/2?documentUUID=b703ebdb-8235-470e-830d-33622f851a8f; YEAR=2006; ORIGINAL_YEAR=2006; TOXICOLOGICAL_EFFECT=gross pathology|histopathology: non-neoplastic; TOXICOLOGICAL_EFFECT_CATEGORY=gross pathology|nonneoplastic histopathology; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15843394_15845506_15849531: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_e0d52aebc09d8ebc29b71a67380f40a7 |
| ECHA | LOAEL | =1000 | mg/kg bw/day | Rat | oral | subchronic; 11 weeks | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacf9e4b0a7c65d1c1cd0; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15833479_15846221_15850466: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_93c1d94c543fe5a8f7901cc7fad45a80 |
| ECHA | LOAEL | ~1080 | mg/kg bw/day | Rat | oral | subchronic; 10 weeks | subchronic | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacf9e4b0a7c65d1c1cc8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15829898_15844449_15850464_15850465:-:--; 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_9532b15e9d0ac947aca33e8a60849db1 |
| ECHA | NOAEL | =3.9 | mg/kg bw/day | Rat | oral | chronic; 17 weeks | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaec9e4b0a7c65d1cafdd; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23278/7/6/2?documentUUID=da8d09a8-236b-4588-8c8b-906fd051ede5; YEAR=1980; ORIGINAL_YEAR=1980; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15844855_15850467: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_001dc74ed3b177e3504894f282990fb3 |
| ECHA | NOAEL | =50 | mg/kg bw/day | Rat | oral | chronic; 2 years | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacf9e4b0a7c65d1c1cde; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15843394_15845506_15849531: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_3935f812974f96857be1e4431902908d |
| ECHA | NOAEL | ~60 | mg/kg bw/day | Rat | injection | - | reproduction developmental | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d199e4b0a7c65d22f375; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/9/3?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; TOXICOLOGICAL_EFFECT=maternal: body weight and weight gain|maternal: food consumption and compound intake; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|food and/or water consumption; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822153_15822891:F:-maternal; 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_07663934999e2f203a59f983032f8675 |
| ECHA | NOAEL | =75 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa64e4b0a7c65d1b5ab5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/9/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15855154_15856670_15863175:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_9cd5d296278c0552edcece5ecf246c73 |
| ECHA | NOAEL | >=78 | mg/kg bw/day | Rat | oral | chronic; 2 years | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eae65e4b0a7c65d1c8f62; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/13593/7/6/2?documentUUID=b703ebdb-8235-470e-830d-33622f851a8f; YEAR=2006; ORIGINAL_YEAR=2006; TOXICOLOGICAL_EFFECT=body weight and weight gain|clinical signs|gross pathology|haematology|histopathology: neoplastic|histopathology: non-neoplastic|mortality|organ weights and organ / body weight ratios; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|cancer|clinical signs|gross pathology|hematology|mortality/survival|nonneoplastic histopathology|organ weight; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15843394_15845506_15849531:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_86215c1a529b925fb1dbb88bff864215 |
| ECHA | NOAEL | =100 | mg/kg bw/day | Rat | injection | - | developmental | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d199e4b0a7c65d22f37f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/9/3?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; TOXICOLOGICAL_EFFECT=fetus: fetal/pup body weight changes|fetus: external malformations|fetus: skeletal malformations|fetus: visceral malformations; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15821594_15823189: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_307960d3e8400980a834d8ef2a03ae39 |
| ECHA | NOAEL | =167 | mg/kg bw/day | Dog | oral | chronic; 6 months | chronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaec9e4b0a7c65d1cafe4; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23278/7/6/2?documentUUID=da8d09a8-236b-4588-8c8b-906fd051ede5; YEAR=1980; ORIGINAL_YEAR=1980; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15847336_15847530:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_fd5b7b2ea6053856cdd1fc94acd76299 |
| ECHA | NOAEL | =180 | mg/kg bw/day | Rat | oral | subchronic; 12 weeks | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaec9e4b0a7c65d1cafc7; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23278/7/6/2?documentUUID=da8d09a8-236b-4588-8c8b-906fd051ede5; YEAR=1980; ORIGINAL_YEAR=1980; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15837592_15850468: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_bf7f4f22a81bafd080cfd6434e4a2907 |
| ECHA | NOAEL | =250 | ppm | Dog | oral | subchronic; 59 days | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaec9e4b0a7c65d1cafb1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23278/7/6/2?documentUUID=da8d09a8-236b-4588-8c8b-906fd051ede5; YEAR=1980; ORIGINAL_YEAR=1980; STUDY_GROUP=ECHA IUCLID:15831119: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_76e43cf0b596e7af01866d58f46b8eab |
| ECHA | NOAEL | =250 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa64e4b0a7c65d1b5ab5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/9/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Toxicity Reproduction_15855154_15856670_15863175:M/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_a2686a875f1a7e342ed4c92dbc6b0442 |
| ECHA | NOAEL | =300 | mg/kg bw/day | Dog | oral | short-term; 3 days | short-term | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca26e4b0a7c65d2208d3; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15840352_15842660: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_824605e5b68f075238c5fffde35f0fa1 |
| ECHA | NOAEL | =450 | mg/kg bw/day | Rat | oral | subchronic; 11 weeks | subchronic | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacf9e4b0a7c65d1c1cca; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15833479_15846221_15850466:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_696e8db4af108840dbdbcd6b9547d02d |
| ECHA | NOAEL | =500 | mg/kg bw/day | Mouse | oral | - | reproduction developmental | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eab47e4b0a7c65d1b98f0; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23278/7/9/2?documentUUID=da8d09a8-236b-4588-8c8b-906fd051ede5; YEAR=1980; ORIGINAL_YEAR=1980; STUDY_GROUP=ECHA IUCLID:15860563:M/F:P0-; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_eb28c7b17438e1ed88cd53c4a877187f |
| ECHA | NOAEL | ~864 | mg/kg bw/day | Rat | oral | subchronic; 10 weeks | subchronic | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacf9e4b0a7c65d1c1cc8; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/2?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15829898_15844449_15850464_15850465:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_4b2a66294645d2289a5cec7c6bbedd15 |
| ECHA | NOEC | =8 | mg/m3 | Rat | inhalation | chronic; 4 months | chronic | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/3?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID:15828668: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_0cd2e30ba3f78218e7e4ed7dde7ec723 |
| ECHA | NOEC | =700 | mg/m3 | Rat | inhalation | short-term; 4 weeks | short-term | QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/19733/7/6/3?documentUUID=90a9c6a5-ac66-4269-ae02-5ea7eac1f9ec; YEAR=2003; ORIGINAL_YEAR=2003; STUDY_GROUP=ECHA IUCLID:15827455: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_c6bf09736ca1327983b113b181d32239 |
ToxValDB GESTIS DNEL 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB GESTIS DNEL | DNEL systemic | =7.05 | 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_dup_-_15633499_15633500_15633501:-:--; 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_3b935e4c79b6fcd475386e50ae31f4d9 |
| ToxValDB GESTIS DNEL | DNEL systemic | =9.87 | 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_dup_-_15633499_15633500_15633501:-:--; 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_b526a3bf60a475db4fbac3303362a007 |
| ToxValDB GESTIS DNEL | DNEL systemic | =17.5 | 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_dup_-_15633499_15633500_15633501:-:--; 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_f94df72fabb8220e3bcf1453aea71234 |
WHO/JECFA 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| WHO/JECFA | ADI | <=0.5 | mg/kg | Human | oral | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/650b0065e4b0d99f5a883833; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://apps.who.int/food-additives-contaminants-jecfa-database/; SUBSOURCE_URL=https://apps.who.int/food-additives-contaminants-jecfa-database/Home/Chemical/341; YEAR=2001; ORIGINAL_YEAR=2001; STUDY_GROUP=WHO JECFA ADI:15715609:-:--; 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_9a8d1a62bddf57588e4d8403daf084c2 |
Regulatory source 36 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| Regulatory source | - | 0.9 | % | rat | oral | 12 weeks | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=0.9; DOSE=In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations.; EFFECT=in bones (femur, humerus, tibia, and radius). The effects of methyl salicylate administration on bones have been reproduced in rats in a series of short-term experiments conducted by Abbott and Harrisson (1978). In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations. At the highest level, there were observations of increased density in the femur, humerus, tibia and radius. The NOAEL for bone effects was determined to be 0.9%, which was equivalent to approximately 863 mg/kg bw/day. The authors noted that the effects on bone appeared to be species-specific as they were only observed in rats and not in other experimental animals. Webb and Hansen (1963) also investigated the effects of chronic exposure in beagle dogs (n=2/sex/group), whereby methyl salicylate was administered as oral capsules containing 0, 50, 150, 350 mg/kg/day, 6 days a week for 2 years. The animals were weighed weekly and hema; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations.","duration":"12 weeks","effect":"in bones (femur, humerus, tibia, and radius). The effects of methyl salicylate administration on bones have been reproduced in rats in a series of short-term experiments conducted by Abbott and Harrisson (1978). In these experiments, Sprague-Dawley rats were administered 0.2 – 2% methyl salicylate in the diet (equivalent to 100-1000 mg/kg bw/day) for 11-12 weeks, and then subjected to X-ray examinations. At the highest level, there were observations of increased density in the femur, humerus, tibia and radius. The NOAEL for bone effects was determined to be 0.9%, which was equivalent to approximately 863 mg/kg bw/day. The authors noted that the effects on bone appeared to be species-specific as they were only observed in rats and not in other experimental animals. Webb and Hansen (1963) also investigated the effects of chronic exposure in beagle dogs (n=2/sex/group), whereby methyl salicylate was administered as oral capsules containing 0, 50, 150, 350 mg/kg/day, 6 days a week for 2 years. The animals were weighed weekly and hema","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"%","noael_value":"0.9","page":40,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_003"} |
| Regulatory source | - | 2.52 | % | - | oral | 6 years | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=2.52; EFFECT=SCCS/1654/23 Final version Scientific Advice on methyl salicylate (methyl 2-hydroxybenzoate) - children exposure ___________________________________________________________________________________________ _________________________________________________________________________ 21 rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. For systemic effects, considering all dermally applied products include in the table 2 above and oral exposure via toothpastes, the MOS is above 100 for individual exposure as well as for aggregated exposure. 4. CONCLUSION In the SCCS/1633/21 Opinion, the Committee concluded that Methyl Salicylate in toothpaste is safe for children under 6 years of age when used up to the maximum concentration of 2.52%. 1. In light of the data provided and taking under consideration the conclusions of SCCS/1633/21 and th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"","duration":"6 years","effect":"SCCS/1654/23 Final version Scientific Advice on methyl salicylate (methyl 2-hydroxybenzoate) - children exposure ___________________________________________________________________________________________ _________________________________________________________________________ 21 rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. For systemic effects, considering all dermally applied products include in the table 2 above and oral exposure via toothpastes, the MOS is above 100 for individual exposure as well as for aggregated exposure. 4. CONCLUSION In the SCCS/1633/21 Opinion, the Committee concluded that Methyl Salicylate in toothpaste is safe for children under 6 years of age when used up to the maximum concentration of 2.52%. 1. In light of the data provided and taking under consideration the conclusions of SCCS/1633/21 and th","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"%","noael_value":"2.52","page":21,"route":"oral","species":"","study_id":"sccs_o_274_noael_009"} |
| Regulatory source | - | 8 | - | - | oral | 6 years | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=unclear:able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.; EFFECT=able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"","duration":"6 years","effect":"able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"","noael_value":"unclear:able 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in children between 0.5 and 6 years old For systemic effects, considering exposure to methyl salicylate via toothpastes, the margin of safety is above 100. • Aggregated exposure Table 8: MoS calculation for dermally applied and oral products (toothpaste) containing methyl salicylate in children below between 0.5 and 6 years old Age categories Dermal MeS in products (µg/kg bw/d) ToothPaste (µg/kg bw/d) Aggregated (µg/kg bw/d) NOAEL Adj (µg/kg bw/d) MOS Infants 0.5 -1 34.7 0 35 75000 2161 Toddlers 1-3 32.7 430 463 75000 162 Children 3-6 83.9 370 454 75000 165 For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100.","page":19,"route":"oral","species":"","study_id":"sccs_o_274_noael_007"} |
| Regulatory source | - | 8 | - | - | oral | - | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=unclear:Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Age categories | Dermal MeS in products (µg/kg bw/d) | ToothPaste (µg/kg bw/d) | Aggregated (µg/kg bw/d) | NOAEL Adj (µg/kg bw/d) | MOS; EFFECT=Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Age categories | Dermal MeS in products (µg/kg bw/d) | ToothPaste (µg/kg bw/d) | Aggregated (µg/kg bw/d) | NOAEL Adj (µg/kg bw/d) | MOS; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"","duration":"","effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Age categories | Dermal MeS in products (µg/kg bw/d) | ToothPaste (µg/kg bw/d) | Aggregated (µg/kg bw/d) | NOAEL Adj (µg/kg bw/d) | MOS","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"","noael_value":"unclear:Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Age categories | Dermal MeS in products (µg/kg bw/d) | ToothPaste (µg/kg bw/d) | Aggregated (µg/kg bw/d) | NOAEL Adj (µg/kg bw/d) | MOS","page":19,"route":"oral","species":"","study_id":"sccs_o_274_noael_010"} |
| Regulatory source | - | 31 | - | - | inhalation | - | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=unclear:Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed; DOSE=L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed; EFFECT=Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","duration":"","effect":"Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"","noael_value":"unclear:Table 31: MoS calculation for Adults: L | o | cal effect by | inhalation: the | NOAEL of 7 | 0 | 0 mg/m3 ( | 120 | ppm) f | rom | G | age (197 | 0) is u | sed","page":57,"route":"inhalation","species":"","study_id":"sccs_o_255_noael_023"} |
| Regulatory source | - | 50 | mg/kg bw/day | rat | - | chronic | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=50; DOSE=The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers.; EFFECT=SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 41 ovary/uterus. The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers. Microscopically, these livers had larger hepatic cells than those in control. The NOAEL was determined to be 50 mg/kg bw/day on the basis of reduced body weight and liver effects observed at the next dose level (150 mg/kg bw/day). No treatment-related, adverse effects were observed when weanling albino rats were administered methyl salicylate derived from the oil of sweet birch, which can comprise up to 90.4% of the extract (Tisserand and Young, 2014). In a two-year chronic study, the experimental animals (n=25/sex/group, unknown strain) were administered 700 and 2100 ppm of oil of sweet birch throu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers.","duration":"chronic","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 41 ovary/uterus. The administration of 150 and 350 mg/kg bw/day resulted in reduced body weight gains and enlarged livers. Microscopically, these livers had larger hepatic cells than those in control. The NOAEL was determined to be 50 mg/kg bw/day on the basis of reduced body weight and liver effects observed at the next dose level (150 mg/kg bw/day). No treatment-related, adverse effects were observed when weanling albino rats were administered methyl salicylate derived from the oil of sweet birch, which can comprise up to 90.4% of the extract (Tisserand and Young, 2014). In a two-year chronic study, the experimental animals (n=25/sex/group, unknown strain) were administered 700 and 2100 ppm of oil of sweet birch throu","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":41,"route":"","species":"rat","study_id":"sccs_o_255_noael_004"} |
| Regulatory source | - | 75 | mg/kg bw/d | rat | oral | 3 years | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=75; DOSE=To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=dermal, oral and by inhalation – therefore, aggregated exposure has to be taken into consideration. These products could be used by adults but also by children below 3 years old and above. The SED have been calculated for adults and for children, taking into account the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calcula; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","duration":"3 years","effect":"dermal, oral and by inhalation – therefore, aggregated exposure has to be taken into consideration. These products could be used by adults but also by children below 3 years old and above. The SED have been calculated for adults and for children, taking into account the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calcula","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"75","page":56,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_013"} |
| Regulatory source | - | 75 | mg/kg | - | - | 6 years | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=75; DOSE=SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 be...; EFFECT=SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 below). Table 32: MoS calculation for children SED (mg/kg bw/d) (P95) NOAEL MoS Toothpaste, 1-6 years 0,579 75 130 Toothpaste, 6-10 years 0,248 75 302 Toothpaste, 10-14 years 0,118 75 636 Toothpaste, 14-18 years 0,077 75 974 mouthwash, 6-10 years [MeS = 0.1%] 0,155 75 484 mouthwash, 10-14 years [MeS = 0.6%] 0,442 75 170 mouthwash, 14-18 years [MeS = 0.6%] 0,289 75 260 mouthwash + toothpaste, 6-10 years 0,403 75 186 all other skin products (Total from Ficheux, et al.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 be...","duration":"6 years","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 58 The MoS was calculated considering the NOAEL of 75 mg/kg/bw /day as for adults (see table 32 below). Table 32: MoS calculation for children SED (mg/kg bw/d) (P95) NOAEL MoS Toothpaste, 1-6 years 0,579 75 130 Toothpaste, 6-10 years 0,248 75 302 Toothpaste, 10-14 years 0,118 75 636 Toothpaste, 14-18 years 0,077 75 974 mouthwash, 6-10 years [MeS = 0.1%] 0,155 75 484 mouthwash, 10-14 years [MeS = 0.6%] 0,442 75 170 mouthwash, 14-18 years [MeS = 0.6%] 0,289 75 260 mouthwash + toothpaste, 6-10 years 0,403 75 186 all other skin products (Total from Ficheux, et al.","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg","noael_value":"75","page":58,"route":"","species":"","study_id":"sccs_o_255_noael_017"} |
| Regulatory source | - | 75 | mg/kg bw/d | rat | oral | 6 years | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=75; DOSE=The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=lation of the MoS) Methyl salicylate can be used in different product categories of cosmetic products that could lead to exposure depending on age by dermal or oral routes – therefore, aggregated exposure has to be taken into consideration. In this section to answer the mandate addressed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all produc; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","duration":"6 years","effect":"lation of the MoS) Methyl salicylate can be used in different product categories of cosmetic products that could lead to exposure depending on age by dermal or oral routes – therefore, aggregated exposure has to be taken into consideration. In this section to answer the mandate addressed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all produc","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"75","page":17,"route":"oral","species":"rat","study_id":"sccs_o_274_noael_005"} |
| Regulatory source | - | 75 | mg/kg bw/d | rat | oral | 6 years | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=75; DOSE=The SCCS has used as PoD the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=the oral mucosa. The Systemic Exposure Doses (SED) of methyl salicylate following dermal application and oral uses of cosmetic products were calculated by age categories taken into account the amount of products applied as reported in table 2. Aggregated exposure has also been considered. To assess the risk of methyl salicylate by systemic exposure and in complement to opinion SCCS/1633/21, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used as PoD the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The SCCS has used as PoD the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","duration":"6 years","effect":"the oral mucosa. The Systemic Exposure Doses (SED) of methyl salicylate following dermal application and oral uses of cosmetic products were calculated by age categories taken into account the amount of products applied as reported in table 2. Aggregated exposure has also been considered. To assess the risk of methyl salicylate by systemic exposure and in complement to opinion SCCS/1633/21, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used as PoD the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"75","page":20,"route":"oral","species":"rat","study_id":"sccs_o_274_noael_008"} |
| Regulatory source | - | 120 | ppm | - | - | - | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=120; DOSE=A NOAEL of 700 mg/m3 (120 ppm) was determined.; EFFECT=ondition and behaviour recorded throughout the exposure period. Urine and blood were collected for further analyses. After gross examination of the organs, the following organs were also taken for microscopic examination: lungs, liver, kidneys, spleen, adrenals, occasionally heart, jejunum, ileum, and thymus. The authors reported “no toxic signs” (i.e., the animals remained in good condition) and “organs normal” (i.e., histopathological examinations revealed no changes that could be attributed to the treatment). A NOAEL of 700 mg/m3 (120 ppm) was determined.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"A NOAEL of 700 mg/m3 (120 ppm) was determined.","duration":"","effect":"ondition and behaviour recorded throughout the exposure period. Urine and blood were collected for further analyses. After gross examination of the organs, the following organs were also taken for microscopic examination: lungs, liver, kidneys, spleen, adrenals, occasionally heart, jejunum, ileum, and thymus. The authors reported “no toxic signs” (i.e., the animals remained in good condition) and “organs normal” (i.e., histopathological examinations revealed no changes that could be attributed to the treatment). A NOAEL of 700 mg/m3 (120 ppm) was determined.","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"ppm","noael_value":"120","page":41,"route":"","species":"","study_id":"sccs_o_255_noael_005"} |
| Regulatory source | - | 120 | ppm | - | oral | 6 years | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=120; DOSE=Local effect by inhalation: the NOAEL of 700 mg/m3 (120 ppm) from Gage (1970) is used to compare with the concentration of MeS in the lungs.; EFFECT=r 0.002 0.0000008 0.0000000288 0 0.00000 75 90492278 Lip products 0.030 0.00027 0.000003744 0 0.00027 75 273979 Toothpaste* 2.520 0 0 0.0544 0.0544 75 1379 Mouthwash* 0.600 0 0 0.19524 0.19524 75 384 Mouth Spray* 0.650 0 0 0.173 0.173 75 434 Total 0.0900446 0.003307965 0.42264 0.51599 75 145 * 100% oral/mucosal absorption as a worst case scenario For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100. Local effect by inhalation: the NOAEL of 700 mg/m3 (120 ppm) from Gage (1970) is used to compare with the concentration of MeS in the lungs. For spray products, for an adult, the dose of MeS would be 108 µg in 10 m3 equivalent to a concentration of 10.8 µg/m3, which leads to a MoS of around 65 000. For dermally applied products, part of the dose will volatilize. Based on the hypothesis described above, the concentration is 14.73 µg/m3 which leads to a MoS of around 47 000. For Children The SCCS considers that for children above 6 years old, toothp; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"Local effect by inhalation: the NOAEL of 700 mg/m3 (120 ppm) from Gage (1970) is used to compare with the concentration of MeS in the lungs.","duration":"6 years","effect":"r 0.002 0.0000008 0.0000000288 0 0.00000 75 90492278 Lip products 0.030 0.00027 0.000003744 0 0.00027 75 273979 Toothpaste* 2.520 0 0 0.0544 0.0544 75 1379 Mouthwash* 0.600 0 0 0.19524 0.19524 75 384 Mouth Spray* 0.650 0 0 0.173 0.173 75 434 Total 0.0900446 0.003307965 0.42264 0.51599 75 145 * 100% oral/mucosal absorption as a worst case scenario For systemic effects, considering all products taken individually and also the aggregated exposure, the margin of safety is above 100. Local effect by inhalation: the NOAEL of 700 mg/m3 (120 ppm) from Gage (1970) is used to compare with the concentration of MeS in the lungs. For spray products, for an adult, the dose of MeS would be 108 µg in 10 m3 equivalent to a concentration of 10.8 µg/m3, which leads to a MoS of around 65 000. For dermally applied products, part of the dose will volatilize. Based on the hypothesis described above, the concentration is 14.73 µg/m3 which leads to a MoS of around 47 000. For Children The SCCS considers that for children above 6 years old, toothp","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"ppm","noael_value":"120","page":57,"route":"oral","species":"","study_id":"sccs_o_255_noael_016"} |
| Regulatory source | - | 1633 | - | - | oral | - | - | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=unclear:SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin; DOSE=MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002...; EFFECT=SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002...","duration":"","effect":"SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1633/21 Final version Opinion on methyl salicylate (methyl 2-hydroxybenzoate) ___________________________________________________________________________________________ _________________________________________________________________________ 57 For adult Table 31: MoS calculation for Adults Products Concentration % SED dermal mg/kg bw/d Sed inhal mg/kg bw/d SED oral mg/kg bw/d SED Tot mg/kg bw/d NOAEL MOS Hydroalcoholic - based Fragrances 0.600 0.014 0.00038 0 0.01438 75 5216 Shower gel 0.060 0.0008 0.000023 0 0.00082 75 91130 Shampoo 0.060 0.00045 0.00013 0 0.00058 75 129310 Hair conditioner 0.060 0.0002 0.0000054 0 0.00021 75 365141 Hand soap 0.600 0.0099 0.001 0 0.01090 75 6881 Body lotion 0.060 0.03696 0.001 0 0.03796 75 1976 Face cream 0.060 0.007242 0.0002016 0 0.00744 75 10076 Hand cream 0.060 0.00981 0.0002736 0 0.01008 75 7438 Deodorant non- spray 0.060 0.006624 0.0001872 0 0.00681 75 11011 Hair Stylin","page":57,"route":"oral","species":"","study_id":"sccs_o_255_noael_015"} |
| Regulatory source | - | 75000 | - | - | oral | - | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=75000; EFFECT=Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Infants | 0.5 -1 | 34.7 | 0 | 35 | 75000 | 2161; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"","duration":"","effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Infants | 0.5 -1 | 34.7 | 0 | 35 | 75000 | 2161","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"","noael_value":"75000","page":19,"route":"oral","species":"","study_id":"sccs_o_274_noael_011"} |
| Regulatory source | - | 75000 | - | - | oral | - | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=75000; EFFECT=Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Toddlers | 1-3 | 32.7 | 430 | 463 | 75000 | 162; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"","duration":"","effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Toddlers | 1-3 | 32.7 | 430 | 463 | 75000 | 162","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"","noael_value":"75000","page":19,"route":"oral","species":"","study_id":"sccs_o_274_noael_012"} |
| Regulatory source | - | 75000 | - | - | oral | - | - | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=75000; EFFECT=Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Children | 3-6 | 83.9 | 370 | 454 | 75000 | 165; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"","duration":"","effect":"Table 8: MoS calculation for oral products (toothpaste) containing methyl salicylate in: Children | 3-6 | 83.9 | 370 | 454 | 75000 | 165","endpoint":"","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"","noael_value":"75000","page":19,"route":"oral","species":"","study_id":"sccs_o_274_noael_013"} |
| Regulatory source | dermal absorption | 50 | % | rat | oral | - | dermal absorption | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=50; DOSE=To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=t the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For lipstick and oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product ty; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","duration":"","effect":"t the age of children (as the use of cosmetic products may differ due to age-related different behaviors).The exposure to product (Eproduct) value has also been normalised by weight. To assess the risk of MeS by systemic exposure, the SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of MeS from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For lipstick and oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product ty","endpoint":"dermal absorption","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"%","noael_value":"50","page":56,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_014"} |
| Regulatory source | dermal absorption | 50 | % | rat | oral | 6 years | dermal absorption | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=50; DOSE=The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=essed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product types are given; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971).","duration":"6 years","effect":"essed to SCCS and in complement to opinion SCCS/1633/21, to assess the risk of methyl salicylate by systemic exposure, the MOS was calculated separately for children between 0.5 to 1, 1 to 3 and 3 to 6 years old. The SCCS has used the NOAEL of 75 mg/kg bw/d derived from the 3-generation study in rats by oral route (Collins et al., 1971). Because of the evidence for rapid and almost complete absorption of methyl salicylate from the oral route, the SCCS has not applied any adjustment for oral bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in section 3.2.4. A generic maximal value for skin penetration of methyl salicylate of 50% (see section 3.2.1) has been used for all products in these calculations where dermal absorption needs to be factored in to calculate a systemic exposure dose (SED). For oral care products, a worst-case value of 100% absorption is used for passage across the oral mucosa. The calculations of MoS for different product types are given","endpoint":"dermal absorption","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"%","noael_value":"50","page":17,"route":"oral","species":"rat","study_id":"sccs_o_274_noael_006"} |
| Regulatory source | developmental toxicity | <60 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=< 60; DOSE=rved in the top-dose group.; EFFECT=rved in the top-dose group. There are also several studies with some shortcomings and unusual routes of administration, such as dermal application or intraperitoneal injection, where the effects varied from severe toxicity and 100 % resorption (Infurna et al., 1990 – only abstract available) to neural tube defects (Overman & White, 1983) and lethality, external malformations, visceral and skeletal anomalies and effects on differentiation indices (Kavlock et al., 1982; Daston et al., 1988). The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3- generation study in rats by oral route (Collins et al., 1971). This value will be used for the margin of Safety (MoS) calculation. With respect to developmental toxicity, RAC was of the opinion that MeS should be classified in Cat. 2, mainly due to the weight of evidence put on the human data with ASA which do not indicate that ASA is a human teratogen. Among the salicylates, the vast majority of human data d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"rved in the top-dose group.","duration":"developmental","effect":"rved in the top-dose group. There are also several studies with some shortcomings and unusual routes of administration, such as dermal application or intraperitoneal injection, where the effects varied from severe toxicity and 100 % resorption (Infurna et al., 1990 – only abstract available) to neural tube defects (Overman & White, 1983) and lethality, external malformations, visceral and skeletal anomalies and effects on differentiation indices (Kavlock et al., 1982; Daston et al., 1988). The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3- generation study in rats by oral route (Collins et al., 1971). This value will be used for the margin of Safety (MoS) calculation. With respect to developmental toxicity, RAC was of the opinion that MeS should be classified in Cat. 2, mainly due to the weight of evidence put on the human data with ASA which do not indicate that ASA is a human teratogen. Among the salicylates, the vast majority of human data d","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"< 60","page":49,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_012"} |
| Regulatory source | developmental toxicity | 75 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=75; DOSE=The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","duration":"developmental","effect":"ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"75","page":61,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_021"} |
| Regulatory source | developmental toxicity | 75 | mg/kg bw/d | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=75; DOSE=The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result was provided. Based on the results, methyl salicylate can be considered to pose no genotoxic hazard. Carcinogenicity The overall totality of evidence, even if limited, indicate; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","duration":"developmental","effect":"ation for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result was provided. Based on the results, methyl salicylate can be considered to pose no genotoxic hazard. Carcinogenicity The overall totality of evidence, even if limited, indicate","endpoint":"developmental toxicity","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"75","page":16,"route":"oral","species":"rat","study_id":"sccs_o_274_noael_004"} |
| Regulatory source | reproductive toxicity | 0.5 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=0.5; DOSE=The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...; EFFECT=as also been conducted by the applicant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","duration":"2-year","effect":"as also been conducted by the applicant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by th","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg/day","noael_value":"0.5","page":29,"route":"oral","species":"dog","study_id":"sccs_o_255_noael_001"} |
| Regulatory source | reproductive toxicity | 34 | - | - | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=unclear:Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental; EFFECT=Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"","duration":"developmental","effect":"Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"","noael_value":"unclear:Table 34. The l: An oral NOAEL of 100 m | g/kg/day is | establi | shed | for reproductive | and | developmental","page":47,"route":"oral","species":"","study_id":"sccs_o_255_noael_022"} |
| Regulatory source | reproductive toxicity | 50 | mg/kg/day | dog | oral | 2-year | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=50; DOSE=The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...; EFFECT=icant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by the Frenc; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl...","duration":"2-year","effect":"icant for this dossier to include all up-to-date references to January 2020. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2002), United States Environmental Protection Agency Biopesticide and Pollution Prevention Division (US-EPA 2005), Norwegian Food Safety Authority (NFSA (Mattilsynet) 2012), and the European Food Safety Authority (EFSA 2012a) currently define an acceptable daily intake (ADI) for methyl salicylate of 0.5 mg/kg/day. This ADI is based on using the no observed adverse effect level (NOAEL) of 50 mg/kg/day as the point of departure reported in the selected 2-year oral study in dogs and rodents (Webb & Hansen, 1963). Since then, studies by the US National Toxicology Programme (NTP 1984a, 1984b) and high quality OECD guideline reproductive and developmental studies have also been performed in 2006 (US-FDA, 2012), which were not available when JECFA set the ADI, and have not been reviewed comprehensively in other foods and cosmetic safety dossiers. In 2013, methyl salicylate was proposed by the Frenc","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg/day","noael_value":"50","page":29,"route":"oral","species":"dog","study_id":"sccs_o_255_noael_002"} |
| Regulatory source | reproductive toxicity | 50 | mg/kg bw/day | human | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=50; DOSE=For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation:; LOAEL_VALUE=585 mg/kg bw/day; EFFECT=f animals were examined. Furthermore, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at a lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following value could be identified: For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation: A NOAEL of 700 mg/m3 (120 ppm) 3.3.5 Reproductive toxicity Human data No human data are available on MeS. However, because human data are available for another salicylate ester, ASA, several – mostly retrospective – publications with aspirin during pregnancy could be used as supportive information to assess the reproductive toxicity of MeS. It is difficult or even impossible to estimate the causal relationship betwe; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation:","duration":"","effect":"f animals were examined. Furthermore, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at a lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following value could be identified: For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation: A NOAEL of 700 mg/m3 (120 ppm) 3.3.5 Reproductive toxicity Human data No human data are available on MeS. However, because human data are available for another salicylate ester, ASA, several – mostly retrospective – publications with aspirin during pregnancy could be used as supportive information to assess the reproductive toxicity of MeS. It is difficult or even impossible to estimate the causal relationship betwe","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"585 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"50","page":42,"route":"oral","species":"human","study_id":"sccs_o_255_noael_006"} |
| Regulatory source | reproductive toxicity | 50 | mg/kg bw/day | - | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=50; DOSE=Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):; LOAEL_VALUE=150 mg/kg bw/day; EFFECT=rthermore, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at a lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity Concerning fertility and reproductive function, there is insufficient evidence that MeS exhibits adverse effects on sexual function and fertility. Therefore the SCCS concurs with the proposal by RAC that no classification is justified for MeS for adverse effects on sexual function and fertility. Conc; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","duration":"","effect":"rthermore, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at a lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity Concerning fertility and reproductive function, there is insufficient evidence that MeS exhibits adverse effects on sexual function and fertility. Therefore the SCCS concurs with the proposal by RAC that no classification is justified for MeS for adverse effects on sexual function and fertility. Conc","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"150 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"50","page":61,"route":"oral","species":"","study_id":"sccs_o_255_noael_018"} |
| Regulatory source | reproductive toxicity | 50 | mg/kg bw/day | - | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=50; DOSE=Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):; LOAEL_VALUE=150 mg/kg bw/day; EFFECT=re, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","duration":"","effect":"re, it is not indicated if a statistical analysis was performed on histopathological findings. Therefore, it cannot be excluded that effects can occur at lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles, clothing,","loael_value":"150 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"50","page":15,"route":"oral","species":"","study_id":"sccs_o_274_noael_001"} |
| Regulatory source | reproductive toxicity | <60 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=< 60; DOSE=The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=and fertility. Concerning effects on development, a CMR category 2 classification has been agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","duration":"developmental","effect":"and fertility. Concerning effects on development, a CMR category 2 classification has been agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"< 60","page":61,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_020"} |
| Regulatory source | reproductive toxicity | <60 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=< 60; DOSE=The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).; EFFECT=tion and fertility. Concerning effects on development, a CMR category 2 classification was agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971).","duration":"developmental","effect":"tion and fertility. Concerning effects on development, a CMR category 2 classification was agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for methyl salicylate is consistent with the 2016 CMR category 2 classification decision for salicylic acid. Salicylic acid is the principal primary metabolite of methyl salicylate via the dermal and oral routes: systemically the body is exposed to more salicylic acid metabolite than to the parent compound. The lowest developmental NOAEL are < 60 mg/kg bw/d in rats exposed subcutaneously from GD6 to LD21 (FDA, 2006b) and 75 mg/kg bw/d in a 3-generation study in rats by oral route (Collins et al., 1971). The NOAEL of 75 mg/kg bw/d is used by SCCS for the calculation of the MoS. Mutagenicity / genotoxicity The genotoxicity of methyl salicylate was investigated with valid in vitro genotoxicity tests for bacterial gene mutations and chromosomal aberrations with negative results. Additionally, a valid in vivo micronucleus in rats with negative result","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles, clothing,","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"< 60","page":16,"route":"oral","species":"rat","study_id":"sccs_o_274_noael_003"} |
| Regulatory source | reproductive toxicity | 75 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=75; DOSE=20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only).; EFFECT=ls: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertility and reproductive function A number of studies have been conducted to investigate adverse effects on s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only).","duration":"developmental","effect":"ls: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertility and reproductive function A number of studies have been conducted to investigate adverse effects on s","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":48,"route":"","species":"rat","study_id":"sccs_o_255_noael_011"} |
| Regulatory source | reproductive toxicity | 100 | mg/kg/day | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=100; DOSE=Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data.; EFFECT=determine which sex was affected by the treatment. Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data.","duration":"developmental","effect":"determine which sex was affected by the treatment. Greene et al (2017) performed a quantitative dose-response assessment using benchmark dose (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":47,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_008"} |
| Regulatory source | reproductive toxicity | 100 | mg/kg/day | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=100; DOSE=Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34.; EFFECT=e (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP: No; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34.","duration":"developmental","effect":"e (BMD) modelling of the Gulati et al data. Data on average pup weight and litters per mating pair were modelling using Benchmark Dose Modelling Software BMDS (USEPA, version available in 2016) and the results are presented in Table 34. The lowest oral BMDL for reproductive effects with the best fit was observed at 220 mg/kg/day. This is approximately double the value of the NOAEL at 100 mg/kg/day determined in Gulati et al. The main effects via the oral route were reduced pup size and reduced litter size. An oral NOAEL of 100 mg/kg/day is established for reproductive and developmental toxicity in mice (Gulati et al (NTP), 1984). An oral BMDL 1SD of 220 mg/kg/day was calculated from the dose-response data for reductions in the litter size per mating pair. Collins, 1971 Three-generation study (each generation mated twice) in rats Guidelines/Guidances: Several deficiencies from OECD 416, GLP: No","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":47,"route":"oral","species":"rat","study_id":"sccs_o_255_noael_009"} |
| Regulatory source | reproductive toxicity | 120 | ppm | human | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=120; DOSE=For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation:; LOAEL_VALUE=585 mg/kg bw/day; EFFECT=topathological findings. Therefore, it cannot be excluded that effects can occur at a lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following value could be identified: For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation: A NOAEL of 700 mg/m3 (120 ppm) 3.3.5 Reproductive toxicity Human data No human data are available on MeS. However, because human data are available for another salicylate ester, ASA, several – mostly retrospective – publications with aspirin during pregnancy could be used as supportive information to assess the reproductive toxicity of MeS. It is difficult or even impossible to estimate the causal relationship between the effects observed in retrospective studies and the salicylate exposure, because the drug had been; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation:","duration":"","effect":"topathological findings. Therefore, it cannot be excluded that effects can occur at a lower doses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following value could be identified: For oral exposure: a NOAEL of 50 mg/kg bw/day For dermal exposure: a LOAEL of 585 mg/kg bw/day For exposure by inhalation: A NOAEL of 700 mg/m3 (120 ppm) 3.3.5 Reproductive toxicity Human data No human data are available on MeS. However, because human data are available for another salicylate ester, ASA, several – mostly retrospective – publications with aspirin during pregnancy could be used as supportive information to assess the reproductive toxicity of MeS. It is difficult or even impossible to estimate the causal relationship between the effects observed in retrospective studies and the salicylate exposure, because the drug had been","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"585 mg/kg bw/day","noael_unit":"ppm","noael_value":"120","page":42,"route":"oral","species":"human","study_id":"sccs_o_255_noael_007"} |
| Regulatory source | reproductive toxicity | 120 | ppm | - | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=120; DOSE=Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):; LOAEL_VALUE=150 mg/kg bw/day; EFFECT=ses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity Concerning fertility and reproductive function, there is insufficient evidence that MeS exhibits adverse effects on sexual function and fertility. Therefore the SCCS concurs with the proposal by RAC that no classification is justified for MeS for adverse effects on sexual function and fertility. Concerning effects on development, a CMR category 2 classification has been agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for me; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","duration":"","effect":"ses in organs that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence can be detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity Concerning fertility and reproductive function, there is insufficient evidence that MeS exhibits adverse effects on sexual function and fertility. Therefore the SCCS concurs with the proposal by RAC that no classification is justified for MeS for adverse effects on sexual function and fertility. Concerning effects on development, a CMR category 2 classification has been agreed by the RAC on September 2019 for methyl salicylate. The CMR category 2 classification for me","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"150 mg/kg bw/day","noael_unit":"ppm","noael_value":"120","page":61,"route":"oral","species":"","study_id":"sccs_o_255_noael_019"} |
| Regulatory source | reproductive toxicity | 120 | ppm | - | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_274; REPORT_TITLE=SCIENTIFIC ADVICE – children exposure on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1654/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 14 September 2023; VALUE_TEXT=120; DOSE=Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):; LOAEL_VALUE=150 mg/kg bw/day; EFFECT=gans that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970):","duration":"","effect":"gans that were not examined. In addition, considering the small number of animals examined at histopathology, only the effects occurring at a high incidence could have been detected in these studies. Based on the data available for the calculation of the MoS; the following values could be identified: - For oral exposure (Webb and Hansen, 1963): a NOAEL of 50 mg/kg bw/day (LOAEL = 150 mg/kg bw/day) - For dermal exposure (Webb and Hansen, 1963): a LOAEL of 585 mg/kg bw/day - For exposure by inhalation (Gage,1970): A NOAEL of 700 mg/m3 (120 ppm) Reproductive toxicity","endpoint":"reproductive toxicity","ingredient":"s, toys, textiles, clothing,","loael_value":"150 mg/kg bw/day","noael_unit":"ppm","noael_value":"120","page":15,"route":"oral","species":"","study_id":"sccs_o_274_noael_002"} |
| Regulatory source | reproductive toxicity | 250 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_255; REPORT_TITLE=Final opinion Scientific Committee on Consumer Safety SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate); OPINION_NUMBER=SCCS/1633/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=250; DOSE=0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals:; EFFECT=oses: 0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertil; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"119-36-8","citation":"","dose":"0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals:","duration":"developmental","effect":"oses: 0, 500, 1500, 3000 and 5000 ppm (equivalent to 25, 75, 150, 250 mg/kg bw as MeS) Experimental animals: Species: Rats Strain: Osborne-Mendel Sex: male and female Animal numbers: 20/sex/dose Examination: fertility index, litter size, viability at birth, on day 4 and at weaning, external examination of newborn and weanling rats (all generations, all mattings), histopathological examination of liver and kidney (for the 3rd generation only). Limited statistical analysis. Study period: before 1971 Results: NOAEL (fertility): 250 mg/kg bw/day (male/female) based on no statistically significant effect reported. NOAEL (development): 75 mg/kg bw/day based on statistically significant decrease of litter size, viability (D0), survival (D4), weaning data in the second generation and decreased pup body weight at 150 mg/kg bw/day. The addition of calcium carbonate did not markedly differ from those obtained after administration of methyl salicylate alone. Summary on fertility and developmental toxicity of methyl salicylate Fertil","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"250","page":48,"route":"","species":"rat","study_id":"sccs_o_255_noael_010"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | LAV5U5022Y | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"LAV5U5022Y"} |
| openFDA substances | FDA UNII substance identifier | LAV5U5022Y | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"LAV5U5022Y"} |
| openFDA substances | FDA UNII substance identifier | LAV5U5022Y | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"LAV5U5022Y"} |
| openFDA substances | FDA UNII substance identifier | LAV5U5022Y | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H8O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"LAV5U5022Y"} |