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Fragrance materials are widely used in cosmetics and other consumer products. The Research Institute for Fragrance Materials (RIFM) evaluates the safety of these ingredients and skin absorption is an important parameter in refining systemic exposure. Currently, RIFM's safety assessment process assumes 100% skin absorption when experimental data are lacking. This 100% absorption default is not supportable and alternate default values were proposed. This study aims to develop and validate a practical skin absorption model (SAM) specific for fragrance material. It estimates skin absorption based on the methodology proposed by Kroes et al. SAM uses three default absorption values based on the maximum flux (J(max)) - namely, 10%, 40%, and 80%. J(max) may be calculated by using QSAR models that determine octanol/water partition coefficient (K(ow)), water solubility (S) and permeability coefficient (K(p)). Each of these QSAR models was refined and a semi-quantitative mechanistic model workflow is presented. SAM was validated with a large fragrance-focused data set containing 131 materials. All resulted in predicted values fitting the three-tiered absorption scenario based on Jmax ranges. This conservative SAM may be applied when fragrance material lack skin absorption data.

A toxicologic and dermatologic review of 4-(isopropyl)-1-methylcyclohexyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of octahydro-4,7-methano-1H-indenemethyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of decahydro-β-naphthyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of carveol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of d,l-menthol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 3,7-dimethyl-1-octanol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of cedrenol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of tetrahydromyrcenol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of tetrahydrolinalool when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of cis-3-hexenyl cinnamate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of iso-methyl-beta-ionone when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of trans-beta-Ionone when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 4-(1,2-epoxy-2,6,6-trimethylcyclohexyl)-3-buten-2-one when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 6-methyl-β-ionone when used as a fragrance ingredient is presented.

Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family. These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles. The 8 nitriles were assessed for genotoxicity using an Ames test, in vitro chromosome aberration test or in vitro micronucleus test. The positive results observed in the in vitro tests were further investigated using an in vivo micronucleus test. The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic. Dodecanitrile and 2,2,3-trimethylcyclopent-3-enylacetonitrile were negative in the in vitro chromosome aberration test and in vitro micronucleus test, respectively. While citronellyl nitrile, 3-methyl-5-phenylpentanenitrile, cinnamyl nitrile, and 3-methyl-5-phenylpent-2-enenitrile revealed positive results in the in vitro tests, but confirmatory in vivo tests determined these nitriles to be negative in the in vivo micronucleus assay. The remaining two nitriles (benzonitrile and α-cyclohexylidene benzeneacetonitrile) were negative in the in vivo micronucleus test. This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients.

A toxicologic and dermatologic review of 3-phenylpropyl cinnamate when used as a fragrance ingredient is presented. 3-Phenylpropyl cinnamate is a member of the fragrance structural group cinnamyl phenylpropyl compounds. The common characteristic structural element of cinnamyl phenylpropyl materials is an aryl substituted primary alcohol/aldehyde/ester. They are simple aromatic compounds with saturated propyl or unsaturated propenyl side chains containing a primary oxygenated functional group which has little toxic potential. 3-Phenyl-1-propyl derivatives participate in the same beta-oxidation pathways as do their parent cinnamic acid derivatives. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 3-phenylpropyl cinnamate was evaluated then summarized and includes physical properties, acute toxicity, skin irritation and skin sensitization. A safety assessment of all cinnamyl phenylpropyl compounds will be published simultaneously with this document. Please refer to Belsito et al. (2011) for an overall assessment of the safe use of this material and all the cinnamyl phenylpropyl materials in fragrances. Belsito, D., Bickers, D., Bruze, M., Dagli, M.L., Fryer, A., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A toxicologic and dermatologic assessment of cinnamyl phenylpropyl compounds when used as fragrance ingredients.

A toxicologic and dermatologic review of 3-phenyl-1-propanol when used as a fragrance ingredient is presented. 3-Phenyl-1-propanol is a member of the fragrance structural group cinnamyl phenylpropyl compounds. The common characteristic structural element of cinnamyl phenylpropyl materials is an aryl substituted primary alcohol/aldehyde/ester. They are simple aromatic compounds with saturated propyl or unsaturated propenyl side chains containing a primary oxygenated functional group which has little toxic potential. 3-Phenyl-1-propyl derivatives participate in the same beta-oxidation pathways as do their parent cinnamic acid derivatives. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 3-phenyl-1-propanol was evaluated then summarized and includes physical properties, acute toxicity, skin irritation, skin sensitization, in vitro skin absorption and mutagenicity. A safety assessment of all cinnamyl phenylpropyl compounds will be published simultaneously with this document; please refer to Belsito et al. (2011) for an overall assessment of the safe use of this material and all cinnamyl phenylpropyl materials in fragrances (Belsito, D., Bickers, D., Bruze, M., Dagli, M.L., Fryer, A., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A toxicologic and dermatologic assessment of cinnamyl phenylpropyl compounds when used as fragrance ingredients.).

A toxicologic and dermatologic review of isotridecan-1-ol (isomeric mixture) when used as a fragrance ingredient is presented. Isotridecan-1-ol (isomeric mixture) is a member of the fragrance structural group branched chain saturated alcohols. The common characteristic structural elements of the alcohols with saturated branched chain are one hydroxyl group per molecule, and a C(4)-C(12) carbon chain with one or several methyl side chains. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. A safety assessment of the entire branched chain saturated alcohol group will be published simultaneously with this document; please refer to Belsito et al. (2010) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances.

A toxicologic and dermatologic review of tricyclodecanyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of amylcyclohexyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of Cyclohexyl cyclopent-2-ene-1-acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 1,3,3-trimethyl-2-norbornanyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of myraldyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 1-ethynylcyclohexyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of α-methylcyclohexylmethyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of cyclohexyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 3-tert-butylcyclohexyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 4-tert-butylcyclohexyl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of isopulegol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of farnesol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of alpha-santalol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of hydroxycitronellol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of octahydro-7,7,8,8-tetramethyl-2,3b-methano-3bH-cyclopenta[1,3]cyclopropa[1,2]benzene-4-methanol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of cedrol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of terpineol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of l-citronellol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of dihydrocarveol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 3,7-dimethyloct-7-en-1-ol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of nerolidol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of ocimenol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of isoborneol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of fenchyl alcohol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of l-borneol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of myrcenol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of dihydrocarveol (R,R,R) when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 4-thujanol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of p-menth-8-en-1-ol when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of geranyl linalool when used as a fragrance ingredient is presented.