1-Butanol absorption in poly(styrene-divinylbenzene) ion exchange resins for catalysis.

The swelling behaviour of poly(styrene-co-divinylbenzene), P(S-DVB), ion exchange resins in 1-butanol (BuOH) has been studied by means of atomistic classical molecular dynamics simulations (MD). The topological characteristics reported for the resin in the dry state, which exhibited complex internal loops (macropores), were considered for the starting models used to examine the swelling induced by BuOH contents ranging from 10% to 50% w/w. Experimental measurements using a laser diffraction particle size analyzer indicate that swelling causes a volume variation with respect to the dry resin of 21%. According to MD simulations, such a volume increment corresponds to a BuOH absorption of 31-32% w/w, which is in excellent agreement with the indirect experimental estimation (i.e. 31% w/w). Simulations reveal that, independently of the content of BuOH, the density of the swelled resin is higher than that of the dry resin, evidencing that the alcohol provokes important structural changes in the polymeric matrix. Thus, BuOH molecules cause a collapse of the resin macropores when the content of alcohol is ≤20% w/w. In contrast, when the concentration of BuOH is close to the experimental value (∼30% w/w), P(S-DVB) chains remain separated by pores faciliting the access of the reactants to the reaction centers. On the other hand, evaluation of both bonding and non-bonding interactions indicates that the mixing energy is the most important contribution to the absorption of BuOH into the P(S-DVB) resin. Overall, the results displayed in this work represent a starting point for the theoretical study of the catalytic conversion of BuOH into di-n-butyl ether in P(S-DVB) ion exchange resins using sophisticated electronic methods.

RIFM low-exposure fragrance ingredients safety assessment.

The existing information supports the use of these materials as described in this safety assessment. The 167 materials identified in this assessment were evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Target data, read-across analogs and TTC show that these materials are not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for their respective Cramer Classes (see Fig. 1 below) and the exposure to these materials is below the TTC. The skin sensitization endpoint was completed using the DST for non-reactive and reactive materials (900 µg/cm2 and 64 µg/cm2, respectively); exposures are below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; these materials are not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; the materials were found not to be PBT as per the IFRA Environmental Standards, and their risk quotients, based on their current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.

RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1,3,6-octatriene, CAS registry number 13877-91-3.

The existing information supports the use of this material as described in this safety assessment. 3,7-Dimethyl-1,3,6-octatriene was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from 3,7-dimethyl-1,3,6-octatriene and read-across analog myrcene (ß-myrcene; CAS # 123-35-3) show that 3,7-dimethyl-1,3,6-octatriene is not expected to be genotoxic and provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity and developmental and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 µg/cm 2 ); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 3,7-dimethyl-1,3,6- octatriene is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 3,7-dimethyl-1,3,6-octatriene is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 3,7-dimethyl-1,3,6- octatriene was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental oncentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, p-tolualdehyde, CAS Registry Number 104-87-0.

The existing information supports the use of this material as described in this safety assessment. p-Tolualdehyde was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, and environmental safety. Data from read-across analog benzaldehyde (CAS # 100-52-7) show that p-tolualdehyde is not expected to be genotoxic. Data from read-across analog cuminaldehyde (CAS # 122-03-2) provided p-tolualdehyde a No Expected Sensitization Induction Level (NESIL) of 1100 µg/cm2 for the skin sensitization endpoint. The repeated dose toxicity, developmental and reproductive toxicity, and local respiratory toxicity endpoints were completed using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to p-tolualdehyde is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on data from read-across analog 4-ethylbenzaldehyde (CAS # 4748-78-1); p-tolualdehyde is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; p-tolualdehyde was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, hexyl hexanoate, CAS Registry Number 6378-65-0.

The existing information supports the use of this material as described in this safety assessment. Hexyl hexanoate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog hexyl isobutyrate (CAS # 2349-07-7) show that hexyl hexanoate is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to hexyl hexanoate is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; hexyl hexanoate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; hexyl hexanoate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, furfuryl thioacetate, CAS Registry Number 13678-68-7.

Furfuryl thioacetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that furfuryl thioacetate is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to furfuryl thioacetate is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for reactive materials (64 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; furfuryl thioacetate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; furfuryl thioacetate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol, CAS Registry Number 526218-21-3.

The existing information supports the use of this material as described in this safety assessment. 1-(2-Methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not genotoxic. Data on 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity endpoint. The reproductive and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is below the TTC (0.0015 mg/kg/day and 0.47 mg/day, respectively). Data show that there are no safety concerns for 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.

RIFM fragrance ingredient safety assessment, decanoic acid, CAS Registry Number 334-48-5.

The existing information supports the use of this material as described in this safety assessment. Decanoic acid was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data on the target material and from read-across analog nonanoic acid (CAS # 112-05-0) show that decanoic acid is not expected to be genotoxic. Data on read-across analog octanoic acid (CAS # 124-07-2) provide a calculated MOE >100 for the repeated dose and reproductive toxicity endpoints. Based on the existing data, decanoic acid does not present a concern for skin sensitization under the current, declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; decanoic acid is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the TTC for a Cramer Class I material, and the exposure to decanoic acid is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; decanoic acid was found not to be PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.

RIFM fragrance ingredient safety assessment, 2,2-dimethyl-3-methyl-3-butenyl propanoate, CAS Registry Number 104468-21-5.

The existing information supports the use of this material as described in this safety assessment. 2,2-Dimethyl-3-methyl-3-butenyl propanoate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog rhodinyl formate (CAS # 141-09-3) show that 2,2-dimethyl-3-methyl-3-butenyl propanoate is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 2,2-dimethyl-3-methyl-3-butenyl propanoate is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2,2-dimethyl-3-methyl-3-butenyl propanoate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 2,2-dimethyl-3-methyl-3-butenyl propanoate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 4-methylpentanoic acid, CAS Registry Number 646-07-1.

The existing information supports the use of this material as described in this safety assessment. 4-Methylpentanoic acid was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 2-ethylbutyric acid (CAS # 88-09-5) show that 4-methylpentanoic acid is not expected to be genotoxic and provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 4-methylpentanoic acid is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 4-methylpentanoic acid is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 4-methylpentanoic acid was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, phenylacetaldehyde, CAS Registry Number 122-78-1.

The existing information supports the use of this material as described in this safety assessment. The material (phenylacetaldehyde) was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization, and environmental safety. Data show that phenylacetaldehyde is not genotoxic and provide a calculated margin of exposure (MOE) > 100 for the repeated dose and developmental and reproductive toxicity endpoints. Data from phenylacetaldehyde provided a No Expected Sensitization Induction Level (NESIL) of 590 µg/cm2 for the skin sensitization endpoint. The local respiratory toxicity endpoint was completed using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to phenylacetaldehyde was below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on data and ultraviolet (UV) spectra; phenylacetaldehyde is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; phenylacetaldehyde was not found to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) environmental standards and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]) are <1.

RIFM fragrance ingredient safety assessment, 3,7-dimethyl-3,6-octadienal, CAS registry number 55722-59-3.

The existing information supports the use of this material as described in this safety assessment. 3,7-Dimethyl-3,6-octadienal was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog citral (CAS # 5392-40-5) show that 3,7-dimethyl-3,6-octadienal is not expected to be genotoxic and provided a calculated margin of exposure (MOE) >100 for the repeated dose toxicity and developmental and reproductive endpoints. Data from the read-across analog citronellal (CAS # 106-23-0) provided 3,7-dimethyl-3,6-octadienal a No Expected Sensitization Induction Level (NESIL) of 7000 µg/cm2 for the skin sensitization endpoint. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 3,7-dimethyl-3,6-octadienal is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 3,7-dimethyl-3,6-octadienal is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 3,7-dimethyl-3,6-octadienal was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 2-phenylpropionaldehyde, CAS Registry Number 93-53-8.

The existing information supports the use of this material as described in this safety assessment. 2-Phenylpropionaldehyde was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data on read-across analogs 3-phenylbutanal (CAS # 16251-77-7) and isopropylphenylbutanal (CAS # 125109-85-5) show that this material is not expected to be genotoxic. Data from the target material provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity endpoint and a No Expected Sensitization Induction Level (NESIL) of 380 µg/cm2 for the skin sensitization endpoint. The developmental and reproductive toxicity and the local respiratory toxicity endpoints were completed using the threshold of toxicological concern (TTC) for a Cramer Class I material (0.03 mg/kg/day and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-phenylpropionaldehyde is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 2-phenylpropionaldehyde was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 1-nonanol, 2,4,6,8-tetramethyl-,acetate, CAS Registry Number 68922-14-5.

The existing information supports the use of this material as described in this safety assessment. 1-Nonanol, 2,4,6,8-tetramethyl-,acetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from 1-nonanol, 2,4,6,8-tetramethyl-,acetate and read-across analog isotridecyl acetate (CAS # 69103-23-7) show that this material is not expected to be genotoxic. Data on read-across material 3,5,5-trimethylhexyl acetate (CAS # 58430-94-7) provide a calculated MOE >100 for the repeated dose and reproductive toxicity endpoints. Based on the existing data and the additional material acetic acid, C11-14-isoalkyl esters, C13-rich (CAS # 84712-50-5), 1-nonanol, 2,4,6,8-tetramethyl-,acetate does not present a concern for skin sensitization under the current, declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on data and UV spectra; 1-nonanol, 2,4,6,8-tetramethyl-,acetate is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the TTC for a Cramer Class I material and the exposure to 1-nonanol, 2,4,6,8-tetramethyl-,acetate is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 1-nonanol, 2,4,6,8-tetramethyl-,acetate was found not to be PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.

RIFM fragrance ingredient safety assessment, propyl propionate, CAS Registry Number 106-36-5.

The existing information supports the use of this material as described in this safety assessment. Propyl propionate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that propyl propionate is not genotoxic. Data on propyl propionate provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity, reproductive toxicity, and local respiratory toxicity endpoints. Data from read-across analog pentyl propionate (CAS # 624-54-4) show that there are no safety concerns for propyl propionate for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; propyl propionate is not expected to be phototoxic/photoallergenic. For the hazard assessment based on the screening data, propyl propionate is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, propyl propionate was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.

RIFM fragrance ingredient safety assessment, 2-methylpropyl pentanoate, CAS Registry Number 10588-10-0.

The existing information supports the use of this material as described in this safety assessment. 2-Methylpropyl pentanoate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog ethyl 2-methylbutyrate (CAS # 7452-79-1) show that 2-methylpropyl pentanoate is not expected to be genotoxic and provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. Data from read-across analog isoamyl acetate (CAS # 123-92-2) show that there are no safety concerns for 2-methylpropyl pentanoate for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-methylpropyl pentanoate is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material; exposure is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 2-methylpropyl pentanoate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, dodecane, CAS Registry Number 112-40-3.

Dodecane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog nonane (CAS # 111-84-2) show that dodecane is not expected to be genotoxic. Data on read-across analog undecane (CAS # 1120-21-4) provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/vis) spectra; dodecane is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to dodecane is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; dodecane was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, tetrahydro-α-pentylfurfuryl acetate, CAS Registry Number 67634-08-6.

The existing information supports the use of this material as described in this safety assessment. Tetrahydro-α-pentylfurfuryl acetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that tetrahydro-α-pentylfurfuryl acetate is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to tetrahydro-α-pentylfurfuryl acetate is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; tetrahydro-α-pentylfurfuryl acetate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; tetrahydro-α-pentylfurfuryl acetate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 2-decanone, CAS Registry Number 693-54-9.

The existing information supports the use of this material as described in this safety assessment. 2-Decanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 2-heptanone (CAS # 110-43-0) show that 2-decanone is not expected to be genotoxic. Data on read-across analog 2-heptanone (CAS # 110-43-0) provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-decanone is not expected to be phototoxic/photoallergenic. For the local respiratory endpoint, a calculated MOE >100 was provided by the read-across analog 4-methyl-2-pentanone (CAS # 108-10-1). The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 2-decanone is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 2-decanone was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.

RIFM fragrance ingredient safety assessment, 4-(2-butenylidene)-3,5,5-trimethylcyclohex-2-en-1-one, CAS registry number 13215-88-8.

The existing information supports the use of this material as described in this safety assessment. 4-(2-Butenylidene)-3,5,5-trimethylcyclohex-2-en-1-one was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 4-(2-butenylidene)-3,5,5-trimethylcyclohex-2-en-1-one is not genotoxic. Data on 4-(2-butenylidene)-3,5,5-trimethylcyclohex-2-en-1-one provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity endpoint. The reproductive and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 4-(2-butenylidene)-3,5,5-trimethylcyclohex-2-en-1-one is below the TTC (0.03 mg/kg/day and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for reactive materials (64 µg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on data; 4-(2-butenylidene)-3,5,5-trimethylcyclohex-2-en-1-one is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 4-(2-butenylidene)-3,5,5-trimethylcyclohex-2-en-1-one was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.