Search

The existing information supports the use of this material as described in this safety assessment. 2-Methyl-4-phenylbutyraldehyde was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog β-methyl-benzenepentanal (CAS # 55,066-49-4) show that 2-methyl-4-phenylbutyraldehyde is not expected to be genotoxic and provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity endpoint. Data on read-across analog phenylacetaldehyde (CAS # 122-78-1) provide a calculated MOE >100 for the reproductive toxicity endpoint. Data show that there are no safety concerns for 2-methyl-4-phenylbutyraldehyde for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 2-methyl-4-phenylbutyraldehyde is not expected to be photoirritating/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 2-methyl-4-phenylbutyraldehyde is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 2-methyl-4-phenylbutyraldehyde 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 (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The MOE is greater than 100. Without adjustment for specific uncertainty factors related to inter-species and intra-species variation, the material exposure by inhalation at 0.0040 mg/day is deemed to be safe under the most conservative consumer exposure scenario., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The safety assessment of fragrance materials for photoirritation utilized by The Research Institute for Fragrance Materials has recently been modified and is described in detail. Materials demonstrating significant absorbance in the ultraviolet and visible light (UV/VIS) range (290-700 nm) may present a concern for photoirritation and require further investigation. If there are no photoirritation data or data are insufficient, then data on read-across materials are considered before a tiered approach for testing begins. The hazard-based 3T3-Neutral Red Uptake (NRU) Phototoxicity Test (OECD TG 432) is used as a first-tier assay; if it predicts photoirritation, it is followed by the reconstructed human epidermis (RhE) phototoxicity assay (OECD TG 498). The RhE phototoxicity assay is used to determine a No Observed Effect Level (NOEL) for photoirritation that is used in a confirmatory human photoirritation test. Data are presented on 108 fragrance materials exhibiting significant UV/VIS absorbance and evaluated in the 3T3-NRU Phototoxicity Assay. Twenty-one materials were predicted to be phototoxic; twenty were evaluated in the RhE Phototoxicity Assay to establish a NOEL. Fourteen materials were then evaluated in a confirmatory human phototoxicity test. The tiered testing approach presented represents a scientifically pragmatic method to minimize the likelihood of photoirritation from fragrance materials., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

In addition, the total systemic exposure for citronellyl propionate (0.54 μg/kg/day) is below the TTC (30 μg/kg/day; Kroes, 2007) for the repeated dose toxicity endpoint at the current level of use., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In addition, the total systemic exposure to (2-endo,3-exo)-ethyl 3-(1-methylethyl)bicyclo[2.2.1]hept-5-ene-2-carboxylate (3.3 μg/kg/day) is below the TTC (9 μg/kg/day; Kroes, 2007) for the repeated dose toxicity endpoint of a Cramer Class II material at the current level of use., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

The existing information supports the use of this material as described in this safety assessment. Methyl 2-nonenoate 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 trans-2,cis-4-decadienoate (CAS # 3025-30-7) show that methyl 2-nonenoate is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class I material, and the exposure to methyl 2-nonenoate is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). Data from the target and read-across analog isobutyl-2-butenoate (CAS # 589-66-2) do not indicate the material is a sensitizer. The phototoxicity/photoallergenicity endpoints were evaluated based on data and UV spectra; methyl 2-nonenoate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; methyl 2-nonenoate 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The existing information supports the use of this material as described in this safety assessment. Isobutyl propionate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog isobutyl acetate (CAS # 110-19-0) show that isobutyl propionate is not expected to be genotoxic. Data from read-across analog isoamyl acetate (CAS # 123-92-2) show that there are no safety concerns for isobutyl propionate for skin sensitization under the current declared levels of use. The repeated dose and reproductive endpoints were evaluated using the TTC for a Cramer Class I material, and the exposure to isobutyl propionate is below the TTC (0.03 mg/kg/day and 0.03 mg/kg/day, respectively). For the local respiratory endpoint, a calculated MOE >100 was provided by read-across analog butyl acetate (CAS # 123-86-4). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; isobutyl propionate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; isobutyl propionate is not PBT as per the IFRA Environmental Standards. For the risk assessment, isobutyl propionate was not able to be risk screened as there were no reported volumes of use for North America or Europe in the 2015 IFRA Survey., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There are insufficient toxicity data on the target material propanal diethyl acetal (CAS # 4744-08-5). Hence, in silico evaluation was conducted to determine read-across analogs for this material. Based on structural similarity, reactivity, metabolism data, physical-chemical properties, and expert judgment, analogs acetal (CAS # 105-57-7) and butane, 1,1'-[methylenebis(oxy)]bis- (CAS # 2568-90-3) were identified as read-across materials with sufficient data for toxicological evaluation of genotoxicity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ethyl 2-methyl-1,3-dioxolane-2-acetate (CAS # 6413-10-1) was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that ethyl 2-methyl-1,3-dioxolane-2-acetate is not genotoxic. Data from ethyl 2-methyl-1,3-dioxolane-2-acetate show that there are no safety concerns for skin sensitization under the current, declared levels of use. Data on ethyl 2-methyl-1,3-dioxolane-2-acetate provide a calculated MOE >100 for the repeated dose, developmental, and reproductive toxicity endpoints. The local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class III material, and the exposure to ethyl 2-methyl-1,3-dioxolane-2-acetate is below the TTC (0.47 mg/day). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; ethyl 2-methyl-1,3-dioxolane-2-acetate is not expected to be phototoxic/photoallergenic. For the environmental endpoints, ethyl 2-methyl-1,3-dioxolane-2-acetate is not PBT as per the IFRA Environmental Standards, and its risk quotients (i.e., PEC/PNEC) for the aquatic environment based on its current volume of use in Europe and North America are <1., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The use of this material under current conditions is supported by existing information. 1,1-Diethoxyheptane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from the read-across analog octanal dimethyl acetal (CAS # 10022-28-3) show that 1,1-diethoxyheptane is not expected to be genotoxic. Based on the application of the non-reactive DST, 1,1-diethoxyheptane does not present a concern for skin sensitization. The repeated dose, developmental and reproductive, and local respiratory toxicity endpoints were completed using the TTC for a Cramer Class I material (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on UV spectra. The environmental endpoints were evaluated; 1,1-diethoxyheptane 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The use of this material under current conditions is supported by existing information. The material (dihydro-β-terpinyl acetate) was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the read across analog menthyl acetate (1α,2β,5α) (CAS # 89-48-5) show that dihydro-β- terpinyl acetate is not genotoxic nor does it have skin sensitization potential. The repeated dose, reproductive and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (0.03, 0.03 mg/kg/day and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on UV spectra. The environmental endpoints were evaluated, dihydro-β-terpinyl 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data show that this material is not genotoxic nor does it have skin sensitization potential. The repeated dose, developmental and reproductive, and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (0.03, 0.03 mg/kg/day and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the suitable read across analog benzyl acetate (CAS # 140-11-4) show that this material is not genotoxic nor does it have skin sensitization potential and also provided a MOE > 100 for the repeated dose, developmental and reproductive, and local respiratory toxicity endpoints. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data show that this material is not genotoxic. Data from the suitable read across analog linalyl phenylacetate (CAS # 7143-69-3) show that this material does not have skin sensitization potential. The repeated dose toxicity endpoint was completed using linalyl cinnamate (CAS # 78-37-5) as a suitable read across analog, which provided a MOE > 100. The developmental and reproductive toxicity endpoint was completed using linalool (CAS # 78-70-6), dehydrolinalool (CAS # 29171-20-8), benzoic acid (CAS # 65-85-0) and sodium benzoate (CAS # 532-32-1) as suitable read across analogs, which provided a MOE > 100. The local respiratory toxicity endpoint was completed using linalool (CAS # 78-70-6) and benzoic acid (CAS # 65-85-0) as suitable read across analogs, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework along with data from the suitable read across analog linalyl cinnamate (CAS # 78-375)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization, as well as environmental safety. Data show that this material is not genotoxic. Data from the suitable read across analog 2-butyloctan-1-ol (CAS # 3913-02-8) show that this material does not have skin sensitization potential. The reproductive and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (0.03 and 1.4 mg/day, respectively). The developmental and repeat dose toxicity endpoints were completed data on the target material which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework., (Copyright © 2016 Elsevier Ltd. All rights reserved.)