•This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees.•This process incorporates advances in approaches in risk assessment used by RIFM ...over the past ten years.•A framework for choosing structural analogs and consideration of the Threshold of Toxicological Concern (TTC) are included.•Quantitative Risk Assessment (QRA) for dermal sensitization and aggregate exposure assessment methodologies are included.•The latest alternatives to animal testing methodology and environmental risk assessment are included.
The Research Institute for Fragrance Materials, Inc. (RIFM) has been engaged in the generation and evaluation of safety data for fragrance materials since its inception over 45 years ago. Over time, RIFM's approach to gathering data, estimating exposure and assessing safety has evolved as the tools for risk assessment evolved. This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees, reflecting advances in approaches in risk assessment and new and classical toxicological methodologies employed by RIFM over the past ten years. These changes include incorporating 1) new scientific information including a framework for choosing structural analogs, 2) consideration of the Threshold of Toxicological Concern (TTC), 3) the Quantitative Risk Assessment (QRA) for dermal sensitization, 4) the respiratory route of exposure, 5) aggregate exposure assessment methodology, 6) the latest methodology and approaches to risk assessments, 7) the latest alternatives to animal testing methodology and 8) environmental risk assessment. The assessment begins with a thorough analysis of existing data followed by in silico analysis, identification of ‘read across’ analogs, generation of additional data through in vitro testing as well as consideration of the TTC approach. If necessary, risk management may be considered.
•Acetyl cedrene; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, ...and/or TTC.
The existing information supports the use of this material as described in this safety assessment. 2-Tridecanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local ...respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 2-heptanone (CAS # 110-43-0) show that 2-tridecanone 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 2-heptanone (CAS # 110-43-0) show that there are no safety concerns for 2-tridecanone for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 2-tridecanone 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 II material, and the exposure to 2-tridecanone is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; 2-Tridecanone 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.
•2-Tridecanone; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, and/or TTC.
•4-Methylpentanoic acid; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, ...read-across, and/or TTC.
•Cyclohexyl salicylate; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, ...read-across, and/or TTC.
•Acetaldehyde, diphenethyl acetal; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target ...data, read-across, and/or TTC.
•Linalyl cinnamate; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, ...and/or TTC.
•Diethyldimethylcyclohex-2-en-1-one; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target ...data, read-across, and/or TTC.
•Cyclohexanol, 2-methoxy-4-propyl-; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target ...data, read-across, and/or TTC.
•Spiro1,3-dioxolane-2,8′(5′H)-2H-2,4amethanonaphthalene,hexahydro-1′,1′,5′,5′-tetramethyl-, 2′S-(2′α,4′aα,8′aα)-; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human ...health endpoints plus environmental.•All endpoints were cleared using target data, read-across, and/or TTC.
