Update to RIFM fragrance ingredient safety assessment, hydroxycitronellal dimethyl acetal, CAS Registry number 141-92-4

A M Api ¹, A Bartlett ¹, D Belsito ²

¹Research Institute for Fragrance Materials, Inc., 1200 MacArthur Boulevard, Suite 306, Mahwah, NJ, 07430, USA.
²Member Expert Panel for Fragrance Safety, Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY, 10032, USA.
³Member Expert Panel for Fragrance Safety, Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo, SE-20502, Sweden.
⁴Member Expert Panel for Fragrance Safety, Pharmaceutical Sciences, Wayne State University, 42 W. Warren Ave., Detroit, MI, 48202, USA.
⁵Member Expert Panel for Fragrance Safety, School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI, 58109, USA.
⁶Member Expert Panel for Fragrance Safety, Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, Liverpool, United Kingdom.
⁷Member Expert Panel for Fragrance Safety, University of Sao Paulo, School of Veterinary Medicine and Animal Science, Department of Pathology, Av. Prof. Dr. Orlando Marques de Paiva, 87, Sao Paulo, CEP 05508-900, Brazil.
⁸Member Expert Panel for Fragrance Safety, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078, Würzburg, Germany.
⁹Member Expert Panel for Fragrance Safety, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA.
¹⁰Member Expert Panel for Fragrance Safety, Rutgers University Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
¹¹Member of Expert Panel for Fragrance Safety, University of Pennsylvania, Perelman School of Medicine, Center of Excellence in Environmental Toxicology, 1316 Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA, 19104-3083, USA.
¹²Member Expert Panel for Fragrance Safety, Utrecht University, Institute for Risk Assessment Sciences (IRAS), Netherlands.
¹³Member Expert Panel for Fragrance Safety, Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA.

⁰Research Institute for Fragrance Materials, Inc., 1200 MacArthur Boulevard, Suite 306, Mahwah, NJ, 07430, USA.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association +

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May 11, 2025

View abstract on PubMed

Summary

Hydroxycitronellal dimethyl acetal demonstrates no genotoxicity, reproductive, or local respiratory toxicity concerns. Environmental safety assessments confirm it is not Persistent, Bioaccumulative, and Toxic (PBT), with risk quotients below 1.

Area Of Science

Fragrance chemistry and toxicology
Environmental risk assessment
Chemical safety evaluation

Background

Hydroxycitronellal dimethyl acetal is a fragrance ingredient requiring comprehensive safety evaluation.
Existing data from read-across analog hydroxycitronellal diethyl acetal (CAS # 7779-94-4) informed initial assessments.
Regulatory compliance necessitates thorough toxicological and environmental safety profiling.

Purpose Of The Study

To evaluate the genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety of hydroxycitronellal dimethyl acetal.
To determine if exposure levels are below established safety thresholds.
To assess environmental impact based on Persistence, Bioaccumulation, and Toxicity (PBT) criteria and risk quotients (RQs).

Main Methods

Genotoxicity assessed via read-across from a structural analog.
Repeated dose, reproductive, and local respiratory toxicity evaluated using the Threshold of Toxicological Concern (TTC) for Cramer Class I materials.
Photoirritation/photoallergenicity assessed using ultraviolet/visible (UV/Vis) spectra.
Environmental safety evaluated against International Fragrance Association (IFRA) Environmental Standards, including PBT assessment and calculation of RQs (Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]).

Main Results

Hydroxycitronellal dimethyl acetal is not expected to be genotoxic.
Exposure levels are below the TTC for repeated dose, reproductive, and local respiratory toxicity.
No safety concerns identified for skin sensitization at current usage levels.
No expectation of photoirritation or photoallergenicity based on UV/Vis spectra.
The substance is not PBT, and RQs are <1, indicating no environmental risk.

Conclusions

Hydroxycitronellal dimethyl acetal is considered safe for use regarding genotoxicity, systemic toxicity, local respiratory effects, and skin sensitization.
The ingredient poses no risk of photoirritation or photoallergenicity.
Environmental risk assessment confirms hydroxycitronellal dimethyl acetal is not PBT and presents a low environmental risk under current usage conditions.