RIFM fragrance ingredient safety assessment, p-t-butyl-α-methylhydrocinnamic aldehyde, CAS Registry Number 80-54-6

Api, A.M.; Belsito, D.; Biserta, S.; Botelho, D.; Bruze, M.; Burton, G.A.; Buschmann, J.; Cancellieri, M.A.; Dagli, M.L.; Date, M.; Dekant, W.; Deodhar, C.; Fryer, A.D.; Gadhia, S.; Jones, L.; Joshi, K.; Lapczynski, A.; Lavelle, M.; Liebler, D.C.; Na, M.; O’Brien, D.; Patel, A.; Penning, T.M.; Ritacco, G.; Rodríguez-Ropero, F.; Romine, J.; Sadekar, N.; Salvito, D.; Schultz, T.W.; Siddiqi, F.; Sipes, I. G.; Sullivan, G.; Thakkar, Y.; Tokura, Y.; Tsang, S.

doi:10.1016/j.fct.2020.111430

Cited by 3 publications

(7 citation statements)

References 31 publications

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“…2 ) probably as further hydroxylation and oxidation products of lysmerylic acid 39 . In vitro metabolism of 14 C-lilial using liver microsomes and hepatocytes of rats, rabbits, mice and humans revealed that lysmerol and lysmerylic acid were the primary metabolites, while secondary metabolites included hydroxy-lysmerylic acid and p - tert -butylbenzoic acid 3 , 4 . Similar products were detected in urine of 40 human volunteers 39 .…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, the effect of lilial was very weak compared to estrogen (only 2.4 doublings with 100 µM vs. 5.2 doublings with 10 nM estrogen compared to 1.8 doublings of unaffected control). However, there were no adverse effects on fertility and reproductive performance in the parental rats F0 and F1 in vivo 3 . Furthermore, the mode of action of lilial in sensitive species appears to be not dependent on an endocrine effect but related to overt toxicity to seminiferous tissues 4 .…”

Section: Introductionmentioning

confidence: 85%

“…In a human maximization test, no skin sensitization reactions were observed at a concentration of 4%. However, in another test, lilial showed skin sensitization reactions at a concentration of 5%, but this may be caused by the spread of phenylacetaldehyde 3 . Lilial is listed as one of 26 fragrance ingredients that cause allergic contact dermatitis, which must be declared on cosmetic products 11 .…”

Section: Introductionmentioning

confidence: 93%

“…The repeated dose toxicity data on several species after ingestion was investigated. Oral administration at doses of ≥ 50 mg/kg/day (rats) and ≥ 200 mg/kg/day (dogs) reduced body weight, had signs of clinical toxicity, and induced systemic toxicity such as decreasing in plasma cholinesterase activity levels 3 . However, no statistical significance and histopathological correlations were observed.…”

Section: Introductionmentioning

confidence: 99%

“…Pure lilial causes eye and skin irritation in rabbits 4 . The dermal absorption values were 13.5% for hydroalcoholic-based fragrances and deodorant/antiperspirant products, 8.9% for oil-in-water-based products including make-up products, body lotions, hair styling and bath cleaning products, and 10.5% for water-in-oil-based products such as face and hand cream products 3 . Lalko et al 9 demonstrated the sensitization potential of lilial using the Local Lymph Node Assay.…”

Section: Introductionmentioning

confidence: 99%

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Toxicological investigation of lilial

Jablonská,

Míchal,

Křížkovská

et al. 2023

Sci Rep

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Lilial (also called lysmeral) is a fragrance ingredient presented in many everyday cosmetics and household products. The concentrations of lilial in the final products is rather low. Its maximum concentration in cosmetics was limited and recently, its use in cosmetics products was prohibited in the EU due to the classification as reproductive toxicant. Additionally, according to the European Chemicals Agency, it was under assessment as one of the potential endocrine disruptors, i.e. a substance that may alter the function of the endocrine system and, as a result, cause health problems. Its ability to act as an androgen receptor agonist and the estrogenic and androgenic activity of its metabolites, to the best of our knowledge, have not yet been tested. The aim of this work was to determine the intestinal absorption, cytotoxicity, nephrotoxicity, mutagenicity, activation of cellular stress-related signal pathways and, most importantly, to test the ability to disrupt the endocrine system of lilial and its Phase I metabolites. This was tested using set of in vitro assays including resazurin assay, the CHO/HPRT mutation assay, γH2AX biomarker-based genotoxicity assay, qPCR and in vitro reporter assays based on luminescence of luciferase for estrogen, androgen, NF-κB and NRF2 signalling pathway. It was determined that neither lilial nor its metabolites have a negative effect on cell viability in the concentration range from 1 nM to 100 µM. Using human cell lines HeLa9903 and MDA-kb2, it was verified that this substance did not have agonistic activity towards estrogen or androgen receptor, respectively. Lilial metabolites, generated by incubation with the rat liver S9 fraction, did not show the ability to bind to estrogen or androgen receptors. Neither lilial nor its metabolites showed a nephrotoxic effect on human renal tubular cells (RPTEC/TERT1 line) and at the same time they were unable to activate the NF-κB and NRF2 signalling pathway at a concentration of 50 µM (HEK 293/pGL4.32 or pGL4.37). Neither lilial nor its metabolites showed mutagenic activity in the HPRT gene mutation test in CHO-K1 cells, nor were they able to cause double-strand breaks in DNA (γH2AX biomarker) in CHO-K1 and HeLa cells. In our study, no negative effects of lilial or its in vitro metabolites were observed up to 100 µM using different in vitro tests.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxicological investigation of lilial

Jablonská,

Míchal,

Křížkovská

et al. 2023

Sci Rep

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Fragrances in the Environment: Properties, Applications, and Emissions

Rocha

Ratola

Homem

2023

The Handbook of Environmental Chemistry

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Aldehydes: What We Should Know About Them

Catalano,

Mariconda,

D’Amato

et al. 2024

Organics

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From Egyptian mummies to the Chanel N° 5 perfume, aldehydes have been used for a long time and continue to impact our senses in a wide range of perfumes, foods, and beverages. Aldehydes represent one of the categories of volatile organic compounds (VOCs), which are categorized as chemicals with boiling points up to 260 °C and can be found in indoor environments in the gaseous phase. Because of their potential or known hazardous properties for humans, the World Health Organization (WHO)-Europe provided some guidelines that may prevent several health risks. Indeed, some aldehydes, reported to be risky for humans, have been retired from the market, such as butylphenyl methylpropional (BMHCA). The purpose of this review is to summarize the most important aldehydes found indoors and outdoors and analyse in depth the toxicological aspects of these compounds, whose presence in perfumes is often underestimated. In addition, the ingredients’ synonyms that are reported in the literature for the same compound were unified in order to simplify their identification.

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RIFM fragrance ingredient safety assessment, p-t-butyl-α-methylhydrocinnamic aldehyde, CAS Registry Number 80-54-6

Cited by 3 publications

References 31 publications

Toxicological investigation of lilial

Toxicological investigation of lilial

Fragrances in the Environment: Properties, Applications, and Emissions

Aldehydes: What We Should Know About Them

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