Toxicological perspectives on potential mixture toxicity of alpha-hexylcinnamaldehyde and lilial in consumer products.

Bibliographic Details
Title:	Toxicological perspectives on potential mixture toxicity of alpha-hexylcinnamaldehyde and lilial in consumer products.
Authors:	Orola K; Department of Animal Science and Technology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, Republic of Korea., Moon SH; Department of Animal Science and Technology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, Republic of Korea., Shin SH; Department of Animal Science and Technology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, Republic of Korea., Ryu BY; Department of Animal Science and Technology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, Republic of Korea.
Source:	Toxicology mechanisms and methods [Toxicol Mech Methods] 2026 Jun; Vol. 36 (5), pp. 623-637. Date of Electronic Publication: 2026 Mar 09.
Publication Type:	Journal Article; Review
Language:	English
Journal Info:	Publisher: Informa Healthcare Country of Publication: England NLM ID: 101134521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6524 (Electronic) Linking ISSN: 15376516 NLM ISO Abbreviation: Toxicol Mech Methods Subsets: MEDLINE
Imprint Name(s):	Publication: London : Informa Healthcare Original Publication: London : Taylor and Francis, c2002-
MeSH Terms:	Acrolein/analogs & derivatives , Acrolein/toxicity , Acrolein/chemistry , Perfume/toxicity , Perfume/chemistry , Aldehydes/toxicity , Aldehydes/chemistry , Consumer Product Safety, Oxidative Stress/drug effects ; Animals ; Humans ; Risk Assessment ; Personal Care Products
Abstract:	Alpha-hexylcinnamaldehyde (HCA) and 3-(4-tert-butylphenyl)-2-methylpropanal (Lilial) are widely used synthetic fragrance aldehydes found in personal care and household products. Individually, HCA is primarily recognized as a weak skin sensitizer with mild cytotoxic potential, whereas Lilial has been classified as a Category 1B reproductive toxicant under the European Union Classification, Labeling and Packaging (CLP) Regulation due to evidence of reproductive and developmental toxicity. Despite regulatory restrictions in parts of Europe, both compounds continue to be detected globally in consumer products, and co-occurrence within fragrance formulations has been documented. Although their individual toxicological profiles have been investigated, limited information exists regarding their potential combined effects. Mechanistically, HCA is an α,β-unsaturated aldehyde capable of Michael addition with nucleophilic residues, while Lilial is a saturated aromatic aldehyde that may form reversible Schiff base adducts. Both compounds have been associated with oxidative stress, mitochondrial damage, and modulation of endocrine-related pathways. Emerging mixture data suggests that co-exposure may influence steroidogenesis and cellular stress responses beyond what is observed for individual compounds, although experimental evidence remains limited. This review synthesizes available in vitro, in vivo, mechanistic, and regulatory data on HCA and Lilial, examines plausible interaction pathways including electrophile-mediated protein modification and metabolic competition, and identifies key gaps requiring mixture-oriented investigation. Greater integration of mechanistic toxicology with cumulative risk assessment frameworks is needed to better reflect real-world co-exposure scenarios involving fragrance aldehydes.
Contributed Indexing:	Keywords: 3-(4-tert-butylphenyl)-2-methylpropanal (lilial); Alpha-hexylcinnamaldehyde (HCA); fragrance toxicity; mixture toxicity; reproductive toxicity
Substance Nomenclature:	7864XYD3JJ (Acrolein) 0 (Perfume) 0 (Aldehydes) T7540GJV69 (lilial) 0 (Personal Care Products)
Entry Date(s):	Date Created: 20260309 Date Completed: 20260710 Latest Revision: 20260710
Update Code:	20260711
DOI:	10.1080/15376516.2026.2640479
PMID:	41801035
Database:	MEDLINE

Description
ISSN:	1537-6524
DOI:	10.1080/15376516.2026.2640479