Risk assessment of drometrizole trisiloxane as a UV filter in cosmetics

Drometrizole trisiloxane is a cosmetic ingredient used as an ultraviolet (UV) filter in sunscreen products. The acute toxicity, repeated-dose toxicity, skin irritation, ocular irritation, skin sensitization, reproductive and developmental toxicity, genotoxicity, carcinogenicity, as well as toxicokinetics and dermal absorption of drometrizole trisiloxane were evaluated. The oral and dermal LD₅₀ values of drometrizole trisiloxane were greater than 2 g/kg in rats. Drometrizole trisiloxane did not induce skin irritation in rabbits or ocular irritation following ocular exposure. In skin sensitization studies conducted in guinea pigs, no sensitization potential was observed. In reproductive and developmental toxicity studies in rats and rabbits, no treatment-related adverse effects were observed in parental animals or offspring at doses up to 1000 mg/kg/day. Genotoxicity assessments, including bacterial reverse mutation assays, in vitro chromosomal aberration assays, gene mutation assays, and in vivo micronucleus tests, yielded consistently negative results. Long-term dermal carcinogenicity studies in mice showed no evidence of treatment-related tumor formation. Based on repeated-dose oral toxicity studies, the no-observed-adverse-effect level (NOAEL) for drometrizole trisiloxane was determined to be 1000 mg/kg/day, corresponding to the highest dose tested. To assess systemic exposure, a conservative dermal absorption rate of 5.94% was applied. The resulting systemic exposure dose was estimated to be 2.52 mg/kg/day for adults under maximum cosmetic use conditions. The calculated margin of safety exceeded 100 when drometrizole trisiloxane was used at concentrations up to 15% in cosmetic products, indicating that its use as a cosmetic UV filter does not raise safety concerns under current conditions of use, based on the overall toxicological profile and low systemic exposure.