Toxicokinetic Differences between Dermal and Oral Exposure to Ultraviolet Absorbers: Exploring Pathway-Specific...

Ultraviolet absorbers (UVAs) are a group of emerging contaminants with high production volumes. Their applications include but are not limited to sunscreens and food contact materials. Dermal and oral exposures are generally regarded as the main human exposure pathways, but pathway-specific toxicokinetics of UVAs are still unclear. Here, major metabolites and pathway-specific toxicokinetics of five typical UVAs were investigated using in vitro experiments, animal administration experiments, and consecutively collected 24 h human urine. Unlike other UVAs, 2-ethylhexyl p-methoxycinnamate (EHMC) exhibited a significantly longer biological elimination half-life (T_1/2β) and a larger volume of distribution (Vd) following oral administration compared to dermal exposure, suggesting a potentially higher risk via the oral pathway. 2-(2H-Benzotriazol-2-yl)-4,6-ditertpentylphenol (UV-328) showed the greatest bioaccumulation but limited systematic absorption and restricted tissue distribution for both pathways. It indicated entrapment of UV-328 in the enterohepatic circulation, which was also supported by its high lipophilicity and low metabolic rate. The oxidative metabolite of UV-328 was found to be indicative of oral exposure. Further monitoring of 24 h human urine (n = 220 from environmentally exposed participants) shows that non-oral exposure is probably the main exposure pathway for UV-328 in the general population. In summary, this study addresses a key gap in understanding pathway-specific toxicokinetics of UVAs and provides valuable data to improve the accuracy of assessing systemic exposure levels from multiple pathways.