Human metabolism and kinetics of the UV absorber 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) after oral administration

Abstract

Abstract2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328; CAS: 25973-55-1) is an ultraviolet light (UV) absorber which belongs to the class of hydroxy phenol benzotriazoles. Therefore, UV 328 is added to plastics and other polymers due to its photostability to prevent discoloration and prolong product stability which may result in an exposure of consumers. However, information about the toxic effects on humans and the human metabolism are still lacking. In the present study, human metabolism pathways of UV 328 and its elimination kinetics were explored. For that purpose, three healthy volunteers were orally exposed to a single dose of 0.3 mg UV 328/kg bodyweight. UV 328 and its metabolites were investigated in blood and urine samples collected until 48 and 72 h after exposure, respectively. Thereby, previously published analytical procedures were applied for the sample analysis using dispersive liquid–liquid microextraction and subsequent measurement via gas chromatography coupled to tandem mass spectrometry with advanced electron ionization. UV 328 was found to be oxidized at its alkyl side chains leading to the formation of hydroxy and/or oxo function with maximum blood concentrations at 8–10 h after exposure for UV 328-6/3-OH, UV 328-4/3-OH and UV 328-4/3-CO. In contrast, a plateau for UV 328-4/3-CO-6/3-OH levels was reached around 10 h post-dosage. The highest blood levels were found for native UV 328 at 8 h after ingestion. Furthermore, biphasic elimination kinetics in blood were revealed for almost all detected metabolites. UV 328 and its metabolites did not occur in blood as conjugates. The renal elimination kinetics were very similar with the kinetics in blood. However, the prominence of the metabolites in urine was somewhat different compared to blood. In contrast, mostly conjugated metabolites occurred for renal elimination. In urine, UV 328-4/3-CO-6/3-OH was found to be the most dominant urinary biomarker followed by UV 328-6/3-OH and UV 328-4/3-OH. In total, approximately 0.1% of the orally administered dose was recovered in urine within 72 h. Although high levels of UV 328 in blood proved good resorption and high systemic availability of the substance in the human body, the urine results revealed a rather low quantitative metabolism and urinary excretion rate. Consequently, biliary excretion as part of the enterohepatic cycle and elimination via feces are assumed to be the preferred pathways instead of renal elimination.

Concentrations, Compound Profiles, and Possible Sources of Organic UV Filters in Human Milk in China

“…The mass fraction of UV-328 in textiles should not be >0.1% according to Oeko-Tex . Previous studies have reported that UV-328, UV-329, UV-9, and UV-326 were seldom detected in textiles − or in plastics in China. , In a kinetics study involving oral exposure to UV-328, the UV-328 excretion rate in urine was quite low and the UV-328 concentration was much higher in serum than urine . UV-328 may have a similarly low excretion rate in human breast milk.…”

Correspondence regarding the Perspective “Addressing the importance of microplastic particles as vectors for long-range transport of chemical contaminants: perspective in relation to prioritizing research and regulatory actions”

“…The high concentrations found for bisphenol A and nonylphenol therefore do not result from bioaccumulation but from high exposure levels. This is different for substances such as UV-328 that are only slowly metabolized [21,22]. Experimental results show here that leaching into digestive fluids of seabirds is a relevant exposure pathway [17,18].…”

Human metabolism and excretion kinetics of benzotriazole UV stabilizer UV-327 after single oral administration

“…For example, propyl paraben reached maximum serum levels 1.4 ± 1.1 h after oral administration (Shin et al 2019) and the natural product N,N-dimethyltyramine reached plasma peak levels 30-90 min after oral administration (Sommer et al 2020). Nevertheless, the structurally related BUVS 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV-328) showed retarded resorption kinetics as well and reached maximum blood levels 8 h after oral administration (Denghel et al 2021). The comparable findings for UV-327 and UV-328 indicate similar resorption processes for these substituted BUVSs.…”

“…Most of the substance must, therefore, be excreted via an alternative route. Consistently, biliary excretion was assumed to be the main route of excretion for UV-328, too (Denghel et al 2021).…”