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

• Published in: Archives of toxicology 2023-01, Vol.97 (1), p.165-176
• Main Authors: Fischer, Corinna, Leibold, Edgar, Hiller, Julia, Göen, Thomas
• Format: Article
• Language: English
• Subjects: Administration, Oral; Benzotriazole; Biomedical and Life Sciences; Biomedicine; Blood; Environmental Health; Excretion; Exposure; Humans; In vivo methods and tests; Intestine; Kinetics; Metabolism; Metabolites; Occupational Medicine/Industrial Medicine; Oral administration; Pharmacology/Toxicology; Phenols; Plasma; Plasma levels; Toxicokinetics and Metabolism; Triazoles; Ultraviolet radiation; UV stabilizers
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-022-03401-3

UV-327 (2-(5-chloro-benzotriazol-2-yl)-4,6-di-( tert -butyl)phenol) is used as an ultraviolet (UV) absorber in plastic products and coatings. Due to its ubiquitous distribution in the environment, human exposure is conceivable. In the study presented herein, initial information on the human in vivo metabolism of UV-327 was obtained by single oral administration to three volunteers. Urine and blood samples were collected up to 72 h after exposure. One study participant additionally donated plasma samples. Maximum blood and plasma levels of UV-327 and its two monohydroxylated metabolites UV-327-6- m OH and UV-327-4- m OH were reached 6 h post-exposure. Almost the entire amount found in blood and plasma samples was identified as UV-327, whereas the two metabolites each accounted for only 0.04% of the total amount, indicating that UV-327 is well-absorbed from the intestine, but only partially metabolized. Plasma to blood ratios of UV-327, UV-327-6- m OH, and UV-327-4- m OH ranged from 1.5 to 1.6. Maximum urinary excretion rates of UV-327, UV-327-6- m OH, UV-327-4- m OH, and UV-327-4 + 6- di OH were reached 9–14 h post-exposure. However, only about 0.03% of the orally administered dose of UV-327 was recovered as UV-327 and its metabolites in urine, indicating that biliary excretion may be the major route of elimination of UV-327 and its hydroxylated metabolites. The present study complements the insight in the complex absorption, distribution, metabolism, and elimination (ADME) processes of benzotriazole UV stabilizers (BUVSs).