인체 경피 노출을 통한 벤조페논-3의 약물동태학 연구

Abstract

Benzophenone-3 (BP-3) is a component that blocks ultraviolet rays. It is mainly used in sunscreen agents and functional cosmetics, and is mostly exposed through the skin. several studies have reported the possibility of endocrine disturbance. Whereas pharmacokinetic studies on BP-3 have been reported in animal, it is not well known to the fate of BP-3 in human body following dermal exposure. The aim of this study is to determine pharmacokinetic characteristics of BP-3 in male subjects following single dermal application of 1 mg/cm2 of deuterium labeled BP-3. Blood and urine were collected for 72 hours and analyzed BP-3 and its metabolites using UPLC-MS/MS. In blood, after peak time eliminated decline two distinct phases in time-profile, while the metabolites followed first-order kinetics. Based on time-profiles, a multi-compartmental model constructed and validated. As a results, unconjugated BP-3 concentration in serum was lower than conjugated BP-3 concentration in serum. But it was similar to that of total BP-1 concentration in serum. Almost of the BP-3 and BP-1 in urine undergo conjugation or demethylation. And the fraction of urinary excretion for conjugated BP-3 (0.76 ± 0.19%) was 4-fold upper than total BP-1 (0.19 ± 0.13%), which was approximately 580-fold upper than unconjugated BP-3 (0.0013 ± 0.0005%). This study provides information on absorption, distribution, metabolism and elimination of BP-3 in human body and the pharmacokinetic model can be utilized for estimating exposure dose of BP-3, contributing to more realistic exposure assessment in the Korean population based upon biomonitoring data.