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

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-mOH and UV-327-4-mOH 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-mOH, and UV-327-4-mOH ranged from 1.5 to 1.6. Maximum urinary excretion rates of UV-327, UV-327-6-mOH, UV-327-4-mOH, and UV-327-4 + 6-diOH 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).

Tissue-Specific Accumulation, Biotransformation, and Physiologically Based Toxicokinetic Modeling of Benzotriazole Ultraviolet Stabilizers in Zebrafish (Danio rerio).

Benzotriazole ultraviolet stabilizers (BUVSs) are high-production-volume chemicals with ubiquitous occurrence in the aquatic environment. However, little is known about their bioconcentration and biotransformation, and physiologically based toxicokinetic (PBTK) models for BUVSs are lacking. This study selected six BUVSs for which experiments were performed with zebrafish (Danio rerio) exposed to two different levels (0.5 and 10 µg·L-1). Higher kinetic bioconcentration factors (BCFs) were observed at the lower exposure level with environmental relevance, with BCF of 3.33 × 103 L·kg-1 for 2-(2-hydroxy-3,5-di-tert-butylphenyl)-5-chlorobenzotriazole (UV-327). This phenomenon was interpreted by a nonlinear adsorption mechanism, where binding with specific protein sites contributes to bioconcentration. Muscle exhibited the lowest accumulation, in which depuration half-life of UV-327 was 19.5 d. In kidney, muscle, ovary, gill, and skin, logBCF increased with increase in log KOW of the BUVSs until log KOW was ca. 6.5, above which logBCF decreased. However, the trend was not observed in the liver and intestine. Six biotransformation products were identified and mainly accumulated in the liver and intestine. Considering the nonlinear adsorption mechanism in the PBTK model, the prediction accuracy of the model was improved, highlighting the binding of xenobiotics with specific protein sites in assessing the bioconcentration of chemicals for their risk assessment.

Hollow tube covalent organic framework for syringe filter-based extraction of ultraviolet stabilizer in food contact materials.

In this work, a novel hollow tube covalent organic framework constructed by cyclotricatechylene and tetrafluoroterephthalonitrile (CTC-TFPN-COF) with polyether bond was synthesized, and it was coated on filter membrane for extraction of ultraviolet stabilizer in migration from food contact materials. Since the monomers of the polymer were linked by polyether bond, the CTC-TFPN-COF exhibited strong chemical stability in severe conditions such as acid, alkali and various organic solvent. The excellent features of high porosity and robust structure endowed the CTC-TFPN-COF good candidate as adsorbent for extraction of ultraviolet stabilizer. Moreover, the CTC-TFPN-COF coated membranes were immobilized on syringe filter and coupled with multiple channel injection pump to realize high throughput sample pretreatment strategy. Subsequently, a sensitive analytical method for ultraviolet stabilizer was established followed by ultra-high performance liquid chromatography-tandem mass spectrometry. The flow rate of extraction and desorption, elution solvent and the volume of desorption solvent were optimized. The method was assessed, which showed wide linear ranges with R2 greater than 0.99, low limits of detection (0.9-91 ng L-1) and low limits of quantification (3-300 ng L-1). The developed method was successfully applied to determine trace ultraviolet stabilizer in the migration of food contact materials with different simulated solution, which demonstrated its promising potential in practical analysis.