Phenolic benzotriazoles: a class comparison of toxicokinetics of ultraviolet-light absorbers in male rats
Creators: name: Waidyanatha, Suramya
name: Mutlu, Esra
name: Gibbs, Seth
name: Pierfelice, Jessica
name: Smith, Jeremy P.
name: Burback, Brian
name: Blystone, Chad T.
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biochemistry
subject: Cell Biology
subject: Neuroscience
subject: Physiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Evolutionary Biology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Ecology
subject: 80699 Information Systems not elsewhere classified
subject: FOS: Computer and information sciences
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: 60506 Virology
subject: Computational Biology

description: Phenolic benzotriazoles are ultraviolet-light absorbers used in a variety of industrial and consumer applications. We investigated the toxicokinetic behaviour of 9 compounds, covering unsubstituted, monosubstituted, disubstituted, and trisubstituted compounds, following a single gavage (30 and 300 mg/kg) and intravenous (IV) (2.25 mg/kg) administration in male rats.Following IV administration, no distinct pattern in plasma elimination was observed for the compounds with half-lives ranging from 15.4–84.8 h. Systemic exposure parameters, maximum concentration (C<sub>max</sub>) and area under the concentration time curve (AUC), generally increased with the degree of substitution.Following gavage administration, C<sub>max</sub> and AUC of unsubstituted compound were lower compared to the substituted compounds. C<sub>max</sub> and AUC increased ≤7-fold with a 10-fold increase in the dose except for the AUC of the unsubstituted compound where the increase was 30-fold. Plasma elimination half-lives for the class ranged from 1.57 to 192 h with the exception of 30 mg/kg drometrizole.Oral bioavailability was low with ∼ 6% estimated for unsubstituted compound and 12.8–23% for others at 30 mg/kg dose. Bioavailability was lower following administration of the higher dose.Taken collectively, these data point to low oral absorption of phenolic benzotriazoles. The absorption decreased with increasing dose. Substituted compounds may be less metabolized compared to the unsubstituted. Phenolic benzotriazoles are ultraviolet-light absorbers used in a variety of industrial and consumer applications. We investigated the toxicokinetic behaviour of 9 compounds, covering unsubstituted, monosubstituted, disubstituted, and trisubstituted compounds, following a single gavage (30 and 300 mg/kg) and intravenous (IV) (2.25 mg/kg) administration in male rats. Following IV administration, no distinct pattern in plasma elimination was observed for the compounds with half-lives ranging from 15.4–84.8 h. Systemic exposure parameters, maximum concentration (C<sub>max</sub>) and area under the concentration time curve (AUC), generally increased with the degree of substitution. Following gavage administration, C<sub>max</sub> and AUC of unsubstituted compound were lower compared to the substituted compounds. C<sub>max</sub> and AUC increased ≤7-fold with a 10-fold increase in the dose except for the AUC of the unsubstituted compound where the increase was 30-fold. Plasma elimination half-lives for the class ranged from 1.57 to 192 h with the exception of 30 mg/kg drometrizole. Oral bioavailability was low with ∼ 6% estimated for unsubstituted compound and 12.8–23% for others at 30 mg/kg dose. Bioavailability was lower following administration of the higher dose. Taken collectively, these data point to low oral absorption of phenolic benzotriazoles. The absorption decreased with increasing dose. Substituted compounds may be less metabolized compared to the unsubstituted.