Assessing the Toxicity of Benzotriazole Ultraviolet Stabilizers to Fishes: Insights into Aryl Hydrocarbon Receptor-Mediated Effects.

Benzotriazole ultraviolet stabilizers (BUVSs) are chemicals used to mitigate UV-induced damage to manufactured goods. Their presence in aquatic environments and biota raises concerns, as certain BUVSs activate the aryl hydrocarbon receptor (AhR), which is linked to adverse effects in fish. However, potencies of BUVSs as AhR agonists and species sensitivities to AhR activation are poorly understood. This study evaluated the toxicity of three BUVSs using embryotoxicity assays. Zebrafish (Danio rerio) embryos exposed to BUVSs by microinjection suffered dose-dependent increases in mortality, with LD50 values of 4772, 11 608, and 56 292 ng/g-egg for UV-P, UV-9, and UV-090, respectively. The potencies and species sensitivities to AhR2 activation by BUVSs were assessed using a luciferase reporter gene assay with COS-7 cells transfected with the AhR2 of zebrafish and eight other fishes. The rank order of potency for activation of the AhR2 from all nine species was UV-P > UV-9 > UV-090. However, AhR2s among species differed in sensitivities to activation by up to 100-fold. An approximate reversed rank order of species sensitivity was observed compared to the rank order of sensitivity to 2,3,7,8-tetrachlorodibenzo[p]dioxin, the prototypical AhR agonist. Despite this, a pre-existing quantitative adverse outcome pathway linking AhR activation to embryo lethality could predict embryotoxicities of BUVSs in zebrafish.

Alkylation of Benz[a]anthracene Affects Toxicity to Early-Life Stage Zebrafish and In Vitro Aryl Hydrocarbon Receptor 2 Transactivation in a Position-Dependent Manner.

Polycyclic aromatic hydrocarbons (PAHs) are structurally diverse organic chemicals that can have adverse effects on the health of fishes through activation of aryl hydrocarbon receptor 2 (AhR2). They are ubiquitous in the environment, but alkyl PAHs are more abundant in some environmental matrices. However, relatively little is known regarding the effects of alkylation on the toxicity of PAHs to fishes in vivo and how this relates to potency for activation of AhR2 in vitro. Therefore, the objectives of the present study were to determine the toxicity of benz[a]anthracene and three alkylated homologs representing various alkylation positions to early life stages of zebrafish (Danio rerio) and to assess the potency of each for activation of the zebrafish AhR2 in a standardized in vitro AhR transactivation assay. Exposure of embryos to each of the PAHs caused a dose-dependent increase in mortality and malformations characteristic of AhR2 activation. Each alkyl homolog had in vivo toxicities and in vitro AhR2 activation potencies different from those of the parent PAH in a position-dependent manner. However, there was no statistically significant linear relationship between responses measured in these assays. The results suggest a need for further investigation into the effect of alkylation on the toxicity of PAHs to fishes and greater consideration of the contribution of alkylated homologs in ecological risk assessments. Environ Toxicol Chem 2022;41:1993-2002. © 2022 SETAC.