A case study on the application of an expert-driven read-across approach in support of quantitative risk assessment of p,p’-dichlorodiphenyldichloroethane

Publication date: Available online 19 February 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Lucina E. Lizarraga, Jeffry L. Dean, J. Phillip Kaiser, Scott C. Wesselkamper, Jason C. Lambert, Q. Jay ZhaoAbstractDeriving human health risk estimates for environmental chemicals has traditionally relied on in vivo toxicity databases to characterize potential adverse health effects and associated dose-response relationships. In the absence of in vivo toxicity information, new approach methods (NAMs) such as read-across have the potential to fill the required data gaps. This case study applied an expert-driven read-across approach to identify and evaluate analogues to fill non-cancer oral toxicity data gaps for p,p’-dichlorodiphenyldichloroethane (p,p’-DDD), an organochlorine contaminant known to occur at contaminated sites in the U.S. The source analogue p,p’-dichlorodiphenyltrichloroethane (DDT) and its no-observed-adverse-effect level of 0.05 mg/kg-day were proposed for the derivation of screening-level health reference values for the target chemical, p,p’-DDD. Among the primary similarity contexts (structure, toxicokinetics, and toxicodynamics), toxicokinetic considerations were instrumental in separating p,p’-DDT as the best source analogue from other potential candidates (p,p’-DDE and methoxychlor). In vitro high-throughput screening (HTS) assays from ToxCast were used to evaluate similarity in bioactivity profiles and make inferences toward plausib...
Source: Regulatory Toxicology and Pharmacology - Category: Toxicology Source Type: research