A case study on the application of an expert-driven read-across approach in support of quantitative risk assessment of p,p'-dichlorodiphenyldichloroethane.
In vitro high-throughput screening
Quantitative risk assessment
Read-across
Toxicokinetics
Journal
Regulatory toxicology and pharmacology : RTP
ISSN: 1096-0295
Titre abrégé: Regul Toxicol Pharmacol
Pays: Netherlands
ID NLM: 8214983
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
01
10
2018
revised:
14
02
2019
accepted:
16
02
2019
pubmed:
23
2
2019
medline:
21
5
2019
entrez:
23
2
2019
Statut:
ppublish
Résumé
Deriving 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 plausible mechanisms of toxicity to build confidence in the read-across approach. This work demonstrated the value of NAMs such as read-across and in vitro HTS in human health risk assessment of environmental contaminants with the potential to inform regulatory decision-making.
Identifiants
pubmed: 30794837
pii: S0273-2300(19)30055-8
doi: 10.1016/j.yrtph.2019.02.010
pmc: PMC6854443
mid: NIHMS1540622
pii:
doi:
Substances chimiques
Environmental Pollutants
0
Insecticides
0
Dichlorodiphenyldichloroethane
V14159DF29
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
301-313Subventions
Organisme : Intramural EPA
ID : EPA999999
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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