The 2-year rodent bioassay in drug and chemical carcinogenicity testing: Performance, utility, and configuration for cancer hazard identification.

Autor: Suarez-Torres JD; Department of Pharmacy (Faculty of Sciences), Department of Toxicology (Faculty of Medicine), Universidad Nacional de Colombia, Bogotá, D.C., Colombia; Laboratory of Neuropeptides, Institute of Pharmaceutical Research, Faculty of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela. Electronic address: jdsuarezto@unal.edu.co., Orozco CA; Department of Animal Health, Faculty of Veterinary Medicine and Zootechnics, Universidad Nacional de Colombia, Bogotá, D.C., Colombia., Ciangherotti CE; Laboratory of Neuropeptides, Institute of Pharmaceutical Research, Faculty of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela.
Jazyk: angličtina
Zdroj: Journal of pharmacological and toxicological methods [J Pharmacol Toxicol Methods] 2021 Jul-Aug; Vol. 110, pp. 107070. Date of Electronic Publication: 2021 Apr 25.
DOI: 10.1016/j.vascn.2021.107070
Abstrakt: For several intended uses of chemicals, the 2-year rodent bioassay (RCB) has been the benchmark method to screen the carcinogenicity to humans of substances, according to the hazard identification sphere. Despite the ongoing controversy around this traditional testing, the RCB is in force and being used by stakeholders. After assembling the RCB's ability to forecast the carcinogenicity to humans of substances, the current review aimed to provide a discussion on the RCB's (1) sensitivity and specificity; (2) utility; (3) configuration, and (4) provisional role in the regulatory policy. In general, RCBs conducted at maximum tolerated doses (MTDs) exhibited a functional ability to (1) not missing the great majority of human carcinogens, and to (2) not responding to the large majority of human non-carcinogens. There is citable evidence supporting the use of MTDs to render RCBs as sensitive as possible, particularly provided the ethically-justified small samples used in RCBs. The literature shows that rodent-specific mechanisms of chemical carcinogenesis contribute significant unspecificity to RCBs. Nonetheless, the paradox between a functional sensitivity and a significant unspecificity can be predictively resolved through the application of Bayesian forecasting. In terms of performance to forecast the carcinogenicity to humans of either genotoxic or non-genotoxic substances, 2-species-RCBs added no value over the rat-RCB. Nevertheless, there is preliminary evidence cautioning that 15% of the rodent carcinogens probably carcinogenic to humans could be missed if mouse-RCBs are indiscriminately discontinued. More than thirteen RCB-related issues relevant to regulatory pharmacology and toxicology were discussed and summarized in this review.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: