The 2-year rodent bioassay in drug and chemical carcinogenesis testing: Sensitivity, according to the framework of carcinogenic action.

Autor: Suarez-Torres JD; Department of Pharmacy, Universidad Nacional de Colombia, Bogotá, Colombia.; Department of Toxicology, Universidad Nacional de Colombia, Bogotá, Colombia.; Institute of Pharmaceutical Research, School of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela., Jimenez-Orozco FA; Department of Pharmacology, Faculty of Medicine, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico., Ciangherotti CE; Institute of Pharmaceutical Research, School of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela.; Laboratory of Neuropeptides, School of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela.
Jazyk: angličtina
Zdroj: Toxicology mechanisms and methods [Toxicol Mech Methods] 2020 Jul; Vol. 30 (6), pp. 462-475. Date of Electronic Publication: 2020 Jun 17.
DOI: 10.1080/15376516.2020.1760986
Abstrakt: The long-term rodent bioassay (RCB) has been the gold-standard for the pre-marketing prediction of chemical and drug carcinogenicity to humans. Nonetheless, the validity of this toxicity test has remained elusive for several decades. In the quest to uncover the performance of the RCB, its sensitivity (SEN) was charted as the first step. This appraisal was based on (a) chemicals with sufficient epidemiological evidence of carcinogenicity, and (b) other substances with limited epidemiological evidence, or remarkable classifications of carcinogenicity based on mechanistic or pharmacological data. In the present study, chemicals evaluated for their carcinogenicity to humans in IARC Monographs volumes 1-123, U.S. EPA IRIS Assessments, and U.S. NTP RoC were considered. This investigation gathered additional evidence supporting that, in hazard identification, the RCB is unwarranted for mutagenic or direct-acting genotoxicants. However, for purposes of risk assessment or management, the RCB might be justified whenever there is a lack of reliable and/or comprehensive epidemiological data. The RCB exhibited a significantly different SEN for threshold-based human carcinogens compared to non-threshold-based ones. With threshold-based chemicals, to increase the SEN of the testing from 80% (rat-RCB) to 90%, the 2-species RCB might be warranted. Nevertheless, the resolve would depend on the viewpoint, and on the future analysis of the overall performance of the RCB. In terms of SEN, and cancer hazard identification, the comparison between the RCB and alternative methods (e.g. rasH2 mouse, Tg.AC mouse) is now enabled.
Databáze: MEDLINE
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