Toxicokinetic and mechanistic considerations in the interpretation of the rodent bioassay.

Abstract:

:When chemicals that are nongenotoxic in conventional assays produce increases in tumor incidence in rodents in chronic bioassays, the determination of the significance of these data for human safety is a challenging task. An important first step in this process is consideration of available data on the mechanism of action and biological properties of the chemical as well as pharmacokinetic and metabolism data in the species showing the response. In recent years, there has been an increase in the understanding of so-called "secondary mechanisms" of carcinogenesis (e.g., thyroid tumors in rats following exposure to enzyme inducers). Application of these data may assist in determination of human risk. There are 2 important questions that will be explored and developed: Are there biological effects produced in the test species that could explain the increase in tumor incidence, and will these effects be reproduced in humans? What is the exposure to the chemical that is associated with the increase in tumors, and how does this relate to exposure in humans?

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

MacDonald JS,Lankas GR,Morrissey RE

doi

10.1177/019262339402200206

subject

Has Abstract

pub_date

1994-03-01 00:00:00

pages

124-40

issue

2

eissn

0192-6233

issn

1533-1601

journal_volume

22

pub_type

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