A New Approach to Evaluating Carcinogenic Risk

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Feb 1

PMID 1736302

Citations 2

Authors

M W Pariza

Affiliations

Soon will be listed here.

Abstract

Carcinogenic risk assessments are based on extrapolating from high-dose chronic rodent-feeding studies to human-exposure levels. A serious problem is that about half of all substances tested at their respective maximum tolerated dose (MTD) are found to induce cancer. The MTD as currently defined has been criticized because it may stimulate cell proliferation in susceptible tissues. Such chemically induced mitogenesis is postulated to increase the probability that neoplasia will develop at the affected site. It is proposed that, in the development of an MTD for a given substance, chemically induced mitogenesis be considered an undesirable toxic manifestation. Hence, mitogenesis should not be induced by a substance fed at its true MTD. Since MTDs determined in this fashion are likely to be lower than those developed using current criteria, an added level of protection is introduced by employing a safety factor similar to that used now in determining acceptable daily intakes for noncarcinogenic food additives. In calculating acceptable daily intakes, the usual safety factor is 100; i.e., the acceptable daily intake is set at 1% of the no-observed-effect level. Hence it is proposed that the acceptable daily level of exposure to a substance that does not induce cancer at its MTD as defined herein be set at 1% of that MTD. On the other hand, a chemical that induces cancer at its MTD as defined herein would continue to be regulated as is customary now.

Citing Articles

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Industrial ecology: concepts and approaches.

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