Biomedical subjects

M Szyszkowicz

Publications and source records attributed to M Szyszkowicz.

4 recordsLinked to original sources

PubMed1993

An overview of the report: correlation between carcinogenic potency and the maximum tolerated dose: implications for risk assessment.

Current practice in carcinogen bioassay calls for exposure of experimental animals at doses up to and including the maximum tolerated dose (MTD). Such studies have been used to compute measures of carcinogenic potency such as the TD50 as well as unit risk factors such as q1 * for predicting low-dose risks. Recent studies have indicated that these measures of carcinogenic potency are highly correlated with the MTD. Carcinogenic potency has also been shown to be correlated with indicators of mutagenicity and toxicity. Correlation of the MTDs for rats and mice implies a corresponding correlation in TD50 values for these two species. The implications of these results for cancer risk assessment are examined in light of the large variation in potency among chemicals known to induce tumors in rodents.

Animals↗

PubMed1991

A model-free approach to low-dose extrapolation.

Estimates of risk associated with exposure to low levels of carcinogenic substances present in the environment are generally obtained by linear extrapolation from higher exposure levels at which risks can be estimated directly. In this paper, we examine the scientific basis for the assumption of low-dose linearity in carcinogenic risk assessment and the different statistical methods that have been proposed for linear extrapolation. A model-free approach to linear extrapolation is described and illustrated using epidemiological data on radiation carcinogenesis. The statistical properties of this method are empirically assessed using 572 selected sets of bioassay data.

Carcinogens, Environmental↗

PubMed1990

Quantitative factors in chemical carcinogenesis: variation in carcinogenic potency.

The quantitative assessment of toxicological data on the carcinogenic potential of chemicals requires consideration of a number of factors, including mathematical models of the mechanism of carcinogenic action and pharmacokinetic models for the metabolic activation of the parent compound to its reactive metabolite. In this article, the use of such models in estimating carcinogenic potency and in predicting risks at low levels of exposure is discussed, along with other factors involved in the evaluation of carcinogen bioassay data. The Carcinogenic Potency Database (CPDB) established by Gold et al. (1984, Environ. Health Perspect. 58, 9-322) is used to illustrate the application of quantitative approaches to carcinogenic risk assessment and to examine the variation in the potency of chemical carcinogens. Based on an analysis of 585 experiments selected from the CPDB, the risk-specific (10(-6) doses (RSDs) obtained by linear extrapolation from the TD50 were generally within a factor of 5-10 of those derived from the linearized multistage model. The RSDs obtained by linear extrapolation from the TD50 are roughly log-normally distributed with a median of about 20-90 ng/kg/day, depending on the subset of the CPDB considered. This distribution has been used by Rulis (1986, in Food Protection Technology (C. W. Felix, Ed.), pp. 29-37, Lewis, Chelsea, MI) to explore the concept of a threshold of regulation for chemical carcinogens present in the environment at low levels.

Animals↗

PubMedDate not supplied

Life expectancy.

Explore the source record for details and available documents.

Algorithms↗