PubMed Health⌕ Search

Biomedical subjects

E A Crouch

Publications and source records attributed to E A Crouch.

10 recordsLinked to original sources
PubMed1992

Monte Carlo techniques for quantitative uncertainty analysis in public health risk assessments.

Most public health risk assessments assume and combine a series of average, conservative, and worst-case values to derive a conservative point estimate of risk. This procedure has major limitations. This paper demonstrates a new methodology for extended uncertainty analyses in public health risk assessments using Monte Carlo techniques. The extended method begins as do some conventional methods--with the preparation of a spreadsheet to estimate exposure and risk. This method, however, continues by modeling key inputs as random variables described by probability density functions (PDFs). Overall, the technique provides a quantitative way to estimate the probability distributions for exposure and health risks within the validity of the model used. As an example, this paper presents a simplified case study for children playing in soils contaminated with benzene and benzo(a)pyrene (BaP).

Carcinogens, Environmental↗
PubMed1988

One-hit models of carcinogenesis: conservative or not?

One-hit formulas are widely believed to be "conservative" when used to analyze carcinogenesis bioassays, in the sense that they will rarely underestimate risks of cancer at low exposures. Such formulas are generally applied to the lifetime incidence of cancer at a specific site, with risks estimated from animal data at zero dose (control), and two or more additional doses that are appreciable fractions of a maximum tolerated dose. No empirical study has demonstrated that the one-hit formula is conservative in the sense described. The Carcinogenesis Bioassay Database System contains data on 1212 separate bioassays of 308 chemical substances tested at exactly three evaluable doses. These provided sufficient data to examine 8432 specific combinations of cancer site with sex, species, and chemical. For each of these we fitted a one-hit formula to the zero and maximum dose data points, then examined the relation of the fitted curve to the incidence rate observed at the mid-dose, with and without adjustment for intercurrent mortality. Both underestimates and overestimates of risk at mid-dose occurred substantially more often than expected by chance. We cannot tell whether such underestimates would occur at lower doses, but offer six biological reasons why underestimates might be expected. In a high percentage of animal bioassays, the one-hit formula is not conservative when applied in the usual way to animal data. It remains possible that the one-hit formula may indeed be conservative at sufficiently low doses (below the observational range), but the usual procedure, applied to the usual dose range, can be nonconservative in estimating the slope of the formula at such low doses. Risk assessments for regulation of carcinogens should incorporate some measure of additional uncertainty.

Animals↗
PubMed1987

Risk assessment and comparisons: an introduction.

Risk assessment is presented as a way of examining risks so that they may be better avoided, reduced, or otherwise managed. Risk implies uncertainty, so that risk assessment is largely concerned with uncertainty and hence with a concept of probability that is hard to grasp. The results of even the simplest risk assessments need to be compared with similar assessments of commonplace situations to give them some meaning. We compare and contrast some risk estimates to display their similarities and differences.

Accidents↗
PubMed1987

Dose-response relationships for carcinogens: a review.

We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites.

Animals↗
PubMed1983

Uncertainties in interspecies extrapolations of carcinogenicity.

The usual classification of results of animal carcinogenicity tests is positive or negative. Attempting to observe correlations between species using such results is complicated by differing test sensitivities. In these circumstances it is helpful to use models to represent the experimental data in a consistent way. Fitting the model parameters to the data allows computation of confidence limits and an assessment of concordance or discordance between different species in a way which accounts for differing test sensitivities. This paper describes this approach in detail for one class of models applied to the carcinogenicity test results of 187 of the NCI bioassay series, allowing comparison between B6C3F1 mice, Fischer 344 rats and Osborne Mendel rats. It is shown that the uncertainties in extrapolating between species are larger than generally acknowledged (a standard deviation of a factor of approximately 4.5), but that within these uncertainties there are few if any discordances.

Age Factors↗