Edmund A. C. Crouch

Cancer risk management A review of 132 federal regulatory decisions.

Various federal agencies are responsible for promulgating regulations and standards to protect the public from exposure to environmental carcinogens. Although many factors are considered in the decision to regulate a carcinogen, one important issue concerns the probability that individuals in an exposed population will develop cancer. What has not been clear, however, is the level of cancer risk that triggers regulation, or whether there is consistency within and between agencies in arriving at the risk decisions that underpin regulatory action. The authors retrospectively reviewed the use of cancer risk estimates in prevailing federal standards and in withdrawn regulatory initiatives to determine whether any simple patterns emerge to correlate risk level with regulatory action. The results show that there are definite patterns and a surprising degree of consistency in the federal regulator process.

Interspecies comparison of carcinogenic potency

For guidance in decisions on how to safeguard humans from carcinogens, it is necessary to use data on carcinogenesis in animals. This paper discusses how such data, combined with human experience, may be used quantitatively in such decisions. It is demonstrated empirically that good correlations exist between different species for suitably defined carcinogenic potencies for various chemicals. This allows sufficient accuracy in extrapolating from animal data to human risk to support a logical scheme for the evaluation of such risks. Some recommendations for future research are given.

The Carcinogenic Risk of Some Organic Vapors Indoors: A Theoretical Survey

This exploratory report examines the risk of selected organic air pollutants measured in homes in the United States and the Netherlands. After several theoretical assumptions, estimates are made for the carcinogenic potency of each chemical; combined with the exposure measurements, these give estimates of cancer risk. These estimates are compared with risks of these same pollutants outdoors and in drinking water and also with other well-known indoor air pollutants: cigarette smoke, radon gas, and formaldehyde. These comparisons indicate priorities for action. Some suggestions are made for future studies.

The Evaluation of Integrals of the form ∫+∞ −∞ f(t)exp(−t 2) dt: Application to Logistic-Normal Models

Abstract Logistic-normal distributions and related functions arise in a variety of statistical applications of current interest, including binary measurement-error models and the analysis of teratogenicity experiments. Analytic intractability has led to the development of numerous approximations to the desired forms, often with consequences that have not been well studied. A method is developed to compute these forms to arbitrary accuracy, and comparative calculations are made that show when the common numerical alternative, 20-point Gaussian quadrature, begins to fail. By using a simple matrix transformation, this method can be used with multiple covariate regression models of the logistic-normal form. We conducted a simulation study that compares the ability of 20-point Gaussian quadrature and our new method to obtain the maximum likelihood estimator of relative risk in the logistic-normal measurement-error model. Using standard subroutines to maximize the likelihood equations, 27 of 50 trials failed to...

Tautology or not tautology

It has been suggested that the good correlations found between carcinogenic potency in mice and in rats could be an artifact. The artifact suggested arises because there are four correlations to consider--interspecies correlations of toxicity, interspecies correlations of carcinogenic potency, and two intraspecies correlations between toxicity and carcinogenic potency--and the existence of any three implies the fourth. It was argued that the intraspecies correlations between toxicity and potency were due to criteria for data selection. Here we discuss the correlations in detail and show that they are principally due to the experimental observation that there are few cases where most or all animals in a bioassay get cancer. We conclude that the correlations between carcinogenic potency are valid.

A Possible Relationship Between Toxicity and Carcinogenicity

Carcinogenic response is compared to noncarcinogenic toxicity in that group of chemicals tested by the National Cancer Institute (NCI) and National Toxicology Program (NTP) between 1976 and 1982 and reported in the Carcinogenesis Technical Report Series. A positive finding of carcinogenicity in the bioassay is correlated with the degree of noncarcinogenic chronic toxicity of the dose applied. Comparisons of acute toxicity (LD50) with carcinogenic potency show that they are correlated, but the correlation may in part be an artifact, since doses used in the NCI/NTP carcinogenesis bioassays are toxic and because reliable measures of potency can only be derived for positive carcinogenic responses. The high correlations for certain classes of chemicals and the relationship of chronic toxicity to positive carcinogenic finding suggest that these relationships are more than spurious. Since toxicities in different species are highly correlated, these findings imply that carcinogenicities in different species are also correlated.

Risk Assessment and Comparisons

Every day we take risks and avoid others. It starts as soon as we wake up. One of us lives in an old house that had old wiring. Each time he turned on the light, there was a small risk of electrocution. Every year about 200 people are electrocuted in the United States in accidents involving home wiring or appliances, representing a risk of death of about 10-6 per year, or 7 × 10-5 per lifetime. To reduce this risk, he got the wiring replaced. When we walk downstairs, we recall that 7000 people die each year in falls in U.S. homes. But most are over 65, so we pay little attention to this risk since both of us are younger than that.

Organ Specificity of Rodent Tumor Induction: A Test of Statistical and Graphical Methods by Examination of Tumor Induction from Ingestion of Selected Substances

With few exceptions current federal risk assessment policy regards the induction of tumors at one site as equivalent to the induction of tumors at any other site for purposes of risk assessment.1 Sufficient bioassay data exist to test this policy with the closely related rodent species, mouse and rat.

Carcinogenic Risk Assessment—The Consequences of Believing Models

To estimate risks to humans from carcinogens requires extrapolation from animal or other data. Any such extrapolation must be made in the context of a model or models, but no current consensus exists as to which models are correct. There is no shortage of suggested models for this task, each motivated by theoretical arguments, but the differences among them can lead to enormously different predictions. Furthermore, they often lack any practical demonstration of validity.

Problems in Interspecies Comparisons

In discussing the risk of cancer, we are concerned with the risk to man. But we rarely have data on man — and hope to get little more, because to have data implies that exposure has been excessive. Accordingly we must use data on animals, and it is then necessary to find out how to use these data to predict human cancers.