Biomedical subjects

R J Moolenaar

Publications and source records attributed to R J Moolenaar.

4 recordsLinked to original sources

PubMed1990

A scheme for classifying carcinogens.

We present a scheme for classifying chemical carcinogens according to the weight of the evidence that each substance poses a human cancer hazard. The approach represents a logical extension of and builds upon those previously developed by the International Agency for Research on Cancer, the U.S. Environmental Protection Agency, and the so-called Tripartite Group of industrial scientists. It takes into account new scientific knowledge about chemical carcinogenesis and animal models. Eight categories are presented: known human carcinogen (Category 1), carcinogenic activity in animals, probable human carcinogen (Category 2), possible human carcinogen (Category 3), equivocal evidence for carcinogenic activity (Category 4), evidence inadequate for classification (Category 5), carcinogenic activity in animals; probably not a human cancer hazard (Category 6), carcinogenic activity in animals; considered not a human cancer hazard (Category 7), evidence of noncarcinogenicity (Category 8). Evidence useful for categorization includes human studies, animal bioassays, corroborative evidence from bioassays, and mechanistic studies relevant to determining the predictivity of animal responses for human hazard. Weighing this evidence to derive a conclusion about classification is a process that requires expert judgment; it cannot now be reduced to a simple set of decision rules. However, we identify the kinds of information that can be useful in this process, and indicate how each might most appropriately be used.

Animals↗

PubMed1989

IARC and HHS lists of carcinogens: regulatory use based on misunderstanding of the scope and purpose of the lists.

In the last two decades there has been a tremendous increase in data on carcinogenic activity in experimental animals. While there have been few additions to the list of human carcinogens based on human data, the number of carcinogens based on animal data continues to increase unabated. The International Agency for Research on Cancer (IARC) list of carcinogens grew out of the IARC Monograph Series. The evidence classification system used to prepare the IARC lists in 1980, 1982, and 1988 is based on the sufficiency, i.e., strength, of the evidence of carcinogenic activity in one or more studies, not a full weight-of-the-evidence evaluation of all relevant data. Titles of categories of animal evidence referring to human risk potential were based on a presumption: "for practical purposes . . . as if." No evaluation was made of the predictive relevance of animal data to human risk. The IARC listing did not involve evaluation of potency or mechanism and was intended as a useful input but not as a basis for regulatory or legislative decisions. The Department of Health and Human Services (HHS) lists in the Annual Reports on Carcinogens are selected from the IARC lists and from reports of positive bioassay experiments conducted by the National Toxicology Program (NTP). The reports on the NTP bioassays relate to the strength of the evidence in each experiment and recognize that a "wider analysis" is necessary for determination of human risk. Because of a misunderstanding of the limited scope of the analysis involved, the IARC and HHS lists have recently been used as a basis for legislative and regulatory decisions. Examples of unanticipated use of the lists as triggers for regulatory and legislative decisions will be discussed. Some recommendations to mitigate the consequences of past unanticipated use of the lists and to prevent further misuse are discussed.

Animals↗

PubMed1989

Commentary on EPA carcinogen risk assessment guidelines.

EPA has indicated the Agency's Cancer Risk Assessment Guidelines are intended to be evergreen, i.e., subject to revision as advances are made in scientific understanding or difficulties are encountered. Several changes could be made in the Guidelines to better utilize advances in science, some of which EPA has already incorporated into risk assessment procedures, and also to alleviate difficulties encountered by the Agency. The hazard identification step of risk assessment should be more clearly defined, especially with respect to describing the best use of animal data to predict human hazard. The classification system for summarizing carcinogenic hazard should be expanded, and the titles revised, to better describe the varying degrees of knowledge concerning human carcinogenic hazard derived from experimental data. Current dose response estimation procedures should be supplemented to provide risk managers more perspective on human risk. Suggested additions are a central estimate of the upper bound of the dose response curve and a most plausible estimate of human response as a function of dose. The central estimate of the upper bound still includes the calculation of a statistical upper limit, but utilizes central estimates for some of the critical policy options. The most plausible estimate relies heavily on evaluation of the mechanism of carcinogenic activity and its implications for dose response estimation in humans. Thus, the outcome of dose response evaluation would include the current upper bound (worst case), a more central estimate of the upper bound, a most plausible estimate, and the lower bound.

Animals↗

PubMed1986

The industrial role in risk assessment.

Industry has a major role in the assessment and management of risk to society from its operations. Much of the basic knowledge of manufacturing operations, product distribution, use and ultimate disposal of products and byproducts resides in industry. Basic data on the health and environmental effects of materials in commerce has been generated by industry. This information must be utilized in the evaluation of risk so that appropriate management decisions can be made. Experience gained in the industrial sector with risk assessment and management should be of value to government in its oversight role on behalf of society. There is growing realization in both industry and government of the need for more effective communication of risk to the general public in the context of management decisions.

Communication↗