Risk assessment approaches: General definitions, limitations, and research needs

Walsh, Philip; Jones, T.D.; Griffin, Guy D.; Dudney, C.S.; Calle, E.E.; Easterly, C.E.

doi:10.1080/10934528209375056

Cited by 4 publications

(5 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These tests represent a fairly recent development in the testing of potential mutagens (and by default, potential carcinogens) and represent one of the most important achie,,ements in modern toxicology, The significance of these tests in helping to elucidate potential mechanisms of genetically Induced disease is unequivocal, Nonetheless, this is a vastly different activity from hazard assessment, where the goal is to estimate the likelihood o[' the compound to produce human disease, One way this issue could be partially resolved would be to demonstrate a correlation between the results obtained from the chronic and the short-term bioassays. While this does not resolve the critical issue of extrapolation to the human population, it provides supportive evidence of human hazard by demonstrating consistency of response in other species and across levels of biological organization (Purchase, 1980a;Walsh et al, 1982;Dudney et al, 1983;DuMouchel and Harris, 1983). Many investigators have attempted to demonstrate this correlation but, in general, have limited their investigations to the study of individual experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, in the near term, data from laboratory investigations are likely to continue to be the sole source of information on the hazard posed by many environmental, occupational, and dietary contaminants. Therefore, it is imperative to develop methods which would allow for the scientifically defensible setting of priorities to guide research needs (Doll and Peto, 1981;Walsh et al, 1982). This is particularly true for the short-term tests, given their inherent potential for rapid and comparatively inexpensive results.…”

Section: Correlation Of Tumorigenicity and Mutagenicitymentioning

confidence: 99%

“…No method taken alone should be recognized as having the capacity to address ali of the c,Jmplex issues that arise irl the evaluation of human risk. Alternatively, comprehensive reviews of the quality and quantity of the data can be employed as means of distinguishing comparative or relative estimates of risk (Walsh et al, 1982;Dudney et al, 1983;Interdisciplinary Panel on Carcinogenicity, 1984). In this way priorities can be established, yet remain flexible and responsive to the respective state of knowledge.…”

Section: Critical Syn'i'hf_is Of Previous Liq'eraturementioning

confidence: 99%

“…Methods have been developed which are not model dependent, can utilize diverse data, and do not mask deficiencies in the existing data (Jones et al, 1985;. Further, since the approach reduces data to a common scale, it can provide a scientifically justifiable framework for the necessary integration of data and subsequent comparison of the endpoints observed in the toxicologic bioassays (Walsh et al, 1982;Dudney et al, 1983).…”

Section: Critical Syn'i'hf_is Of Previous Liq'eraturementioning

confidence: 99%

See 3 more Smart Citations

Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

Glass¹,

Jones²,

Easterly³

et al. 1990

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Correlation Of Tumorigenicity and Mutagenicitymentioning

confidence: 99%

Section: Critical Syn'i'hf_is Of Previous Liq'eraturementioning

confidence: 99%

Section: Critical Syn'i'hf_is Of Previous Liq'eraturementioning

confidence: 99%

See 2 more Smart Citations

Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

Glass¹,

Jones²,

Easterly³

et al. 1990

Self Cite

View full text Add to dashboard Cite

“…Other studies, such as the IARC monograph series (1979)(1980)(1981)(1982)(1983), provide comprehensive reviews of a given chemical from which one can make some qualitative judgment of the risk level. The Oak Ridge National Laboratory has worked extensively in both theory of risk analysis and technologyspecific applications (Walsh et al, 1982;Dudney et al, 1983;Jones et al, 1983;Jones, 1984;Jones et al, 1984). A heuristic approach to health-effects analysis, based on currently available, and constantly increasing, biological test data is shown in Table 1.…”

Section: Introduction and Objectivementioning

confidence: 99%

Permissible Concentrations of Chemicals in Air and Water Derived From Rtecs Entries: a "Rash" Chemical Scoring System

1985

View full text Add to dashboard Cite

Many chemicals are of concern to human health, but only a few have epidemiologically derived risk estimates. About 45,000 chemicals are listed in RTECS, most of which have had some testing in subhuman models. RTECS entries range from cellular effects through organoleptic damage to lethality, with many pathological endpoints listed, including mutagenic changes, irritation, teratogenesis, cancer, mortality, etc. However, it is difficult to extend any biological test results to human risk assessments. If the results are extended, the degree of validity is highly uncertain. This paper describes a logical basis for using the entire complex spectrum of test results to evaluate the overall toxicological potency of a chemical to be assayed (i.e., an interviewing chemical) and describes how to derive tentative, permissible concentrations in air and water for any particular chemical for which no regulatory guidance exists. This approach has been tested for 16 reference chemicals discussed in NIOSH Criteria Documents, EPA-CAG reports, etc. The evaluations are uncomplicated, but occasionally it is difficult to match RTECS entries for two different chemicals. Difficult comparisons may require some familiarity with experimental design and the toxicological literature. One important product of this novel approach is that a distribution or array of potency values is obtained for any chemical evaluated. This distribution reflects many uncertainties stemming from low statistical power, experimental design, pharmacological processes, interspecies variability, dose rate, biological effect monitored, route of treatment, etc. The array of relative values for a particular chemical reflects many different biological and physical conditions. The distribution of the array helps to index a composite toxicological profile for many different biological effects resulting from numerous treatment protocols. To minimize the effect of extreme sensitivity of certain (perhaps novel) biological test models, possible errors in the RTECS data-base, and possible human pharmacological insensitivity to a particular chemical and/or a particular route of administration, we consider the interquartile range (i.e., the central 50%) of the array of relative potency values between two chemicals being compared as a practical measure of uncertainty. Thus, the range in response derived from variability in relative potency should be useful in addressing the range of response in man as estimated from extrapolations of test data.

show abstract

Animal studies and prediction of human tumors can be aided by graphical sorting of animal data: Neoplastic risk from B(a)P, benzene, benzidine, and chromium

Jones

Walsh

1985

American J Industrial Med

View full text Add to dashboard Cite

This work is a graphical study of all known dose-response data for neoplasia induced by B(a)P, benzene, benzidine, and chromium administered to test animals. Doses are put in units of lifetime intake given in micromoles of chemical per kilogram body weight, and responses are in percent increased effect per unit dose. Space limitations do not permit experiment-by-experiment critiques; however, computer graphics have been used to compare the relationship of any individual dose-response point estimate to other such point estimates for the chemical of interest. Graphics are also used to study variability resulting from different experimental parameters such as species, route of intake, number of treatments, pathological classification of neoplasia, etc. Graphical sorting, according to various physical and biological classification parameters, permits one to judge, from visual inspection, such questions as whether mice as a species are more sensitive than rats as a species, whether intravenous injection is generally more effective than inhalation, whether a single well-defined dose-response function, which ignores these classification parameters, can be evaluated numerically from the composite data base deriving from all oncogenic studies with a given chemical, etc.

show abstract

Risk assessment approaches: General definitions, limitations, and research needs

Cited by 4 publications

References 2 publications

Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

Permissible Concentrations of Chemicals in Air and Water Derived From Rtecs Entries: a "Rash" Chemical Scoring System

Animal studies and prediction of human tumors can be aided by graphical sorting of animal data: Neoplastic risk from B(a)P, benzene, benzidine, and chromium

Contact Info

Product

Resources

About