Bioassay, animal

No studies were located regarding cancer in humans after oral exposure to endosulfan. Carcinogenic effects of endosulfan were investigated in a number of chronic animal bioassays with rats and mice the available data provide no evidence that endosulfan is carcinogenic. 

The above example illustrates the inherent problems that can arise in the use of standardised protocols for assessing chemicals naturally occurring in the food chain. Had work on comparative metabolism and pharmacokinetics been undertaken before any animal bioassay work, it could have given more useful information. The extrapolation of effects obtained in high-dose animal studies to a large number of people exposed to a low dose is not the most effective use of resources. Nor are such experiments consistent with biological reality. There are few chemicals that would not cause illness or death if the daily intake was increased some 100-1000 fold as is the situation in many... 

An inadequate intake in the diet of those food chemicals that are essential nutrients results in health risks. Indeed these risks are by far the most important in terms of the world s population where malnutrition is a major public health problem. But, unlike the toxic chemicals, they would show a very different dose-response if they were subject to similar animal bioassays. At very low doses there would be a high risk of disease that would decrease as the dose was increased, the curve would then plateau until exposure was at such a level that toxicity could occur. Figure 11.2 shows this relationship which is U- or J-shaped rather than the essentially linear dose-response that is assumed for chemicals that are only toxic. The plateau region reflects what is commonly regarded as the homeostatic region where the cell is able to maintain its function and any excess nutrient is excreted, or mechanisms are induced that are completely reversible. 

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

Given the problems associated with using standard animal bioassays and doses above the level where hormetic effects might be observed (which... 

Anderson, S.L., F.L. Harrison, G. Chan, and D.H. Moore II. 1990. Comparison of cellular and whole-animal bioassays for estimation of radiation effects in the polychaete worm Neanthes arenaceodentata (Poly-chaeta). Arch. Environ. Contam. Toxicol. 19 164-174. 

Farrar, D.B. and Crump, K.S. (1988). Exact statistical tests for any carcinogenic effect in animal bioassays. Fundam. Appl. Toxicol. 11 652-663. 

Evidence from animal bioassays supports the hypothesis that it is the cytosolic system and not the microsomal oxidative system that is responsible for the carcinogenicity of 1,2-dibromoethane. 

The investigation of the presence of marine biotoxins in water, phytoplankton, and food has been achieved by several in vitro assays. However, alternatives to the animal bioassay for marine toxins have not been sufficiently evaluated in interlaboratory studies needed to demonstrate their scientific validity. In addition, these methods continue to be time consuming and expensive for intensive monitoring programs, and present some difficulties for their automation. 

Gold, L.S., C.B. Sawyer, R. Magaw, et al. 1984. A carcinogenic potency database of the standardized results of animal bioassay. Environ. Health Perspect. 58 9-319. 

Preliminary testing on whole animal (bioassay) and isolated tissue preparations (voltage-clamped squid giant axons) showed effects similar to those measured for STX and neo-STX. Again the presence of anionic cryptic forms of the toxins was indicated. 

Animal bioassays showed that camphor was not carcinogenic in rats injected subcutaneously however, when the cancer promoter croton oil was concurrently applied to the skin of mice, 2 of 110 treated mice developed carcinomas. ... 

In an animal bioassay a dose-related increase in the incidence of adrenal cortical adenomas (with a few carcinomas at this site as well) has been observed in one strain of rats in both sexes. The significance of these lesions in aged rats in unclear. Other bioassays in mice and rats had sufficient limitations, such that the lARC deemed them inadequate for evaluation and concluded that there are insufficient data to evaluate the carcinogenicity of parathion for animals and no data for humans. ... 

The first step in risk assessment is to gather health-related information associated with an exposure. Ideally, hazard identification starts before there is significant use of the agent. The structure of the compound is compared with that of compounds with known toxicity profiles. Cell-based studies are often performed to screen for toxicity. Finally, animal bioassays and human studies are performed to characterize and develop a toxicity profile. Multiple health-related endpoints are evaluated to determine if the compound is associated with adverse effects. Advantages of animal studies include experimental control and accurate knowledge of the dose. 

In 1980, the NAS (38) reported that a review of 10 epidemiological studies failed to support or refute the results of the positive animal bioassays. This report suggested that chloroform may cause cancer in humans. The NAS stated that any association between THMs and bladder cancer was small and had a large margin of error both because of statistical variance and the nature of the studies that had been conducted. The NAS reached the following conclusion (38) ... 

The advantages of an animal bioassay are that protein digestibility, amino acid bioavailability, and the presence of antinutritional factors can be ascertained. However, animal-based feeding studies can be difficult. First, these assays are expensive to conduct and time-consuming. Secondly, these assays require animals... 

Values for a test protein will be lower than for the reference protein. The reliability of results for chemical scoring methods depends upon the accuracy of the amino acid determinations that form the basis for these assays. Chemical scoring and animal bioassays tend to provide similar relative rankings of protein quality however, the actual values may be different. Chemical scoring methods should not replace a bioassay for testing the quality of a food protein for which there is very little nutritional information. 

Alarie, Y., Nielsen, G.D. and Schaper, M.M. (2000) Animal bioassays for evaluation of indoor air quality, in Indoor Air Quality Handbook (eds ). Spengler, J.M. Samet and ).F. McCarthy), McGraw-Hill, New York, USA. 

Structure-Activity Analysis In Vitro Tests Animal Bioassays Epidemiology... 

---