Animal testing predictive value

McCann, J. Ames, B. "The Salmonella/Microsome Mutagenicity Test Predictive Value for Animal Carcinogenicity " in "Origins of Human Cancer " Hiatt, H. H., Watson, J. D., Winsten, J. A., Eds., Cold Springs Harbor Laboratory Cold Springs Harbor, New York, 1977, pp. 1431-50. 

McCann, J. and Ames, B. N., The Salmonella/Microsome Mutagenicity Test Predictive Value for Animal Carcinogenicity, (p. 1431 in ref. 1)... 

McCann, J., and B.N. Ames. The Salmonella/microsome mutagenicity test predictive value for animal carcinogenicity, pp. 87-108. In W.G. Flaimn and M.A. 

Mutagenicity Test Predictive Value for Animal Carcinogenicity. 

J. McCann and B. N. Ames, The Salmonella/m Qvos>oxnt mutagenicity test Predictive value for animal carcinogenicity, in Origins of Human Cancer (H. H. Hiatt, J. D. Watson, andj. 

J. McCann and B. N. Ames, The Salmonella/micvosomt mutagenicity test Predictive value for animal carcinogenicity, in Origins of Human Cancer (H. H. Hiatt, J. D. Watson, and J. A. Winsten, eds.), Book C, Human Risk Assessment, Cold Spring Harbor Conferences on Cell Proliferation, Vol. 4, pp. 1513-1520, Cold Spring Harbor Laboratory (1977). 

Suppose a pathologist is uncertain about an animal s cause of death and obtains a positive test result for a certain pathology. Even if the pathologist knows the sensitivity and specificity of the test, that does not solve the problem, because to calculate the positive predictive value, it is necessary to know the prevalence of the particular tissue or effect that the test is designed to detect. The prevalence is thought of as the expected prevalence in the population from which the animal comes. The actual prevalence is usually not known, but often a reasonable estimate can be made. 

The use of the Draize tests has been receiving attention for a number of years because of animal welfare considerations. Consequently, the modifications of the existing protocol and the development of alternative methods have been extensively examined by the cosmetic and chemical industry to reduce animal usage and the occurrence of severe reactions. One modification of this model uses reduced volumes of 0.01 mL and 0.01 g, which reduces severe reactions but does not compromise the predictive value of the test. 

It should be emphasized that this kind of comparison is quite theoretical, and it does not provide absolute unsafe exposures, nor does it specify safe levels. However, with the present understanding of the animal experiments it would appear prudent to lower the TLV values for the compounds for which the human exposure may be up to 1/100 of the effective human dose. Even though the extrapolation from animal tests is compounded by uncertainties, the revision of the hygienic standards concerning the pregnant worker appears justifiable in such cases. With ever-increasing female participation in the work force, more emphasis should be placed on reproductive hazards and their prediction, in the absence of adequate epidemiologic data, from experimental results. 

Tissue Cross-Reactivity Studies for Monoclonal Antibodies Predictive Value and Use for Selection of Relevant Animal Species for Toxicity Testing... 

Tissue cross-reactivity studies, although burdensome, provide a rational in vitro assay to determine the range and intensity of distribution of potential epitopes reactive with a monoclonal antibody test article prior to its administration to humans. In addition, cross-reactivity studies provide a useful tool to identify animal species for safety assessment. The cross-reactivity profiles of different species can be compared to the profiles obtained in human tissues. The predictive value of the assay lies in incorporating the characteristics of the monoclonal antibody (isotype, subtype, and other molecular modifications) with the biological activity of the molecule itself, and the potential in vivo distribution of it. 

The human predictive value of combined animal toxicity testing... 

The actual record of evidence for the predictive value of animal studies and how they have benefited man and domestic animals will be reviewed in the following. However, the negative image needs to be rebutted. First, it must be remembered that predictive animal testing in toxicology, as we now know it, arose largely out of three historical events. 

A discussion of the predictive value of animal tests on phenothiazines has been given by Irwin°° and a comprehensive review of structure-activity relationships in the tricyclic compounds was published. ... 

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