Extrapolation of experimental data from animals to man.

Abstract

Conditions for extrapolating toxicologic data from animals to man were studied. In the search for general regularities associated with the comparative sensitivity of humans and various species of animals to toxins, it was shown that the toxicity parameters of compounds and the biological constants of mammals correlate with body weight. This relationship is well described by a rectilinear regression equation which holds for more than 100 of the most diverse mammalian biological constants. The toxicity parameters for 80% of the substances also are subordinated to this regularity. This made it possible to develop a computational method for extrapolating toxicologic data from animals to the "average" man. In order to increase the reliability of extrapolation, it is necessary to take into consideration the limits of variability of sensitivity of various population contingents to the effect of chemical compounds, estimate the accuracy of establishing the threshold and no-effect doses of substances under chronic experiment conditions with animals and determine the maximally possible error associated with extrapolating experimental data to the "average" man. In this respect, it is advisable to use a coefficient of reserve whose value should not be less than 10 in order to ensure safe conditions for the transfer of the results of toxicologic studies to public health practice.

Effects of 8-prenylnaringenin on the hypothalamo-pituitary-uterine axis in rats after 3-month treatment

“…Hence, intake of high quantities (mg) of 8PN is possible. Pharmacologists claim that doses per kg/BW applied to rats must be 10-15-fold higher than in man in order to exert equipotent effects (Krasovskii 1976, Davidson et al 1986, Vocci & Farber 1988. Hence, the dose used in the present experiments may well be of importance for human physiology and -in agreement with earlier reports (Milligan et al 2000) -may have adverse effects in the uterus that require addition of a progestin to prevent endometrial hyperplasia and carcinoma (Lethaby et al 2004).…”

Soviet-American cooperation in environmental health science.

“…In order to improve the scientific base for extrapolation of laboratory animal data to man, R. L. Dixon (National Institute of Environmental Health Sciences) and G. N. Krasovskii (A. N. Sysin Institute of General and Communal Hygiene) undertook a joint effort aimed at understanding strain and species differences between biological organisms with regard to toxicological response. Soviet scientists have shown that the toxicity parameters of compounds and the biological constants of mammals correlate with body weight and other biological parameters enabling the development of a computational method for extrapolating toxicologic data from animals to the "average" man (25).…”

Strategy for the assessment of neurobehavioral consequences of environmental factors.

“…An important corollary of this argument is that behavioral changes may precede histopathological or morphological changes in nerve tissue and thereby prove to be a highly sensitive component in toxicological evaluations. In fact, many countries, most notably the Soviet Union, have relied heavily upon behavioral tests in their toxicology testing for several years, and it is relevant to this point that the acceptable limits of many toxic substances in the Soviet Union are below those established in this country (8,9). This kind of precedent has stimulated the use of behavioral toxicological testing in the United States, with the subsequent reduction of acceptable limits for chemicals such as trichloroethylene (5).…”

“…Another organismal variable is the age of the subject. Developing organisms and older, senescent animals differ from the mature adult in their sensitivities to chemicals (8). Unless the research program is specifically aimed at elucidating the effects of chemicals in the developing animal or in older animals, mature adult organisms should be considered as the normative population.…”