Dose-response analysis in animal studies: prediction of human responses.
Environ Health Perspect 1981 Dec; 42:9-13
Twenty five airborne chemical sensory irritants were evaluated for their potency in causing eyes, nose and throat irritation using an animal model. The model is based on the principle that when airborne chemicals impinge on the nasal mucosa, the trigeminal nerve endings are stimulated, and inhibition of respiration occurs, resulting in a decrease in respiratory rate. The decrease in respiratory rate is dependent on the exposure concentration of each chemical. By plotting the percentage decrease in respiratory rate versus the Logarithm of the exposure concentration, a Linear relationship is obtained. The exposure concentration necessary to evoke a 50 percent decrease in respiratory rate (RD50) was obtained in each case , and the potency of these 25 chemicals compared on the basis of their RD50 and predictions made from this value. A good correlation was found between the predictions and available data from literature. The proposed approach combines quantity, quality of the effect, and duration of administration required for an airborne contaminant and ranges for 0.001 from completely safe chemicals over a continuous period of years to 10 which is lethal in effects and requiring only minutes of exposure. Predictions corresponded well with the type of responses in humans at various multiples of RD50 values found in mice for Toluene-diisocyanate (584849), chlorobenzylidene-malononitrile (2698411), chloroacetophenone (1341248), acrolein (107028), formaldehyde (50000), chloropicrin (76062), chlorine (7782505), sulfur-dioxide (7446095), ammonia (7664417), hydrogen-chloride (7647010), and ethyl- acetate (141786). The authors conclude that appropriate choice of models should take precedence in toxicological evaluations rather than mere dose-response analyses.
NIOSH-Publication; NIOSH-Grant; Toxicology; Comparative-toxicology; Eye-irritants; Respiratory-irritants; Analytical-methods; Screening-methods; Dose-response
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Environmental Health Perspectives
University of Pittsburgh, Pittsburgh, Pennsylvania