title: Estimating dose response in chronic toxicity studies: 24-month administration of acrylonitrile in drinking water of Fischer 344 rats.
abstract: It is shown that low-dose extrapolation based on observed numbers of animals with tumors cannot be used within the standard frameworks of either toxicological or statistical methods since the conclusions cannot be examined critically with additional experiments. The traditional methods of examining dose response in toxicology are considered, and it is shown that they cannot be used as long as the studies are carried out to the animals' old age and the controls have senile lesions. Traditional multivariate statistical methods are proposed to examine the effect of dose on the shift in senile lesions that is induced by treatment. One method (using standard software for the computation of linear discriminant functions) is then applied to the tumorous and non-tumorous lesions found in this study. It is shown that doses as low as 3 ppm have a statistically significant effect, and 1 ppm is proposed as the "no mean effect level".
authors.affiliation: Pfizer Central Research, Groton, CT 06320.
authors.forename: D
authors.initials: D
authors.lastname: Salsburg
mesh_terms: D000181:Acrylonitrile / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D015999:Multivariate Analysis; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014881:Water Supply
chemical_list: D000181:Acrylonitrile