A METHOD FOR EVALUATING MECHANISTIC ASPECTS OF CHEMICAL-MIXTURE TOXICITY

A method for relating mixture toxicity models and mechanisms of action has been. developed. The approach utilizes a 1.2-factor matrix design to generate seven binary mixture concentration-response curves. The X -2 goodness-of-fit test is used to compare the experimental responses to the theoretical effects calculated for the dose-addition and indepe ndence models. In testing, induction of osteolathyrism in. Xenopus emb ryos was the response evaluated. Testing was for 96-h with daily solut ion removal and replacement. Analysis of the response curves indicated that thiosemicarbazide (TSC) and semicarbazide (SC) induced osteolath yrism in a dose-additive manner Along with the similarity in chemical structures, the results indicate, in theory, that TSC and SC disrupt c onnective tissue cross-linking in the notochord by the same specific m echanism. The results support further evaluation of the method.