A METHOD FOR EVALUATING MECHANISTIC ASPECTS OF CHEMICAL MIXTURE TOXICITY

Abstract

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 independence models. In testing, induction of osteolathyrism in Xenopus embryos was the response evaluated. Testing was for 96-h with daily solution removal and replacement. Analysis of the response curves indicated that thiosem icarbazide (TSC) and semicarbazide (SC) induced osteolathyrism in a dose-additive manner. Along with the similarity in chemical structures, the results indicate, in theory, that TSC and SC disrupt connective tissue cross-linking in the notochord by the same specific mechanism. The results support further evaluation of the method.

Keywords: :

• Concentration Response Dose Addition Independence Mechanism Of Action Osteolathyrism Xenopus