Developmental Toxicity of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T): I. Multireplicated Dose-Response Studies in Four Inbred Strains and One Outbred Stock of Mice

A large-scaled multireplicated developmental toxicity studywas conducted in various strains/stocks of mice with the herbicide,2,4,5-trichiorophenoxyacetic acid (2,4,5-T), by gavage on GestationalDays 6 through 14. The most important attributes of the studydesign were replicated test groups, a minimum of four dose levelsper replicate, use of multiple stocks/strains of animals toobtain an estimate of the range in sensitivities due to genotype,complete pathological evaluation of maternal animals, and histopathologicalas well as teratological evaluation of the fetuses. Developmentaltoxicity was observed at doses below those producing discernibleor measurable maternal toxicity. Regression and/or probit analyseswere conducted to determine whether a dose-response relationshipexisted. Reduced fetal weight and increased incidence of cleftpalate and embryolethality were the most significant prenataleffects of 2,4,5-T exposure observed in this study. Each strain/stockexhibited a dose-related decrease in fetal weight with the CD-1mice having the steepest slope and the A/J mice having the shallowestslope. There was a striking similarity among the slopes of thedose-response curves for the various strains/stocks. The meanincidence of embryolethality in the A/J strain was significantlygreater than that of the other strains or stocks. There wassubstantial variation among replicates within strains. The useof the replicated study design was logistically necessary dueto the magnitude of the study and it also served to increasethe statistical power of the study.