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© 1992 Oxford University Press

research-article

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

J. F. HOLSON*, T. B. GAINES{dagger}, C. J. NELSON{ddagger}, J. B. LABORDE§, D. W. GAYLOR, D. M. SHEEHAN§ and J. F. YOUNG§

*WIL Research Laboratories, Inc. Ashland, Ohio 44805–9281 {dagger}Number 6 Athena Court, Little Rock Arkansas 72205 {ddagger}USEPA (MD.56,i, Alexander Drive, Research Triangle Park North Carolina 27711 §Division of Reproductive & Developmental Toxicology Arkansas 72079 Biometrv Staff National Center for Toxicological Research, Food and Drug Administration, Department of Health and Human Services, Jefferson Arkansas 72079

Received October 15, 1991; accepted March 6, 1992

A large-scaled multireplicated developmental toxicity study was conducted in various strains/stocks of mice with the herbicide, 2,4,5-trichiorophenoxyacetic acid (2,4,5-T), by gavage on Gestational Days 6 through 14. The most important attributes of the study design were replicated test groups, a minimum of four dose levels per replicate, use of multiple stocks/strains of animals to obtain an estimate of the range in sensitivities due to genotype, complete pathological evaluation of maternal animals, and histopathological as well as teratological evaluation of the fetuses. Developmental toxicity was observed at doses below those producing discernible or measurable maternal toxicity. Regression and/or probit analyses were conducted to determine whether a dose-response relationship existed. Reduced fetal weight and increased incidence of cleft palate and embryolethality were the most significant prenatal effects of 2,4,5-T exposure observed in this study. Each strain/stock exhibited a dose-related decrease in fetal weight with the CD-1 mice having the steepest slope and the A/J mice having the shallowest slope. There was a striking similarity among the slopes of the dose-response curves for the various strains/stocks. The mean incidence of embryolethality in the A/J strain was significantly greater than that of the other strains or stocks. There was substantial variation among replicates within strains. The use of the replicated study design was logistically necessary due to the magnitude of the study and it also served to increase the statistical power of the study.


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