Abstract for ORST800001

Evaluation of 2,4-dichiorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in C57BL/6 mice: Reproduction and Fertility in Treated Male Mice and Evaluation of Congenital Malformations in Their Offspring

Report Date: 1980


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

This study was undertaken to determine the effects of mixtures (simulated Agent Orange) of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproduction and fertility of treated male mice.

Male C57BL/6 mice were given feed containing varying concentrations of 2,4-D, 2,4,5-T and TCDD such that daily doses of approximately 40 mg/kg 2,4-D, 40 mg/kg 2,4,5-T and 2.4 µg/kg TCDD (Group II) or 40 mg/kg 2,4-D, 40 mg/kg 2,4,5-T and 0.16 µg/kg TCDD (Group IV) or 20 mg/kg 2,4D, 20 mg/kg 2,4,5-T and 1.2 µg/kg TCDD (Group III) would be achieved. Controls (Group I) were given a diet with only the corn oil vehicle added to the feed. In the treated animals, dose-related liver and thymus toxicity were found and body weight gain was significantly reduced. Liver and thymus toxicity showed significant or complete recovery when the mice were returned to a control diet. Sperm concentration, motility and percent sperm abnormalities were evaluated and no significant effect was noted during or after the dosing period.

At the conclusion of an eight week dosing period treated males were mated to untreated virgin females (three per male per week for eight weeks). Mating frequency, average fertility, percent implantation and resorption sites and percent fetal malformations were all measured in relation to the treatment. No significant decrement in fertility or reproduction was noted in the study. There was no evidence of germ cell toxicity. Survival of offspring and neonatal development were apparently unaffected by paternal exposure to the simulated mixtures of Agent Orange.