The effect of exposure to a commercial 2,4-D herbicide formulation during gestation on urethan-induced lung adenoma formation in CD-1 mice.

Female CD-1 mice were exposed to a commercial amine formulation of 2,4-dichlorophenoxyacetic acid (2,4-D) on days 6-16 of gestation in drinking water at concentrations ranging from 0 to 1.0% of the formulated product, equivalent to approximately 0-650 mg/kg/d expressed as the amine derivative. The effect of 2,4-D on urethan-induced pulmonary adenoma formation was evaluated in female offspring 19 w after birth. Urethan-induced sleeping times observed following ip injection of 1.5 mg urethan/g bw 7 w after birth were not altered by 2,4-D (p = 0.10), indicating that 2,4-D did not affect the rate of urethan elimination. 2,4-D exposure did not affect the number of tumors produced (p = 0.58), but did reduce the mean tumor diameter in the highest dose group (p < 0.01). This minor antineoplastic activity of 2,4-D may be related, in part, to inhibitory effects of 2,4-D on various enzymatic or metabolic pathways, essential for cellular growth and tissue development. Since exposure to 2,4-D during pregnancy had little impact of tumor production, it is unlikely that persistent alteration to developing immune cells involved in the cell-mediated immunosurveillance mechanisms occurred. The subtle alteration in tumor size and the mild impairment of growth in the offspring were observed almost exclusively in the highest treatment group. Since this level of exposure is well in excess of those associated with normal application of 2,4-D, the hazard to non-target mammalian populations appears minimal.