Chronic toxicity of 2,4-dichlorophenoxyacetic acid in rats and dogs

Abstract

Starting at 3 wk of age, rats (25 female and 25 male per group) were fed for 2 yr either 0, 5, 25, 125, 625, or 1250 ppm of 2,4-dichlorophenoxyacetic acid (2,4-D) in the diet. No significant effect on growth rate, survival rate, organ weights, or hematologic values was noted. Total (male plus female) tumor incidence in the control and experimental groups was 15, 14, 18, 20, 23, and 22, respectively. No target organ tumors were observed; the individual tumor types were randomly and widely distributed and of the type normally found in aging Osborne-Mendel rats. Statistical analysis of the randomly distributed tumor types indicated a tendency for the proportion of females with tumors to increase with 2,4-D dosage, and a trend toward dose related increases in the proportion of males with malignant tumors. These tendencies do not reflect important pathologic differences. Groups of 3 male and 3 female beagle dogs each were fed 0, 10, 50, 100, or 500 ppm of 2,4-D in the diet for 2 yr, starting at 6–8 mo of age. Twenty-eight dogs surviving the 2-yr period were clinically normal, and no 2,4-D related effects were noted. One female at 100 ppm that was emaciated at autopsy at two years showed no significant lesions. Moderate depletion of cellular elements was noted at 10 ppm in 1 male that died after 10 mo. In a 3-generation 6-litter rat reproduction study, no deleterious effect of dietary 2,4-D at 100 or 500 ppm was evident. At 1500 ppm, however, 2,4-D, while apparently affecting neither fertility of either sex nor litter size, did sharply reduce the percent of pups born surviving to weaning and the weights of weanlings.