Chronic Dietary Toxicity Study on 2,4-Dichlorophenoxybutyric Acid in the Dog

Abstract

2,4-Dichlorophenoxybutyric acid (2,4-DB) is principally used in the United States as a herbicide on peanuts, soybeans, and alfalfa. In Europe, it is used on cereals, undersown cereals, lucerne (alfalfa), clover, and clover mixtures. A 1-year chronic toxicity study in the dog was performed on 2,4-DB. Doses in the study of 0, 75, 225, and 450 ppm were administered to six animals/sex/group. The top dose was reduced from 675 ppm during week 7 of the study due to body weight loss and decreased food consumption. Four animals/sex/group were euthanized after 52 weeks of treatment and two animals/sex/group were placed on control diet for 4 weeks and euthanized at week 56. Treatment-related findings included reductions in body weight gain and food consumption, and minor increases in inorganic phosphorus, blood urea nitrogen, creatinine, aspartate aminotransferase, and alanine aminotransferase. After the 4-week recovery period, the only parameter that did not return to control levels was the aspartate aminotransferase. Gross pathology evaluation noted distended gallbladders and decreased organ weights were noted in females for the adrenal, spleen, and ovaries. Histologically, the liver and kidney were the target organs. The data from the study support a chronic no observed adverse effect level of 75 ppm (2.39 and 2.15 mg/kg/day for males and females, respectively) for 2,4-DB. There was no indication of any immunotoxic or oncogenic response in the studies. In conclusion, the findings in this study indicate the general low toxicity of 2,4-DB following chronic dietary exposure in the dog.