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.
4-(2,4-Dichlorophenoxy)butyric acid (2,4-DB) is principallyused in the USA on peanuts, soybeans, and alfalfa. The developmental toxicity in rats (25/group) was studied at dose levels of 0, 31.25, 62.5, and 125 mg/kg/day. The maximum tolerated dose (MTD) was clearly exceeded at 125 mg/kg/day, as evidenced by a net weight loss in the dams during the dosing period, resulting in four dams totally resorbing their fetuses.The no-observed-effectlevel (NOEL) for maternal toxicity was 31.25 mg/kg/day based on a slight, but consistent, body weight effect at 62.5 mg/kg/day. The NOEL for embryo/fetal toxicity was 31.25 mg/kg/day based on increases in fetal skeletal variations at 62.5 mg/kg/day. The developmental toxicity in rabbits (16/group) was evaluated at dose levels of 0, 15, 30, or 60 mg/kg/day. The MTD was clearly exceeded at 60 mg/kg/day as evidenced by severe weight-gain depression during the dosing period in the does, resulting in two does aborting and two does being sacri® ced in a moribund condition. The NOEL for maternal toxicity was 30 mg/kg/day based on the above noted effects at 60 mg/kg/day. The NOEL for embryo/fetal toxicity was 60 mg/kg/day due to the lack of any effects noted. The reproductive toxicity of 2,4-DB was investigated in a two-generation study with two litters bred per generation. Rats (28/sex/group for the F0 generation and 24/sex/group for the F1 generation) were fed dietary concentrations of 0, 60, 300, and 1500 ppm during the ® rst generation, but because it proved impossible to rear a ® lial generation at 1500 ppm, the second generation was continued at doses of 0, 60, and 300 ppm. Mating performance, fertility, and pregnancy rate were unimpaired. A NOEL for reproductive toxicity was 1500 ppm (111.8 mg/kg/day for males and 110.6 mg/kg/day for females); however, severe postnatal toxicity was produced at this level. The NOEL for postnatal toxicity was 300 ppm (22.5± 32.6 mg/kg/day for males and 26.4± 36.7 mg/kg/day for females depending on the generation). The NOELs for developmental and reproductive toxicity are in general agreement with those reported for 2,4-dichlorophenoxyacetic acid (2,4-D), the major metabolite of 2,4-DB.4-(2,4-Dichlorophenoxy)butyric acid (2,4-DB) is principally used in the USA as a foliar-applied, selective systemic auxintype herbicide on peanuts, soybeans, and alfalfa for the control of many annual and perennial broad-leaved dicotyledenous weeds. After application, 2,4-DB is readily absorbed by the leaves and roots and is then translocated around the plant. 2,4-DB owes its selectivity to the ability of susceptible broad-leaved plants to translocate and rapidly oxidize it via b -oxidation to the acetic acid (2,4-dichlorophenoxyacetic acid; 2,4-D), which is the toxicant. Leguminous plants are not adversely affected because they perform b -oxidation so slowly that the amounts formed do not reach toxic dose levels.Long-term studies in dogs, rats, and mice indicate low chronic toxicity of 2,4-DB and a lack of oncogenic response to 2,4-DB following chronic dietary exposur...
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