Search

2,4-Dichlorophenoxybutyric acid (2,4-DB) is principally used in the United States on peanuts, soybeans, and alfalfa. In Europe, it is used on cereals, undersown cereals, lucerne (alfalfa), clover, and clover mixtures. Doses in the 2-year chronic/oncogenicity rat study were 0, 60, 600, and 1800 ppm. No evidence of an oncogenic potential for 2,4-DB was evident and the study clearly established a NOEL of 2.48 mg/kg/day (60 ppm, males) and 3.23 mg/kg/day (60 ppm, females), as well as an MTD of 78.0 (1800 ppm, males) and 110.6 mg/kg/day (1800 ppm, females), for chronic effects of 2,4-DB in the rat. Doses in the 18-month mouse oncogenicity study were 0, 25, 250, and 750 ppm. No oncogenic effect was noted in the study. In summary, the findings of these studies indicate low chronic toxicity of 2,4-DB and the lack of oncogenic response to 2,4-DB following chronic dietary exposure of 2,4-DB in the rat and mouse.

Forms of 2,4-dichlorophenoxyacetic acid (2,4-D) are herbicides used in the control of a wide variety of broadleaf and woody plants. Subchronic toxicity studies in dogs were conducted on three forms of 2,4-D: the parent form, 2,4-D acid (ACID); 2,4-D dimethylamine salt (DMA); and 2,4-D 2-ethylhexyl ester (2-EHE). The three studies were designed to allow for comparison of the toxicity of the three forms. Doses in the subchronic studies, on an acid equivalent basis, were 0, 0.5 (ACID only), 1.0, 3.75, and 7.5 mg/kg/day. Treatment related findings in the three studies included reductions in body weight gain, and food consumption, and minor increases in blood urea nitrogen, creatinine, and alanine aminotransferase. The data from the three subchronic studies demonstrated the comparable toxicity of ACID, DMA, and 2-EHE and support a subchronic no observed adverse effect level (NOAEL) of 1.0 mg/kg/day for all three forms. Due to the similarity in toxicity of the three forms of 2,4-D, a 1-year chronic toxicity study was performed on the parent ACID to fully characterize the potential toxicity of 2,4-D in the dog. ACID was well tolerated at doses of 0, 1.0, 5.0, and 7.5 mg/kg/day. The clinical pathology alterations were similar to those seen in the subchronic studies and were not progressive. The histopathology alterations observed were not severe in nature and the no observed effect level in the chronic study was determined to be 1.0 mg/kg/day. There was no indication of any immunotoxic or oncogenic response in the studies. In conclusion, the findings of these studies indicate comparable toxicity among representative forms of 2,4-D and their generally low toxicity following subchronic and chronic dietary exposure in the dog.

Inhibition of the enzyme acetylcholinesterase (AChE) using a carbamate compound was measured in 30 Crl: CD®BR Sprague Dawley rats. Erythrocyte, plasma, and brain tissues were analyzed using modifications of the Ellman technique 1 on two different clinical chemistry analyzers. Both EDTA and heparin anticoagulated whole blood were used for the erythrocyte and plasma tests. Results demonstrated similar inhibition of the enzyme in all three tissues between the control and dosed groups using the two technique modifications and instruments. Final inhibition of plasma and erythrocyte AChE for the control vs . treated groups (males and females combined) was 89.5% vs . 82% and 39% vs . 38% for the Technicon AutoAnalyzer™ vs . the Boehringer Mannheim Hitachi™ 704, respectively. Inhibition of the left and right brain segments for the control vs . treated groups (males and females combined) was 35% vs . 39% and 33.2% vs . 29% for the Technicon and the Hitachi, respectively. All inhibitions were significant at the 5% level using two tailed Dunnett's t -Test. Hemolysates prepared from EDTA whole blood packed cells gave more consistent results on the Hitachi 704.