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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.

The commercial formulations of 3 commonly used herbicides (the amine salt of 2,4-dichlorophenoxyacetic acid, trifluralin and triallate) were evaluated for effects on immune function in male Fisher 344 rats. The herbicides were prepared in an olive oil vehicle and administered by oral gavage twice weekly for 28 d at the following doses: 10.0 mg 2,4-D/kg; 17.5 mg trifluralin/kg; 5.0 mg triallate/kg/treatment. Normal body weight and organ/body weight ratios indicated the rats tolerated the herbicide treatments without difficulty. Exposure to 2,4-D did not alter lymphocyte blastogenesis, 1 gm antibody production (anti-sheep red blood cell), lymphocyte cell surface marker expression or phagocytic function of peritoneal macrophages. Trifluralin acted as a weak mitogen, but impaired T-lymphocyte blastogenesis induced by phytohemagglutinin and concanavalin A. Other immunological measurements were unaffected by trifluralin exposure. Triallate exposure reduced peritoneal macrophage phagocytosis by 33%, showed weak mitogenic properties and impaired T-lymphocyte blastogenesis in the presence of phytohemagglutin. Triallate also increased the anti-sheep red blood cell response expressed/spleen by 43%, a phenomenon suggestive of a compensatory response to minimize the impact on overall immune function. The changes in lymphocyte or macrophage function due to the herbicide treatments were not associated with changes in lymphocyte cell surface antigen expression.

The acute, subchronic and chronic toxicities of 2,4-dichlorophenoxyacetic acid (2,4-D) were studied ir rats. Animals were exposed acutely (600 mg/kg), subchronically (200 ppm for 30 d) and chronically (200 ppm for 180 d) to 2,4-D by the oral route. Clinical, laboratory and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased locomotor activity and induced ataxia, sedation, muscular weakness (mainly of the hind quarters) and gasping for breath; increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), amylase activities and creatinine levels; decreased total protein (TP) and glucose levels; and increased hematocrit values. Subchronic and chronic 2,4-D exposures did not induce overt clinical signs or symptoms of intoxication. However, subchronic herbicide exposure increased AST activity and albumin and hematocrit values, and chronic exposure increased AST, AP and LDH activities, decreased amylase and glucose levels, but did not change hematocrit values. Chromatographic analysis of the serum of chronically exposed rats showed the presence of the herbicide; the amount found (3.76 +/- 1.16 micrograms/ml) suggested the absence of 2,4-D accumulation within the body. Although macroscopic or histopathological lesions were not observed in acutely, subchronically or chronically 2,4-D exposed rats, the laboratory data obtained suggest tissue injuries after dosing, since the results are considered early indicators of primarily hepatic and muscle tissue damage.

The acute toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in cattle. Steers were dosed po with 100, 300 or 600 mg 2,4-D/kg bw. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), O-glutamyl transferase (O-GT), creatine kinase (CK), lactate dehydrogenase (LDH) activities and urea, creatinine, glucose, total proteins and albumin levels were determined at intervals after dosing. The lowest 2,4-D dose did not change the biochemical parameters studied; the 300 mg/kg dose decreased AST, O-GT and CK activities and increased urea and glucose levels; the highest dose of 2,4-D increased LDH and CK activities and protein, urea, creatinine and glucose levels. These changes were time and dose-dependent and completely reversible. Acute 2,4-D intoxication disrupted the serum levels of several enzymes and blood components which mainly reflect kidney and muscle damage induced by the herbicide.

The acute toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in cattle. Steers were orally treated with 100, 300 or 600 mg 2,4-D/kg. Behavioral alterations, heart and respiratory functions, rectal temperature and ruminal movements were observed at 2, 4, 8, 12, 24, 48, 72 and 96 h after treatment. At these moments, blood and urine samples were collected and serum 2,4-D levels were determined. Results show that animals' vital function and hematocrit were not modified by the herbicide. Other signs were doses and time-dependent and included motor alterations (weakness, lethargy, decreased general activity) and decreased ruminal movements and proteinuria. The herbicide was rapidly excreted and the intoxication signs were completely reserved. 2,4-D is an herbicide of small toxicological consequences for cattle kept under in natural grazing systems.

English Pointer dogs dosed po with encapsulated 2,4-dichlorophenoxyacetic acid (2,4-D) or 2-methoxy-3,6-dichlorobenzoic acid (dicamba) developed varying degrees of myotonia. Dogs given 175 or 220 mg of 2,4-D/kg body weight rapidly developed clinical and electromyographic (EMG) manifestations consistent with a diagnosis of myotonia or pseudomyotonia. Dogs given 2,4-D at 86.7, 43.7 or 8.8 mg/kg body weight developed subclinical manifestations of myotonia detectable only with an electromyograph. The administration of 2,4-D at 1.3 or 1.0 mg/kg body weight failed to produce detectable EMG changes. One dog given dicamba at 86.7 mg/kg body weight developed clinical and EMG manifestations of myotonia similar to those induced by the highest doses of 2,4-D.

Female CD-1 mice were exposed to Tordon 202c, a herbicide containing 2,4-dichlorophenoxyacetic acid and picloram, in the drinking water for 15 w at concentrations ranging from 0 to 0.3% of the product formulation. After 3 w of the 15-w treatment period, the mice received 1.5 mg/g urethan ip. Pulmonary adenoma production was evaluated 12 w later. Tordon 202c exposure produced a dose-dependent increase in tumor number, but had no effect on tumor size. Urethan-induced sleeping times which reflected the rate of urethan metabolism or excretion were altered, but a specific dose-related effect which could be correlated with tumor production was not observed. This suggests that Tordon 202c exposure influences adenoma formation by immunological mechanisms rather than by causing indirect effects on urethan metabolism or excretion.