Toxicological studies of phenoxyacetic herbicides in animals.

The main purpose of the present work was to study the long-term effects of 2,4-dichlorophenoxyacetic acid (2,4-D) in swine, rats and chickens. In preliminary short-term experiments with calves and pigs, definite although reversible toxic effects were seen after single doses of 200 and 100 mg/kg, respectively. Rats and chickens seemed to tolerate 100 and 300 mg/kg, respectively, without ill-effects. On repeated administration daily doses of 50 mg/kg could be toxic to pigs, whereas chickens tolerated 300 mg/kg/day for several weeks without visible effects. Symptoms of acute poisoning in calves were dysphagia, anorexia, tympanites and muscular weakness. Anorexia was apparent also in acutely or subacutely poisoned pigs together with locomotory disturbances, transient diarrhoea and, in severe cases, vomiting, muscular weakness and general depression. In all animals showing symptoms of poisoning a reduced disappearance rate of 2,4-D from plasma was apparent. On autopsy the pigs showed signs of gastro-intestinal irritation and pneumonia and renal degeneration. In the rats and chickens no gross pathological changes were seen. In the long-term studies 5 young pigs were fed 2,4-D (500 p.p.m.) for up to 12 months. Main clinical signs were growth depression, locomotory disturbances, anaemia and albuminuria. Morphological changes included moderate hepatic and renal degeneration. In another experiment 2,4-D was fed to a pregnant sow throughout the gestation period and for 6 further weeks. The sow exhibited no characteristic signs, and on autopsy no changes attributable to 2,4-D were noted. The newborn piglets, however, were underdeveloped and apathetic. Ten out of 15 died within 24 hours. On continued feeding of 2,4-D to the survivors until 7–8 months of age the main effects were a marked growth depression, persistent anaemia and moderate degenerative changes of liver and kidneys. Pregnant rats were given 2,4-D (1000 p.p.m.) in the drinking water during the gestation and further for up to 10 months. The administration of 2,4-D was continued to the second generation rats for up to 2 years. Except for a retarded growth and an increased mortality in the second generation no unequivocal clinical or morphological changes were seen. In chickens continued administration of 2,4-D (500 p.p.m. in the feed or 1000 p.p.m. in the drinking water) caused a reduced eggproduction and pronounced kidney enlargement due to epithelial proliferations, this latter lesion appearing only when very young chicks were used as experimental animals. The experimental results indicate the chronic toxicity of 2,4-D for the species examined to be moderate. Apart from the nephrotoxicity demonstrated in chicks the long-term effects were non-specific. Of particular interest, however, are the high mortality in the newborn piglets and the reduced production in the chickens as indications of a possible interference with reproduction.