Toxicologic studies on monochloroacetaldehyde 2,4-dinitrophenylhydrazone, a foliar fungicide

Abstract

Toxicologic studies on monochloroacetaldehyde 2,4-dinitrophenylhydrazone (Olin 1763), a foliar fungicide, have been reported. In rats and dogs, single oral doses of 10 g/kg caused no deaths. In rabbits, an LD 50 of 1.4 ± 0.07 g/kg was obtained. In rats, 50,000 ppm in the diet was lethal in less than 2 weeks and a trend in this direction is suggestive for males on 6250 ppm. Feeding at 3200 ppm for 52 weeks had no effect on mortality but depressed growth in both sexes; 1250 ppm also depressed growth in males in subacute studies. Slight depression in hematocrit and hemoglobin values occurred in rats on 1600 and 3200 ppm for 97 and 52 weeks, respectively, and in rats on 6250 ppm for 3 months. Organ-to-body weight ratios were significantly increased for spleen and liver in females, and spleen, liver, and kidneys in males on 1250 ppm for 3 months. Feeding at 1600 and 3200 ppm for 97 and 52 weeks, respectively, caused increased spleen and decreased testes ratios. Testicular atrophy occurred in rats on 1600 and 3200 ppm diets for 97 and 52 weeks, respectively; splenic congestion resulted from 3200 ppm in the diet. Decreased fertility occurred in rats fed 1600 ppm for 11 weeks prior to mating. In 60-day feeding studies in chickens, 10,000 ppm proved lethal but 5,000 ppm did not; 2500 ppm depressed growth, but 1000 ppm did not. Death was preceded by inability to stand and development of twisted or curled necks. Histopathologic studies revealed no lesions attributable to treatment. In subacute studies, dogs fed 1500 ppm and higher concentrations developed marked rigidity of their hind legs and an inability to stand which was reversible on return to control diet. Dogs fed 1000 ppm for two years displayed brief episodes of hindlimb ataxia during the fifteenth month, and 2 of 4 subsequently became subject to convulsive seizures. Similar effects did not occur on 100 and 400 ppm, and there was no effect on body weight at either level. Hematocrit and hemoglobin values were somewhat lower in dogs receiving 1000 ppm, particularly during the first 6 months. Liver-to-body weight ratios were significantly higher in dogs receiving 400 and 1000 ppm, but liver function tests indicated no adverse trends. Histopathologic studies revealed no lesions to explain the neuromuscular effects. Hemosiderin was demonstrated in the kidney tubules and in focal areas in the liver, but there was no necrosis of the cells.