Toxicologic studies on 2,4-dichlorophenyl- p-nitrophenyl ether

Abstract

Studies on 2,4-dichlorophenyl- p-nitrophenyl ether (TOK ®, a new selective herbicide, were undertaken in several animal species to characterize its toxicity. In rats, the single po LD50 ± SD value for technical grade TOK (95%) was 2.63 ± 0.13 g/kg as compared to 3.58 ± 0.14 g/kg for 100% TOK. It did not produce skin irritation in rabbits or cutaneous sensitization in guinea pigs. Rats on dietary levels of 100 and 500 ppm for 13 wk, and on 10, 100, and 1000 ppm for 97 wk, showed no definite differences in growth, feed consumption, and mortality, as compared to respective controls. In the 13-wk study in rats, liver-to-body weight ratios at all dietary levels of TOK, except for males on 100 ppm, were significantly higher. Kidney ratios were elevated for female rats on 12,500 ppm and above and for male rats on 2,500 and 12,500 ppm. In the 97-wk study, organ-tobody weight ratios showed significant increases for kidneys and liver for male rats only on the 1000 ppm diet. No dose-related effects were noted on hemograms, urinary findings, and in microscopic examination of tissues in both the subchronic and chronic studies. In a 2-yr study in dogs given 20, 200, and 2000 ppm diets, no adverse trends were noted on growth, feed consumption, hematology, urinary findings, BSP, SGOT, SAP, BUN, and histopathologic findings. Significantly higher liver-to-body weight ratios appeared only in dogs on the 2000 ppm diet. Three-generation reproduction studies in rats throughout 2 mating cycles revealed no adverse trends in fertility, gestation, viability, and lactation indices for rats on 10 and 100 ppm diets; however, 1000 ppm diet affected the incidence of stillbirths and decreased pup survival, to a point where no pups were available for the F 1b generation, and 100 ppm caused some increase in stillbirths. Overall, in these studies, the highest no-effect level found was 10 ppm.