Comparative Subchronic Studies on 2,4-Dichlorophenoxyacetic Acid, Amine, and Ester in Rats

Phenoxy Herbicides (2,4-D)

“…The changes reported in the rat kidney were the loss of epithelial cells in the proximal tubule brush border; the changes in the thyroid were follicular cell hypertrophy in association with a reduction in serum thyroxine levels. These changes were consistent over all forms of 2,4-D tested, with a reported no-observed-adverse-effect level (NOAEL) of 15 mg/kg body weight/day (Charles et al, 1996b;Szabo and Rachunek, 1991;Yano et al, 1991aYano et al, , 1991b. Some of these findings were reported at lower doses in older rat studies using the acid form of 2,4-D (Gorzinski et al, 1981a(Gorzinski et al, , 1981b; however, the histological effects were not statistically significant at 15 mg/kg body weight/day, which is consistent with the more recent studies.…”

“…No lesions or overt clinical signs of central nervous system toxicity were observed in any of the subchronic toxicity studies in rats (Charles et al, 1996b;Szabo and Rachunek, 1991;Yano et al, 1991aYano et al, , 1991b or mice (Schulze, 1991), at doses up to 300 to 560 mg/kg body weight/day.…”

“…In rats fed 0, 1, 15, 100, or 300 mg/kg body weight/day of either 2,4-D acid, 2,4-D dimethylamine salt, or 2,4-D 2-ethylhexyl ester for 90 days, only minimal effects were noted in testes at the top dose of 300 mg/kg body weight/day (Charles et al, 1996b). These effects, consisting of decreased testes/body weight ratios accompanied by slight histological evidence of atrophy, occurred only at a dose which exceeded the MTD.…”

“…Several subchronic and chronic toxicity studies have provided no evidence from hematological, clinical chemistry, or histopathologic evaluations that 2,4-D is likely to induce immune system dysfunction (Charles et al, 1996a(Charles et al, , 1996b(Charles et al, , 1996cSzabo and Rachunek, 1991;Yano et al, 1991aYano et al, , 1991b. Studies that were conducted specifically to examine the possible impact of 2,4-D on various immune system functional parameters have not provided definitive results (Blakley, 1986;Blakley and Schiefer, 1986;Zhamsaranova et al, 1987).…”

“…Other animal studies have yielded electromyogram results considered indicative of skeletal muscle myotonia following administration of high doses of 2,4-D (50 to 100 mg/kg body weight/day) Elo and MacDonald, 1989;Kwiecinski, 1981;Steiss et al, 1987;Toyoshima et al, 1985). In a subchronic toxicity study on 2,4-D 2-ethylhexyl ester, some of the highdose animals were reported to show clinical signs that could possibly be related to myotonia (e.g., hunched posture, languid behavior, ataxia) (Charles et al, 1996b).…”