Neurobehavioral toxicity of 2,4-D-n-butyl ester (2,4-D ester): tolerance and lack of cross-tolerance.

Daily administration of 2,4-dichlorophenoxyacetic acid-n-butyl ester to rats (2,4-D ester, 150 mg/kg/day SC) initially produced depressions in photocell locomotor activity and increases in landing foot splay. Maximal tolerance developed to these effects following ten days of repeated exposure. By themselves, physostigmine sulfate (0.01-0.10 mg/kg) and (0.3-10.0 mg/kg) n-butanol produced locomotor activity depression in a dose-related manner. n-Butanol produced increases in landing foot splay while physostigmine had no effect at the doses employed. No cross-tolerance was observed between 2,4-D ester and physostigmine sulfate or n-butanol when locomotor activity was the dependent variable. Similarly, a lack of cross-tolerance was observed between 2,4-D ester and n-butanol when landing foot splay was measured. Unlike physostigmine, prior exposure to n-butanol tended to enhance its toxicity upon subsequent exposures, an effect which was blocked when 2,4-D ester was administered between n-butanol exposures.