The improbable association between the herbicide 2,4-D and polyneuropathy

Isolated case reports have circumstantially linked the use of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) to polyneuropathy. However, a critical review of the literature reveals numerous reasons for doubting a relationship of 2,4-D to polyneuropathy: (1) too few cases given the wide use of the chemical; (2) no valid toxicologic or epidemiologic evidence; (3) the diversity of antecedent illness; (4) an unlikely time sequence of antecedent illness to exposure (pharmacokinetics); (5) the lack of polyneuropathy in medical patients given repetitive doses of 2,4-D; (6) the lack of polyneuropathy in heavily exposed military personnel involved in operation Ranch Hand; (7) the biological properties of 2,4-D which minimize penetration of 2,4-D into the nervous system under normal exposure conditions; and (8) the lack of polyneuropathy in a variety of experimental animal species given 2,4-D by several routes of exposure and at dose levels and durations of exposure many times greater than human applicator exposure. Thus, the weight of evidence indicates that 2,4-D is an unlikely cause of polyneuropathy.