Rotenone 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
FIGURE 56–1 Chemical structures of selected herbicides and pesticides.
China resulted in marked effects on the CNS, including convulsions. Other previously unreported toxic manifestations have been observed in pyrethrin-exposed individuals.
2,4-Dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and their salts and esters have been used as herbicides for the destruction of weeds (Figure 56–1). These compounds are of relatively low acute human toxicity. However, despite their low acute hazard, they cause serious longterm human and environmental toxicity. 2,4-D remains in wide commercial and domestic use for lawn weed control. 2,4,5-T had similar uses but was infamously incorporated into Agent Orange, used as a defoliant during the Vietnam conflict. Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (a potent animal carcinogen and likely human carcinogen) and other toxic, persistent, and undesirable polychlorinated compounds. When this toxicity was discovered, the US Department of Agriculture canceled the domestic pesticide registrations for trichlorophenoxy herbicides, and these compounds are no longer used. However, other, less thoroughly studied compounds, eg, chlorinated xanthenes, are present in both the dichlorophenoxy and trichlorophenoxy herbicides (see below).
In humans, 2,4-D in large doses can cause coma and generalized muscle hypotonia. Rarely, muscle weakness and marked hypotonia may persist for several weeks. In laboratory animals, signs of liver and kidney dysfunction have also been reported with chlorphenoxy herbicides. Several epidemiologic studies performed by the U.S. National Cancer Institute confirmed the causal link between 2,4-D and non-Hodgkin’s lymphoma. Evidence for a causal link to soft tissue sarcoma, however, is considered equivocal.
The dichlorophenoxy and related herbicides have been found to contain and to generate dimethylnitrosamine (N-nitrosodimethylamine; NDMA), a potent human carcinogen, during environmental transformation as well as non-chlorine water disinfection. Studies by Environment Canada and others have questioned the use of this compound because of water contamination. Studies of related nitrosamine-forming herbicidal compounds have raised questions about the suitability of these compounds for general weed control. Because of the extremely high economic value of herbicides to the agricultural community, however, long-term decisions on their use have been delayed.