Regulatory progress, toxicology, and public concerns with 2,4-D: Where do we stand after two decades?

2,4-D is member of the phenoxy family of herbicides and has major uses in agriculture, forestry, turf, non-crop and aquatic weeds. Since its introduction in 1946, the toxicology of 2,4-D has been studied extensively and repeatedly. Beginning in 1980, regulatory agencies in North America and Europe initiated re-registration/re-evaluation activities for 2,4-D, which resulted in the formation of the Industry Task Force II on 2,4-D Research Data, and has resulted in the submission of 60 toxicology studies conducted to GLP standards using 2,4-D acid and its dimethylamine salt and 2-ethylhexyl ester forms. The various forms of 2,4-D were toxicologically equivalent. 2,4-D in all three forms has low-to-moderate acute oral toxicity (rat LD50 699–896 mg/kg) and is not well absorbed through skin. In rat and mouse subchronic and chronic studies, overall dietary no-observed-adverse-effect-levels (NOAEL) were 15 and 5 mg/kg/day, respectively. 2,4-D was not carcinogenic in either rodent species, consistent with a lack of genotoxicity in in vitro and in vivo test systems. Mild kidney toxicity was the primary toxic effect in these studies. 2,4-D was not a developmental toxicant in rat (overall NOAEL 25 mg/kg/day) and rabbit (overall NOAEL 75 mg/kg/day) studies, had a low potential for multi-generation reproductive toxicity and neurotoxicity (NOAELs 5 mg/kg/day, respectively). When compared to estimated human exposure levels, the overall toxicology NOAEL of 5 mg/kg/day represents a margin of exposure (MOE) of 1700 for commercial applicators and 50,000 for home and garden users. Thus, coupled with the extensive toxicology data, 2,4-D meets safety standards for all countries where it is registered. Additional 2,4-D information is available on the Industry Task Force II on 2,4-D Research Data website www.24d.org.