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1992-95. This information is organized under the headings of toxicokinetics, mechanism of action, and disease outcomes and mechanisms of toxicity.
Toxicity Profile Update of 2,4-D
Studies published during the period 1992-95 provide evidence that 2,4-D binds covalently to hepatic proteins and lipids; the molecular basis of this interaction and its biologic consequences are unknown. 2,4-D has also been shown to accumulate in the brain. This process is mediated through an active anion transport system. 2,4-D is not considered to be particularly toxic because high concentrations are often required to modulate cellular and biochemical processes. Impairment of motor functions has been reported in rats orally administered a single high oral dose of 2,4-D.
Measurable amounts of 2,4-D can be detected in the blood and urine of dogs several days after exposure to contaminated lawns under natural conditions (Reynolds et al., 1994). Among 44 dogs potentially exposed to 2,4-D-treated lawns for an average of 10.9 days, 33 dogs (75 percent) had urine concentrations of 2,4-D greater than or equal to 10 µg/l, and 17 dogs (39 percent) had urine concentrations of ≥; 50 µg/l. Among 15 dogs with no known exposure to 2,4-D-treated lawns in the previous 42 days, 4 (27 percent) had 2,4-D in urine, 1 at a concentration of ≥; 50 µg/l. The highest mean concentration of 2,4-D in urine (21.3 mg/l) was found in dogs sampled within two days after application of the herbicide.
The hepatocellular distribution of 2,4-D was examined by Evangelista et al. (1993). The herbicide decreases total lipids, especially phospholipids, both in total liver and in microsomes. 2,4-D crosses the liver plasma membrane and can be detected in all subcellular fractions. 2,4-D binds covalently to hepatic proteins and lipids, with protein binding being ten-fold higher than lipid. The mechanism of and implications for covalent binding of 2,4-D remain to be defined.
2,4-D has been demonstrated to accumulate in the brain without damaging the blood–brain barrier. This accumulation is related to the biochemical properties of 2,4-D, which is a very strong acid and is partially soluble in water. Recent experiments have demonstrated that the mechanism that mediates the accumulation of 2,4-D in the brain is the saturation of an active organic anion transport system in the choroid plexus (Kim et al., 1988; Kim et al., 1994). The brain depends on the active transport of organic anions by the choroid plexus to keep potentially toxic anions, including foreign chemicals, as 2,4-D and endogenous neurotransmitter metabolites, at low concentrations in the central nervous system.