The Central Nervous System Toxicity of Chlorophenoxyacetic Acid Herbicides

The concentrations of chlorophenoxyacetic acids and some other exogenous substances in rat brain are greatly increased in acute intoxication by 2-methyl-4-chlorophenoxyacetic acid (MCPA) or 2,4-dichlorophenoxyacetic acid (2,4-D). In the first part of the study, the ability of 2,4-D, MCPA, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) to damage the blood-brain barrier (BBB) was investigated in rats. Evans blue was used to demonstrate albumin leakage into the brain. In the second part, intracerebral distribution of 14C-labelled MCPA, 2,4-D, and 2,4,5-T were studied in rats during the intoxication caused by these herbicides (LD50, 1/2LD50). Rats were pretreated with a single oral toxic dose of herbicide. At different times (3, 7 or 11 h after herbicide exposure), Evans blue or 14C-labelled chlorophenoxyacetic acid was injected i.v., and 1 h later the cerebral distribution of the extravasated Evans blue-albumin complex or radioactivity were determined. An LD50 dose of MCPA (950 mg/kg) and of 2,4-D (600 mg/kg), but not that of 2,4,5-T (475 mg/kg), caused BBB damage resulting in Evans blue extravasation in the medulla oblongata and cerebral cortex. At large chlorophenoxyacetic acid doses, the cerebral concentrations of 14C-MCPA and 14C-2,4-D also increased more than those of 14C-2,4,5-T. No significant differences were found in the distribution of these chlorophenoxyacetic acids into different brain regions. The results suggest that 2,4-D and MCPA intoxications impair the function of rat BBB more than 2,4,5-T intoxication.