Transport of the anionic herbicide, 2, 4, 5-tnchlorophenoxyacetic acid (2, 4, 5-T) across the blood-cerebrospinal fluid bamer was investigated using the isolated choroid plexus of the adult rabbit in vitro and ventnculocistemal perfusion in vivo. In vitro, 2, 4, 5-T transport was effective, with tissue concentrations 20 times those in the medium after only 5 mm of incubation with 1 M 2, 4, 5-T. The tissue to medium ratios reached steady state by 20 mm at ‘-45-fold. Uptake was energy dependent and inhibited by ouabain, phlondzin and several organic anions (probenecid, 2, 4-dichlorophenoxyacetic acid and octanoate). Neither tyrosine (transported by a separate system) nor the neurotoxin, quinolinic acid, inhibited 2, 4, 5-T transport. Kinetic analysis yielded an apparent Km of 58 M and V of 111 nmol g1 min1 in the lateral ventricular choroid plexus with similar values(57 MM and 87 nmol g1 min1) in the fourth ventricular plexus. In vivo, the steady-state clearance of 2, 4, 5-T from the cerebrospinal fluid exceeded that of inulin and was reduced in a dose-dependent fashion by 2, 4-dichlorophenoxyacetic acid and probenecid. Together, these data indicate that 2, 4, 5-T is cleared from the brain and cerebrospinal fluid by the organic anion transport system and that alterations in such transport may have a significant impact on the toxicity of this agent in the central nervous system.

Since their discovery in the early 1940s, the phenoxyacetic acid herbicides have been widely used throughout the world in forestry management and agriculture(Calesnick, 1984). In the United States alone, their consumption reached 48 million pounds by the early 1970s. Worldwide, they accounted for 20% of total pesticide usage (IARC, 1977). Two of these anionic herbicides, 2, 4-D and 2, 4, 5-T, were also components of the defoliant, Agent Orange. Because oftheir extensive use, considerable attention has been devoted to the toxicology of these herbicides. Certainly, some of the health effects of 2, 4, 5-T were related to its contamination with TCDD, a highly toxic byproduct produced during manufacture of 2, 4, 5-T. However, recent studies using 2, 4-D, which does not contain TCDD, or purified 2, 4, 5-T (< 0.1 ppm of TCDD) indicate that the anionic herbicides themselves also produce toxic effects (Fagan and Pollak, 1984)).