title: Distribution of three common chlorophenoxyacetic acid herbicides into the rat brain.
abstract: The distribution of three common 14C-labelled chlorophenoxyacetic acid herbicides (2,4-dichlorophenoxyacetic acid or 2,4-D, 2-methyl-4-chlorophenoxyacetic acid or MCPA, 2,4,5-trichlorophenoxyacetic acid or 2,4,5-T) into the different brain areas was studied in rats pretreated with toxic doses of the herbicides (238-475 mg/kg). Also, their binding to proteins in rat plasma was determined in vitro by increasing the concentrations of chlorophenoxyacetic acids in the incubate from 0 to 1 mg/ml. Both 2,4-D and MCPA pretreatments increased brain concentrations of 14C-labelled herbicides more markedly than 2,4,5-T pretreatments did. No essential differences were found in the distribution between the different brain areas. Protein-unbound fractions of 2,4-D and MCPA in the plasma were clearly higher than those of 2,4,5-T but the highest herbicide concentration increased the protein-unbound fraction of 2,4,5-T more (7-13-fold) than of 2,4-D and MCPA (5-fold). The results suggest that the greater increase in the penetration into the brain of 2,4-D and MCPA than of 2,4,5-T during their intoxication is due to some factors other than the changes in their binding to plasma proteins and mere enhanced diffusion through the blood-brain barrier.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Tyynelä
authors.forename: H A
authors.initials: HA
authors.lastname: Elo
authors.forename: P
authors.initials: P
authors.lastname: Ylitalo
mesh_terms: D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D015084:2,4-Dichlorophenoxyacetic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D006016:Glycolates / Q000493:pharmacokinetics*; D006540:Herbicides / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; D006016:Glycolates; D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid; D015085:2,4,5-Trichlorophenoxyacetic Acid; D008456:2-Methyl-4-chlorophenoxyacetic Acid