Abstract
The distribution of three common14C-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 of14C-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.
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References
Desi I, Sos J, Olasz J, Sule F, Markus V (1962) Nervous system effects of a chemical herbicide. Arch Environ Health 4: 95–102
Elo H (1976) Distribution and elimination of 2-methyl-4-chlorophenoxyacetic acid (MCPA) in male rats. Acta Pharmacol Toxicol 39: 58–64
Elo HA, MacDonald E (1989) Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats. Arch Toxicol 63: 127–130
Elo H, Ylitalo P (1977) Substantial increase in the levels of chlorophenoxyacetic acids in the CNS of rats as a result of severe intoxication. Acta Pharmacol Toxicol 41: 280–284
Elo HA, Ylitalo P (1979) Distribution of 2-methyl-4-chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid in male rats: evidence for the involvement of the central nervous system in their toxicity. Toxicol Appl Pharmacol 51: 439–446
Elo HA, Hervonen H, Ylitalo P (1988) Comparative study on cerebrovascular injuries by three chlorophenoxyacetic acids (2,4-D, 2,4,5-T and MCPA). Comp Biochem Physiol 90C: 65–68
Fang SC, Fallin E, Montgomery ML, Freed HV (1973) The metabolism and distribution of 2,4,5-trichlorophenoxyacetic acid in female rats. Toxicol Appl Pharmacol 24: 555–563
Glowinski J, Iversen L (1966) Regional studies of catecholamines in the rat brain. I. The disposition of3H-norepinephrine,3H-dopamine and3H-DOPA in various regions of the brain. J Neurochem 13: 655–669
Grantham JJ, Whittier F, Diederich D (1978) Uremia: Strategies in the search for toxins. In: Andreoli TE, Hoffman JF, Fanestil DD (eds) Physiology of membrane disorders. Plenum Press, New York, pp 955–965
Grunow W, Böhme C (1974) Über den Stoffwechsel von 2,4,5-T und 2,4-D bei Ratten und Mäusen. Arch Toxicol 32: 217–225
Hervonen H, Elo HA, Ylitalo P (1982) Blood-brain barrier damage by 2-methyl-4-chlorophenoxyacetic acid herbicide in rats. Toxicol Appl Pharmacol 65: 23–31
Khanna S, Fang SC (1966) Metabolism of C14-labeled 2,4-dichlorophenoxyacetic acid in rats. J Agr Food Chem 14: 500–503
Kim CS, O'Tuama LA (1981) Choroid plexus transport of 2,4-dichlorophenoxyacetic acid: interaction with the organic acid carrier. Brain Res 224: 209–212
Kim CS, O'Tuama LA, Mann JD, Roe CR (1983) Saturable accumulation of the anionic herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), by rabbit choroid plexus: early developmental origin and interaction with salicylates. J Pharmacol Exp Ther 225: 699–704
Kim CS, Keizer RF, Ambrose WW, Breese GR (1987) Effects of 2,4,5-trichlorophenoxyacetic acid and quinolinic acid on 5-hydroxy-3-indoleacetic acid transport by the rabbit choroid plexus: pharmacology and electron microscopic cytochemistry. Toxicol Appl Pharmacol 90: 436–444
Kim CS, Keizer RF, Pritchard JB (1988) 2,4-Dichlorophenoxyacetic acid intoxication increases its accumulation within the brain. Brain Res 440: 216–226
Koschier FJ, Hong SK, Berndt WO (1979) Serum protein and renal tissue binding of 2,4,5-trichlorophenoxyacetic acid. Toxicol Appl Pharmacol 49: 237–244
Lorenzo AV, Spector R (1973) Transport of salicylic acid by the choroid plexus in vitro. J Pharmacol Exp Ther 184: 465–471
Mason RW (1975) Binding of some phenoxyalkanoic acids to bovine serum albumin in vitro. Pharmacology 13: 177–186
Matsumura A (1970) Effect of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) on oxidative phosphorylation. Ind Health 8: 141–149
McKinney SE, Peck HM, Bochey JM, Byham BB, Schuchardt GS, Beyer KH (1951) Benemid,p-(DL-n-propylsulfamyl)benzoic acid: toxicological properties. J Pharmacol Exp Ther 102: 208–214
Pritchard JB (1980) Accumulation of anionic pesticides by rabbit choroid plexus in vitro. J Pharmacol Exp Ther 212: 354–359
Raskin NH, Fishman RA (1976) Neurological disorders in renal failure. N Engl J Med 294: 143–148
Sauerhoff MW, Braun WH, Blau GE, Gehring PJ (1976) The dose-dependent pharmacokinetic profile of 2,4,5-trichlorophenoxyacetic acid following intravenous administration to rats. Toxicol Appl Pharmacol 36: 491–501
Ylitalo P, Heikkinen ER, Myllylä VV (1976) Evaluation of successive collection of cisternal cerebrospinal fluid in rats, rabbits, and cats. Exp Neurol 50: 330–336
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Tyynelä, K., Elo, H.A. & Ylitalo, P. Distribution of three common chlorophenoxyacetic acid herbicides into the rat brain. Arch Toxicol 64, 61–65 (1990). https://doi.org/10.1007/BF01973378
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DOI: https://doi.org/10.1007/BF01973378