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

https://doi.org/10.1016/0041-008X(79)90368-5Get rights and content

Abstract

The effects of different 2-methyl-4-chlorophenoxyacetic acid (MCPA) or 2,4-dichlorophenoxyacetic acid (2,4-D) pretreatments on the distribution of labeled [14C]MCPA or [14C]2,4-D given iv were studied in male rats. Single subcutaneous MCPA or 2,4-D pretreatment increased 14C activity in the brain, cerebrospinal fluid (CSF), liver, muscle, heart, or testis and decreased that in the plasma or kidney, while in the lung 14C activity remained approximately unchanged. Changes in the distribution of 14C activity as well as toxic signs such as myotonia and lethargy appeared within 0.5–1.5 hr after subcutaneous MCPA administration and disappeared in a few days. 14C activities in the brain and CSF of both saline-treated adult and 10- or 21-day-old animals were very low as compared to the other tissues, but in the treated animals these and also absolute MCPA concentration increased to about the level in the muscle or testis. Chronic MCPA exposure had only a slight effect on the distribution of 14C activity. The decreased binding of [14C]MCPA to plasma proteins caused by MCPA pretreatments may explain the increase of 14C activity in many tissues but not the high increase in the brain and CSF during intoxication. The results indicate that at large doses either the influx of MCPA and 2,4-D into the brain is highly increased or their efflux out of the brain is decreased. A potent increase in cerebral 14C activity coincided with the appearance of MCPA intoxication, which suggests that the central nervous system (CNS) is involved in the toxicity of chlorophenoxyacetic acids.

References (23)

  • S. Dalgaard-Mikkelsen et al.

    Toxicology of herbicides

    Pharmacol. Rev.

    (1962)
  • Cited by (42)

    • Kidney biomarkers in MCPA-induced acute kidney injury in rats: Reduced clearance enhances early biomarker performance

      2014, Toxicology Letters
      Citation Excerpt :

      Animal experiments were performed according to the OECD425 up-down procedure guideline (OECD, 2008). The doses were approximately 5%, 10%, 25%, and 50% of the 7 day LD50 in rats (800 mg/kg) (Elo and Ylitalo, 1979; EPA, 2004; Roberts et al., 2005; Rowe and Hymas, 1954; Yasuda and Maeda, 1972). Control rats were gavaged with water.

    • Renal Organic Cation and Anion Transport: From Physiology to Genes

      2010, Comprehensive Toxicology, Second Edition
    • Phenoxy Herbicides (2,4-D)

      2010, Hayes' Handbook of Pesticide Toxicology
    • Phenoxy Herbicides (2,4-D)

      2010, Hayes' Handbook of Pesticide Toxicology, Third Edition: Volume 1
    • Intentional self-poisoning with the chlorophenoxy herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA)

      2005, Annals of Emergency Medicine
      Citation Excerpt :

      The poor correlation between clinical toxicity and plasma concentrations may reflect poor correlation between plasma (measured) and intracellular (mitochondrial) concentrations. Mechanisms that alter the distribution of MCPA between these 2 spaces include MCPA-induced damage to cell membranes, which increases penetration of the herbicide through cell membranes.5,26-30 In rats, high plasma concentrations of MCPA damage cell membranes and induce toxicity, but the correlation between plasma levels, membrane damage, and toxicity is poor.29,30

    View all citing articles on Scopus
    View full text