A review of potential neurotoxic mechanisms among three chlorinated organic solvents

Toxicol Appl Pharmacol. 2011 Aug 15;255(1):113-26. doi: 10.1016/j.taap.2011.05.008. Epub 2011 May 15.


The potential for central nervous system depressant effects from three widely used chlorinated solvents, trichloroethylene (TCE), perchloroethylene (PERC), and dichloromethane (DCM), has been shown in human and animal studies. Commonalities of neurobehavioral and neurophysiological changes for the chlorinated solvents in in vivo studies suggest that there is a common mechanism(s) of action in producing resultant neurotoxicological consequences. The purpose of this review is to examine the mechanistic studies conducted with these chlorinated solvents and to propose potential mechanisms of action for the different neurological effects observed. Mechanistic studies indicate that this solvent class has several molecular targets in the brain. Additionally, there are several pieces of evidence from animal studies indicating this solvent class alters neurochemical functions in the brain. Although earlier evidence indicated that these three chlorinated solvents perturb the lipid bilayer, more recent data suggest an interaction between several specific neuronal receptors produces the resultant neurobehavioral effects. Collectively, TCE, PERC, and DCM have been reported to interact directly with several different classes of neuronal receptors by generally inhibiting excitatory receptors/channels and potentiating the function of inhibitory receptors/channels. Given this mechanistic information and available studies for TCE, DCM, and PERC, we provide hypotheses on primary targets (e.g. ion channel targets) that appear to be most influential in producing the resultant neurological effects.

Publication types

  • Review

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Cognition / drug effects
  • Humans
  • Methylene Chloride / toxicity*
  • Motor Activity / drug effects
  • Sleep / drug effects
  • Solvents / toxicity*
  • Tetrachloroethylene / toxicity*
  • Trichloroethylene / toxicity*
  • Vision, Ocular / drug effects


  • Solvents
  • Trichloroethylene
  • Methylene Chloride
  • Tetrachloroethylene