The toxicity of crude 4-methylcyclohexanemethanol (MCHM): review of experimental data and results of predictive models for its constituents and a putative metabolite

Crit Rev Toxicol. 2015:45 Suppl 2:1-55. doi: 10.3109/10408444.2015.1076376.

Abstract

Crude 4-methylcyclohexanemethanol (MCHM) is an industrial solvent used to clean coal. Approximately 10 000 gallons of a liquid mixture containing crude MCHM were accidently released into the Elk River in West Virginia in January 2014. Because of the proximity to a water treatment facility, the contaminated water was distributed to approximately 300 000 residents. In this review, experimental data and computational predictions for the toxicity for crude MCHM, distilled MCHM, its other components and its putative metabolites are presented. Crude MCHM, its other constituents and its metabolites have low to moderate acute and subchronic oral toxicity. Crude MCHM has been shown not to be a skin sensitizer below certain doses, indicating that at plausible human exposures it does not cause an allergic response. Crude MCHM and its constituents cause slight to moderate skin and eye irritation in rodents at high concentrations. These chemicals are not mutagenic and are not predicted to be carcinogenic. Several of the constituents were predicted through modeling to be possible developmental toxicants; however, 1,4-cyclohexanedimethanol, 1,4-cyclohexanedicarboxylic acid and dimethyl 1,4-cyclohexanedicarboxylate did not demonstrate developmental toxicity in rat studies. Following the spill, the Centers for Disease Control and Prevention recommended a short-term health advisory level of 1 ppm for drinking water that it determined was unlikely to be associated with adverse health effects. Crude MCHM has an odor threshold lower than 10 ppb, indicating that it could be detected at concentrations at least 100-fold less than this risk criterion. Collectively, the findings and predictions indicate that crude MCHM poses no apparent toxicological risk to humans at 1 ppm in household water.

Keywords: 1,4-cyclohexanedicarboxylic acid; 1,4-cyclohexanedimethanol; 4-(methoxymethyl)cyclohexanemethanol; 4-methylcyclohexanecarboxylate; 4-methylcyclohexanemethanol; Elk River incident; chemical spill; dimethyl 1,4-cyclohexanedicarboxylate; drinking water.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biotransformation
  • Chemical Hazard Release*
  • Computer Simulation
  • Cyclohexanes / pharmacokinetics
  • Cyclohexanes / toxicity*
  • Dose-Response Relationship, Drug
  • Environmental Exposure / adverse effects*
  • Humans
  • Models, Theoretical
  • Risk Assessment
  • Risk Factors
  • Toxicity Tests*
  • Water Pollutants, Chemical / pharmacokinetics
  • Water Pollutants, Chemical / toxicity*
  • Water Pollution, Chemical / adverse effects*
  • Water Quality
  • Water Supply*

Substances

  • Cyclohexanes
  • Water Pollutants, Chemical
  • 4-methylcyclohexanemethanol