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

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:

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

Acknowledgements

The authors would like to thank Caroline Gillie, Carrie Kahn, Marisa Kreider, Claressa Mazzetti, Andrew Monnot and Andrew Patton for their technical assistance with the preparation of this manuscript. The authors are very grateful for the comments and suggestions from the four anonymous reviewers. These helpful comments allowed us to improve the scientific context, the conclusions and clarity of the paper.

Declaration of interest

DJP, RMN, and BW are employed by Cardno ChemRisk, a consulting firm that provides scientific advice to the government, corporations, law firms and various scientific/professional organizations. Scientists within Cardno ChemRisk also provided expert testimony in litigation. SMG is employed by Eastman Chemical Company, a manufacturer of crude MCHM. Cardno ChemRisk has been engaged by Eastman Chemical Company to provide general consulting and expert advice on scientific matters, as well as litigation support. It is likely that this work will be relied upon in toxicological research, risk assessment, and litigation. Each of the authors may be called upon to serve as an expert or fact witness in litigation related to MCHM. It should be noted that DJP and SMG have given depositions in litigation associated with the Elk River spill. Funding for the preparation of this paper was provided by Eastman Chemical Company.