| IDENTIFICATION AND USE: 4-Methylcyclohexanemethanol (MCHM) is a clear, colorless liquid, which is reported to smell like licorice. It is used in a coal industry in the separation of usable coal from rocks, debris and cold dust. HUMAN EXPOSURE AND TOXICITY: Symptoms of MCHM exposure include: nausea, vomiting, dizziness, headaches, diarrhea, reddened skin, itching, and rashes. In the days immediately following January 9, 2014, the West Virginia Poison Center received calls from over 1,900 patients reporting chemical exposures related to the drinking water. Most reported symptoms included mild rashes and reddened skin from dermal exposure, or GI distress (nausea, vomiting and/or diarrhea) from ingesting contaminated water. The symptoms tended to be mild and self-limiting. It was possible that the symptoms reported to be caused by exposure to MCHM could have been caused by other mild clinical illness such as colds or flu or other viral infections. Results of laboratory tests done in the Emergency Department did not indicate any people had new kidney or liver damage. With human A549 cells, MCHM mainly induced DNA damage-related biomarkers. ANIMAL STUDIES: Rats dosed with 800 mg/kg of MCHM showed signs of CNS depression resulting in decreased activity levels and ataxia. Administration of 400 mg/kg/day of the test article to rats by gavage for four weeks was associated with erythropoietic, kidney, and liver effects. The no-observed-effect level for this subacute toxicity study was 100 mg/kg/day. MCHM was a strong skin irritant in guinea pigs and moderate eye irritant in rabbits. NTP mouse study found MCHM is a skin irritant; however, it did not induce hypersensitivity unlike crude MCHM. An acute dermal toxicity study was conducted in male and female rats administered a single limit dose of 2000 mg/kg of the test substance topically. Two female rats died (on Day 1 and Day 3); the cause of death was not determined. For female rats, clinical sign observed included prostration, stumbling, transient weakness, and skin abnormalities (erythema, desquamation, and induration). Additionally, lack of feces, red urine, and inguinal hair wet with urine was observed for the female rats. For male rats, clinical signs observed were limited to erythema and desquamation of the skin at the site of application. All animals which survived to scheduled necropsy gained weight during the study. Treatment-related gross or microscopic changes were observed only for female rats. For the two female rats which died, treatment-related gross lesions included distention of the urinary bladder with red urine, and/or hemorrhage in the glandular gastric mucosa; darker than normal spleens were also observed in these rats. The lesions observed in the glandular gastric mucosa may have been due to consumption of test substance during grooming or may have been due to stress. Microscopic lesions consisted of atrophy and congestion of the splenic red pulp and/or atrophy and necrosis of the splenic white pulp. The white pulp atrophy may have been secondary to stress and the red pulp atrophy and congestion may have been related to stress and/or hemorrhage. In addition, splenic effects have not been associated with wrapping, and therefore, may be associated with test substance toxicity. Treatment-related lesions observed for one of the female rats that survived the 14-day observation period consisted of desquamation and minor induration of the skin at the application site grossly and consisted of focal necrosis and eschar formation on the skin at the application site microscopically. The test substance was a dermal irritant as evidenced by focal necrosis and eschar formation on the skin at the application site. In prenatal developmental toxicity study in rats NTP found that MCHM decreased fetal weight and induced malformations in fetuses (400 mg/kg/day). A small decrease in fetal weight was also observed (200 mg/kg/day). In zebrafish studies, MCMH did not have effects on embryonic and larval development and behavior, but it affected zebrafish photomotor response. In the yeast library, MCHM induced chemical stress related to transmembrane transport and transporter activity, while MCHM metabolites induced oxidative stress related to antioxidant activity and oxidoreductase activity. In the mutagenicity study with Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA (pKM101) MCHM was not active with or without metabolic activation. MCHM was negative in the in vivo rat micronucleus assay conducted by NTP. ECOTOXICITY STUDIES: LC50; Fathead minnow; Conditions: freshwater, static; Concentration 54.7 mg/L for 96 hr. EC50; Species: Daphnia magna (Water flea); Conditions: freshwater, static; Concentration: 98.1 mg/L for 48 hr; effect: stress and immobility. Others reported EC50 for Daphnia magna approximately 50 mg/L for 48 hr. |