Acute Hepatic Failure After Occupational Exposure to 2- Nitropropane

On June 28, July 1, and July 2, 1985, two construction workers applied an epoxy resin coating to a water main in an underground concrete vault in San Jose, California. Over the 3 work days, the men applied 10 gallons of the resin coating. The vault was unventilated, and the workers used no respiratory or skin protection.

In the evening of July 2, both men went to a local hospital because of persistent nausea, vomiting, weakness, and dizziness. Initial laboratory tests showed slightly elevated serum glutamic-oxaloacetic transaminase (SGOT)--60 units per liter (U/L) for worker 1 and 79 U/L for worker 2 (normal SGOT is less than 40 U/L). The men were admitted for observation and discharged the following day, after their symptoms had subsided.

Three days later, worker 1 returned to the hospital with persistent nausea, vomiting, anorexia, and onset of scleral icterus. Laboratory tests showed marked hepatic dysfunction (SGOT and serum glutamic-pyruvic transaminase (SGPT) greater than 10,000 U/L, and hyperbilirubinemia), severe metabolic acidosis, and renal insufficiency. He was transferred to a university medical center, where his hospital course was marked by gastrointestinal bleeding, arrhythmia, pulmonary edema, and renal failure. He died 9 days after his initial presentation. Autopsy findings were consistent with fulminant hepatic necrosis.

Worker 2 has remained clinically well, although for at least 6 weeks he continued to have elevation of liver enzymes (SGOT and SGPT) in a range of 1.5 to 2 times the normal maximum. Both men had histories of moderate alcohol use (12 cans of beer/week); neither had significant past medical histories, including previous hepatic disease.

According to the manufacturer's labelling information, the coating material contained a mixture of cyclohexanone, toluene, tri(dimethylaminomethyl) phenol, and 2-nitropropane (2-NP), combined with coal tar pitch and epoxy resin. The analysis of leftover compound by the California Department of Health Services confirmed the presence of 2-NP.

The analysis of sera obtained on July 2 showed 13 ug/ml and 8.5 ug/ml of 2-NP for workers 1 and 2, respectively; 2-NP was undetectable in all subsequent samples. No other volatile compounds, including ethanol, were detected in the sera. Reported by RJ Harrison, MD, G Pasternak, MD, Div of Occupational and Environmental Medicine, P Blanc, MD, P Basuk, MD, Div of Gastroenterology, University of California, San Francisco, G Letz, MD, Hazard Evaluation System and Information Svc, California State Dept of Health Svcs; Div of Surveillance, Hazard Evaluations, and Field Studies, Div of Safety Research, National Institute for Occupational Safety and Health, CDC.

Editorial Note

Editorial Note: 2-Nitropropane (2-NP), a nitroparaffin, CH((3))CH(NO((2)))CH((3)), is used industrially as a solvent in coatings, printing inks, and adhesives (1). In 1977, 15 million pounds of nitroparaffins were used in paint and coatings in the United States, and 2-NP accounted for about 80% (2). Estimates by the National Institute for Occupational Safety and Health (NIOSH) indicate that 185,000 U.S. workers are potentially exposed to 2-NP during its production and use (1).

At least five occupationally related deaths have resulted from exposure to 2-NP (3,4). Typically, workers coated the surface of an enclosed structure (tank, vault, or shiphold), using sealant containing 2-NP. No forced ventilation or personal protection was used. After many hours of exposure, they complained of headache, nausea, vomiting, dyspepsia, and chest pain. A few days later, acute jaundice, hematemesis, enlarged liver, edema, and oliguria/anuria developed, followed by coma and death. One nonfatal case involved a 30-minute exposure to 2-NP vapor caused by a spill (4). No estimate concerning the frequency of 2-NP-induced hepatitis is available; however, a review of 62 cases of liver transplant recipients showed that two patients had liver failure secondary to 2-NP exposure (5).

In short-term toxicologic experiments, high concentrations of 2-NP (700 ppm for several hours) have produced parenchymal degeneration and focal necrosis of the liver in experimental animals (6). In chronic-exposure studies, 2-NP has produced hepatomas in rats at 207 ppm for 6 months, and it is considered a potential human carcinogen (7). Although the current permissible exposure limit as determined by the Occupational Safety and Health Administration (OSHA) is 25 ppm or 90 mg/m((3)) (8-hour, time-weighted average), NIOSH has recommended that based on the evidence of animal carcinogenicity, occupational exposure to 2-NP be reduced to the lowest feasible levels (1).

The following control measures should be considered for preventing acute toxicity and potential long-term health consequences of 2-NP exposure: (1) paint, sealant, or other coating materials must not be applied in confined spaces without sufficient forced ventilation and respiratory and cutaneous protection, (2) products containing 2-NP should be labelled to reflect its toxicity; workers should be warned that odor does not serve as a warning sign, since toxic levels are below the odor threshold of 83 ppm (6), and (3) 2-NP should be replaced whenever possible by other less toxic solvents in paint and coating formulations. Reportedly, 2-NP has been replaced by 1-NP in many paint formulations (2). However, since these two chemicals have very similar characteristics, the same precautions should be taken in handling them.

References

1. Occupational Safety and Health Administration (OSHA) and National Institute for Occupational Safety and Health (NIOSH). Health hazard alert: 2-nitropropane, 1980; DHHS (NIOSH) publication no. 80-142.

2. National Paint and Coatings Association (NPCA). Information released from NPCA's data bank, 1985.

3. Gaultier M, Fournier PE, Gervais P, et al. Intoxication par le nitropropane. Arch Mal Prof 1964;25:425-8.

4. Hine CH, Pasi A, Stephens BG. Fatalities following exposure to 2-nitropropane. J Occup Med 1978;20:333-7.

5. Demetris AJ, Lasky S, Van Thiel DH, Starzl TE, Dekker A. Pathology of hepatic transplantation: a review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid regimen. Am J Pathol 1985;118:151-61.

6. Treon JF, Dutra FR. Physiological response of experimental animals to the vapor of 2-nitropropane. Arch Indust Hyg Occup Med 1952;5:52-61.

7. Lewis TR, Ulrich CE, Busey WM. Subchronic inhalation toxicity of nitromethane and 2-nitropropane. J Environ Pathol Toxicol 1979;2:233-49.

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