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n-Hexane--Related Peripheral Neuropathy Among Automotive Technicians --- California, 1999--2000

Solvents, glues, spray paints, coatings, silicones, and other products contain normal (n-) hexane, a petroleum distillate and simple aliphatic hydrocarbon. n-Hexane is an isomer of hexane and was identified as a peripheral neurotoxin in 1964 (1). Since then, many cases of n-hexane--related neurotoxicity have occurred in printing plants, sandal shops, and furniture factories in Asia, Europe, and the United States (2). This report describes an investigation of n-hexane--associated peripheral neuropathy in an automotive technician, an occupation in which this condition has not been reported, and summarizes the results of two other case investigations in the automotive repair industry. The findings suggest that solvent manufacturers should avoid using hexane when producing automotive degreasing products, and automotive technicians should avoid regular contact with hexane-based cleaning solvents.

In December 1998, the California Department of Health Services (CDHS) received a report from an occupational-medicine physician of a patient with peripheral neuropathy associated with occupational exposure to n-hexane at an automotive repair facility. The index patient was a 24-year-old male automotive technician who had worked in the industry during June 1995--April 1997. In January 1997, numbness and tingling developed in his hands and feet then spread proximally to his forearms and waist. In March, a neurologic evaluation revealed bilaterally diminished reflexes of the biceps, patellar, and Achilles' deep tendon. Vibration and pinprick sensations were reduced from the lower third of the forearms and downward from the waist; the result of his Romberg test was positive. Tests evaluating his metabolic and thyroid function; urinary cadmium, arsenic, lead, and mercury levels; and central nervous system imaging were normal; however, nerve conduction velocity studies revealed a subacute progressive mixed motor-sensory neuropathy with distal nerve involvement. He had reported using from one to nine 15-oz. aerosol cans of brake cleaner per day during the 22 months of his employment. This brake cleaner contained 50%--60% hexane (composed of 20%--80% n-hexane), 20%--30% toluene, and 1%--10% each of methyl ethyl ketone (MEK), acetone, isopropanol, methanol, and mixed xylenes. The technician sprayed the product on brakes, tools, small spills, and engine surfaces. He occasionally used a rag. He reported wearing latex gloves daily and drinking alcohol occasionally. His condition improved with cessation of n-hexane exposure; however, he continues to have paresthesias in the hands and feet.

To assess the possible occurrence of n-hexane--related peripheral neuropathy at other automotive repair facilities, during 1999, CDHS screened for n-hexane--related peripheral neuropathy at a local automotive dealership that used an aerosol product containing 1%--5% n-hexane and 2% MEK. This facility was chosen for convenience and the employees' willingness to participate. A case of n-hexane--related peripheral neuropathy was defined as symptoms and results of nerve conduction velocity tests consistent with peripheral neuropathy in an automotive technician who had chronic occupational exposure to hexane-containing solvents and no other explanation for peripheral neuropathy. Screening included a medical history, an exposure questionnaire, physical and neurologic examinations, nerve conduction velocity studies, and neurophysiologic testing for cognitive and motor function, reaction time, and color vision. At CDC's National Institute for Occupational Safety and Health (NIOSH), recent exposure to n-hexane was estimated by measuring 2,5hexanedione (2,5-HD), a urinary metabolite, in acid-hydrolyzed urine samples. Air samples were not tested because management had removed the hexane-containing solvent from the facility at the onset of the investigation.

Six (40%) of 15 technicians from this facility participated in the screening. All participants had worked >20 years as technicians; one met the case definition for n-hexane--related peripheral neuropathy. Three of the six had detectable 2,5-HD levels, which were 7.0%, 26.0%, and 6.4% of the biologic exposure index (BEI) of 5 mg 2,5-HD/g creatinine. The BEI is a biomarker that correlates to the American Conference of Governmental Industrial Hygienists' 8-hour threshold limit value (ACGIH TLV) of 50 ppm (3). The exposure values identified are considered acceptable by this standard.

During August 2000, CDHS surveyed California neurologists* to identify additional cases of n-hexane--related peripheral neuropathy and to determine whether exposure had occurred among persons while working in automotive repair facilities. A total of 58 (20%) of 291 neurologists responded to the survey. One automotive technician was identified with n-hexane--related peripheral neuropathy. CDHS reviewed the medical records and verified that the technician met the case definition for n-hexane--related peripheral neuropathy.

In July 2000, CDHS guidelines were published outlining the diagnosis and management of n-hexane--related peripheral neuropathy (4). The guidelines and notification of the identified cases were distributed to the Association of California Neurologists and to members of the Association of Occupational and Environmental Clinics. The northern California district of the International Association of Machinists and the California Motor Car Dealer Association also were notified.

Reported by: R Harrison, MD, L Israel, DO, P Larabee, MD, Dept of Medicine, Univ of California, San Francisco; J Cone, MD, C Baker, MPH, M Brewer, R Das, MD, S Brumis, MPH, Occupational Health Br, California Dept of Health Svcs; R Bowler, PhD, San Francisco State Univ; MP Wilson, MPH, SK Hammond, PhD, School of Public Health, Univ of California, Berkeley. Div of Applied Research and Technology, National Institute for Occupational Safety and Health; and an EIS Officer, CDC.

Editorial Note:

The three cases of peripheral neuropathy described in this report are related to occupational exposure to n-hexane among automotive technicians. Hexane-containing degreasing products are used in automotive repair facilities and usually are dispensed in an aerosol spray. Inhalation is the primary exposure route. Dermal exposure also may occur, and latex gloves provide ineffective protection from organic solvents. The neurotoxic effects of n-hexane may be intensified when used with other chemicals found in automotive degreasers (e.g., acetone, MEK, and isopropanol) (5). Acid-hydrolyzed urinary levels of 2,5-HD, sampled at the end of a shift, correlate with workplace concentrations of n-hexane. Because 2,5-HD has a half-life of 13--14 hours, accumulation may occur during the workweek (6).

Chronic n-hexane exposure produces a gradual sensorimotor neuropathy with demyelinating features. The most common initial complaint is numbness and tingling of the toes and fingers; a progressive loss of motor function may develop. Chronic polyneuropathy with demyelinating features also is associated with other underlying conditions. Other causes of peripheral neuropathy should be considered when evaluating persons with possible n-hexane--related peripheral neuropathy. Removal from n-hexane exposure is the only known treatment for n-hexane--related neurotoxicity.

The prognosis for n-hexane neuropathy generally is favorable, but recovery may take months to years, depending on disease severity. The current Occupational Safety and Health Administration permissible exposure limit (PEL) for n-hexane, adopted in 1971, is 500 ppm in air. NIOSH established a recommended PEL of 50 ppm in 1989; the PEL for ACGIH TLV and California are 50 ppm (7).

Other cases of n-hexane--related peripheral neuropathy may be occurring in this industry, but the nature of these exposures and the extent of illness are unknown. The methods used to identify the cases in this report were not intended to represent all automotive repair facilities. An exposure assessment and additional case ascertainment are in progress. Cases of n-hexane--related neuropathy in the automotive repair industry could be prevented through reformulation of hexane-containing products and greater use of aqueous cleaning systems.

References

  1. Yamada S. An occurrence of polyneuritis by n-hexane in the polyethylene laminating plants. Jpn J Ind Health 1964;6:192.
  2. Arlien-Soborg P. Solvent neurotoxicology. Boca Raton, Florida: CRC Press, 1992:155--83.
  3. American Conference of Governmental Industrial Hygienists. 2000 TLVs® and BEIs®: threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, Ohio: American Conference of Governmental Industrial Hygienists, 2000.
  4. Hazard Evaluation System and Information Service. Medical guidelines: n-hexane, July 2000. Available at <http://www.dhs.ca.gov/ohb/HESIS/nhexane.htm>. Accessed November 2001.
  5. Ralston W, Hilderbrand R, Uddin D, Andersen M, Gardier R. Potentiation of 2,5- hexanedione neurotoxicity by methyl ethyl ketone. Toxicol Appl Pharmacol 1985;81:319--27.
  6. Perbellini L, Mozzo P, Brugnone F, Zedde A. Physiologico-mathematical model for studying human exposure to organic solvents: kinetics of blood/tissue n-hexane concentrations and of 2,5-hexanedione in urine. Br J Ind Med 1986;43:760--8.
  7. Lanska DJ. Limitations of occupational air contaminant standards, as exemplified by the neurotoxin n-hexane. J Pub Health Policy 1999;20:441--58.

* List generated by Dun and Bradstreet directory (June--August 2000). Standard Industry Code 8011-6107.



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