Neurologic Illness Associated with Occupational Exposure to the Solvent 1-Bromopropane --- New Jersey and Pennsylvania, 2007--2008

1-Bromopropane (1-BP) (n-propyl bromide) is a solvent increasingly used as a substitute for ozone-depleting chloro-fluorocarbons and similar regulated compounds. 1-BP is used in vapor and immersion degreasing operations and other manufacturing processes, and as a solvent in industries using aerosol-applied adhesives. In some states, 1-BP is used as a solvent in dry cleaning because of restrictions on use of perchloroethylene (tetrachloroethylene), a possible human carcinogen (1). Published studies of workers exposed to 1-BP have raised concerns about occupational health risks associated with exposure (2--5). This report describes two cases involving workers exposed to 1-BP and diagnosed with clinical manifestations of neurotoxicity. The cases, when coupled with previously reported studies of workers exposed to 1-BP, illustrate potential health risks of 1-BP exposure. Clinicians and public health professionals should be alert to potential health effects among workers exposed to 1-BP, particularly in dry cleaning and other workplaces where 1-BP use might be increasing, and effective control methods to limit exposure to 1-BP should be implemented at worksites.

Both cases involved neurotoxic effects that likely resulted from occupational exposure to 1-BP in the electronics and dry cleaning industries. The cases were reported to regional poison control centers in Pennsylvania (2007) and New Jersey (2008) by attending physicians who treated the affected workers. The cases were investigated by federal and state health agencies, and more in-depth investigations of the New Jersey case currently are being conducted by the New Jersey Department of Health and Senior Services and CDC.

Case 1. In 2007, a male aged 50 years visited an emergency department in Pennsylvania with a history of confusion, dysarthria, dizziness, paresthesias, and ataxia for 24--48 hours. The patient had worked for 8 years at an electronics plant in Pennsylvania, where for 3 years 1-BP had been used to clean circuit boards by vapor and immersion degreasing. His duties at the plant included mechanically submerging and spraying circuit boards with 1-BP, and maintenance (draining, cleaning, and charging) of the bath tank. The patient typically did not use personal protective equipment (PPE), and ventilation was reported by the patient to be poor within the process room. Neurologic examination revealed that the patient was alert but had slowed mental activity and mild confusion. His cranial nerve function and motor strength were intact, but his gait was wide based and ataxic, and a Romberg's test was positive. Serum laboratory results were notable for an anion gap of -31 mmol/L (normal range: 5--17 mmol/L) and a chloride concentration of 146 mmol/L (normal range: 101--111 mmol/L). The patient was hospitalized. Mild sensory peripheral neuropathy was detected by electromyogram in his upper and lower extremities.

One week after the patient went to the emergency department, the Occupational Safety and Health Administration (OSHA) evaluated his workplace and found a 1-BP concentration of 178 ppm by short-term area air sampling. Two weeks after his initial visit to the emergency department, the patient's serum bromide concentration was 48 mg/dL (normal range: 0--10 mg/dL). His peripheral neuropathy and ataxia persisted 1 year after the initial visit. The patient also reported having trouble maintaining mental focus and stopped working at the electronic plant because of continuing medical problems.

Case 2. A previously healthy male aged 43 years visited his primary-care physician in New Jersey in February 2008 with a history of headache, nausea, dizziness, and malaise, which began after he had begun using 1-BP in his dry cleaning facility. Six weeks earlier, the patient had switched from using perchloroethylene to DrySolv™ (Enviro Tech International, Melrose Park, Illinois) (>95% by weight 1-BP) as the solvent in his dry cleaning machine (7). The patient also used DrySolv as a cleaner to prepare the dry cleaning machine for use. In early February 2008, he manually charged the machine using 50--60 gallons of the solvent and did not use PPE. The patient then began using DrySolv in the daily operation of the dry cleaning machine. During the next 2 days, he reported unusual fatigue and headaches and developed arthralgias, visual disturbances (difficulty focusing), paresthesias, and muscular twitching.

The patient was referred by his personal physician to an emergency department, where physical examination and computed tomography of his head were normal, except for a slight tremor in his upper extremities. Tests of the patient's serum revealed an anion gap and chloride concentration within normal ranges. A site visit to the dry cleaning facility in April 2008 by the New Jersey Department of Health and Senior Services revealed background and high peak concentrations (75 to 250 times background levels) of 1-BP during the handling of clothes. The patient continued to use 1-BP in the dry cleaning machine but adjusted temperature settings on the machine to account for the physical properties of 1-BP, improved his use of ventilation, and began using PPE.

Reported by: J Perrone, MD, Univ of Pennsylvania School of Medicine. SM Marcus, MD, Univ of Medicine and Dentistry of New Jersey and New Jersey Poison Information and Education System; JD Blando, PhD, D Schill, MS, New Jersey Dept of Health and Senior Svcs. D Trout, MD, P Schulte, PhD, CL Geraci, PhD, GS Dotson, PhD, K Hanley, MSPH, KR Mead, PhD, DVL Myers, PhD, C Curran, PhD, National Institute for Occupational Safety and Health, CDC.

Editorial Note:

1-BP has received increased global attention since the 1990s as a potential alternative for ozone-depleting chlorofluorocarbons and similar regulated compounds. Since its introduction within the United States, 1-BP has been applied as a solvent in many industrial processes, including vapor degreasing, foam cushion manufacturing, and dry cleaning. The incidence of 1-BP toxicity is unknown, and the signs and symptoms are not described fully. In this report, case 1 demonstrated severe neurologic illness in a worker in the electronics industry using 1-BP as a cleaning solvent. The elevated serum bromide concentration and negative anion gap in a worker with neurologic abnormalities exposed to 1-BP provides strong evidence of occupational 1-BP toxicity. Although bromide levels were not measured in case 2, the patient's clinical presentation and course, and his exposure to 1-BP, strongly favor the conclusion that his illness was caused by 1-BP. However, the exact etiology of the neurologic illnesses of the two workers remains unclear and nonwork-related factors potentially contributing to the illnesses are not fully characterized. Additionally, personal exposure information was not available for these workers to help establish their workplace exposures to 1-BP or to other potential workplace hazards.

CDC does not have a recommended exposure limit for 1-BP, nor does OSHA have a permissible exposure limit. Manufacturers of 1-BP and professional organizations, such as the American Conference of Governmental Industrial Hygienists, have recommended occupational exposure limits ranging from 10 ppm to 100 ppm as an 8-hour time-weighted average (6). On the basis of limited exposure and human health effects data, the National Toxicology Program concluded that exposure to 1-BP is toxic to the developmental and reproductive health of animals (8). Animal toxicity studies with 1-BP and human case reports of occupational exposures to 1-BP have raised concerns that exposure to 1-BP might cause reproductive and neurologic effects (2--6). Workers exposed to 1-BP vapors from spray adhesives at two seat-cushion--manufacturing facilities were found to have severe neurologic illnesses (4,5). CDC evaluated workers at one of those facilities and found nonspecific acute effects (e.g., headache and feeling drunk) possibly associated with central nervous system responses to 1-BP exposure (2).

In accordance with its Significant New Alternatives Program, the Environmental Protection Agency (EPA) has reviewed available scientific literature on 1-BP and promulgated a final rule to accept 1-BP as an alternative for ozone-depleting solvents in the solvent cleaning sector.* EPA also published a proposed rule not to accept 1-BP for use as an aerosol solvent vehicle for adhesives because of higher exposures and the potential for adverse health effects to workers in these settings.^† These new rules do not apply to dry cleaning.

Case 2 likely represents a sentinel case of neurologic toxicity in the dry cleaning industry, and additional cases could occur as dry cleaners switch from perchloroethylene use to 1-BP. The U.S. dry cleaning and laundry industry employs an estimated 110,000 persons at approximately 30,000 establishments and is one of the largest industry sectors characterized by small businesses with fewer than 10 employees. In recent years, an estimated 85%--90% of the dry cleaning industry has used perchloroethylene as a solvent. In response to environmental and health concerns, certain states, including California and New Jersey (9,10), have passed or proposed legislation to eliminate use of perchloroethylene as the primary solvent in the dry cleaning industry. To use 1-BP as an alternative solvent, dry cleaning businesses must modify existing equipment to adjust heating/drying cycles, upgrade solvent vapor control systems, replace natural rubber seals, and provide adequate exhaust ventilation. Manufacturer literature on the use of DrySolv recommends wearing a full-facepiece organic vapor respirator if ventilation is inadequate, and chemical-resistant gloves for skin protection (7). Previous CDC research and communication efforts have emphasized application of a hierarchy of controls (e.g., engineering controls and work practices) for reducing worker exposures to perchloroethylene.^§ Similar controls should be used within the dry cleaning industry to limit worker exposure to 1-BP.

Clinicians and public health officials should be alert to potential adverse health effects from exposures to 1-BP in industries where such use might increase, such as the dry cleaning industry, and in workplaces where 1-BP use might be more established. A thorough occupational history always should be part of the clinical evaluation of persons who have unexplained or onset of nonspecific neurologic symptoms. Exposure to electronics cleaning solvents or dry cleaning solvents should prompt a more through inquiry concerning exposure to 1-BP. In the evaluation of a worker with occupational exposure to 1-BP and neurologic abnormalities, diagnosis of 1-BP poisoning is suggested by an elevated urinary or serum bromide concentration and a negative serum anion gap. Findings of potential 1-BP poisoning in a potentially exposed worker should prompt removal of the worker from the exposure while an evaluation of workplace exposures is conducted by a qualified professional.

Acknowledgment

The findings in this report are based, in part, on contributions by JB Nemhauser, MD, National Center for Environmental Health, CDC.

References

1. Drycleaning and Laundry Institute. A DLI white paper: key information on industry solvents. Laurel, MD: Drycleaning and Laundry Institute; 2007. Available at http://www.startadrycleaners.com/docs2008/dli%20white%20paper.final.pdf.
2. CDC. Health hazard evaluation report: Marx Industries, Inc. Cincinnati, OH: US Department of Health and Human Services, Public Health Service, CDC, National Institute for Occupational Safety and Health; 2003. HETA 99-0260-2906. Available at http://www.cdc.gov/niosh/hhe/reports/pdfs/1999-0260-2906.pdf.
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4. Raymond LW, Ford MD. Severe illness in furniture makers using a new glue: 1-bromopropane toxicity confounded by arsenic. J Occup Environ Med 2007;49:1009--19.
5. Majersik JJ, Caravati EM, Steffens JD. Severe neurotoxicity associated with exposure to the solvent 1-bromopropane (n-propyl bromide). Clin Toxicol 2007;45:270--6.
6. Hanley KW, Petersen M, Curwin BD, Sanderson WT. Urinary bromide and breathing zone concentrations of 1-bromopropane from workers exposed to flexible foam spray adhesives. Ann Occup Hyg 2006;50:599--607.
7. Dry Cleaning Technologies. Material safety data sheet for DrySolv. Melrose Park, IL: Enviro Tech International; 2008. Available at http://www.dctco.com/drysolv_msds.pdf.
8. National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction. NTP-CERHR expert panel report on the reproductive and developmental toxicity of 1-bromopropane. Reproduc Toxicol 2004;18:157--88.
9. California Environmental Protection Agency. Dry cleaning alternative solvents: health and environmental impacts. Sacramento, CA: California Environmental Protection Agency, Air Resources Board; 2008. Available at http://www.arb.ca.gov/toxics/dryclean/alternativesolvts_e.pdf.
10. New Jersey Department of Environmental Protection. Control and prohibition of air pollution by toxic substances. Trenton, NJ: New Jersey Department of Environmental Protection; 2007. Available at http://www.nj.gov/dep/rules/proposals/121707b.pdf.

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Date last reviewed: 12/3/2008