December 5, 2008 / V o l. 57 No.48

full issue available a t: http:// www .cdc.gov/mmw r/PDF/w k /mm5748.pdf

(This ar ticle ma ybe found on pages 1 300 - 13 02 of the full issu e)



# Neur ologic Illness Associated with Occupational Exposur e to the Solvent 1-
Br omopr o pane --- New Jersey and Pennsylvania, 2007--2008

1-Brom opropane (1-BP) (n-propyl br om ide) is a s o lvent incre a singly used as a substitute for ozone-depleting chloro-fluorocarbons and sim ilar regulated compounds. 1-BP is used in vapor and imm e rsion degreasing operations and other m a nufacturing processes, and as a solvent in industries using aer osol-applied adhesives. In som e states, 1-BP is used as a solvent in dry clean ing b ecause of restrictions on use of perchloroethylen e (tetrachloroethylene), a possible hum an carcinogen ( 1 ). Published studies of workers exposed to 1-BP have raised concerns aboutoccupational health ri sks associated with exposure ( 2-- 5 ). This report describes two cases involving workers exposed to 1-BP and diagnosed w ith clinical m a nifestations of neurotoxicity. The cases, when coupled with previous ly reported s t ud ies of workers exposed to 1-BP, illus trate poten tial health ris k s of 1-BP exposure. Clinicians and public health professionals should be alert to potential
health effects am ong workers exposed to 1-BP , particularly in dr y cleaning and other workplaces where 1-BP use m i ght be increasi ng, and effectiv e contro l m e thods to lim it exposure to 1-BP should be imple m e n ted at worksites.

Both cases involved neurotoxic e ffects that likely resulted from occupational exposure to 1-BP in the electronics and dry cleaning indus tries. 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 andstate health agencies, and more in-depth inve stigations of the New Jersey case currently are being conducted by the New Jersey Departme nt 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, dizz iness, 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 pl ant 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 pr otective equipment (PPE), and ventilation was reported by the patient to be poor with in the process room. Neurologic examination revealed that the patient was alert but had sl owed 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. Se rum 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 em ergency department, the Occupational Safety and Health Administration (OSHA) eval uated his workplace and found a 1-BP concentration of 178 ppm by short-term area air sampling. Two week s after his initial visit to the emergency department, the pa tient's serum bromide concentration was 48 mg/dL (normal range: 0--10 mg/dL). His peri pheral neuropathy and ataxia persisted 1 year after the initial visit. The patient also reported having trouble maintaining mental focus and stopped working at the electron ic plant because of continuing medical problems.

Case 2. A previously healthy male aged 43 y ears visited his primary-care physician in New Jersey in February 2008 with a history of headache, naus ea, dizziness, and malaise, which began after he had begun using 1-BP in his dry cleaning facili ty. Six weeks earlier, the patient had switched from using perc hloroethylene to DrySolvTM (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 cl eaning machine. During the next 2 days, he reported unusual fatigue and headaches and de veloped arthralgias, visual disturbances (difficulty focusing), paresthe sias, and muscular twitching.

The patient was referred by his personal phys ician 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 range s. A site visit to the dry cleaning facility in April 2008 by the New Jersey Department of Health and Senior Services revealedbackground 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 Pennsylvani a 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 Sch ill, MS, New Jersey Dept of Health and Senior Svcs. D Trout, MD, P Schulte, PhD, CLGeraci, 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 a lternative for ozone-depleting chlorofluor ocarbons and similar regul ated compounds. Since its introduction within the United States, 1-BP has been applied as a solvent in many industrial processes, including vapor degr easing, 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 demonstr ated 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 wo rker with neurologic abnormalities exposed to 1-BP provides strong evidence of occupa tional 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 conc lusion that his illness was caused by 1-BP. However, the exact etiology of the neurolog ic illnesses of the two workers remains
unclear and nonwork-related fact ors 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 exposur e 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 recommendedoccupational exposure limits ranging from 10 ppm to 100 ppm as an 8-hour timeweighted 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 reproduc tive health of animals ( 8 ). Animal toxicity studies with 1-BP and human case reports of occupational exposur es to 1-BP have ra ised concerns that exposure to 1-BP might cause repr oductive and neurologic effects ( 2--6). Workers exposed to 1-BP vapors from spray adhe sives 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 ner vous system responses to 1-BP exposure ( 2 ).In accordance with its Significant New Alternatives Program, the Environmental Protection Agency (EPA) has reviewed avai lable scientific lite rature 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 publishe d a proposed rule not to accept 1-BP for
use as an aerosol solvent vehicle for adhe sives 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 ne urologic toxicity in the dry cleaning industry, and additional cases could occur as dry clea ners switch from perchloroethylene use to 1- BP. The U.S. dry cleaning and laundry indus try employs an estimated 110,000 persons at approximately 30,000 establishments and is one of the largest industry sectors characterized by small businesses with fewe r than 10 employees. In recent years, an estimated 85%--90% of the dry cleaning i ndustry has used perchloroethylene as a solvent. In response to environmental and health concerns, cert ain states, including California and New Jersey ( 9,10 ), have passed or proposed legi slation 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-resistan t gloves for skin protection ( 7 ). Previous CDC research and communication efforts have emphasized appl ication of a hierarchy of controls (e.g., engineering controls and work practices) for reduci ng 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 a dverse 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 alwa ys should be part of the cl inical evaluation of persons who have unexplained or onset of nonsp ecific neurologic symptoms. Exposure to electronics cleaning solvents or dry clean ing solvents should prompt a more through inquiry concerning exposure to 1-BP. In th e 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 wo rkplace 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.



### References1. Drycleaning and Laundry Institute. A DLI white paper: key information on industry solvents. Laurel, MD: Dr ycleaning and Laundry Institute; 2007.
Available at http://www.startadrycleaners.com/doc s2008/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

. 3. Ichihara G. Neuro-reproductive t oxicities of 1-bromopropane and 2- bromopropane. Int Arch Occup E nviron Health 2005;78:79--96.
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-br omopropane from workers exposed to flexible foam spray adhesive s. 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 pane l report on the reproductive and developmental toxicity of 1-bromopr opane. Reproduc Toxicol 2004;18:157--88.
9. California Environmental Protection Agen cy. Dry cleaning alternative solvents: health and environmental impacts. S acramento, CA: California Environmental Protection Agency, Air Resour ces Board; 2008. Available at http://www.arb.ca.gov/toxics/drycl ean/alternativ esolvts_e.pdf

. 10. New Jersey Department of Environmenta l 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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* Environmental Protection Agency. 40 CFR part 82. Protection of stratospheric ozone: listing of substitutes for ozone depleting substances; n-Propyl bromide in solvent cleaning; final rule. Federal Register 2007;72:30142--67. Available at http://www.epa.gov/fedrgstr/EPA-AIR/2007/May/Day30/a9707.pdf

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† Environmental Protection Agency. 40 CFR part 82. Pr otection of stratospheric ozone: listing of substitutes for ozone depleting substances; n-Propyl bromide for use in adhesives, coatings, and aerosols; notice of proposed rulemaking. Federal Register 2007;72:30168--207. Available at http://www.epa.gov/fedrgstr/EPA -AIR/2007/May/Day-30/a9706.pdf

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§ Available at http://www.cdc.gov/niosh/topics/dryclean

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