Good for the Ozone — Neurotoxic for Workers

A chemical solvent introduced to replace traditional ozone-depleting solvents in industrial settings has proven highly neurotoxic, according to a study presented October 5, 2004, at the 129th annual meeting of the American Neurological Association in Toronto.

Five workers whose job involved gluing foam cushions together with a glue containing the solvent 1-bromopropane (1-BP, also known as n-propyl bromide) developed severe neurological symptoms, some of which appear to be permanent.

“Two of the workers became profoundly weak, such that even now, eighteen months later, they cannot walk by themselves,” said lead author Jennifer J. Majersik, MD, of the University of Utah. “Several others still have severe pain in their feet and legs, and several have lingering headaches.”

1-BP is an organic solvent used to clean metals and electronics and as a solvent in adhesives. Although it has been used for many years in Asia, 1-BP only became a popular industrial solvent in the United States when it was tabbed to replace banned chlorofluorocarbon solvents that deplete the ozone layer of the atmosphere.

All six workers that Majersik and her colleagues examined had high blood levels of bromide, which indicates high exposure to 1-BP. The air concentration of 1-BP in the workplace was measured at approximately 130 parts per million (ppm) one day after use of the solvent was halted.

The Environmental Protection Agency (EPA) recommends a maximum 1-BP air concentration of 25 ppm. However, this figure is only a recommendation, and there has been no testing to discover whether even this concentration of 1-BP is safe in humans. What little is know about the health effects of 1-BP comes mainly from animal studies. “When rats are exposed to high levels of 1-BP, they suffer peripheral nerve and spinal cord damage resulting in profound leg weakness, just like our patients,” said Majersik.

There have been a few warnings about the neurotoxic effects of 1-BP in humans. Workers who make 1-BP in China have recently been shown to have numbness of their toes and cognitive deficits with only minimal exposures. In addition, several workers in North Carolina, also gluing cushions together, were found to have neurological symptoms following 1-BP exposure.

There is no requirement that most chemicals be evaluated for health effects before they are introduced into industrial settings. Interestingly, 1-BP is an exception: Because it was designed to replace ozone-depleting substances, the EPA has undertaken a process to test the chemical. “But companies can still use the product while the testing is taking place, which can take years,” said toxicologist Martin Caravati, MD, MPH, also of the University of Utah and another author of the report. “Even though there are workplace standards for protective clothing and ventilation, we know that they are not always followed, and workers get exposed to high doses of chemicals with unknown health effects.”

The authors see a number of implications from their findings. “Physicians seeing patients who work in the manufacturing industry should take a careful occupational history of patients who come in with leg weakness or numbness. A high serum chloride is a tip-off to look for elevated serum bromide,” said Majersik.

In terms of wider significance, the authors recommend greater involvement of national safety organizations such as the Occupational Safety and Health Administration (OSHA) to protect workers by mandating specific workplace requirements such as ventilation fans and respiratory masks. “It does appears from our work and that of others that appropriate air circulation protects workers from the toxic effects of the solvent,” said Majersik.

[abstract]
316. Chronic Exposure to 1-Bromopropane Associated with Spastic Paraparesis and Distal Neuropathy: A Report of Six Foam Cushion Gluers, Jennifer J. Majersik, John D. Steffens, and E. Martin Caravati; Salt Lake City, UT

1-Bromopropane (1-BP) is being substituted for traditional ozone-depleting solvents in the industrial setting. We describe six cases of 1-BP neurotoxicity in foam cushion gluers exposed to 1-BP vapors from spray adhesives over several months. All patients complained of subacute onset of lower extremity pain or paresthesias and 5 of 6 complained of difficulty walking. On exam, five patients had bilateral lower extremity spastic paraparesis, distal sensory loss, and hyperreflexia. Serum bromide concentrations ranged from 44 to 170 mg/dL (reference 0-40 mg/dL). Factitious hyperchloremia was present with serum chloride concentrations of 105 to 139 mmol/L (reference 98-107 mmol/L). Air samples taken at the workplace one day after gluing operations ceased revealed a 1-BP mean air concentration of 130 ppm (range 91-176 ppm), well above the EPA-recommended 25 ppm. Fifteen months later, the two most severely affected patients had only regained minimal function and still required assistance to walk; three patients continued to experience chronic neuropathic pain. Chronic exposure to high vapor concentrations of 1-BP in the workplace was associated with a distinct and incapacitating neurotoxic syndrome.