Exposure to Specific Solvents May Increase Risk for Parkinson's

Occupational exposure to specific chemical solvents, primarily trichloroethylene or tetrachloroethylene, was associated with increased odds for developing Parkinson’s disease in a case-control study of pairs of twins who were discordant for the condition.

Exposure to trichloroethylene (TCE) at any time while at work increased the odds of developing Parkinson’s disease sixfold, although the 95% confidence interval of the estimate ranged from 1.2 to 33. The odds ratio for development of Parkinson’s increased to 8.9 when occupational exposure to either trichloroethylene or tetrachloroethylene – also known as perchloroethylene (PERC) – was considered as a combined variable, but this too had a wide confidence interval of 1.7 to 47, Dr. Samuel M. Goldman and his colleagues reported online Nov. 14 in Annals of Neurology.

Researchers have long suspected that solvents such as those might contribute to the risk for Parkinson’s disease, but most of the available evidence has been anecdotal. To examine the issue more rigorously, during 1993-1995 Dr. Goldman and his associates attempted to contact 19,842 twins from the National Academy of Sciences/National Research Council World War II Veteran Twins Registry, an all-male twin cohort established in the 1960s. The investigators collected the occupational histories of 99 pairs (49 identical, 50 fraternal) in which only one of the twins developed Parkinson’s disease (Ann. Neurol. 2011 Nov. 14 [doi:10.1002/ana.22629]).

The study team assessed the twins’ lifetime exposures to six specific solvents based on being previously linked to Parkinson’s disease or parkinsonism in case reports or analytic studies: n-hexane, xylene, toluene, carbon tetrachloride (CCl₄), TCE, and PERC.

They asked the twins (or proxy informants) for detailed information about the jobs in which they had worked for more than 6 months since age 10 years, as well as about their hobbies. The researchers also collected information on head injuries and smoking history, which can affect an individual’s risk for Parkinson’s disease. Expert evaluators, unaware of which subjects had Parkinson’s, used probability databases to calculate lifelong exposure to the six chemicals.

The frequencies of either twin being exposed to each solvent ranged from 6% of work time for PERC to 27% for toluene, the researchers found. For TCE, the frequency of exposure was 12%. In 48% of pairs, at least one twin was exposed to one or more of the six solvents studied.

Exposure to PERC was associated with more than 10 times greater odds for developing Parkinson’s disease (OR, 10.5; 95%; CI, 0.97-113) and the odds were more than doubled with exposure to CCl₄ (OR, 2.3; 95%; CI, 0.9-6.1), although neither comparison was statistically significant.

TCE, PERC, and CCl₄ are known to increase markers of oxidative and nitrative stress and disrupt mitochondrial function. "The potential importance is great, since both solvents persist in the environment and are commonly used," said Dr. Goldman said in a statement issued by the National Institute of Neurological Disorders and Stroke, one of the sources of funding for the study.

TCE and PERC are used as dry cleaning and degreasing agents. The Food and Drug Administration banned the use of TCE as an anesthetic, skin disinfectant, grain fumigant, and coffee decaffeinating agent in 1977. Both compounds have been used as additives in many common household products, including typewriter correction fluid, adhesives, paints, and carpet cleaners and spot removers. TCE also is the most common organic contaminant in groundwater, according to the investigators.

To limit reporting and recall bias, the investigators used validated exposure assessment methods and questionnaires that inferred exposure to chemicals based on job tasks rather than self-reported exposures to specific compounds. However, the ability of the study to draw firm conclusions was limited by its small sample size and reliance on retrospective recall and proxy informants for a large proportion of subjects.

"Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are considerable," the researchers wrote. "One remarkable observation made in all the reports linking TCE exposure with [Parkinson’s disease] is the very long time lag (10-40 years) between exposure and clinical disease. These observations suggest that exposure may trigger a degenerative cascade dependent on the passage of time, providing a critical window of opportunity to arrest the disease process before clinical symptoms are manifested."

Besides the National Institute of Neurological Disorders and Stroke, the study was supported by grants from the Michael J. Fox Foundation, Parkinson’s Unity Walk, the Valley Foundation, and James and Sharron Clark. Many of the authors disclosed receiving grants from many research institutions and foundations focused on Parkinson’s disease and receiving financial compensation for various relationships with pharmaceutical companies that manufacture Parkinson’s disease medications.

Occupational exposure to specific chemical solvents, primarily trichloroethylene or tetrachloroethylene, was associated with increased odds for developing Parkinson’s disease in a case-control study of pairs of twins who were discordant for the condition.

Exposure to trichloroethylene (TCE) at any time while at work increased the odds of developing Parkinson’s disease sixfold, although the 95% confidence interval of the estimate ranged from 1.2 to 33. The odds ratio for development of Parkinson’s increased to 8.9 when occupational exposure to either trichloroethylene or tetrachloroethylene – also known as perchloroethylene (PERC) – was considered as a combined variable, but this too had a wide confidence interval of 1.7 to 47, Dr. Samuel M. Goldman and his colleagues reported online Nov. 14 in Annals of Neurology.

Researchers have long suspected that solvents such as those might contribute to the risk for Parkinson’s disease, but most of the available evidence has been anecdotal. To examine the issue more rigorously, during 1993-1995 Dr. Goldman and his associates attempted to contact 19,842 twins from the National Academy of Sciences/National Research Council World War II Veteran Twins Registry, an all-male twin cohort established in the 1960s. The investigators collected the occupational histories of 99 pairs (49 identical, 50 fraternal) in which only one of the twins developed Parkinson’s disease (Ann. Neurol. 2011 Nov. 14 [doi:10.1002/ana.22629]).

The study team assessed the twins’ lifetime exposures to six specific solvents based on being previously linked to Parkinson’s disease or parkinsonism in case reports or analytic studies: n-hexane, xylene, toluene, carbon tetrachloride (CCl₄), TCE, and PERC.

They asked the twins (or proxy informants) for detailed information about the jobs in which they had worked for more than 6 months since age 10 years, as well as about their hobbies. The researchers also collected information on head injuries and smoking history, which can affect an individual’s risk for Parkinson’s disease. Expert evaluators, unaware of which subjects had Parkinson’s, used probability databases to calculate lifelong exposure to the six chemicals.

The frequencies of either twin being exposed to each solvent ranged from 6% of work time for PERC to 27% for toluene, the researchers found. For TCE, the frequency of exposure was 12%. In 48% of pairs, at least one twin was exposed to one or more of the six solvents studied.

Exposure to PERC was associated with more than 10 times greater odds for developing Parkinson’s disease (OR, 10.5; 95%; CI, 0.97-113) and the odds were more than doubled with exposure to CCl₄ (OR, 2.3; 95%; CI, 0.9-6.1), although neither comparison was statistically significant.

TCE, PERC, and CCl₄ are known to increase markers of oxidative and nitrative stress and disrupt mitochondrial function. "The potential importance is great, since both solvents persist in the environment and are commonly used," said Dr. Goldman said in a statement issued by the National Institute of Neurological Disorders and Stroke, one of the sources of funding for the study.

TCE and PERC are used as dry cleaning and degreasing agents. The Food and Drug Administration banned the use of TCE as an anesthetic, skin disinfectant, grain fumigant, and coffee decaffeinating agent in 1977. Both compounds have been used as additives in many common household products, including typewriter correction fluid, adhesives, paints, and carpet cleaners and spot removers. TCE also is the most common organic contaminant in groundwater, according to the investigators.

To limit reporting and recall bias, the investigators used validated exposure assessment methods and questionnaires that inferred exposure to chemicals based on job tasks rather than self-reported exposures to specific compounds. However, the ability of the study to draw firm conclusions was limited by its small sample size and reliance on retrospective recall and proxy informants for a large proportion of subjects.

"Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are considerable," the researchers wrote. "One remarkable observation made in all the reports linking TCE exposure with [Parkinson’s disease] is the very long time lag (10-40 years) between exposure and clinical disease. These observations suggest that exposure may trigger a degenerative cascade dependent on the passage of time, providing a critical window of opportunity to arrest the disease process before clinical symptoms are manifested."

Besides the National Institute of Neurological Disorders and Stroke, the study was supported by grants from the Michael J. Fox Foundation, Parkinson’s Unity Walk, the Valley Foundation, and James and Sharron Clark. Many of the authors disclosed receiving grants from many research institutions and foundations focused on Parkinson’s disease and receiving financial compensation for various relationships with pharmaceutical companies that manufacture Parkinson’s disease medications.

Occupational exposure to specific chemical solvents, primarily trichloroethylene or tetrachloroethylene, was associated with increased odds for developing Parkinson’s disease in a case-control study of pairs of twins who were discordant for the condition.

Exposure to trichloroethylene (TCE) at any time while at work increased the odds of developing Parkinson’s disease sixfold, although the 95% confidence interval of the estimate ranged from 1.2 to 33. The odds ratio for development of Parkinson’s increased to 8.9 when occupational exposure to either trichloroethylene or tetrachloroethylene – also known as perchloroethylene (PERC) – was considered as a combined variable, but this too had a wide confidence interval of 1.7 to 47, Dr. Samuel M. Goldman and his colleagues reported online Nov. 14 in Annals of Neurology.

Researchers have long suspected that solvents such as those might contribute to the risk for Parkinson’s disease, but most of the available evidence has been anecdotal. To examine the issue more rigorously, during 1993-1995 Dr. Goldman and his associates attempted to contact 19,842 twins from the National Academy of Sciences/National Research Council World War II Veteran Twins Registry, an all-male twin cohort established in the 1960s. The investigators collected the occupational histories of 99 pairs (49 identical, 50 fraternal) in which only one of the twins developed Parkinson’s disease (Ann. Neurol. 2011 Nov. 14 [doi:10.1002/ana.22629]).

The study team assessed the twins’ lifetime exposures to six specific solvents based on being previously linked to Parkinson’s disease or parkinsonism in case reports or analytic studies: n-hexane, xylene, toluene, carbon tetrachloride (CCl₄), TCE, and PERC.

They asked the twins (or proxy informants) for detailed information about the jobs in which they had worked for more than 6 months since age 10 years, as well as about their hobbies. The researchers also collected information on head injuries and smoking history, which can affect an individual’s risk for Parkinson’s disease. Expert evaluators, unaware of which subjects had Parkinson’s, used probability databases to calculate lifelong exposure to the six chemicals.

The frequencies of either twin being exposed to each solvent ranged from 6% of work time for PERC to 27% for toluene, the researchers found. For TCE, the frequency of exposure was 12%. In 48% of pairs, at least one twin was exposed to one or more of the six solvents studied.

Exposure to PERC was associated with more than 10 times greater odds for developing Parkinson’s disease (OR, 10.5; 95%; CI, 0.97-113) and the odds were more than doubled with exposure to CCl₄ (OR, 2.3; 95%; CI, 0.9-6.1), although neither comparison was statistically significant.

TCE, PERC, and CCl₄ are known to increase markers of oxidative and nitrative stress and disrupt mitochondrial function. "The potential importance is great, since both solvents persist in the environment and are commonly used," said Dr. Goldman said in a statement issued by the National Institute of Neurological Disorders and Stroke, one of the sources of funding for the study.

TCE and PERC are used as dry cleaning and degreasing agents. The Food and Drug Administration banned the use of TCE as an anesthetic, skin disinfectant, grain fumigant, and coffee decaffeinating agent in 1977. Both compounds have been used as additives in many common household products, including typewriter correction fluid, adhesives, paints, and carpet cleaners and spot removers. TCE also is the most common organic contaminant in groundwater, according to the investigators.

To limit reporting and recall bias, the investigators used validated exposure assessment methods and questionnaires that inferred exposure to chemicals based on job tasks rather than self-reported exposures to specific compounds. However, the ability of the study to draw firm conclusions was limited by its small sample size and reliance on retrospective recall and proxy informants for a large proportion of subjects.

"Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are considerable," the researchers wrote. "One remarkable observation made in all the reports linking TCE exposure with [Parkinson’s disease] is the very long time lag (10-40 years) between exposure and clinical disease. These observations suggest that exposure may trigger a degenerative cascade dependent on the passage of time, providing a critical window of opportunity to arrest the disease process before clinical symptoms are manifested."

Besides the National Institute of Neurological Disorders and Stroke, the study was supported by grants from the Michael J. Fox Foundation, Parkinson’s Unity Walk, the Valley Foundation, and James and Sharron Clark. Many of the authors disclosed receiving grants from many research institutions and foundations focused on Parkinson’s disease and receiving financial compensation for various relationships with pharmaceutical companies that manufacture Parkinson’s disease medications.