Observed versus predicted carboxyhemoglobin levels in cellulose triacetate workers exposed to methylene chloride.

BACKGROUND: Occupational exposure to methylene chloride, together with carboxyhemoglobin concentrations, has not been studied previously. METHODS: Carboxyhemoglobin levels were measured in non-smoking employees exposed to varying concentrations of methylene chloride during the manufacture of cellulose triacetate fibers. The observed carboxyhemoglobin levels were compared to predicted concentrations using a pharmacokinetic model. RESULTS: The presence of carboxyhemoglobin in non-smokers exposed to methylene chloride results primarily from the metabolism of methylene chloride in the liver and exhibits a linear dose-response relationship. The observed levels of carboxyhemoglobin in non-smokers at the end of an 8-hour shift depend upon exposures to methylene chloride that day but are independent of occupational exposures on previous days. The observed daily concentrations of carboxyhemoglobin are consistent with predicted concentrations using a pharmacokinetic model. While varying exposure patterns were shown to change the rate of metabolite formation at the end of shift, these same exposure patterns had almost no effect on the total amount of carbon monoxide in the blood. CONCLUSION: While the present study addresses the relationship between methylene chloride, carbon monoxide, carboxyhemoglobin and ischemic heart disease, it does not address the issue of tumorigenicity, which is also the basis for the current U.S. Occupational Health and Safety workplace exposure limit of 25 ppm. This study provides support for the conclusion that the current American Conference of Governmental Industrial Hygienists 8-hour Threshold Limit Value of 50 ppm adequately protects human health with regard to ischemic heart disease and carboxyhemoglobin formation among non-smokers.

Carboxyhemoglobin levels in methylene chloride-exposed employees.

The Occupational Safety and Health Administration (OSHA) has proposed a reduction in the permissible exposure limit for methylene chloride from 500 parts per million (ppm) to 25 ppm (8-hour time-weighted average [TWA]). Part of the rationale for lowering the standard is a concern over potentially adverse cardiac effects secondary to elevated carboxyhemoglobin (COHb) levels as a by-product of methylene chloride metabolism. Employees exposed to methylene chloride as part of a triacetate fiber production process had average values of COHb ranging between 1.77% and 4.00% in the nonsmoking group and between 4.95% and 6.35% in a smoking group, with individually measured methylene chloride exposures averaging up to 99 ppm (8-hour TWA). A dose-response effect was seen only in the nonsmoking group. Additional daily cumulative exposure to methylene chloride did not produce increased levels of COHb. Data from this study support the fact that the COHb levels resulting from exposure to methylene chloride at or below the current American College of Government Industrial Hygienists limit of 50 ppm (8-hour TWA) are of a sufficiently low level that they are unlikely to produce adverse cardiac effects in humans.

Mortality among synthetic fiber workers exposed to glycerol polyglycidyl ether.

We studied mortality among 8,878 employees who worked at any time from 1965 to 1988 at a synthetic fibers plant in North Carolina that used a finishing agent containing glycerol polyglycidyl ether. Some glycidyl ethers are mutagenic and tumorigenic in laboratory animals. The main route of exposure to workers was inhalation of the spray mist, although there was also skin contact. We identified 553 deaths in the cohort and the standardized mortality ratio (SMR) from all causes of death combined was 0.80. For most causes of death, mortality rates in the cohort were similar to mortality rates in the U.S. population. Among categories with at least five observed deaths, the largest effect estimate was for cancer of the central nervous system (SMR = 1.77), and the SMR for lung cancer was 0.94. The cancer categories of central nervous system (brain) and "other" lymphopoietic cancers (lymphoma and myeloma) showed weak associations with duration of employment. In case-control analyses in which we utilized work history data to compute effect estimates by duration of exposure, we found no increased risk of lung cancer or brain cancer among employees with more than 5 years of exposure. Effect estimates for lymphoma and myeloma tended to increase with duration of exposure, although there were only seven deaths in this category and the effect estimates were very imprecise. To date, this study has identified no clear carcinogenic effect of glycerol polyglycidyl ether, but plausible induction periods have not yet elapsed. The cohort should continue to be monitored to obtain more precise estimates after moderate or long induction times.

Mortality update of cellulose fiber production workers.

Mortality ascertainment was extended through 1990 for a cohort of 1271 workers involved in the production of cellulose triacetate fiber at a plant in Rock Hill, South Carolina. Each subject was employed for at least three months between 1 January 1954 and 1 January 1977 in jobs that entailed exposure to the highest concentrations of methylene chloride. Median exposures in 1977 ranged from 140 to 745 ppm (8-h time-weighted average). The observed numbers of deaths from specific causes were compared with the expected numbers of deaths computed from rates in York County, South Carolina. For most causes of death, there was little if any association with employment. Among causes of particular interest, no new deaths were observed from cancer of the liver and biliary tract, although the excess from the earlier study persisted (4 observed, 1.34 expected). No excess mortality was observed for cancer of the pancreas (2 observed, 2.42 expected) or for ischemic heart disease (43 observed, 47.8 expected).

An evaluation of chronic methylene chloride exposure.

Various groups including the Occupational Safety and Health Administration, Environmental Protection Agency, and Consumer Product Safety Commission have expressed concern over methylene chloride and its possible effects on human health. A group of employees exposed to relatively high levels of methylene chloride (average = 475 ppm 8-hour time-weighted average) for greater than 10 years were compared to a similar nonexposed group of employees for selected health parameters. All were participants in an employee health monitoring program. Selected questions evaluating cardiac and neurologic health effects revealed no differences between the two groups. Likewise, hematologic assessment also revealed no clinically significant differences between the two groups for SGOT(AST), SGPT(ALT), total bilirubin, and hematocrit. Therefore, it appears that chronic exposure to even high levels of methylene chloride produces no difference in symptoms or adverse health effects in this population as judged by selected liver, cardiac, and neurologic health parameters.

Mortality of cellulose fiber production workers.

Mortality was studied among 1271 employees of a cellulose fiber production plant in Rock Hill, South Carolina, in the United States. Each subject was employed for at least three months between 1 January 1954 and 1 January 1977 in jobs that entailed exposure to the highest concentrations of methylene chloride. In the cohort 122 deaths were identified through 1 September 1986, and mortality rates for the cohort were compared with mortality rates for York County, South Carolina. Deficit mortality was observed for cancers of the respiratory system, breast, and pancreas and from ischemic heart disease. Excess mortality was observed for cancers of the buccal cavity and pharynx and the liver and biliary tract, and for melanoma as well. The largest relative excess was for liver and biliary tract cancers. There were only four deaths in this category; however, three of the four deaths were cancer of the biliary tract (3 observed, 0.15 expected, standardized mortality ratio 20).