O(6)-methylguanine DNA adducts associated with occupational nitrosamine exposure.

Occupational nitrosamine exposures from a rubber vehicle seal (VS) curing operation were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts, N(7)-methylguanine (N(7)mdG) and O(6)-methylguanine (O(6)mdG), and with the activity of the enzyme that repairs O(6)mdG adducts, O(6)-alkylguanine-DNA alkyltransferase (AGT). The occupational personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 microg/m(3) in the VS area, from 0.1-2 microg/m(3) in an area remote from the VS and were not detected at a nearby rubber plant. Workers from all three of these locations had detectable concentrations of N(7)mdG adducts, ranging from 0.1 to 133.2 adducts/10(7) deoxyguanosine nucleosides. Although N(7)mdG concentrations were elevated for those who worked in the VS area (median 3.60 compared with 1.44), the difference was not statistically significant after controlling for confounding factors. The O(6)mdG adduct concentrations were much lower than those of N(7)mdG, ranging from non-detectable to 12.7 O(6)mdG adducts/10(7) deoxyguanosine nucleosides and many of the participants (40/78 successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 O(6)mdG adducts/10(7) deoxyguanosine nucleosides). Analysis of the ordinal exposure categories (high, medium/high, medium/low, low and no exposure) yielded a statistically significant association with having detectable O(6)mdG adducts (Kendall's taub = -0.253, asymptotic SE = 0.096). There was no significant association between AGT activity and nitrosamine exposure or exposure category (P > 0.30). Although no association was found between PBZ exposure and either the N(7)mdG adduct concentrations or AGT activity, the significant positive association between working in and near the VS department and the presence of O(6)mdG adducts, which have mutagenic potential, provides evidence to link nitrosamine exposure one step closer to human cancer by demonstrating an association between external nitrosamine exposures and cancer-related biological effects.

Health effects associated with sulfuryl fluoride and methyl bromide exposure among structural fumigation workers.

OBJECTIVES: This study assessed the health effects associated with occupational exposure to methyl bromide and sulfuryl fluoride among structural fumigation workers. METHODS: A cross-sectional study of 123 structural fumigation workers and 120 referents in south Florida was conducted. Nerve conduction, vibration, neurobehavioral, visual, olfactory, and renal function testing was included. RESULTS: The median lifetime duration of methyl bromide and sulfuryl fluoride exposure among workers was 1.20 years and 2.85 years, respectively. Sulfuryl fluoride exposure over the year preceding examination was associated with significantly reduced performance on the Pattern Memory Test and on olfactory testing. In addition, fumigation workers had significantly reduced performance on the Santa Ana Dexterity Test of the dominant hand and a nonsignificantly higher prevalence of carpal tunnel syndrome than did the referents. CONCLUSIONS: Occupational sulfuryl fluoride exposures may be associated with subclinical effects on the central nervous system, including effects on olfactory and some cognitive functions. However, no widespread pattern of cognitive deficits was observed. The peripheral nerve effects were likely caused by ergonomic stresses experienced by the fumigation workers.

Genotoxicity in workers exposed to methyl bromide.

To address the genotoxicity of in vivo methyl bromide (CAS 74-83-9) exposure in humans, we collected blood and oropharyngeal cells as part of a cross-sectional morbidity study of methyl bromide-exposed fumigation workers and their referents. Micronuclei were measured in lymphocytes and oropharyngeal cells, and hypoxanthine-guanine phosphoribosyl transferase gene (hprt) mutations were measured in lymphocytes. A total of 32 workers and 28 referents provided specimens. Among current non-smokers, mean hprt variant frequencies (Vfs) were found to be elevated among workers compared to referents (geometric mean: workers=4.49x10(-6), referents=2.96x10-(6); two-sided p=0.22); this difference was more pronounced among workers with 4 h or more of recent methyl bromide exposure compared to referents (geometric mean: workers=6.56x10(-6), referents=2.96x10(-6); two-sided p=0.06). Mean oropharyngeal cell micronuclei were higher among workers compared to referents (mean: workers=2.00, referents=1.31; two-sided p=0.08); the results were similar when workers with 4 h or more of recent methyl bromide exposure were compared to referents (mean: workers=2.07, referents=1.31; two-sided p=0.13). No consistent differences between workers and referents were observed for frequencies of kinetochore-negative lymphocyte micronuclei, or kinetochore-positive lymphocyte micronuclei. The study was limited by a sample size sufficient only for detecting relatively large differences, absence of a reliable method to measure the intensity of workplace methyl bromide exposures, and relatively infrequent methyl bromide exposure (e.g., the median length of exposure to methyl bromide during the 2 weeks preceding the survey was 4 h). In conclusion, our findings provide some evidence that methyl bromide exposure may be associated with genotoxic effects in lymphocytes and oropharyngeal cells. Further study on the genotoxicity of methyl bromide exposure in humans is warranted.

Agreement between company-recorded and self-reported estimates of duration and frequency of occupational fumigant exposure.

Investigators must often rely on self-reported work history information collected with questionnaires. However, little is known about the agreement between self-reported estimates of exposure and records kept by companies. As part of a cross-sectional medical study of structural fumigation workers, self-reported work history information was collected on both duration and frequency of exposure using an interviewer-administered questionnaire. All company records available on these workers were also collected. Only 15 of 81 structural fumigation companies identified by study participants as current or past structural fumigation employers had records suitable for comparison. These 15 companies employed 32 of the workers who participated in the cross-sectional medical study. The exposure information provided by the 32 workers was compared to information obtained from company records. By examining the agreement between these two data sources, potential limitations were identified in both the self-reported and company-recorded exposure data. By recognizing these limitations in the exposure data, we identified the most appropriate exposure measures to be used in subsequent data analyses. This exercise also demonstrated the difficulties in undertaking these exposure comparisons in an industry consisting of many small, independent companies. Similar difficulties with assessing exposures may be experienced by investigators studying other service industries consisting of many small, independent companies (e.g., dry cleaning, auto repair).

Worker exposures to nitrosamines in a rubber vehicle sealing plant.

Occupational nitrosamine exposures were measured during a National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation at a rubber vehicle sealing plant. All of the 28 personal breathing zone samples had detectable concentrations of nitrosodimethylamine (NDMA), nitrosodiethylamine, nitrosopiperidine (NPIP), and nitrosomorpholine; and 27 of the 28 samples had detectable concentrations of nitrosopyrrolidine. The NDMA exposures were the highest, ranging from 0.47 to 11.44 micrograms/m3. The next highest exposures were to NPIP, ranging from 0.20 to 4.39 micrograms/m3. Several general area air samples were also collected, which revealed concentrations of NDMA ranging from 2.29 to 88.47 micrograms/m3 at the drills along the salt bath lines. The salt bath curing process appears to be the primary source of nitrosamine formation, and personal exposures were highest for the salt bath line operators and assistant operators. Although there are no numerical occupational nitrosamine standards in the United States to reference, the exposures in this plant were much higher than the German standard of 1 micrograms/m3 total nitrosamines for general industry and 2.5 micrograms/m3 total nitrosamines for certain processes such as vulcanization. NIOSH investigators recommended that the ventilation systems be improved to reduce the exposures to the lowest feasible concentrations until the process can be redesigned so that nitrosamines are not formed.

Mortality study of workers employed in 1,3-butadiene production units identified from a large chemical workers cohort.

The IARC has given the designations of "sufficient evidence" of carcinogenicity of 1,3-butadiene in experimental animals and "limited evidence" of carcinogenicity in humans. To investigate the carcinogenic effect in humans, a cohort mortality study was conducted among 364 men who were assigned to any of three 1,3-butadiene production units located within several chemical plants in the Kanawha Valley of West Virginia, including 277 men employed in a U.S. Rubber Reserve Plant which operated during World War II. The butadiene production units included in this study were selected from an index developed by the Union Carbide Corporation which listed for each chemical production unit within their South Charleston and Institute plants all products, by-products and reactants. Departments included in the study were those where butadiene was a primary product and neither benzene nor ethylene oxide was present. A total of 185 deaths were observed; the standardized mortality ratio (SMR) for all causes of death was 91, reflecting lower mortality among the study population than the U.S. population. The study found a significantly elevated standardized mortality ratio (SMR) for lymphosarcoma and reticulosarcoma based on four observed cases (SMR = 577; 95% confidence interval (CI) = 157-1480), which persisted in an analysis using county referent rates. An excess of lymphosarcoma and reticulosarcoma among all workers and among workers with routine exposure to 1,3-butadiene was also observed in the only other cohort of 1,3-butadiene production workers previously studied. A statistically non-significant excess of stomach cancer was observed in the overall cohort (five cases; SMR = 243; CI = 79-568) that was most pronounced among workers employed in the Rubber Reserve plant for 2 or more years (five cases; SMR = 657; CI = 213-1530). We conclude that the results of this study add to the weight of evidence suggesting that butadiene is carcinogenic in humans.

Mortality study of workers in 1,3-butadiene production units identified from a chemical workers cohort.

The International Agency for Research on Cancer has given the designations of "sufficient evidence" of carcinogenicity of 1,3-butadiene in experimental animals and "limited evidence" of carcinogenicity in humans. To investigate the carcinogenic effect in humans, we conducted a cohort mortality study among 364 men who were assigned to any of three 1,3-butadiene production units located within several chemical plants in the Kanawha Valley of West Virginia, including 277 men employed in a U.S. Rubber Reserve Plant which operated during World War II. The butadiene production units included in this study were selected from an index developed by the Union Carbide Corporation, which listed for each chemical production unit within their South Charleston, West Virginia and Institute, West Virginia, plants all products, by-products, and reactants. Departments included in the study were those where butadiene was a primary product and neither benzene nor ethylene oxide was present. A total of 185 deaths were observed; the standardized mortality ratio (SMR) for all causes of death was 91, reflecting lower mortality among the study population than the U.S. population. The study found a significantly elevated standardized mortality ratio (SMR) for lymphosarcoma and reticulosarcoma based on four observed cases (SMR = 577; 95% CI = 157-1480), which persisted in an analysis using county referent rates. An excess of lymphosarcoma and reticulosarcoma among all workers and among workers with routine exposure to 1,3-butadiene was also observed in the only other cohort of 1,3-butadiene production workers previously studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Industrial exposure to 1,3-butadiene in monomer, polymer and end-user industries.

Researchers from the National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention conducted an extent-of-exposure study of 1,3-butadiene monomer, polymer and end-user industries to assess occupational exposure to butadiene and to evaluate control technologies. The findings of the exposure assessment are reported here. Walk-through surveys were conducted in 11 monomer, 17 polymer and two end-user plants; in-depth industrial hygiene surveys were conducted at four monomer, five polymer and two end-user plants. Airborne exposure concentrations of butadiene were determined for various job categories by personal sampling. The samples were analysed by a new method developed at NIOSH that is sensitive to 0.2 microgram per sample. A total of 687 personal (full-shift and short-term) and 232 area samples were taken. The results indicate that all exposures were well below the current permissible exposure limit of the US Occupational Safety and Health Administration of 1000 ppm. The US Occupational Safety and Health Administration (1990) has proposed a new standard that would reduce exposure to 2 ppm. Exposures ranged from less than 0.005 ppm to 374 ppm, and 3.7% of the samples contained more than 10 ppm, 7.8% more than 2 ppm but less than 10 ppm and 88.5% less than 2 ppm. We recommend means for reducing exposure by the use of engineering controls.

Effects of exposure to carbon disulphide on low density lipoprotein cholesterol concentration and diastolic blood pressure.

The relation of carbon disulphide (CS2) exposure to risk factors for ischaemic heart disease was recently examined using data from a 1979 cross sectional study of 410 male textile workers, of whom 165 were exposed and 245 were unexposed to CS2. Average eight hour CS2 exposure concentrations ranged from 0.6 to 11.8 ppm by job title category among the exposed workers. A significant and positive linear trend in low density lipoprotein cholesterol concentration (LDLc) and diastolic blood pressure with increasing CS2 exposure was found after adjustment for potential confounders. When exposure was examined as a categorical variable (none, low, moderate, and high), the high exposure group had an adjusted mean LDLc that was 0.32 mmol/l greater than the non-exposed group (p = 0.02), and an adjusted mean diastolic blood pressure that was 3.16 mm Hg greater than the non-exposed group (p = 0.09). The effect of CS2 on diastolic blood pressure was strengthened in analyses limited to exposed workers: the high exposure group had an adjusted mean diastolic blood pressure that was 5 mm Hg greater than that of the low exposed group (p = 0.03). Triglyceride, high density lipoprotein cholesterol, and fasting glucose concentration, and systolic blood pressure were not affected by exposure. Blood lead concentration was positively associated with systolic and diastolic blood pressure. The results indicate that relatively modest exposure to CS2 may raise LDLc concentration and diastolic blood pressure and suggest mechanisms by which exposure to CS2 may influence risk of ischaemic heart disease. Also the results provide further support for the hypothesis of a possible association between blood lead concentration and blood pressure.

Environmental epidemiologic investigations in the styrene-butadiene rubber production industry.

A review of the literature and an update that is in progress of a previous retrospective cohort mortality study of the styrene-1,3-butadiene industry are discussed. The follow-up has now been extended from April 1, 1976, through December 31, 1981, for plant B and December 31, 1982, for plant A. The person-years at risk of death have gone from 34,187 to 43,341 in plant A and from 19,742 to 26,314 in plant B. Among the death certificates received to date, observed deaths have increased in both plants, with increases in cancers of the trachea, bronchus and lung and in lymphosarcomas, reticulosarcomas, and cancers of the overall lymphatic and hematopoietic system.

Occupational exposure of workers to 1,3-butadiene.

Researchers from the National Institute for Occupational Safety and Health (NIOSH) conducted an extent-of-exposure study of the 1,3-butadiene monomer, polymer, and end-user industries to determine the size of the exposed workforce, evaluate control technologies and personal protective equipment programs, and assess occupational exposure to 1,3-butadiene. A new analytical method was developed for 1,3-butadiene that increased the sensitivity and selectivity of the previous NIOSH method. The new method is sensitive to 0.2 microgram per 1,3-butadiene sample. Walk-through surveys were conducted in 11 monomer, 17 polymer, and 2 end-user plants. In-depth industrial hygiene surveys were conducted at 4 monomer, 5 polymer, and 2 end-user plants. Airborne exposure concentrations of 1,3-butadiene were determined using personal sampling for each job category. A total of 692 full shift and short-term personnel and 259 area air samples were examined for the presence of 1,3-butadiene. Sample results indicated that all worker exposures were well below the current OSHA PEL of 1000 ppm. Exposures ranged from less than 0.006 ppm to 374 ppm. The average exposure for all samples was less than 2 ppm. The present American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value for 1,3-butadiene is 10 ppm. To reduce the potential for occupational exposure, it is recommended that quality control sampling be conducted using a closed loop system. Also all process pumps should be retrofitted with dual mechanical seals, magnetic gauges should be used in loading and unloading rail cars, and engineering controls should be designed for safely voiding quality control cylinders.

Mortality of chrome leather tannery workers and chemical exposures in tanneries.

A retrospective mortality analysis was conducted in a cohort of 9,365 individuals employed as of 1940 in two chrome leather tanneries in the United States and followed to the end of 1982. Vital status as of the closing date was determined for over 95% of the cohort. Potential hazardous workplace exposures varied with department and included nitrosamines, chromate pigments, benzidine-based direct dyestuffs, formaldehyde, leather dust, and aromatic organic solvents. Mortality from all causes combined was lower than expected for each tannery, the standardized mortality ratio being 81 for one and 93 for the other. Deaths from cancer of each site, including the lung, were also lower than expected compared to those of either the population of the United States or of local state rates. A significant excess of deaths was observed, however, due to accidental causes in one tannery and cirrhosis of the liver, suicide, and alcoholism in the other. These excesses did not appear to be causally associated with occupational exposures. The findings of this study are consistent with those of the only other mortality investigation of leather tannery employees.

N-Nitrosamines in the factory environment.

Under the NIOSH-sponsored contract, a total of 40 surveys were conducted at 28 manufacturing plants. The industries investigated were the fish, dye, leather, rubber and manufacturers and users of cutting fluids. NDELA, NMOR, NDMA and NDPhA were found in the air of several factories. In a chrome tannery, NDMA was identified at levels as high as 47 micrograms/m3 and NMOR was found at 27 micrograms/m3 in a rubber tire plant. This study has resulted in an increased understanding of man's exposure to exogenous N-nitrosamines. It is conceivable, from the information obtained in this study, that nitrosamine exposure comparable to that in the tire and rubber industry exists in other industries not yet surveyed. NIOSH is continuing its research on nitrosamines in the industrial environment. A full, industry-wide report on the 40 plant surveys is being compiled for publication.

N-nitrosamines in the rubber and tire industry.

Airborne N-nitrosomorpholine (0 to 27 micrograms per cubic meter) was found in two of four rubber industry factories. N-Nitrosodimethylamine was also found in two factories, but at lower levels. These findings may be relevant to the reported increased risk of certain types of cancer in rubber workers in some of the same areas where the N-nitrosomorpholine levels were highest.