John M. Fajen

Sister-chromatid exchanges, glutathione S-transferase τ deletion and cytogenetic sensitivity to diepoxybutane in lymphocytes from butadiene monomer production workers☆

The magnitude of health risks to workers associated with current and past exposures to butadiene has been the subject of considerable recent debate. Butadiene is metabolized in-vivo and in-vitro to the genotoxic intermediates 3,4-epoxybutene and diepoxybutane. Studies in animals and in-vitro systems have clearly demonstrated that 1,3-butadiene is a genotoxin and a potent inducer of sister-chromatid exchanges (SCEs). Data on the genotoxicity of butadiene in humans is, however, limited. Epidemiologic data indicate that butadiene is a probable human carcinogen. Recent work has further demonstrated that cultured lymphocytes from the approximately 20% of the Caucasian population that lack the glutathione S-transferase class theta gene (GSTT1) are relatively sensitive to the induction of cytogenetic damage by butadiene metabolites. In order to test whether butadiene exposure was associated with increases in SCE frequencies in peripheral blood lymphocytes and whether any increase observed could be affected by the DEB sensitivity-GSTT1 deletion, we studied 40 workers employed in the production of butadiene. In these workers baseline frequencies of SCEs, diepoxybutane-induced SCE frequencies and GSTT1 deletion status were assessed. Questionnaires were administered to each worker and exposure to 1,3-butadiene was determined using three separate approaches. Industrial hygiene personal sampling was used to measure breathing zone butadiene exposure and urine was collected to use in measurement of the urinary butadiene metabolite 1,2-dihydroxy-4-(N-acetylcysteinyl-S-)-butane (M1). Exposure to butadiene was generally below 2 ppm. The urinary metabolite M1 was found in all workers, but it did not correlate significantly with exposure. Six of 40 of the workers were GST theta-deleted DEB sensitive. No measure of acute or chronic exposure to butadiene was associated with an increase in SCE frequency. However, smoking and DEB sensitivity-GSTT1 null status were each significantly associated with elevations in baseline SCE frequency.

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.

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.

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.

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).

Determination of 1,3-Butadiene down to Sub-part-per-million Levels in Air by Collection on Charcoal and High-Resolution Gas Chromatography

Abstract The need for a more sensitive method for the determination of 1,3-butadiene in air led to the development of NIOSH Method 1024, in which samples are collected on tandem 400- and 200-mg coconut-shell charcoal samplers; desorbed in dichloromethane; separated by gas chromatography on an aluminum oxide, porous-layer, open-tubular, fused silica capillary column fitted with a backflushable precolumn; and detected by flame ionization. This article reports the development of the method and an assessment of its performance based on laboratory evaluations and field use. A sample volume of 25 L is recommended for 1,3-butadiene concentrations up to 100 ppm. Samples stored in a freezer are stable; a loss of 1.5 percent per day occurs at ambient temperature. The lower quantitation limit, based on maintaining desorption efficiency ≥ 75 percent, is about 40 μg/sample. The estimated limit of detection is 0.2 μg/sample. The estimated precision of the total sampling and analytical method is 6 percent relative stand...