BACKGROUND: Elevated bladder cancer incidence has been reported in a cohort of 1875 workers manufacturing chemicals used in the rubber industry and employed any time during 1946-2006. o-Toluidine (OT), an aromatic amine, was the prime suspect agent. Using the available environmental data and process characterization, previous investigators assigned ranks to volatile chemical air concentrations across time in departments and jobs, reflecting probabilities of exposure and use of personal protective equipment for airborne and dermal exposures. Aniline, another aromatic amine, was present at comparable concentrations and is known to be an animal carcinogen but produced lower levels in post-shift urine and of hemoglobin adducts than OT in a group of workers. METHODS: A quantitative risk assessment was performed based on this same population. In this study, cumulative OT exposures were estimated (a) based on previously assigned ranks of exposure intensity and reported actual exposures in jobs with the highest assigned rank, and (b) directly from the historical environmental sampling for OT. Models of bladder cancer incidence were evaluated taking into account possible healthy worker survivor effects. RESULTS: Under various assumptions regarding workforce turnover, the excess lifetime risk of bladder cancer from OT exposure at 1 ppb was estimated to be in the range 1-7 per thousand. CONCLUSIONS: The current ACGIH TLV and OSHA standards for OT are 2 and 5 ppm, respectively, 1000-fold higher than the exposure estimated here for 1-7 per thousand excess lifetime risk.

The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in flux core arc welding fume at three facilities. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Sixty-seven worker-days were monitored for either total or respirable Mn. The samples were analyzed using an experimental method to separate four Mn fractions based on chemical solubility: soluble Mn in a mild ammonium acetate solution; Mn0,2+ in 25% acetic acid; Mn3+,4+ in hydroxylamine hydrochloride in 25% acetic acid; and insoluble Mn fractions in hydrochloric/nitric acid. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.51 to 43; 2.9 to 850; 1.7 to 620; and 0.56 to 331 gm-3, for the different Mn fractions, respectively. The summation of all the total particulate Mn fractions yielded results that ranged from 16 to 1,530 g m-3. The ranges of respirable size Mn TWA concentrations were 0.27 to 75 for soluble Mn; 1.6 to 690 for Mn0,2+; 1.3 to 740 for Mn3+,4+; 0.52 to 570 for insoluble Mn; and 3.8 to 1,800 gm-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn(sum) were 56 (GSD = 4.0), 380 (GSD = 2.7), and 176 (GSD = 3.3) gm-3 for the shipyard, structural steel and custom parts facilities. Although most of the workers exposures measured were below the NIOSH Recommended Exposure Limit for Mn (1,000 gm-3), 44 welders exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 gm-3) and 46 exceeded the new respirable Mn TLV (20 gm-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding in enclosed or confined spaces.

The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume at three factories where heavy equipment was manufactured. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. One hundred nine worker-days were monitored for either total or respirable Mn during gas metal arc welding. The samples were analyzed using an experimental method to separate different Mn fractions based on selective chemical solubility. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged 0.38-26 for soluble Mn in a mild ammonium acetate solution; 3.2-170 for Mn0,2+ in acetic acid; 3.1-290 for Mn3+,4+ in hydroxylamine-hydrochloride; and non-detectable (ND)-130 microg m-3 for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all the total particulate Mn TWA fractions yielded results that ranged from 6.9 to 610 microg m-3. The range of respirable size Mn TWA concentrations were 0.33-21 for soluble Mn; 15-140 for Mn0,2+; 14-170 for Mn3+,4+; 5.3-230 for insoluble Mn; and 36-530 microg m-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn (sum) were 53 (GSD = 2.5), 150 (GSD = 1.7), and 120 (GSD = 1.8) microg m-3 for the three separate factories. Although all of the workers' exposures were measured below the OSHA regulatory permissible exposure limit and NIOSH recommended exposure limit for Mn, 70 welders' exposures exceeded the ACGIH Threshold Limit Values(R) for total Mn (100 microg m-3) and 29 exceeded the recently adopted respirable Mn TLV (20 microg m-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding parts that impede air circulation.

The objective of this laboratory study was to identify and measure manganese (Mn) fractions in chamber-generated welding fumes (WF) and to evaluate and compare the results from a sequential extraction procedure for Mn fractions with that of an acid digestion procedure for measurement of total, elemental Mn. To prepare Mn-containing particulate matter from representative welding processes, a welding system was operated in short circuit gas metal arc welding (GMAW) mode using both stainless steel (SS) and mild carbon steel (MCS) and also with flux cored arc welding (FCAW) and shielded metal arc welding (SMAW) using MCS. Generated WF samples were collected onto polycarbonate filters before homogenization, weighing and storage in scintillation vials. The extraction procedure consisted of four sequential steps to measure various Mn fractions based upon selective solubility: (1) soluble Mn dissolved in 0.01 M ammonium acetate; (2) Mn(0,ii) dissolved in 25% (v/v) acetic acid; (3) Mn(iii,iv) dissolved in 0.5% (w/v) hydroxylamine hydrochloride in 25% (v/v) acetic acid; and (4) insoluble Mn extracted with concentrated hydrochloric and nitric acids. After sample treatment, the four fractions were analyzed for Mn by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). WF from GMAW and FCAW showed similar distributions of Mn species, with the largest concentrations of Mn detected in the Mn(0,ii) and insoluble Mn fractions. On the other hand, the majority of the Mn content of SMAW fume was detected as Mn(iii,iv). Although the concentration of Mn measured from summation of the four sequential steps was statistically significantly different from that measured from the hot block dissolution method for total Mn, the difference is small enough to be of no practical importance for industrial hygiene air samples, and either method may be used for Mn measurement. The sequential extraction method provides valuable information about the oxidation state of Mn in samples and allows for comparison to results from previous work and from total Mn dissolution methods.

The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume of construction workers rebuilding tanks, piping, and process equipment at two oil refineries. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Seventy-two worker-days were monitored for either total or respirable Mn during stick welding and associated activities both within and outside of confined spaces. The samples were analyzed using an experimental method to separate different Mn fractions by valence states based on selective chemical solubility. The full-shift total particulate Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.013 - 29 for soluble Mn in a mild ammonium acetate solution; from 0.26 - 250 for Mn0,2+ in acetic acid; from non-detectable (ND) - 350 for Mn3+,4+ in hydroxylamine-hydrochloride; and from ND - 39 micrograms per cubic meter (microg/m3) for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all Mn fractions in total particulate TWA ranged from 0.52 to 470 microg/m3. The range of respirable particulate Mn TWA concentrations were from 0.20 - 28 for soluble Mn; from 1.4 - 270 for Mn0,2+; from 0.49 - 150 for Mn3+,4+; from ND - 100 for insoluble Mn; and from 2.0 - 490 microg/m3 for Mn (sum of fractions). For all jobs combined, total particulate TWA GM concentrations of the Mn(sum) were 99 (GSD=3.35) and 8.7 (GSD=3.54) microg/m3 for workers inside and outside of confined spaces; respirable Mn also showed much higher levels for welders within confined spaces. Regardless of particle size and confined space work status, Mn0,2+ fraction was the most abundant followed by Mn3+,4+ fraction, typically >50% and 30-40% of Mn(sum), respectively. Eighteen welders' exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 microg/m3) and 25 exceeded the recently adopted respirable Mn TLV (20 microg/m3). This study shows that a welding fume exposure control and management program is warranted, especially for welding jobs in confined spaces.

BACKGROUND: We updated through 2007 the mortality experience of 1,874 workers employed at a New York State chemical manufacturing plant between 1946 and 2006. METHODS: Reassessed exposures to vinyl chloride, carbon disulfide, and shift work and categories of o-toluidine exposure were based on year, department and job title. Standardized mortality ratios (SMR) compared mortality to that of the US population. Internal comparisons used directly standardized rate ratios. RESULTS: Hepatobiliary cancer mortality was elevated among workers ever exposed to vinyl chloride (SMR = 3.80, 95% confidence interval 1.89-6.80); directly standardized rates increased with increasing vinyl chloride exposure duration. No increase in non-Hodgkin lymphoma mortality was observed with vinyl chloride and shift work exposures. Internal comparisons showed increased coronary artery disease mortality among long-term workers exposed to carbon disulfide and shift work for 4 years or more. CONCLUSIONS: Excess coronary artery disease mortality confirms earlier results; further investigation is needed to understand risk factors.

BACKGROUND: An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation. METHODS: Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking. RESULTS: Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence. CONCLUSIONS: Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits.

The National Institute for Occupational Safety and Health previously conducted a retrospective cancer incidence and mortality study of workers employed at a rubber chemical manufacturing plant. Compared with New York State incidence, the bladder cancer risk was 6.5 times higher for workers considered to have definite exposure to ortho-toluidine and aniline, and 4 times higher for workers with possible exposure. Exposure characterization in the original study utilized a surrogate measure based only on departments in which each worker was ever employed. As part of an update of that study, some departments in the three original exposure groups were reclassified based on a follow-up site visit; interviews with employees, management, and union representatives; and review of records including exposure data. An additional evaluation of department-job combinations, rather than only departments, was used to stratify exposure into four categories. An approximate rank of "relative" exposure level for each department-job-year combination was also assigned using a ranking scale of 0 to 10. The ranks were supported by quantitative exposure levels and by professional judgment. The numerical ranking scale was applied to each worker by multiplying the exposure rank by duration for each job held based on comprehensive individual work histories. The cumulative rank scores for this cohort ranged from 0 to 300 unit-years. The medians of the cumulative rank scores for the exposure categories showed very good agreement with increasing exposure classifications (e.g., 0.72, 4.6, 11, 14 unit-years for the four exposure categories). Workers' breathing zone air sampling data collected at this plant from 1976-2004 were well below published occupational exposure limits for these chemicals, but additional cases of bladder cancer have been reported. The exposure assessment revisions and rank estimates will be used to analyze the updated bladder cancer incidence data.

Three metabolites of 1-bromopropane (1-BP) were measured in urine samples collected from 30 workers exposed to 1-BP at two facilities making furniture seat cushions and evaluated for use as biomarkers of exposure. The mercapturic acid metabolite,N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys), 3-bromopropionic acid (3-BPA), and bromide ion levels (Br(-)) were quantitated for this evaluation. The high exposure group consisted of 13 workers employed as adhesive sprayers who assembled foam cushions using 1-BP containing spray adhesives and the low exposure group consisted of 17 non-sprayers, who worked in various jobs without spraying adhesives. All workers' urine voids were collected over the same 48 hour period at work, and at home before bedtime, and upon awakening. Urinary AcPrCys and Br(-)levels were elevated in the sprayers compared to that ofnon-sprayers. Following HPLC-MS/MS analysis of mercapturic acid metabolite levels, 50 urine samples having the highest levels of AcPrCys were analyzed for 3-BPA. No 3-BPA was detected in any of the samples. The data collected from this study demonstrate that ACPrCys and Br(-) are effective biomarkers of 1-BP exposure, but 3-BPA is not.

OBJECTIVES: 1-Bromopropane (1-BP) is an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, and cleaning solvents. There is concern that 1-BP may be a reproductive and neurological toxicant. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. The main objectives were to evaluate urinary bromide [Br((-))] and N-acetyl-S-(n-propyl)-L: -cysteine (AcPrCys) for assessing 1-BP exposure in workers with low exposure. METHODS: Workers' 1-BP exposures were measured in their breathing zones with gas chromatography-flame ionization detection via NIOSH 1025. Urine specimens were obtained over a 48-h period at five facilities using vapor degreasers and one adhesive manufacturer. All of the workers' urine was collected into composite samples and analyzed separately representing daily time intervals: at work, after work but before bedtime, and upon awakening. Urinary metabolites were analyzed using intra-coupled plasma-mass spectroscopy for Br((-)), and high-performance liquid chromatography and electro-spray ionization mass spectroscopy for AcPrCys. RESULTS: Time-weighted average (TWA) geometric mean (GM) breathing zone concentrations of 1-BP at vapor degreasing facilities were 2.6 and 0.31 ppm, respectively, for workers near degreasers and those remote from degreasers. Urine metabolites showed the same trend as TWA exposures: higher levels were observed for workers near degreasers (48-h GM Br((-)) = 8.9 vs. 3.7; 48-h GM AcPrCys = 1.3 vs. 0.12, respectively). Associations of Br((-)) and AcPrCys concentrations with 1-BP TWA were statistically significant near degreasers (p < 0.01). CONCLUSIONS: This study shows that urinary Br((-)) and AcPrCys are useful biomarkers of workers' 1-BP exposures using analyses sensitive enough to measure low exposure jobs.

INTRODUCTION: In 1991, the U.S. National Institute for Occupational Safety and Health (NIOSH) reported an increased bladder cancer risk in a cohort of 1749 workers potentially exposed to o-toluidine and aniline at a chemical manufacturing plant. Additional information showed that workers in certain departments had been misclassified regarding o-toluidine exposure; therefore, we conducted a reanalysis of the data using updated exposure categories. METHODS: We updated exposure categories based on information ascertained during a plant walkthrough, documents on file at the plant, interviews with current and former employees, and answers provided by company and union officials on specific questions. Bladder cancer incidence was determined through 31 December 1988 and mortality through 31 December 1994. RESULTS: Thirteen cases of bladder cancer were observed, versus 3.57 expected (New York State rates excluding New York City) [standardized incidence ratio (SIR) 3.64, 95% confidence interval (CI) 1.94-6.23]. Among workers classified as definitely exposed, increasing risks were observed for longer duration of employment [for ≥10 years, standardized rate ratio (SRR) 6.07, 95% CI 0.77-48.17] and time since first employment in the exposed departments (for ≥20 years, SRR 3.39, 95% CI 0.40-29.03). One bladder cancer death was observed among those definitely exposed. CONCLUSION: These findings are comparable to the results reported earlier by NIOSH, and confirm that workers in this plant have an increased risk of bladder cancer.

1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, metal, precision, and electronics cleaning solvents. Mechanisms of toxicity of 1-BP are not fully understood, but it may be a neurological and reproductive toxicant. Sparse exposure information prompted this study using 1-BP air sampling and urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. Research objectives were to evaluate the utility of urinary N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) for assessing exposure to 1-BP and compare it to urinary bromide [Br((-))] previously reported for these workers. Forty-eight-hour urine specimens were obtained from 30 workers at two factories where 1-BP spray adhesives were used to construct polyurethane foam seat cushions. Urine specimens were also obtained from 21 unexposed control subjects. All the workers' urine was collected into composite samples representing three time intervals: at work, after work but before bedtime, and upon awakening. Time-weighted average (TWA) geometric mean breathing zone concentrations were 92.4 and 10.5 p.p.m. for spraying and non-spraying jobs, respectively. Urinary AcPrCys showed the same trend as TWA exposures to 1-BP: higher levels were observed for sprayers. Associations of AcPrCys concentrations, adjusted for creatinine, with 1-BP TWA exposure were statistically significant for both sprayers (P < 0.05) and non-sprayers (P < 0.01). Spearman correlation coefficients for AcPrCys and Br((-)) analyses determined from the same urine specimens were highly correlated (P < 0.0001). This study confirms that urinary AcPrCys is an important 1-BP metabolite and an effective biomarker for highly exposed foam cushion workers.