Rubber Industry Workers Research Articles

Percutaneous absorption of aromatic amines – A contribution for human health risk assessment

Several aromatic amines (AA) are human carcinogens. AA are widely-used, e.g., in the rubber industry. The uptake of AA at the workplace occurs by inhalation and percutaneous absorption. At present there are no risk assessment studies for percutaneous AA absorption using occupationally relevant concentrations. We conducted diffusion cell experiments for aniline (ANI), o-toluidine (OT), 4,4′-methylenedianiline (MDA) and N-phenyl-2-naphthylamine (PBNA). Excised human skin was exposed to different AA concentrations in vehicles containing water and solvents. Recovery for ANI in receptor fluid was about 20–38% and for MDA 15% over 24h. PBNA could not be detected in the receptor fluid. Further data for OT and β-naphthylamine (BNA) were considered from our recent study. A semi-quantitative percutaneous absorption ranking for AA was derived: BNA>OT>ANI>MDA>PBNA. For aqueous ANI solutions up to saturation a linear relationship of exposed dose and penetrated amount was observed. However, a linear extrapolation of the flux of neat compounds, as often recommended for risk assessment policies, underestimates considerably the percutaneous uptake. The in vitro data support our recent findings in rubber industry workers that the percutaneous absorption may significantly contribute to overall exposure of AA.

Influence of glutathione-related genes on symptoms and immunologic markers among vulcanization workers in the southern Sweden rubber industries

The aim was to elucidate the role of genetic variants on symptoms of the eyes and airways, headache and nausea, as well as on immunologic markers, among vulcanization workers in the contemporary Swedish rubber industry. Polymorphisms in genes, which are involved in the defense against reactive oxygen species and metabolism of toxic substances present in the vulcanization fumes, were analyzed. One hundred and forty-five exposed and 117 unexposed workers were included in the study. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded and immunologic markers analyzed in blood. Polymorphisms in glutathione-related genes (glutamate cysteine ligase catalytic subunit (GCLC)-129, glutamate cysteine ligase modifier subunit (GCLM)-588, glutathione S-transferase alpha 1 (GSTA1)-52, GSTM1*O, GSTP1-105, GSTP1-114, and GSTT1*O) were analyzed by Taqman-based allelic discrimination and ordinary PCR. A protective effect of GSTA1-52 (G/A + A/A) genotype on symptoms and immunologic cells, in particular among exposed workers, was suggested. Exposed workers with GSTT1*O had increased risk of nosebleed compared to exposed workers with GSTT1*1. Exposed workers with GSTP1-105 (ile/val + val/val) had decreased levels of total immunoglobulin E (IgE) compared to exposed workers with GSTP1-105 ile/ile. GCLC-129 variant genotype demonstrated increased levels of immunologic cells among exposed workers, although statistical significance was not reached. Our data indicate that hereditary factors influence the susceptibility to symptoms and the immunologic response of workers in the rubber industry.

Enhancement of percutaneous penetration of aniline and o-toluidine in vitro using skin barrier creams

Aniline (ANI) and the human carcinogen o-toluidine (OT) are released at the workplace during the production and processing of rubber. Recently, we showed in rubber industry workers that a frequent use of skin barrier creams (SBC) increased the internal exposure of ANI and OT. In the present study, diffusion cells were used to investigate the effects of two SBC and one skin care cream (SCC) on percutaneous penetration of neat ANI and OT as well as of OT from a mixture with a workplace specific lubricant. The experiments were carried out with untreated and with skin creams treated human skin. A considerable percutaneous penetration enhancement of test compounds was observed for treated skin compared with untreated skin; the highest enhancement (mean factors 6.2–12.3) was found for SBC (based on oil in water emulsion) treated skin. The lowest penetration enhancement showed SCC treated skin (mean factors 4.2–9.7). The in vitro data support our findings in workers that the percutaneous absorption of aromatic amines significantly increases in presence of skin creams. The efficacy of skin creams to protect the percutaneous penetration of aromatic amines is not confirmed by our own experiments.

Percutaneous absorption of aromatic amines in rubber industry workers: impact of impaired skin and skin barrier creams

Background: Several aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption of chemicals via impaired...

1,3-Butadiene and leukemia among synthetic rubber industry workers: Exposure–response relationships

Previous research updated the mortality experience of North American synthetic rubber industry workers during the period 1944-1998, determined if leukemia and other cancers were associated with several employment factors and carried out Poisson regression analysis to examine exposure-response associations between estimated exposure to 1,3-butadiene (BD) or other chemicals and cancer. The present study used Cox regression procedures to examine further the exposure-response relationship between several unlagged and lagged, continuous, time-dependent BD exposure indices (BD parts per million (ppm)-years, the total number of exposures to BD concentrations >100 ppm ("peaks") and average intensity of BD) and leukemia, lymphoid neoplasms and myeloid neoplasms. All three BD exposure indices were associated positively with leukemia. Using continuous, untransformed BD ppm-years the regression coefficient (beta) from an analysis that controlled only for age was 2.9 x 10(-4) (p<0.01); the regression coefficient adjusted for all covariates (age, year of birth, race, plant, years since hire and dimethyldithiocarbamate) was similar in magnitude (beta=3.0 x 10(-4), p=0.04). Lagging exposure had minimal impact on the results for leukemia for any of the three BD exposure indices. In models that controlled only for age, lymphoid neoplasms were associated with BD ppm-years and myeloid neoplasms, with BD peaks, but neither trend was statistically significant after adjusting for multiple covariates. The present results support the presence of a causal relationship between high cumulative exposure and high intensity of exposure to BD and leukemia.

Validation of 1,3-butadiene exposure estimates for workers at a synthetic rubber plant

This investigation assessed the validity of estimates of exposure to 1,3-butadiene (BD) developed for a plant included in a study of mortality among synthetic rubber industry workers. The estimates were developed without using historical measurement data and have not been validated previously. Personal BD measurements came from an exposure-monitoring program initiated in 1977. For each job, we computed the year-specific difference between the BD estimate and the mean of BD measurements. We also computed rank correlation coefficients and calculated the mean, across all measurements, of the difference between the estimate and the measurement. The mean BD concentration was 5.2 ppm for 4978 measurements and 4.7 ppm for the corresponding estimates. The mean difference between estimates and measurements was -0.50 ppm (standard deviation, 26.5 ppm) overall and ranged from -227.9 to +27.0 ppm among all 306 job/year combinations. Estimates were correlated with measurements for all 306 combinations (rank correlation coefficient, r=0.45, p<0.0001), for 82 combinations pertaining to jobs that were well-defined by a specific set of tasks and typically found in styrene-BD rubber (SBR) plants (r=0.81, p<0.0001), for 70 combinations pertaining to jobs that were well-defined but not typical (r=0.29, p=0.01) and for 92 combinations pertaining to poorly-defined jobs typically found in SBR plants (r=0.56, <0.0001). Estimates were not correlated with measurements for poorly defined jobs not typically found in SBR plants (r=0.01, p=0.93). For well-defined typical SBR jobs with measurement means that were over 7.0 ppm, estimates were consistently lower than measurements. Possible reasons for differences between estimates and measurements included faulty assumptions used in developing BD estimates, unstable or nonrepresentive measurements and errors in linking measurement data to the job-exposure matrix. Exposure misclassification may have been more severe for subjects from the validation study plant than for subjects from other plants in the mortality study. BD estimates for typical SBR jobs, which comprise most operations at all but one of the plants in the mortality study, appeared to be useful for ranking workers by cumulative exposure. Uncertainty analyses would enhance the utility of the BD exposure estimates for quantitative risk assessment.

Cancer risk assessment for 1,3-butadiene: Dose–response modeling from an epidemiological perspective

The dose-response assessment of the association between 1,3-butadiene (BD) and leukemia mortality among workers in the North American synthetic rubber industry is explored. Analyses are based on the most recent University of Alabama at Birmingham epidemiological study and exposure estimation. The U.S. EPA Science Advisory Board recommendations of using the most recent data and giving consideration to peak exposures to BD have been followed. If cumulative BD ppm-years is to be used as the predictor of the leukemia rate ratio, then the performance of that predictor is statistically significantly improved if the slope in the predictor is estimated with age and the cumulative number of BD peaks (where a BD peak is any exposure, regardless of duration, to a BD concentration above 100 ppm) added as categorical covariates. After age and the cumulative number of BD peaks are incorporated as categorical covariates in the Poisson regression model, the estimated concentration (EC(001)) corresponding to an excess risk of 0.001 as a result of continuous environmental exposure is 11.2 ppm; however, the estimated slope for BD cumulative ppm-years in the linear rate ratio for leukemia used to derive this EC(001) is not statistically significantly different from zero. Sensitivity analyses using alternative models indicate either essentially no risk or estimated EC(001) values of 9 and 77 ppm. Analyses suggesting the absence of a statistically significant low-dose risk versus cumulative BD ppm-years are presented. Sensitivity analyses of other malignant neoplasms of lymphatic and hematopoietic tissue (specifically, lymphoid and myeloid neoplasms) resulted in conclusions about the dose-response modeling methodology that were supportive of the methodology used for leukemia.

Mortalidade por câncer em trabalhadores da indústria da borracha de São Paulo

To investigate cancer deaths among rubber industry workers according to company size. This historical cohort study included 9,188 male workers, engaged as members of a workers' union in São Paulo, Southeastern Brazil, between 1975 and 1985, alive in January 1990 and followed until the end of 2000. Overall and specific cancer deaths were compared within the cohort, with subjects stratified according to company size and economic activity, sector of work, and worker qualification. Risk set assessment and conditional logistic regression were used to estimate relative risks, adjusted for age, time since first job, and duration of employment in the rubber industry. When compared to employees of larger companies, workers employed in small companies showed greater risk of death due to any type of cancer (RR=2.33, 95% CI: 0.90-6.03), stomach tumors (RR=3.47; 95% CI: 2.57-4.67), and upper aero-digestive tract tumors (RR=2.49; 95% CI: 1.78-3.48). Risk of death was greater among workers employed in maintenance (RR=2.23; 95% CI: 0.73-6.76); expedition, storage and transportation (RR=2.97; 95% CI: 0.77-11.38); and production (RR=3.51; 95% CI: 1.07-11.57), when compared to workers engaged in clerical work and support activities. Our results provide further evidence for an increased risk of stomach and upper aero-digestive tract tumors--and possibly of all types of cancer--among rubber industry workers employed in small companies when compared to employees of larger companies.

Styrene and Ischemic Heart Disease Mortality Among Synthetic Rubber Industry Workers

We examined the relation between styrene and ischemic heart disease (IHD) mortality among 16,579 men in the synthetic rubber industry. Associations were measured using stratified and multivariable analysis. Compared with workers with no exposure to styrene, men in the highest quintile of average intensity of exposure (5.50+ parts per million [ppm]) and in the highest quintile of cumulative exposure (60.67+ ppm-years) had IHD rate ratios of 1.14 (95% confidence interval [CI]=0.96-1.35) and 1.07 (95% CI=0.90-1.27), respectively. Acute IHD was not associated with average intensity of exposure within the most recent 2 years or with other indices of exposure. Chronic IHD rates were elevated in subjects with the highest exposure; these associations were weak and imprecise, and evidence of a positive exposure-response relation was limited. This study does not indicate that exposure to styrene causes fatal IHD.

An updated study of mortality among North American synthetic rubber industry workers

Aim: This study evaluated the mortality experience of workers from the styrene-butadiene industry. Methods: The authors added seven years of follow up to a previous investigation of mortality among 17...

Chemical Exposures in the Synthetic Rubber Industry and Lymphohematopoietic Cancer Mortality

This study evaluated the association between exposure to several chemicals and mortality from lymphohematopoietic cancer (LHC) among 16,579 synthetic rubber industry workers who were followed up from 1943 to 1998. Poisson regression analyses examined LHC rates in relation to butadiene, styrene, and DMDTC exposure. Models provided maximum likelihood estimates of the relative rate for the contrast between categories of one agent, adjusting for other agents and for additional potential confounders. Cumulative exposure to 1,3-butadiene was associated positively with all leukemia (relative rates of 1.0, 1.4, 1.2, 2.9, and 3.7, respectively, for exposures of 0, >0 to <33.7, 33.7 to <184.7, 184.7 to <425.0, and 425.0+ ppm-years), chronic myelogenous leukemia and to a lesser extent with chronic lymphocytic leukemia. Adjusting for styrene and DMDTC attenuated these associations. After controlling for butadiene, neither styrene nor DMDTC displayed a consistent exposure-response trend with all leukemia, chronic myelogenous leukemia, or chronic lymphocytic leukemia. This study found a positive association between butadiene and leukemia that was not explained by exposure to other agents examined.

Biological monitoring of carbon disulphide and phthalate exposure in the contemporary rubber industry

We studied the range in urinary levels of 2-thiothiazolidine-4-carboxyl acid (TTCA), a metabolite of CS2 and phthalic acid (PA), a common metabolite of phthalates, across factories and departments in the contemporary rubber manufacturing industry. Spot urine samples from 101 rubber workers employed in nine different factories were collected on Sunday and during the workweek on Tuesday, Wednesday and Thursday at approximately 4 pm. In total, 386 urine samples were successfully analyzed. Levels of both biomarkers increased significantly by a factor 2 (paired t-test P-value <0.05) during the working week as compared to the Sunday biomarker levels with absolute increases of approximately 70 microg/l and 5 micromol/mol creatinine for PA and TTCA, respectively. Levels in both biomarkers did not differ markedly between working days. Increases seemed to be restricted to specific factories and/or departments (e.g. molding and curing). The results of this study demonstrate that rubber workers in the contemporary rubber industry are exposed to phthalates and low levels of CS2 ( approximately 0.05 ppm) as measured by PA and TTCA, respectively. Exposures to both compounds are largely driven by specific circumstances in factories. Therefore, when estimating exposures to phthalates and CS2 detailed information should be collected on the type and amount of phthalate containing ester plasticizers, dithiocarbamates and thiurams used. Preferably, personal exposure data should be collected. In this case, biological monitoring seems a reasonable approach. However, in the case of PA attention should be given to individual background levels as this could lead to a substantial overestimation of the occupational contribution to total phthalate exposure.

Risks of Brain Tumors in Rubber Workers: A Metaanalysis

To better understand whether rubber industry workers suffer increased risks of brain tumor, a concern that has persisted for over 40 years despite numerous well-conducted studies. We performed a formal metaanalysis of brain tumor risk estimates reported in cohort studies of rubber and tire workers. Twenty unique cohorts were identified who met a priori inclusion criteria. Metaanalysis was performed using the general variance-based method; the variance of risk estimates was calculated for each study using a chi-squared method. Homogeneity was tested by means of the Q statistic. The metaanalysis determined an overall relative risk of 0.90 (95% CI = 0.79-1.02). The analytical results are consistent with a conclusion that risks of brain tumor are not increased as a result of occupational exposures in the rubber and tire industry.

Bladder tumours in rubber workers: a factory study 1946-1995.

Prior to December 1949, some British rubber industry workers were inadvertently exposed to the human bladder carcinogen beta-naphthylamine, which was present as a contaminant (at 0.25%) in antioxidants used in manufacturing. This study follows a composite cohort of 6450 men employed at a large tyre factory either during the 'at-risk' period or just after it. A group of 2090 at-risk men (employed 1945-1949) and 3038 men, first employed only after January 1950, when the carcinogen had been removed, were followed for their bladder cancer morbidity and mortality experiences. Fifty-eight tumours were registered for those at risk, whereas only 33.9 were expected at national standardized registration rates [SRRN = 171 and 95% confidence interval (CI) = 130-221]. Thirty-nine bladder tumours were reported for the post-1950 intake, whereas 38.3 were expected (SRRN = 102 and 95% CI = 72-139). The use of mortality data did not reveal any underlying hazard because 12 of the 58 at-risk workers with tumours were still alive at the study end date. In only 16 instances was bladder cancer actually certified as the underlying cause of death. Plotting cases by their location of work on a factory plan assisted the interpretation. A statistically significant elevated risk of bladder cancer for the exposed workforce was evident, but this reversed when the carcinogen was removed from processing in October 1949. The use of morbidity (incidence) data in long-term studies of occupational bladder cancer should be the required methodology if the hazard and risk are not to be underestimated.

Occupational Risk Factors for Lung Cancer in Men and Women: A Population-Based Case–Control Study in Italy

We investigated the role of occupation in lung cancerogenesis in two Northern Italian areas. During 1990-1992, occupational histories were obtained for 1171 incident lung cancer cases (956 men, 176 women) and 1553 population controls (1253 men, 300 women) and were evaluated for having been employed in jobs entailing exposure to known or suspected lung carcinogens. A further exploratory analysis on other job titles and branches of industry was conducted. Among men, we found a smoking-adjusted odds ratio (OR) of 2.1 (95% confidence interval: 1.6-2.8) for exposure to known carcinogens, corresponding to a population attributable risk of 9.5% (6.0-13.0). Non-ferrous metal workers and painters had a significantly increased risk. No association was found for exposure to suspected carcinogens. In the exploratory analysis, the OR was increased for cleaners (OR: 2.7; 1.0-7.4), bakers (5.7; 1.4-24), tailors (6.9; 1.2-39), plumbers and pipe fitters (2.6; 1.0-6.4), welders and flame-cutters (5.6; 2.1-15), dockers and freight handlers (1.7; 1.0-2.7) and construction workers (1.4; 1.1-1.9). Female glass workers, laundry/dry cleaners and workers in rubber industry had an increased risk. The study indicates that a sizable proportion of lung cancers among men may be due to occupational exposures and suggests that exposure to lung carcinogens occurs in different jobs in women compared to men.

Latex hypersensitivity in spinal cord injured adult patients.

Latex hypersensitivity is a major cause of anaphylaxis during anaesthesia. Patients with spina bifida, health care or rubber industry workers have been considered at risk for latex sensitization. By analogy, the existence of other at-risk subsets of patients with latex exposure due to frequent surgical procedures has been suggested. The aim of this study was to evaluate the prevalence of latex sensitization in a cohort of adult patients with spinal cord injury and repeated latex exposure. Forty-two adult patients with spinal cord injury were studied and retrospectively compared to a group of 30 children with spina bifida evaluated using a similar protocol. Patients were administered a questionnaire concerning history of latex hypersensitivity, atopy, and surgical procedures. Latex sensitivity was investigated by skin prick-tests and latex-specific IgE assay. The search for atopy was based on in vivo and in vitro tests against a panel of environmental allergens. No chronic spinal cord injured patient had a history of latex allergy. When compared with spina bifida, the number of surgical procedures was not statistically different. Although not significantly different, the prevalence of atopy was higher in spina bifida patients. The high level of latex sensitization in spina bifida patients contrasted sharply with the absence of sensitization observed on both skin and in vitro tests in patients with spinal cord injury (P<0.0001). This study confirms that adult patients with chronic neurologic defects resulting from spinal cord injury exhibit a low risk of latex sensitization. These results suggest that considering adult patients with repeated surgical procedures as a group at risk for latex sensitization because of a high degree of latex exposure should be re-examined.

Leukemia and exposure to 1,3-butadiene, styrene and dimethyldithiocarbamate among workers in the synthetic rubber industry

This study evaluated relations between exposure to 1,3-butadiene (BD), styrene (STY) and dimethyldithiocarbamate (DMDTC) and mortality from leukemia among synthetic rubber industry workers. Subjects were 13 130 men employed for at least 1 year during 1943–1991 at any of six plants that manufactured synthetic rubber. Death certificates and medical records identified workers with leukemia. Cumulative exposure estimates were based on plant- and time period-specific process and task characteristics, linked to subjects’ work histories. Poisson regression estimated relative rates (RRs) for workers exposed to each agent compared to unexposed workers. Leukemia ( N=59) was positively associated with BD ppm-years (RRs of 1.0, 1.2, 2.0 and 3.8, for exposures of 0, >0–<86.3, 86.3–<362.2 and 362.2+ ppm-years; only the RR for the highest exposure category was statistically significant), STY ppm-years (RRs of 1.0, 1.2, 2.3 and 3.2, for exposures of 0, >0–<20.6, 20.6–<60.4 and 60.4+ ppm-years; only the RR for the highest exposure category was statistically significant) and DMDTC mg-years/cm (RRs of 1.0, 2.3, 4.9 and 2.9, for 0, >0–<566.6, 566.6–<1395.1 and 1395.1+ mg-years/cm; the RR for each non-zero exposure category was statistically significant) after adjusting for age and years since hire. After further adjusting each agent-specific set of RRs for the other two agents, a positive but imprecise relation remained for BD and DMDTC but not for STY. The association with BD was stronger for ppm-years due to exposure intensities >100 ppm than for ppm-years due to lower concentrations. BD and DMDTC, but not STY, were positively associated with leukemia in multivariable analyses. The independent effect of each agent was difficult to evaluate because of correlations with other agents and imprecision.

Latex allergy

Coined the next major health concern of the decade, allergy to natural rubber latex affects people routinely exposed to rubber products. Groups at highest risk include health care workers, rubber industry workers, and persons who have undergone multiple surgical procedures, especially those with spina bifida. Allergy to latex is a type I, immediate, IgE-mediated reaction, which can lead to anaphylaxis and death. Much of latex research is published in allergy journals. Dermatologists may not be aware of the prevalence, symptoms, risks, diagnosis, and treatment of latex allergy. These topics are the subject of this review. Research concerning antigenic proteins, as well as sources of latex alternatives, is also summarized. (J Am Acad Dermatol 1998;39:1-24.) Learning objective: At the completion of this learning activity, participants should have a clear understanding of the history, biology, epidemiology, mechanism, clinical characteristics, diagnostic work-up, and treatment of latex allergy. Readers should also have a greater understanding of multiple potential allergenic latex proteins and their importance in preventing future latex-sensitization.

Butadiene inhalation accelerates arteriosclerotic plaque development in cockerels

1,3-Butadiene (BD), a gas widely used in the rubber industry, is also present in automotive exhaust and in the vapor phase of environmental tobacco smoke (ETS; ~ 400 μg/cigarette). The threshhold limit value (TLV) for BD which was 10 ppm, has now been reduced to 2 ppm. Extensive investigations of workers have identified very few statistically significant increases in BD-associated cancer mortality. However, two studies have reported increased BD-associated mortality from arteriosclerotic heart disease in black workers in the BD rubber industry. The cockerel is a sensitive animal model for studying effects of environmental agents on arteriosclerosis development. Previous studies showed that inhaled environmental levels of ETS significantly accelerate arteriosclerosis. Surprisingly, the carcinogen-rich tar fraction of ETS was ineffective. The elevated risk of death from arteriosclerotic heart disease in black BD workers and the high BD level in the vapor phase of ETS, raised the question of whether BD would accelerate arteriosclerosis in cockerels. Here, cockerels breathed either 20 ppm BD or filtered air (6 h/day, 80 days). Blinded measurements showed no differences between groups in plaque frequency or location. However, plaque sizes were significantly larger in BD-treated cockerels than in controls — results nearly identical to those reported earlier for ETS-exposed vs. air-exposed cockerels. This indicates that BD may contribute to the atherogenicity of ETS and provides experimental support for the recent reduction in the TLV for BD.

Leukemia and cumulative exposure to butadiene, styrene and benzene among workers in the synthetic rubber industry

Retrospective, quantitative estimates of exposure to 1,3-butadiene, styrene and benzene were developed for a follow-up study of leukemia mortality among 16610 subjects employed at six North American styrene-butadiene rubber manufacturing plants (418846 person-years, 58 leukemia deaths). The estimation procedure entailed identifying work areas within each manufacturing process, historical changes in exposure potential and specific tasks involving exposure, and using mathematical models to calculate job- and time-period-specific average exposures. The resulting estimates were linked with the subjects' work histories to obtain cumulative exposure estimates, which were employed in stratified and Poisson regression analyses of mortality rates. Mantel-Haenszel rate ratios adjusted by race, age, and cumulative styrene exposure increase with cumulative butadiene exposure from 1 in the nonexposed category to 4.5 in the category of 80 ppm-years or more ( P = 0.01). The risk pattern is less clear and statistically nonsignificant for styrene exposure. A trend of increasing risk with butadiene exposure is still present after exclusion of the nonexposed category ( P = 0.03). A parsimonious interpretation of the findings presented here, in light of previous epidemiologic studies, is that exposure to butadiene in the synthetic rubber industry produces a dose-related increase in the occurrence of leukemia.