The present study aimed to investigate the distribution of lymphocyte subsets and cytokines expression in the peripheral blood of bitumen fumes-exposed workers.

In this study, 129 workers from molding and roasting workshops were recruited as the exposed group and 99 office and quality inspection staff were chosen as the control. The polycyclic aromatic hydrocarbons (PAHs) levels of bitumen fumes in individual and fixed-point air samples and the urinary levels of 1-hydroxypyrene (1-OH-P), 1-hydroxynaphthols (1-OH-N) and 2-hydroxynaphthols (2-OH-N) in workers were measured using High Performance Liquid Chromatography. The lymphocyte subsets and serum cytokines concentrations were analyzed by flow cytometry and cytometric bead array, respectively.

The median values of PAHs were 0.08 mg/m3 for permissible concentration-time weighted average and 0.12 mg/m3 for permissible concentration-short term exposure (PC-STEL) in molding and roasting workshops, which were higher than that in the control area (< 0.01 mg/m3). Multivariate linear regression models were used to adjust for influential covariates, including age, gender, work age, smoking status, and alcohol consumptions. After adjusting for these covariates, we compared levels of urinary PAHs metabolites, the percentages of lymphocyte subsets, and serum cytokines concentrations between the two groups. The 1-OH-P, 1-OH-N, and 2-OH-N levels in the urine of bitumen fumes exposed workers were significantly higher than that in the controls (P < 0.05). Compared with the control group, the percentage of the natural killer (NK) cell (CD56+ cell) was significantly increased in the exposed group (P < 0.001). There was a significant decrease in the percentages of CD3+ T cell, CD4+ T cell, and CD8+ T cell in the exposed group compared to the control (P < 0.001). The serum levels of interleukin-1β (IL-1β) and IL-6 in bitumen fumes exposed workers were significantly higher than that of the controls (P < 0.05). Moreover, positive correlations were observed between the serum levels of IL-1β, IL-6, and urinary 1-OH-P levels in bitumen fumes-exposed workers, respectively (P < 0.05). There were no significant differences in the serum levels of IL-8, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β) and monocyte chemotactic protein-1 (MCP-1) between the exposed group and the control group (P > 0.05).

Our study suggested that low dose of bitumen fumes exposure could decrease the percentage of T cell, increase the percentage of NK cell and stimulate the release of serum IL-1β and IL-6 in the peripheral blood of exposed workers. The serum levels of IL-1β and IL-6 were positive correlated with the urinary 1-OH-P levels in bitumen fumes exposed workers. These results may inform the search for potential effective biomarkers and provide evidences for early health monitoring in workers occupationally exposed to bitumen fumes.

To evaluate whether cancer risks are increased among bitumen (asphalt) workers.

Systematic review and meta-analysis of cancer risks (lung, upper aerodigestive tract (UADT), esophagus, bladder, kidney, stomach, and skin) and bitumen exposure. Certainty in the epidemiological evidence that bitumen-exposed workers experience increased cancer risks was rated using Grading of Recommendations Assessment, Development and Evaluation criteria.

After excluding lower-quality studies, lung cancer risks were not increased among bitumen-exposed workers (meta-relative risk [RR] 0.94, 95% CI 0.74 to 1.20, eight studies). Increased risks of UADT and stomach cancers were observed (meta-RR 1.31, 95% CI 1.03 to 1.67, 10 studies and meta-RR 1.29, 95% CI 1.03 to 1.62, seven studies, respectively).

Except for lung cancer, evidence for increased cancer risks among bitumen-exposed workers was judged to be of low certainty, due to inadequate exposure characterization and unmeasured confounders (coal tar exposure, smoking, and alcohol consumption).

Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length.

We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR.

Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt workers compared to controls. Relative telomere length did not differ across occupational groups, but it was positively associated with increment of 2-OH-PH (β = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis showed no difference in either increment of 1-OH-PYP, or changes in effect biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt.

Road asphalt paving in open areas resulted in PAHs exposure, as shown by elevation of PAH metabolites in urine. Asphalt workers may experience oxidative stress, evidenced by alternation in mtDNAcn; however the effects could not be fully explained by exposure to PAHs from the asphalt mixture.

Crystalline silica is considered as one of the most common and serious occupational hazards to workers' health. Although its association with lung cancer has been studied for many decades, the conclusion remains somewhat controversial. Our objectives are to review and summarize the epidemiological evidence on the relationship between occupational silica exposure and risk of lung cancer and to provide an update on this major occupational health concern.

Eligible studies up to 29 April 2016 were identified. Pooled effect estimates were calculated according to the reported outcome and the study design. Cohort, case control and proportional mortality studies were examined separately. Studies reporting results according to silicotic status were grouped together and analyzed. Due to the significant amount of heterogeneity expected, random effects models were implemented. Subgroup and meta-regression analyses (both univariate and multivariate) were performed in an attempt to explain heterogeneity. Studies which had adequate exposure characterization were selected to find out whether there was an exposure-response relationship between silica and lung cancer.

The risk of lung cancer was found to be elevated in both silicotics and non-silicotics. The pooled standardized mortality ratio (SMR) was 2.32 with a 95 % confidence interval (95 % CI) of 1.91-2.81 and 1.78 (95 % CI 1.07-2.96) respectively. The pooled standardized incidence ratio (SIR) was 2.49 (95 % CI 1.87-3.33) and 1.18 (95 % CI 0.86-1.62) respectively. Subgroup analysis showed that workers in the mining industry had the highest risk of lung cancer with a pooled SMR of 1.48 (95 % CI 1.18-1.86) and the weakest association was seen in potteries with a pooled SMR of 1.14 (95 % CI 1.05-1.23). A positive exposure-response relation was found between cumulative silica exposure and risk of lung cancer.

The results of our meta-analysis supported the carcinogenic role of silica on the lungs, which was more pronounced at higher levels of exposure, in the presence of silicosis and in the mining industry. Further research is needed to evaluate whether non-silicotics are truly at risk, whether a predisposing factor would explain this potential risk, and to determine the mechanism of carcinogenicity of silica in humans.

Pancreatic cancer (PC) is one of the most aggressive diseases. Only 10 % of all PC cases are thought to be due to genetic factors. Here, we analyzed the most recently published case-control association studies, meta-analyses, and cohort studies with the aim to summarize the main environmental factors that could have a role in PC. Among the most dangerous agents involved in the initiation phase, there are the inhalation of cigarette smoke, and the exposure to mutagenic nitrosamines, organ-chlorinated compounds, heavy metals, and ionizing radiations. Moreover, pancreatitis, high doses of alcohol drinking, the body microbial infections, obesity, diabetes, gallstones and/or cholecystectomy, and the accumulation of asbestos fibers seem to play a crucial role in the progression of the disease. However, some of these agents act both as initiators and promoters in pancreatic acinar cells. Protective agents include dietary flavonoids, marine omega-3, vitamin D, fruit, vegetables, and the habit of regular physical activity. The identification of the factors involved in PC initiation and progression could be of help in establishing novel therapeutic approaches by targeting the molecular signaling pathways responsive to these stimuli. Moreover, the identification of these factors could facilitate the development of strategies for an early diagnosis or measures of risk reduction for high-risk people.

Individual epidemiological studies generally lack the power to examine the association between silica exposure or silicosis and laryngeal cancer. We summarized pertinent evidence from published literature by using meta-analysis.

A systematic literature search was performed to identify cohort and case-control studies, and the method of meta-analysis was used to combine standardized mortality ratios (SMRs) or standardized incidence ratios (SIRs) from cohort studies and odds ratios (ORs) from case-control studies.

A significantly increased risk of laryngeal cancer (pooled OR = 1.39, 95% confidence interval (95% CI): 1.17-1.67) among workers exposed to silica dust was observed by combining six case-control studies with adjustment for smoking and alcohol consumption. A similarly increased but statistically non-significant risk estimate was observed from cohort studies, with a pooled SMR of 1.38 (95% CI: 0.79-1.96) for silicosis cases; and a pooled SMR of 1.13 (95% CI: 0.82-1.45) and a pooled SIR of 1.50 (95% CI: 0.59-2.42) for workers with silica dust exposure.

This systematic review demonstrated a weak association between silica or silicosis and laryngeal cancer. Owing to the inherent limitations of the original studies, interpretation of the results of this meta-analysis should be cautious.

Several occupational exposures have been linked to excess risk of pancreatic cancer; however, most associations are not well established. The objective of this review article is to report on the more recently published studies (1998-2010), and provide a summary of the most consistently reported occupational risk factors for pancreatic cancer, including exposure to chlorinated hydrocarbon compounds, pesticides, polycyclic aromatic hydrocarbons (PAHs), metals, nitrosamines, radiation, various airborne particles, and employment in sedentary occupations. We conclude that the strongest and most consistent findings linking occupational exposures with pancreatic cancer risk to date are for chlorinated hydrocarbons and PAHs.

We conducted a nested case-control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed.

We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers.

Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002-2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar.

A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84-1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88-1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate.

We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role.

To evaluate mortality due to lung cancer, silicosis, renal cancer, renal disease and other causes among German porcelain production workers potentially exposed to crystalline silica.

Seventeen thousand six hundred forty-four medical surveillance participants (1985-1987) were followed through 2005 for mortality. Cause-specific Standardized Mortality Ratios (SMR) and 95% confidence intervals were estimated.

Women (SMR = 0.85; 95% CI = 0.78 to 0.93), but not men, demonstrated a healthy worker effect. Lung and renal cancers, and renal disease (non-malignant renal disease) were not associated with employment or exposure surrogates. Mortality was increased from silicosis (SMR = 7.20; 95% CI = 2.32 to 16.8) liver (SMR = 1.99; 95% CI = 1.29 to 2.93) and pancreatic (SMR = 1.71; 95% CI = 1.18 to 2.41) cancers among men, and diabetes among women (SMR = 1.74; 95% CI = 1.07 to 2.65). A sub-cohort of Bavarian workers generated similar but generally higher SMRs.

Silicosis mortality was increased in this, among the largest studies to date. However, associations previously observed between crystalline silica exposure and renal or lung cancers or non-malignant renal disease were not supported.

To examine the association between occupational exposure to silica and lung cancer from a systematic review (and meta-analysis) of the epidemiologic literature, with special reference to the methodological quality of observational studies.

We searched Medline, Toxline, BIOSIS, and Embase (1966-December 2007) for original articles published in any language. Observational studies (cohort and case-control studies) were selected if they reported the result of dose-response analyses relating lung cancer to occupational exposure to silica after appropriate adjustment for smoking.

Ten studies (4 cohort studies and 6 case-control studies) met the inclusion criteria of the meta-analysis, nine of which contributing to the main analysis (dose-response analysis, no lag time). We found increasing risk of lung cancer with increasing cumulative exposure to silica, with heterogeneity across studies however. Posthoc analyses identified a set of seven more homogeneous studies. Their meta-analysis resulted in a dose-response curve that was not different from that obtained in the main analysis.

Silica is a lung carcinogen. This increased risk is particularly apparent when the cumulative exposure to silica is well beyond that resulting from exposure to the recommended limit concentration for a prolonged period of time.

Excessive exposures to airborne crystalline silica have been known for over 100 years to pose a serious health hazard. Work practices and regulatory standards advanced as the knowledge of the hazards of crystalline silica evolved. This article presents a comprehensive historical examination of the literature on exposure, health effects, and personal protective equipment related to silica and abrasive blasting operations over the last century. In the early 1900s, increased death rates and prevalence of pulmonary disease were observed in industries that involved dusty operations. Studies of these occupational cohorts served as the basis for the first occupational exposure limits in the 1930s. Early exposure studies in foundries revealed that abrasive blasting operations were particularly hazardous and provided the basis for many of the engineering control and respiratory protection requirements that are still in place today. Studies involving abrasive blasters over the years revealed that engineering controls were often not completely effective at reducing airborne silica concentrations to a safe level; consequently, respiratory protection has always been an important component of protecting workers. During the last 15-20 yr, quantitative exposure-response modeling, experimental animal studies, and in vitro methods were used to better understand the relationship between exposure to silica and disease in the workplace. In light of Occupational Safety and Health Administration efforts to reexamine the protectiveness of the current permissible exposure limit (PEL) for crystalline silica and its focus on protecting workers who are known to still be exposed to silica in the workplace (including abrasive blasters), this state-of-the-science review of one of the most hazardous operations involving crystalline silica should provide useful background to employers, researchers, and regulators interested in the historical evolution of the recognized occupational health hazards of crystalline silica and abrasive blasting operations and the related requirements for respiratory protection.

To explore the healthy worker survivor effect (HWSE) in a study of Vermont granite workers by distinguishing "prevalent" from "incident" hires based on date of hire before or after the start of follow-up.

Records of workers between 1950 and 1982 were obtained from a medical surveillance programme. Proportional hazards models were used to model the association between silica exposure and lung cancer mortality, with penalised splines used to smooth the exposure-response relationship. A sensitivity analysis compared results between the original cohort and subcohorts defined by restricting date of hire to include varying proportions of prevalent hires.

Restricting to incident hires reduced the 213 cases by 74% and decreased the exposure range. The maximum mortality rate ratio (MRR) was close to twofold in all subcohorts. However, the exposure at which the maximum MRR was achieved decreased from 4.0 to 0.6 mg-year/m3 as the proportion of prevalent hires decreased from 50% in the original cohort to 0% in the subcohort of incident hires.

Despite loss in power and restricted exposure range, decreasing the relative proportion of prevalent to incident hires reduced HWSE bias, resulting in stronger evidence for a dose-response between silica exposure and lung cancer mortality.

In 1997, a Monograph from the International Agency for Research on Cancer (IARC) classified occupational exposure to crystalline silica as carcinogenic to humans. Large amounts of epidemiological data have been published subsequently.

We conducted a systematic review of epidemiological investigations on silica exposure and lung cancer risk published after the IARC Monograph, including 28 cohort, 15 case-control and two proportionate mortality ratio (PMR) studies. These were identified in the available literature.

The pooled RR of lung cancer, calculated using random effects models, from all cohort studies considering occupational exposure to silica was 1.34. The RRs were 1.69 in cohort studies of silicotics only, 1.25 in studies where silicosis status was undefined and 1.19 among non silicotic subjects. The pooled RR was 1.41 for all case-control studies. The RRs were 3.27 in case-control studies of silicotics only, 1.41 in studies where silicosis status was undefined and 0.97 among non silicotic subjects. The RR was 1.24 for PMR studies.

In this re-analysis, the association with lung cancer was consistent for silicotics, but the data were limited for non silicotic subjects and not easily explained for undefined silicosis status workers. This leaves open the issue of dose-risk relation and pathogenic mechanisms and supports the conclusion that the carcinogenic role of silica per se in absence of silicosis is still unclear.

A complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal tar, standard reference material (SRM) 1597, has been shown to initiate tumor formation in mouse initiation-promotion assays in our laboratory [(2001) Carcinogenesis 22 (7), 1077-1086]. To determine the effects of SRM 1597 on PAH activation in human cells, we investigated the PAH-DNA adduct formation in the human mammary carcinoma-derived cell line MCF-7. We examined the effects of SRM 1597 on the metabolic activation to DNA binding derivatives of two carcinogenic PAHs, the bay region containing benzo[a]pyrene (B[a]P) and the more carcinogenic fjord region containing dibenzo[a,l]pyrene (DB[a,l]P). PAH-DNA adduct analysis by 33P-postlabeling and reversed phase high-performance liquid chromatography revealed a significant decrease in the levels of both B[a]P and DB[a,l]P DNA adduct formation on cotreatment with SRM 1597 in comparison to cells exposed to B[a]P or DB[a,l]P alone. However, the inhibition of PAH-DNA adduct formation only occurred within the first 48 h of exposure in cells cotreated with SRM 1597 and B[a]P. In contrast, SRM 1597 significantly inhibited the level of DB[a,l]P DNA adducts throughout the 120 h of exposure. Induction of human cytochrome P450 (P450) enzymes 1A1 and P4501B1 on treatment with SRM 1597 was observed by immunoblots. These results suggest that the important factors in determining the carcinogenic activity of PAH within a complex mixture would depend on the ability of other components of the mixture to promote or inhibit the activation of carcinogenic PAH by the induction of P450 enzymes followed by the formation of DNA adducts.

Inhalation of bitumen fumes is potentially carcinogenic to humans.

We conducted a study of 29,820 male workers exposed to bitumen in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers unexposed to bitumen, and 17,757 workers not classifiable as bitumen workers, from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality follow-up during 1953-2000. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates. Poisson regression analyses compared mortality of bitumen workers to that of building or ground construction workers.

The overall mortality was below expectation in the total cohort (SMR 0.92, 95% CI 0.90-0.94) and in each group of workers. The SMR of lung cancer was higher among bitumen workers (1.17, 95% CI 1.04-1.30) than among workers in ground and building construction (SMR 1.01, 95% CI 0.89-1.15). In the internal comparison, the relative risk (RR) of lung cancer mortality among bitumen workers was 1.09 (95% CI 0.89-1.34). The results of cancer of the head and neck were similar to those of lung cancer, based on a smaller number of deaths. There was no suggestion of an association between employment in bitumen jobs and other cancers.

European workers employed in road paving, asphalt mixing and other jobs entailing exposure to bitumen fume might have experienced a small increase in lung cancer mortality risk, compared to workers in ground and building construction. However, exposure assessment was limited and confounding from exposure to carcinogens in other industries, tobacco smoking, and other lifestyle factors cannot be ruled out.

An increased risk of lung cancers among asphalt workers has been suggested in epidemiological studies based on large scale statistical analyses.

In a multi-country study of 29,820 male workers employed in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers and 17,757 other workers from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality that was documented from 1953-2000. Exposures to bitumen fume, coal tar, 4-6 ring polycyclic aromatic hydrocarbons, organic vapor, diesel exhaust, asbestos, and silica dust were assessed via a job-exposure matrix. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates, as well as relative risks (RRs) based on Poisson regression models were calculated.

The SMR of lung cancer among workers exposed to bitumen fume (1.08, 95% CI 0.99-1.18) was comparable to that of non-exposed workers (SMR 1.05, 95% CI 0.92-1.19). In a sub-cohort of bitumen-exposed workers without exposure to coal tar, the SMR of lung cancer was 1.23 (95% CI 1.02-1.48). The analysis based on the semi-quantitative, matrix-based exposures in the whole cohort did not suggest an increased lung cancer risk following exposure to bitumen fume. However, in an analysis restricted to road pavers, based on quantitative estimate of bitumen fume exposure, a dose-response was suggested for average level of exposure, applying a 15-year lag, which was marginally reduced after adjustment for co-exposure to coal tar. The results for cancer of the head and neck were similar to those of lung cancer, although they were based on a smaller number of deaths. There was no clear suggestion of an association with bitumen fume for any other neoplasm.

The results of the analysis by bitumen fume exposure do not allow us to conclude on the presence or absence of a causal link between exposure to bitumen fume and risk of cancer of the lung and the head and neck.

Using data from a Dutch cohort of workers in road construction and asphalt mixing companies, this article describes possible confounding of the association between exposure to bitumen fume and lung cancer mortality by smoking.

A retrospective cohort of 3,714 workers with at least one season of employment was identified. Semi-quantitative exposure to bitumen fume was assessed by a job-exposure matrix. Information on smoking habits was available for a sub-cohort of 1,138 workers, who underwent medical examinations by the occupational health services in the past.

Smoking habits differed between occupational title groups and there was a positive association between cumulative exposure and smoking. Internal analyses using the non-exposed subjects as reference category, showed a positive association between semi-quantitative bitumen fume exposure and lung cancer risk. After adjusting for differences in smoking habits, all relative risks were reduced, but a weak positive association could still be observed.

Confounding by smoking on the association between exposure to bitumen fume and lung cancer mortality is possible, although the positive trend (not statistically significant) for lung cancer mortality remained. Only a nested case-control study may allow proper treatment of potential (residual) confounding by smoking in this population.