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We conducted a systematic review and meta-analysis of epidemiological studies that evaluated occupational exposure to man-made vitreous fibers (MMVF) including glass, rock, and slag wools, and respiratory tract cancers (RTC) including cancers of the larynx, trachea, bronchus, and lung. The MEDLINE/PubMed and Web of Science databases were searched in order to identify epidemiological studies that evaluated the association between occupational MMVF exposure and RTCs. We performed random-effects meta-analyses of relevant studies identified by our literature search, and evaluated sources of between-study heterogeneity. The pooled relative risk (RR) of RTC among workers exposed to MMVFs was 1.09 (95% CI = 0.97, 1.22). The RR was closer to 1.0 when limiting the analysis to effect estimates from studies that accounted for the main a priori risk factors for RTC, asbestos exposure and smoking (RR = 1.03, 95% CI = 0.90, 1.18). Overall, our synthesis of the epidemiological literature suggests that occupational MMVF exposure is not associated with risk of RTC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All the authors are employed by Cardno ChemRisk, a consulting firm that provides scientific advice to the government, corporations, law firms and various scientific/professional organizations. GM is also Professor of Biostatistics and Director and Founder of the Center for Occupational Biostatistics and Epidemiology at the University of Pittsburgh Graduate School of Public Health. Financial support for the research described in the manuscript was provided by the North American Insulation Manufacturers Association (NAIMA). The funding association had no involvement or influence in the analysis, writing or conclusions of this review. This article was prepared and written exclusively by the authors without review or comment by any outside entity., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Pollution related to traffic is a major problem in urban centers and a large portion of the population is vulnerable to its health effects. This study sought to identify a potential association between hospital admissions due to respiratory tract cancer and vehicular traffic density in the city of São Paulo, Brazil. It is an ecological study of the public (Hospital Inpatient Authorization - AIH, in Portuguese) and private (Hospital Inpatient Communication - CIH, in Portuguese) health care systems, from 2004 to 2006, geocoded by individuals' residential addresses. Using a Besag-York-Mollié ecological model, we initially evaluated the relationship between number of cases of hospital admission due to respiratory tract cancer in each weighting area and the standardized co-variables: traffic density and Municipal Human Development Index (MHDI) as indicator of socioeconomic status. Using a classic Poisson model, we then evaluated the risk associated with growing traffic density categories. The Besag-York-Mollié model estimated a RR = 1.09 (95%CI: 1.02-1.15) and RR = 1.19 (95%CI: 1.10-1.29) of admission due to respiratory tract cancer for each increase of one standard deviation of traffic and MHDI, respectively. The Poisson model also showed a clear exposure-response gradient for admission due to respiratory tract cancer (IRR = 1.11; 95%CI: 1.07-1.15, for each 10 units of added traffic density). This study suggests that there is an association between residing in areas with high traffic density and hospital admissions due to respiratory tract cancer in the city of São Paulo.

In a previous analysis of a cohort of shipyard workers, we found excess mortality from all causes, lung cancer, and mesothelioma for longer work durations and in specific occupations. Here, we expand the previous analyses by evaluating mortality associated with 5 chemical exposures: asbestos, solvents, lead, oils/greases, and wood dust. Data were gathered retrospectively for 4,702 workers employed at the Coast Guard Shipyard, Baltimore, MD (1950-1964). The cohort was traced through 2001 for vital status. Associations between mortality and these 5 exposures were calculated via standardized mortality ratios (SMRs). We found all 5 substances to be independently associated with mortality from mesothelioma, cancer of the respiratory system, and lung cancer. Findings from efforts to evaluate solvents, lead, oils/greases, and wood dust in isolation of asbestos suggested that the excesses from these other exposures may be due to residual confounding from asbestos exposure.

Objective: To estimate the social cost of respiratory cancers attributable to occupational risk factors in France in 2010., Methods: We estimated the number of cases of respiratory cancers attributable to each identified occupational risk factor according to the attributable fractions method. We also estimated direct (costs of hospital stays, drugs, outpatient care) and indirect costs (production losses) related to morbidity (absenteeism and presenteeism) and mortality (years of lost production). Production losses for paid work and unpaid domestic activities were taken into account., Results: The social cost of respiratory cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons, painting occupations (unidentified carcinogen), crystalline silica, wood and leather dust in France in 2010 was estimated to be between €960 and 1,866 million. The cost of lung cancer represents between €804 and 1,617 million. The three risk factors with the greatest impact are asbestos (€530 to 890 million), diesel engine exhaust (€227 to 394 million), and crystalline silica (€116 to 268 million)., Conclusion: These results provide a conservative estimate of the public health and economic burden of respiratory cancers attributable to occupational risk factors from a societal perspective.

Respiratory cancer mortality and incidence were examined in an updated cohort of >56,000 Canadian nickel mining and refining workers. There was little evidence to suggest increased lung cancer risk in workers who had no experience in high-risk sintering operations that were closed by 1972, apart from that which would be expected from probable increased smoking prevalence relative to the comparison population. There was no substantive evidence of increased laryngeal cancer risk in the cohort, nor was there evidence of increased pharyngeal cancer risk in nonsinter workers. Nasal cancer incidence was elevated in nonsinter workers, but excess risks appeared to be confined to those hired prior to 1960. These findings lead us to tentatively conclude that occupationally-related respiratory risks in workers hired over the past 45 years are either very low or nonexistent.

In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m 3 (0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure-response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA's direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin's lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m 3 and at peak exposures ≥2.5 mg/m 3 ; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies., Competing Interests: The authors declare that they have no conflict of interest.

Aim of this study was the investigation of the genotoxic properties of XLR-11 [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone, a widely consumed synthetic cannabinoid (SC), and of the benzoyl indole RCS-4 (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone). We characterized the DNA-damaging properties of these drugs in different experimental systems. No evidence for induction of gene mutations was detected in bacterial (Salmonella/microsome) tests, but clear dose-dependent effects were found in in vitro single cell gel electrophoresis (SCGE) assays with human lymphocytes and with buccal- and lung-derived human cell lines (TR-146 and A-549). These experiments are based on the determination of DNA migration in an electric field and enable the detection of single- and double-strand breaks and apurinic sites. Furthermore, we found that both drugs induce micronuclei which are formed as a consequence of chromosomal aberrations. The lack of effects in SCGE experiments with lesion-specific enzymes (FPG, Endo III) shows that the DNA damage is not caused by formation of oxidatively damaged bases; experiments with liver enzyme homogenates and bovine serum albumin indicate that the drugs are not converted enzymatically to DNA-reactive intermediates. Furthermore, results with buccal- and lung-derived human cells show that gaseous treatment of the cells under conditions which reflect the exposure situation in drug users may cause damage of the genetic material in epithelia of the respiratory tract. Since DNA instability is involved in the etiology of cancer, these findings can be taken as an indication that consumption of the SCs may cause tumors in the respiratory tract of consumers., Competing Interests: The authors state that they have no conflict of interest.

This paper presents statistical data of 2012-2015 on the diseases caused by the atmospheric air and water pollutions in Ajara region. The research on the content of dust, sulfur dioxide and nitrogen dioxide as well as carbon monoxide in the atmospheric air was held together with the National Environment Agency Ajara Monitoring Service. The results of the research have shown that the average content of the dust reached its maximum in 2012 (0.60 mg/m3) and it dropped to the minimum in 2015 (0.441 mg/m3). As for average content of carbon monoxide the maximum was observed in 2013 (3.1 mg/m3) and minimum in 2015 (2.1 mg/m3). Average content of the sulfur dioxide was at maximum in 2015 (0.159 mg/m3) and at minimum in 2012 (0.07 mg/m3). The average content of nitrogen dioxide reached its maximum in 2015 (0.153 mg/m3) and was found to be at its minimum in 2012 (0.13 mg/m3). In parallel statistical research of the registered diseases (chronic and undetermined bronchitis, asthma, allergic rhinitis and trachea/bronchi/lung malignant cancer) in Ajara during 2012-2015 has been performed. These diseases were especially common among the population over the age of 40. It may be concluded that in 2015 the cases of diseases caused by the atmospheric air pollution in Ajara have become more frequent compared to the previous years. Therefore, it is evident that monitoring of atmosphere air should be improved and corresponding preventive measures should be undertaken.

Background: Previous research suggests a possible link between sleep-medication use and mortality, especially cancer deaths, but findings are mixed, and large population-based studies are lacking., Methods: Data from the Finnish Public Sector study were linked to the Finnish Cancer Register and the Drug Prescription Register of Finland. A total of 5053 cancer cases (mean age of 57.4 years) diagnosed in 2002-2011, and their 24,388 controls free of cancer and matched for sex, age, socioeconomic status, employer, and geographical area, were identified. The use of sleep medications was defined as purchases of prescribed sleep medications., Results: Both quantity and duration of prior sleep-medication use during the seven years studied were associated with increased odds of having cancer. Compared with participants not using sleep medications, the odds ratio was 1.18-fold (95% confidence interval (CI): 1.01-1.39) for those who used >100 defined daily doses per year and 1.16-fold (95% CI: 1.01-1.34) for those who had such a medication for >3 years. Site-specific analyses showed a more pronounced association of quantity and duration of sleep-medication use with subsequent cancer of the respiratory system (odds ratio for >100 defined daily doses per year vs. no use: 3.47; 95% CI: 1.97-6.11). No associations were found with other cancer sites., Conclusion: In this register-based study, sleep-medication use was associated with an increased cancer incidence of the respiratory system. Further studies are needed to examine potential carcinogenic mechanisms associated with hypnotic medications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesics and preventative agents for vascular events. It is unclear whether their long-term use affects cancer risk. Data on the chemopreventative role of these drugs on the risk of the upper aerodigestive tract cancer (UADT) are insufficient and mostly refer to oesophageal cancer. The aim of this study was to investigate the effect of aspirin and other NSAIDs on the risk of UADT cancers., Methods: A nested case-control study using the Primary Care Clinical Informatics Unit (PCCIU) database. Conditional logistics regression was used for data analysis., Results: There were 2392 cases of UADT cancer diagnosed between 1996 and 2010 and 7165 age-, gender- and medical practice-matched controls from 131 general medical practices. Mean age of cases was 66 years (s.d. 12) and most were male (63%). Aspirin was prescribed in a quarter of cases and controls, COX-2 inhibitors in 4% of cases and 5% of controls and other NSAIDs in 33% of cases and 36% of controls. Aspirin prescription was associated with a nonsignificant risk reduction of cancer of UADT (adjusted OR=0.9, 95% CI=0.8, 1.0), head and neck (HN; adjusted OR=0.9, 95% CI=0.7, 1.1) or the oesophagus (adjusted OR=0.8, 95% CI=0.7, 1.0). Similar results were found for COX-2 inhibitors prescription. Prescription of other NSAIDs was associated with significantly reduced risk of cancer of UADT (adjusted OR=0.8, 95% CI=0.7, 0.9), HN (adjusted OR=0.8, 95% CI=0.7, 0.9) and the oesophagus (adjusted OR=0.8, 95% CI=0.7, 0.9). An increased volume of aspirin prescriptions was associated with a significant risk reduction (test for trend P<0.001)., Conclusions: The decreased risk of cancer of the UADT associated with the use of non-COX-2 inhibitors, NSAIDs and long-term aspirin therapy warrants further exploration of the benefits vs risks of the use of these agents.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with an excess risk of respiratory tract and bladder cancers in several industries, but the issue requires further quantification. We updated a previous systematic review by reviewing in details cohort studies on workers employed in selected industries with potential PAH exposure published between 2006 and 2014, and we summarized through a meta-analytic approach the main results of all available cohort studies published between 1958 and 2014 investigating cancers of the respiratory and urinary tracts. Thirteen papers on cohort studies investigating cancer risk in workers exposed to PAHs were retrieved through the literature search. These included workers from aluminum production industries (seven studies), iron and steel foundries (two studies), asphalt workers (two studies), and carbon black production (two studies). In the meta-analysis, an excess risk of respiratory tract cancers (mainly lung cancer) was found in iron and steel foundries [pooled relative risk (RR) 1.31, 95 % confidence interval (CI) 1.08-1.59 from 14 studies], while a weak excess risk (pooled RR 1.08, 95 % CI 0.95-1.23 from 11 studies) emerged for aluminum production. A borderline increase risk was also observed for cancer of the bladder in the aluminum production (pooled RR 1.28, 95 % CI 0.98-1.68 from 10 studies) and in iron and steel foundries (pooled RR 1.38, 95 % CI 1.00-1.91 from 9 studies). This updated review and meta-analysis confirm the increased risk from respiratory tract and bladder cancers in selected PAH-related occupations. It cannot be ruled out whether such excesses are due, at least in part, to possible bias or residual confounding.

Propargyl alcohol (PA) is a high production volume chemical used in synthesis of many industrial chemicals and agricultural products. Despite the potential for prolonged or accidental exposure to PA in industrial settings, the toxicity potential of PA was not well characterized. To address the knowledge gaps relevant to the toxicity profile of PA, the National Toxicology Program (NTP) conducted 2-week, 14-week and 2-year studies in male and female F344/N rats and B6C3F1/N mice. For the 2-week inhalation study, the rats and mice were exposed to 0, 31.3, 62.5, 125, 250 or 500ppm. Significant mortality was observed in both rats and mice exposed to ≥125ppm of PA. The major target organ of toxicity in both mice and rats was the liver with exposure-related histopathological changes (250 and 500ppm). Based on the decreased survival in the 2-week study, the rats and mice were exposed to 0, 4, 8, 16, 32 or 64ppm of PA in the 14-week study. No treatment-related mortality was observed. Mean body weights of male (≥8ppm) and female mice (32 and 64ppm) were significantly decreased (7-16%). Histopathological changes were noted in the nasal cavity, and included suppurative inflammation, squamous metaplasia, hyaline droplet accumulation, olfactory epithelium atrophy, and necrosis. In the 2-year inhalation studies, the rats were exposed to 0, 16, 32 and 64ppm of PA and the mice were exposed to 0, 8, 16 and 32ppm of PA. Survival of male rats was significantly reduced (32 and 64ppm). Mean body weights of 64ppm male rats were significantly decreased relative to the controls. Both mice and rats showed a spectrum of non-neoplastic changes in the nose. Increased neoplastic incidences of nasal respiratory/transitional epithelial adenoma were observed in both rats and mice. The incidence of mononuclear cell leukemia was significantly increased in male rats and was considered to be treatment-related. In conclusion, the key findings from this study indicated that the nose was the primary target organ of toxicity for PA. Long term inhalation exposure to PA led to nonneoplastic changes in the nose, and increased incidences of respiratory/transitional epithelial adenomas in both mice and rats. Increased incidences of harderian gland adenoma may also have been related to exposure to PA in male mice., (Copyright © 2013. Published by Elsevier Ireland Ltd.)

Objectives/hypothesis: To evaluate the degree of dysplasia following cidofovir injections while documenting human papillomavirus (HPV) type in patients with recurrent respiratory papillomatosis (RRP)., Study Design: Retrospective chart review., Methods: Demographic data, operative reports, and pathology results were reviewed from 25 patients with RRP who had had cidofovir injections. All patients included had adult onset RRP, no history of immunosuppression, well-controlled laryngopharyngeal reflux, and no current smoking history. Eight patients were excluded because they did not meet the inclusion criteria., Results: Seventeen patients had adequate data for analysis and 40 subsites were identified with sufficient data for analysis. Patients negative for both low and high risk did not have progressive dysplasia at the conclusion of the study. Of the patients with positive viral typing, 70% had progressive disease at the conclusion of the study. No patients progressed to carcinoma or carcinoma in situ. The average pre- and post-treatment dysplasia scores were analyzed using a Student paired t test. There was no difference in mean dysplasia score, indicating that there was no increased risk of dysplasia following cidofovir treatment., Conclusions: To our knowledge, this is the first study looking at the degree of dysplasia while documenting HPV types in RRP. Our study suggests that HPV type appears to be relevant in the disease progression of RRP and that cidofovir does not increase the risk of dysplasia., (Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Background: Drywall joint compound contained asbestos fibers, primarily chrysotile, in the 1950s through the 1970s. Workers in a variety of construction trades and homeowners were exposed to respirable asbestos from the use of these products, including during handling, mixing, sanding, and sweeping. Disturbance of in-place asbesto-containing joint compound continues to be a potential source of exposure during demolition or repair of wallboard. Studies from the 1970s and 1980s report air fiber measurements above current and historic regulatory limits during intended usage, and typical asbestos-related disease in drywall construction workers., Objectives: We present three cases of mesothelioma in which the only known exposure to asbestos was from joint compound and review the literature on exposure circumstances, dose and fiber types., Conclusions: Physicians treating mesothelioma patients should obtain a history of exposure to these products during work or home remodeling.

Background: The question of whether chrysotile asbestos-containing brake dust can plausibly serve as a cause of mesothelioma in an exposed individual has become a matter of heated debate in the medical literature despite multiple international, federal, and state governmental agencies acknowledging a causal association., Objectives: We describe and provide an analysis of various industry and academic perspectives contributing to the debate., Methods: A framework is presented for evaluating the general and specific causal relationship between brake dust exposure and mesothelioma utilizing the principles of forensic epidemiology, and by applying the Bradford-Hill criteria., Results and Conclusions: We conclude that there is a "net" of evidence favoring a causal relationship between brake dust-associated chrysotile exposure and mesothelioma. The industry-sponsored position that there is insufficient evidence to support a contiguous "chain" of causation is specious from both a methodologic and evidentiary perspective. Finally, we suggest a semiquantitative approach for the evaluation of individual causation in putative cases of mesothelioma with a history of significant brake dust exposure.

Whether treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) increases the risk of cancer is controversial. Collaborative transplant study data were analyzed according to whether kidney transplant recipients were treated with ACEi/ARB at year 1. Twenty-four thousand and ninety patients were studied of whom 9079 (38%) patients received ACEi/ARB. There were 872 nonskin malignancies during years 2-8 posttransplant, including 107 respiratory/intrathoracic tumors. The standardized incidence ratio (SIR) for all nonskin malignancies was similar between the ACEi/ARB (1.91) and no ACEi/ARB (1.81) groups (p = 0.42). For respiratory/intrathoracic tumors, however, SIR was significantly higher with ACEi/ARB (1.65 vs. 1.09 for no ACEi/ARB, p = 0.033). Multivariate Cox regression analysis showed that ACEi/ARB treatment was not associated with an increased risk of respiratory/intrathoracic tumors in nonsmokers. In patients with a history of smoking, however, the risk of respiratory/intrathoracic tumors was 2.77 (95% CI 1.19-6.43, p = 0.018) in patients without ACEi/ARB treatment as compared to 7.10 (95% CI 3.27-15.4, p < 0.001) in patients treated with ACEi/ARB. Our data indicate that in kidney transplant recipients, ACEi/ARB treatment is associated with a significant increase in the rate of respiratory/intrathoracic tumors in the subpopulation of patients with a history of smoking., (©2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Recently, various regulatory authorities have been reexamining the potential carcinogenic hazards and risks associated with exposures to nickel and certain nickel compounds. In making their assessments, the authorities have focused on occupational cohorts at facilities where nickel-containing sulfidic ores were processed and where increased lung and nasal cancer risks were found in specific groups of workers. Little attention, however, has been paid to the vast number of workers in nickel-using industries, where no excess respiratory cancer risks have been observed. In this paper, the historical exposures of one such group of workers engaged in the production of nickel alloys are reconstructed, and the implications for cancer risk assessments are analyzed. The results indicate that nickel alloy workers were exposed to insoluble oxidic and metallic nickel species at levels comparable to those found in certain nickel processing cohorts; yet they experienced no increase in respiratory cancer risks. This suggests that extrapolating risks from certain primary nickel producers to other nickel industry sectors may not be appropriate.

Background: Inhalation of high levels of airborne inorganic arsenic is a recognized cause of respiratory cancer. Although multiple epidemiologic studies have demonstrated this association, there have been few analyses of the mathematical relationship between cumulative arsenic exposure and risk of respiratory cancer, and no assessment as to whether and how arsenic concentration may modify this association., Objectives: The objective is an evaluation of the shape of the relationship between respiratory cancer mortality and cumulative inhaled arsenic exposure among copper smelter workers, and the modification of that relationship by arsenic concentration., Methods: We used Poisson regression methods to analyze data from a cohort of arsenic-exposed copper smelter workers under a linear-exponential model for the excess relative risk., Results: Within categories of arsenic concentration, the association between respiratory cancer and cumulative arsenic exposure was consistent with linearity. The slope of the linear relationship with cumulative exposure increased with increasing arsenic concentration category., Conclusions: Our results suggested a direct concentration effect from inhaled inorganic arsenic, whereby the excess relative risk for a fixed cumulative exposure was greater when delivered at a higher concentration and shorter duration than when delivered at a lower concentration and longer duration.

In a series of articles and a health-risk assessment report, scientists at the CIIT Hamner Institutes developed a model (CIIT model) for estimating respiratory cancer risk due to inhaled formaldehyde within a conceptual framework incorporating extensive mechanistic information and advanced computational methods at the toxicokinetic and toxicodynamic levels. Several regulatory bodies have utilized predictions from this model; on the other hand, upon detailed evaluation the California EPA has decided against doing so. In this article, we study the CIIT model to identify key biological and statistical uncertainties that need careful evaluation if such two-stage clonal expansion models are to be used for extrapolation of cancer risk from animal bioassays to human exposure. Broadly, these issues pertain to the use and interpretation of experimental labeling index and tumor data, the evaluation and biological interpretation of estimated parameters, and uncertainties in model specification, in particular that of initiated cells. We also identify key uncertainties in the scale-up of the CIIT model to humans, focusing on assumptions underlying model parameters for cell replication rates and formaldehyde-induced mutation. We discuss uncertainties in identifying parameter values in the model used to estimate and extrapolate DNA protein cross-link levels. The authors of the CIIT modeling endeavor characterized their human risk estimates as "conservative in the face of modeling uncertainties." The uncertainties discussed in this article indicate that such a claim is premature.

Objective: The investigation updates the mortality experience through 2002 for a cohort of workers exposed to acrylonitrile (AN)., Methods: Standardized mortality ratios (SMR) were estimated based on two reference populations: the US population and a regional employee population. Exposure-response analyses were conducted using Cox regression models for cumulative and mean intensity exposure measures., Results: In the cohort of 2548 workers, 839 deaths have occurred with 91 deaths due to respiratory system cancer. Most standardized mortality ratio estimates are at or near no-effects levels. Hazard ratio (HR) estimates indicate no increased mortality risk for respiratory system cancer (adjusted HR = 0.96, 95% confidence interval: 0.74, 1.25)., Conclusions: In summary, no mortality outcome of a priori interest, principally respiratory system cancer, is associated with increased AN exposure among fiber production workers over five decades of follow-up.

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been reported in several industries, including those of the aluminum production, coal gasification, coke production, iron and steel foundries, coal tar and related products, carbon black and carbon electrodes production., Patients and Methods: This paper reviews the results from cohort studies conducted on workers exposed to PAHs in these industries, with a focus on cancers of the respiratory and urinary tract., Results: An excess risk from lung/respiratory cancers was found in most industries, the pooled relative risk (RR) being 2.58 (95% CI 2.28-2.92) for coal gasification, 1.58 (95% CI 1.47-1.69) for coke production, 1.40 (95% CI 1.31-1.49) for iron and steel foundries, 1.51 (95% CI 1.28-1.78) for roofers and 1.30 (95% CI 1.06-1.59) for carbon black production. The evidence for cancers of the bladder and of the urinary system is less consistent, with a significant increased risk only for workers in aluminum production (pooled RR = 1.29, 95% CI 1.12-1.49), coal gasification (pooled RR = 2.39, 95% CI 1.36-4.21), and iron and steel foundries (pooled RR = 1.29, 95% CI 1.06-1.57)., Conclusions: Increased risks from lung and bladder cancers were found in PAH-related occupations. These were modest in most industries, apart from those for coal gasification, and whether they are due at least partially to some bias or confounding remains open to discussion.

Based on previously published studies, this review describes the pulmonary consequences of marijuana smoking. Smoking of marijuana is significantly associated with chronic bronchitis (cough and phlegm), but it has not been firmly established whether it also leads to a reduction in lung function. Both epidemiological studies and case reports suggest that regular smokers of marijuana have a higher risk of developing malignancies in both the upper and lower airways. Smoking of marijuana contaminated with fungus spores has been reported to lead to pulmonary aspergillus infections in immunocompromised patients, and sharing of marijuana water pipes has been associated with transmission of tuberculosis.

Objective: Glutaraldehyde is a substance that represents a substantial portion of the human exposure to aldehydes in medicine and industry. Other aldehydes such as formaldehyde have been associated with increased cancer rates of the upper respiratory tract and leukemia. Our study is the only one, to our knowledge, to examine cancer rates among exposed glutaraldehyde workers., Methods: In an extended follow up using death certificates, we calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) for three cumulative exposure categories of glutaraldehyde. There were 99,730 person-years of observation among unexposed workers, 2934 person-years in the lower exposure category, < 0-100.0 parts per billion (ppb)-years, and 2805 person-years in the higher exposure category of 100.0+ ppb-years., Results: For all respiratory cancers for these exposure categories, the SMRs were 0.9 (95% CI = 0.7-1.1), 1.0 (95% CI = 0.2-3.0), and 0.3 (95% CI = 0.0-1.5). No increasing trend of SMR with increasing exposure is observed for any cause of death examined. We observed no cancers of the nasal cavity and sinus (0.03 expected), nasopharynx (0.02 expected), or leukemia (0.6 expected) among all glutaraldehyde-exposed workers., Conclusions: Although our study findings should be tempered by the small size and the potentially low prevalence of smoking among glutaraldehyde workers, we found no increased rates of respiratory tract cancer or leukemia related to glutaraldehyde exposure.

Human studies prior to 1990 have shown an association between respiratory cancer and exposure to some nickel compounds, but not to metallic nickel. Numerous reviews have examined the nature of the association between nickel compounds and respiratory cancer, but little has been published on metallic nickel. This paper reviews the animal and human cancer-related data on metallic nickel to determine whether the conclusions regarding metallic nickel reached a decade ago still apply. Based upon past and current human studies, metallic nickel appears to show little evidence of carcinogenicity when present at the same or higher concentrations than those seen in current workplace environments. By comparison, animal studies currently available have shown mixed results. A number of studies have shown evidence of carcinogenicity in animals exposed to nickel powders via injection, but other studies have shown no or inconsistent results in animals exposed via inhalation or intratracheal instillation. Further studies in animals via inhalation and humans would be helpful in elucidating the respiratory carcinogenic potential of metallic nickel.

Nose-only exposure of male and female Wistar rats to a surrogate for environmental tobacco smoke, termed room-aged sidestream smoke (RASS), to diesel engine exhaust (DEE), or to filtered, fresh air (sham) was performed 6 hours/day, 7 days/week for 2 years, followed by a 6-month post-exposure period. The particulate concentrations were 3 and 10 mg/m3. Markers of inflammation in bronchoalveolar lavage showed that DEE (but not RASS) produced a dose-related and persistent inflammatory response. Lung weights were increased markedly in the DEE (but not RASS) groups and did not decrease during the 6-month post-exposure period. Bulky lung DNA adducts increased in the RASS groups, but not in the DEE groups. Cell proliferation in the lungs was unaffected by either experimental treatment. Histopathological responses in the RASS groups were minimal and almost completely reversible; lung tumors were similar in number to those seen in the sham-exposed groups. Rats exposed to DEE showed a panoply of dose-related histopathological responses: largely irreversible and in some cases progressive. Malignant and multiple tumors were seen only in the DEE groups; after 30 months, the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5%in the high RASS groups, and 46% in the high DEE groups (sexes combined). Our results suggest that in rats exposed to DEE, but not to RASS, the following series of events occurs: particle deposition in lungs --> lung "overload" --> pulmonary inflammation --> tumorigenesis, without a significant modifying role of cell proliferation or DNA adduct formation.

Objective: To critically review and summarise all of the available epidemiological evidence, both published and unpublished, to date on the carcinogenicity of methyl methacrylate (MMA) to humans., Methods: The review focused on studies of cast acrylic sheet manufacturing workers because this industry has historically had a potential for exposure to high levels of MMA. The majority of papers for review were identified through Medline (National Library of Medicine) but there is some discussion of two cohort studies and a nested case-control study, which to date have not been published., Results: An increased risk of colorectal cancer was reported in one group of workers highly exposed to MMA and ethyl acrylate (EA) in the manufacture of acrylic sheet. Analysis of colon cancer by cumulative exposure to MMA indicated that the excess was largely confined to the group with the highest exposure. However, a large excess of colon cancer deaths occurred among workers who never worked in a job entailing more than minimal exposure. Studies of other large occupational cohorts of workers potentially exposed to MMA, including some with potentially comparable exposures, have failed to strengthen the evidence that there is a causal association between colorectal cancer and MMA exposure although one reported an excess that did not appear to be exposure-related. Excesses of cancers of the respiratory system and stomach were seen in some cohorts, but not among the acrylic sheet workers who had the increased risk of colorectal cancer., Conclusions: Excesses of respiratory, stomach and colorectal cancers were observed in some cohorts of workers exposed to MMA. There was little to suggest that MMA exposure was responsible for the excesses of respiratory and stomach cancer and it is more likely that they resulted from unexplained contributions of lifestyle exposures such as cigarette smoking and diet. An excess of colorectal cancer in one group of workers exposed to high levels of MMA and EA during the 1930s and 1940s remains unexplained. However, the lack of consistency in the results of various studies, the absence of dose response and the lack of support from animal toxicology do not provide persuasive evidence that exposure to MMA is a human carcinogen.

Background: Formaldehyde is mutagenic and, when inhaled at high concentrations, carcinogenic in rats. Some epidemiologic studies have linked occupational exposure to formaldehyde with cancers of the nose, nasopharynx, and lung, but the evidence for human carcinogenicity has been inconsistent and requires clarification., Methods: We extended by 11 years the follow-up of an existing cohort of 14 014 men employed after 1937 at six British factories where formaldehyde was produced or used. Subjects had been identified from employment records, and their jobs had been classified for potential exposure to formaldehyde. Standardized mortality ratios (SMRs) were derived using the person-years method and were compared with the expected numbers of deaths for the national population., Results: During follow-up through December 31, 2000, 5185 deaths were recorded, including two from sino-nasal cancer (2.3 expected) and one from nasopharyngeal cancer (2.0 expected). Relative to the national population, mortality from lung cancer was increased among those who worked with formaldehyde, particularly in men in the highest of four estimated exposure categories (>2 ppm) (SMR = 1.58, 95% confidence interval = 1.40 to 1.78), and the increase persisted after adjustment for local geographic variations in mortality (SMR = 1.28, 95% confidence interval = 1.13 to 1.44). However, there was a statistically nonsignificant decrease in the risk of death from lung cancer with duration of high exposure (P(trend) =.18), and this risk showed no trend with time since first high exposure (P(trend) =.99)., Conclusions: The evidence for human carcinogenicity of formaldehyde remains unconvincing. Although a small effect on sino-nasal or nasopharyngeal cancer cannot be ruled out, a possible increase in the risk of lung cancer is a greater concern.

Background: Observations of an increased incidence of cancers of the upper aero-digestive tract (pharynx, esophagus, larynx, lung) among workers of local German foundries gave rise to concern about a potentially elevated occupational risk of those cancer sites. The purpose of the study was to examine whether occupational exposure in iron foundries increases the risk of cancer., Methods: A historical cohort study of 17,708 male German production workers in 37 iron foundries who were first employed in 1950-1985 with a minimum employment period of 1 year was initiated. Employment and occupational histories were collected. Mortality was compared with that of the German general population during 1950-1993 using a new method for computing the SMR when not all causes of death are available (called SMR*)., Results: Mortality from all causes was elevated to SMR = 115.4 (95% confidence interval (CI) = 111.9-119.1), as was for total cancer (SMR* = 123.8, CI = 102.1-152.6), especially cancers of the lung (SMR* = 163.9, CI = 123.9-223.0) and liver (SMR* = 322.5, CI = 149.5-844.8), and diseases of the respiratory system (SMR* = 147.6, CI = 100.4-221.5). Non-significant elevations of mortality were also found for cancers of the mouth and pharynx (SMR* = 153.5, CI = 82.3-359.8) and larynx (SMR* = 173.1, CI = 85.5-550.5). Mortality from various causes of death was higher among workers with shorter exposure periods than among long-term employees. The elevated mortality persisted for years and decades after termination of employment., Conclusions: The results provide further evidence for an increased risk of lung cancer and possibly other cancers of the upper aero-digestive tract among foundry workers. Special attention should be paid to the strongly increased mortality from liver cancer and the mortality pattern among employees having terminated work., (Copyright 2003 Wiley-Liss, Inc.)

From experiments or epidemiological studies designed to search for a particular toxic effect, it is in general possible to determine an upper bound for that effect. This observed bounded effect level (OBEL) is defined for both positive and negative experiments. It is non-zero even for negative experiments, and it is inversely related to the size of the exposed group. The OBEL can be used to determine the linearly extrapolated bounded effect level (LEBEL) for various effect doses. Contrary to no-observed-effect' levels (NOELs), LEBEL values are designed to protect against type II (false negative) errors. It is proposed that LEBEL values replace NOELs as a tool for decision-making., (Copyright 2002 John Wiley & Sons, Ltd.)

Objective: To study the mortality experience of workers at a hydrometallurgical nickel refinery and fertiliser complex in Fort Saskatchewan, Alberta, Canada., Methods: A total of 1649 male employees of Sherritt International who worked for at least 12 continuous months during the years 1954 to 1978 at the Fort Saskatchewan, Alberta hydrometallurgical nickel refinery and fertiliser complex were followed up for an additional 17 years. Mortality was ascertained from the Canadian mortality data base maintained by Statistics Canada and covered the years 1954-95. Statistics were analysed with Monson's computer program., Results: Total mortality, when compared with the Canadian population, was significantly below expectation. Fewer deaths were found for circulatory disease, ischaemic heart disease, respiratory disease, neoplasms, digestive cancer, and accidents, poisonings, and violence. Among the 718 men in the group exposed to nickel, there were no deaths due to nasal cavity or paranasal sinus cancer. Fewer deaths were found for all causes, circulatory disease, ischaemic heart disease, neoplasms and digestive cancer. Lower death rates were observed than expected for respiratory malignancies and cancer of the bronchus and lung., Conclusion: No association was found in this study between exposure to nickel concentrate or metallic nickel in the hydrometallurgical refining process and the subsequent development of respiratory cancer.

Intratracheal instillations of 7H-dibenzo(c, g)carbazole (DBC), a tobacco smoke component, into Syrian golden hamsters, resulted in preneoplastic lesions and benign and malignant respiratory neoplasms. Neoplastic progression was associated with specific changes in the extracellular matrix (ECM), dependent on the stage of tumor development. DBC-induced tracheobronchial squamous metaplasia was associated with an increase in collagen type I and type III deposition in the subepithelial ECM, as observed by computer-assisted image analysis of immunohistochemical staining for the aminoterminal propeptides of collagen type I (PINP) and collagen type III (PIIINP). Increased collagen matrix synthesis was detected in dysplasia by in situ hybridization of alpha1(I) mRNA for collagen I and alpha1(III) mRNA for collagen type III after continued exposure to DBC. In well-differentiated squamous cell carcinomas with an expansive growth pattern, collagen deposition increased, as did fiber size. In moderately differentiated neoplasms, basement membrane (BM) destruction and invasion was associated with a destructive growth pattern and decreases in collagen synthesis and the deposition of new collagen. Preserved deposition of mature collagen was detected by staining for the telopeptide of collagen type I propeptide. In less differentiated tumors, ECM development was minimal, with few and small fibers, possibly explaining the rapid development of these neoplasms. Transforming growth factor beta (TGFbeta1) immunoreactivity was increased in hyperplastic epithelium and well differentiated neoplasms and decreased in dysplasia and less differentiated squamous cell carcinomas, while TGFbeta2 and TGFbeta3 expression was also distinct in neoplastic cells. Collagen synthesis and epithelial differentiation were associated with an increased number of myofibroblasts in the ECM and with increased TGFbeta3 immunoreactivity in differentiated cells and in the matrix. The nature of the composition of the ECM was related to neoplastic growth and progression when analyzed by computer-associated image analysis, revealing alterations in collagen structure, size, and shape.

As part of the 1992 update of an historical cohort study of 32,110 workers employed for at least 1 year in any of 10 US fiberglass manufacturing plants, a nested case-control study was done in which data on tobacco smoking were obtained for 631 male case subjects with respiratory system cancer (RSC) and 570 control subjects matched on age and year of birth. In this more extensive analysis of the nested case-control data, we provide a detailed assessment of the most prominent findings from the initial report. We expand the scope of the analysis to consider quantitative measures of exposure to respirable fibers (RFib), formaldehyde (FOR), and silica (Sil) and consider these and other exposures together in the same model. We investigate the functional form of possible exposure-response relationships between RSC risk, RFib, and FOR. In addition, we address the statistical issues of collinearity, effect modification, and potential confounding by coexposures. All analyses are adjusted for smoking. Neither measure of exposure to RFib (average intensity of exposure or cumulative exposure) was statistically significantly associated with RSC risk in any of the hundreds of fractional polynomial models considered. This more extensive analysis has substantiated our initial finding of no apparent exposure-response relationship between RSC risk and either cumulative or average intensity of exposure to RFib at the levels experienced by these workers. This study provides some evidence of increased RSC risk among workers at the higher observed levels of average intensity of exposure to FOR and/or Sil. No positive associations were identified between RSC risk and any of the other exposures considered in this case-control study.

As part of our ongoing mortality surveillance program for the US man-made vitreous fiber (MMVF) industry, we examined mortality from malignant mesothelioma using data from our 1989 follow-up of 3478 rock/slag wool workers and our 1992 follow-up of 32,110 fiberglass workers. A manual search of death certificates for 1011 rock/slag wool workers and 9060 fiberglass workers revealed only 10 death certificates with any mention of the word "mesothelioma." A subsequent review of medical records and pathology specimens for 3 of the 10 workers deemed two deaths as definitely not due to mesothelioma and one as having a 50% chance of being caused by mesothelioma. Two other deaths, for which only medical records were available, were given less than a 50% chance of being due to mesothelioma. Eight of the 10 decedents had potential occupational asbestos exposure inside or outside the MMVF industry. We also estimated the mortality risk from malignant mesothelioma in the cohort using two cause-of-death categorizations that included both malignant and benign coding rubrics. Using the more comprehensive scheme, we observed overall deficits in deaths among the total cohort and fiberglass workers and an overall excess among rock/slag wool workers. The excess in respiratory system cancer is largely a reflection of elevated lung cancer risks that we attributed mainly to confounding by smoking, to exposures outside the MMVF industry to agents such as asbestos, or to one or more of the several co-exposures present in many of the study plants (including asbestos). The second scheme, which focused on pleural mesothelioma in time periods when specific malignant mesothelioma coding rubrics were available, classified only one cohort death as being caused by malignant mesothelioma, compared with 2.19 expected deaths (local county comparison). We conclude that the overall mortality risk from malignant mesothelioma does not seem to be elevated in the US MMVF cohort.

To date, the US cohort study of man-made vitreous fiber workers has provided no consistent evidence of a relationship between man-made vitreous fiber exposure and mortality from malignant or non-malignant respiratory disease. Nevertheless, there have been small, overall excesses in respiratory system cancer (RSC) among workers from the fiberglass and rock/slag wool production plants included in the study that were unexplained by estimated worker exposures to respirable fiber or other agents present in the plants. The present investigation was designed to provide a quantitative estimate of the extent to which the overall excess in RSC mortality observed at the total cohort level among male fiberglass and rock/slag wool workers is a result of the positive confounding effects of cigarette smoking. Because cigarette-smoking data were neither available nor obtainable at the individual level for all members of the fiberglass and rock/slag wool cohorts, we used the "indirect" method to adjust RSC standardized mortality ratios (SMRs) at the group (cohort and plant) level. Our adjustment suggested that cigarette smoking accounts for all of the 7% and 24% excesses in RSC observed, respectively, for the male fiberglass and rock/slag wool cohorts in the latest mortality updates. The same conclusion was reached regardless of which of several alternative formulations were used to adjust local rate-based RSC SMRs. We found that our smoking adjustments were robust with respect to several alternative characterizations and (with the exception of one fiberglass plant) produced adjusted RSC SMRs that were lower than their unadjusted counterparts. Further, all statistically significantly elevated unadjusted SMRs were reduced to not statistically significant levels. These results reaffirm that RSC SMRs based on US and local rates must take into account the potential confounding effects of cigarette smoking. They also suggest that the use of local county mortality rate-based SMRs may not help to adjust for cigarette smoking to the degree suggested by some investigators.

The most recent findings of our nested case-control study of respiratory system cancer (RSC) among male fiberglass workers showed some evidence of elevated RSC risk associated with non-baseline levels of average intensity of exposure (AIE) to respirable fibers (RFib). When adjusted for smoking, this was not statistically significant, and no trend was apparent with increasing levels of exposure. Similar findings for RSC were noted for both cumulative exposure (Cum) and AIE to formaldehyde (FOR). In this reanalysis of our nested case-control study, we explored a possible exposure-response relationship between RSC and exposure to RFib or FOR using exposure weighting as an alternative characterization of exposure. Because of the uncertainties in selecting an appropriate exposure-weighting scheme, a range of plausible time lags and unlagged/lagged time windows was considered. As in the initial analysis of the nested case-control study, RFib and FOR exposures were categorized at the deciles of the RSC case distribution. For none of the exposure weighting schemes considered did we observe an increasing RSC risk with increasing levels of RFib&#95;Cum or RFib&#95;AIE. The exposure-weighted estimated risk ratios (RR) for both RFib&#95;Cum and RFib&#95;AIE were generally lower than those obtained from an unweighted model. For FOR&#95;Cum, RRs were generally lower for the time-lagged and unlagged time window models than for the unweighted models, although some decile-specific RRs were higher for the lagged time window models. The exposure-weighted RRs for FOR&#95;AIE were generally lower than the unweighted RRs for all of the weighting schemes considered. This reanalysis in terms of categorized exposures reveals no exposure-response relationships that were undetected in the original analysis where unweighted exposure measures were used. In the schemes considered, exposure weighting generally reduced the estimated risk of RSC.

Objective: This study evaluates whether wood dust and/or wood preservatives develop a carcinogenic potential against the tissues of the airways of rats., Methods: The formation of tumors of the respiratory tract after exposure to wood dust was studied in six groups of approximately 60 female Fischer 344 rats exposed by long-term inhalation to mean concentrations of (1) 18 mg/m3 of untreated oak wood dust, (2) wood preservatives containing ca. 1 microgram/m3 lindane and 0.2 microgram/m3 of pentachlorophenol (PCP) in the exposure air, or lindane and 18 micrograms/m3 of PCP (group lindane/PCP vapors, and group oak wood treated with lindane/PCP), (3) 21 or 39 micrograms/m3 of sodium dichromate (calculated as CrO3, group chromate aerosol and group oak wood with chromate), and 72 micrograms/m3 of N-nitrosodimethylamine vapors as positive control. The negative control group consisted of 115 animals (sham-exposed)., Results: Tumors of the nasal cavity developed in two rats exposed to chromate aerosol or in combination with wood dust (2/102, 2%). Malignant tumors of the lower respiratory tract were induced only in exposed groups of rats (three adenocarcinomas of the lung and four bronchiolar lung carcinomas, 7/254, 2.8%). More respiratory tract tumors were observed in rats exposed to chromate or wood with chromate (5/102, 5%), also in groups exposed to oak wood dust (oak untreated, oak + chromate, oak + lindane/PCP; together 5/155, 3.2%). Analysis of 'unpreserved' oak wood dust revealed up to 5 micrograms/m3 of chromate. When this exposure was taken into account, eight of nine animals with respiratory tract tumors (including nasal cavity) had exposure to chromate, while only one tumor occurred in the group lindane/PCP. Otherwise the incidence of systemic tumors was increased in animals exposed to lindane/PCP, due in particular to a significantly increased incidence of liver tumors (OR = 3.7; 1.24-11.3; P = 0.019). Fatal (mucoepidermoid) tumors were induced by N-nitrosodimethylamine (NDMA) in the positive control (14/46, 30%). No such tumors of the respiratory tract were observed in the negative control., Conclusions: Tumors in the respiratory tract were found only in exposed animals, predominantly in the groups which inhaled oak wood dust and chromate stain. Chromate may play a decisive role for the etiology of tumors of the nasal cavity in wood workers. This assumption should be supported by further dose-response studies.

A case-control study on respiratory cancers was conducted in New Caledonia (South Pacific), where a high incidence of malignant pleural mesothelioma had been observed. The disease pattern suggested an environmental exposure to asbestos. The first results showed that, in some areas, tremolite asbestos derived from local outcroppings was used as whitewash (locally named "pö"). All cases diagnosed between 1993 and 1995 (including 15 pleural mesotheliomas, 228 lung cancers, and 23 laryngeal cancers) and 305 controls were included in the study. Detailed information on past or present use of the whitewash, residential history, smoking, diet, and occupation was collected. The risk of mesothelioma was strongly associated with the use of the whitewash (odds ratio (OR) = 40.9; 95% confidence interval (CI): 5.15, 325). All Melanesian cases had been exposed. Among Melanesian women, exposure to the whitewash was associated with an increased risk of lung cancer (OR = 4.89; 95% CI: 1.13, 21.2), and smokers exposed to po had an approximately ninefold risk (OR = 9.26; 95% CI: 1.72, 49.7) compared with women who never smoked and had never used the whitewash. In contrast, no association was noted between exposure to pö and lung cancer risk among Melanesian men, probably because of lower exposure levels. Among non-Melanesians, the numbers of exposed subjects were too small to assess the effect of exposure to po. There was no indication of elevated risks for the other cancer sites.

The aim of the cohort retrospective study was to analyze and evaluate the influence of certain factors (age, profession, smoking) on the characteristics and the incidence rate of the upper respiratory tract diseases (URTDs) in the occupational contact with ammonium. Subjects were 180 men, divided into 3 professional groups. The average shift concentrations of ammonium were measured in the permanent work places and individually by personal passive dosemeters. The URTDs were classified into 15 groups according to localization and the stage of the inflammatory process. The relationships "time-response" and "dose (concentration)-response" were determined. The factor "cumulative exposure" was used in order to evaluate the actual noxious effect of NH3 on the mucose of the upper respiratory tract (URT). There was a statistically reliable difference found in the incidence rate of atrophic rhinitis, hypertrophic pharyngitis and laryngitis, and neoplasms of the URT in the workers with the highest cumulative exposure. For this group relative risk was 4.00, 2.22, 3.20 and 4.00, respectively, with 95% Cl. The "cumulative exposure" factor gives the best proofs for the toxic effect of ammonium and a possibility for assessment of the relative risk.

Fermented milk products might be used for cancer chemoprevention due to their putative anticarcinogenic and antitumor activities. The diet was supplemented with freeze-dried milk fermented by Lactobacillus bulgaricus strain LBB.B 144 (product FFM.B 144) added throughout the experiment at doses of 1.3 g and 2.5 g per rat, 5 times a week starting 3 weeks before the first carcinogen injection. This treatment significantly inhibited, by 26.2-28.6% and by 34.2%, the total intestinal carcinogenesis induced by 1,2-dimethylhydrazine (DMH, 21 mg/kg, s.c., once per week for 20 weeks) in male and female BD6 rats, respectively. FFM.B144 decreased the tumor incidence and multiplicity in large bowel, caecum, and duodenum. Protective effects were better expressed in female animals, with exception of that observed in duodenum. Supplementation of diet with freeze-dried milk fermented by Lactobacillus bulgaricus strain LBB.B5 (product FFM.B5) inhibited DMH-induced carcinogenesis only in the large bowel, but had no significant protective effect when all intestinal tumors were taken into account. However, both freeze-dried products favorably shifted the differentiation of large bowel tumors by increasing the proportion of benign and highly differentiated malignant tumors and decreasing in parallel the number of poorly differentiated carcinomas without influencing the tumor size. A lower number of cases with visible mesenterial metastasis was also observed in FFM-treated rats. In addition, both FFM.B 144 and FFM.B5 significantly inhibited, by 26-33%, the induction in the same rats of ear-duct tumors. FFM.B144 but not FFM.B5 was also effective in inhibiting the tracheal carcinogenesis induced in Syrian golden hamsters by diethylnitrosamine (DEN, 100 mg/kg, two s.c. injections), the protective effect being better expressed in female animals. The anticarcinogenic potential of some fermented milk products might be exploited in chemoprevention of cancer in humans.

Objective: To update the mortality experience of a cohort of 8508 workers with potential exposure to acrylamide at three plants in the United States from 1984-94., Methods: Analyses of standardised mortality ratios (SMR) with national and local rates and relative risk (RR) regression modelling were performed to assess site specific cancer risks by demographic and work history factors, and exposure indicators for acrylamide and muriatic acid., Results: For the 1925-94 study period, excess and deficit overall mortality risks were found for cancer sites of interest: brain and other central nervous system (CNS) (SMR 0.65, 95% confidence interval (95% CI) 0.36 to 1.09), thyroid gland (SMR 2.11, 95% CI 0.44 to 6.17), testis and other male genital organs (SMR 0.28, 95% CI 0.01 to 1.59), and cancer of the respiratory system (SMR 1.10, 95% CI 0.99 to 1.22); however, none was significant or associated with exposure to acrylamide. A previously reported excess mortality risk of cancer of the respiratory system at one plant remained increased among workers with potential exposure to muriatic acid (RR 1.50, 95% CI 0.86 to 2.59), but was only slightly increased among workers exposed or unexposed to acrylamide. In an exploratory exposure-response analysis of rectal, oesophageal, pancreatic, and kidney cancer, we found increased SMRs for some categories of exposure to acrylamide, but little evidence of an exposure-response relation. A significant 2.26-fold risk (95% CI 1.03 to 4.29) was found for pancreatic cancer among workers with cumulative exposure to acrylamide > 0.30 mg/m3.years; however, no consistent exposure-response relations were detected with the exposure measures considered when RR regression models were adjusted for time since first exposure to acrylamide., Conclusion: The contribution of 1115 additional deaths and nearly 60,000 person-years over the 11 year follow up period corroborate the original cohort study findings of little evidence for a causal relation between exposure to acrylamide and mortality from any cancer sites, including those of initial interest. This is the most definitive study of the human carcinogenic potential of exposure to acrylamide conducted to date.

Background: Tobacco smoking is an established risk factor for cancers of the upper aerodigestive tract, and measurement of chromosomal aberrations, i.e., chromatid breaks, induced in lymphocytes in vitro by bleomycin has been shown to be a predictor of risk for these cancers. In a case-control study, we recruited case subjects who were previously treated with surgery and/or radiotherapy for stage I or stage II squamous cell carcinoma of the head and neck to test the hypothesis that lymphocytic chromatid breaks induced by benzo[a]pyrene diol epoxide (BPDE), a tobacco mutagen, may also be associated with risk of developing cancers of the upper aerodigestive tract., Methods: Case subjects were matched to control subjects on the basis of age, sex, ethnicity, and smoking status. Primary lymphocytes from 67 case subjects and 81 control subjects were treated with 2 microM BPDE for 24 hours, and the frequency of induced chromatid breaks was determined. All statistical tests were two-sided., Results: Lymphocytes from case subjects compared with lymphocytes from control subjects showed significantly more breaks per cell induced by BPDE (mean+/-standard deviation, 0.77+/-0.38 versus 0.49+/-0.25; P<.001). Lymphocytes from 64.2% of case subjects were sensitive to BPDE (using a cutoff value of > or =0.60 break per cell). Subjects in the highest quartile of chromatid breaks had an approximately 20-fold increased risk of cancer compared with those in the lowest quartile after adjustment for age, sex, ethnicity, and smoking status. The association between BPDE sensitivity and cancer risk was higher in former smokers than in current smokers and higher in younger patients than in older patients. Subjects with sensitivity to both BPDE and bleomycin were at a 19.2-fold increased risk of cancer compared with those who were not sensitive to either agent., Conclusions: Mutagen sensitivity assays may aid in identifying individuals at risk of cancer, and use of parallel assays with two mutagens may improve risk predictability.

To examine the risk of upper aerodigestive tract cancers (UADC: oral cavity, pharynx, larynx, and esophagus) associated with dietary heterocyclic amine (HCA) exposure, a case-control study involving 140 cases and 286 controls was conducted in Montevideo, Uruguay. Beef and red meat intakes were positively associated with risk of UADC [odds ratio (OR) for red meat intake = 2.8, 95% confidence interval (CI) = 1.4-6.0], whereas no association was observed with white meat (poultry plus fish) intake. When meat intake was examined by cooking method, no association was observed for fried meat. On the other hand, broiled and boiled meat were associated with a significant increase in risk of UADC (OR for broiled meat = 2.0, 95% CI = 1.0-4.3). Total HCA intake was associated with an increased risk (OR = 2.2, 95% CI = 1.1-4.2) of UADC. The HCA effect was similar among the different cancer sites.

In this study, we summarize 47 epidemiologic studies related to formaldehyde exposure and use meta-analytic techniques to assess findings for cancers of the lung, nose/nasal sinuses, and nasopharynx. Our analyses indicate that workers with formaldehyde exposure have essentially null findings for lung cancer and a slight deficit of sinonasal cancer. Nasopharyngeal cancer rates were elevated moderately in a minority of studies. Most studies, however, did not find any nasopharyngeal cancers, and many failed to report their findings. After correcting for underreporting, we found a meta relative risk of 1.0 for cohort studies. Case-control studies had a meta relative risk of 1.3. Our review of the exposure literature indicated that the nasopharyngeal cancer case-control studies represented much lower and less certain exposures than the cohort studies. We conclude that the available studies do not support a causal relation between formaldehyde exposure and nasopharyngeal cancer. This conclusion conflicts with conclusions from two previous meta-analyses, primarily because of our consideration of unreported data.

This review identified and evaluated 25 epidemiologic studies pertaining to the carcinogenicity of mists containing sulfuric acid (MSA). Few studies were designed with acid mists as the principal exposure under investigation, and in all studies exposure assessment was limited. The results of the follow-up studies from industries with high or moderate exposure potential and the case-control studies indicate, in aggregate, a moderate association between MSA and larynx cancer. The data suggest a dose-response relationship. However, many of the results from individual studies are imprecise, and confounding by smoking, alcohol, and other occupational agents is not adequately adjusted for. The biologic plausibility and the possible carcinogenic mechanism remain uncertain. There is little evidence in support of a causal relationship between exposure to MSA and lung cancer. Information is inadequate for drawing any meaningful inference about the association between exposure to MSA and nasal cancer.

The prevalence of cigarette smoking is higher among African Americans than among whites. African Americans have higher rates of lung cancer than whites, although they smoke fewer cigarettes. To explore this black-white difference in lung cancer rates, I examine various aspects of tobacco use in African-American smokers, including the age of initiation of smoking, quantity of cigarettes smoked, quit rates, level of nicotine dependence, biochemical differences, and brand preferences, specifically menthol brand cigarettes. I also review briefly the sequelae of patterns of tobacco use, including rates of lung and other tobacco-related cancers. A preference for mentholated cigarettes by African Americans is well documented and is one of the most striking differences between African-American and white smokers. Menthol brand preference has been investigated in an attempt to explain the black-white differences in rates of cancers of the lungs and the upper respiratory and digestive tracts. Also, studies have evaluated smoking behavior both with and without menthol and have explicitly examined the question of whether menthol use helps explain the black-white difference in lung cancer rates. The results of these studies are so far inconclusive with regard to the use of menthol and the risk of lung cancer developing. I provide practical suggestions for clinicians in counseling African-American smokers to quit smoking and to maintain a nonsmoking status.