Carcinogenicity of occupational nickel exposures: an evaluation of the epidemiological evidence

The health effects documented in recent epidemiological studies of nickel-exposed workers relate to past exposures, mostly of unknown magnitude and unknown nickel speciation. Major studies have been carried out at nickel smelters and refineries. Although each study suffers from some deficiencies, as is common in such retrospective studies, the findings in concert strongly indicate that nickel emitted from the calcining and sintering operations is a potent carcinogen resulting in nasal and pulmonary cancers. Some risk appears to be present in other refinery operations, such as Orford furnace, copper and nickel sulfate, and crushing departments, and one study has suggested a risk associated with soluble nickel compounds in the electrolysis department, although this finding has not been confirmed. Only one study demonstrated an exposure-response relationship, which, however, was not statistically significant. Other studies showed a relationship between increased exposure time and augmented cancer risk. In nickel-using industries, no excess cancer related to nickel exposures has been demonstrated beyond doubt; concurrent exposures to other potential carcinogens constitute a confounding variable that makes interpretation difficult. However, the studies have not excluded that a cancer hazard may be present outside the nickel-producing facilities. Further, case-referent studies of respiratory cancers suggest that a nickel-related etiology may well exist in the nickel-using industries. As the exact identity of the carcinogenic form or forms of nickel remains unknown, exposure to all nickel compounds should be kept as low as reasonably achievable.     

Can lung cancer risk among nickel refinery workers be explained by occupational exposures other than nickel?

BACKGROUND: Exposures in nickel refineries represent complex chemical mixtures, but only the effect of nickel has been evaluated quantitatively in epidemiologic studies of nickel workers. METHODS: For a Norwegian refinery, time- and department-specific exposure estimates were developed for arsenic, sulfuric acid mists, and cobalt in air on the basis of personal measurements and chemical data on raw materials and process intermediates. Exposure to asbestos, as well as employment in high-risk occupations outside the refinery, were assessed. We conducted a case-control study nested in a cohort of refinery workers, with 213 cases (diagnosed 1952-1995) and 525 age-matched controls. We analyzed lung cancer risk, adjusted for smoking, by cumulative exposure and duration of work. RESULTS: There was a substantial association between cumulative exposure to water-soluble nickel and lung cancer risk. Weaker effects were suggested for exposure to arsenic at the refinery and for occupational exposures outside the refinery for 15 years or more. No detectable excess risk was found for refinery exposure to asbestos or sulfuric acid mists, and no dose-related increase in risk was seen from cobalt. CONCLUSIONS: Exposure to water-soluble nickel remained the most likely explanation for the excess lung cancer risk in the cohort. Other occupational exposures did not confound the strong dose-related effect of nickel to any appreciable degree.     

A review and meta-analysis of formaldehyde exposure and pancreatic cancer

BACKGROUND: Most reviews on the carcinogenicity of formaldehyde have focused on cancers of the respiratory tract. Two recent studies have suggested that exposure to formaldehyde may increase the risk for pancreatic cancer. METHODS: We examine 14 epidemiology studies of workers exposed to formaldehyde where pancreatic cancer rates were reported and use meta-analytic techniques to summarize the findings. We also rank formaldehyde exposures for the industries in these studies. RESULTS: We found a small increase of pancreatic cancer risk in the studies overall (meta Relative Risk [mRR] 1.1, 95%CI 1.0-1.3); however, this increased risk was limited to embalmers (mRR 1.3, 95%CI 1.0-1.6) and pathologists and anatomists (mRR 1.3, 95%CI 1.0-1.7). There was no increased risk among industrial workers (mRR 0.9, 95%CI 0.8-1.1) who on average had the highest formaldehyde exposures. CONCLUSIONS: A small increased risk of pancreatic cancer from formaldehyde exposure cannot be ruled out from the studies examined. However, the null findings among industrial workers and the lack of biological plausibility would argue against formaldehyde as a cause. The increased risk of pancreatic cancer among embalmers, pathologists, and anatomists may be due to a diagnostic bias or to occupational exposures other than formaldehyde in these professions.     

Critical review of the epidemiology literature on the potential cancer risks of methyl methacrylate

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.     

Occupational exposure to carcinogens in Finland.

Finland has kept a registry on the manufacture and use of carcinogenic agents involving occupational exposure since 1979. Employers must report annually to the labor safety authorities the employees who have been exposed to carcinogens and provide information on carcinogenic agents produced, used, or formed. Out of 131 substances or groups of agents listed as carcinogenic, occupational exposure to 78 of them was reported in 1987. About half of the agents reported were used or produced in industry and half were handled on a laboratory scale. About 15,000 employees from 1,700 work departments were reported to the registry; 17% of them were women. The number of workers reported in 1987 accounted for 0.6% of the total work force. It has been estimated that at least 60,000 workers are exposed annually to carcinogens in Finland. The three most prevalent exposures--hexavalent chromium compounds, nickel and its inorganic compounds, and asbestos--accounted for over 60% of all exposed workers; only five carcinogenic chemicals were produced in Finland in 1987.     

Evidence of carcinogenicity in humans of water-soluble nickel salts

Background  

Increased risks of nasal cancer and lung cancer in nickel refiners have been investigated scientifically and discussed since they were detected in the 1930s. Nickel compounds are considered to be the main cause of the cancer excess. Parts of the nickel producing industry and their consultants oppose the classification of water-soluble nickel salts as human carcinogens, and argue that the risk in exposed workers should be ascribed to other occupational exposures and smoking.     

Characterization of occupational exposures to cleaning products used for common cleaning tasks-a pilot study of hospital cleaners

Background  

In recent years, cleaning has been identified as an occupational risk because of an increased incidence of reported respiratory effects, such as asthma and asthma-like symptoms among cleaning workers. Due to the lack of systematic occupational hygiene analyses and workplace exposure data, it is not clear which cleaning-related exposures induce or aggravate asthma and other respiratory effects. Currently, there is a need for systematic evaluation of cleaning products ingredients and their exposures in the workplace. The objectives of this work were to: a) identify cleaning products' ingredients of concern with respect to respiratory and skin irritation and sensitization; and b) assess the potential for inhalation and dermal exposures to these ingredients during common cleaning tasks.     

Hazardous air pollutants and asthma

Asthma has a high prevalence in the United States, and persons with asthma may be at added risk from the adverse effects of hazardous air pollutants (HAPs). Complex mixtures (fine particulate matter and tobacco smoke) have been associated with respiratory symptoms and hospital admissions for asthma. The toxic ingredients of these mixtures are HAPs, but whether ambient HAP exposures can induce asthma remains unclear. Certain HAPs are occupational asthmagens, whereas others may act as adjuncts during sensitization. HAPs may exacerbate asthma because, once sensitized, individuals can respond to remarkably low concentrations, and irritants lower the bronchoconstrictive threshold to respiratory antigens. Adverse responses after ambient exposures to complex mixtures often occur at concentrations below those producing effects in controlled human exposures to a single compound. In addition, certain HAPs that have been associated with asthma in occupational settings may interact with criteria pollutants in ambient air to exacerbate asthma. Based on these observations and past experience with 188 HAPs, a list of 19 compounds that could have the highest impact on the induction or exacerbation of asthma was developed. Nine additional compounds were identified that might exacerbate asthma based on their irritancy, respirability, or ability to react with biological macromolecules. Although the ambient levels of these 28 compounds are largely unknown, estimated exposures from emissions inventories and limited air monitoring suggest that aldehydes (especially acrolein and formaldehyde) and metals (especially nickel and chromium compounds) may have possible health risk indices sufficient for additional attention. Recommendations for research are presented regarding exposure monitoring and evaluation of biologic mechanisms controlling how these substances induce and exacerbate asthma.     

Occupational health and safety risks and potential health consequences perceived by U.S. workers, 1985

Data from the Health Promotion and Disease Prevention Questionnaire, part of the 1985 National Health Interview Survey, were used to report workers' perceptions of occupational risk in their present jobs. This information will be used to monitor progress between 1985 and 1990 toward achieving broad goals in health promotion and disease prevention. The proportions of currently employed persons who perceived exposure to health-endangering substances, work conditions, or risks of injuries were reported for age, race, sex, and occupation groups. Occupational groups were further characterized by the proportion of men and women who reported specific exposures (such as exposure to chemicals or to loud noise) and specific health consequences of exposure (such as risk of developing cancer or hearing impairment). Greater proportions of men than women reported perceived risk from exposure to health-endangering substances, work conditions, and injuries in their present job. Also, a greater proportion of workers perceived risk of injury in their present job than other occupational risk categories. The greatest proportions of perceived exposure to occupational risk were reported by farm operators and managers, police and firefighters, and by workers in forestry and fishing occupations. Among workers reporting perceived exposures, chemicals, noise, and risk of injuries from vehicles were cited by the greatest proportion of workers, as were such health consequences as lung and respiratory problems and hearing impairment. Data from this study may be used to target employment groups for health promotion or education and to develop indepth studies of specific occupational groups to reduce or prevent risk at the worksite.     

Work-related asthma and implications for the general public

Asthma has been increasing over the last two decades in the United States. The onset of asthma has also been increasingly reported as a result of occupational exposures to over 350 different agents. Work-related asthma (WRA) has become the most frequently diagnosed occupational respiratory illness. Epidemiologic studies from the United States reported WRA incidence rates of 29-710 cases per million workers per year and suggest that 10-25% of adult asthma is work related. Much can be learned about asthma in the general population from investigations of asthma in the workplace. Surveillance of WRA continues to highlight an important role for low molecular weight chemical sensitizers, as well as high molecular weight antigens. Additionally, recent reports implicate mixed exposures, including commercial cleaning solutions, solvents, and other respiratory irritants, as well as contamination in nonindustrial environments, including schools and offices. Investigations of WRA have demonstrated a clear dose-related increase in sensitization and symptoms for exposures to both chemical and protein sensitizers. High proportions of exposed working groups can be affected. Skin exposures may affect the likelihood of individuals developing respiratory symptoms. Atopy increases the risk of sensitization and illness from workplace exposure to antigens but not to chemical sensitizers. Irritant exposures can act as adjuvants among individuals exposed to sensitizing substances, increasing the proportion who become sensitized. Atopy might also be a result of irritant exposures in some persons. Occupational asthma often has important long-term adverse health and economic consequences but can resolve completely with timely control of exposures. Detailed study of such asthma "cures" may prove useful in understanding factors that influence asthmatic airway inflammation in the general population.     

Possible causes of increased lung cancer incidence among butchers and slaughterhouse workers

An excess of lung cancer among butchers and slaughterhouse workers has been reported in several record-linkage studies. In this case-referent investigation on the possibility of occupational exposures being related to the lung cancer excess, cases and referents were selected from butchers and slaughterhouse workers registered in the Swedish national census of 1960. The case group comprised all men in the study population dying from lung cancer between 1971 and 1982. Two reference groups were formed, ie, all individuals dying from other cancers and a random sample of all dead men in the study population during the same time period. The history of occupations, occupational exposures, and smoking habits was obtained from the next-of-kin by questionnaire. None of the occupational exposures that were studied (work with live animal care, in the bleeding area, on the killing floor, or with meat cutting, processing, curing, smoking, chilling and packaging) were associated with an increased lung cancer rate. Tobacco smoking habits may have contributed to the overall excess of lung cancer found previously for this occupational group.     

Experience with early detection of toluene diisocyanate-associated occupational asthma

There is good reason to expect that regular respiratory surveillance and early removal of workers who develop toluene diisocyanate (TDI)-associated occupational asthma can effectively protect these workers from accelerated pulmonary function decline. Application of this simple principle in operating industrial workplaces presents numerous challenges. The experience of one corporation is presented. One approach is to remove from future diisocyanate work, all workers who develop symptoms consistent with occupational asthma. However, the experience within this one corporation concurs with earlier, more carefully controlled investigations that such a strategy would be unduly restrictive of workers' occupational options. Fewer than half of the workers, who might have triggered such a practice, have required removal after more thorough occupational medical evaluation. Diisocyanates are such well known occupational asthmagens that other exposures tend to be ignored when considering respiratory health problems in a workplace. A small series of workers with work-related respiratory symptoms will be discussed. The usual industrial hygiene air monitoring demonstrated excellent control of the polyisocyanate hazard. Further investigation demonstrated poor control of a mold-release solution. Control of that exposure has allowed previously restricted workers to return to their former work making polyurethane parts. The number of cases available for analysis and discussion from this single, albeit large, corporation is small. Significant advances in understanding whether time-weighted average (TWA), task-specific, or dermal exposures to TDI and other polyisocyanates are most hazardous will require either many more years of experience within one corporation, or pooling of experience across the industry.     

Biological monitoring of nickel

Measurements of nickel in body fluids, excreta, and tissues from humans with occupational, environmental, and iatrogenic exposures to nickel compounds are comprehensively reviewed. Correlations between levels of human exposures to various classes of nickel compounds via inhalation, oral, or parenteral routes and the corresponding concentrations of nickel in biological samples are critically evaluated. The major conclusions include the following points: Measurements of nickel concentrations in body fluids, especially urine and serum, provide meaningful insights into the extent of nickel exposures, provided these data are interpreted with knowledge of the exposure routes, sources, and durations, the chemical identities and physical-chemical properties of the nickel compounds, and relevant clinical and physiological information, such as renal function. Nickel concentrations in body fluids should not, at present, be viewed as indicators of specific health risks, except in persons exposed to nickel carbonyl, for whom urine nickel concentrations provide prognostic guidance on the severity of the poisoning. In persons exposed to soluble nickel compounds (e.g., NiCl2, NiSO4), nickel concentrations in body fluids are generally proportional to exposure levels; absence of increased values usually indicates non-significant exposure; presence of increased values should be a signal to reduce the exposure. In persons exposed to less soluble nickel compounds (e.g., Ni3S2,NiO), increased concentrations of nickel in body fluids are indicative of significant nickel absorption and should be a signal to reduce the exposures to the lowest levels attainable with available technology; absence of increased values does not necessarily indicate freedom from the health risks (e.g., cancers of lung and nasal cavities) associated with exposures to certain relatively insoluble nickel compounds.     

Investigations on the quantitative determination of nickel and chromium in human lung tissue

Summary Nickel (Ni) and some of its relatively insoluble compounds as well as chromates may be able to induce cancer in the region of the lungs, as well as in the nose and paranasal sinuses after occupational exposure. Latency periods may amount to 20 years and more. The results of recent investigations have shown that these metals cumulate in the lung tissue after inhalation of relatively insoluble chromium and nickel compounds. The quantitative detection of these heavy metals in samples of pulmonary tissue hence permits the amount of past exposure to be estimated. To establish the normal values, samples of pulmonary tissue from 30 normal subjects were investigated for chromium and nickel content. The samples were taken from different segments and lobes of the lungs, taking topographical anatomical criteria into consideration. In addition, 15 persons who had formerly been exposed to nickel and/or chromium (11 nickel refinery workers, of whom 10 had died of lung cancer, 2 stainless steel welders, 1 foundry worker, 1 electrical technician) were also investigated. From the results of 495 tissue samples from the normal group, median chromium concentrations between 130 and 280 ng/g were calculated, with median nickel concentrations of 20–40 ng/g (wet weight). If these values are related to the nickel concentrations measured in refinery workers, values 112-5,860 times higher were found. The concentrations were about 500 times higher than normal for nickel, and about 60 times higher than normal for chromium in the stainless steel welders. For the foundry workers who died of lung cancer, chromium and nickel concentrations in the normal range were calculated, with the exception of the nickel concentrations in the upper and lower lobes of the right lung. The very high nickel concentrations found in the samples of lung tissue from former nickel refinery workers should be regarded as a guideline with regard to the appraisal of the causal relationship between lung cancer and occupational exposure to relatively insoluble nickel compounds. This result is also supported by epidemiological investigations on this subgroup and must thus be considered etiologically conclusive. For the welders, chromium and nickel concentrations were found that were markedly above normal, but as yet there is no epidemiologically reliable verification for the increased occurrence of malignancies in this occupational group. On the basis of present scientific knowledge, no indications were found of relevant chromium and/or nickel exposure of the lung tissue that might be able to induce lung cancer in either foundry workers or for electric technicians.Dedicated to Professor V. Becker on his 65th birthday     

Working conditions and occupational pathology in electrolytic nickel refinery workers

The working conditions during electrolytic nickel refinery correspond to Class 3, Grade 3-4, which may give rise to health problems in workers of all occupations employed in this production. Their risk and prevalence are significantly higher in the most exposed occupational group, such as electrolysis workers (40.1% of all cases). The structure of occupational diseases is dominated by respiratory diseases (68.8%), mainly due to exposure to aerosols of nickel compounds. It is concluded that working conditions and medical prevention interventions should be improved for this group of workers.     

Health effects of working in pulp and paper mills: Exposure,obstructive airways diseases,hypersensitivity reactions,and cardiovascular diseases

Workers in the pulp and paper industry are exposed to different substances, such as hydrogen sulfide and other reduced sulfur compounds, chlorine, chlorine dioxide, sulfur dioxide, terpenes, and paper dust. The exposure level depends on the process, i.e., sulfite, sulfate, groundwood, bleachery, or paper production. Hitherto, exposures have been poorly described and more studies are certainly needed. Workers with repeated exposure peaks to chlorine, e.g., bleachery workers, seem to have an impaired lung function and an increased prevalence of respiratory symptoms. Exposure to high levels of paper dust, (>5 mg/m³) causes impaired lung function. Therefore, exposure to respiratory irritants is an important, and probably overlooked, occupational risk among certain groups of pulp and paper workers. Some studies indicate that sulfate workers with high exposure to reduced sulfur compounds have an increased mortality due to ischemic heart disease. However, before any definite conclusions can be drawn, the impact of important confounders, such as shift-work and smoking habits have to be further evaluated. © 1996 Wiley-Liss, Inc.     

Health effects and occupational exposures among office workers near the World Trade Center disaster site

The extent of health effects and exposure to environmental contaminants among workers and residents indirectly affected by the September 11, 2001, attack on the World Trade Center (WTC) is unknown. The objective of this study was to evaluate concerns related to health effects and occupational exposures three months after the WTC disaster among a population of employees working in a building close to the disaster site. A cross-sectional questionnaire survey was performed of Federal employees working near the WTC site in New York City (NYC) and a comparison group of Federal employees in Dallas, Texas. An industrial hygiene evaluation of the NYC workplace was conducted. Constitutional and mental health symptoms were reported more frequently among workers in NYC compared to those in Dallas; level of social support was inversely related to prevalence of mental health symptoms. Post-September 11th counseling services were utilized to a greater degree among workers in NYC, while utilization of other types of medical services did not differ significantly between the groups. No occupational exposures to substances at concentrations that would explain the reported constitutional symptoms were found; however, we were unable to assess potential occupational exposures in the time immediately after the WTC disaster. There is no evidence of ongoing hazardous exposure to airborne contaminants among the workers surveyed. Specific causes of reported constitutional health symptoms have not been determined. Health care providers and management and employee groups should be aware of the need to address mental health issues as well as constitutional symptoms among the large number of workers in the NYC area who have been indirectly affected by the WTC disaster.     

Respiratory cancer in a cohort of copper smelter workers: results from more than 50 years of follow-up

Several studies have linked inhalation of airborne arsenic with increased risk of respiratory cancer, but few have analyzed the shape of the exposure-response curve. In addition, since inhaled airborne arsenic affects systemic levels of inhaled arsenic, there is concern that inhaled arsenic may be associated with cancers of the skin, bladder, kidney, and liver, which have been linked to ingested arsenic. The authors followed 8,014 white male workers who were employed for 12 months or more prior to 1957 at a Montana copper smelter from January 1, 1938 through December 31, 1989. A total of 4,930 (62%) were deceased, including 446 from respiratory cancer. Significantly increased standardized mortality ratios (SMRs) were found for all causes (SMR = 1.14), all cancers (SMR = 1.13), respiratory cancer (SMR = 1.55), diseases of the nervous system and sense organs (SMR = 1.31), nonmalignant respiratory diseases (SMR = 1.56), emphysema (SMR = 1.73), ill-defined conditions (SMR = 2.26), and external causes (SMR = 1.35). Internal analyses revealed a significant, linear increase in the excess relative risk of respiratory cancer with increasing exposure to inhaled airborne arsenic. The estimate of the excess relative risk per mg/m3-year was 0.21/(mg/m3-year) (95% confidence interval: 0.10, 0.46). No other cause of death was related to inhaled arsenic exposure.     

Prevalence of respiratory symptoms among workers in industries of south Tehran, Iran

OBJECTIVE: The aim of the present study was to determine the prevalence of respiratory symptoms from occupational lung hazards among workers in industries of south Tehran, IRAN. METHODOLOGY: This was a cross-sectional study in which by multistage random sampling items on demographic characteristics, cigarette smoking, occupational history and respiratory symptoms were collected of workers. RESULTS: The mean age of the workers was 38.5 (SD = 10.2) yr: age ranged from 19 to 70 yr. Of 880 workers under study, 252 (28.7%) were smoking. Also, it has been observed that workers exposed in the workplace with occupational chemical exposures such as dust, gas and fume pollutants. The prevalence of respiratory symptoms was cough (20.7%), phlegm (41.6%), dyspnea (41.7%), feel tightness (27.4%) and nose irritation (23.5%). CONCLUSIONS: Occupational exposures among workers in industries of south Tehran may cause respiratory symptoms and respiratory disorders, engineering controls and industrial hygiene is recommended.     

Occupational contact dermatitis to nickel: experience of the British dermatologists (EPIDERM) and occupational physicians (OPRA) surveillance schemes

Aims: To examine, from occupational surveillance reporting data, whether scheme reporters considered nickel exposure to play a role in occupational contact dermatitis (OCD) in the UK.

Methods: Data on occupational skin disease in the UK are collected by two occupational disease surveillance schemes, EPIDERM and OPRA. Cases of OCD believed to have relevant nickel exposure reported to EPIDERM or OPRA from February 1993 to January 1999 were studied.

Results: An estimate of 1190 cases of occupational contact dermatitis thought to have relevant nickel exposure (12% of total estimated OCD) was derived from reports by dermatologists, an average of 198 per year. The highest incidence rates were seen in hairdressers (23.9/100 000 workers/year), bar staff (4.7), chefs and cooks (4.4), retail cash and checkout operators (2.8), and catering assistants (2.5). From May 1994 to January 1999, 158 cases of nickel associated dermatitis (1.9% of total OCD cases) were estimated; the most frequently reported occupations were electronic assemblers, nurses, sales assistants, and general assemblers. From July 1997 to January 1999, 547 positive patch tests to nickel were reported; in 195 cases (36%), nickel was felt to be a relevant occupational allergen (for example, coin handling). In hairdressers, nurses, cooks, and beauticians, nickel was usually considered, if relevant at all, to be only one of several causes of dermatitis.

Conclusions: Up to 12% of total estimated cases of OCD were thought to be due in part to nickel. Results suggest that nickel hypersensitivity is one of several contributors to OCD in subjects with multiple occupational exposures. Coin handling may be a source of OCD to nickel.