Respiratory cancer risks associated with low-level nickel exposure: an integrated assessment based on animal, epidemiological, and mechanistic data (original) (raw)

Respiratory carcinogenicity assessment of soluble nickel compounds

Environmental Health Perspectives, 2002

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

Carcinogenicity Assessment of Selected Nickel Compounds

Toxicology and Applied Pharmacology, 1997

Advisory Document (EPA, 1986). As a result of this project, Carcinogenicity Assessment of Selected Nickel Compounds. the International Committee on Nickel Carcinogenesis in OLLER, A. R., COSTA, M., AND OBERDÖ RSTER, G. (1997). Toxicol. Man (ICNCM) was formed (as a joint effort between indus-Appl. Pharmacol. 143, 152-166.

Occupational exposure to nickel and hexavalent chromium and the risk of lung cancer in a pooled analysis of case‐control studies (SYNERGY)

International Journal of Cancer

There is limited evidence regarding the exposure‐effect relationship between lung‐cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung‐cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case‐control studies from Europe and Canada, including 16 901 lung‐cancer cases and 20 965 control subjects. A measurement‐based job‐exposure‐matrix estimated job‐year‐region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95%...

Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

Toxics, 2013

Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration-and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D). Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm 2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm 2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent

Derivation of PM10 size-selected human equivalent concentrations of inhaled nickel based on cancer and non-cancer effects on the respiratory tract

Inhalation toxicology, 2014

Nickel (Ni) in ambient air is predominantly present in the form of oxides and sulfates, with the distribution of Ni mass between the fine (particle aerodynamic diameter < 2.5 µm; PM2.5) and coarser (2.5-10 µm) size-selected aerosol fractions of PM10 dependent on the aerosol's origin. When deriving a long-term health protective reference concentration for Ni in ambient air, the respiratory toxicity and carcinogenicity effects of the predominant Ni compounds in ambient air must be considered. Dosimetric adjustments to account for differences in aerosol particle size and respiratory tract deposition and/or clearance among rats, workers, and the general public were applied to experimentally- and epidemiologically-determined points of departure (PODs) such as no(low)-effect concentrations, for both cancer and non-cancer respiratory effects. This approach resulted in the derivation of threshold-based PM10 size-selected equivalent concentrations (modified PODs) of 0.5 µg Ni/m(3) bas...

Nickel: Human Health and Environmental Toxicology

International Journal of Environmental Research and Public Health

Nickel is a transition element extensively distributed in the environment, air, water, and soil. It may derive from natural sources and anthropogenic activity. Although nickel is ubiquitous in the environment, its functional role as a trace element for animals and human beings has not been yet recognized. Environmental pollution from nickel may be due to industry, the use of liquid and solid fuels, as well as municipal and industrial waste. Nickel contact can cause a variety of side effects on human health, such as allergy, cardiovascular and kidney diseases, lung fibrosis, lung and nasal cancer. Although the molecular mechanisms of nickel-induced toxicity are not yet clear, mitochondrial dysfunctions and oxidative stress are thought to have a primary and crucial role in the toxicity of this metal. Recently, researchers, trying to characterize the capability of nickel to induce cancer, have found out that epigenetic alterations induced by nickel exposure can perturb the genome. The ...

Lung cancer risk associated with occupational exposure to nickel, chromium VI, and cadmium in two population-based case-control studies in Montreal

American Journal of Industrial Medicine, 2010

Background Nickel, chromium VI, and cadmium have been identified as lung carcinogens in highly exposed cohorts. The purpose of this study was to examine the etiological link between lung cancer and these metals in occupations, that usually entail lower levels of exposure than those seen in historical cohorts. Methods Two population-based case-control studies were conducted in Montreal, from 1979 to 1986 and from 1996 to 2001, comprising 1,598 cases and 1,965 controls. A detailed job history was obtained to evaluate lifetime occupational exposure to many agents, including nickel, chromium VI, and cadmium compounds. Results Lung cancer odds ratios were increased only among former or non-smokers: 2.5 (95% CI: 1.3-4.7) for nickel exposure, 2.4 (95% CI: 1.2-4.8) for chromium VI, and 4.7 (95% CI: 1.5-14.3) for cadmium. The metals did not increase risk among smokers. Conclusions While excess risks due to these metal compounds were barely discernable among smokers, carcinogenic effects were seen among non-smokers. Am. J. Ind. Med. 53:476-485,

Nickel essentiality, toxicity, and carcinogenicity

Critical Reviews in Oncology Hematology, 2002

The increasing utilization of heavy metals in modern industries leads to an increase in the environmental burden. Nickel represents a good example of a metal whose use is widening in modern technologies. As the result of accelerated consumption of nickel-containing products nickel compounds are released to the environment at all stages of production and utilization. Their accumulation in the environment may represent a serious hazard to human health. Among the known health related effects of nickel are skin allergies, lung fibrosis, variable degrees of kidney and cardiovascular system poisoning and stimulation of neoplastic transformation. The mechanism of the latter effect is not known and is the subject of detailed investigation. This review provides an analysis of the current state in the field.