Effects derived from long-term low-level chromium exposure in ferro-alloy metallurgy. Study of absorption and renal function in workers

Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepted that chromium in this form is not able to cross biological barriers. However, the data on the toxic and carcinogenic effects of hexavalent chromium in man are now firmly established. Some studies have questioned these data, calling for a clarification as to whether exposure to trivalent chromium can also produce human effects, perhaps with different latency time. A study was carried out on the exposure conditions (type and degree) in a ferro-chromium foundry that had been in operation since 1972. The absorption levels in the working population of the foundry, and the possible toxic effects on the kidney have been investigated. A total of 236 workers (142 employed in production departments, 33 office workers and 61 sub-contractor employees) were examined with measurement of the indicators of dose (urinary-chromium) and of effect on the kidney (albumin, retinol binding protein, and renal tubular epithelium antigens in the urine). Environmental hygiene measurements showed relatively low values of total chromium in the air (always less than 0.160 mg/m3). Hexavalent chromium was absent or, if present, at levels below the sensitivity of the analytical method used (0.001 mg/m3). The values of urinary chromium measured at the beginning and at the end of the working day and at the end of the work shift were always less than 5 micrograms/g creatinine, which has been proposed as a biological limit in chromium exposure. However, differences were observed between groups of subjects employed on different jobs, which is indicative of an absorption process varying according to the degree of exposure. The indicators of effect did not reveal any renal impairment, even early, that could be attributed to the toxic action of chromium.     

Nutritional role of chromium

Chromium is an essential trace element required for normal carbohydrate metabolism. The biological function of chromium is closely associated with that of insulin and most chromium-stimulated reactions are also insulin dependent. Proper chromium nutrition leads to a decreased requirement for insulin and also an improved blood lipid profile. Most fresh foods and minimally processed foods are good sources of dietary chromium. Inorganic chromium does not potentiate insulin action and must be converted to an organic biologically active form. An organic form of chromium capable of potentiating insulin action has been isolated from brewer's yeast and was shown to contain: Cr, nicotinic acid and a combination of amino acids. Synthetic insulin potentiating organic chromium complexes containing chromium, nicotinic acid, glycine, cysteine, and glutamic acid or chromium, nicotinic acid and glutathione have been prepared. These complexes have not been purified to homogeneity since they dissociate during purification. Suitable analytical bioassays are available to measure total chromium and the organic biologically-active forms of chromium, respectively.     

Chromium carcinogenicity: California strategies

Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route.     

Acute and chronic systemic chromium toxicity

Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.     

Chromium in urine, serum and red blood cells in the biological monitoring of workers exposed to different chromium valency states

Using personal air sampling exposure to hexavalent and trivalent chromium was measured in 22 workers mainly exposed to Cr(VI) and in 15 workers mainly exposed to Cr(III) as basic chromium sulphate. Determination of Cr(VI) in the urine of all the subjects using a selective technique by ETA-AAS and liquid anion exchangers failed to show detectable amounts of the hexavalent form, the detection limit of the technique being 0.05 micrograms/L. A clear relationship between exposure and postshift urinary total chromium was found in subjects exposed to Cr(VI), while urinary levels in workers exposed to chromic sulphate high concentration proved lower. Determination of total chromium in serum and red blood cells showed a significant increase of chromium levels in erythrocytes of workers exposed to Cr(VI) while in subjects mainly exposed to Cr(III) an increase of the serum fraction was observed. The results demonstrate that Cr(III) is absorbed through the respiratory tract, but its kinetics and distribution in the body are not the same as for Cr(VI), and are not adequately monitored by short-term urinary determinations. Oxidation states of chromium largely influence uptake, mechanism of absorption, transport and organ distribution as well as toxicity of chromium-containing compounds. In particular, hexavalent derivatives are known to induce adverse effects, both acute and chronic, in occupationally exposed subjects, while there is little conclusive evidence for toxic effects caused by trivalent chromium compounds. Biological monitoring of exposure to chromium(VI) has usually been performed by determining total chromium levels in urine, whereas biological monitoring data in subjects occupationally exposed to Cr(III) are still scanty.(ABSTRACT TRUNCATED AT 250 WORDS)     

Locational differences in heavy metals and metalloids in Pacific Blue Mussels Mytilus [edulis] trossulus from Adak Island in the Aleutian Chain, Alaska

Increasingly there is a need to implement biomonitoring plans that can be sustained cost-effectively, focusing on single widespread (or closely-related species) in different parts of the world to detect exposure, potential damage to the organisms themselves, and risk to their consumers, including humans. Blue Mussels (Mytilus edulis and its relatives) have been widely used for environmental monitoring. One successful program that has achieved great coverage in time and space is "Mussel Watch", and related programs exist in several regions. In this paper we use the Pacific Blue Mussel Mytilus [edulis] trossulus collected from five locations on Adak Island in the Aleutian Chain to examine five heavy metals and two metalloids, to test for locational differences as a function of anthropogenic activities, and to consider potential human health risks. Until the late 1990s Adak hosted a large U.S. military base, with multiple areas of contamination, some of which have been remediated. In June 2004 we identified four presumably human-impacted sites and a presumed unimpacted reference site, the latter on Clam Lagoon Beach, about 3 km from former military activity. No single site had the highest level of more than two metals, and the reference site had the highest levels of chromium and manganese. We subsequently found historic records of a former landfill within 1 km of the reference site. All of the locational differences were less than an order of magnitude, the greatest difference between the highest and lowest values being 4.5 times for lead. The highest correlations were between mercury and arsenic, mercury and lead, arsenic and lead, and chromium and manganese. Shell length was a better indicator of metals' levels than soft body weight, but the relationships were weak. There was no significant correlation between body size or weight with arsenic, lead, or selenium levels. There is substantial comparative data on these metals in mussels. Our results from Adak are generally within the range of mean values reported in the literature, except for the consistently elevated levels of chromium.     

The total body burden of chromium associated with skin disease and smoking among cement workers

BACKGROUND: Hand eczema and other skin diseases have been associated with the exposure of chromium among cement workers. Studies on skin disease and other factors associated with the body burden of chromium are limited. OBJECTIVE: The present study investigated the role of skin disease and smoking in the association with body burden of chromium among cement workers. METHODS: Forty-five workers (38 men and 7 women) were recruited for this study and interviewed to obtain information on demographic status, lifestyle, employment history, and affecting factors. Urine samples were collected to measure the urinary chromium concentration to represent the body burden of chromium. RESULTS: The average urinary chromium concentration was approximately 6 times higher in non-smoking workers with hand eczema than in non-smoking workers with no skin disease (45.5 vs. 7.6 microg/L). The average chromium level increase to 87.0 microg/L for smokers with the disease. Compared with workers with no hand eczema, the odds ratio of having urinary chromium concentration exceeding the biological exposure index level significantly increased to 11.6 (95% CI=1.3-102.2) for non-smoking workers with skin disease, and to 48.0 (95% CI=4.5-510.8) for smoking workers with skin disease. The multiple regression analysis showed that the use of gloves may reduce significantly the chromium exposure. CONCLUSIONS: Inadequate protection and personal behavior increase the internal dose of chromium in cement workers. Total body burden of chromium are higher among cement workers with skin disease and smoking habit. These workers deserve intervention education on personal hygiene to reduce the exposure of chromium.     

Suppression of IL-6 level in human peripheral blood mononuclear cells stimulated with PHA/LPS after occupational exposure to chromium

The toxic metals alter the immune response of animals as well as humans. In addition to the well documented and numerous toxic effect of chromium on various target organs, number of studies shown that acute and chronic exposure to inorganic chromium may result in impairment of immune functions in the experimental systems. Immunosuppression appears to be more subtle effect of exposure to heavy metals. Therefore, we have taken two different groups of chromium exposed individuals. These were leather tanning workers and chromeplaters. These groups of individuals were regularly exposed to chromium. All the leather tanning workers were highly exposed to chromium having a mean of 96.60+/-113.95 mg/dl (range 12.4-417.21 mg/dl). A suspension of exposed and unexposed human PBMC (0.5x10(6) cells/ml) prepared and cultured in RPMI-1640 supplemented with 10% FCS for 18 h in the presence or absence of PHA (5 microg/ml) and LPS (10 ng/ml) which used for stimulation of IL-2, IL-4, TNF-alpha, IL-10 and IL-6, respectively. The levels of Th1/Th2 cytokine: IL-2, IL-4, TNF-alpha, IL-10 and IL-6 were evaluated in the sera and PHA/LPS stimulated culture supernatant of human PBMCs of chromium exposed workers. In these workers the level of IL-6 was 543.95+/-123.75 pg/ml and 388.40+/-61.24 pg/ml in PHA/LPS stimulated culture supernatant of normal individuals and highly chromium exposed workers, which was significant (P<0.05). This observation suggests that IL-6 levels were suppressed in chromium exposed groups as compared to unexposed healthy volunteers. Although the level of IL-2 in PHA stimulated culture supernatant of PBMCs was suppressed in chromium exposed individuals but it was not significant, IL-4 and IL-10 could not be detected. However, there was no difference in TNF-alpha levels in sera samples as well as unstimulated culture supernatant of h-PBMCs of chromium exposed individuals as compared to control.     

Review of occupational epidemiology of chromium chemicals and respiratory cancer

Several epidemiologic studies have investigated the association between cancer risk and employment in chromium producing and using industries. Strong and consistent associations have been found between employment in the primary chemical producing industry and the risk for respiratory cancer. Workers employed in chromate pigment production and possibly spray painters of chromate pigment paints appear to be at excess risk of respiratory cancer. Chrome platers may also be at excess risk, although the evidence is limited. A few studies indicate that chromium alloy welding may also be an exposure source of concern. Some studies of ferrochromium alloy workers have shown an excess risk for respiratory cancer, although the risk may in part be due to concomitant exposures. The evidence indicates that the hexavalent form of chromium is the primary agent of chromium carcinogenesis. Solubility and other characteristics of chromium compounds may also play a role in determining risk.     

Human health risk assessment of chlorinated disinfection by-products in drinking water using a probabilistic approach

The presence of chlorinated disinfection by-products (DBPs) in drinking water is a public health issue, due to their possible adverse health effects on humans. To gauge the risk of chlorinated DBPs on human health, a risk assessment of chloroform (trichloromethane (TCM)), bromodichloromethane (BDCM), dibromochloromethane (DBCM), bromoform (tribromomethane (TBM)), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in drinking water was carried out using probabilistic techniques. Literature data on exposure concentrations from more than 15 different countries and adverse health effects on test animals as well as human epidemiological studies were used. The risk assessment showed no overlap between the highest human exposure dose (EXP(D)) and the lowest human equivalent dose (HED) from animal test data, for TCM, BDCM, DBCM, TBM, DCAA and TCAA. All the HED values were approximately 10(4)-10(5) times higher than the 95th percentiles of EXP(D). However, from the human epidemiology data, there was a positive overlap between the highest EXP(D) and the lifetime average daily doses (LADD(H)) for TCM, BDCM, DCAA and TCAA. This suggests that there are possible adverse health risks such as a small increased incidence of cancers in males and developmental effects on infants. However, the epidemiological data comprised several risk factors and exposure classification levels which may affect the overall results.     

Essentiality of chromium in humans

Chromium is an essential nutrient required for normal sugar and fat metabolism. Insufficient dietary chromium is associated with maturity-onset diabetes and/or cardiovascular diseases. Dietary chromium intake in the U.S. and other developed countries is roughly half of the minimum suggested intake of 50 micrograms. Well controlled studies involving human subjects have demonstrated beneficial effects of supplemental chromium on fasting glucose, glucose tolerance, blood lipids, insulin binding, and hypoglycemic blood glucose values and symptoms. Since chromium is a nutrient and not a therapeutic agent, it will only benefit those people whose signs and symptoms are due to marginal or overt chromium deficiency. Stresses including high sugar diets, strenuous exercise, physical trauma, infection and certain diseases exacerbate the signs and symptoms associated with marginal intakes of dietary chromium. While excessive levels of chromium are usually limited to industrial settings, marginal dietary chromium intake is widespread in the general population and may lead to serious health problems.     

Dynamic characteristics and comfort assessment of airflows in indoor environments: A review

During the past few decades, both positive and negative aspects of indoor air movement on human comfort perception have been studied. However, most research has focused on collecting empirical evidence to support the potential application of airflows in practice. In this context, numerous studies have encouraged the use of moving air to promote comfort in warm environments, especially with regard to the application of dynamic airflows. Through these studies, the effects of different airflow parameters(such as air velocity, turbulence intensity, and fluctuation frequency) on human comfort perception have gradually been identified and even quantified. This article aims to summarize the progress in the literature concerning dynamic characteristics and comfort assessment of airflows in four main sections: demand for indoor airflows, parameters of indoor airflows, comfort assessment of indoor airflows, and dynamic airflows and their application.This paper will hopefully aid the understanding of human perception of indoor airflows and guide future research.     

Revealing the relationship of human convergence–divergence patterns and land use: A case study on Shenzhen City,China

Understanding the relationship between human mobility and land use has been a longstanding topic in multiple disciplines, including transport geography and urban planning. Recently, urban collective mobility patterns have become a hot research direction and has been explored at an unprecedented space–time scale due to the emerging big human tracking datasets (e.g., mobile phone data). However, only a few studies have comprehensively quantified the effects of land use on human mobility patterns while considering the influence of the scale of spatial analysis units. This study attempts to reinforce this knowledge by investigating urban human convergence–divergence patterns and their relationship with land use distribution characteristics at three popular types of spatial analysis units of human mobility studies (voronoi polygons, grid cells, and traffic analysis zones) using mobile phone data. A case study on Shenzhen, China is implemented, and results indicate that eight distinct convergence–divergence patterns could be extracted to describe urban collective mobility patterns despite the use of different types of spatial analysis unit. Moreover, the scale of spatial analysis units exerts a few effects on the quantification of the influence of land use distribution on human convergence–divergence patterns, but some common characteristics could be summarized from these discrepant results. The findings can help policy makers understand urban human mobility and can serve as a guide for urban management and planning.     

The effects of chromium VI on the fitness and on the beta-tubulin genes during in vivo development of the nematode Steinernema feltiae

The entomopathogenic nematode (EPN), Steinernema feltiae, is a commonly occurring nematode in the soil in Ireland. Consequently, we have conducted investigations as to the utility of this species as a candidate organism for the detection of chromium in Irish soils. These experiments have demonstrated that S. feltiae can survive and reproduce in the presence of high concentrations of chromium VI. It was observed that concentrations as high as 1000 ppm have little effect on the ability of this organism to produce large numbers of progeny. Nematodes were not observed to reproduce above 1800 ppm. However, an increase in development times for the nematode in vivo was noted at concentrations of 400 ppm upwards. This paper also illustrates the effects upon the beta-tubulin genes within nematode populations exposed to chromium VI in vivo. DNA sequencing has shown that elevated levels of variations occur among the population treatments, although these variations do not appear to be dependent upon chromium concentration. These findings constitute this organism appropriate for further investigation for the development of sub-lethal end points and biomarkers for the detection and biomonitoring of chromium VI contamination in soil.     

Evaluation of issues relating to the carcinogen risk assessment of chromium

Important issues in the carcinogenic risk assessment of chromium compounds are whether both trivalent and hexavalent chromium compounds are carcinogenic, the role of solubility in the carcinogenic response, and the carcinogenicity of ingested chromium. Hexavalent chromium compounds are carcinogenic to animals via several routes of exposure, while trivalent chromium compounds, although they demonstrate evidence of genotoxicity, have not been shown in animal studies to be carcinogenic. Workers in chromate production plants, where the risk of lung cancer is elevated, are exposed to both trivalent and hexavalent chromium compounds. A cancer unit risk estimate for Wistar rats exposed to a hexavalent chromium aerosol (sodium dichromate) is less than the risk estimate for workers in chromate production. If this difference is biologically real, a possible explanation may be that trivalent compounds also have a carcinogenic effect. For hexavalent chromium compounds, it is contended that only sparingly soluble hexavalent chromium compounds are carcinogenic. Recent evidence, however, indicates that highly soluble hexavalent chromium compounds are also carcinogenic. Animal ingestion studies have not found trivalent chromium compounds to be carcinogenic by ingestion; hexavalent compounds have not been studied. Research by EPA to address the issue of valence state and solubility with respect to carcinogenicity is currently being conducted.     

Role of epidemiologic studies in evaluating the carcinogenicity of chromium compounds

Epidemiologic and animal studies have identified intermediately-soluble chromates as human carcinogens. Epidemiologic studies also provide moderately strong evidence to conclude that chromates do not cause cancer at sites other than the respiratory tract. This information, combined with the evidence from animal studies and in vitro experiments, has led to the conclusion that chromates do not present a carcinogenic risk from ingestion. Unfortunately, epidemiologic studies have not provided definitive answers to other questions: (i) does trivalent chromium present a cancer risk?; (ii) is there a threshold for carcinogenic effects?; and (iii) what is the appropriate model for predicting cancer risk? Mechanistic research with supporting evidence from animal studies has provided the most useful information to answer these questions. Working hypotheses are: (i) trivalent chromium is not a carcinogen; (ii) there are probably substantial differences in carcinogenic potency between chromates, with the water-soluble compounds having lower potency than intermediately-soluble compounds; (iii) only respiratory tract cancers are caused by exposure to chromates, and ingestion and chromates does not constitute a carcinogenic risk; (iv) there is probably a threshold for carcinogenic effects from chromium due to detoxification mechanisms and lack of bioavailability of low doses; and (v) currently used models for quantitative risk assessment (e.g. the low dose linearized multi-stage model) are inappropriate to predict low dose cancer risks from exposure to chromates.     

Experimental study and modelling of Cr (VI) removal from wastewater using Lemna minor

The removal of Cr(VI) from wastewater by Lemna minor was studied both at laboratory and pilot scale. Laboratory tests were conducted under different conditions of initial Cr(VI) concentration (0.5 and 2.0 mg/l) and temperature (285 and 291 K). Batch experiments were carried out during 16 days in which the chromium concentrations, both in the biomass and in wastewater were measured. Data were used to characterize the biouptake capacity of the biomass; results showed that it increases with the temperature and when the initial Cr concentration decreases. The biouptake process could be fitted by an equation, with a correlation coefficient of 0.98. The removal process was assessed using the data of the variation of chromium concentration in the wastewater with respect to time; this allowed obtaining constant parameters which were applied in a mathematical model for the assessment of duckweed systems in a pilot scale plant.     

Effect of chromium on the level of IL-12 and IFN-gamma in occupationally exposed workers

Chromium may affect humoral and cellular immunity, acting on T lymphocytes as well as on granulocytes and monocytes cells. Cytokines play an important role in the immune balance. In this study, the level of IL-12 and IFN-γ were evaluated in the sera and PHA/LPS stimulated culture supernatant of human PBMCs of healthy volunteers and occupationally exposed chromium workers. All the workers were highly exposed to chromium having mean of 104.65 ± 77.21 µg/dL (range 23.7-316.8 µg/dL). A suspension of exposed and unexposed human PBMC (0.5 × 10⁶ cells/ml) prepared and cultured in RPMI-1640 supplemented with 10% FCS for 18 h in the presence or absence of LPS (10 ng/ml) which used for stimulation of IL-12 and IFN-γ. The level of IL-12 and IFN-γ were evaluated in the sera samples as well as LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers. In these chromium exposed workers the level of IL-12 was 433.66 ± 197.49 pg/ml and 983.45 ± 330.99 pg/ml in LPS stimulated culture supernatant of normal individuals and highly chromium exposed workers, which was significant (P < 0.05). Although the level of IL-12 was (78.61 ± 61.03 pg/ml to 146.52 ± 46.37 pg/ml) elevated in unstimulated culture supernatant of h-PBMCs of chromium exposed individuals as compared to control, but it was not significant. This observation also suggests that a significant increase in IFN-γ production in LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers as compared to control. However, IFN-γ level have a significant positive correlation between blood chromium level (r = 0.833, t = 6.3872, P 0.05) and exposure time (in years) (r = 0.8916, t = 8.3540, P 0.05) of the occupationally exposed workers.     

Distribution and mobility of chromium, copper, and arsenic in soils collected near CCA-treated wood structures in Korea

Chromated copper arsenate (CCA) is currently the most commonly used wood preservative in Korea. Questions, however, have been raised regarding the potential environmental impacts of metal leaching from CCA-treated wood to soil. Although a number of researchers from other countries have reported that chromium, copper, and arsenic do leach from CCA-treated wood over time, to date few field studies have been performed on those metals in soils adjacent to CCA-treated wood structures in Korea. The present study was conducted to determine the lateral and vertical distributions and accumulation of chromium, copper, and arsenic in soils collected from CCA-treated wood structures. A total of fifty-five composite soil samples were collected from four CCA-treated wood structures of approximately one year in age. The samples were analyzed for physicochemical properties as well as for the total chromium, copper, and arsenic concentrations. The chromium, copper, and arsenic concentrations in soil samples adjacent to the structures were as high as 79.0, 98.9, and 128 mg/kg, respectively, compared to background soil samples (48.2, 26.9, and 6.27 mg/kg, respectively). Arsenic was more mobile in soil than chromium and copper. The concentration gradient of arsenic in soil was observed only to the depth of approximately 5 cm in one year of outdoor exposure, whereas chromium and copper apparently remained near the surface (approximately less than 1 cm) after their release. Future efforts should be made to observe seasonal impacts on the release of metals and incorporate metal speciation into determining more detailed mobility and distribution.     

Response to Buchanan et al.'s comment on Urban et al. “Assessment of human health risks posed by consumption of fish from the Lower Passaic River (LPR), New Jersey” (2009, doi:10.1016/jscitotenv.2009.03.004)

Buchanan et al. assert that our recent fish ingestion risk assessment for a section of the Lower Passaic River (LPR) (Urban et al., 2009) utilizes inappropriate ingestion rates and is inconsistent with state and USEPA guidelines and risk assessment procedures, and therefore underestimates the human health risks associated with angler exposure along this stretch of the river. However, they fail to support these assertions with evidence; indeed, in a recent response to similar allegations, we demonstrated that the utilized ingestion rates are, in fact, the most appropriate for this parameter (Urban et al., 2010). Our reliance on data from a comprehensive, independently validated, peer-reviewed, and site-specific creel angler survey (CAS) in order to define fish and crab ingestion rates for this region of the LPR is fully compliant with USEPA guidelines. In fact, the crab ingestion survey and risk assessment cited by Buchanan et al. as evidence of crabbing activity and crab ingestion for this region was less comprehensive than the CAS in question, was not overseen by an independent panel, has yet to be peer-reviewed, and does not provide any activity or consumption data for this section of the LPR. Contrary to the implications of Buchanan et al., our effort provides a transparent, comprehensive, and scientifically legitimate human health risk assessment of fish ingestion for the lowest 6 miles of the LPR. Thus we adamantly disagree with the characterization and assertions put forth by Buchanan et al., and stand by the conclusions presented in Urban et al. (2009) and defended in Urban et al. (2010).