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.     

Inorganic chemistry of chromium and its speciation in Whetlerite

Chromium compounds are among the impregnants that enhance the ability of carbon air filters to absorb and destroy toxic agents such as CK and AC. The possibility of inhaling chromium-containing carbon dust from such filters has caused concern because, in addition to being an essential nutrient, chromium has been identified as a chemical carcinogen in humans. The essentiality or carcinogenicity of chromium depends upon its chemical speciation. Solubility and oxidation state are particularly important factors in assessing the potential hazards associated with the possible inhalation of chromium-containing dusts from these impregnated carbons or Whetlerites. The chemical speciation of the chromium in Whetlerite was found to be: from 0.6 to 1.3% insoluble trivalent chromium; from 1.0 to 1.3% insoluble hexavalent chromium; and from 0.7 to 0.9% soluble hexavalent chromium. The impregnation process, and the resulting speciation of chromium in Whetlerite, is consistent with the inorganic chemistry of chromium.     

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.     

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)     

Chromium carcinogenicity; a review of experimental animal data

Since 1932 exposure to various hexavalent chromium compounds has been known to constitute a cancer hazard to industrial workers. A number of animal studies have been performed and chromates have been administered by inhalation, intratracheally, by intravenous and subcutaneous injection, intraperitoneally and orally. The human epidemiological studies have provided convincing evidence that zinc chromate is a potent carcinogen and there is some evidence that calcium chromate and chromium trioxide also constitute a cancer hazard in humans. The human studies have not selectively confirmed carcinogenic potency for other chromium compounds. The animal studies confirm the carcinogenic potency of calcium chromate and zinc potassium chromate and present strong evidence that chromates of lead and strontium are carcinogenic in animals. The significance of the water solubility for the carcinogenic potency of the chromates has not been clarified by animal studies.     

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.     

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.     

A critique of benzene exposure in the general population

Benzene risk assessment indicates that exposure to a time-weighted average (TWA) of 1-5 parts per million (ppm) benzene in ambient air for 40 years is associated with an increased risk of acute myeloid leukemia. Decreased white blood cell count, platelet count and other hematological indices have also been observed in persons exposed to as low as 1 ppm airborne benzene. Evidence from studies worldwide consistently shows elevated levels of benzene biomarkers that are equivalent to 0.1-2 ppm benzene in ambient air, or even higher in the general population without occupational exposure to benzene (including children). The public health significance of these observations depends on to what extent these levels reflect actual benzene exposure, and whether such exposures are life-long or at least occur frequently enough to pose a possible health threat. We reviewed the evidence and discussed possible explanations for these observations. It was concluded that while there is reason to suspect that benzene contributes significantly to elevated levels of biomarkers in the general population, there is growing concern that this cannot be definitively ascertained without concomitant consideration of the role of other factors such as metabolic polymorphisms and sources of biomarkers other than benzene, which have been insufficiently studied to date. Such studies are urgently needed for valid assessment of this potential public health problem.     

Chromium exposure assessment of outdoor workers in Hudson County, NJ.

A large quantity of chromate chemical production waste, containing hexavalent chromium, has been used as fill at over 150 sites in Hudson County, New Jersey. One site is in a state park, and several other sites are adjacent to the park. Blood and urinary chromium levels were compared between 17 employees at the Hudson County park and 35 employees from two other state parks. A limited number of soil and personal air samples were also taken. Urinary and RBC chromium levels between the two groups were similar, even after adjusting for potentially confounding variables. The air sampling results demonstrated slightly higher chromium levels at Hudson County, but these were still very low level in nature (mean = 0.18 micrograms/m3). These results call into question the utility of chromium biomonitoring under environmental exposure conditions.     

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.     

Spatial analysis of annual air pollution exposure and mortality

The aim of this study was to relate ambient air pollution levels to mortality in Auckland, New Zealand. We used urban airshed modelling and GIS-based techniques to quantify long-term exposure to ambient air pollution levels and associated mortality. After adjusting for age, sex, ethnicity, socio-economic status, and urban/rural domicile there was a 1.3% (95%CI: 1-1.5%) increase in non-external cause mortality, and 1.8% (95%CI: 1.5-2.1%) increase in circulatory and respiratory causes per 1 microg/m(3) increase in annual average NO(2). Based on these exposure-response relationships and applying an annual average threshold of 13 microg/m(3), the average annual (for 1996-1999) number of people estimated to die from non-external causes and circulatory and respiratory causes attributable to air pollution in Auckland is 268 (95% range: 227-310) (3.9% of total all cause deaths) and 203 (95% range: 169-237) (5.9% of total circulatory and respiratory deaths) per year, respectively. The number of attributable deaths found in this study are consistent with a previous New Zealand risk assessment using a different methodology, and is approximately twice the number of people dying from motor vehicle accidents in the region, which is on average (1996-1999) 103 per year. The GIS-based exposure maps identify high exposure areas for policy developers and planners in a simple and realistic manner. Taken together with overseas studies the study provides additional evidence that long-term exposure to poor air quality, even at levels below current standards, is a hazard to the public health.     

Assessment of risk from exposure to acrylonitrile: the general approach used by a consultant

The concern from low-level exposure to acrylonitrile is primarily due to its potential for carcinogenicity. Several epidemiology studies provide suggestive evidence for an association of lung cancer in workers exposed to acrylonitrile; however, smoking may be a contributing factor and therefore the role of acrylonitrile as a causative factor is unclear. Seven animal bioassays, using three routes of exposure and two strains of rats, have provided consistent results. Tumors were induced in all studies, with the primary sites of tumor induction being the brain, ear canal, gastrointestinal tract and mammary glands. The linearized multistage model was used for extrapolation purposes. The risk based on brain tumors (astrocytomas) and stomach tumors following oral exposures ranged from 1 x 10(-1) to 4 x 10(-1)mg-1kg-1day-1. The risk of inhalation exposure is somewhat less, (2-3) x 10(-2). Support for carcinogenic potential is obtained from mutagenicity studies. Acrylonitrile has been found to be mutagenic and also binds with DNA. It has been speculated that acrylonitrile is metabolized to 2-cyanoethylene oxide, which is the proximate carcinogen.     

Biological monitoring of occupational exposure in the chromate pigment production industry

A survey of occupational exposure to hexavalent chromium in chromate pigment production was undertaken in factories producing lead chromate (PbCrO4) and strontium chromate (SrCrO4). Sampling pre and post-shift in a factory where SrCrO4 production had just started showed the optimum strategy for biological monitoring is the measurement of urinary chromium, in urine samples taken at the end of Friday shift and pre-shift the following Monday. However, short-term uptake may be assessed under these circumstances by the increase in urinary chromium over a shift. Body burden, representing long-term chromate exposure is best assessed by measuring chromium in whole blood or pre-shift urinary chromium at the beginning of the working week. Exceptionally high levels of chromium in blood (387-4160 nmol l-1) and urine (41-1250 nmol nmol-1 creatinine) as well as skin and nasal lesions, were discovered amongst the workforce at the strontium chromate plant. These contrasted with occupationally unexposed levels of less than 20 nmol l-1 and less than 1 nmol nmol-1 creatinine, respectively, and led to the continuation of the biological monitoring programme. At the same time, improved working practices and respiratory protection equipment were introduced. A steady elimination of chromium from whole blood with a half-life of approximately 24 days was found. This elimination rate was confirmed over a 14 day period when the workforce were completely removed from exposure. The study confirms the usefulness of biological monitoring in assessing the uptake of hexavalent chromium and control of exposure.     

Mercury exposure in the population from Wuchuan mercury mining area, Guizhou, China

Mercury (Hg) exposure in the population from Wuchuan mercury mining area (WMMA), Guizhou, China, was evaluated by human hair Hg investigation. Total gaseous mercury (TGM) in the ambient air and Hg in rice were measured to assess human risk of Hg exposure. High TGM concentrations in the ambient air were found near smelting workshop. Rice not only contained high total mercury (T-Hg) which ranged from 6.0-113 ng/g, but also contained highly elevated methylmercury (Me-Hg) which ranged from 3.1-13.4 ng/g. The means of hair T-Hg concentrations were 33.9 microg/g and 21.5 microg/g at YQG and JXC sites, respectively. Residents from other sites also reflected a certain level of Hg exposure. Age had no significant effect on hair Hg levels, but male had higher hair T-Hg concentrations due to occupational exposure and also higher Me-Hg levels which might be related to larger amount of rice consumption. Hair may be a useful tool for monitoring human exposure of Hg vapor in Hg-mining areas. By a preliminary estimation, the inhalation of Hg polluted air was the main route of inorganic Hg exposure to the smelting workers and vicinal residents; but the population in the study area was also at a potential risk of Me-Hg exposure via rice intake.     

Evaluation of the health risk of platinum group metals emitted from automotive catalytic converters

A health risk assessment of platinum (Pt) emitted from automotive catalytic converters is presented. Following a stepwise approach, the relevant literature is discussed in order to characterize Pt emissions as well as the toxic potential of Pt and its compounds. In an exposure assessment, ambient Pt concentrations in air are predicted to range from approximately 4 pg/m3 (street canyon, typical conditions) up to approximately 112 pg/m3 (express motorway, severe conditions). These values agree well with the few measured concentrations, which are also in the low pg/m3 range. Pt is emitted from catalytic converters in very small amounts (ng/km range), mainly in the (0)-oxidation state (elemental Pt). The nanocrystalline Pt particles are attached to microm-sized aluminum oxide particles. Whether free ultrafine Pt particles may be emitted and result in biological effects has not been studied sufficiently. Hence, risk assessment can only be based on the respiratory sensitizing potential of halogenated Pt salts. The presence of such compounds in automotive Pt emissions cannot definitely be excluded. From recent occupational studies conducted in catalytic converter production, a conservative no-effect level (NOEL) of 1.5 ng/m3 can be derived for the sensitizing effect of halogenated Pt salts. In a (reasonable) worst case approach, it is assumed that such compounds comprise 1% (0.1%) of the total Pt emissions. Applying a safety factor of 10 to account for interindividual variability, a guidance value of 15 (150) ng/m3 is derived for catalyst-borne Pt. The exposure to Pt in ambient air as measured or predicted is at least two orders of magnitude below this guidance range. Rhodium is also contained in automotive catalysts, palladium has increasingly substituted Pt, and iridium-based catalysts have recently been introduced. Although the database on these platinum group metals is rather small, there is no evidence that they pose a health risk to the general population.     

Selection and evaluation of air pollution exposure indicators based on geographic areas

Geographic exposure indicators (GEIs) use point estimates of ambient air pollutant concentrations to characterize the exposure of populations residing within a specified area. Both zone- and proximity-type GEIs have been widely employed in epidemiological studies and other applications to identify regions or populations at high risk. Their use requires a number of assumptions, for example, pollutant concentrations should be homogeneous within the area, and concentrations should differ between areas in a predictable manner. These assumptions have not been rigorously examined. This paper evaluates the most common types of GEIs as surrogate measures of ambient air pollutant exposures. Statistical measures proposed to evaluate GEIs include accuracy, homogeneity, misclassification and statistical power. GEIs and statistical measures are evaluated in two case studies that use different air pollution sources and an air quality dispersion model. The case studies show that pollutant levels may vary substantially within a small area, and significant errors and exposure misclassification may result if the GEI represents a large geographic area. GEIs based on residential proximity to a pollution source should not be used for elevated emission sources, and the use of proximity measures is discouraged for ground level sources. A systematic evaluation is suggested to evaluate and improve the accuracy of the GEIs used in epidemiological and other applications.     

Evaluation of the total Cr-levels in the ambient air in Belgium

As a part of the general network for the monitoring of heavy metals in the ambient air in Belgium, total Cr-levels were measured at 14 stations distributed over the country from April 1982 until March 1985. The most important statistical results are summarized and discussed. In two regions, Liège and Genk, with important ferrous industries, elevated chromium pollution with important peak values has been detected. In the last five years, a marked increase has been noted for the Liège region, while at the other sites only small changes occurred. The relationship between chromium and the other metals measured in the ambient air is examined and discussed. On the basis of pollution data an attempt of source identification is presented.     

Weight-of-evidence evaluation in environmental assessment: Review of qualitative and quantitative approaches

Assessments of human health and ecological risk draw upon multiple types and sources of information, requiring the integration of multiple lines of evidence before conclusions may be reached. Risk assessors often make use of weight-of-evidence (WOE) approaches to perform the integration, whether integrating evidence concerning potential carcinogenicity, toxicity, and exposure from chemicals at a contaminated site, or evaluating processes concerned with habitat loss or modification when managing a natural resource. Historically, assessors have relied upon qualitative WOE approaches, such as professional judgment, or limited quantitative methods, such as direct scoring, to develop conclusions from multiple lines of evidence. Current practice often lacks transparency resulting in risk estimates lacking quantified uncertainty. This paper reviews recent applications of weight of evidence used in human health and ecological risk assessment. Applications are sorted based on whether the approach relies on qualitative and quantitative methods in order to reveal trends in the use of the term weight of evidence, especially as a means to facilitate structured and transparent development of risk conclusions from multiple lines of evidence.     

Ultrafine particle concentrations and exposures in seven residences in northern California

Human exposures to ultrafine particles (UFP) are poorly characterized given the potential associated health risks. Residences are important sites of exposure. To characterize residential exposures to UFP in some circumstances and to investigate governing factors, seven single-family houses in California were studied during 2007-2009. During multiday periods, time-resolved particle number concentrations were monitored indoors and outdoors and information was acquired concerning occupancy, source-related activities, and building operation. On average, occupants were home for 70% of their time. The geometric mean time-average residential exposure concentration for 21 study subjects was 14,500 particles per cm(3) (GSD = 1.8; arithmetic mean ± standard deviation = 17,000 ± 10,300 particles per cm(3)). The average contribution to residential exposures from indoor episodic sources was 150% of the contribution from particles of outdoor origin. Unvented natural-gas pilot lights contributed up to 19% to exposure for the two households where present. Episodic indoor source activities, most notably cooking, caused the highest peak exposures and most of the variation in exposure among houses. Owing to the importance of indoor sources and variations in the infiltration factor, residential exposure to UFP cannot be characterized by ambient measurements alone. PRACTICAL IMPLICATIONS: Indoor and outdoor sources each contribute to residential ultrafine particle (UFP) concentrations and exposures. Under the conditions investigated, peak exposure concentrations indoors were associated with cooking, using candles, or the use of a furnace. Active particle removal systems can mitigate exposure by reducing the persistence of particles indoors. Eliminating the use of unvented gas pilot lights on cooking appliances could also be beneficial. The study results indicate that characterization of human exposure to UFP, an air pollutant of emerging public health concern, cannot be accomplished without a good understanding of conditions inside residences.     

水泥水溶性六价铬来源及防治措施研究动态

目前大部分水泥原料存在废物利用,虽然节约了成本,但随之而来的毒性控制问题仍有待技术进步。毒性的主要来源是水溶性六价铬,对水溶性六价铬的源头研究和防治迫在眉睫。本文介绍了水泥中水溶性六价铬的来源及防治措施的相关研究。