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Introduction: Esophageal carcinoma causes over 380 000 deaths per year, ranking sixth worldwide in mortality amongst all malignancies. Globally, the squamous cell subtype is most common and accounts for 80% of esophageal cancers. Nonetheless, esophageal squamous cell carcinoma is much more poorly understood than esophageal adenocarcinoma, including what is driving such high prevalences, why it often presents in young patients, and shows such marked geographical delineations Areas covered: The current literature was searched for articles focusing on aetiopathogenesis of squamous cell esophageal carcinoma via a systematic review, particularly in low-resource settings. This was supplemented by papers of interest known to the authors. Expert commentary: Current putative mechanisms include polycyclic aromatic hydrocarbons, nitrosamines, acetaldehyde, cyclo-oxygenase-2 pathways, androgen and their receptor levels, as well as smoking & alcohol, micronutrient deficiencies and diet, mycotoxins, thermal damage, oral hygiene and microbiotal factors, inhaled smoke, viral infections such as HPV, and chronic irritative states. Etiology is likely multifactorial and varies geographically. Though smoking and alcohol play a predominant role in high-income settings, there is strong evidence that mycotoxins, diet and temperature effects may play an under-recognized role in low and middle-income settings.

Background: Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As(+3)) on DNA biosynthesis and cell death., Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry., Results: We show that As(+3) ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As(+3) (7.5 µg/ml). Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest., Conclusion: Our results indicate that sudden exposure of cells to arsenite (As(+3)) resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.

Human biomarker measurements in tissues including blood, breath, and urine can serve as efficient surrogates for environmental monitoring because a single biological sample integrates personal exposure across all environmental media and uptake pathways. However, biomarkers represent a "snapshot" in time, and risk assessment is generally based on long-term averages. In this study, a statistical approach is proposed for estimating long-term average exposures from distributions of spot biomarker measurements using intraclass correlations based upon measurement variance components from the literature. This methodology was developed and demonstrated using a log-normally distributed data set of urinary OH-pyrene taken from our own studies. The calculations are generalized for any biomarker data set of spot measures such as those from the National Health and Nutrition Evaluation Studies (NHANES) requiring only spreadsheet calculations. A three-tiered approach depending on the availability of metadata was developed for converting any collection of spot biomarkers into an estimated distribution of individual means that can then be compared to a biologically relevant risk level. Examples from a Microsoft Excel-based spreadsheet for calculating estimates of the proportion of the population exceeding a given biomonitoring equivalent level are provided as an appendix.

The objective of this study was to explore whether magnesium (Mg) levels in drinking water modified the effects of nitrate on esophageal cancer risk occurrence. A matched cancer case-control study was used to investigate the relationship between the risk of death from esophageal cancer and exposure to nitrate in drinking water in Taiwan. All esophageal cancer deaths of Taiwan residents from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N) and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N and Mg exposure via drinking water. Evidence of an interaction was noted between drinking water NO(3)-N and Mg intake. This is the first study to report effect modification by Mg intake originating from drinking water on an association between NO(3)-N exposure and increased risk mortality attributed to esophageal cancer.

Lung carcinogenesis is a complex process requiring the acquisition of genetic mutations that confer the malignant phenotype as well as epigenetic alterations that may be manipulated in the course of therapy. Inflammatory signals in the lung cancer microenvironment can promote apoptosis resistance, proliferation, invasion, metastasis, and secretion of proangiogenic and immunosuppressive factors. Here, we discuss several prototypical inflammatory mediators controlling the malignant phenotype in lung cancer. Investigation into the detailed molecular mechanisms underlying the tumor-promoting effects of inflammation in lung cancer has revealed novel potential drug targets. Cytokines, growth factors and small-molecule inflammatory mediators released in the developing tumor microenvironment pave the way for epithelial-mesenchymal transition, the shift from a polarized, epithelial phenotype to a highly motile mesenchymal phenotype that becomes dysregulated during tumor invasion. Inflammatory mediators within the tumor microenvironment are derived from neoplastic cells as well as stromal and inflammatory cells; thus, lung cancer develops in a host environment in which the deregulated inflammatory response promotes tumor progression. Inflammation-related metabolic and catabolic enzymes (prostaglandin E(2) synthase, prostaglandin I(2) synthase and 15-hydroxyprostaglandin dehydrogenase), cell-surface receptors (E-type prostaglandin receptors) and transcription factors (ZEB1, SNAIL, PPARs, STATs and NF-kappaB) are differentially expressed in lung cancer cells compared with normal lung epithelial cells and, thus, may contribute to tumor initiation and progression. These newly discovered molecular mechanisms in the pathogenesis of lung cancer provide novel opportunities for targeted therapy and prevention in lung cancer.

A large number of scientific studies and reviews have addressed the potential for dietary components to influence the risk of developing cancer. One topic of particular interest has been the impact of food contaminants. Two complementary programs, among others, have reviewed and synthesized information on the carcinogenic potential of food contaminants and judged the degree of evidence linking different food contaminants to the risk of cancer in humans. These programs, the International Agency for Research on Cancer's IARC Monographs on the Evaluation of Carcinogenic Risks to Humans and the US National Toxicology Program's Report of Carcinogens have reviewed hundreds of chemicals, mixtures, and natural products and then graded the cancer risk posed to humans. Contaminants with the highest level of evidence include aflatoxin, alcoholic beverages, 2,3,7,8-tetracholordibenzo-p-dioxin. Agents with a moderate level of evidence include acetaldehyde, polycyclic aromatic hydrocarbons, some nitrosamines, and yerba mate. Agents with a low level of evidence include bracken fern, fumonsin B(1), ochratoxin, and others. This review presents a summary of the evidence for the carcinogenicity of these and other agents and the ranks provided by two important assessment programs.

Superficial 'nonmuscle-invasive' bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.

Foundry workers have increased mortality and morbidity risks from numerous causes, including various cancers. A retrospective Chinese iron-steel cohort study was conducted to examine the mortality effects of exposure to foundry work. Standardized mortality ratios (SMRs) and standardized rate ratios (SRRs) were calculated to evaluate mortality risks among male workers with exposure to 15 hazardous factors, adjusting for confounders. During 14 years of follow-up, 13,363 of 121,846 male workers died. SMR analysis showed a healthy-worker effect in comparison with the general population. SRR analysis showed increased risks for all causes, all neoplasms, and others among the exposed workers compared with non-exposed blue-collar workers. Combined exposure to polycyclic aromatic hydrocarbons and two or more dusts increased the risks of lung cancer (SRR = 654; 95% CI: 113-3,780) and other malignancies. Foundry work has adverse health effects, including carcinogenic risks.

Assessment of relative biological effectiveness (RBE) for a radiation in the cases of inhalation of radon progeny and incorporation of plutonium in lung is based on simulation of lung cancer radiation risk for alpha and external reference types of radiation. Specific radiation risk models developed on the results of direct epidemiological studies are used for simulation. These include published risk models for nuclear workers of the Mayak facilities in the former Soviet Union exposed to incorporated plutonium (Kreisheimer et al., 2003; Gilbert et al., 2004) and underground miners exposed to radon progenies (BEIR VI, 1999). Additionally, a lung cancer risk model is developed for a case of population indoor radon exposure. Lung cancer risk related to external exposure is estimated using the risk model developed for the analyses of Japanese atomic bomb survivors (Preston et al., 2003). Uncertainties of risk models parameters are considered and the uncertainties of RBE are estimated using the results of lifetime lung cancer risk simulation, which is done implementing a Monte Carlo approach. Estimated median value of RBE in case of indoor radon exposure is 1.5 with 90% range 0.4-7. In the case of the two models developed by BEIR VI for lung cancer risk due to radon exposure in underground miners, the median values of RBE are 2.1 and 4.4 with 90% ranges 0.3-17 and 0.7-45, respectively. The two different models for lung cancer risk related to plutonium exposure resulted in close estimates of RBE: median value of 12 and 13 with 90% range 4-104 and 4-136, respectively.

Indoor radon measurements were carried out in cave dwellings of the Chinese loess plateau in Gansu province, where previously the Laboratory of Industrial Hygiene (LIH), China, and the U.S. National Cancer Institute (NCI) had conducted an international collaborative epidemiological study. The LIH-NCI study showed an increased lung cancer risk due to high residential radon levels, and estimated the excess odds ratio at 100 Bq/m3 to be 0.19 (Wang et al., 2002). The present study used two types of newly developed passive monitors: One is a discriminative monitor for radon and thoron; the other is a selective monitor for thoron decay products. The arithmetic mean concentrations of indoor radon and thoron were 91 and 351 Bq/m3, respectively. As reported by our previous study in Shanxi and Shaanxi provinces (Tokonami et al., 2004), the presence of high thoron concentration was confirmed and thoron was predominant over radon in the cave dwellings. However, the mean equilibrium equivalent thoron concentration (EETC) was found to be much lower than expected when assuming the equilibrium factor of 0.1 provided by the UNSCEAR (2000) report. The effective dose by radon and thoron decay products was estimated to be 3.08 mSv/yr. It was significantly lower than the dose of 8.22 mSv/yr estimated from the measurements that did not take into consideration any discrimination between radon and thoron. Excess relative risk of lung cancer per sievert may be much higher than the risk estimated from the LIH-NCI study, considering that discriminative measurements were not used in their study.

As other epidemiological exposure variables, indoor radon levels have a right-skewed, approximately lognormal distribution. The continuous linear trend estimator is then known to be sensitive to outlying observations. We consider trend estimators based on replacing the exposure x by a transformed variable z: (1) trimmed estimators, that is, extreme values are deleted in z; (2) winsorized estimators, that is, extreme values are replaced by a lower value; (3) categorical estimators, that is, x is categorized and the continuous variable z takes on scores such as the mean or median within categories. The latter approach is often used in meta-analyses of published odds ratios. Statistically optimal categories can be defined. The corresponding scores are the expected values within the categories, based on the assumption of a lognormal distribution. In a simulation study, it turned out that procedures with different cutpoints for cases and controls, winsorized estimators, and categorical estimators based on category medians can be badly biased upward. Categorical estimators using category means are not always robust against outlying observations. However, categorical estimators employing optimal categories with expected values are nearly unbiased, even in the presence of outliers. Cutpoints should be determined according to the overall distribution of cases and controls combined. Trimmed estimators based on this distribution are unbiased, but highly variable. For right-skewed exposure variables, we therefore suggest sensitivity analyses based on the categorical estimator with optimal cutpoints and expected value scores. In the West German case-control study on indoor radon and lung cancer, these sensitivity analyses lead to increased risk estimates.

Case-control studies on lung cancer and residential radon exposure were conducted in West and East Germany. Odds ratio (OR) estimates from primary analysis are now subject to correction for measurement error in exposure. We apply the regression calibration method adopting a bivariate multiplicative error model of the classical type; that is, we investigate the impact of errors in the exposure of primary interest, radon, and of errors in the most potent confounder, smoking. The OR estimates per 100 Bq/m3 are throughout higher after correcting for errors in radon exposure (e.g., 1.02 and 1.11 for the West and the East German study, respectively, corrected for an error of size 0.4); ignoring the clear but small correlation between radon exposure and smoking of about -0.06 would lead to less conservative corrections (1.10 and 1.13 for West and East, respectively). Accounting for a realistically sized error in the smoking variable additionally increases the OR estimates slightly. Remarkable is the fact that the naive OR estimate of the West study of 0.97 exceeds unity after correcting for errors in radon exposure larger than 0.3. We conclude that correcting for errors in radon exposure has a meaningful impact on OR estimates, that the correlation between radon exposure and the smoking variable affects the correction even if the smoking variable was error-free, and that such an analysis is extremely valuable to grasp an important issue in epidemiology, that is, the dimension of residual confounding due to adjusting for an imprecisely measured smoking variable.

Radon concentration alone may not be an adequate surrogate to measure for lung cancer risk in all residential radon epidemiologic lung cancer studies. The dose delivered to the lungs per unit radon exposure can vary significantly with exposure conditions. These dose-effectiveness variations can be comparable to spatial and temporal factor variations in many situations. New technologies that use surface-deposited and implanted radon progeny activities make more accurate dose estimates available for future epidemiologic studies.

Radon is a well-established cause of lung cancer in miners. Residents of homes with high levels of radon are potentially also at risk. Although most individual studies of indoor radon have failed to demonstrate significant risks, results have generally been consistent with estimates from studies of miners. We studied 1474 incident lung cancer cases aged 40-79 yr in Connecticut, Utah, and southern Idaho. Population controls (n = 1811) were identified by random telephone screening and from lists of Medicare recipients, and were selected to be similar to cases on age, gender, and smoking 10 yr before diagnosis/interview using randomized recruitment. Complete residential histories and information on known lung cancer risk factors were obtained by in-person and telephone interviews. Radon was measured on multiple levels of past and current homes using 12-mo alpha-track etch detectors. Missing data were imputed using mean radon concentrations for informative subgroups of controls. Average radon exposures were lower than anticipated, with median values of 23 Bq/m3 in Connecticut and 45 Bq/m3 in Utah/southern Idaho. Overall, there was little association between time-weighted average radon exposures 5 to 25 yr prior to diagnosis/interview and lung cancer risk. The excess relative risk (ERR) associated with a 100-Bq/m3 increase in radon level was 0.002 (95% CI -0.21, 0.21) in the overall population, 0.134 (95% CI -0.23, 0.50) in Connecticut, and -0.112 (95% CI -0.34, 0.11) in Utah/Idaho. ERRs were higher for some subgroups less prone to misclassification, but there was no group with a statistically significant linear increase in risk. While results were consistent with the estimates from studies of miners, this study provides no evidence of an increased risk for lung cancer at the exposure levels observed.

Cohort studies have consistently shown underground miners exposed to high levels of radon to be at excess risk of lung cancer, and extrapolations based on those results indicate that residential radon may be responsible for nearly 10-15% of all lung cancer deaths per year in the United States. However, case-control studies of residential radon and lung cancer have provided ambiguous evidence of radon lung cancer risks. Regardless, alpha-particle emissions from the short-lived radioactive radon decay products can damage cellular DNA. The possibility that a demonstrated lung carcinogen may be present in large numbers of homes raises a serious public health concern. Thus, a systematic analysis of pooled data from all North American residential radon studies was undertaken to provide a more direct characterization of the public health risk posed by prolonged radon exposure. To evaluate the risk associated with prolonged residential radon exposure, a combined analysis of the primary data from seven large scale case-control studies of residential radon and lung cancer risk was conducted. The combined data set included a total of 4081 cases and 5281 controls, representing the largest aggregation of data on residential radon and lung cancer conducted to date. Residential radon concentrations were determined primarily by a-track detectors placed in the living areas of homes of the study subjects in order to obtain an integrated 1-yr average radon concentration in indoor air. Conditional likelihood regression was used to estimate the excess risk of lung cancer due to residential radon exposure, with adjustment for attained age, sex, study, smoking factors, residential mobility, and completeness of radon measurements. Although the main analyses were based on the combined data set as a whole, we also considered subsets of the data considered to have more accurate radon dosimetry. This included a subset of the data involving 3662 cases and 4966 controls with a-track radon measurements within the exposure time window (ETW) 5-30 yr prior to the index date considered previously by Krewski et al. (2005). Additional restrictions focused on subjects for which a greater proportion of the ETW was covered by measured rather than imputed radon concentrations, and on subjects who occupied at most two residences. The estimated odds ratio (OR) of lung cancer generally increased with radon concentration. The OR trend was consistent with linearity (p = .10), and the excess OR (EOR) was 0.10 per Bq/m3 with 95% confidence limits (-0.01, 0.26). For the subset of the data considered previously by Krewski et al. (2005), the EOR was 0.11 (0.00, 0.28). Further limiting subjects based on our criteria (residential stability and completeness of radon monitoring) expected to improve radon dosimetry led to increased estimates of the EOR. For example, for subjects who had resided in only one or two houses in the 5-30 ETW and who had a-track radon measurements for at least 20 yr of this 25-yr period, the EOR was 0.18 (0.02, 0.43) per 100 Bq/m3. Both estimates are compatible with the EOR of 0.12 (0.02, 0.25) per 100 Bq/m3 predicted by downward extrapolation of the miner data. Collectively, these results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted by extrapolation of results from occupational studies of radon-exposed underground miners.

Following initial in vitro and in vivo studies and important studies of uranium miners, scientists have now completed impressive case-control studies of lung cancer risk from exposure to residential radon. Researchers have pooled these studies, in which all the information from the individual studies was reanalyzed. These pooled analyzes confirm that in the context of residential exposure, radon is now an established risk factor for lung cancer. Many of the initial uncertainties have been reduced, and health risk assessors are now confident that radon may contribute to as much as 10% of the total burden of lung cancer--that is, 2% of all cancers in the population, worldwide. To reduce residential radon lung cancer risk, national authorities must have methods and tools based on solid scientific evidence and sound public health policies. To meet these needs, the World Health Organization (WHO) has initiated the WHO International Radon Project. This three year project, to be implemented during the period 2005-2008, will include (1) a worldwide database on national residential radon levels, radon action levels, regulations, research institutions, and authorities; (2) public health guidance for awareness-raising and mitigation; and (3) an estimation of the global burden of disease (GDB) associated with radon exposure.

The earliest evidence of increased lung cancer risk associated with radon came largely from studies of highly exposed underground miners. In the United States, concerns about residential exposures became prominent in the early 1980s with the identification of the Watras home, which had remarkably elevated radon concentrations. By then, the problem of indoor radon was already recognized in Europe and the first epidemiological studies on indoor radon had been reported. The concern about the risk of indoor radon motivated a series of case-control studies of residential radon and lung cancer in the United States, Canada, China, and a number of European countries. In 1999, the U.S. National Research Council Committee on the Biological Effects of Ionizing Radiation (BEIR VI) weighed the scientific evidence available at that time on this issue and concluded that residential radon was an important contributor to the lung cancer burden and that risks were appropriately estimated by a linear nonthreshold model. Since individual case-control studies have not provided consistent direct evidence of excess lung cancer risk at residential exposure levels, combined analyses of residential radon studies have been undertaken in both North America and Europe. These combined analyses, including the North American pooled analysis described in this issue, represent an important complement to the findings of the miner studies and further support the linear no-threshold model for cancer risk adopted by the BEIR VI Committee and other groups.

Lung cancer has held the distinction as the most common cancer type worldwide since 1985 (Parkin et al., 1993). Recent estimates suggest that lung cancer accounted for 1.2 million deaths worldwide in 2002, which represents 17.6% of the global cancer deaths (Parkin et al., 2005). During 2002, the highest lung cancer rates for men worldwide reportedly occurred in North America and Eastern Europe, whereas the highest rates in females occurred in North America and Northern Europe (Parkin et al., 2005). While tobacco smoking is the leading risk factor for lung cancer, because of the magnitude of lung cancer mortality, even secondary causes of lung cancer present a major public health concern (Field, 2001). Extrapolations from epidemiologic studies of radon-exposed miners project that approximately 18,600 lung cancer deaths per year (range 3000 to 41,000) in the United States alone are attributable to residential radon progeny exposure (National Research Council, 1999). Because of differences between the mines and the home environment, as well as differences (such as breathing rates) between miners and the general public, there was a need to directly evaluate effects of radon in homes. Seven major residential case-control radon studies have been conducted in North America to directly examine the association between prolonged radon progeny (radon) exposure and lung cancer. Six of the studies were performed in the United States including studies in New Jersey, Missouri (two studies), Iowa, and the combined states study (Connecticut, Utah, and southern Idaho). The seventh study was performed in Winnipeg, Manitoba, Canada. The residential case-control studies performed in the United States were previously reviewed elsewhere (Field, 2001). The goal of this review is to provide additional details regarding the methodologies and findings for the individual studies. Radon concentration units presented in this review adhere to the types (pCi/L or Bq/m3) presented in the individual studies. One picocurie per liter is equivalent to 37 Bq/m3. Because the Iowa study calculated actual measures of exposure (concentration x time), its exposures estimates are presented in the form WLM(5-19) (Field et al., 2000a). WLM(5-19) represents the working level months for exposures that occurred 5-19 yr prior to diagnosis for cases or time of interview for control. Eleven WLM(5-19) is approximately equivalent to an average residential radon exposure of 4 pCi/L for 15 yr, assuming a 70% home occupancy.

Hexavalent chromium [Cr(VI)] has been detected in groundwater across the United States due to industrial and military operations, including plating, painting, cooling-tower water, and chromate production. Because inhalation of Cr(VI) can cause lung cancer in some persons exposed to a sufficient airborne concentration, questions have been raised about the possible hazards associated with exposure to Cr(VI) in tap water via ingestion, inhalation, and dermal contact. Although ingested Cr(VI) is generally known to be converted to Cr(III) in the stomach following ingestion, prior to the mid-1980s a quantitative analysis of the reduction capacity of the human stomach had not been conducted. Thus, risk assessments of the human health hazard posed by contaminated drinking water contained some degree of uncertainty. This article presents the results of nine studies, including seven dose reconstruction or simulation studies involving human volunteers, that quantitatively characterize the absorbed dose of Cr(VI) following contact with tap water via all routes of exposure. The methodology used here illustrates an approach that permits one to understand, within a very narrow range, the possible intake of Cr(VI) and the associated health risks for situations where little is known about historical concentrations of Cr(VI). Using red blood cell uptake and sequestration of chromium as an in vivo metric of Cr(VI) absorption, the primary conclusions of these studies were that: (1) oral exposure to concentrations of Cr(VI) in water up to 10 mg/L (ppm) does not overwhelm the reductive capacity of the stomach and blood, (2) the inhaled dose of Cr(VI) associated with showering at concentrations up to 10 mg/L is so small as to pose a de minimis cancer hazard, and (3) dermal exposures to Cr(VI) in water at concentrations as high as 22 mg/L do not overwhelm the reductive capacity of the skin or blood. Because Cr(VI) in water appears yellow at approximately 1-2 mg/L, the studies represent conditions beyond the worst-case scenario for voluntary human exposure. Based on a physiologically based pharmacokinetic model for chromium derived from published studies, coupled with the dose reconstruction studies presented in this article, the available information clearly indicates that (1) Cr(VI) ingested in tap water at concentrations below 2 mg/L is rapidly reduced to Cr(III), and (2) even trace amounts of Cr(VI) are not systemically circulated. This assessment indicates that exposure to Cr(VI) in tap water via all plausible routes of exposure, at concentrations well in excess of the current U.S. Environmental Protection Agency (EPA) maximum contaminant level of 100 microg/L (ppb), and perhaps those as high as several parts per million, should not pose an acute or chronic health hazard to humans. These conclusions are consistent with those recently reached by a panel of experts convened by the State of California.

Hexavalent chromium [Cr(VI)] is recognized as an inhalation carcinogen, based primarily on the increased incidence of lung cancer among occupationally exposed workers. To assess the carcinogenic potency of Cr(VI), both the U.S. Environmental Protection Agency and the Occupational Safety and Health Administration have relied on data from a 1930s cohort of workers from the Painesville, Ohio, chromate production plant. However, the exposure information for this cohort has several shortcomings. In an effort to provide better exposure information, we present here recently identified historical exposure data for the Painesville workers. More than 800 measurements of airborne Cr(VI) from 23 newly identified surveys conducted from 1943 to 1971 are presented. The results indicate that the highest Cr(VI) concentrations recorded at the plant occurred in shipping (e.g., bagging of dichromate), lime and ash, and filtering operations, with maximum yearly average Cr(VI) concentrations of 8.9, 2.7, and 2.3 mg/m(3), respectively. The locker rooms, laboratory, maintenance shop, and outdoor raw liquor storage areas had the lowest average Cr(VI) air concentrations over time, with yearly average concentrations that rarely exceeded the historical and current Threshold Limit Value TLV(R) of 0.05 mgCr(VI)/m(3) (0.1 mgCrO(3)/m(3)). Concentrations generally decreased in the plant over time. The average airborne concentration of Cr(VI) in the indoor operating areas of the plant in the 1940s was 0.72 mg/m(3), that from 1957 through 1964 was 0.27 mg/m(3), and that from 1965 through 1972 was 0.039 mg/m(3). Although in some ways limited, these data are of sufficient quality to allow for exposure reconstruction for workers employed at this plant from 1940 to 1972, and to provide the basis for an improved cancer risk assessment.

Polycyclic aromatic hydrocarbons (PAHs) are a class of environmental contaminants that has long been of interest in the fields of organic chemistry, theoretical chemistry, physical chemistry, environmental science, toxicology, cancer research, and energy sciences. Concerning environmental science and cancer research, majority of the research has focused on the occurrence, environmental fate, degradation/remediation, chemical transformation, genotoxicity, metabolism and metabolic activation, DNA adduct formation, mutagenesis, and carcinogenesis. Although many books and reviews on these subjects have been published, PAH photochemistry and phototoxicity have received much less attention. Therefore, it is intended for this article to provide an up-to-date source of photochemical reaction, photo-transformation, and phototoxicity of PAHs and their oxygenated, nitrated, halogenated, and amino substituted derivatives on a molecular basis. A perspective for future work is also discussed.

The aim of this study was to investigate whether exposure to hexavalent chromium induces lipid peroxidation in human. This study involved 25 chrome-plating factory workers and a reference group of 28 control subjects. The whole-blood and urinary chromium concentrations were determined by graphite furnace atomic absorption spectrophotometry. Malondialdehyde (MDA), the product of lipid peroxidation, was determined by high-performance liquid chromatography, and the activities of protective enzymes were measured by ultraviolet-visible spectrophotometry. In the chrome-plating workers, the mean concentrations of chromium in blood and urine were 5.98 microg/L and 5.25 microg/g creatinine, respectively; the mean concentrations of MDA in blood and urine were 1.7 micromol/L and 2.24 micromol/g creatinine. The concentrations of both chromium and MDA in blood and urine were significantly higher in the chromium-exposed workers. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were not markedly different between control and exposed workers. Data suggest that MDA may be used as a biomarker for occupational chromium exposure. Antioxidant enzymic activities are not a suitable marker for chromium exposure.

A case-control study was conducted to investigate the environmental causes of sinonasal cancers among pet dogs. Sinonasal cancer (SNC) cases and digestive cancer controls from the years 1989 through 1993 were obtained from a veterinary histopathology database. Owners were mailed a self-administered survey requesting information on canine factors, owner demographics, household exposures (including environmental tobacco smoke), and local pollution. A total of 129 case owners and 176 control owners returned completed surveys: a response rate of approximately 72%. Only household exposures were associated with increased SNC risk. Use of indoor coal or kerosene heaters represented the strongest risk factors, with significant adjusted odds ratios of 4.2 and 2.2 respectively. Environmental tobacco smoke exposure was not a risk factor and was suggestive of a nonsignificant, mildly protective effect at the lower exposure levels. Increasing nasal length was a significant risk factor, and there was effect modification between nasal length and coal or kerosene combustion. No self-reported measures of local pollution, such as urban status or residence within 1 mile of a factory, were associated with SNC risk. These results suggest that canine SNC has a strong environmental component and highlight the importance of indoor exposures, especially from fossil fuel combustion products. These results also suggest that pet dogs represent excellent sentinels for indoor cancer risk and that canine SNC cases can be used as early markers of household exposure to carcinogenic combustion products.

The uptake and elimination of Cr(VI) in a male volunteer who ingested 2 L/d of water containing 2 mg/L for 17 consecutive days was measured. Total chromium was measured in urine, plasma, and red blood cells (RBCs) for 4 d prior to and 2 wk after dosing (34 d total). The estimated bioavailability (2%) and the plasma elimination half-life (36 h) were consistent with our previous studies of Cr(VI) ingestion in humans. Steady-state chromium concentrations in urine and blood were achieved after 7 d of Cr(VI) ingestion. Both plasma and red blood cell (RBC) chromium concentrations returned rapidly to background levels within a few days after cessation of dosing. Since the concentration of chromium in the RBC should not decrease quickly if the chromium had entered the RBC as Cr(VI), these data support our prior work suggesting that concentrations of 10 mg Cr(VI)/L or less in drinking water of exposed humans appears to be completely reduced to Cr(III) prior to systemic distribution. Clinical chemistry data indicate that no toxicity occurred.

Chromosome painting (target chromosomes 1, 4, 12) was performed in peripheral lymphocytes from 25 occupants of nine houses with indoor radon concentrations of 210-3000 Bqm-3. Compared to a control group, the mean frequency of symmetrical translocations of the radon group was slightly but not significantly (p < 0.10) increased. A similar tendency became apparent for a comparison of two groups of subjects with cumulative radon exposures above and below 2800 Bqm-3 y. It is concluded that FISH-based measurements of stable symmetrical translocations should reflect the cumulative radon exposure to haematopoietic compartments such as the red bone marrow rather than to mature blood lymphocytes. Since, however, radon-derived bone marrow doses are low and control frequencies of translocations are very high (about 10-fold higher than the value for conventionally scored dicentrics), the observed relative increase (1.5-fold) of the translocation frequency in blood lymphocytes is too small to discriminate chronic radon exposure from background.