Airborne concentrations of chrysotile asbestos during operation of industrial crane controls and maintenance of associated arc chutes.

Some industrial crane control panels were historically equipped with chrysotile-containing arc chutes. Because of the paucity of data regarding potential exposure from such equipment, we used a simulation approach to quantify the release of chrysotile from arc chutes in two functional 1970s-era industrial crane control panels during operation and maintenance. Two experienced operators separately simulated operation of crane controls under load; one of these operators then simulated two arc chute maintenance protocols: sanding (protocol 1) and scraping, sanding, and blowing (protocol 2). The original arc chutes contained approximately 36% chrysotile. Personal breathing zone (PBZ) (n = 8) and area samples (n = 8) were collected and analyzed using phase contrast microscopy (PCM) and transmission electron microscopy. PCM-equivalent (PCME) concentrations were derived, from which 8-h time-weighted averages (TWA) were calculated. During operation, chrysotile was identified in one of the four PBZ samples, equivalent to a PCME concentration of 0.012 f/cm3 (8-h TWA: 0.011 f/cm3). During protocols 1 and 2, chrysotile was identified in all PBZ samples (n = 4); PCME concentrations (and corresponding 8-h TWA) were <0.013 and 0.021 f/cm3 (0.001 and 0.004 f/cm3) and 0.013 and 0.017 f/cm3 (0.003 f/cm3), respectively. Many of the airborne chrysotile fibers had matrix attached, supporting the low exposure potential during this work. These data indicate very low, if any, exposures to chrysotile asbestos during the simulated scenarios. In addition, these data could assist with refining assumptions in exposure reconstruction and inform the state-of-the science on low-level chrysotile exposure.

Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis.

As the first case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis (mTVT), the paper by Marinaccio et al (1) is potentially an important epidemiologic contribution. A careful review of the paper, however, raises a number of methodological issues. Any case-control study can be viewed as being nested within a conceptual cohort, with controls being sampled from the at-risk cohort as cases arise over time. This view of case-control studies leads to the concept of incidence-density sampling of controls (eg, 2, 3). For Marinaccio et al (1) this would mean that, as cases were registered over the study period, each would be matched to an individual control or set of controls of the same gender, age, and region of the country (since asbestos exposure varies by time and region [4]). For example, if a case were 50 years old in 1995, then any matched control should be close to age 50 in 1995 and of the same gender and from the same region as the case. Matching for age in this fashion automatically results in matching for year of birth, which is essential in this context because birth-cohort effects are determinants of asbestos exposure and mesothelioma incidence (eg, 5-8). If Marinaccio et al (1) used this scheme for age-matching, one would expect to see similar distributions of cases (table 1) and controls (table S3 in the supplemental material) by period of birth. Among males, however, the distributions of mesothelioma cases (whether pericardial or mTVT) and controls by period of birth are clearly different (P<0.001). Among females, the distributions of cases of pericardial mesothelioma and controls by birth year are less dissimilar (P≈0.05). Thus, the female cases of pericardial mesothelioma are better matched to controls on year of birth than are male cases of either mTVT or pericardial mesothelioma. We note also that the distributions of male and female controls by year of birth are distinctly different (P<0.002), whereas the birth-year distributions of cases of mesothelioma by site and gender are not (P≈0.8). In the Marinaccio et al (1) sensitivity analysis restricted to subjects born before 1950, the distributions of cases and controls by period of birth remain significantly different. Therefore, based on the reported evidence, cases and controls were not matched on birth cohort, thereby possibly biasing the results. Similarly, bias may result from the lack of matching on geographic region; while cases were registered from across Italy, controls were selected from only six regions. Although a sensitivity analysis restricted cases and controls to those from only the six regions, a comparison of tables S1 and S3 indicates that the regional distribution of controls is different from that of person-time observed; that is, the controls do not appear to be representative of the underlying population at risk by region. The second major issue of concern has to do with ascertainment of asbestos exposure. Information on exposure for the cases was presumably obtained at the time of registration. The two sets of controls, obtained from previously unpublished case-control studies, were interviewed during 2014-2015 and 2014-2016; that is, many years after the exposure for most cases was ascertained (1993-2015). Few other details of the control groups are provided, except that participation by one set of controls was <50%, raising additional concerns about selection bias. For details on the second set of controls, Marinaccio et al (1) reference a paper by Brandi et al (9). On review of that paper, however, we found no description of the control group, only references to three earlier papers. Marinaccio et al (1) present analyses only with both sets of controls combined; to evaluate potential sources of bias from the use of different sets of controls, they should also report results using each set of controls separately. The authors also did not detail their methods of exposure classification. For example, what does probable or possible exposure mean? The authors should at least present separate analyses of definite occupational exposure. Eighty cases of mTVT were registered, but only 68 were included in the analyses. Information on the 12 omitted cases (eg, age, year of birth, and region) would be helpful. Marinaccio et al (1) did not provide clear information on what occupations and/or industries they considered as exposed to asbestos. In an earlier study, Marinaccio et al (10) remarked on the absence of pericardial mesothelioma and mTVT in industries with the highest exposures to asbestos, saying, "[t]he absence of exposures in the shipbuilding, railway and asbestos-cement industries … for all the 67 pericardial and testicular cases is noteworthy but not easy to interpret." By contrast, Marinaccio et al (1) stated, "[t]he economic sectors more frequently associated with asbestos exposure were construction, steel mills, metal-working industry, textile industry and agriculture." The possibility of exposure in the "agriculture economic sector" was not mentioned in Marinaccio et al (10) and appears not to have been considered in previous epidemiologic studies in Italy. In general, epidemiologic studies indicate that farmers and agricultural workers are not at increased risk of developing mesothelioma (eg, 11-17). The fact that few, if any, cases of mTVT and pericardial mesothelioma occurred in industries traditionally associated with high asbestos exposure raises the possibility that the results of Marinaccio et al (1) are attributable to deficiencies in study design, very possibly bias in the selection of controls, and deficiencies in exposure assessment and classification as described above, leading to a spurious association of occupational exposure with mTVT and male pericardial mesothelioma. Conflict of interest This research has received no outside funding. All authors are employees of Exponent, Inc., an international scientific and engineering consulting company. All authors have worked as both consulting and testifying experts in litigation matters related to asbestos exposure and asbestos-related disease. References 1. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 2. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 2008; Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 3. Richardson DB. An incidence density sampling program for nested case-control analyses. Occup Environ Med 2004 Dec;61(12):e59. https://doi.org/10.1136/oem.2004.014472. 4. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 5. La Vecchia C, Decarli A, Peto J, Levi F, Tomei F, Negri E. An age, period and cohort analysis of pleural cancer mortality in Europe. Eur J Cancer Prev 2000 Jun;9(3):179-84. https://doi.org/10.1097/00008469-200006000-00005. 6. Price B, Ware A. Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003. Am J Epidemiol 2004 Jan;159(2):107-12. https://doi.org/10.1093/aje/kwh025. 7. Moolgavkar SH, Meza R, Turim J. Pleural and peritoneal mesotheliomas in SEER: age effects and temporal trends, 1973-2005. Cancer Causes Control 2009 Aug;20(6):935-44. https://doi.org/10.1007/s10552-009-9328-9. 8. Moolgavkar SH, Chang ET, Mezei G, Mowat FS. Chapter 3. Epidemiology of mesothelioma. In Testa JR. Asbestos and mesothelioma; 2017. pp. 43-72. Cham, Switzerland: Springer International Publishing. 9. Brandi G, Di Girolamo S, Farioli A, de Rosa F, Curti S, Pinna AD et al. Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis. Cancer Causes Control 2013 May;24(5):911-8. https://doi.org/10.1007/s10552-013-0167-3. 10. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 11. Teschke K, Morgan MS, Checkoway H, Franklin G, Spinelli JJ, van Belle G et al. Mesothelioma surveillance to locate sources of exposure to asbestos. Can J Public Health 1997 May-Jun;88(3):163-8. https://doi.org/10.1007/BF03403881. 12. Bouchardy C, Schüler G, Minder C, Hotz P, Bousquet A, Levi F et al. Cancer risk by occupation and socioeconomic group among men--a study by the Association of Swiss Cancer Registries. Scand J Work Environ Health 2002;28(1 Suppl 1):1-88. 13. Hemminki K, Li X. Time trends and occupational risk factors for pleural mesothelioma in Sweden. J Occup Environ Med 2003a Apr;45(4):456-61. https://doi.org/10.1097/01.jom.0000058341.05741.7e. 14. Hemminki K, Li X. Time trends and occupational risk factors for peritoneal mesothelioma in Sweden. J Occup Environ Med 2003b Apr;45(4):451-5. https://doi.org/10.1097/01.jom.0000052960.59271.d4. 15. Pukkala E, Martinsen JI, Lynge E, Gunnarsdottir HK, Sparén P, Tryggvadottir L et al. Occupation and cancer - follow-up of 15 million people in five Nordic countries. Acta Oncol 2009;48(5):646-790. https://doi.org/10.1080/02841860902913546. 16. Rolland P, Gramond C, Berron H, Ducamp S, Imbernon E, Goldberg M et al. Mesotheliome pleural: Professions et secteurs d'activite a risque chez les hommes [Pleural mesothelioma: Professions and occupational areas at risk among humans]. 2005; Institut de VeilleSanitaire, Departement Sante Travai, Saint-Maurice, France. 17. Rolland P, Gramond C, Lacourt A, Astoul P, Chamming's S, Ducamp S et al. PNSM Study Group. Occupations and industries in France at high risk for pleural mesothelioma: A population-based case-control study (1998-2002). Am J Ind Med 2010 Dec;53(12):1207-19. https://doi.org/10.1002/ajim.20895.

A 37-year Update on Mortality Patterns in an Expanded Cohort of Vermont Talc Miners and Millers.

OBJECTIVES: The aim of this study was to update a cohort of Vermont talc workers to include 37 additional years of follow-up time. METHODS: Standardized mortality ratios (SMR) and 95% confidence intervals (CIs) were calculated for 70+ causes of death. US population mortality rates were used as reference. RESULTS: All-cause mortality was 30% higher than the US population (SMR 133.4, 95% CI, 119.7 to 148.3). Significant elevations occurred in nonmalignant respiratory disease (NMRD) (SMR 273.0, 95% CI, 210.2 to 348.6) and other nonmalignant respiratory disease (ONMRD) (SMR 413.1, 95% CI, 287.7 to 574.5). ONMRD was elevated across all length of employment categories and a test for linear trend was significant (P = 0.007). CONCLUSIONS: This study provides further evidence that excess deaths among Vermont talc workers are due largely to excess mortality from NMRD; there is no evidence of increased risk of respiratory cancer.

Therapeutic radiation for lymphoma and risk of second primary malignant mesothelioma.

PURPOSE: This large, population-based U.S. study of lymphoma patients followed for up to four decades enables detailed analysis of second primary mesothelioma risk after radiotherapy. METHODS: U.S. Surveillance, Epidemiology, and End Results data were used to identify second primary mesothelioma among patients diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) between 1973 and 2014. Standardized incidence ratios (SIRs) were calculated by radiotherapy. Multivariate adjusted associations were examined using competing risks survival analysis. RESULTS: Among 47,219 HL patients (19,538 irradiated) and 252,090 NHL patients (52,454 irradiated), second primary mesothelioma developed among 28 lymphoma patients who received radiotherapy and 59 who did not. Mesothelioma risk was increased among HL and NHL patients treated with radiotherapy [SIR = 1.78, 95% confidence interval (CI) 1.18-2.58], but not without radiotherapy. After multivariate adjustment, radiotherapy was associated with increased mesothelioma risk (relative risk = 1.64, 95% CI 1.05-2.57), especially in lymphoma patients diagnosed before 1995 and after a latency of at least 10 years, and apparently with younger age at diagnosis. CONCLUSIONS: The increase in second primary mesothelioma risk following radiotherapy for lymphoma is independent of several patient and disease characteristics, and is higher with earlier treatment era and longer latency.

Epidemiology of mesothelioma of the pericardium and tunica vaginalis testis.

PURPOSE: Malignant mesothelioma most commonly arises in the pleura and peritoneum but also occurs rarely at other anatomical sites with mesothelial tissue, namely, the pericardium and tunica vaginalis testis (TVT). This review provides a better understanding of the epidemiology of mesothelioma of these extrapleural sites. METHODS: We conducted a systematic review of the epidemiologic and clinical literature on pericardial mesothelioma and mesothelioma of the TVT. We also analyzed U.S. Surveillance, Epidemiology, and End Results cancer registry data to describe incidence patterns of these malignancies. RESULTS: An etiologic role of asbestos exposure has been hypothesized for pericardial and TVT mesotheliomas, but no analytical case-control epidemiologic studies exist to test this relationship. A substantial proportion of cases with these malignancies report no known asbestos exposure. In large occupational cohorts with heavy asbestos exposures, no cases of pericardial or TVT mesothelioma have been reported. Trends in the incidence of these malignancies do not match those of pleural mesothelioma, which correspond to historical trends of commercial asbestos use. A male preponderance of pericardial mesothelioma is not evident. CONCLUSIONS: In the absence of analytic epidemiologic studies, the etiologic role of environmental risk factors for mesothelioma of the pericardium and TVT remains elusive.

An international assessment of ovarian cancer incidence and mortality.

OBJECTIVE: To assess and characterize the temporal variation in ovarian cancer incidence and mortality by age within countries in the Americas, Europe, Asia, and Oceania. METHODS/MATERIALS: Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in the United States (U.S.) were used to assess ovarian cancer incidence rates (1998-2008) and mortality rates, (1988-2007 for 12-month survival, 1988-2006 for 24-month survival, and 1988-2003 for 60-month survival), stratified by age at diagnosis. Data from GLOBOCAN were used to calculate country-specific incidence rates for 2010 and 2020 and case-fatality rates for 2010. RESULTS: A statistically significant decrease in Annual Percent Change (APC) of ovarian cancer incidence was observed in the U.S. for all women (-1.03%), among women who were diagnosed at <65 years of age (-1.09%) and among women who were diagnosed at ≥65 years of age (-0.95%). There was a statistically significant increase in the observed APC for survival at 12-months (0.19%), 24-months (0.58%), and 60-months (0.72%) for all women; however, 5-year survival for advanced stage (III or IV) disease was low at less than 50% for women <65 years and less than 30% for women ≥65 years. Global results showed a wide range in ovarian cancer incidence rates, with China exhibiting the lowest rates and the Russian Federation and the United Kingdom exhibiting the highest rates. CONCLUSIONS: Ovarian cancer survival has shown modest improvement from a statistical perspective in the U.S. However, it is difficult to ascertain how clinically relevant these improvements are at the population or patient level.

Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors.

BACKGROUND: Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. METHODS: Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. RESULTS: Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7-7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5-1.7); carcinoembryonic antigen level, 1.9 (1.1-3.2); extrahepatic disease, 1.9 (1.5-2.4); poor tumor grade, 1.9 (1.3-2.7); positive margin, 2.0 (1.7-2.5); >1 liver metastases, 1.6 (1.4-1.8); and >3 cm tumor diameter, 1.5 (1.3-1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. CONCLUSION: The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival.

Use of electronic medical records (EMR) for oncology outcomes research: assessing the comparability of EMR information to patient registry and health claims data.

UNLABELLED: Electronic medical records (EMRs) are used increasingly for research in clinical oncology, epidemiology, and comparative effectiveness research (CER). OBJECTIVE: To assess the utility of using EMR data in population-based cancer research by comparing a database of EMRs from community oncology clinics against Surveillance Epidemiology and End Results (SEER) cancer registry data and two claims databases (Medicare and commercial claims). STUDY DESIGN AND SETTING: DEMOGRAPHIC, CLINICAL, AND TREATMENT PATTERNS IN THE EMR, SEER, MEDICARE, AND COMMERCIAL CLAIMS DATA WERE COMPARED USING SIX TUMOR SITES: breast, lung/bronchus, head/neck, colorectal, prostate, and non-Hodgkin's lymphoma (NHL). We identified various challenges in data standardization and selection of appropriate statistical procedures. We describe the patient and clinic inclusion criteria, treatment definitions, and consideration of the administrative and clinical purposes of the EMR, registry, and claims data to address these challenges. RESULTS: Sex and 10-year age distributions of patient populations for each tumor site were generally similar across the data sets. We observed several differences in racial composition and treatment patterns, and modest differences in distribution of tumor site. CONCLUSION: Our experience with an oncology EMR database identified several factors that must be considered when using EMRs for research purposes or generalizing results to the US cancer population. These factors were related primarily to evaluation of treatment patterns, including evaluation of stage, geographic location, race, and specialization of the medical facilities. While many specialty EMRs may not provide the breadth of data on medical care, as found in comprehensive claims databases and EMR systems, they can provide detailed clinical data not found in claims that are extremely important in conducting epidemiologic and outcomes research.

Mesothelioma in vehicle mechanics: is the risk different for Australians?

BACKGROUND: The question of whether vehicle mechanics have an increased risk of mesothelioma has important public health implications. Calculations of relative risk using case reports from the Australian Mesothelioma Registry (AMR) indicate increased risks; however, this contrasts with the results of 19 epidemiologic studies that have found no association. AIM: To evaluate potential explanations for the discrepancy of findings from epidemiologic studies and AMR reports. METHODS: We evaluated three hypotheses as possible explanations for the inconsistency between the AMR-based calculations and the findings from published epidemiologic studies: (i) differences in exposure characteristics of Australian vehicle mechanics versus vehicle mechanics in North America and Europe, (ii) limitations of the AMR data and (iii) errors in the risk calculations based on AMR data. We reviewed available exposure information specific to Australian vehicle mechanics and AMR data, obtained from the Australian National Occupational Health and Safety Commission, for this evaluation. RESULTS: We did not identify differences in workplace exposures, processes or fibre type among Australian vehicle mechanics compared to vehicle mechanics in other countries. Our analysis of primary AMR data identified several errors in exposure classification and in the assumptions used to calculate relative risk. CONCLUSIONS: Discrepancies between epidemiologic studies and AMR-based calculations cannot be explained by differences in exposure. These discrepancies are most likely attributable to inadequate occupational information and classification in the AMR from 1986 forward and to erroneous assumptions used to derive relative risk estimates for mesothelioma among Australian vehicle mechanics.

State-of-the-science review: Does manganese exposure during welding pose a neurological risk?

Recent studies report that exposure to manganese (Mn), an essential component of welding electrodes and some steels, results in neurotoxicity and/or Parkinson's disease (PD) in welders. This "state-of-the-science" review presents a critical analysis of the published studies that were conducted on a variety of Mn-exposed occupational cohorts during the last 100 yr, as well as the regulatory history of Mn and welding fumes. Welders often perform a variety of different tasks with varying degrees of duration and ventilation, and hence, to accurately assess Mn exposures that occurred in occupational settings, some specific information on the historical work patterns of welders is desirable. This review includes a discussion of the types of exposures that occur during the welding process--for which limited information relating airborne Mn levels with specific welding activities exists--and the human health studies evaluating neurological effects in welders and other Mn-exposed cohorts, including miners, millers, and battery workers. Findings and implications of studies specifically conducted to evaluate neurobehavioral effects and the prevalence of PD in welders are also discussed. Existing exposure data indicate that, in general, Mn exposures in welders are less than those associated with the reports of clinical neurotoxicity (e.g., "manganism") in miners and smelter workers. It was also found that although manganism was observed in highly exposed workers, the scant exposure-response data available for welders do not support a conclusion that welding is associated with clinical neurotoxicity. The available data might support the development of reasonable "worst-case" exposure estimates for most welding activities, and suggest that exposure simulation studies would significantly refine such estimates. Our review ends with a discussion of the data gaps and areas for future research.

Cumulative asbestos exposure for US automobile mechanics involved in brake repair (circa 1950s-2000).

We analyzed cumulative lifetime exposure to chrysotile asbestos experienced by brake mechanics in the US during the period 1950-2000. Using Monte Carlo methods, cumulative exposures were calculated using the distribution of 8-h time-weighted average exposure concentrations for brake mechanics and the distribution of job tenure data for automobile mechanics. The median estimated cumulative exposures for these mechanics, as predicted by three probabilistic models, ranged from 0.16 to 0.41 fibers per cubic centimeter (f/cm(3)) year for facilities with no dust-control procedures (1970s), and from 0.010 to 0.012 f/cm(3) year for those employing engineering controls (1980s). Upper-bound (95%) estimates for the 1970s and 1980s were 1.96 to 2.79 and 0.07-0.10 f/cm(3) year, respectively. These estimates for US brake mechanics are consistent with, but generally slightly lower than, those reported for European mechanics. The values are all substantially lower than the cumulative exposure of 4.5 f/cm(3) year associated with occupational exposure to 0.1 f/cm(3) of asbestos for 45 years that is currently permitted under the current occupational exposure limits in the US. Cumulative exposures were usually about 100- to 1,000-fold less than those of other occupational groups with asbestos exposure for similar time periods. The cumulative lifetime exposure estimates presented here, combined with the negative epidemiology data for brake mechanics, could be used to refine the risk assessments for chrysotile-exposed populations.

Pleural plaques: a review of diagnostic issues and possible nonasbestos factors.

The authors reviewed nonasbestos etiologies and diagnostic issues related to pleural plaques. Through searches of PUBMED and DIALOG using the term pleural plaques, they identified 125 articles. The authors found additional references by reviewing citations of these 125 articles. Exposure to nonasbestos agents (eg, erionite, silicates, manmade fibers) was cited as a possible factor in plaque development, although this association was based on limited data; empyema, tuberculosis, rib fractures, and hemothorax also were cited as potential etiologies. Rib companion shadows, fat, intercostal vessels, and muscles can appear as plaques; thus, radiographic diagnosis requires careful evaluation. Chest x-rays show large false negative and varying false positive rates. The terms calcification and thickening often were used as synonymous with plaques; however, these terms have different meanings. The authors concluded that plaques may be associated with nonasbestos exposures and certain medical conditions. Without a thorough exposure/medical history, plaque reports can be misleading.

Human health risk and exposure assessment of chromium (VI) in tap water.

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.