Dose-Response and Risk Assessment of Airborne Hexavalent Chromium and Lung Cancer Mortality

This study evaluates the dose-response relationship for inhalation exposure to hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate production facility, and provides estimates of the carcinogenic potency. The data were analyzed using relative risk and additive risk dose-response models implemented with both Poisson and Cox regression. Potential confounding by birth cohort and smoking prevalence were also assessed. Lifetime cumulative exposure and highest monthly exposure were the dose metrics evaluated. The estimated lifetime additional risk of lung cancer mortality associated with 45 years of occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was 0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI: 0.00143, 0.00302) for the additive risk model assuming a linear dose response for cumulative exposure with a five-year lag. Extrapolating these findings to a continuous (e.g., environmental) exposure scenario yielded an environmental unit risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for the additive risk model. The relative risk model is preferred because it is more consistent with the expected trend for lung cancer risk with age. Based on statistical tests for exposure-related trend, there was no statistically significant increased lung cancer risk below lifetime cumulative occupational exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average monthly exposure did not exceed the current Permissible Exposure Limit (52 microg/m3). It is acknowledged that this study had limited power to detect increases at these low exposure levels. These cancer potency estimates are comparable to those developed by U.S. regulatory agencies and should be useful for assessing the potential cancer hazard associated with inhaled Cr(VI).     

Urinary Excretion of Chromium Following Ingestion of Chromite-Ore Processing Residues in Humans: Implications for Biomonitoring

Biomonitoring programs for urinary chromium (Cr) typically attempt to evaluate occupational exposure via the inhalation route. This study investigated whether Cr can be detected in the urine of people following the ingestion of soils that contain relatively high concentrations of chromium in chromite ore processing residue (COPR). To evaluate the reasonableness of using urinary monitoring to assess environmental exposure, six volunteers ingested 400 mg of soil/day (low-dose group), two others ingested 2.0 g of soil/day (high-dose group) for 3 consecutive days, and one person ingested a placebo on each of 3 days. The soil and COPR mixture contained concentrations of total chromium (Cr) and hexavalent chromium [Cr(VI)] of 103 ± 20 and 9.3 ± 3.8 mg/kg, respectively. Therefore, the low-dose group ingested 41 μg Cr/day [including 3.7 μg Cr(VI)] and the high-dose group ingested 206 μg Cr/day [including 18.6 μg Cr(VI)] on each of 3 consecutive days. All urine samples were collected and analyzed individually for total Cr on the day prior to dosing, during the 3 days of dosing, and up to the first void 48 h after the last dose. No significant increases in urinary Cr excretion were found when background excretion data were compared with data following each of the 3 days of dosing or in daily mean urine concentrations of the high- vs the low-dose groups. It appears that Cr present in a soil and COPR mixture at Cr doses up to 200 μg/day is not sufficiently bioavailable for biomonitoring of urine to be informative. These results are consistent with previously published findings suggesting that incidental exposure to dusts and soils containing comparable levels of Cr will not result in increased concentrations of Cr in urine.     

Assessment of Airborne Exposure to Trihalomethanes from Tap Water in Residential Showers and Baths

This study evaluates airborne concentrations of common trihalomethane (THM) compounds in bathrooms during showering and bathing in homes supplied with chlorinated tap water. Three homes in an urban area were selected, each having three bedrooms, a full bath, and approximately 1,000 square feet of living area. THMs were concurrently measured in tap water and air in the shower/bath enclosure and the bathroom vanity area using Summa canisters. Chloroform (TCM), bromodichloromethane (BDCM), and chlorodibromomethane (CDBM) were quantified using U.S. Environmental Protection Agency (EPA) Method TO-14. Air samples were collected prior to, during, and after the water-use event for 16 shower and 7 bath events. Flow rate and temperature were measured, but not controlled. The increase in average airborne concentration (+/- standard error) during showers (expressed as microg/m3 in shower enclosure or bathroom air per microg/L in water) was 3.3+/-0.4 for TCM, 1.8+/-0.3 for BDCM, and 0.5+/-0.1 for CDBM (n = 12), and during baths was 1.2+/-0.4 for TCM, 0.59+/-0.21 for BDCM, and 0.15+/-0.05 for CDBM (n = 4). The relative contribution of each chemical to the airborne concentrations was consistent for all shower and bath events, with apparent release of TCM > BDCM > CDBM. The results are therefore consistent with their relative concentration in tap water and their vapor pressures. When the shower findings for TCM are normalized for water concentration, flow rate, shower volume, and duration, the average exposure concentrations in these urban residences are about 30% lower than those reported by other investigators using EPA analytical methods. This difference is likely attributable primarily to greater air exchange rates in residential shower/bath stalls compared to more "airtight" laboratory shower chambers. This appears to be the first field study to thoroughly evaluate THM exposures from residential showers and baths, and can be used to validate previously published models of tap water volatile chemical transfer to indoor air.     

Recommended Distributions for Exposure Factors Frequently Used in Health Risk Assessment

Although there has been nearly complete agreement in the scientific community that Monte Carlo techniques represent a significant improvement in the exposure assessment process, virtually all state and federal risk assessments still rely on the traditional point estimate approach. One of the rate-determining steps to a timely implementation of Monte Carlo techniques to regulatory decision making is the development of "standard" data distributions that are considered applicable to any setting. For many exposure variables, there is no need to wait any longer to adopt Monte Carlo techniques into regulatory policy since there is a wealth of data from which a robust distribution can be developed and ample evidence to indicate that the variable is not significantly influenced by site-specific conditions. In this paper, we propose several distributions that can be considered standard and customary for most settings. Age-specific distributions for soil ingestion rates, inhalation rates, body weights, skin surface area, tapwater and fish consumption, residential occupancy and occupational tenure, and soil-on-skin adherence were developed. For each distribution offered in this paper, we discuss the adequacy of the database, derivation of the distribution, and applicability of the distribution to various settings and conditions.     

An Empirical Approach for Deriving Information on Total Duration of Exposure from Information on Historical Exposure

Exposure duration is an important component in determining long-term dose rates associated with exposure to environmental contaminants. Surveys of exposed populations collect information on individuals' past behaviors, including the durations of a behavior up to the time of the survey. This paper presents an empirical approach for determining the distribution of total durations that is consistent with the distribution past durations obtained from surveys. This approach is appropriate where the rates of beginning and ending a behavior are relatively constant over time. The approach allows the incorporation of information on the distribution of age in a population into the determination of the distribution of durations. The paper also explores the impact of "longevity" bias on survey data. A case study of the application of this approach to two angler populations is also provided. The results of the case study have characteristics similar to the results reported by Israeli and Nelson ( Risk Anal. 12, 65-72 (1992)) from their analytical model of residential duration. Specifically, the average period of time for the total duration in the entire population is shorter than the average period of time reported for historical duration in the surveyed individuals.     

The Use of Multizone Models to Estimate an Airborne Chemical Contaminant Generation and Decay Profile: Occupational Exposures of Hairdressers to Vinyl Chloride in Hairspray During the 1960s and 1970s

Vinyl chloride (VC) was used as a propellant in a limited percentage of aerosol hairspray products in the United States from approximately 1967 to 1973. The question has arisen whether occupational exposures of hairdressers to VC-containing hairsprays in hair salons were sufficient to increase the risk for developing hepatic angiosarcoma (HAS). Transient two-zone and steady-state three-zone models were used to estimate the historical airborne concentration of VC for individual hairdressers using hairspray as well as estimated contributions from other hairdressers in the same salon. Concentrations of VC were modeled for small, medium, and large salons, as well as a representative home salon. Model inputs were determined using published literature, and variability in these inputs was also considered using Monte Carlo techniques. The 95th percentile for the daily time-weighted average exposure for small, medium, and large salons, assuming a market-share fraction of VC-containing hairspray use from the Monte Carlo analysis, was about 0.3 ppm, and for the home salon scenario was 0.1 ppm. The 95th percentile value for the cumulative lifetime exposure of the hairdressers was 2.8 ppm-years for the home salon scenario and 2.0 ppm-years for the small, medium, and large salon scenarios. If using the assumption that all hairsprays used in a salon contained VC, the 95th percentile of the theoretical lifetime cumulative dose was estimated to be 52–79 ppm-years. Estimated lifetime doses were all below the threshold dose for HAS of about 300 to 500 ppm-years reported in the published epidemiology literature.     

Evaluation of Take‐Home Exposure and Risk Associated with the Handling of Clothing Contaminated with Chrysotile Asbestos

The potential for para‐occupational (or take‐home) exposures from contaminated clothing has been recognized for the past 60 years. To better characterize the take‐home asbestos exposure pathway, a study was performed to measure the relationship between airborne chrysotile concentrations in the workplace, the contamination of work clothing, and take‐home exposures and risks. The study included air sampling during two activities: (1) contamination of work clothing by airborne chrysotile (i.e., loading the clothing), and (2) handling and shaking out of the clothes. The clothes were contaminated at three different target airborne chrysotile concentrations (0–0.1 fibers per cubic centimeter [f/cc], 1–2 f/cc, and 2–4 f/cc; two events each for 31–43 minutes; six events total). Arithmetic mean concentrations for the three target loading levels were 0.01 f/cc, 1.65 f/cc, and 2.84 f/cc (National Institute of Occupational Health and Safety [NIOSH] 7402). Following the loading events, six matched 30‐minute clothes‐handling and shake‐out events were conducted, each including 15 minutes of active handling (15‐minute means; 0.014–0.097 f/cc) and 15 additional minutes of no handling (30‐minute means; 0.006–0.063 f/cc). Percentages of personal clothes‐handling TWAs relative to clothes‐loading TWAs were calculated for event pairs to characterize exposure potential during daily versus weekly clothes‐handling activity. Airborne concentrations for the clothes handler were 0.2–1.4% (eight‐hour TWA or daily ratio) and 0.03–0.27% (40‐hour TWA or weekly ratio) of loading TWAs. Cumulative chrysotile doses for clothes handling at airborne concentrations tested were estimated to be consistent with lifetime cumulative chrysotile doses associated with ambient air exposure (range for take‐home or ambient doses: 0.00044–0.105 f/cc year).     

A Calibrated Human PBPK Model for Benzene Inhalation with Urinary Bladder and Bone Marrow Compartments

A physiologically‐based pharmacokinetic (PBPK) model of benzene inhalation based on a recent mouse model was adapted to include bone marrow (target organ) and urinary bladder compartments. Empirical data on human liver microsomal protein levels and linked CYP2E1 activities were incorporated into the model, and metabolite‐specific conversion rate parameters were estimated by fitting to human biomonitoring data and adjusting for background levels of urinary metabolites. Human studies of benzene levels in blood and breath, and phenol levels in urine were used to validate the rate of human conversion of benzene to benzene oxide, and urinary benzene metabolites from Chinese benzene worker populations provided model validation for rates of human conversion of benzene to muconic acid (MA) and phenylmercapturic acid (PMA), phenol (PH), catechol (CA), hydroquinone (HQ), and benzenetriol (BT). The calibrated human model reveals that while liver microsomal protein and CYP2E1 activities are lower on average in humans compared to mice, the mouse also shows far lower rates of benzene conversion to MA and PMA, and far higher conversion of benzene to BO/PH, and of BO/PH to CA, HQ, and BT. The model also differed substantially from existing human PBPK models with respect to several metabolic rate parameters of importance to interpreting benzene metabolism and health risks in human populations associated with bone marrow doses. The model provides a new methodological paradigm focused on integrating linked human liver metabolism data and calibration using biomonitoring data, thus allowing for model uncertainty analysis and more rigorous validation.