Quantitative Assessment of Exposure to the Mycotoxin Ochratoxin A in Food

This article presents the methodology and the simulation results concerning the quantitative assessment of exposure to the fungus toxin named Ochratoxin A (OA) in food, in humans in France. We show that is possible to provide reliable calculations of exposure to OA with the conjugate means of a nonparametric-type method of simulation, a parametric-type method of simulation, and the use of bootstrap confidence intervals. In the context of the Monte Carlo simulation, the nonparametric method takes into account the consumptions and the contaminations in the simulations only via the raw data whereas the parametric method depends on the random samplings from distribution functions fitted to consumption and contamination data. Our conclusions are based on eight types of food only. Nevertheless, they are meaningful due to the major importance of these foodstuffs in human nourishment in France. This methodology can be applied whatever the food contaminant (pesticides, other mycotoxins, Cadmium, etc.) when data are available.     

Significance of Exposure Assessment to Analysis of Cancer Risk from Inorganic Arsenic in Drinking Water in Taiwan

The primary source of evidence that inorganic arsenic in drinking water is associated with increased mortality from cancer at internal sites (bladder, liver, lung, and other organs) is a large ecologic study conducted in regions of Southwest Taiwan endemic to Blackfoot disease. The dose-response patterns for lung, liver, and bladder cancers display a nonlinear dose-response relationship with arsenic exposure. The data do not appear suitable, however, for the more refined task of dose-response assessment, particularly for inference of risk at the low arsenic concentrations found in some U.S. water supplies. The problem lies in variable arsenic concentrations between the wells within a village, largely due to a mix of shallow wells and deep artesian wells, and in having only one well test for 24 (40%) of the 60 villages. The current analysis identifies 14 villages where the exposure appears most questionable, based on criteria described in the text. The exposure values were then changed for seven of the villages, from the median well test being used as a default to some other point in the village's range of well tests that would contribute to smoothing the appearance of a dose-response curve. The remaining seven villages, six of which had only one well test, were deleted as outliers. The resultant dose-response patterns showed no evidence of excess risk below arsenic concentrations of 0.1 mg/l. Of course, that outcome is dependent on manipulation of the data, as described. Inclusion of the seven deleted villages would make estimates of risk much higher at low doses. In those seven villages, the cancer mortality rates are significantly high for their exposure levels, suggesting that their exposure values may be too low or that other etiological factors need to be taken into account.     

Leukemia Risk Associated with Benzene Exposure in the Pliofilm Cohort: I. Mortality Update and Exposure Distribution

The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital status update adding 6 years of observation on the rubber workers known as the Pliofilm cohort. Using traditional standardized mortality ratio (SMR) analysis, we investigate the impact of the additional information gathered in the NIOSH update. We also compare the effect of using three sets of job-, plant-, and year-specific exposure estimates on the evaluation of benzene's leukemogenicity. The lack of any additional cases of multiple myeloma does not support trends toward elevated risks for this endpoint (as had been observed earlier), and there is no indication of increased incidences of solid tumors (as predicted by animal studies). Qualitatively, which exposure estimates are used does not alter the conclusions. The data added in the update did not greatly modify the estimated relative risk of leukemia associated with benzene exposure, but did confirm previous findings that occupational exposure to high concentrations had leukemogenic potential. The fact that leukemia has not been observed in any individual who started employment in Pliofilm production after 1950 suggests that the observed leukemia cases could be a response to very high levels of benzene exposure that occurred during the early years of this manufacturing process.     

Benzene Inhalation by Parts Washers: New Estimates Based on Measures of Occupational Exposure to Solvent Coaromatics

Questions persist regarding assessment of workers’ exposures to products containing low levels of benzene, such as mineral spirit solvent (MSS). This study summarizes previously unpublished data for parts‐washing activities, and evaluates potential daily and lifetime cumulative benzene exposures incurred by workers who used historical and current formulations of a recycled mineral spirits solvent in manual parts washers. Measured benzene concentrations in historical samples from parts‐washing operations were frequently below analytical detection limits. To better assess benzene exposure among these workers, air‐to‐solvent concentration ratios measured for toluene, ethylbenzene, and xylenes (TEX) were used to predict those for benzene based on a statistical model, conditional on physical‐chemical theory supported by new thermodynamic calculations of TEX and benzene activity coefficients in a modeled MSS‐type solvent. Using probabilistic methods, the distributions of benzene concentrations were then combined with distributions of other exposure parameters to estimate eight‐hour time‐weighted average (TWA) exposure concentration distributions and corresponding daily respiratory dose distributions for workers using these solvents in parts washers. The estimated 50th (95th) percentile of the daily respiratory dose and corresponding eight‐hour TWA air concentration for workers performing parts washing are 0.079 (0.77) mg and 0.0030 (0.028) parts per million by volume (ppm) for historical solvent, and 0.020 (0.20) mg and 0.00078 (0.0075) ppm for current solvent, respectively. Both 95th percentile eight‐hour TWA respiratory exposure estimates for solvent formulations are less than 10% of the current Occupational Safety and Health Administration permissible exposure limit of 1.0 ppm for benzene.     

Exposure Assessment: Then, Now, and Quantum Leaps in the Future

Health risk assessments have become so widely accepted in the United States that their conclusions are a major factor in many environmental decisions. Although the risk assessment paradigm is 10 years old, the basic risk assessment process has been used by certain regulatory agencies for nearly 40 years. Each of the four components of the paradigm has undergone significant refinements, particularly during the last 5 years. A recent step in the development of the exposure assessment component can be found in the 1992 EPA Guidelines for Exposure Assessment. Rather than assuming worst-case or hypothetical maximum exposures, these guidelines are designed to lead to an accurate characterization, making use of a number of scientific advances. Many exposure parameters have become better defined, and more sensitive techniques now exist for measuring concentrations of contaminants in the environnment. Statistical procedures for characterizing variability, using Monte Carlo or similar approaches, eliminate the need to select point estimates for all individual exposure parameters. These probabilistic models can more accurately characterize the full range of exposures that may potentially be encountered by a given population at a particular site, reducing the need to select highly conservative values to account for this form of uncertainty in the exposure estimate. Lastly, our awareness of the uncertainties in the exposure assessment as well as our knowledge as to how best to characterize them will almost certainly provide evaluations that will be more credible and, therein, more useful to risk managers. If these refinements are incorporated into future exposure assessments, it is likely that our resources will be devoted to problems that, when resolved, will yield the largest improvement in public health.     

Wildfire Exposure Analysis on the National Forests in the Pacific Northwest,USA

We analyzed wildfire exposure for key social and ecological features on the national forests in Oregon and Washington. The forests contain numerous urban interfaces, old growth forests, recreational sites, and habitat for rare and endangered species. Many of these resources are threatened by wildfire, especially in the east Cascade Mountains fire‐prone forests. The study illustrates the application of wildfire simulation for risk assessment where the major threat is from large and rare naturally ignited fires, versus many previous studies that have focused on risk driven by frequent and small fires from anthropogenic ignitions. Wildfire simulation modeling was used to characterize potential wildfire behavior in terms of annual burn probability and flame length. Spatial data on selected social and ecological features were obtained from Forest Service GIS databases and elsewhere. The potential wildfire behavior was then summarized for each spatial location of each resource. The analysis suggested strong spatial variation in both burn probability and conditional flame length for many of the features examined, including biodiversity, urban interfaces, and infrastructure. We propose that the spatial patterns in modeled wildfire behavior could be used to improve existing prioritization of fuel management and wildfire preparedness activities within the Pacific Northwest region.     

Probabilistic Risk Assessment of Wastes Buried in the Ground

The differences between probabilistic risk assessment (PRA) and safety analysis (SA) are discussed, and it is shown that PRA is more suitable than SA for determining the acceptability of a technology. Since a PRA by the fault tree-event tree analysis method used for reactor safety studies does not seem to be practical for buried waste, an alternative approach is suggested using geochemical analogs. This method is illustrated for the cases of high-level and low-level radioactive waste and for chemical carcinogens released in coal burning.     

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).     

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).     

An Analysis of the Portfolio of Sites to Characterize for Selecting a Nuclear Repository

The U.S. Department of Energy has selected three sites, from five nominated, to characterize for a nuclear repository to permanently dispose of nuclear waste. This decision was made without the benefit of an analysis of this "portfolio" problem. This paper analyzes different portfolios of three sites for simultaneous characterization and strategies for sequential characterization. Characterization of each site, which involves significant subsurface excavation, is now estimated to cost $1 billion. Mainly because of the high characterization costs, sequential characterization strategies are identified which are the equivalent of $1.7-2.0 billion less expensive than the selected DOE simultaneous characterization of the three sites. If three sites are simultaneously characterized, one portfolio is estimated to be the equivalent of $100-400 million better than the selected DOE portfolio. Because of these potential savings and several other complicating factors that may influence the relative desirability of characterization strategies, a thorough analysis of characterization strategies that addresses the likelihood of finding disqualifying conditions during site characterization, uncertainties, and dependencies in forecast site repository costs, preclosure and postclosure health and safety impacts, potential delays of both sequential and simultaneous characterization strategies, and the environmental, socioeconomic, and health and safety impacts of characterization activities is recommended.     

Exposure Misclassification and Threshold Concentrations in Time Series Analyses of Air Pollution Health Effects

Linear, no-threshold relationships are typically reported for time series studies of air pollution and mortality. Since regulatory standards and economic valuations typically assume some threshold level, we evaluated the fundamental question of the impact of exposure misclassification on the persistence of underlying personal-level thresholds when personal data are aggregated to the population level in the assessment of exposure-response relationships. As an example, we measured personal exposures to two particle metrics, PM2.5 and sulfate (SO4(2-)), for a sample of lung disease patients and compared these with exposures estimated from ambient measurements Previous work has shown that ambient:personal correlations for PM2.5 are much lower than for SO4(2-), suggesting that ambient PM2.5 measurements misclassify exposures to PM2.5. We then developed a method by which the measured:estimated exposure relationships for these patients were used to simulate personal exposures for a larger population and then to estimate individual-level mortality risks under different threshold assumptions. These individual risks were combined to obtain the population risk of death, thereby exhibiting the prominence (and the value) of the threshold in the relationship between risk and estimated exposure. Our results indicated that for poorly classified exposures (PM2.5 in this example) population-level thresholds were apparent at lower ambient concentrations than specified common personal thresholds, while for well-classified exposures (e.g., SO4(2-)), the apparent thresholds were similar to these underlying personal thresholds. These results demonstrate that surrogate metrics that are not highly correlated with personal exposures obscure the presence of thresholds in epidemiological studies of larger populations, while exposure indicators that are highly correlated with personal exposures can accurately reflect underlying personal thresholds.     

Drinking Water as a Proportion of Total Human Exposure to Volatile N‐Nitrosamines

Some volatile N‐nitrosamines, primarily N‐nitrosodimethylamine (NDMA), are recognized as products of drinking water treatment at ng/L levels and as known carcinogens. The U.S. EPA has identified the N‐nitrosamines as contaminants being considered for regulation as a group under the Safe Drinking Water Act. Nitrosamines are common dietary components, and a major database (over 18,000 drinking water samples) has recently been created under the Unregulated Contaminant Monitoring Rule. A Monte Carlo modeling analysis in 2007 found that drinking water contributed less than 2.8% of ingested NDMA and less than 0.02% of total NDMA exposure when estimated endogenous formation was considered. Our analysis, based upon human blood concentrations, indicates that endogenous NDMA production is larger than expected. The blood‐based estimates are within the range that would be calculated from estimates based on daily urinary NDMA excretion and an estimate based on methylated guanine in DNA of lymphocytes from human volunteers. Our analysis of ingested NDMA from food and water based on Monte Carlo modeling with more complete data input shows that drinking water contributes a mean proportion of the lifetime average daily NDMA dose ranging from between 0.0002% and 0.001% for surface water systems using free chlorine or between 0.001% and 0.01% for surface water systems using chloramines. The proportions of average daily dose are higher for infants (zero to six months) than other age cohorts, with the highest mean up to 0.09% (upper 95th percentile of 0.3%).     

Uncertainty and Variation in Indirect Exposure Assessments: An Analysis of Exposure to Tetrachlorodibenzo-p-Dioxin from a Beef Consumption Pathway

Indirect exposures to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and other toxic materials released in incinerator emissions have been identified as a significant concern for human health. As a result, regulatory agencies and researchers have developed specific approaches for evaluating exposures from indirect pathways. This paper presents a quantitative assessment of the effect of uncertainty and variation in exposure parameters on the resulting estimates of TCDD dose rates received by individuals indirectly exposed to incinerator emissions through the consumption of home-grown beef. The assessment uses a nested Monte Carlo model that separately characterizes uncertainty and variation in dose rate estimates. Uncertainty resulting from limited data on the fate and transport of TCDD are evaluated, and variations in estimated dose rates in the exposed population that result from location-specific parameters and individuals'behaviors are characterized. The analysis indicates that lifetime average daily dose rates for individuals living within 10 km of a hypothetical incinerator range over three orders of magnitude. In contrast, the uncertainty in the dose rate distribution appears to vary by less than one order of magnitude, based on the sources of uncertainty included in this analysis. Current guidance for predicting exposures from indirect exposure pathways was found to overestimate the intakes for typical and high-end individuals.     

Using Probabilistic Modeling to Evaluate Human Exposure to Organotin in Drinking Water Transported by Polyvinyl Chloride Pipe

The leaching of organotin (OT) heat stabilizers from polyvinyl chloride (PVC) pipes used in residential drinking water systems may affect the quality of drinking water. These OTs, principally mono- and di-substituted species of butyltins and methyltins, are a potential health concern because they belong to a broad class of compounds that may be immune, nervous, and reproductive system toxicants. In this article, we develop probability distributions of U.S. population exposures to mixtures of OTs encountered in drinking water transported by PVC pipes. We employed a family of mathematical models to estimate OT leaching rates from PVC pipe as a function of both surface area and time. We then integrated the distribution of estimated leaching rates into an exposure model that estimated the probability distribution of OT concentrations in tap waters and the resulting potential human OT exposures via tap water consumption. Our study results suggest that human OT exposures through tap water consumption are likely to be considerably lower than the World Health Organization (WHO) "safe" long-term concentration in drinking water (150 μg/L) for dibutyltin (DBT)—the most toxic of the OT considered in this article. The 90th percentile average daily dose (ADD) estimate of 0.034 ± 2.92 × 10⁻⁴μg/kg day is approximately 120 times lower than the WHO-based ADD for DBT (4.2 μg/kg day).     

Impact of Cooking Procedures and Storage Practices at Home on Consumer Exposure to Listeria Monocytogenes and Salmonella Due to the Consumption of Pork Meat

The objective of this research was to analyze the impact of different cooking procedures (i.e., gas hob and traditional static oven) and levels of cooking (i.e., rare, medium, and well‐done) on inactivation of Listeria monocytogenes and Salmonella in pork loin chops. Moreover, the consumer's exposure to both microorganisms after simulation of meat leftover storage at home was assessed. The results showed that well‐done cooking in a static oven was the only treatment able to inactivate the tested pathogens. The other cooking combinations allowed to reach in the product temperatures always ≥73.6 °C, decreasing both pathogens between 6 log₁₀ cfu/g and 7 log₁₀ cfu/g. However, according to simulation results, the few cells surviving cooking treatments can multiply during storage by consumers up to 1 log₁₀ cfu/g, with probabilities of 0.059 (gas hob) and 0.035 (static oven) for L. monocytogenes and 0.049 (gas hob) and 0.031 (static oven) for Salmonella . The key factors affecting consumer exposure in relation to storage practices were probability of pathogen occurrence after cooking, doneness degree, time of storage, and time of storage at room temperature. The results of this study can be combined with prevalence data and dose–response models in risk assessment models and included in guidelines for consumers on practices to be followed to manage cooking of pork meat at home.     

Modeling Long-Term Exposure of the Whole Population to Chemicals in Food

This paper discusses a statistical exposure model (STEM) that can be used to estimate the percentage of the population exceeding ingestion intake criteria (e.g., ADI or TDI). In addition, STEM may be linked to toxicokinetic models to evaluate the interindividual variability in internal doses that results from variability in consumption habits. The assumptions of STEM are investigated by analyzing dioxin and cadmium intake data for the Dutch population.     

Acute Exposure to Extremely Hazardous Substances: An Analysis of Environmental Equity

Although environmental equity research has focused primarily on chronic pollution sources, recent advances in environmental modeling and geographic information systems (GIS) provide a foundation for developing measures that can be used to evaluate differential exposure to acute pollution events. This article describes a methodology that uses facility-specific information to develop a risk surface representing the spatial distribution of accidental exposure to hazardous substances in a study area. Environmental pollution models recommended by the U.S. Environmental Protection Agency were used in conjunction with GIS software to achieve this objective. The methodology was implemented in a large metropolitan region (Hillsborough County, Florida) to examine disproportionate exposure to worst-case releases of extremely hazardous substances. The environmental inequity hypothesis was investigated by directly comparing the distribution of potential exposures within each racial (non-White versus White) and income (below poverty versus above poverty) subgroup. The results indicate that a significantly large proportion of both non-White and impoverished individuals resided in areas potentially exposed to multiple accidental releases.     

Integration of Probabilistic Exposure Assessment and Probabilistic Hazard Characterization

A method is proposed for integrated probabilistic risk assessment where exposure assessment and hazard characterization are both included in a probabilistic way. The aim is to specify the probability that a random individual from a defined (sub)population will have an exposure high enough to cause a particular health effect of a predefined magnitude, the critical effect size ( CES ). The exposure level that results in exactly that CES in a particular person is that person's individual critical effect dose ( ICED ). Individuals in a population typically show variation, both in their individual exposure ( IEXP ) and in their ICED . Both the variation in IEXP and the variation in ICED are quantified in the form of probability distributions. Assuming independence between both distributions, they are combined (by Monte Carlo) into a distribution of the individual margin of exposure ( IMoE ). The proportion of the IMoE distribution below unity is the probability of critical exposure ( PoCE ) in the particular (sub)population. Uncertainties involved in the overall risk assessment (i.e., both regarding exposure and effect assessment) are quantified using Monte Carlo and bootstrap methods. This results in an uncertainty distribution for any statistic of interest, such as the probability of critical exposure ( PoCE ). The method is illustrated based on data for the case of dietary exposure to the organophosphate acephate. We present plots that concisely summarize the probabilistic results, retaining the distinction between variability and uncertainty. We show how the relative contributions from the various sources of uncertainty involved may be quantified.     

Quantitative Risk Assessment of Listeria monocytogenes in French Cold-Smoked Salmon: I. Quantitative Exposure Assessment

A quantitative assessment of the exposure to Listeria monocytogenes from cold-smoked salmon (CSS) consumption in France is developed. The general framework is a second-order (or two-dimensional) Monte Carlo simulation, which characterizes the uncertainty and variability of the exposure estimate. The model takes into account the competitive bacterial growth between L. monocytogenes and the background competitive flora from the end of the production line to the consumer phase. An original algorithm is proposed to integrate this growth in conditions of varying temperature. As part of a more general project led by the French Food Safety Agency (Afssa), specific data were acquired and modeled for this quantitative exposure assessment model, particularly time-temperature profiles, prevalence data, and contamination-level data. The sensitivity analysis points out the main influence of the mean temperature in household refrigerators and the prevalence of contaminated CSS on the exposure level. The outputs of this model can be used as inputs for further risk assessment.     

Exposure to Environmental Tobacco Smoke in the Workplace and the Impact of Away-From-Work Exposure

Concentrating on exposure in workplaces where smoking occurs, we examined environmental tobacco smoke (ETS)-related concentration data from the 16-City Study.^(1,2) This study involved a large population of nonsmokers, used personal monitors, and encompassed a wide selection of ETS-related constituents. This first article in a series of three describes the 16-City Study, considers the impact of demographic variables, and concludes that these variables did not explain differences in exposure to ETS. We compared 16-City Study concentrations obtained in the workplace to previously reported workplace concentrations and determined that data from this study were representative of current ETS exposure in nonmanufacturing workplaces where smoking occurs. Considering factors other than demographic factors, we found that, not surprisingly, the number of cigarettes observed in the workplace had an impact on exposure concentrations. Finally, we compared people from homes where smoking occurs with people from nonsmoking homes and found that people from smoking homes observed more smoking in the workplace and experienced higher concentrations of ETS-related compounds in the workplace, even when they observed the same number of cigarettes being smoked in the workplace. In two subsequent articles in this series, we discuss relationships between various ETS markers and provide estimates of distributions of doses to nonsmoking workers employed in workplaces where smoking occurs.