An approach to estimating the environmental burden of cancer from known and probable carcinogens: application to Ontario, Canada.

BACKGROUND: Quantifying the potential cancer cases associated with environmental carcinogen exposure can help inform efforts to improve population health. This study developed an approach to estimate the environmental burden of cancer and applied it to Ontario, Canada. The purpose was to identify environmental carcinogens with the greatest impact on cancer burden to support evidence-based decision making. METHODS: We conducted a probabilistic assessment of the environmental burden of cancer in Ontario. We selected 23 carcinogens that we defined as "environmental" (e.g., pollutants) and were relevant to the province, based on select classifications provided by the International Agency for Research on Cancer. We evaluated population exposure to the carcinogens through inhalation of indoor/outdoor air; ingestion of food, water, and dust; and exposure to radiation. We obtained or calculated concentration-response functions relating carcinogen exposure and the risk of developing cancer. Using both human health risk assessment and population attributable fraction models in a Monte Carlo simulation, we estimated the annual cancer cases associated with each environmental carcinogen, reporting the simulation summary (e.g., mean and percentiles). RESULTS: We estimated between 3540 and 6510 annual cancer cases attributable to exposure to 23 environmental carcinogens in Ontario. Three carcinogens were responsible for over 90% of the environmental burden of cancer: solar ultraviolet (UV) radiation, radon in homes, and fine particulate matter (PM2.5) in outdoor air. Eight other carcinogens had an estimated mean burden of at least 10 annual cancer cases: acrylamide, arsenic, asbestos, chromium, diesel engine exhaust particulate matter, dioxins, formaldehyde, and second-hand smoke. The remaining 12 carcinogens had an estimated mean burden of less than 10 annual cancer cases in Ontario. CONCLUSIONS: We found the environmental burden of cancer in Ontario to fall between previously estimated burdens of alcohol and tobacco use. These results allow for a comparative assessment across carcinogens and offer insights into strategies to reduce the environmental burden of cancer. Our analysis could be adopted by other jurisdictions and repeated in the future for Ontario to track progress in reducing cancer burden, assess newly classified environmental carcinogens, and identify top burden contributors.

Arsenic exposure and bladder cancer: quantitative assessment of studies in human populations to detect risks at low doses.

While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers.

Dietary exposure to dioxins and dioxin-like PCBs of Hong Kong adults: results of the first Hong Kong Total Diet Study.

Dioxins and dioxin-like polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) covered by the Stockholm Convention on POPs. To assess the associated health risk of the Hong Kong population, the dietary exposure of the Hong Kong population and various age-gender subgroups to dioxins and dioxin-like PCBs was estimated in the first Hong Kong Total Diet Study (TDS), where food samples were collected and prepared "as consumed". A total of 142 composite food samples, mainly foods of animal origin and their products and oily food, were analysed for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxin-like PCBs by the high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS) system. Dietary exposures were estimated by combining the analytical results with the food consumption data of Hong Kong adults. The mean and 95th percentile exposures to dioxins and dioxin-like PCBs of the Hong Kong population were 21.9 and 59.7 pg toxic equivalent (TEQ) kg⁻¹ body weight (bw) month⁻¹ respectively, which amounted to 31.3% and 85.2% of the provisional tolerable monthly intake (PTMI). The main dietary source of dioxins and dioxin-like PCBs was "Fish and seafood and their products" (61.9% of the total exposure), followed by "Meat, poultry and game and their products" (20.0%) and "Mixed dishes" (6.95%). The study findings suggest that the Hong Kong population is unlikely to experience the major undesirable health effects of dioxins and dioxin-like PCBs.

Aflatoxin m1 in milk products in china and dietary risk assessment.

This study was conducted to investigate the occurrence of aflatoxin M1 (AFM1) in milk products in China using the competitive enzyme-linked immunosorbent assay method and to estimate the dietary exposure to this toxin through a probabilistic approach. Based on the exposure assessment results, a quantitative cancer potency formula developed by the Joint Food and Agriculture Organization and World Health Organization Expert Committee on Food Additives was applied to assess the cancer risk. AFM1 was detected in 48.07% of the milk samples and 4.49% of the yoghurt samples. No samples contained AFM1 above the current regulatory limit in China. The simulated AFM1 intake (90% confidence interval) in various sex-age groups ranged from 0.023 (0.021 to 0.023) ng/kg of body weight per day for 30- to 45-year-old men to 0.382 (0.354 to 0.386) ng/kg of body weight per day for 2- to 4-year-old girls at the 99th percentile. The cancer risk of AFM1 to the general population of China was assessed to be 0.129 cancer cases per year per 10(8) persons at the 99th percentile. These results indicate that the health risk associated with AFM1 in milk in China is relatively low.

Development of a cancer-based chronic inhalation reference value for hexavalent chromium based on a nonlinear-threshold carcinogenic assessment.

The carcinogenicity of hexavalent chromium(CrVI) is of significant interest to regulatory agencies for the protection of public health and to industry. Additionally, the mode of action (MOA) and conditions under which CrVI may induce carcinogenicity (e.g., reductive capacity considerations) have recently been the subject of significant scientific debate. Epidemiological data supported by data relevant to the carcinogenic MOA support considering nonlinear-threshold carcinogenic assessments for comparison to default linear low-dose extrapolation approaches. This study reviews epidemiological studies available in the scientific literature and conducts additional statistical dose-response analyses to identify potential carcinogenic thresholds and points of departure (PODs) in the context of supportive MOA information for a nonlinear-threshold inhalation carcinogenic assessment. Dosimetric adjustments and application of appropriate uncertainty factors (total UF of 30) to the selected cumulative exposure POD results in a cancer-based chronic inhalation reference value (ReV) of 0.24 µgCrVI/m(3). This chronic ReV is 300 times higher than the 1 in 100,000 excess cancer risk air concentration of 8E-04 µg/m(3) based on USEPA's unit risk factor.

Fungal and microbial volatile organic compounds exposure assessment in a waste sorting plant.

In the management of solid waste, pollutants over a wide range are released with different routes of exposure for workers. The potential for synergism among the pollutants raises concerns about potential adverse health effects, and there are still many uncertainties involved in exposure assessment. In this study, conventional (culture-based) and molecular real-time polymerase chain reaction (RTPCR) methodologies were used to assess fungal air contamination in a waste-sorting plant which focused on the presence of three potential pathogenic/toxigenic fungal species: Aspergillus flavus, A. fumigatus, and Stachybotrys chartarum. In addition, microbial volatile organic compounds (MVOC) were measured by photoionization detection. For all analysis, samplings were performed at five different workstations inside the facilities and also outdoors as a reference. Penicillium sp. were the most common species found at all plant locations. Pathogenic/toxigenic species (A. fumigatus and S. chartarum) were detected at two different workstations by RTPCR but not by culture-based techniques. MVOC concentration indoors ranged between 0 and 8.9 ppm (average 5.3 ± 3.16 ppm). Our results illustrated the advantage of combining both conventional and molecular methodologies in fungal exposure assessment. Together with MVOC analyses in indoor air, data obtained allow for a more precise evaluation of potential health risks associated with bioaerosol exposure. Consequently, with this knowledge, strategies may be developed for effective protection of the workers.

Environmental risk assessment of arsenic and fluoride in the Chaco Province, Argentina: research advances.

The arsenic (As) and fluoride (F⁻) concentration in groundwater and potential adverse human health risk was investigated in the Central-West Region of the Chaco Province, northern Argentina. The mean concentration of As in shallow groundwater was 95 µg/L, where 76% of samples exceeded the World Health Organization (WHO) guideline value of 10 µg/L, while in deep groundwater it was 90 µg/L, where 63% samples exceeded 10 µg/L. For As health risk assessment, the average daily dose, hazard quotient (HQ), and cancer risk were calculated. The values of HQ were found to be >1 in 77% of samples. This level of contamination is considered to constitute a high chronic risk compared with U.S. Environmental Protection Agency (EPA) guidelines. Further, a significant portion of the population has lifetime carcinogenic risk >10⁻4 and may suffer from cancer. A positive correlation was observed between As and F⁻ in groundwater. The Código Alimentario Argentino (CAA) suggested a limit of F⁻ in drinking water as low as 0.8 mg/L under tropical environmental conditions; however, in shallow (39%) and deep groundwater (32%), samples exceeded these values. Exposure to F⁻ was calculated and compared with the adequate intake of minimal safe level exposure dose of 0.05 mg/kg/d and it was noted that 42% of population may be at high risk of fluorosis. Chronic exposure to high As and F⁻ levels in this population represents a concern due to possible adverse health effects attributed to these elements.

Occurrence of fumonisins in Catalonia (Spain) and an exposure assessment of specific population groups.

Fumonisin B1 (FB1) and B2 (FB2) are mycotoxins produced by Fusarium verticillioides and F. proliferatum and common contaminants of cereal crops. The objectives of this study were to (1) study the occurrence of fumonisins in Catalonia (north-eastern region of Spain) and (2) assess the exposure of the Catalonian population to these mycotoxins. Contamination data was provided by a wide survey where 928 individual samples were pooled to analyse 370 composite samples. Fumonisins were extracted and purified using immunoaffinity columns and determined by HPLC with fluorescence detection. The raw consumption data came from a nutritional study specifically designed to assess the dietary intake of the main foodstuffs related to fumonisin contamination for all population age groups. In addition, two specific groups were selected with respect to maize consumption: immigrants and celiac sufferers. Contamination and consumption data were combined by simulation using an essentially parametric-parametric (P-P) method. The P-P method draws sampling values from distribution functions fitted to consumption and contamination datasets. Moreover, to quantify the accuracy and reliability of the statistical estimates, we built related confidence intervals using a Pseudo-Parametric bootstrap method. The results of this study show that fumonisins are commonly found in some commodities on the Catalonian market, such as beer, corn snacks and ethnic foods; however, the values were well below the permitted maximum EU levels. The most exposed group were infants followed by immigrants but, in all cases, they were below the TDI of 2 µg/kg bw/day.

Human health risk assessment of synthetic turf fields based upon investigation of five fields in Connecticut.

Questions have been raised regarding possible exposures when playing sports on synthetic turf fields cushioned with crumb rubber. Rubber is a complex mixture with some components possessing toxic and carcinogenic properties. Exposure is possible via inhalation, given that chemicals emitted from rubber might end up in the breathing zone of players and these players have high ventilation rates. Previous studies provide useful data but are limited with respect to the variety of fields and scenarios evaluated. The State of Connecticut investigated emissions associated with four outdoor and one indoor synthetic turf field under summer conditions. On-field and background locations were sampled using a variety of stationary and personal samplers. More than 20 chemicals of potential concern (COPC) were found to be above background and possibly field-related on both indoor and outdoor fields. These COPC were entered into separate risk assessments (1) for outdoor and indoor fields and (2) for children and adults. Exposure concentrations were prorated for time spent away from the fields and inhalation rates were adjusted for play activity and for children's greater ventilation than adults. Cancer and noncancer risk levels were at or below de minimis levels of concern. The scenario with the highest exposure was children playing on the indoor field. The acute hazard index (HI) for this scenario approached unity, suggesting a potential concern, although there was great uncertainty with this estimate. The main contributor was benzothiazole, a rubber-related semivolatile organic chemical (SVOC) that was 14-fold higher indoors than outdoors. Based upon these findings, outdoor and indoor synthetic turf fields are not associated with elevated adverse health risks. However, it would be prudent for building operators to provide adequate ventilation to prevent a buildup of rubber-related volatile organic chemicals (VOC) and SVOC at indoor fields. The current results are generally consistent with the findings from studies conducted by New York City, New York State, the U.S. Environmental Protection Agency (EPA), and Norway, which tested different kinds of fields and under a variety of weather conditions.

Benzothiazole toxicity assessment in support of synthetic turf field human health risk assessment.

Synthetic turf fields cushioned with crumb rubber may be a source of chemical exposure to those playing on the fields. Benzothiazole (BZT) may volatilize from crumb rubber and result in inhalation exposure. Benzothiazole has been the primary rubber-related chemical found in synthetic turf studies. However, risks associated with BZT have not been thoroughly assessed, primarily because of gaps in the database. This assessment provides toxicity information for a human health risk assessment involving BZT detected at five fields in Connecticut. BZT exerts acute toxicity and is a respiratory irritant and dermal sensitizer. In a genetic toxicity assay BZT was positive in Salmonella in the presence of metabolic activation. BZT metabolism involves ring-opening and formation of aromatic hydroxylamines, metabolites with mutagenic and carcinogenic potential. A structural analogue 2-mercaptobenzothiazole (2-MBZT) was more widely tested and so is used as a surrogate for some endpoints. 2-MBZT is a rodent carcinogen with rubber industry data supporting an association with human bladder cancer. The following BZT toxicity values were derived: (1) acute air target of 110 µg/m(3) based upon a BZT RD(50) study in mice relative to results for formaldehyde; (2) a chronic noncancer target of 18 µg/m(3) based upon the no-observed-adverse-effect level (NOAEL) in a subchronic dietary study in rats, dose route extrapolation, and uncertainty factors that combine to 1000; (3) a cancer unit risk of 1.8E-07/µg-m(3) based upon a published oral slope factor for 2-MBZT and dose-route extrapolation. While there are numerous uncertainties in the BZT toxicology database, this assessment enables BZT to be quantitatively assessed in risk assessments involving synthetic turf fields. However, this is only a screening-level assessment, and research that better defines BZT potency is needed.

Traffic air pollution and risk of death from gastric cancer in Taiwan: petrol station density as an indicator of air pollutant exposure.

To investigate the relationship between air pollution and risk of death attributed to gastric cancer, a matched cancer case-control study was conducted using deaths that occurred in Taiwan from 2004 through 2008. Data for all eligible gastric cancer deaths were obtained and compared to a control group consisting of individuals who died from causes other than neoplasms and diseases that were associated with gastrointestinal (GIT) disorders. The controls were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was randomly selected from the set of possible controls for each cancer case. Data for the number of petrol stations in study municipalities were collected from two major petroleum supply companies. The petrol station density (per square kilometer) (PSD) for study municipalities was used as an indicator of a subject's exposure to benzene and other hydrocarbons present in ambient evaporative losses of petrol or to air emissions from motor vehicles. The exposed individuals were subdivided into three categories (≤25th percentile; 25th-75th percentile; >75th percentile) according to PSD in the residential municipality. Results showed that individuals who resided in municipalities with the highest PSD were at an increased risk of death attributed to gastric cancer compared to those subjects living in municipalities with the lowest PSD. The findings of this study warrant further investigation of the role of traffic air pollution exposure in the etiology of gastric cancer.

Simulation of deoxynivalenol intake from wheat consumption in Japan using the Monte Carlo method.

The aim of this study was to evaluate the current advisory level in Japan for deoxynivalenol (DON) in foods. To this end, we estimated the intake of DON based on its presence in wheat using a probabilistic computer simulation method. Values for the concentration of DON in wheat were based on those reported in surveys of 638 wheat samples conducted from 2002 to 2004. Data regarding consumption of 108 wheat-based products according to age group were obtained from the 2002 Japan national survey on food consumption. Two data sets on the consumption of wheat-based products and contamination of DON in wheat were analysed using three DON regulatory scenarios: no regulation, 1100 µg kg(-1) and 2000 µg kg(-1). Because consumption distributions contained two peaks for each age category, it was assumed that two log-normal distributions for each age category were needed to achieve a better fit to the distribution models. The results of simulated DON intake using the Monte Carlo method showed that children aged 1-6 years have the highest DON intake. However, the 95th percentile of simulated intake of DON in each age group was below the provisional maximum tolerable daily intake (TDI) of 1 µg kg(-1) body weight using any regulation scenario. The 99th percentile of simulated DON intake in the 1-6-year-old group was greater than TDI at approximately 2 µg kg(-1) body weight. These results suggest that the current dietary intake of DON from wheat consumption does not exert a significant health effect, but we may need to reconsider the current regulation value for the 1-6-year-old age group. In addition, we may need a better method to fit the distribution to the log-normal distribution better.

The significance of the Druckrey-Küpfmüller equation for risk assessment--the toxicity of neonicotinoid insecticides to arthropods is reinforced by exposure time.

The essence of the Druckrey-Küpfmüller equation dtn = constant (where d = daily dose and t = exposure time-to-effect, with n > 1) for chemical carcinogens is that the total dose required to produce the same effect decreases with decreasing exposure levels, even though the exposure times required to produce the same effect increase with decreasing exposure levels. Druckrey and Küpfmüller inferred that if both receptor binding and the effect are irreversible, exposure time would reinforce the effect. The Druckrey-Küpfmüller equation explains why toxicity may occur after prolonged exposure to very low toxicant levels. Recently, similar dose-response characteristics have been established for the toxicity of the neonicotinoid insecticides imidacloprid and thiacloprid to arthropods. This observation is highly relevant for environmental risk assessment. Traditional approaches that consider toxic effects at fixed exposure times are unable to allow extrapolation from measured endpoints to effects that may occur at other times of exposure. Time-to-effect approaches that provide information on the doses and exposure times needed to produce toxic effects on tested organisms are required for prediction of toxic effects for any combination of concentration and time in the environment.

Uncertainty evaluation of human risk analysis (HRA) of chemicals by multiple exposure routes.

The application of an ISO standard procedure (Guide to the Expression of Uncertainty in Measurement (GUM)) is here discussed to quantify uncertainty in human risk estimation under chronic exposure to hazardous chemical compounds. The procedure was previously applied to a simple model; in this article a much more complex model is used, i.e., multiple compound and multiple exposure pathways. Risk was evaluated using the usual methodologies: the deterministic reasonable maximum exposure (RME) and the statistical Monte Carlo method. In both cases, the procedures to evaluate uncertainty on risk values are detailed. Uncertainties were evaluated by different methodologies to account for the peculiarity of information about the single variable. The GUM procedure enables the ranking of variables by their contribution to uncertainty; it provides a criterion for choosing variables for deeper analysis. The obtained results show that the application of GUM procedure is easy and straightforward to quantify uncertainty and variability of risk estimation. Health risk estimation is based on literature data on a water table contaminated by three volatile organic compounds. Daily intake was considered by either ingestion of water or inhalation during showering. The results indicate one of the substances as the main contaminant, and give a criterion to identify the key component on which the treatment selection may be performed and the treatment process may be designed in order to reduce risk.

Bioavailability and risk assessment of orally ingested polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are a family of toxicants that are ubiquitous in the environment. These contaminants generate considerable interest, because some of them are highly carcinogenic in laboratory animals and have been implicated in breast, lung, and colon cancers in humans. These chemicals commonly enter the human body through inhalation of cigarette smoke or consumption of contaminated food. Of these two pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs have been published, factors affecting the accumulation of PAHs in the diet, their absorption following ingestion, and strategies to assess risk from exposure to these hydrocarbons following ingestion have received much less attention. This review, therefore, focuses on concentrations of PAHs in widely consumed dietary ingredients along with gastrointestinal absorption rates in humans. Metabolism and bioavailability of PAHs in animal models and the processes, which influence the disposition of these chemicals, are discussed. The utilitarian value of structure and metabolism in predicting PAH toxicity and carcinogenesis is also emphasized. Finally, based on intake, disposition, and tumorigenesis data, the exposure risk to PAHs from diet, and contaminated soil is presented. This information is expected to provide a framework for refinements in risk assessment of PAHs from a multimedia exposure perspective.

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.

Assessing human health response in life cycle assessment using ED10s and DALYs: part 1--Cancer effects.

Life cycle assessment (LCA) is a framework for comparing products according to their total estimated environmental impact, summed over all chemical emissions and activities associated with a product at all stages in its life cycle (from raw material acquisition, manufacturing, use, to final disposal). For each chemical involved, the exposure associated with the mass released into the environment, integrated over time and space, is multiplied by a toxicological measure to estimate the likelihood of effects and their potential consequences. In this article, we explore the use of quantitative methods drawn from conventional single-chemical regulatory risk assessments to create a procedure for the estimation of the cancer effect measure in the impact phase of LCA. The approach is based on the maximum likelihood estimate of the effect dose inducing a 10% response over background, ED10, and default linear low-dose extrapolation using the slope betaED10 (0.1/ED10). The calculated effects may correspond to residual risks below current regulatory compliance requirements that occur over multiple generations and at multiple locations; but at the very least they represent a "using up" of some portion of the human population's ability to accommodate emissions. Preliminary comparisons are performed with existing measures, such as the U.S. Environmental Protection Agency's (U.S. EPA's) slope factor measure q1*. By analyzing bioassay data for 44 chemicals drawn from the EPA's Integrated Risk Information System (IRIS) database, we explore estimating ED10 from more readily available information such as the median tumor dose rate TD50 and the median single lethal dose LD50. Based on the TD50, we then estimate the ED10 for more than 600 chemicals. Differences in potential consequences, or severity, are addressed by combining betaED10 with the measure disability adjusted life years per affected person, DALYp. Most of the variation among chemicals for cancer effects is found to be due to differences in the slope factors (betaED10) ranging from 10(-4) up to 10(4) (risk of cancer/mg/kg-day).

A quantitative risk assessment for fumonisins B1 and B2 in US corn.

Quantitative risk analysis permits modifying risk estimates with changes in variables such as exposure. This analysis for exposure to the mycotoxin fumonism describes the magnitude of adverse effects, variability in the population and uncertainty of models as a range of possible outcomes. The most sensitive adverse response in rats, nephrotoxic lesions, was used for the dose-response analysis. Dietary intake of corn products was estimated from a 3-day consumption survey. Levels of corn in each product were estimated by standard methods. Fumonisin levels in corn products were estimated from Food and Drug Administration (FDA) surveillance data and distributions of fumonisin consumption were modelled for each eater in the survey population. Uncertainty for predictions made from each model and uncertainty resulting from model selection were described. Results of the dose-response and exposure analyses were assimilated in a two-dimensional Monte-Carlo simulation. Distributions representing variability and uncertainty were iteratively selected to form an array of estimates of the risk. On the basis of this analysis, current dietary levels of fumonisin would not result in renal lesions even at upper levels of exposure. To avoid toxicity at much higher doses, limiting corn intake would be more effective than would limiting the level of fumonisin in corn.

An evaluation of risk estimation procedures for mixtures of carcinogens.

The estimation of health risks from exposure to a mixture of chemical carcinogens is generally based on the combination of information from several available single compound studies. The current practice of directly summing the upper bound risk estimates of individual carcinogenic components as an upper bound on the total risk of a mixture is known to be generally too conservative. Gaylor and Chen (1996, Risk Analysis) proposed a simple procedure to compute an upper bound on the total risk using only the upper confidence limits and central risk estimates of individual carcinogens. The Gaylor-Chen procedure was derived based on an underlying assumption of the normality for the distributions of individual risk estimates. In this paper we evaluated the Gaylor-Chen approach in terms of the coverage probability. The performance of the Gaylor-Chen approach in terms the coverages of the upper confidence limits on the true risks of individual carcinogens. In general, if the coverage probabilities for the individual carcinogens are all approximately equal to the nominal level, then the Gaylor-Chen approach should perform well. However, the Gaylor-Chen approach can be conservative or anti-conservative if some or all individual upper confidence limit estimates are conservative or anti-conservative.