Environmental Protection Agency Model Research Articles

Incidence risk assessment of secondary cancer due to radiotherapy of women with rectal cancer using BEIR VII, EPA, and ICRP models.

Radiotherapy has a significant side effect known as radiation-induced secondary cancer. This study aims to evaluate the dose and secondary cancer risk for women with rectal cancer treated with three-dimensional conformal radiation therapy (3D-CRT) to the organs at risk (OARs) and some sensitive organs using different types of radiation-induced cancer risk prediction models, including Biological Effects of Ionizing Radiation (BEIRVII), Environmental Protection Agency (EPA) and International Commission on Radiological Protection (ICRP), and compare the results of the different models for same organs. Thirty female patients with rectal cancer were considered and dose calculations were based on the PCRT-3D treatment planning system, while the radiotherapy of the patients had been performed using Shinva linear accelerator with a total dose of 45 Gy at 25 fractions. Planning target volume (PTV), OARs, and some sensitive organs were contoured, three models were used to evaluate secondary cancer risk (SCR) using the excess relative risk (ERR) and excess absolute risk (EAR). The bladder presents the highest risk, in terms of ERR, and the femur head and uterus in terms of EAR from the three models (BEIR VII, EPA, and ICRP). Based on the obtained results, radiotherapy of rectal cancer is relatively higher for the bladder and femur head, compared to the risk for other organs, the kidney risk is significantly lower. It was observed that the SCR from the ICRP model was higher compared to BEIR VII and EPA models.

A Mechanistic High-Content Analysis Assay Using a Chimeric Androgen Receptor That Rapidly Characterizes Androgenic Chemicals.

Human health is at risk from environmental exposures to a wide range of chemical toxicants and endocrine-disrupting chemicals (EDCs). As part of understanding this risk, the U.S. Environmental Protection Agency (EPA) has been pursuing new high-throughput in vitro assays and computational models to characterize EDCs. EPA models have incorporated our high-content analysis-based green fluorescent protein estrogen receptor (GFP-ER): PRL-HeLa assay, which allows direct visualization of ER binding to DNA regulatory elements. Here, we characterize a modified functional assay based on the stable expression of a chimeric androgen receptor (ARER), wherein a region containing the native AR DNA-binding domain (DBD) was replaced with the ERα DBD (amino acids 183-254). We demonstrate that the AR agonist dihydrotestosterone induces GFP-ARER nuclear translocation, PRL promoter binding, and transcriptional activity at physiologically relevant concentrations (<1 nM). In contrast, the AR antagonist bicalutamide induces only nuclear translocation of the GFP-ARER receptor (at μM concentrations). Estradiol also fails to induce visible chromatin binding, indicating androgen specificity. In a screen of reference chemicals from the EPA and the Agency for Toxic Substances and Disease Registry, the GFP-ARER cell model identified and mechanistically grouped activity by known (anti-)androgens based on the ability to induce nuclear translocation and/or chromatin binding. Finally, the cell model was used to identify potential (anti-)androgens in environmental samples in collaboration with the Houston Ship Channel/Galveston Bay Texas A&M University EPA Superfund Research Program. Based on these data, the chromatin-binding, in vitro assay-based GFP-ARER model represents a selective tool for rapidly identifying androgenic activity associated with drugs, chemicals, and environmental samples.

Quantitative differences between common occupational health risk assessment models.

ObjectivesMethodological studies on occupational health risk assessment (OHRA) models are rarely reported. This study aimed to explore the quantitative differences between common OHRA models.MethodsThe risk ratios (RRs) in five typical industries (leather, wooden furniture manufacturing, printing and dyeing, printing, and garment manufacturing) were investigated using six OHRA models, namely the models from the US Environmental Protection Agency (EPA), Singapore, the Control of Substances Hazardous to Health (COSHH), Australia, Romania, and International Council on Mining and Metals (ICMM). The consistency, correlation, and reliability were evaluated for quantitative differences between the models.ResultsThe order of the RRs obtained from the EPA, Singaporean, and COSHH models in the five industries was consistent with the order of the inherent risk levels in those industries. The EPA and Singaporean models could effectively distinguish the inherent risk levels of risk factors like xylene and ethyl acetate. The order of RR between the six models was: RR EPA > RR COSHH > RR Singaporean > RR Australian > RR Romanian and RR ICMM (P < .05). The EPA model had the weakest correlations with other models. The Singaporean model had positive correlations in RRs with the other models (P＜0.01).ConclusionsThe EPA and Singaporean models exhibited good reliability since they could distinguish the inherent risk of the industry or risk factor and tended to get higher risk levels. The EPA model was independent and the Singaporean model had a good correlation with other models. More studies on OHRA methodology are needed.

Estimating daily PM2.5 concentrations in New York City at the neighborhood-scale: Implications for integrating non-regulatory measurements

Previous PM2.5 related epidemiological studies mainly relied on data from sparse regulatory monitors to assess exposure. The introduction of non-regulatory PM2.5 monitors presents both opportunities and challenges to researchers and air quality managers. In this study, we evaluated the advantages and limitations of integrating non-regulatory PM2.5 measurements into a satellite-based daily PM2.5 model at 100 m resolution in New York City in 2015. Two separate machine learning models were developed, one using only PM2.5 data from the US Environmental Protection Agency (EPA), and the other with measurements from both EPA and the New York City Community Air Survey (NYCCAS). The EPA-only model obtained a cross-validation (CV) R2 of 0.85 while the EPA + NYCCAS model obtained a CV R2 of 0.73. With the help of the NYCCAS measurements, the EPA + NYCCAS model predicted distinctly different PM2.5 spatial patterns and more pollution hotspots compared with the EPA model, and its predictions were >15% higher than the EPA model along major roads and in densely populated areas. Our results indicated that satellite AOD and non-regulatory PM2.5 measurements can be fused together to capture neighborhood-scale PM2.5 levels and previous studies may have underestimated the disease burden due to PM2.5 in densely populated areas.

An in vitro depth of injury prediction model for a histopathologic classification of EPA and GHS eye irritants

The purpose of this study was to develop Globally Harmonized System (GHS) and U.S. Environmental Protection Agency (EPA) prediction models for classifying irritant materials based on histopathologic in vitro depth of injury (DoI) measurements. Sixteen different materials were selected, representing all classes of toxicity, according to the GHS and EPA classification systems. Food-source rabbit eyes, similar to eyes used for the widely accepted Bovine Corneal Opacity and Permeability and Isolated Chicken Eye ocular irritation tests, were used. Tissues were exposed to test material for 1 min, and corneas were collected at 3- and 24-hours post-exposure. Tissues were then fixed and processed for live/dead biomarker fluorescent staining using phalloidin. DoI was then measured, and the percent DoI values for the epithelium and stroma were compared to the EPA and GHS classifications. Excluding surfactants, EPA nonclassified (category IV) materials showed no stromal and very slight epithelial damage (≤10%) to the cornea, whereas EPA corrosive (category I) materials showed significantly greater damage (P < 0.001), ranging from 39% to 100% of the stromal depth. Importantly, EPA reversible (categories II and III) materials showed significant damage to the epithelium (>10%, P < 0.005) but significantly less severe damage to the corneal stroma (P < 0.001), ranging from 1% to 38% of the stromal depth. GHS nonclassified (category NC) irritants caused damage to the epithelium but not to the stroma. All GHS class 2 materials showed damage to the stroma (1–11%), whereas GHS corrosives caused significantly greater damage to the stroma (38–100%; P < 0.001). Additionally, one corrosive material, which produced a stromal DoI of 99% at 24 h, produced no apparent damage at 3-hours post-exposure. Based on these findings, histopathologic EPA and GHS prediction models are proposed that appear to separate and identify reversible irritants from other irritant classes. Furthermore, GHS classification appears to require stromal damage, whereas NC materials may or may not damage the corneal epithelium.

Occupational Health Risk Assessment in the Electronics Industry in China Based on the Occupational Classification Method and EPA Model.

The awareness of occupational health risk management in the electronics industry is weak in China, and many Chinese occupational health management regulations have not been effectively implemented. China’s current occupational hazards classification method and the Environmental Protection Agency (EPA) inhalation risk assessment model recognized internationally were used to perform health risk assessments for a chip manufacturing company in the electronics industry in order to determine the existing problems and put forward the optimization proposals of the occupational hazards classification method in China. The results showed that the detected concentrations of toxic and harmful chemicals in all testing points did not exceed the occupational health exposure limits in China. According to the EPA inhalation risk assessment model, the highest values of non-carcinogenic risks of ammonia, chlorine, fluoride, sulfuric acid, hydrogen chloride, ethylene glycol, phosphine, boron trifluoride, isopropanol, benzene, and xylene were 5.10, 67.12, 1.71, 45.98, 1.83, 1.43, 160.35, 46.56, 2.52, 5.55, and 5.37, respectively, which means workers in electronic chip manufacturing companies exposed to these chemicals have higher occupational health risks. However, on the basis of the occupational hazards classification method, the occupational health risks of exposure to the toxic and hazardous chemicals are relatively harmless operations. The evaluation results of the EPA inhalation risk assessment model are generally higher than those of the occupational hazards classification method. It’s recommended to refine the value of occupational exposure limit B, taking more characteristics of the hazard factors into account and fuzzifying the parameters to optimize the occupational hazards classification method. At the same time, it is suggested that the electronic chip manufacturing company should conduct anti-virus risk management covering in three aspects: increasing the awareness of occupational hazards, enhancing system ventilation, and improving personal health management measures.

Comparative Analysis of Biogas Estimation Models versus &amp;lt;i&amp;gt;In-Situ&amp;lt;/i&amp;gt; Measurement in a Landfill Site in the State of Mexico, Mexico

This paper shows a comparative analysis of theoretical model for biogas estimations in landfill sites in order to determine reliability, accuracy and efficiency by comparing results with actual data obtained in-situ. The model from the Environmental Protection Agency (EPA) and the Mexican model were selected to estimate biogas generation in a landfill site located in the State of Mexico, Mexico with 36 wells. Both models are based on a first order equation for degradation of organic matter assuming that the biogas generation reaches its maximum after a period of time and then biogas generation decreases exponentially while the organic fraction of waste is consumed. Measurement in-situ, using a landfill gas analyser (GA5000), resulted in values of percentage concentration of landfill gas (CH4, CO2 and O2) with an average Frequency of 35.44 Hz (1/s) and emissions of methane of 3355.99 m3/hr in contrast with 4885.74 m3/hr from EPA model and 6780.56 m3/hr from Mexican model. The experiment evidenced significant variations in estimations versus actual measurements. Authors discuss the aspects and parameters that cause such variations in order to provide a comprehensive analysis which will help decision makers to base waste management strategies in Mexico on reliable data.

Occupational hazard risk assessment of workers exposed to benzene in a petrochemical enterprise in Shanghai, China

Objective: To investigate the exposure to benzene, methylbenzene, and dimethylbenzene in workers in a petrochemical enterprise in Shanghai, China, and to conduct occupational hazard risk assessment. Methods: The environmental monitoring data on benzene series in the workplace of this petrochemical enterprise from 2010 to 2014 were collected, as well as workers' general status. The inhalation risk assessment model developed by United States Environmental Protection Agency (EPA) was used for risk assessment to determine the occupational hazard risk level of benzene, methylbenzene, and dimethylbenzene. Results: The pass rate of the monitoring concentration of benzene, methylbenzene, and dimethylbenzene in the workplace of this petrochemical enterprise was 100%. The results of the EPA model showed that benzene had a high carcinogenic risk, benzene and dimethylbenzene had a high non-carcinogenic risk, and methylbenzene had a low non-carcinogenic risk. Conclusion: The workers exposed to benzene in this petrochemical enterprise have a high health risk, and the EPA model can be used for occupational hazard risk assessment in chemical industry.

Source-specific fine particulate air pollution and systemic inflammation in ischaemic heart disease patients

ObjectiveTo compare short-term effects of fine particles (PM2.5; aerodynamic diameter <2.5 µm) from different sources on the blood levels of markers of systemic inflammation.MethodsWe followed a panel of 52 ischaemic...

Nigeria electricity crisis: Power generation capacity expansion and environmental ramifications

Access to clean and stable electricity is essential in actualizing Nigeria's quest for joining the league of twenty most industrious nations by the year 2020 (vision 20:2020). No country can develop and sustain it development without having a minimum access to electricity for it larger percentage of its population. At present, Nigeria depends petroleum reserves and its aged hydro plant instalments for electricity generation to feed the 40% of its total population that are connected to the national grid. This paper summarizes literature on the current energy issues in Nigeria and introduces the difficulty of the issues involved. The paper also analyses the current (2010) electricity generation as well as the future expansion plans of the Government in 20 years period. The plan includes the introduction of new electrify generation technologies that have not been in used in the base year (2010). The electricity generation system of (including the future expansion plan) was simulated using the LEAP System (Long-range Energy Alternative and Planning). We also investigated the potential environmental impact of siting a nuclear power plant in one of the potential sites based on the site's specific micro-meteorology (land use) and meteorology using the US EPA (Environmental Protection Agency) models; AERMOD 12345.

Probabilistic Approach to Estimating Indoor Air Concentrations of Chlorinated Volatile Organic Compounds from Contaminated Groundwater: A Case Study in San Antonio, Texas

This paper describes a probabilistic model, based on the Johnson-Ettinger algorithm, developed to characterize the current and historic exposure to tricholorethylene (TCE) and tetrachlorethylene (PCE) in indoor air from plumes of groundwater contamination emanating from the former Kelly Air Force Base in San Antonio, Texas. We estimate indoor air concentration, house by house, in 30 101 homes and compare the estimated concentrations with measured values in a small subset of homes. We also compare two versions of the Johnson-Ettinger model: one used by the Environmental Protection Agency (EPA) and another based on an alternative parametrization. The modeled mean predicted PCE concentration historically exceeded PCE screening levels (0.41 ug/m(3)) in 5.5% of houses, and the 95th percentile of the predicted concentration exceeded screening levels in 85.3% of houses. For TCE, the mean concentration exceeded the screening level (0.25 ug/m(3)) in 49% of homes, and the 95th percentile of the predicted concentration exceeded the screening level in 99% of homes. The EPA model predicts slightly lower indoor concentrations than the alternative parametrization. Comparison with measured samples suggests both models, with the inputs selected, underestimate indoor concentrations and that the 95th percentiles of the predicted concentrations are closer to measured concentrations than predicted mean values.

Are Coldwater Fish Populations of the United States Actually being Protected by Temperature Standards?

Governmental water quality agencies are faced with identifying water quality goals to protect aquatic biota, applying the best available science in development of water quality standards and associated management principles, implementing water quality laws so that there is consistency with goals, developing guidance documents for applying science to law, monitoring, and enforcement. Deviations in this path from goals to standards to enforcement, however, are common across countries as well as among States within the United States and can result in failure to protect the aquatic biota.The Clean Water Act (CWA) is the key US law for water quality protection. Its goal is to ‘restore and maintain the chemical, physical, and biological integrity of the Nation's waters’ and to fully protect the most sensitive beneficial uses. The US Environmental Protection Agency (EPA) Gold Book guidance for development of protective water temperature standards, dating from 1973, still recommends the use of MWAT (Maximum Weekly Average Temperature) as an index for assigning protective chronic temperature standards to coldwater fisheries. MWAT, applied according to EPA guidance, is typically used in conjunction with an acute upper limit. Unfortunately, MWAT is a criterion that is not protective, as can be shown by reference to several case studies on salmonids. Use of MWAT at a basin scale can result in considerable reduction in available salmonid rearing area and can, in many cases, be little better than recommending the upper incipient lethal temperature as a standard. Although MWAT is not used by many US States in standards, it is problematic in that it is cited as the official EPA model for a protective standard. The conceptual use of MWAT highlights some critical problems in application of the Clean Water Act and its associated federal regulations for protection of coldwater fishes, such as the concepts of full protection, protection of the most sensitive species, restoration of water quality, and support of species' viability at a basin scale.Full implementation of the CWA in support of salmonids' thermal requirements has been patchy, with some States taking criteria development, monitoring, listing, and TMDL (Total Maximum Daily Load) development seriously and others virtually ignoring the problem. In addition, Section 316 of the CWA conflicts with the basic goals of the CWA by giving deference to the thermoelectric power industry to discharge heated effluent under a process where variances granted supersede water quality-based limits. This is exacerbated by EPA 316 guidance permitting evaluation of biological trends amidst shifting or uncertain baselines in a limited set of RIS (Representative Important Species), rather than application of best available science to protect both the most sensitive species and the entire aquatic community that is reflective of high quality habitat conditions. Designing water temperature standards to be fully protective and supportive of species viability (abundance, productivity, spatial structure, and diversity) benefits from application of concepts of optimum growth and survival temperatures distributed at a basin scale with reference to the natural thermal potential along a river continuum. Some notable successes in standards development found in the US Pacific Northwest are offered as future national models.

Mesothelioma Risk and Environmental Exposure to Asbestos: Past and Future Trends in Japan

Although asbestos has been widely distributed in the environment, health risks due to general environmental exposure to asbestos have not been estimated. Future mesothelioma risk from environmental exposure to asbestos in Japan was estimated by comparing historical exposure data and mortality attributed to environmental exposure. We developed an equation to estimate environmentally-attributable mesothelioma based on the US Environmental Protection Agency's model for occupational mesothelioma mortality. Based on our calculations, mesothelioma risks per year of exposure will reach peak levels in 2033 and range from 4.8 × 10−6 to 1.1 × 10−5. The number of deaths is estimated to range from 542–1276 in 2033. The cumulative number of deaths will reach around 17,000–37,000 in the years 1970–2070. Our estimation of risk approximately corresponded to observed risks. Past and predicted future disease suggest the need for social and medical support in these areas.

Mesothelioma Risk and Environmental Exposure to Asbestos: Past and Future Trends in Japan

Although asbestos has been widely distributed in the environment, health risks due to general environmental exposure to asbestos have not been estimated. Future mesothelioma risk from environmental exposure to asbestos in Japan was estimated by comparing historical exposure data and mortality attributed to environmental exposure. We developed an equation to estimate environmentally-attributable mesothelioma based on the US Environmental Protection Agency's model for occupational mesothelioma mortality. Based on our calculations, mesothelioma risks per year of exposure will reach peak levels in 2033 and range from 4.8 x 10(-6) to 1.1 x 10(-5). The number of deaths is estimated to range from 542-1276 in 2033. The cumulative number of deaths will reach around 17,000-37,000 in the years 1970-2070. Our estimation of risk approximately corresponded to observed risks. Past and predicted future disease suggest the need for social and medical support in these areas.

Estimation of Ship Dry Air Emissions

AbstractThe Clean Air Act of 1990 was introduced to achieve and maintain a healthy environment while supporting strong and sustainable economic growth and sound energy policy. The federal regulations that followed require the Maritime shipping industry to work with government agencies to achieve these goals. This paper will estimate the theoretical stack emission from a vessel based on two models used by the maritime industry. The methods being discussed include one presented by the US Environmental Protection Agency (EPA) and the European Commission as done by Entec. Both models utilize published Lloyds Register Engineering Services Data to generate emission factors for each approach and therefore may yield good predictors of emissions. These models quantify both criteria pollutants and greenhouse gases. A comparison is made between the two methods with regard to similarity of emission rates from a model vessel. There are four parameters of NOx, SO2, CO2, and HC, which can be compared between the two methods. The values for NO2 in the EPA method would be equivalent to the NOx in the Entec methodology. The SO2 and CO2 values appear to be consistently higher in the EPA model. Hydrocarbon estimates appear to be consistently at least six times higher using the Entec model.

Update of Potency Factors for Asbestos-Related Lung Cancer and Mesothelioma

The most recent update of the U.S. Environmental Protection Agency (EPA) health assessment document for asbestos (Nicholson, 1986, referred to as "the EPA 1986 update") is now 20 years old. That document contains estimates of "potency factors" for asbestos in causing lung cancer (K(L)'s) and mesothelioma (K(M)'s) derived by fitting mathematical models to data from studies of occupational cohorts. The present paper provides a parallel analysis that incorporates data from studies published since the EPA 1986 update. The EPA lung cancer model assumes that the relative risk varies linearly with cumulative exposure lagged 10 years. This implies that the relative risk remains constant after 10 years from last exposure. The EPA mesothelioma model predicts that the mortality rate from mesothelioma increases linearly with the intensity of exposure and, for a given intensity, increases indefinitely after exposure ceases, approximately as the square of time since first exposure lagged 10 years. These assumptions were evaluated using raw data from cohorts where exposures were principally to chrysotile (South Carolina textile workers, Hein et al., 2007; mesothelioma only data from Quebec miners and millers, Liddell et al., 1997) and crocidolite (Wittenoom Gorge, Australia miners and millers, Berry et al., 2004) and using published data from a cohort exposed to amosite (Paterson, NJ, insulation manufacturers, Seidman et al., 1986). Although the linear EPA model generally provided a good description of exposure response for lung cancer, in some cases it did so only by estimating a large background risk relative to the comparison population. Some of these relative risks seem too large to be due to differences in smoking rates and are probably due at least in part to errors in exposure estimates. There was some equivocal evidence that the relative risk decreased with increasing time since last exposure in the Wittenoom cohort, but none either in the South Carolina cohort up to 50 years from last exposure or in the New Jersey cohort up to 35 years from last exposure. The mesothelioma model provided good descriptions of the observed patterns of mortality after exposure ends, with no evidence that risk increases with long times since last exposure at rates that vary from that predicted by the model (i.e., with the square of time). In particular, the model adequately described the mortality rate in Quebec chrysotile miners and millers up through >50 years from last exposure. There was statistically significant evidence in both the Wittenoom and Quebec cohorts that the exposure intensity-response is supralinear(1) rather than linear. The best-fitting models predicted that the mortality rate varies as [intensity](0.47) for Wittenoom and as [intensity](0.19) for Quebec and, in both cases, the exponent was significantly less than 1 (p or =3:1. Moreover, PCM does not distinguish between asbestos and nonasbestos particles. One possible reason for the discrepancies between the K(L)'s and K(M)'s from different studies is that the category of structures included in PCM counts does not correspond closely to biological activity. In the accompanying article (Berman and Crump, 2008) the K(L)'s and K(M)'s and related uncertainty bounds obtained in this article are paired with fiber size distributions from the literature obtained using transmission electron microscopy (TEM). The resulting database is used to define K(L)'s and K(M)'s that depend on both the size (e.g., length and width) and mineralogical type (e.g., chrysotile or crocidolite) of an asbestos structure. An analysis is conducted to determine how well different K(L) and K(M) definitions are able to reconcile the discrepancies observed herein among values obtained from different environments.

Methylmercury and the Brain: Griffiths et al. Respond

Methylmercury and the Brain: Griffiths et al. Respond

Risk Assessment for Asbestos-Related Cancer From the 9/11 Attack on the World Trade Center

We sought to estimate the lifetime risk of asbestos-related cancer for residents of Lower Manhattan attributable to asbestos released into the air by the 9/11 attack on New York City's World Trade Center (WTC). Exposure was estimated from available data and reasoned projections based on these data. Cancer risk was assessed using an asbestos risk model that differentiates asbestos fiber-types and the US Environmental Protection Agency's model that does not differentiate fiber-types and combines mesothelioma and lung cancer risks. The upper limit for the expected number of asbestos-related cancers is less than one case over the lifetime of the population for the risk model that is specific for fiber-types and 12 asbestos-related cancers with the US Environmental Protection Agency's model. The cancer risk associated with asbestos exposures for residents of Lower Manhattan resulting from the collapse of the WTC is negligible.

Time extrapolation and interspecies extrapolation for locally acting substances in case of limited toxicological data.

In the case of substances with a limited toxicological data base there is often (i) a lack of qualified human toxicological data; and (ii) a paucity of studies with adequate exposure duration. Hence, several extrapolations have to be performed to arrive at appropriate risk assessments or derive occupational exposure limits. The present paper deals with the possibilities for extrapolating the change in effect concentrations over time (time extrapolation, e.g. from subacute to chronic exposure) and for interspecies extrapolation (from animal to human) in connection with locally acting substances (respiratory toxicants). To justify the time extrapolation factors, 46 technical reports produced by the US National Toxicology Program (NTP) involving studies with subacute, subchronic and chronic exposure duration were evaluated. On the basis of geometric mean values, decreases in effect concentrations by factors of 3.2 (subacute --> subchronic), 2.7 (subchronic --> chronic) and 6.6 (subacute --> chronic) were found. Differentiation according to animal species (mouse, rat), sex or substance properties did not result in any relevant changes of the mean value. NTP studies with less than lifetime exposure periods (subacute, subchronic) in many cases showed different locations of respiratory effects compared with chronic studies, and thus offered limited possibilities for qualitative prediction of long-term respiratory effects (occurrence of effects in certain regions of the respiratory tract). With regard to interspecies extrapolation, gaseous and particulate substances were evaluated separately. With some modifications (e.g. consideration of the clearance of particles of low solubility), the 1994 US Environmental Protection Agency (EPA) model for deriving reference concentrations for humans on the basis of experimental data in animals is proposed for inhalable particulate substances. In the case of gaseous substances, the assumptions of the EPA model do not seem to consider sufficiently the local inhomogeneity in substance distribution and anatomical and histological differences between the upper respiratory tracts of rodents and humans. Considerable uncertainty would attach to a default factor for interspecies extrapolation for gaseous substances.

Evaluation of the validity of the US EPA's cancer risk assessment of arsenic for low-level exposures: a likelihood ratio approach

Skin cancers associated with ingesting of arsenic have been documented since the 19th century. A study in the southwestern coastal area of Taiwan where people drank well water containing arsenic is generally recognised as providing the best data available for quantifying the risk, and the US Environmental Protection Agency (EPA) used these data to conduct a risk assessment of arsenic ingestion. However, the lowest exposure category in the Taiwan study included arsenic levels up to 290 µg L−1, which is nearly six times higher than the current EPA maximum contaminant level (MCL), 50 µg L−1. Therefore, the EPA risk assessment model extrapolated data on high-level exposures to generate risk estimates for low-level exposures. To evaluate the validity of this model, we conducted a quantitative review of epidemiological studies observing arsenic exposures below 290 µg L−1. A ratio of the likelihood of the EPA model being inappropriate to that of it being appropriate was calculated for each study population as a measurement of the validity of the EPA model. Although existing human data on low-level exposures are limited, the review suggested that the EPA model is unlikely to be able to predict the risk of skin cancer accurately when the arsenic exposure level is between 170 and 270 µg L−1.