The rationale behind updates to ambient ozone guidelines and standards.

Although air quality has gradually improved in recent years, as shown by the decrease in PM2.5 concentration, the problem of rising ambient ozone has become increasingly serious. To reduce hazards to human health and environmental welfare exposure to ozone, scientists and government regulators have developed ozone guidelines and standards. These answer the questions of which levels of exposure are hazardous to human health and the environment, and how can ambient ozone exposure be guaranteed, respectively. So what are the basis for the ozone guidelines and standards? This paper reviews in detail the process of revising ozone guidelines and standards by the World Health Organization (WHO) and the United States Environmental Protection Agency (EPA). The present study attempts to explore and analyze the scientific basis and empirical methods for updating guidelines and standards, in a view to guide the future revision process and provide directions for further scientific research. We found many epidemiological and toxicological studies and exposure-response relationships provided strong support for developing and revising the ozone guidelines. When setting standards, ozone exposure has been effectively considered, and the economic costs, health, and indirect economic benefits of standard compliance were reasonably estimated. Accordingly, epidemiological and toxicological studies and the establishment of exposure-response relationships, as well as exposure and risk assessment and benefit-cost estimates of standards compliance should be strengthened for the further update of guidelines and standards. In addition, with the increasing prominence of combined air pollution led by ozone and PM2.5, more joint exposure scientific research related to ozone guidelines and standards should be undertaken.

EPA Takes Action Against Harmful "Forever Chemicals" in the US Water Supply.

This Medical News article discusses new EPA advisories for a class of synthetic chemical compounds known as PFAS, which are ubiquitous in the environment and in humans, as well as new National Academies guidance on expanded testing for exposure.

Ability of mathematical models to predict human in vivo percutaneous penetration of steroids.

Human skin is a common route for topical steroids to enter the body. To aid with risk management of therapeutic steroid usage, the US Environmental Protection Agency estimates percutaneous penetration using mathematical models. However, it is unclear how accurate are mathematical models in estimating percutaneous penetration/absorption of steroids. In this study, accuracy of predicted flux (penetration/absorption) by the main mathematical model used by the EPA, the Potts and Guy model based on in vitro data is compared to actual human in vivo data from our laboratory of percutaneous absorption of topical steroids. We focused on steroids due to the availability of steroid in vivo human data in our laboratory. For most steroids the flux was underestimated by a factor 10-60. However, within the group itself, there was an association between the Potts and Guy model and experimental human in vivo data (Pearson Correlation = 0.8925, p = 0.000041). Additionally, some physiochemical parameters used in the Potts and Guy equation, namely log Kp (Pearson Correlation = 0.7307, p = 0.0046) and molecular weight (Pearson correlation = -0.6807, p = 0.0105) correlated significantly with in vivo flux. Current mathematical models used in estimating percutaneous penetration/absorption did not accurately predict in vivo flux of steroids. Why? Proposed limitations to mathematical models currently used include: not accounting for volatility, lipid solubility, hydrogen bond effects, drug metabolism, as well as protein binding. Further research is needed in order to increase the predictive nature of such models for in vivo flux.

Inhalation cancer risk assessment for environmental exposure to hexavalent chromium: Comparison of margin-of-exposure and linear extrapolation approaches.

Hexavalent chromium [Cr(VI)] exists in the ambient air at low concentrations (average upperbound ~0.1 ng/m3) yet airborne concentrations typically exceed EPA's Regional Screening Level for residential exposure (0.012 ng/m3) and other similar benchmarks, which assume a mutagenic mode of action (MOA) and use low-dose linear risk assessment models. We reviewed Cr(VI) inhalation unit risk estimates developed by researchers and regulatory agencies for environmental and occupational exposures and the underlying epidemiologic data, updated a previously published MOA analysis, and conducted dose-response modeling of rodent carcinogenicity data to evaluate the need for alternative exposure-response data and risk assessment approaches. Current research supports the role of non-mutagenic key events in the MOA, with growing evidence for epigenetic modifiers. Animal data show a weak carcinogenic response, even at cytotoxic exposures, and highlight the uncertainties associated with the current epidemiological data used in risk assessment. Points of departure from occupational and animal studies were used to determine margins of exposure (MOEs). MOEs range from 1.5 E+3 to 3.3 E+6 with a median of 5 E+5, indicating that current environmental exposures to Cr(VI) in ambient air should be considered of low concern. In this comprehensive review, the divergent results from default linear and MOE assessments support the need for more relevant and robust epidemiologic data, additional mechanistic studies, and refined risk assessment strategies.

Risk assessment of workers' exposure to BTEX and hazardous area classification at gasoline stations.

Vaporization of benzene, toluene, ethylbenzene, and xylene (BTEX) compounds pollutes the air and causes health hazards at gasoline stations. This study revealed the risk of BTEX exposure according to the hazardous area classification at gasoline stations. The risk assessment of gasoline workers from a representative group of 47 stations, which followed the United States Environmental Protection Agency-IRIS method of assessing BTEX exposure, was expressed as the hazard index (HI). A result of matrix multipliers of the hazardous exposure index and fire possibility from flammable gas classified hazardous area-I and area-II at the fuel dispensers. BTEX concentrations were actively sampled in ambient air and a flammable gas detector was used to measure the flammability level. Results showed that the BTEX concentrations from ambient air monitoring were in the range of 0.1-136.9, 8.1-406.0, 0.8-24.1 and 0.4-105.5 ppb for benzene, toluene, ethylbenzene, and xylene, respectively, which exceeded the NIOSH exposure limit of 100 ppb of benzene concentration. The risk assessment indicated that five stations reached an unacceptable risk of worker exposure to BTEX (HI>1), which correlated with the numbers of gasoline dispensers and daily gasoline sold. The risk matrix classified hazardous area-I at 4 meters and hazardous area-II at 4-8 meters in radius around the fuel dispensers. This study revealed the hazardous areas at gasoline stations and suggests that entrepreneurs must strictly control the safety operation practice of workers, install vapor recovery systems on dispenser nozzles to control BTEX vaporization and keep the hazardous areas clear of fire ignition sources within an eight-meter radius of the dispensers.

US EPA's regulatory pesticide evaluations need clearer guidelines for considering mammary gland tumors and other mammary gland effects.

Breast cancer risk from pesticides may be missed if effects on mammary gland are not assessed in toxicology studies required for registration. Using US EPA's registration documents, we identified pesticides that cause mammary tumors or alter development, and evaluated how those findings were considered in risk assessment. Of 28 pesticides that produced mammary tumors, EPA's risk assessment acknowledges those tumors for nine and dismisses the remaining cases. For five pesticides that alter mammary gland development, the implications for lactation and cancer risk are not assessed. Many of the mammary-active pesticides activate pathways related to endocrine disruption: altering steroid synthesis in H295R cells, activating nuclear receptors, or affecting xenobiotic metabolizing enzymes. Clearer guidelines based on breast cancer biology would strengthen assessment of mammary gland effects, including sensitive histology and hormone measures. Potential cancer risks from several common pesticides should be re-evaluated, including: malathion, triclopyr, atrazine, propylene oxide, and 3-iodo-2-propynyl butylcarbamate (IPBC).

Identification of component-based approach for prediction of joint chemical mixture toxicity risk assessment with respect to human health: A critical review.

Toxicity risk assessment of chemical mixture possesses huge challenges due to limited evidence on toxicity of compounds, the infinite number of chemical combinations makes the problem even more difficult. Normally, prediction of joint mixture toxicity depends on toxicological data of constituent compounds, although lack of information on dose-response of chemical mixture raises serious concerns on human health. Component-based approaches mainly use dose-addition or response-addition method to assess mixture toxicity risk exposure. Several models based on theoretical concepts of concentration/dose addition and independent/response action were also developed but these models do not address chemical interactions in mixture, and were mostly used to assess ecological risk exposure with limited or no information on human health risk assessment. This paper reviews available models to predict joint toxicity of chemical mixtures, and most applicable one to address human health risk exposure was identified. United States Environmental Protection Agency (US EPA) weight-of-evidence hazard index (HI) based approach seems to be most appropriate to predict joint toxicity of chemical mixtures, and applicability of model is explained using emerging contaminants as an example. The review also identified challenges in implementing the interaction-based EPA approach and highlighted the need for necessary future research actions.

Occupational health risk assessment of volatile organic compounds emitted from the coke production unit of a steel plant.

In this study, cancer and non-cancer risks of exposure to volatile organic compounds in the coke production unit of a steel plant were evaluated. To determine individual exposure to benzene, toluene, xylene and ethylbenzene, personal samples were taken from the breathing zone of workers according to National Institute for Occupational Safety and Health (NIOSH) method 1501. Cancer and non-cancer risk assessment was performed, using US Environmental Protection Agency (US EPA) methods. Samples analysis showed that the concentration of benzene in the energy and biochemistry and the benzol refinement sections was higher than occupational exposure limits. The cancer risk for benzene in all sections was significantly higher than allowable limit; the non-cancer risk for benzene in all sections and toluene in the benzol refinement section was also higher than 1.0. In conclusion, the current control measures are not sufficient and should be improved for efficient control of occupational exposures.

Commentary: An open appeal to the EPA for Superfund ERA reform.

The ecological risk assessment guidance of virtually all federal and state agencies, private companies, and other interests can be traced to that of the essential design of the U.S. Environmental Protection Agency (EPA). The EPA ecological risk assessment paradigm has remained unchanged for all intents and purposes since its inception 30 years ago, this despite criticism expressed repeatedly by some, for many years. Despite the discipline's name, a core paradigm shortcoming is its inability to express risk, the probability of a receptor-of-concern at a contaminated site developing a toxicological endpoint (e.g., reproductive impairment). Further, common site context and biological realities (e.g., site sizes; home ranges of receptors-of concern) allow for the supported challenges that risk assessments aren't needed altogether, and instances of ecological damage at sites being unknown. This commentary is an open appeal to the EPA to replace the paradigm it has set forth, dispensing with failed processes (e.g., endeavoring to assess risk potential at 75 year-old sites; endeavoring to assess risk potential to wide-ranging species at one-acre properties). The commentary invites the EPA to respond, not with counter-arguments, but rather with explanations for the Agency's resistance to acknowledging problems with its guidance, followed by the Agency commitment to sorely needed ERA reform.

Development of a prioritization method for chemical-mediated effects on steroidogenesis using an integrated statistical analysis of high-throughput H295R data.

Synthesis of 11 steroid hormones in human adrenocortical carcinoma cells (H295R) was measured in a high-throughput steroidogenesis assay (HT-H295R) for 656 chemicals in concentration-response as part of the US Environmental Protection Agency's ToxCast program. This work extends previous analysis of the HT-H295R dataset and model by examining the utility of a novel prioritization metric based on the Mahalanobis distance that reduced these 11-dimensional data to 1-dimension via calculation of a mean Mahalanobis distance (mMd) at each chemical concentration screened for all hormone measures available. Herein, we evaluated the robustness of mMd values, and demonstrate that covariance and variance of the hormones measured appear independent of the chemicals screened and are inherent to the assay; the Type I error rate of the mMd method is less than 1%; and, absolute fold changes (up or down) of 1.5 to 2-fold have sufficient power for statistical significance. As a case study, we examined hormone responses for aromatase inhibitors in the HT-H295R assay and found high concordance with other ToxCast assays for known aromatase inhibitors. Finally, we used mMd and other ToxCast cytotoxicity data to demonstrate prioritization of the most selective and active chemicals as candidates for further in vitro or in silico screening.

Evaluating potential refinements to existing Threshold of Toxicological Concern (TTC) values for environmentally-relevant compounds.

The Toxic Substances Control Act (TSCA) mandates the US EPA perform risk-based prioritisation of chemicals in commerce and then, for high-priority substances, develop risk evaluations that integrate toxicity data with exposure information. One approach being considered for data poor chemicals is the Threshold of Toxicological Concern (TTC). Here, TTC values derived using oral (sub)chronic No Observable (Adverse) Effect Level (NO(A)EL) data from the EPA's Toxicity Values database (ToxValDB) were compared with published TTC values from Munro et al. (1996). A total of 4554 chemicals with structures present in ToxValDB were assigned into their respective TTC categories using the Toxtree software tool, of which toxicity data was available for 1304 substances. The TTC values derived from ToxValDB were similar, but not identical to the Munro TTC values: Cramer I ((ToxValDB) 37.3 c. f. (Munro) 30 µg/kg-day), Cramer II (34.6 c. f. 9.1 µg/kg-day) and Cramer III (3.9 c. f. 1.5 µg/kg-day). Cramer III 5th percentile values were found to be statistically different. Chemical features of the two Cramer III datasets were evaluated to account for the differences. TTC values derived from this expanded dataset substantiated the original TTC values, reaffirming the utility of TTC as a promising tool in a risk-based prioritisation approach.

Why toxicologists resisted and radiation geneticists supported EPA'S adoption of LNT for cancer risk assessment.

The linear non-threshold (LNT) dose response model for cancer risk assessment has been a controversial concept since its initial proposal during the 1930s. It was long advocated by the radiation genetics community in the 1950s, some two decades prior to being generally adopted within the chemical toxicology community. This paper explores possible reasons for such major differences in the acceptance of LNT for cancer risk assessment by these two key groups of scientists.

Applying adaptive management and lessons learned from national assessments to address logistical challenges in the National Wetland Condition Assessment.

The National Wetland Condition Assessment (NWCA) is one of a series of probability-based National Aquatic Resource Surveys (NARS) conducted by the U.S. Environmental Protection Agency (USEPA) to provide a comprehensive assessment of the condition of the Nation's waters. Randomized design and standardized training and protocols allow USEPA to analyze data that are nationally consistent and regionally relevant. Each NARS assessment was preceded by careful consideration of key logistical elements that included pre-survey planning, training, sampling logistics, and laboratory analysis. Numerous state, tribal, and contractor crews were supported across the country for each assessment; sampling and sample analyses were tracked from initiation; laboratory analyses were completed at USEPA, state, regional, and contract laboratories; and the data analyses and reporting were completed by USEPA-led workgroups, states, and contractors. The complexity and difficulty of each step offered unique challenges and provided lessons learned for each of the NARS assessments. Major logistical elements for implementing large scale assessments that are constrained by sampling period and number and duration of visits are covered in this paper. These elements include sample transport, equipment and supplies, sampling and sample tracking, information management regional technical expertise, and a sound field training program. This paper describes how lessons from previous assessments were applied to the NWCA and how new challenges faced in the NWCA were addressed and carried forward into future surveys.

Foreword to the USEPA's National Wetland Condition Assessment Topical Collection.

The Environmental Protection Agency's (EPA) National Aquatic Resources Survey (NARS) is a 5-year ongoing cycle of nationwide aquatic resource surveys which provide a report card on the condition of our nation's waters. The surveys are performed using a randomized, statistically valid design and provide statistically robust data which are used to develop the reports. These reports assess how well existing pollution prevention programs are protecting those waters, and how to better target future protection efforts. This presentation will focus on the results and uses of the 2011 National Wetland Condition Assessment (NWCA) outcomes. Some of the outcomes from the NWCA include (1) robust multi-metric indices used to evaluate condition across varying wetland types, streams, and ecoregions and (2) physical, chemical, and biological indicators of stress (risk factors) which identify the factors which contribute most to poor condition. (3) A wealth of quality-assured, statistically valid data which can be mined to pursue other questions within both regulatory and non-regulatory programs by providing a more robust look at wetland and stream condition. There are a variety of ways in which knowledge of condition can be used to better evaluate environmental states and inform decision-making. Knowledge of risk factors, for example, can be used to prioritize restoration efforts to improve the health of streams and wetlands in poor condition, as well as to identify practices to be avoided in reviewing permit applications for work in waters. The use of multi-metric plant condition indices could be useful in better identifying achieved "lift" in wetland mitigation banks, as well as providing a more robust measure of mitigation or restoration success. It is our hope to generate some seeds for future thought and discussion on ways in which the products of these NARS surveys can enhance the protection and restoration of these aquatic resources.

Striving for consistency in the National Wetland Condition Assessment: developing a reference condition approach for assessing wetlands at a continental scale.

One of the biggest challenges when conducting a continental-scale assessment of wetlands is setting appropriate expectations for the assessed sites. The challenge occurs for two reasons: (1) tremendous natural environmental heterogeneity exists within a continental landscape and (2) reference sites vary in quality both across and within major regions of the continent. We describe the process used to set reference expectations and define a disturbance gradient for the United States (US) Environmental Protection Agency's National Wetland Condition Assessment (NWCA). The NWCA employed a probability design and sampled 1138 wetland sites across the conterminous US to make an unbiased assessment of wetland condition. NWCA vegetation data were used to define 10 reporting groups based on ecoregion and wetland type that reduced the naturally occurring variation in wetland vegetation associated with continent-wide differences in biogeography. These reporting groups were used as a basis for defining quantitative criteria for least disturbed and most disturbed conditions and developing indices and thresholds for categories of ecological condition and disturbance. The NWCA vegetation assessment was based on a reference site approach, in which the least disturbed reference sites were used to establish benchmarks for assessing the condition of vegetation at other sites. Reference sites for each reporting group were identified by filtering NWCA sample data for disturbance using a series of abiotic variables. Ultimately, 277 least disturbed sites were used to set reference expectations for the NWCA. The NWCA provided a unique opportunity to improve our conceptual and technical understanding of how to best apply a reference condition approach to assessing wetlands across the US. These results will enhance the technical quality of future national assessments.

Trends in Excess Morbidity and Mortality Associated with Air Pollution above American Thoracic Society-Recommended Standards, 2008-2017.

Rationale: Air quality improvements are increasingly difficult to come by as modern pollution control technologies and measures have been widely implemented in the United States. Although there have been dramatic improvements in air quality over the last several decades, it is important to evaluate changes in the health impacts of air pollution for a more recent time period to better understand the current trajectory of air quality improvements. Objectives: To provide county-level estimates of annual air pollution-related health outcomes across the United States and to evaluate these trends from 2008 to 2017, presented as part of the annual American Thoracic Society (ATS)/Marron Institute "Health of the Air" report. Methods: Daily air pollution values were obtained from the U.S. Environmental Protection Agency's Air Quality System for monitors in the United States from 2008 to 2017. Concentration-response functions used in the ATS/Marron Institute "Health of the Air" report were applied to the pollution increments corresponding to differences between the rolling 3-year design values (reported as the third year) and ATS-recommended levels for annual particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5; 11 µg/m3), short-term PM2.5 (25 µg/m3), and ozone (O3; 60 ppb). Health impacts were estimated at the county level in locations with valid monitor data. Results: Annual excess mortality in the United States due to air pollution levels greater than recommended by the ATS decreased from approximately 12,600 (95% confidence interval [CI], 5,470-21,040) in 2010 to 7,140 (95% CI, 2,290-14,040) in 2017. This improvement can be attributed almost entirely to reductions in PM2.5-related mortality, which decreased by approximately 60% (reduced from 8,330 to 3,260 annual deaths), whereas O3-related mortality remained largely unchanged, other than year-to-year variability, over the same time period (reduced from 4,270 to 3,880 annual deaths). Conclusions: Improvements in health impacts attributable to ambient PM2.5 concentrations have been observed across most regions of the United States over the last decade, although the rate of these improvements has leveled off in recent years. Despite two revisions of the National Ambient Air Quality Standards strengthening the standard for O3 in 2008 and 2015, there has not yet been a substantial improvement in the health impacts attributable to O3 during this time period. In many U.S. cities, an increase in the exposed population over the last decade has outpaced the improvements in ambient O3 concentrations, resulting in a net increase in O3-related health impacts over time.