George M. Woodall

Estimations of historical atmospheric mercury concentrations from mercury refining and present-day soil concentrations of total mercury in Huancavelica, Peru

Detailed Spanish records of cinnabar mining and mercury production during the colonial period in Huancavelica, Peru were examined to estimate historical health risks to the community from exposure to elemental mercury (Hg) vapor resulting from cinnabar refining operations. Between 1564 and 1810, nearly 17,000 metric tons of Hg were released to the atmosphere in Huancavelica from Hg production. AERMOD was used with estimated emissions and source characteristics to approximate historic atmospheric concentrations of mercury vapor. Modeled 1-hour and long-term concentrations were compared with present-day inhalation reference values for elemental Hg. Estimated 1-hour maximum concentrations for the entire community exceeded present-day occupational inhalation reference values, while some areas closest to the smelters exceeded present-day emergency response guideline levels. Estimated long-term maximum concentrations for the entire community exceeded the EPA Reference Concentration (RfC) by a factor of 30 to 100, with areas closest to the smelters exceeding the RfC by a factor of 300 to 1000. Based on the estimated historical concentrations of Hg vapor in the community, the study also measured the extent of present-day contamination throughout the community through soil sampling and analysis. Total Hg in soils sampled from 20 locations ranged from 1.75 to 698 mg/kg and three adobe brick samples ranging from 47.4 to 284 mg/kg, consistent with other sites of mercury mining and use. The results of the soil sampling indicate that the present-day population of Huancavelica is exposed to levels of mercury from legacy contamination which is currently among the highest worldwide, consequently placing them at potential risk of adverse health outcomes.

Summary of the workshop on the power of aggregated toxicity data

In this workshop, ongoing federal agency (i.e., EPA, ATSDR, FDA, NIEHS and others) projects that employ toxicity data were discussed, as well as the possibility of innovative approaches for use of existing and new sources of information in risk assessment. Quantitative risk assessment relies upon having detailed exposure-response data, such as number of animals and incidence by exposure group in dichotomous measures and values by individual animal for continuous measures; this level of detail is often not reported in peer-reviewed studies. Additionally, biologically-based models (e.g., PBPK) are useful in risk assessment but require knowledge or collection of parameters as inputs (both chemical-specific and more general physiological parameters), and this information is not always readily available. Structure activity relationship information is also being called upon to help fill in knowledge gaps about specific chemicals where data from related chemicals may be available. Some existing data sources have been developed by various agencies for specific applications, such as those mentioned, and advantage should be taken of those existing resources; however, a great deal more is possible. The purpose of this workshop was to gather together many of the stakeholders using and developing shared toxicological information, determine the potential for greater collaboration, and determine the best course to facilitate the further development of joint information resources. A number of recommendations (development of a consensus toxicological review format, standardization of terminology and data sharing formats, and agreement on primary data elements) and topics for additional discussion were the major products of this workshop.

The role of developmental toxicity studies in acute exposure assessments: Analysis of single-day vs. multiple-day exposure regimens

In accordance with most toxicity guidelines, developmental studies typically utilize repeated exposures, usually throughout gestation or during organogenesis in particular. However, it is known that developmental toxicity may occur in response to single exposures, especially during specific windows of susceptibility. An overview of the available literature gave sufficient evidence that for many agents, the same endpoints observed in repeated dose, multiple-day studies were also observed in single-day exposures, thus indicating the relevance of developmental toxicity to health assessments of acute exposures. Further, results of benchmark dose modeling of developmental endpoints indicated that for embryo lethality, single-day exposures required a two- to fourfold higher dose than the multiple-day exposures to produce the same level of response. For fused sternebrae, exposures on specific days produced equivalent levels of response at doses that were more similar to those utilized in the repeated exposures. Appreciable differences in biological half-life (and corresponding dose metrics) as well as specific windows of susceptibility may partially explain the observed multiple- vs. single-day exposure dose-response relationships. Our results highlight the need of a more thorough evaluation of outcomes from repeated dose developmental toxicity studies in regards to their importance to chronic and acute risk assessments.

Interpreting Mobile and Handheld Air Sensor Readings in Relation to Air Quality Standards and Health Effect Reference Values: Tackling the Challenges

The US Environmental Protection Agency (EPA) and other federal agencies face a number of challenges in interpreting and reconciling short-duration (seconds to minutes) readings from mobile and handheld air sensors with the longer duration averages (hours to days) associated with the National Ambient Air Quality Standards (NAAQS) for the criteria pollutants-particulate matter (PM), ozone, carbon monoxide, lead, nitrogen oxides, and sulfur oxides. Similar issues are equally relevant to the hazardous air pollutants (HAPs) where chemical-specific health effect reference values are the best indicators of exposure limits; values which are often based on a lifetime of continuous exposure. A multi-agency, staff-level Air Sensors Health Group (ASHG) was convened in 2013. ASHG represents a multi-institutional collaboration of Federal agencies devoted to discovery and discussion of sensor technologies, interpretation of sensor data, defining the state of sensor-related science across each institution, and provides consultation on how sensors might effectively be used to meet a wide range of research and decision support needs. ASHG focuses on several fronts: improving the understanding of what hand-held sensor technologies may be able to deliver; communicating what hand-held sensor readings can provide to a number of audiences; the challenges of how to integrate data generated by multiple entities using new and unproven technologies; and defining best practices in communicating health-related messages to various audiences. This review summarizes the challenges, successes, and promising tools of those initial ASHG efforts and Federal agency progress on crafting similar products for use with other NAAQS pollutants and the HAPs. NOTE: The opinions expressed are those of the authors and do not necessary represent the opinions of their Federal Agencies or the US Government. Mention of product names does not constitute endorsement.

An exposure-response database for detailed toxicity data.

Risk assessment for human health effects often depends on evaluation of toxicological literature from a variety of sources. Risk assessors have limited resources for obtaining raw data, performing follow-on analyses or initiating new studies. These constraints must be balanced against a need to improve scientific credibility through improved statistical and analytical methods that optimize the use of available information. Computerized databases are used in toxicological risk assessment both for storing data and performing predictive analyses. Many systems provide primarily either bibliographic information or summary factual data from toxicological studies; few provide adequate information to allow application of dose-response models. The Exposure-Response database (ERDB) described here fills this gap by allowing entry of sufficiently detailed information on experimental design and results for each study, while limiting data entry to the most relevant. ERDB was designed to contain information from the open literature to support dose-response assessment and allow a high level of automation in performance of various types of dose-response analyses. Specifically, ERDB supports emerging analytical approaches for dose-response assessment, while accommodating the diverse nature of published literature. Exposure and response data are accessible in a relational multi-table design, with closely controlled standard fields for recording values and free-text fields to describe unique aspects of the study. Additional comparative analyses are made possible through summary tables and graphic representations of the data contained within ERDB.

Manganese testing under a clean air act test rule and the application of resultant data in risk assessments

&NA; In the 1990′s, the proposed use of methylcyclopentadienyl manganese tricarbonyl (MMT) as an octane‐enhancing gasoline fuel additive led to concerns for potential public health consequences from exposure to manganese (Mn) combustion products in automotive exhaust. After a series of regulatory/legal actions and negotiations, the U.S. Environmental Protection Agency (EPA) issued under Clean Air Act (CAA) section 211(b) an Alternative Tier 2 Test Rule that required development of scientific information intended to help resolve uncertainties in exposure or health risk estimates associated with MMT use. Among the uncertainties identified were: the chemical forms of Mn emitted in automotive exhaust; the relative toxicity of different Mn species; the potential for exposure among sensitive subpopulations including females, the young and elderly; differences in sensitivity between test species and humans; differences between inhalation and oral exposures; and the influence of dose rate and exposure duration on tissue accumulation of Mn. It was anticipated that development of specific sets of pharmacokinetic (PK) information and models regarding Mn could help resolve many of the identified uncertainties and serve as the best foundation for available data integration. The results of the test program included development of several unique Mn datasets, and a series of increasingly sophisticated Mn physiologically‐based pharmacokinetic (PBPK) models. These data and models have helped address each of the uncertainties originally identified in the Test Rule. The output from these PBPK models were used by the Agency for Toxic Substances and Disease Registry (ATSDR) in 2012 to inform the selection of uncertainty factors for deriving the manganese Minimum Risk Level (MRL) for chronic exposure durations. The EPA used the MRL in the Agencys 2015 evaluation of potential residual risks of airborne manganese released from ferroalloys production plants. This resultant set of scientific data and models likely would not exist without the CAA section 211(b) test rule regulatory procedure.