Probabilistic risk assessment of residential exposure to electric arc furnace steel slag using Bayesian model of relative bioavailability and PBPK modeling of manganese.

Electric arc furnace (EAF) slag is a coproduct of steel production used primarily for construction purposes. Some applications of EAF slag result in residential exposures by incidental ingestion and inhalation of airborne dust. To evaluate potential health risks, an EAF slag characterization program was conducted to measure concentrations of metals and leaching potential (including oral bioaccessibility) in 38 EAF slag samples. Arsenic, hexavalent chromium, iron, vanadium, and manganese (Mn) were identified as constituents of interest (COIs). Using a probabilistic risk assessment (PRA) approach, estimated distributions of dose for COIs were assessed, and increased cancer risks and noncancer hazard quotients (HQs) at the 50th and 95th percentiles were calculated. For the residents near slag-covered roads, cancer risk and noncancer HQs were <1E - 6 and 1, respectively. For residential driveway or landscape exposure, at the 95th percentile, cancer risks were 1E - 6 and 7E - 07 based on oral exposure to arsenic and hexavalent chromium, respectively. HQs ranged from 0.07 to 2 with the upper bound due to ingestion of Mn among children. To expand the analysis, a previously published physiologically based pharmacokinetic (PBPK) model was used to estimate Mn levels in the globus pallidus for both exposure scenarios and further evaluate the potential for Mn neurotoxicity. The PBPK model estimated slightly increased Mn in the globus pallidus at the 95th percentile of exposure, but concentrations did not exceed no-observed-adverse-effect levels for neurological effects. Overall, the assessment found that the application of EAF slag in residential areas is unlikely to pose a health hazard or increased cancer risk.

Use of physiologically based pharmacokinetic modeling to support development of an acute (24-hour) health-based inhalation guideline for manganese.

The toxicokinetics of manganese (Mn) are controlled through homeostasis because Mn is an essential element. However, at elevated doses, Mn is also neurotoxic and has been associated with respiratory, reproductive, and developmental effects. While health-based criteria have been developed for chronic inhalation exposure to ambient Mn, guidelines for short-term (24-h) environmental exposure are also needed. We reviewed US state, federal, and international health-based inhalation toxicity criteria, and conducted a literature search of recent publications. The studies deemed most appropriate to derive a 24-h guideline have a LOAEL of 1500 µg/m3 for inflammatory airway changes and biochemical measures of oxidative stress in the brain following 90 total hours of exposure in monkeys. We applied a cumulative uncertainty factor of 300 to this point of departure, resulting in a 24-h guideline of 5 µg/m3. To address uncertainty regarding potential neurotoxicity, we used a previously published physiologically based pharmacokinetic model for Mn to predict levels of Mn in the brain target tissue (i.e., globus pallidus) for exposure at 5 µg/m3 for two short-term human exposure scenarios. The PBPK model predictions support a short-term guideline of 5 µg/m3 as protective of both respiratory effects and neurotoxicity, including exposures of infants and children.

Cumulative risk assessment toolbox: methods and approaches for the practitioner.

The historical approach to assessing health risks of environmental chemicals has been to evaluate them one at a time. In fact, we are exposed every day to a wide variety of chemicals and are increasingly aware of potential health implications. Although considerable progress has been made in the science underlying risk assessments for real-world exposures, implementation has lagged because many practitioners are unaware of methods and tools available to support these analyses. To address this issue, the US Environmental Protection Agency developed a toolbox of cumulative risk resources for contaminated sites, as part of a resource document that was published in 2007. This paper highlights information for nearly 80 resources from the toolbox and provides selected updates, with practical notes for cumulative risk applications. Resources are organized according to the main elements of the assessment process: (1) planning, scoping, and problem formulation; (2) environmental fate and transport; (3) exposure analysis extending to human factors; (4) toxicity analysis; and (5) risk and uncertainty characterization, including presentation of results. In addition to providing online access, plans for the toolbox include addressing nonchemical stressors and applications beyond contaminated sites and further strengthening resource accessibility to support evolving analyses for cumulative risk and sustainable communities.