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.

Manganese relative oral bioavailability in electric arc furnace steel slag is influenced by high iron content and low bioaccessibility.

Electric arc furnace (EAF) slag is a rock-like aggregate produced with carbon steel and used for construction, including residential ground cover. It is enriched with manganese (Mn) and other metals, including iron (Fe), but because metals are bound in mineral matrices, in vitro bioaccessibility (BA) is limited. We conducted a relative bioavailability (RBA) study using F344 rats to assess Mn RBA from EAF slag ingestion, compared with Mn in diet. Mn and Fe were measured in liver, and Mn in lung and striatum, the target tissue of the brain. Mn levels in each tissue were fit by dose-to-tissue concentration (D-TC) curves. The D-TC relationship was the most highly significant for the linear model using liver Mn, and the RBA was 48%. The D-TC relationship in lung showed a positive slope for chow, but that for EAF slag was slightly negative, and the RBA was 14%. In comparison, the striatum D-TC remained relatively constant, supporting that homeostasis was maintained. Increased Fe was observed in the liver of EAF slag-dosed groups, suggesting that Mn absorption was inhibited by the high Fe content of slag. Lung and striatum D-TC curves demonstrated that systemic delivery of Mn from EAF slag ingestion is limited and support an RBA of 14% for risk assessment. Although Mn levels in slag are elevated compared with health-based screening guidelines, this study supports that incidental ingestion of Mn in EAF slag is unlikely to pose a neurotoxicity hazard due to homeostatic controls, low BA, and high Fe content.

Assessment of dermal hazard from acid burns with fire retardant garments in a full-size simulation of an engulfment flash fire.

There have been concerns that fire-derived acid gases could aggravate thermal burns for individuals wearing synthetic flame retardant garments. A comparative risk assessment was performed on three commercial flame retardant materials with regard to relative hazards associated with acidic combustion gases to skin during a full engulfment flash fire event. The tests were performed in accordance with ASTM F1930 and ISO 13506: Standard Test Method for Evaluation of Flame Resistant Clothing for Protection against Fire Simulations Using an Instrumented Manikin. Three fire retardant textiles were tested: an FR treated cotton/nylon blend, a low Protex(®) modacrylic blend, and a medium Protex(®) modacrylic blend. The materials, in the form of whole body coveralls, were subjected to propane-fired flash conditions of 84kW/m(2) in a full sized simulator for a duration of either 3 or 4s. Ion traps consisting of wetted sodium carbonate-impregnated cellulose in Teflon holders were placed on the chest and back both above and under the standard undergarments. The ion traps remained in position from the time of ignition until 5min post ignition. Results indicated that acid deposition did increase with modacrylic content from 0.9µmol/cm(2) for the cotton/nylon, to 12µmol/cm(2) for the medium modacrylic blend. The source of the acidity was dominated by hydrogen chloride. Discoloration was inversely proportional to the amount of acid collected on the traps. A risk assessment was performed on the potential adverse impact of acid gases on both the skin and open wounds. The results indicated that the deposition and dissolution of the acid gases in surficial fluid media (perspiration and blood plasma) resulted in an increase in acidity, but not sufficient to induce irritation/skin corrosion or to cause necrosis in open third degree burns.