Framework for human health risk assessment of non-cancer effects resulting from short-duration and intermittent exposures to chemicals.

Durations of exposure to chemicals, whether for single, repeated or intermittent periods, may vary from those upon which most guidance values are normally based. Because it is presently not feasible to conduct toxicity studies or develop toxicity reference values (TRVs) specific to each scenario of interest, methods are needed to address these various durations, drawing as much as possible on existing TRVs. A working framework was developed to address the potential for non-cancer effects resulting from continuous short-duration and intermittent exposures to chemicals. The framework presents an integrated, tiered approach that assists the user in identifying when existing TRVs can be applied directly, and the adaptations needed to assess the acceptability of short-duration or intermittent exposure scenarios. Descriptions of when and how toxicokinetic and toxicodynamic aspects need to be taken into consideration are also presented. The framework incorporates the use of TRVs based on exposure periods as similar as possible to the "actual" exposure periods and application of dose averaging under limited, specified conditions. This framework has been developed to aid in improving the scientific basis for the evaluation of short-duration and intermittent exposures in a variety of settings. Copyright © 2016 John Wiley & Sons, Ltd.

Canadian house dust study: lead bioaccessibility and speciation.

Vacuum samples were collected from 1025 randomly selected urban Canadian homes to investigate bioaccessible Pb (Pb(S)) concentrations in settled house dust. Results indicate a polymodal frequency distribution, consisting of three lognormally distributed subpopulations defined as "urban background" (geomean 58 µg g(-1)), "elevated" (geomean 447 µg g(-1)), and "anomalous" (geomean 1730 µg g(-1)). Dust Pb(S) concentrations in 924 homes (90%) fall into the "urban background" category. The elevated and anomalous subpopulations predominantly consist of older homes located in central core areas of cities. The influence of house age is evidenced by a moderate correlation between house age and dust Pb(S) content (R(2) = 0.34; n = 1025; p < 0.01), but it is notable that more than 10% of homes in the elevated/anomalous category were built after 1980. Conversely, the benefit of home remediation is evidenced by the large number of homes (33%) in the background category that were built before 1960. The dominant dust Pb species determined using X-ray Absorption Spectroscopy were as follows: Pb carbonate, Pb hydroxyl carbonate, Pb sulfate, Pb chromate, Pb oxide, Pb citrate, Pb metal, Pb adsorbed to Fe- and Al-oxyhydroxides, and Pb adsorbed to humate. Pb bioaccessibility estimated from solid phase speciation predicts Pb bioaccessibility measured using a simulated gastric extraction (R(2) = 0.85; n = 12; p < 0.0001). The trend toward increased Pb bioaccessibility in the elevated and anomalous subpopulations (75% ± 18% and 81% ± 8%, respectively) compared to background (63% ± 18%) is explained by the higher proportion of bioaccessible compounds used as pigments in older paints (Pb carbonate and Pb hydroxyl carbonate). This population-based study provides a nationally representative urban baseline for applications in human health risk assessment and risk management.

A novel "by difference" method for assessing dermal absorption of polycyclic aromatic hydrocarbons from soil at federal contaminated sites.

A highly precautionary cost-effective method for estimating dermal absorption using data from 24-h skin soap washes from in vitro dermal absorption tests in Bronaugh flow-through diffusion cells with human skin is reported. Skin was dosed with 16 U.S. Environmental Protection (EPA) priority polycyclic aromatic hydrocarbons (PAH) applied in mixture each at 2 µg/ml (ppm) in acetone without soil. Concurrent tests were conducted with an unspiked aqueous suspension of PAH-contaminated soil obtained from a Canadian federal contaminated site. Percentage dermal absorption was estimated "by difference" from the applied dose and that detected by high-performance liquid chromatography (HPLC) in 24-h skin soap washes. The dermal absorption for 11 PAH ranged from 71 to 88.3% without and with soil, respectively. Lower absorption was found for 5 PAH in soil, in the range of 26.4 to 60.8%. Data could not be corrected for evaporative loss due to inconsistent data from Tenax adsorbent. Corroboratory gas chromatography/mass spectroscopy (GC/MS) tests are needed. Previously published in vitro data from the authors' laboratory supported use of the "by difference" method.

Contaminated soils (III): in vitro dermal absorption of ethylene glycol and nonylphenol in human skin.

Dermal absorption of contaminants from soils at federal contaminated sites in Canada was investigated using one hydrophile, (14)C-ethylene glycol (EG), and one lipophile, (14)C-nonylphenol (NP). In vitro dermal absorption of EG and NP was examined in dermatomed (0.4-0.5 mm) human skin using Bronaugh Teflon flow-through cells with Hanks HEPES buffered (pH 7.4) receiver solution with 4% bovine serum albumin (BSA). Tests were conducted under occlusive conditions with and without a commercial gardening soil spiked with EG or NP applied to skin at a soil load of 5 mg/cm(2). With percent absorption in skin depot included, a total of 9.9 + or - 6.28% (n = 6) and 34.8 + or - 8.47% (n = 6) absorption of EG with and without soil, respectively, and 20.6 + or - 5.56% (n = 7) and 41.1 + or - 6.46% (n = 7) of NP, with and without soil, respectively, were obtained. For tests without soil a reverse pattern was observed with significantly lower percent absorption into the receiver than depot with the lipophile NP, but significantly higher percent absorption in receiver versus depot for the hydrophile EG. This pattern was different in tests with soil, and caution needs to be exercised when extrapolating data from in vitro tests conducted without soil in human health risk assessments at contaminated sites.

Contaminated soils (II): in vitro dermal absorption of nickel (Ni-63) and mercury (Hg-203) in human skin.

Dermal absorption of heavy metal soil contaminants was tested in vitro with chloride salts of radioactive nickel (Ni-63) and mercury (Hg-203). Aqueous soil suspensions, spiked with either Ni-63 or Hg-203, were applied to fresh viable human breast skin tissue in Bronaugh diffusion cells perfused with Hanks HEPES buffered (pH 7.4) receptor containing 4% bovine serum albumin (BSA). Receptor fractions were collected every 6 h for 24 h when skin was soap washed. Tests were conducted concurrently in triplicate with and without soil for each skin specimen. Mean percent dermal absorption including the skin depot for Ni-63 was 1 and 22.8% with and without soil, respectively, while for Hg-203, values of 46.6 and 78.3% were obtained. Excluding the skin depot and considering only absorption in receptor, there was 0.5 and 1.8% absorption of Ni-63 with and without soil, respectively, and 1.5 and 1.4% for Hg-203. The potential bioavailability of the skin depot is discussed in relation to dermal exposure to these metals in contaminated soil.

Canadian House Dust Study: population-based concentrations, loads and loading rates of arsenic, cadmium, chromium, copper, nickel, lead, and zinc inside urban homes.

The Canadian House Dust Study was designed to obtain nationally representative urban house dust metal concentrations (µg g(-1)) and metal loadings (µg m(-2)) for arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn). Consistent sampling of active dust of known age and provenance (area sampled) also permitted the calculation of indoor loading rates (mg m(-2) day(-1) for dust and µg m(-2) day(-1) for metals) for the winter season (from 2007 to 2010) when houses are most tightly sealed. Geomean/median indoor dust loading rates in homes located more than 2 km away from industry of any kind (9.6/9.1 mg m(-2) day(-1); n=580) were significantly lower (p<.001) than geomean (median) dust loading rates in homes located within 2 km of industry (13.5/13.4 mg m(-2) day(-1); n=421). Proximity to industry was characterized by higher indoor metal loading rates (p<.003), but no difference in dust metal concentrations (.29≥p≤.97). Comparisons of non-smokers' and smokers' homes in non-industrial zones showed higher metal loading rates (.005≥p≤.038) in smokers' homes, but no difference in dust metal concentrations (.15≥p≤.97). Relationships between house age and dust metal concentrations were significant for Pb, Cd and Zn (p<.001) but not for the other four metals (.14≥p≤.87). All seven metals, however, displayed a significant increase in metal loading rates with house age (p<.001) due to the influence of higher dust loading rates in older homes (p<.001). Relationships between three measures of metals in house dust - concentration, load, and loading rate - in the context of house age, smoking behavior and urban setting consistently show that concentration data is a useful indicator of the presence of metal sources in the home, whereas dust mass is the overriding influence on metal loadings and loading rates.