Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management.

This review is intended to provide risk assessors and risk managers with a better understanding of issues associated with total exposures of human populations to ethylene oxide from endogenous and exogenous pathways. Biomonitoring of human populations and lab animals exposed to ethylene oxide has relied upon the detection of hemoglobin adducts such as 2-hydroxyethylvaline (HEV), which provides a useful measure of total exposure to ethylene oxide from all pathways. Recent biomonitoring data from CDC provide an excellent characterization of total exposure to ethylene oxide to the general U.S. population by demographic factors such as age, gender, and race as well as smoking habit, which might be comparable to previous measurements reported for humans and lab animals. The biochemical pathways including gastrointestinal (production by bacteria) and systemic (enzymatic production) pathways by which endogenous ethylene is generated and converted to ethylene oxide are described. The relative importance of endogenous pathways and exogenous pathways via ambient air or tobacco smoke was quantified based upon available data to characterize their relative importance to total exposure. Considerable variation was noted for HEV measurements in human populations, and important sources of variation for all pathways are discussed. Issues related to risk assessment and risk management of human populations exposed to ethylene oxide are provided within the context of characterizing total exposure, and data needs for supporting future risk assessment identified.

Exposures from chrysotile-containing joint compound: evaluation of new model relating respirable dust to fiber concentrations.

The potential for fiber exposure during historical use of chrysotile-containing joint compounds (JCC) has been documented, but the published data are of limited use for reconstructing exposures and assessing worker risk. Consequently, fiber concentration distributions for workers sanding JCC were independently derived by applying a recently developed model based on published dust measurements from sanding modern-day (asbestos-free) joint compound and compared to fiber concentration distributions based on limited historical measurements. This new procedure relies on factors that account for (i) differences in emission rates between modern-day and JCC and (ii) the number of fibers (quantified by phase contrast microscopy [PCM]) per mass of dust generated by sanding JCC, as determined in a bench-scale chamber study using a recreated JCC, that convert respirable dust concentrations to fiber concentrations. Airborne respirable PCM-fiber concentration medians (and 95% confidence intervals) derived for output variables using the new procedure were 0.26 (0.039, 1.7) f/cm(3) and 0.078 (0.013, 0.47) f/cm(3) , and corresponding total fiber concentrations were 1.2 (0.17, 9.2) f/cm(3) and 0.37 (0.056, 2.5) f/cm(3) , in enclosed and nonenclosed environments, respectively. Corresponding estimates of respirable and total PCM fiber concentrations measured historically during sanding of asbestos-containing joint compound-adjusted for differences between peak and time-weighted average (TWA) concentrations and documented analytical preparation and sampling artifacts-were 0.15 (0.019, 0.95) f/cm(3) and 0.86 (0.11, 5.4) f/cm(3) , respectively. The PCM-fiber concentration distributions estimated using the new procedure bound the distribution estimated from adjusted TWA historical fiber measurements, suggesting reasonable consistency of these estimates taking into account uncertainties addressed in this study.

Potential artifacts associated with historical preparation of joint compound samples and reported airborne asbestos concentrations.

Airborne samples collected in the 1970s for drywall workers using asbestos-containing joint compounds were likely prepared and analyzed according to National Institute of Occupational Safety and Health Method P&CAM 239, the historical precursor to current Method 7400. Experimentation with a re-created, chrysotile-containing, carbonate-based joint compound suggested that analysis following sample preparation by the historical vs. current method produces different fiber counts, likely because of an interaction between the different clearing and mounting chemicals used and the carbonate-based joint compound matrix. Differences were also observed during analysis using Method 7402, depending on whether acetic acid/dimethylformamide or acetone was used during preparation to collapse the filter. Specifically, air samples of sanded chrysotile-containing joint compound prepared by the historical method yielded fiber counts significantly greater (average of 1.7-fold, 95% confidence interval: 1.5- to 2.0-fold) than those obtained by the current method. In addition, air samples prepared by Method 7402 using acetic acid/dimethylformamide yielded fiber counts that were greater (2.8-fold, 95% confidence interval: 2.5- to 3.2-fold) than those prepared by this method using acetone. These results indicated (1) there is an interaction between Method P&CAM 239 preparation chemicals and the carbonate-based joint compound matrix that reveals fibers that were previously bound in the matrix, and (2) the same appeared to be true for Method 7402 preparation chemicals acetic acid/dimethylformamide. This difference in fiber counts is the opposite of what has been reported historically for samples of relatively pure chrysotile dusts prepared using the same chemicals. This preparation artifact should be considered when interpreting historical air samples for drywall workers prepared by Method P&CAM 239.

Re-creation of historical chrysotile-containing joint compounds.

Chrysotile-containing joint compound was commonly used in construction of residential and commercial buildings through the mid 1970s; however, these products have not been manufactured in the United States for more than 30 years. Little is known about actual human exposures to chrysotile fibers that may have resulted from use of chrysotile-containing joint compounds, because few exposure and no health-effects studies have been conducted specifically with these products. Because limited amounts of historical joint compounds are available (and the stability or representativeness of aged products is suspect), it is currently impossible to conduct meaningful studies to better understand the nature and magnitude of potential exposures to chrysotile that may have been associated with historical use of these products. Therefore, to support specific exposure and toxicology research activities, two types of chrysotile-containing joint compounds were produced according to original formulations from the late 1960s. To the extent possible, ingredients were the same as those used originally, with many obtained from the original suppliers. The chrysotile used historically in these products was primarily Grade 7RF9 from the Philip Carey mine. Because this mine is closed, a suitable alternate was identified by comparing the sizes and mineral composition of asbestos structures in a sample of what has been represented to be historical joint compound (all of which were chrysotile) to those in samples of three currently commercially available Grade 7 chrysotile products. The re-created materials generally conformed to original product specifications (e.g. viscosity, workability, crack resistance), indicating that these materials are sufficiently representative of the original products to support research activities.

Cyproheptadine in levodopa-induced dyskinesia in parkinsonism.

The neuroendocrine properties and the beneficial effects of cyproheptadine in tardive dyskinesia led to the testing of this drug in levodopa-induced dyskinesia. Cyproheptadine administered to 6 parkinsonian patients in doses of up to 42 mg/day was of no significant benefit in either dyskinesia or symptom control. Improvement in appetite was reported by 3 patients. These observations suggested that different mechanisms may be responsible in the pathogenesis of phenothiazine and amine-induced dyskinesia. The failure to control levodopa-induced dyskinesia selectively with serotonin agonists and antagonists and the accentuation of the dyskinesia in the presence of anticholinergic agents further suggest that substances that increase directly central cholinergic activity may be effective in the control of levodopa-induced dyskinesia.

Aperture configuration and imaging performance.

It is generally accepted for optical apertures that obstructions of small proportions are relatively harmless for good imaging performance and that larger aperture obstructions should be avoided. This work presents some quantitative data on this subject. Optical simulation was used to measure parameters of images created by different families of aperture configurations. Twenty-four apertures were selected, and the following data given: aperture shape, energy portion within an area equivalent to the Airy disk and to a circle including the third bright ring of the ideal diffraction image, modulation transfer function, and a photograph of the diffraction image. Design criteria are discussed for aperture configurations of large telescope systems.

The health hazards posed by chromium-contaminated soils in residential and industrial areas: conclusions of an expert panel.

Between 1905 and 1971, over 2 million tons of residue from chromite ore processing was generated in Hudson County, New Jersey, of which substantial amounts were used as fill and tank diking. A panel of medical, toxicology, and risk assessment experts was convened in early 1990 to evaluate the potential health hazards posed by the resulting chromium contaminated soil. The Panel concluded that soils containing concentrations of 75 ppm hexavalent chromium [Cr(VI)] and 1000 ppm total chromium compounds (about 95% was trivalent chromium [Cr(III)]) did not pose a significant health hazard to nearby residents and workers. They also determined that exposure to chromium from Hudson County sites posed a negligible cancer hazard to residents. Using risk assessment methods, the Panel estimated that the plausible incremental cancer risk to individuals at residential sites would be substantially less than 1 in 1,000,000. The average measured levels of airborne Cr(VI) at typical industrial sites were more than 1000-fold lower than the current OSHA Permissible Exposure Limit (PEL). The maximum plausible increased cancer risk for an average worker at a dusty industrial site was estimated to be less than 1 in 100,000. The Panel also concluded that chromium-containing crystals, which have occasionally been found in Hudson County buildings, do not pose a significant hazard. However, they suggested that were the concentration to exceed 5000 ppm Cr(VI) in the crystals, site-specific health risk assessments would be conducted and remediation considered. The Panel evaluated the dermal hazard posed by chromium-contaminated soil and acknowledged that there is a small group of persons (approximately 0.1% of the United States population) who currently have a dermal sensitization to Cr(VI) primarily through occupational exposure. Based on published studies of human volunteers, the Panel concluded that a small percentage (less than 5%) of persons already sensitized may respond to Cr(VI) in solution at concentrations above 35 ppm. They decided that a much higher concentration in soil, perhaps 350 ppm Cr(VI), would be necessary to elicit dermatitis because only a fraction of the chromium in soil is soluble. The Panel concluded that it was highly unlikely (if not impossible) for a person to become dermally sensitized to Cr(VI) or Cr(III) at the soil concentrations found in most areas in Hudson County.(ABSTRACT TRUNCATED AT 400 WORDS)

Sediment toxicity evaluation for hexachlorobenzene: spiked sediment tests with Leptocheirus plumulosus, Hyalella azteca, and Chironomus tentans.

Hexachlorobenzene (HCB) is a hydrophobic organic chemical that has shown a lack of toxicity in aquatic tests at concentrations up to and exceeding the solubility limit. The equilibrium partitioning approach to deriving sediment quality benchmarks, which assumes that toxicity can be predicted based on contaminant concentrations in interstitial water, predicts that HCB will not produce direct toxicity to benthic invertebrates as a sediment contaminant. However, the potential for toxicity due to direct exposure to sediment-adsorbed HCB has not been thoroughly established. This study evaluated the survival and growth of the estuarine amphipod Leptocheirus plumulosus, the freshwater amphipod Hyalella azteca, and the midge Chironomus tentans (freshwater) following 10-day exposure to sediment spiked with a range of HCB concentrations. H. azteca was tested under both freshwater and estuarine (10 ppt salinity) conditions. No significant toxicity was observed for any test species at the highest test concentration (60 mg/kg normalized to 1% organic carbon). Minimum detectable differences were less than or equal to 20% for three of eight test endpoints. The observed results add to the available weight of evidence indicating a limited potential for HCB-related sediment toxicity to benthic invertebrates.

An assessment and quantitative uncertainty analysis of the health risks to workers exposed to chromium contaminated soils.

Millions of tons of chromite-ore processing residue have been used as fill in various locations in Northern New Jersey and elsewhere in the United States. The primary toxicants in the residue are trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)]. The hazard posed by Cr(III) is negligible due to its low acute and chronic toxicity. In contrast, Cr(VI) is considered a inhalation human carcinogen at high concentrations. Approximately 40 commercial and industrial properties in Northern New Jersey have been identified as containing chromite ore processing residue in the soil. One site, a partially-paved trucking terminal, was evaluated in this assessment. The arithmetic mean and geometric mean concentrations of total chromium in soil were 977 and 359 mg/kg, respectively. The data were log-normal distributed. The arithmetic mean and geometric mean concentrations of Cr(VI) in surface soil were 37.6 and 3.1 mg/kg, respectively. The data could not be fit to a standard distribution, likely due to the large number of samples with concentrations below the method detection limit (65%). Dose was calculated for each exposure route using a Monte Carlo statistical simulation. Probability distributions of most exposure parameters were incorporated into the analyses to predict the range and probability of uptake for persons in the exposed population. The exposure parameter distributions included in this assessment are: the concentrations of Cr(VI) and total chromium in air and soil, fraction of the year when suspension of airborne soil particulates is likely to occur due to weather conditions, fraction of Cr(VI) in air which is respirable (less than 10 microns), soil loading rate on skin, occupational tenure, and body weight. The techniques used in this assessment are applicable for evaluating the human health risks posed by most industrial sites having contaminated soil. The estimated average daily dose (ADD) via ingestion and dermal absorption for the individual exposed at the 95th percentile was about 48,000- and 91-fold below the U.S. EPA reference dose (RfD) for Cr(III) and Cr(VI), respectively. Since inhalation of Cr(VI) contaminated dust (but not ingestion or dermal contact) poses a cancer hazard, the lifetime average daily doses (LADDs) associated with exposure at the 50th and 95th percentile were calculated to be 9.8 x 10(-8) and 1.3 x 10(-6), respectively. Based on this analysis, industrial sites having soil concentrations of Cr(VI) below 230 ppm do not pose a significant noncarcinogenic or carcinogenic health hazard following acute or chronic exposure. These risks would be even smaller if the sites were paved.

Assessment of the human health risks posed by exposure to chromium-contaminated soils.

Millions of tons of chromite-ore processing residue have been used as fill in various locations in northern New Jersey and elsewhere in the United States. The primary toxicants in the residue are trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)]. The hazard posed by Cr(III) is negligible due to its low acute and chronic toxicity. In contrast, Cr(VI) is a human carcinogen following inhalation of high concentrations. It can also cause allergic contact dermatitis. This evaluation addresses a residential site where the arithmetic mean (x) and geometric mean (gm) concentrations of Cr(III) in soil were 2879 and 1212 mg/kg (ppm). The mean and geometric mean concentrations of Cr(VI) were 180 and 4 mg/kg, respectively. The uptake (absorbed dose) of Cr(III) via soil ingestion, consumption of homegrown vegetables, and ingestion of inspired particles was determined. The uptake of Cr(VI) via dermal absorption from contact with surface soil and building wall surfaces, as well as inhalation, was also evaluated. The techniques used in this assessment are applicable for evaluating the human health risks posed by any residential site having contaminated soil. The potential for both sensitized and unsensitized persons to develop allergic contact dermatitis due to exposure to soil contaminated at these levels was found to be negligible. The estimated average daily dose (ADD) via ingestion and dermal absorption for the maximally exposed individual (MEI) was about 1500- and 40-fold below the EPA reference dose (RfD) for Cr(III) and Cr(VI), respectively. It was shown that for residential sites, the most important route of exposure to Cr(III) was incidental soil ingestion. Although not relevant to these sites specifically, if garden vegetables could be successfully grown in these soils, then they would probably be the predominant source of uptake of Cr(III). Since inhalation of Cr(VI)-contaminated dust (but not ingestion or dermal contact) poses a cancer hazard, the doses and associated risks were assessed. The estimated cancer risks for the MEI and most likely exposed individual (MLEI) were approximately 5 x 10(-9) and 2 x 10(-9), respectively. These levels of risk have always been considered well below those that warrant regulatory concern. For persons living on residential properties, the cancer risk due to inhaling suspended particles is likely to be less than 1 in 1,000,000 if Cr(VI) levels in soil are less than 180 mg/kg (ppm). Based on this analysis, the levels of Cr(III) and Cr(VI) at this and similar sites do not pose a health hazard following acute or chronic exposure.

Review of the allergic contact dermatitis hazard posed by chromium-contaminated soil: identifying a "safe" concentration.

At least 200 sites in the United States contain soil with elevated levels of trivalent and hexavalent chromium [Cr(III) and Cr(VI)]. Although the potential cancer hazard posed by airborne Cr(VI) has been the primary concern for these sites, a soil cleanup standard based on the potential elicitation of allergic contact dermatitis has been proposed for sites in Hudson County, N.J. This paper describes the rationale for identifying a soil concentration of Cr(VI) that should not pose an allergic contact dermatitis hazard-even in sensitized persons. A literature review of eight published patch test studies that evaluated the allergic response to potassium dichromate was conducted. These studies were evaluated for clinical and statistical relevance in establishing a threshold dose of Cr(VI) to which no more than 10% of the subpopulation sensitized to chromium would respond, and that would protect at least 99.84% of the general population. Although each of the studies had certain methodological limitations when evaluated against current test methods, the data set proved useful for deriving an estimated threshold. Using computer data-fitting techniques based on truncated lognormal distributions, a weighted mean 10% threshold of approximately 150 ppm potassium dichromate or 54 ppm Cr(VI) was identified for the eight studies. Due to the types of limitations noted for these studies, this threshold is likely to be somewhat conservative. Test results have shown that between 5 and 10% of the Cr(VI) at concentrations less than about 500 ppm are released from a soil matrix into an isotonic saline solution simulating sweat. Using human sweat as the extractant, it has been shown that only 0.1% of the CR(VI) at concentrations of approximately 1,000 ppm are released from a soil matrix into sweat. Based on 10% solubilization of soil-bound Cr(VI) and the results of our statistical analysis of previous threshold studies, a concentration of approximately 350 to 500 ppm Cr(VI) in soil should be sufficiently low to protect virtually all exposed people, including children, from chromium-induced allergic contact dermatitis.