The SHEDS-Wood Model: Incorporation of Observational Data to Estimate Exposure to Arsenic for Children Playing on CCA-Treated Wood Structures

BACKGROUND: Lumber treated with chromated copper arsenate (CCA) compounds has been used in residential outdoor wood structures and public playgrounds. The U.S. Environmental Protection Agency (EPA) has conducted a probabilistic assessment of children’s exposure to arsenic using the Stochastic Human Exposure and Dose Simulation model for the wood preservative scenario (SHEDS-Wood). The assessment relied on data derived from an experimental study conducted using adult volunteers and designed to result in maximum hand and wipe loadings to estimate the residue–skin transfer efficiency. Recent analyses of arsenic hand-loading data generated by studies of children actively involved in playing on CCA-treated structures indicate that the transfer efficiency coefficient and hand-loading estimates derived from the experimental study significantly overestimate the amount that occurs during actual play. OBJECTIVES: Our goal was to assess the feasibility of using child hand-loading data in the SHEDS-Wood model and their impact on exposure estimates. METHODS: We used data generated by the larger of the studies of children in SHEDS-Wood, instead of the distributions used by U.S. EPA. We compared our estimates of the lifetime average daily dose (LADD) and average daily dose (ADD) with those derived by the U.S. EPA. RESULTS: Our analysis indicates that data from observational studies of children can be used in SHEDS-Wood. Our estimates of the mean (and 95th percentile) LADD and ADD were 27% (10%) and 29% (15%) of the estimates derived by U.S. EPA. CONCLUSION: We recommend that the SHEDS-Woods model use data from studies of children actively playing on playsets to more accurately estimate children’s actual exposures to CCA

Evaluation of Exposure to Arsenic in Residential Soil

In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89–17.7 μg/L, respectively) and older participants (3.8, 1.9, 0.91–19.9 μg/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background

Angiogenin protects motoneurons against hypoxic injury.

Cells can adapt to hypoxia through the activation of hypoxia-inducible factor-1 (HIF-1), which in turn regulates the expression of hypoxia-responsive genes. Defects in hypoxic signaling have been suggested to underlie the degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). We have recently identified mutations in the hypoxia-responsive gene, angiogenin (ANG), in ALS patients, and have shown that ANG is constitutively expressed in motoneurons. Here, we show that HIF-1alpha is sufficient and required to activate ANG in cultured motoneurons exposed to hypoxia, although ANG expression does not change in a transgenic ALS mouse model or in sporadic ALS patients. Administration of recombinant ANG or expression of wild-type ANG protected motoneurons against hypoxic injury, whereas gene silencing of ang1 significantly increased hypoxia-induced cell death. The previously reported ALS-associated ANG mutations (Q12L, K17I, R31K, C39W, K40I, I46V) all showed a reduced neuroprotective activity against hypoxic injury. Our data show that ANG plays an important role in endogenous protective pathways of motoneurons exposed to hypoxia, and suggest that loss of function rather than loss of expression of ANG is associated with ALS

The Puf-Family RNA-Binding Protein Puf2 Controls Sporozoite Conversion to Liver Stages in the Malaria Parasite

Malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus Plasmodium. During host switch the malaria parasite employs specialized latent stages that colonize the new host environment. Previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. Sexual parasite development is controlled by a DEAD-box RNA helicase of the DDX6 family, termed DOZI. Latency of sporozoites, the transmission stage injected during an infectious blood meal, is controlled by the eIF2alpha kinase IK2, a general inhibitor of protein synthesis. Whether RNA-binding proteins participate in translational regulation in sporozoites remains to be studied. Here, we investigated the roles of two RNA-binding proteins of the Puf-family, Plasmodium Puf1 and Puf2, during sporozoite stage conversion. Our data reveal that, in the rodent malaria parasite P. berghei, Puf2 participates in the regulation of IK2 and inhibits premature sporozoite transformation. Inside mosquito salivary glands puf2(-) sporozoites transform over time to round forms resembling early intra-hepatic stages. As a result, mutant parasites display strong defects in initiating a malaria infection. In contrast, Puf1 is dispensable in vivo throughout the entire Plasmodium life cycle. Our findings support the notion of a central role for Puf2 in parasite latency during switch between the insect and mammalian hosts

Determination of Cellular Lipids Bound to Human CD1d Molecules

CD1 molecules are glycoproteins that present lipid antigens at the cell surface for immunological recognition by specialized populations of T lymphocytes. Prior experimental data suggest a wide variety of lipid species can bind to CD1 molecules, but little is known about the characteristics of cellular ligands that are selected for presentation. Here we have molecularly characterized lipids bound to the human CD1d isoform. Ligands were eluted from secreted CD1d molecules and separated by normal phase HPLC, then characterized by mass spectroscopy. A total of 177 lipid species were molecularly identified, comprising glycerophospholipids and sphingolipids. The glycerophospholipids included common diacylglycerol species, reduced forms known as plasmalogens, lyso-phospholipids (monoacyl species), and cardiolipins (tetraacyl species). The sphingolipids included sphingomyelins and glycosylated forms, such as the ganglioside GM3. These results demonstrate that human CD1d molecules bind a surprising diversity of lipid structures within the secretory pathway, including compounds that have been reported to play roles in cancer, autoimmune diseases, lipid signaling, and cell death

Total arsenic in hand washings and time on structure (children 1–6 years of age)

<p><b>Copyright information:</b></p><p>Taken from "The SHEDS-Wood Model: Incorporation of Observational Data to Estimate Exposure to Arsenic for Children Playing on CCA-Treated Wood Structures"</p><p></p><p>Environmental Health Perspectives 2007;115(5):781-786.</p><p>Published online 21 Feb 2007</p><p>PMCID:PMC1867987.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Linear regression line: [total arsenic (μg/cm)] = –4 × 10; [length of playtime (min)] + 0.0031 ( = 0.0048)