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Berger R.G.,Intrinsik Health science Inc. | Aslund M.W.,Intrinsik Environmental Sciences Inc. | Sanders G.,Omnia Ecological Services | Charlebois M.,Omnia Ecological Services | And 2 more authors.
Science of the Total Environment | Year: 2016

To assess the ecological impacts of two independent accidental bitumen releases from two steam assisted gravity drainage (SAGD) wells in the Athabasca oil sands region, a multiple lines of evidence (LOE) approach was developed. Following the release in 2010, action was taken to minimize environmental impact, including the selective removal of the most highly impacted vegetation and the use of oil socks to minimize possible runoff. An ecological risk assessment (ERA) was then conducted based on reported concentrations of bitumen related contaminants in soil, vegetation, and water. Results of biological assessments conducted at the site were also included in the risk characterization. Overall, the conclusion of the ERA was that the likelihood of long-term adverse health effects to ecological receptors in the area was negligible. To provide evidence for this conclusion, a small mammal sampling plan targeting Southern red-back voles (Myodes gapperi) was carried out at two sites and two relevant reference areas. Voles were readily collected at all locations and no statistically significant differences in morphometric measurements (i.e., body mass, length, foot length, and adjusted liver weight) were found between animals collected from impact zones of varying levels of coverage. Additionally, no trends corresponding with bitumen coverage were observed with respect to metal body burden in voles for metals that were previously identified in the source bitumen. Hepatic ethoxyresorufin-O-deethylase (EROD) activity was statistically significantly elevated in voles collected from the high impact zones of sites compared to those collected from the reference areas, a finding that is indicative of continued exposure to contaminants. However, this increase in EROD was not correlated with any observable adverse population-wide biological outcomes. Therefore the biological sampling program supported the conclusion of the initial ERA and supported the hypothesis of no significant long-term population-wide ecological impact of the accidental bitumen releases. © 2015 The Authors. Source


Solano M.E.,University of Hamburg | Kowal M.K.,University of Hamburg | O'Rourke G.E.,University of Hamburg | Horst A.K.,University of Hamburg | And 14 more authors.
Journal of Clinical Investigation | Year: 2015

Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor- or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies. Source


Safruk A.M.,Intrinsik Environmental Sciences Inc. | Safruk A.M.,Intrinsik Health science Inc. | Berger R.G.,Intrinsik Environmental Sciences Inc. | Berger R.G.,Intrinsik Health science Inc. | And 4 more authors.
Science of the Total Environment | Year: 2015

Environmental contaminants associated with soil particles are generally less bioavailable than contaminants associated with other exposure media where chemicals are often found in more soluble forms. In vitro methods, such as Physiological Based Extraction Tests (PBET), can provide estimates of bioaccessibility for soil-based contaminants. The results of these tests can be used to predict exposure to contaminants from soil ingestion pathways within human health risk assessment (HHRA). In the current investigation, an HHRA was conducted to examine the risks associated with elevated concentrations of mercury in soils in the northern Canadian smelter community of Flin Flon, Manitoba. A PBET was completed for residential soils and indicated mean bioaccessibilities of 1.2% and 3.0% for total mercury using gastric phase and gastric+intestinal phase methodologies, respectively. However, as many regulators only allow for the consideration of in vitro results for lead and arsenic in the HHRA process, in vitro bioaccessibility results for mercury were not utilized in the current HHRA. Based on the need to assume 100% bioaccessibility for inorganic mercury in soil, results from the HHRA indicated the need for further assessment of exposure and risk. A biomonitoring study was undertaken for children between 2 and 15. years of age in the community to examine urinary inorganic mercury concentrations. Overall, 375 children provided valid urine samples for analysis. Approximately 50% of urine samples had concentrations of urinary inorganic mercury below the limit of detection (0.1. μg/L), with an average creatinine adjusted concentration of 0.11. μg/g. Despite high variability in mercury soil concentrations within sub-communities, soil concentrations did not appear to influence urinary mercury concentrations. The results of the current investigation indicate that mercury bioaccessibility in residential soils in the Flin Flon area was likely limited and that HHRA estimates would have been better approximated through inclusion of the in vitro study results. © 2015. Source


Arthur A.J.,Senomyx Inc. | Karanewsky D.S.,Senomyx Inc. | Luksic M.,Intrinsik Health science Inc. | Goodfellow G.,Intrinsik Health science Inc. | Daniels J.,Intrinsik Health science Inc.
Food and Chemical Toxicology | Year: 2015

A toxicological evaluation of two structurally related flavors with modifying properties, 3-((4-amino-2,2-dioxido-1. H- benzo[. c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl- N-propylpropanamide (S6973; CAS 1093200-92-0) and ( S)-1-(3-(((4-amino-2,2-dioxido-1. H-benzo[. c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-3-methylbutan-1-one (S617; CAS 1469426-64-9), was completed for the purpose of assessing their safety for use in food and beverage applications. Both compounds exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, were poorly absorbed and rapidly eliminated. Neither compound exhibited genotoxic concerns. S6973 and S617 were not found to be mutagenic or clastogenic, and did not induce micronuclei in vitro or in vivo. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-levels (NOAELs) were 20mg/kg/day and 100mg/kg/day (highest doses tested) for S6973 and S617, respectively, when administered as a food ad-mix for 90 consecutive days. Furthermore, S617 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. © 2014 Elsevier Ltd. Source

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