Bureau of Chemical Safety

Ottawa, Canada

Bureau of Chemical Safety

Ottawa, Canada
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Lefebvre D.E.,Bureau of Chemical Safety | Pearce B.,Bureau of Chemical Safety | Fine J.H.,Bureau of Chemical Safety | Chomyshyn E.,Bureau of Chemical Safety | And 5 more authors.
Toxicological Sciences | Year: 2014

Agglomerated carbon black nanoparticles (CBNPs) administered via respiratory or subcutaneous routes have been shown to promote allergic sensitization to coadministered ovalbumin (OVA) protein in rodents. In the present study, we aimed to model and elucidate the mechanism of this adjuvanticity using an in vitro assay based on T cell sensitization to ovalbumin323-339 peptide (OVAp). CBNP base particles of 22 and 39 nm were characterized and termed CBNP22 and CBNP39 powders. Splenic leukocytes derived from transgenic DO11.10 mice were exposed to suspensions of media alone, concanavalin A mitogen, CBNP agglomerates smaller than 220 nm, OVAp alone, OVAp + anti-CD28 costimulant, OVAp + cyclosporin A immunosuppressant, or OVAp + CBNPs. Samples were analyzed at 72 h post-exposure. Proliferation rate, a marker of cellular mitosis, was assessed. Polymerase chain reaction arrays were used to assess genes involved in allergic response pathways. The mitogen control, costimulatory control, and immunosuppressive control chemicals modified the T helper cell proliferation rate. CBNP22 mildly reduced proliferation at 12 μg/ml, but CBNP39 did not. Gene expression analysis of cells treated with OVAp showed that coincubation with 12 μg/ml CBNP22 enhanced gene expression of interleukin-4 (IL-4), IL-10, and IL-13, all allergy-associated Th2 cytokines. Coincubation of OVAp with 12 μg/ml CBNP39 significantly enhanced IL-13 gene expression concurrent with downregulation of the Th1-associated transcription factor Stat4. IL-4 and IL-13 protein secretion reflected the mRNA trends. The changes were consistently higher in cells exposed to CBNP22 than CBNP39, suggesting that smaller particle size, higher surface area, and higher purity were associated with the direct adjuvant effect on Th2 cells in this genetically susceptible model of OVA allergy. © Crown copyright 2014.

Gill S.,Toxicology Research Division | Kavanagh M.,Toxicology Research Division | Barker M.,Bureau of Chemical Safety | Weld M.,Premarket Toxicology Assessment Section | And 3 more authors.
Toxicologic Pathology | Year: 2011

Furan is a heterocyclic organic compound formed during heat treatment for processing and preservation of various types of food. Rodent studies have previously shown that furan is a hepatocarcinogen. Those studies were conducted over a high dose range, which induced tumors at nearly 100% incidence at all doses. This ninety-day gavage study in mice was conducted to extend the dose to a lower range (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg body weight [bw] per day) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects, including those affecting clinical biochemistry, hematology, tissue morphology, and histopathology. The liver was the primary target organ with dose-dependent toxicity. Liver weights were increased at the 8.0 mg/kg bw dose in females only. Levels of the serum enzyme alanine transaminase, representative of liver damage, were increased three-fold at the highest dose. Histological changes in the liver were observed at 2.0 and 8.0 mg/kg bw in both sexes. Although clinical parameters were also altered for the kidney, these differences were not accompanied by histological changes. Based on these clinical biochemical and histological changes, a no-observed adverse effect level of 0.12 mg/kg bw per day of furan in mice is suggested. © 2011 by The Author(s).

Cao X.-L.,Bureau of Chemical Safety | Zhao W.,Bureau of Chemical Safety | Churchill R.,Bureau of Chemical Safety | Dabeka R.,Bureau of Chemical Safety
Journal of Food Protection | Year: 2013

Polyvinyl chloride (PVC) food-wrapping films plasticized with di-(2-ethylhexyl) adipate (DEHA) are commonly used by grocery stores in Canada to rewrap meat, poultry, fish, cheese, and other foods. DEHA was assessed as part of the Government of Canada's Chemicals Management Plan. The main source of exposure for most age groups was expected to be food. Although the margin of exposure from food and beverages is considered to be adequately protective, the Government of Canada committed to performing targeted surveys of DEHA in foods and food packaging materials to better define Canadian exposure to DEHA through dietary intake. In order to determine whether more-comprehensive targeted surveys on DEHA in foods should be conducted, 26 food composite samples from the 2011 Canadian total diet study were selected and analyzed for DEHA using a method based on solvent and dispersive solid-phase extraction and gas chromatography-mass spectrometry. These 26 food composites include cheese, meat, poultry, fish, and fast foods, and PVC films were likely used in packaging the individual foods used to make the composites. DEHA was detected in most of the meat, poultry, and fish composite samples, with the highest concentration found in ground beef (11 μg/g), followed by beef steak (9.9 μg/g), freshwater fish (7.8 μg/g), poultry liver pâté (7.4 μg/g), fresh pork (6.9 μg/g), cold cuts and luncheon meats (2.8 μg/g), veal cutlets (2.1 μg/g), roast beef (1.3 μg/g), lamb (1.2 μg/g), and organ meats (0.20 μg/g). Targeted surveys should be conducted to investigate the presence of DEHA in various foods packaged with PVC films in more detail and provide updated occurrence data for accurate human exposure assessment.

Bartholomaeus A.,University of Queensland | Bartholomaeus A.,University of Canberra | Parrott W.,University of Georgia | Bondy G.,Bureau of Chemical Safety | Walker K.,ILSI International Food Biotechnology Committee
Critical Reviews in Toxicology | Year: 2013

There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of wellconducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable.

Cao X.-L.,Bureau of Chemical Safety | Zhao W.,Bureau of Chemical Safety | Churchill R.,Bureau of Chemical Safety | Hilts C.,Bureau of Chemical Safety
Journal of Food Protection | Year: 2014

Di-(2-ethylhexyl) adipate (DEHA) and phthalates are commonly used as plasticizers to soften polyvinyl chloride products. Because both DEHA and certain phthalates have been identified as priority chemicals for assessment of human health risk under the Government of Canadás Chemicals Management Plan, a comprehensive targeted survey was conducted to investigate the occurrence of DEHA and eight phthalates (di-methyl phthalate, di-ethyl phthalate, di-n-butyl phthalate, di-iso-butyl phthalate, butyl benzyl phthalate, di-n-hexyl phthalate, d-(2-ethylhexyl) phthalate, and di-n-octyl phthalate) in a total of 118 samples of meat (beef, pork, and chicken), fish, and cheese packaged mostly in cling films. The eight phthalates were not detected in any of the food packaging, but DEHA was detected in most of the cling films, indicating that although DEHA-plasticized films (e.g., polyvinyl chloride film) are currently being used by most grocery stores, nonplasticized cling films such as polyethylene film, are also being used by some stores. DEHA was not detected in any of the 10 cheese samples packaged in nonplasticized rigid plastics but was detected in all 30 cheese samples packaged in DEHA-plasticized cling films at levels from 0.71 to 879 mg/g, with an average of 203 mg/g. Only DEHA was detected in the beef, pork, chicken, and fish samples packaged in DEHA-plasticized cling films but at considerably lower levels than those found in cheese, with averages of 6.3, 9.1, 2.5, and 5.9 mg/g, respectively. Among the eight phthalates, only di-(2-ethylhexyl) phthalate (DEHP) was detected in a few cheese samples at levels from 0.29 to 15 mg/g, with an average of 2.8 mg/g; these levels were very likely due to environmental contamination. Levels of DEHA found in most of the cheese samples from this study are above the European specific migration limit of 18 mg/kg for DEHA in food or food simulants, and levels of phthalates (i.e., DEHP) were low. Copyright © International Association for Food Protection.

Liu H.,Environment Canada | Scott P.M.,Bureau of Chemical Safety
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2011

For the analysis of blue-green algal food supplements for cylindrospermopsin (CYN), a C18 solid-phase extraction column and a polygraphitized carbon solid-phase extraction column in series was an effective procedure for the clean-up of extracts. Determination of CYN was by liquid chromatography with ultraviolet light detection. At extract spiking levels of CYN equivalent to 25-500 μg g-1, blue-green algal supplement recoveries were in the range 70-90%. CYN was not detected in ten samples of food supplements and one chocolate product, all containing blue-green algae. The limit of detection for the method was 16 mg g-1, and the limit of quantification was 52 μg g-1. © 2011 Her Majesty the Queen in right of Canada.

Koerner T.B.,Bureau of Chemical Safety | Cleroux C.,Bureau of Chemical Safety | Poirier C.,Bureau of Chemical Safety | Cantin I.,Bureau of Chemical Safety | And 2 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2011

A growing body of evidence suggests that a majority of people with celiac disease and on a gluten-free diet can safely consume pure oats in moderate amounts; however, previous studies have indicated that the commercial oat supply in other countries, and in Canada to some extent, is contaminated with other grains. This study has confirmed that the commercial oat supply in Canada is heavily contaminated with gluten from other grains. Approximately 88% of the oat samples (n = 133) were contaminated above 20 mg kg-1 and there were no differences between the oat types tested. Only one gluten-free variety of oats was analysed and it consistently provided negative results in all analyses. It is difficult to determine where the contamination originates, but there are possibilities for cross-contamination in the field, in the transport of the grain, in the storage of the grain, and in the milling and packaging facilities. It is clear from this study that only those products that have been certified 'pure' oats would be appropriate for a gluten-free diet. © 2011 Her Majesty the Queen in right of Canada.

Polenta G.A.,Instituto Nacional de Tecnologia Agropecuaria | Weber D.,Bureau of Chemical Safety | Godefroy-Benrejeb S.,Bureau of Chemical Safety | Abbott M.,Bureau of Chemical Safety
Food Analytical Methods | Year: 2012

The present study evaluates the effect of food processing on the antigenicity of pecan proteins as measured by enzyme-linked immunosorbent assay (ELISA). In addition, proteomic tools were used to identify potential pecan markers suitable for confirming the presence of pecan proteins in food and validating new methods developed to detect traces of the commodity. To assess the effects of processing on protein stability and antigenicity, pecan nuts were submitted to heat treatments and extracts were analysed by ELISA, sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot. The ELISA method was able to detect pecan traces even after submitting the commodity to rigorous treatments, though these treatments affected the detectability to varying degrees. Proteomic assessment showed that the majority of pecan proteins were matched by homology to walnut proteins, which are more abundantly populated in the protein sequence databases. However, there were a few important exceptions: 7S vicilin, 11S legumin and putative allergen I1, unambiguously identified as pecan in origin. Interestingly, putative allergen I1 offered unique analytical advantages to be used as a pecan marker for validation and confirmation purposes. © 2011 Springer Science+Business Media, LLC.

PubMed | Bureau of Chemical Safety, The Ottawa Hospital, Healthy Environments and Consumer Safety Branch, Institute National Of Sante Publique Du Quebec Inspq and 2 more.
Type: | Journal: The Science of the total environment | Year: 2016

Phthalates are a group of chemicals found in a number of consumer products; some of these phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009-2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various phthalate metabolites, with the exception of mono-n-octyl phthalate (MnOP), mono-isononyl phthalate (MiNP) and mono(carboxy-isooctyl) phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n=61), the following metabolites were rarely (< 10%) detected: mono-cyclohexyl phthalate (MCHP), mono-isononyl phthalate (MiNP), mono-methyl phthalate (MMP), and mono-n-octyl phthalate (MnOP). While mono-benzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infants urinary phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r=0.35), MEOHP (r=0.35) and MEP (r=0.37) collected at <20weeks gestation with levels in meconium and between MBzP (r=0.78) and MEP (r=0.56) in maternal and infant urine collected 2-3months after birth. These results suggest at least some maternal-fetal-infant transfer of phthalates and that meconium may be a useful matrix for measuring in utero exposure to phthalates.

PubMed | Healthy Environmental and Bureau of Chemical Safety
Type: | Journal: Environmental toxicology and pharmacology | Year: 2016

Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPAR and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal thyroid hormone (TH) homeostasis, in the livers of adult male rats exposed in feed to 50mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes, and global gene expression changes consistent with the involvement of PPAR and CAR/PXR. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122-5p and miR-21-5p were the most decreased, in PFOS-treated rats. Expression of the miR-23b-3p/27b-3p/24-3p cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes suggests involvement of epithelial to mesenchymal transition (EMT), which is a primary process of tumor cell motility and cancer metastasis. Our analysis also revealed transcripts that may mediate PFOS-induced effects on TH homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signaling, suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, the study suggests an important role for miRNAs in PFOS-induced hepatotoxicity and provides insight into the effects of PFOS on TH homeostasis.

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