Effects of Chronic Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants on the Reproductive and Thyroid System in Adult Male Rats
Health Canada is responsible for the assessment and management of potential health risks associated with exposure to chemicals in the environment, as mandated by the Canadian Environmental Protection Act. Brominated flame retardants (BFRs) are one class of environmental chemicals that may pose a health risk. They are incorporated into a variety of consumer products to limit flammability. Although the use of BFRs in new products has been restricted, human exposure continues due to their presence within older household furnishings. In this study, Health Canada, in collaboration with researchers from McGill University, used adult male rats to examine whether BFRs affect the reproductive system, liver, kidneys, or thyroid function. Importantly, Health Canada used a BFR mixture that is representative of the chemicals found in house dust samples in Canadian households, to ensure that exposure reflected that which might be encountered in the environment. Rats were exposed to various concentrations of the BFR mixture by adding it to their food for 70 days, after which various tests were performed on their liver, kidneys, reproductive system and thyroid glands, in addition to measuring blood levels of thyroid hormones. The results showed that while there was no effect on the reproductive system, the highest levels of BFR exposure led to increased weight of the liver and kidneys. In the liver, there was also an increase in proteins that breakdown drugs and other chemicals. In addition, there was evidence of thyroid toxicity, indicated by increased thyroid size and reduced levels of thyroid hormone. These results indicate that BFRs affect liver, kidney and thyroid functioning in male adult rats, but not the reproductive system. Health Canada will use the results of this study to better understand potential health effects associated with exposure to BFRs. Results of this research are published in Toxicological Sciences, 2012, 127(2), 496-507.
Preparation of archival formalin-fixed paraffin-embedded mouse liver samples for use with the Agilent gene expression microarray platform
Health Canada is responsible for the assessment and management of potential health risks associated with exposure to chemicals in the environment, as mandated by the Canadian Environmental Protection Act. An important component of this work is the development and validation of new tools and technologies that facilitate the assessment of potential health risks. Many research organizations, including Health Canada, have archives of diseased tissues that were generated over decades of research in areas including toxicology, pharmacology and oncology. Analyzing these tissues using new technologies that quantify changes in gene expression (changes in the abundance of gene products) can significantly advance understanding of the mechanisms underlying disease, while avoiding the use of additional animal exposures to generate new tissue. However, these archived tissues are commonly preserved using the chemical formaldehyde, which degrades cellular molecules. In this study, Health Canada examined modifications to existing methods to determine whether changes in gene expression expected following exposure to a specific drug treatment (phenobarbital) could be detected in formaldehyde-treated archived tissues. Sixteen-year-old formaldehyde-preserved liver tissues from untreated mice and mice that had been treated with the drug phenobarbital were compared using the newly modified methodologies. The results showed that changes in gene expression that were expected in response to phenobarbital treatment could be clearly detected, even in these archived tissues. Therefore, this technique can be applied to the analysis of the enormous repository of archived tissues from mice and rats exposed to various chemical agents. Health Canada will be able to use the results of this study to design future experiments using archived tissues, in order to understand the various mechanisms by which chemicals have adverse health effects including increased risk of cancer. Results of this research are published in the Journal of Pharmacological and Toxicological Methods, 2013, 68, 260-268.
Size distribution effects of cadmium tellurium quantum dots (CdS/CdTe) immunotoxicity on aquatic organisms
Health Canada is responsible for the assessment and management of health risks associated with exposure to products and chemicals in the environment. Nanoparticles are very small particles, between 1 and 100 nanometers in size, that are increasingly used in a range of fields including physics, medicine, cosmetics, aeronautics, electronics, mechanics, and the textile industry. However, the increasing use of these nanoparticles has raised concern about their potential toxicity. One subtype of nanoparticles is quantum dots (QDs), which are largely composed of cadmium. In this study Health Canada, in an international collaboration that included partners at Environment Canada, examined whether QDs of different sizes had toxic effects on the immune system of aquatic species. Health Canada uses information derived from animal experiments to predict effects in humans in the absence of data on exposed humans. The aquatic species examined included two types of mussels (Mytilus edulis and Elliptio complanata) and one species of fish (Oncorhynchus mykiss). Animals were exposed to QD suspensions of various sizes, and the effects of exposure on measures of immune system activation were evaluated. QDs were found to increase immune system activation, which varied based on the concentration and size of the QDs. Immune response to QDs also differed between the three species. These results provide much needed information on the potential environmental effects of nanoparticles as well as potential health effects. Health Canada and Environment Canada will be able to use the results of this study to better understand safe production and use of nanoparticles. Results of this research are published in Environmental Science Processes and Impacts, 2013, 15, 596-607.
Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan
Health Canada is responsible for the assessment and management of potential health risks associated with exposure to chemicals in the environment, as mandated by the Canadian Environmental Protection Act. Furan is a chemical formed through the heat-treatment of foods that is a common contaminant in coffee and canned/jarred foods. It causes liver cancer in mice and rats, and thus may pose a health risk to humans if present in sufficient amounts. It is thought that furan may lead to cancer by causing cell death in liver cells, which is then followed by liver regeneration. Briefly, the liver has the capacity to regenerate itself upon injury, as the remaining healthy liver cells can divide to replace any damaged cells. Chronic regeneration in this fashion is associated with increased risk of cancer. However, the molecular changes induced by furan that cause these effects have not been well established. In this study, Health Canada applied modern technologies that measure changes in gene expression (changes in the abundance of gene products) to understand the molecular changes induced in liver cells in response to furan. Mice were exposed to furan for 3 weeks, after which gene expression in the liver was compared to non-exposed controls. The observed changes in gene expression were consistent with the previously proposed mechanism of furan carcinogenicity. These results provide an enhanced understanding of how furan acts on liver cells to alter their biological processes. Health Canada can use these results to better understand health risks associated with furan exposure. Furthermore, this case study can be used to support the application of gene expression analysis in the assessment of other chemicals, and for the identification of biological ‘signatures’ that may indicate how a chemical acts on the body. Results of this research are published in Toxicology and Applied Pharmacology, 2014, 274, 63-77.
Simultaneous determination of thirteen organophosphate esters in settled indoor house dust and a comparison between two sampling techniques
Health Canada is responsible for the assessment and management of potential health risks associated with exposure to chemicals in the environment, as mandated by the Canadian Environmental Protection Act. An important component of research to support this aim is the development and validation of new tools that facilitate the assessment of potential health risks. To determine levels of environmental contaminants Canadians are exposed to from household dust, Health Canada launched the Canadian House Dust Study (CHDS), which provides a national estimate of concentration levels of environmental contaminant in urban homes. This current study compared the level of organophosphate esters (OPEs) from fresh or “active” dust collected by technicians following the protocol developed for the CHDS, to matched samples of dust simply taken from the households’ vacuum cleaners. The goal was to understand whether dust collected by vacuum cleaners would be a reliable source to measure chemical contaminants with. Furthermore, in this study, Health Canada developed a method for the simultaneous measurement of 13 OPEs from samples of house dust from 134 Canadian homes. OPEs are an important class of commercial chemicals used as flame retardants and plasticizers and potential human health effects have been described for some OPEs. OPEs are commonly found in Canadian homes released from sources such as consumer products, and it is important to understand how much Canadians are exposed to. The results demonstrated that the new technique to measure 13 OPEs at once is reliable. Furthermore, measurements from dust collected by technicians were similar to measurements from dust within the household vacuum cleaners demonstrating that analysis of household dust from vacuum cleaners may be a cost-effective and informative alternative to the expensive fresh dust collection by trained technicians. Health Canada will use the results of this study to improve experimental designs of future studies of house dust, to understand OPE exposure in Canadian homes, and to investigate potential consequences of OPEs to human health. Results of this research are published in Science of the Total Environment, 2014, 491-492, 80-86.
Effects of a 28-day oral exposure to a 5-chloro-2-methyl-4-isothiazolin-3- one and 2-methyl-4-isothiazolin-3-one biocide formulation in Sprague-Dawley rats
Health Canada conducts research and assessments of chemicals in order to protect Canadians from the potential health risks of various substances. Many governments are encouraging the use of biodiesels, as they are generally less toxic and burn more cleanly than diesel. However, microbes are able to grow in biodiesels, so chemicals called biocides must be added to prevent growth. One particularly effective biocide is called CMIT/MIT (5-Chloro-2-Methyl-2H-Isothiazol-3-one/2-Methyl-2H-Isothiazol-3-one). In this study, Health Canada introduced CMIT/MIT into the stomachs of male and female rats in order to assess potential health risks associated with ingestion. This is particularly important as accidental ingestion of petroleum products is relatively common in humans. Male and female rats had various doses of CMIT/MIT introduced into their stomachs daily for 28 days, after which their organs were weighed and tissues were examined by microscopy. In addition, blood composition was assessed, and the rats were measured for various indicators of immune system activation. Most measures, including general health, food consumption, and growth were unaffected by CMIT/MIT exposure. Subtle differences were detected following microscopic analysis of the liver and spleen. Differences were also observed for one blood measure in male rats, and one in females. However, the observed changes were generally minor and most likely to be caused by the rats simply adapting to the exposure. The highest dose of CMIT/MIT used in this study was above that used in biodiesel, yet the effects of that dose were relatively minor. Health Canada can use the results of this study to inform guidelines for CMIT/MIT usage in biodiesels. Results of this research are published in Drug and Chemical Toxicology, 2014, 37, 149-155.
Correction and comparability of phthalate metabolite measurements of Canadian biomonitoring studies
Health Canada is responsible for the assessment and management of health risks associated with exposure to products and chemicals in the environment. Phthalates are a group of chemicals to which Canadians are exposed through a range of sources including cosmetics, consumer products, drugs, building materials, and certain plastics. To determine whether the level of phthalate exposure is of concern to human health, several studies have been conducted to measure levels of phthalate exposure in human populations within Canada. For three of these previous studies, the chemical tests for phthalate exposure were performed at the Institut National de Santé Publique du Québec, where a total of 105,000 measurements from 9302 different samples were taken. Unfortunately, the Institut National de Santé Publique du Québec reported that some of the measures were not reliable following the release of these studies. They reported that their tests were calibrated against a commercially available ‘standard’, which is meant to always be identical, yet these standards instead varied between different chemicals and over time, resulted in inaccuracies in the measurements. In this study, Health Canada, in collaboration with scientists from the Institut National de Santé Publique du Québec (INSPQ) and Statistics Canada, developed statistical methods to correct the previous measurements in order to obtain accurate and usable data. As a result of these corrections, data from the three studies analyzed at the Institut National de Santé Publique du Québec are now considered correct and comparable to each other. Health Canada will use the results of this study to ensure that there is confidence in the accuracy of data, which may be used to inform phthalate use and exposure for risk assessment. Results of this research are published in Environment International, 2014, 64, 129-133.
Incorporating New Technologies into Toxicity Testing and Risk Assessment: Moving From 21st Century Vision to a Data-Driven Framework
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment as mandated by the Canadian Environmental Protection Act. Traditionally, evaluation of the human health hazards posed by chemical exposure has relied on extensive animal testing. These tests are labour-intensive, expensive, and require the use of large numbers of animals. However, the Canadian government requires the evaluation of thousands of chemicals under the Chemicals Management Plan. Given that it is not possible to conduct extensive animal testing on all of these chemicals in a reasonable timeframe, alternative approaches to testing are needed. In this study, Health Canada, in collaboration with scientists from across Canada and the United States, proposes a novel step-by-step strategy to streamline and expedite chemical risk assessment. In this approach, all chemicals would be subject to high-throughput tests using robotics for a diverse array of toxic effects in cells in petri dishes. Based on these tests, chemicals likely to have the most toxic effects would be subjected to the second level of testing and only chemicals with the highest hazards would be evaluated using standard long-term animal studies. Thus, a significant percentage of less-toxic chemicals could be eliminated from extensive animal tests. This revised approach provides a risk-based, less-expensive and animal-sparing method to evaluate chemical hazards, drawing broadly from previous experience but incorporating technological advances to increase efficiency. Health Canada can use the results of this study to develop an internationally accepted approach for the use of high-throughput testing for human health risk assessment that can be used to protect the health of Canadians. Results of this research are published in Toxicological Sciences, 2013, 136(1), 4-18.
Nationally Representative Levels of Selected Volatile Organic Compounds in Canadian Residential Indoor Air: Population-Based Survey
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment as legislated by the Canadian Environmental Protection Act. Volatile organic compounds (VOCs) are carbon-containing chemicals that can be found in the air, particularly indoor air. Many VOCs are known to be harmful, and exposure in sufficient quantity and duration can result in a variety of negative health outcomes including respiratory problems and asthma. In order to determine the health risks of VOCs for Canadians, it is first necessary to generate nationally representative data on indoor VOC levels. In this study, Health Canada measured levels of 84 different VOCs from indoor air samples collected between 2009 and 2011. A subset of these VOCs had been measured previously in other studies in Canada and Europe. Overall, VOCs were measured within 3218 houses, 546 apartments, and 93 other dwelling types. The results showed that within Canada, more VOCs had declined since 1992 than had increased, and that for most VOCs the current levels were comparable to those found in Europe. In addition, individual VOCs tended to be either similar or higher in houses compared to apartments, and in smoking homes compared to non-smoking homes. Health Canada can use the results of this study to evaluate exposures of Canadians to VOCs, thereby informing assessment of the risks of VOCs to human health. Results of this research are published in Environmental Science and Technology, 2013, 47(23), 13276-13283.
In Vitro Dermal Absorption of Di(2-ethylhexyl) adipate (DEHA) in a Roll-On Deodorant Using Human Skin
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment and in consumer products. Di(2-ethylhexyl) adipate (DEHA) is a chemical found in food packaging such as plastic wraps. However, DEHA is able to leach out of the packaging material into fatty foods, such as cheese and meat, resulting in consumption by humans. This is important, as studies in rats have suggested that when DEHA is ingested it can cause hormonal changes and damage to the ovaries. DEHA is also found in cosmetic and personal care products, so can be regularly applied to the skin. The extent to which it is absorbed by human skin is unknown. In this study, Health Canada determined the extent to which DEHA dissolved in commercially available roll-on deodorant is absorbed by human skin. DEHA-containing deodorants were applied to an isolated sample of human skin for 24 hours, and the amount of DEHA that had either passed through the skin, remained in the skin, or was washed off the surface of the skin was determined. The results showed that while a substantial amount of DEHA was absorbed into the skin sample, very little actually passed through the skin. Furthermore, the amount of DEHA that passed through the skin did not seem to depend on how much DEHA was actually applied to the skin. This study generates new information on how DEHA might enter the human body. Health Canada can use these results to assess the extent to which DEHA in commercial products enters the human body through the skin, which is valuable when determining potential risks of DEHA exposure to human health. Results of this research are published in the Journal of Toxicology and Environmental Health, Part A: Current Issues, 2013, 76(3), 157–166.
Implementation of the indoor air component of cycle 2 of the Canadian health measures survey
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment as mandated by the Canadian Environmental Protection Act. Volatile organic compounds (VOCs) are carbon-containing chemicals that can be found in air. VOCs are released by a number of household products including paints, paint strippers and other solvents, aerosol sprays, cleansers and disinfectants, air fresheners, and hobby supplies. VOCs are particularly common in indoor air, and can have negative impacts on human health ranging from mild irritation to more severe illnesses if present in sufficient quantity. In order to determine the health risks of VOCs for Canadians, it is first necessary to generate nationally representative data on indoor VOC levels. This was one objective of the Canadian Health Measures Survey (CHMS), which collected air samples between 2009 and 2011. One component of the sampling approach was to ask members of the public to collect air samples in their own homes, and return the samples to the testing laboratory. In this study, Health Canada collaborated with Statistics Canada to evaluate whether this strategy for indoor air sample collection was effective. The results showed that as part of the CHMS, 4686 air samplers were given to participants, of which >97% were used and returned to the testing laboratory, with >82% of the original samplers producing samples of high enough quality for inclusion in the study. This demonstrates that the large-scale collection of indoor air samples from Canadian homes can be feasibly conducted by relying on members of the public for sample collection. Health Canada will be able to use the results of this study to design future studies of air quality within Canadian residences. Results of this research are published in Health Reports, 2013, 24(5), 3-10.
In vitro microarray analysis identifies genes in acute-phase response pathways that are down-regulated in the liver of chicken embryos exposed in ovo to PFUdA
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment. Perfluoroalkyl compounds (PFCs) are chemicals used in industry that may be harmful to human health. One PFC found at relatively high levels in wild birds is perfluoroundecanoic acid (PFUdA). High levels in bird populations suggest environmental contamination by this chemical and thus increased probability of human exposure. In this study Health Canada collaborated with scientists from Environment Canada and the University of Ottawa to examine the effects of PFUdA on the livers of chicken embryos, as a general measure of toxic health effects. Two exposure methods were used: (1) liver cells taken from the embryo and exposed in petri dishes to PFUdA, or (2) chicken eggs were injected with PFUdA, with the livers later collected near the time of hatching. To explore biological changes, Health Canada measured the expression of large numbers of genes. Gene expression is part of the process through which a functional product is generated from a gene. The results showed that many genes were affected by PFUdA exposure, including several whose products are normally released by the liver into the blood in response to injury. The effects occurred both in cells in petri dishes and in the livers of chicks exposed inside the eggs. This study suggests that PFUdA may impair immune responses. Furthermore, the similarities between results from the two methods suggest that isolated embryonic liver cells could be useful for analyzing the effect of toxins to minimize the number of animals needed to conduct toxicity testing. Health Canada will be able to use the results of this study to better understand the health effects associated with PFUdA exposure, and to design future toxicity studies. Results of this research are published in Toxicology in Vitro, 2013, 27(6), 1649–1658.
Predictors of indoor BTEX concentrations in Canadian residences
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment. Air pollution can occur within Canadian homes due to the release of chemicals in the form of gases from sources such as paints, cigarette smoke, and building materials. Benzene, toluene, ethylbenzene, and m-, p-xylenes, and o-xylene (BTEX) are four such chemicals that are commonly found at increased levels together as they often originate from the same sources. Long-term exposure to BTEX in sufficient quantity can have serious effects on human health, including increased risk of leukemia. Studies in animals have further suggested risk of lung tumours, and negative effects on hearing and kidneys. Given the potentially negative health implications of BTEX exposure, it is important to understand typical residential concentrations and identify predictors of BTEX levels. In this study, Health Canada collaborated with Statistics Canada to determine levels of BTEX in Canadian homes, and to identify likely sources of elevated BTEX levels. Indoor air samples had been collected from >5000 Canadian homes between 2009-2011 as part of the Canadian Health Measures Survey. Statistical analyses were conducted to determine which factors might contribute to elevated BTEX concentrations. The results showed that in general, BTEX levels were relatively low within Canadian homes, though they were likely to be higher if the home had a garage on the property, if residents regularly smoked in the home, if there had been renovations within the past month, if the residence had a larger number of occupants, or if either paint remover or fragrances had been used in the home. Health Canada will be able to use the results of this study to facilitate investigations of the risks associated with BTEX exposure in Canadian homes. This research is published in Health Reports, 2013, 24(5), 11-17.
Soil ingestion rate determination in a rural population of Alberta, Canada practicing a wilderness lifestyle
Health Canada is responsible for the assessment and management of potential health risks associated with exposure to chemicals in the environment, as mandated by the Canadian Environmental Protection Act. A major pathway by which people can be exposed to potentially toxic chemicals is by inadvertently eating small amounts of soil. According to the Federal Contaminated Sites Inventory, over 11,000 sites in Canada are known to contain contaminated soil. In order to properly assess the risks to human health of exposure to chemicals in the soil, it is important to carefully estimate the amount of soil that is inadvertently eaten by people. Some estimates do exist, but almost all of these are for children in suburban/urban environments. In this study Health Canada, in collaboration with scientists from the University of Ottawa, measured inadvertent soil consumption in people from a rural First Nations population practicing traditional outdoor activities associated with a subsistence lifestyle. This study followed 9 subjects over a 13 day period in Cold Lake, Alberta, near the largest bitumen extraction operation in the world. The results showed that soil ingestion amongst this group exceeded the amounts that are currently used when assessing risks of soil ingestion on human health. Therefore, soil ingestion estimates currently used in human health risk assessments may underestimate true ingestion levels for some populations. Health Canada can use the results of this study to refine human health risk assessments of chemicals found in the soil. Results of this research are published in Science of the Total Environment, 2014, 470-471, 138-146.
Transformation of 2,2',4,4'-tetrabromodiphenyl ether under UV irradiation: Potential sources of the secondary pollutants
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment. Polybrominated diphenyl ethers (PBDEs) are a group of chemicals used in various products including flame retardants, textiles, electrical appliances, and electronics. Exposure of human populations to PBDEs has raised concerns about their effects on human health. However, risk assessment of specific types of PBDEs is complicated by the fact that these chemicals can be degraded by environmental factors such as ultra-violet light, which is a component of sunlight. This degradation converts the initial chemical into different chemicals, which may in turn have separate effects on human health. One specific PBDE is tetrabromodiphenylether (BDE-47), which has been detected in ambient air and in residential homes. In this study Health Canada, in collaboration with scientists from the USA, investigated whether BDE-47 was degraded by ultra-violet light. Liquid and gas forms of BDE-47 were exposed to ultra-violet light and newly-formed chemicals were identified. The results showed that ultra-violet light degraded BDE-47 more quickly when in liquid form and that eight different chemicals were generated. Similar to the original polybrominated diphenyl ether (PBDE), six of the new chemicals were also diphenyl ethers, but contained less bromine than BDE-47. These less-brominated diphenyl ethers could evaporate to form a gas more easily than the original BDE-47 chemical, and may contribute to air pollution. This study demonstrates that ultra-violet light can act on one specific PBDE to generate new chemicals that could also contribute towards environmental pollution, with potential risks on human health. Health Canada will be able to use the results of this study to facilitate future assessments of the risks of PBDEs and their chemical derivatives on human health. Results of this research are published in the Journal of Hazardous Materials, 2013, 263, 778-783.
The Association between Urinary Phthalates and Lung Function
Health Canada is responsible for the assessment and management of health risks associated with exposure to products and chemicals in the environment. Phthalates are a group of chemicals widely used in the manufacture of polyvinyl chloride (PVC) plastics, solvents, clothing, personal care products, and toys. Exposure to phthalates is widespread, and there is concern that phthalate exposure in sufficient quantity may have negative effects on health, including increased risk of allergy and asthma. In this study, Health Canada examined whether there was any evidence that exposure of Canadians to phthalates was associated with any impairment in lung function. Specifically, phthalate exposure of 3147 Canadians was determined by measuring the concentrations of seven different of phthalates in the urine. Lung function was also examined in these people by measuring the amount of air each person could exhale at different stages of a forced breath. The study found that six of the seven phthalates were at higher levels in children than in adults, and that higher phthalate levels were associated with small reductions in lung function, with this risk being potentially greater in males. These data therefore suggest that phthalate exposure may have negative effects on lung function in the Canadian population. Health Canada will be able to use the results of this study to better understand the possible health consequences associated with phthalate exposure for Canadians. Results of this research are published in the Journal of Occupational and Environmental Medicine, 2014, 56(4), 376-381.
Applicability of a high-throughput shotgun plasma protein screening approach in understanding maternal biological pathways relevant to infant birth weight outcome
Health Canada is responsible for the assessment and management of health risks associated with exposure to chemicals in the environment. Several previous studies have shown that factors such as a mother’s nutritional status, smoking habits and exposure to environmental chemicals during pregnancy can affect pregnancy outcomes. Examples of negative effects on pregnancy include reduced size of the infant and the placenta, premature birth, and slow growth of the fetus. Low weight at birth has been associated with increased risk of a number of diseases in later life. However, the biological basis for the association between some of these maternal factors and pregnancy outcomes has yet to be established. In this study, Health Canada collaborated with St-Justine Hospital in Montreal to analyze samples from the Maternal-Infant Research on Environmental Chemicals (MIREC) study. The goal was to identify whether any biological changes were detectable in the blood of mothers in the third trimester of their pregnancy that might relate to pregnancy outcomes. The study focused specifically on measurements of the concentrations of many different proteins in blood. Blood samples were analyzed from 12 mothers who later gave birth to normal-weight infants, and 12 mothers who later gave birth to low-weight infants. While this is a preliminary study, a number of differences in protein concentrations were identified between the two groups of mothers. These data indicate that analyzing the concentrations of many different proteins in maternal blood may be useful in early diagnosis and treatment to prevent negative birth outcomes. Health Canada can use the results of this study to better understand the biological factors that may be associated with, or contribute to negative pregnancy outcomes, and the role environmental contaminants may have in contributing to low weight births. These results are published in the Journal of Proteomics, 2014, 100, 136-146.
Effects of Jatropha oil on rats following 28-day oral treatment
Health Canada conducts research on chemicals in order to support risk assessment and management efforts to protect Canadians from the potential health risks of various substances. Many governments are encouraging the use of biodiesels, as they are generally less toxic and burn more cleanly than diesel. Jatropha is a shrubbery tree, and the oil extracted from Jatropha can be used to make biodiesels. This is particularly important as the Jatropha tree can grow in poor soils and under harsh conditions, allowing for the production of biodiesels without reducing the land available for food production. However, increased use of Jatropha oil could increase the likelihood of accidental human ingestion, which is known to cause abdominal pain, diarrhea and vomiting. Despite these known health risks, there is little information on the toxicity of Jatropha oil. In this study, Health Canada conducted experiments on rats to examine the toxicity of Jatropha oil. Jatropha oil was diluted in corn oil and introduced into the stomachs of male and female rats daily for 28 days. Male and female rats with the highest Jatropha oil exposures had reduced growth relative to those exposed to only corn oil. Reduced growth was accompanied by changes in the number of blood cells of the immune system, mild and reversible changes in the structure of the spleen, and changes in the liver in both male and female rats. Health Canada will be able to use the results of this study to better understand the potential toxicity of Jatropha oil, and to better assess some potential health consequences that may be associated with increased use of this oil in biodiesel synthesis. This research is published in the Journal of Applied Toxicology, 2013, 33(7), 618-625.
Determination of isoflavones in rat serum using liquid chromatography-tandem mass spectrometry with a highly efficient core-shell column
Health Canada conducts research to support risk assessment and management efforts to protect Canadians from the potential health risks of various substances. An important component of this research is the development and assessment of new methodologies and techniques that can be applied towards a better understanding of the dietary factors that promote the health of Canadians. Isoflavones are a class of chemicals found naturally at particularly high levels in soy and soy-based products. Consumption of isoflavones has been linked to a number of positive health outcomes including improved cardiovascular health, lower blood pressure, lower levels of certain fats and cholesterol in the blood, and healthier bones. In order to better understand how isoflavones enter the body and function within the body, scientists need techniques that can detect concentrations of various isoflavones in biological samples. While a number of techniques are already available, they have a number of limitations. In this study, Health Canada modified an existing technique to determine whether this new modification would improve isoflavone detection. Thirty-two samples derived from rat blood were analyzed using the new technique, to quantify the amounts of four different isoflavones. The results showed that the new method was specific, reproducible and reliable. Health Canada will be able to use the modified technique to improve its ability to study isoflavones. This research is published in Analytical and Bioanalytical Chemistry, 2013, 405(8), 2643–2651.
Measurements of selected brominated flame retardants in nursing women: Implications for human exposure
Health Canada conducts research to support the assessment and management of health risks associated with exposure to chemicals in the environment. Brominated flame retardants (BRFs) are a group of chemicals that are used in many products to inhibit or resist the spread of fire. One major class of BFRs is the polybrominated diphenyl ethers (PBDEs). Exposure of human populations to PBDEs has raised concerns about their potential effects on human health, resulting in their production being either restricted or eliminated in many parts of the world. Alternative BFRs have been developed as replacements for PBDEs, but some of these replacements have similarly been detected as contaminants in the environment, including within Canadian homes. However, there has been little research to determine whether these replacement BFRs are detectable within human body fluids. In this study Health Canada, in collaboration with scientists from Université de Sherbrooke, sought to determine whether five of the newer replacement BFRs were detectable in human body fluids. Three other BFRs that had been synthesized previously for several years (including one PBDE) were also included for comparison. Blood serum and milk samples derived from over 100 women from the Sherbrooke region in Canada between 2008-2009 were analyzed for the presence of the eight BFRs. Two of the older BFRs (including the PBDE) were identified in over half of the samples, as was one of the newer replacement BFRs. All other BFRs were also detected, though in a smaller number of samples. These results demonstrate that the replacement non-PBDE BFRs are detectable in humans. Health Canada will be able to use the results of this study to better understand the sources, routes of exposure, and potential human health effects of BFRs on Canadians. Results of this research are published in Environmental Science and Technology, 2014, 48(15), 8873-8880.
Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk
Health Canada conducts research to support the assessment and management of potential health risks associated with exposure to chemicals in the environment. To determine whether a chemical poses potential risks to human health, Health Canada uses information derived from animal experiments to predict effects in humans. For example, chemicals can be introduced into the stomachs of mice, to determine whether those chemicals cause cancer through this route of exposure. Approximately 120 different chemicals are known to induce cancer in a region of the rodent gut called the forestomach. However, the structure of the rodent gut differs from that of humans, as humans do not have a forestomach. It is therefore unclear whether these chemicals are likely to also cause cancer in the human gut. In this study, Health Canada used advanced molecular techniques to determine what biological changes are observed in the forestomachs of mice exposed to a known carcinogen (benzo(a)pyrene), and to explore whether similar changes occur in cancers of the human gut. Benzo(a)pyrene was introduced into the mouse gut daily for 28 days. Three days later after the last exposure, the forestomach was collected and the expression levels of thousands of genes were analyzed. Gene expression is part of the process through which a functional product is generated from a gene. Changes in protein levels were also determined. Over 400 genes were altered in the mouse forestomach, and there was substantial overlap between these genes and those identified as being altered in cancers within the human gut. These data therefore support the use of the mouse forestomach to evaluate potential risks of chemically-induced cancer in humans. Health Canada can use these results to more effectively analyze data from rodent forestomach to predict cancer from chemical ingestion in humans. This research is published in Toxicology and Applied Pharmacology, 2013, 273, 269-280.
Exposure to Free and Conjugated Forms of Bisphenol A and Triclosan among Pregnant Women in the MIREC Cohort
Health Canada has the responsibility to assess the health risks to Canadians associated with exposure to chemicals in the environment. The Maternal-Infant Research on Environmental Chemicals (MIREC) study was designed to measure exposure to and any potential health effects of elevated levels of environmental chemicals during pregnancy. Two of the chemicals for which there are limited data on levels in pregnant women are triclosan and bisphenol A (BPA). Triclosan is used as an antimicrobial in a wide range of cosmetics and personal care products, including non-prescription drugs. BPA is used to make a hard, clear plastic and may also be found in epoxy resin linings on the inside of metal-based food and beverage cans. Thermal papers such as receipts and tickets may also be a source of BPA. In this study, Health Canada undertook to measure these two chemicals in a urine sample from approximately 1,900 pregnant women participating in the MIREC Study. BPA levels were higher in women with a lower household income, under 25 years of age or in smokers. Triclosan levels tended to be higher in women who had never smoked or were 25 years of age or older. Health Canada will use the results of this study to estimate exposure to these chemicals for the Canadian population. The results of this study are published in the journal Environmental Health Perspectives, (Volume 123, Issue 4, April 2015).
Phthalate and Bisphenol A Exposure among Pregnant Women in Canada - Results from the MIREC Study
Health Canada collects population biomonitoring data in order to obtain direct estimates of chemical exposures that help to inform sound decision-making about health risks to Canadians. Bisphenol A (BPA) and phthalates are two groups of chemicals commonly measured in urine in population surveys; however, Canadian data for pregnant women are limited. These chemicals were measured in first trimester urine samples from approximately 2,000 Canadian women in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. Approximately 90% of the women had detectable levels of BPA. An analysis of urinary concentrations of BPA by maternal characteristics showed that concentrations: (1) decreased with increasing maternal age, (2) were higher in current smokers or women who quit during pregnancy compared to never smokers, and (3) tended to be higher in women who provided a fasting urine sample, were born in Canada, and had lower incomes and education. Some phthalates were commonly found in maternal urine and others were rarely found. This study provides the first biomonitoring results for a large population of pregnant women sampled in the first trimester of pregnancy. The results indicate that exposure amongst this population of pregnant women to these chemicals is comparable to, and in some cases lower than, that observed in a national survey of women of reproductive age in Canada - the Canadian Health Measures Survey. Health Canada will use these results on human exposure levels to inform risk assessment and risk management activities related to these chemicals. Results of this research are published in Environment International, 2014, 68, pp. 55-65.
Hexachloronorbornene-Based Flame Retardants in Humans: Levels in Maternal Serum and Milk
Health Canada is currently conducting health risk assessments for a number of flame retardants under the Chemicals Management Plan. Flame retardants are chemicals added to many consumer products to inhibit, suppress, or delay the production of flames to prevent the spread of fire. Due to the persistent nature of some of these chemicals in the environment, concerns have been raised about the potential for human exposure. Human exposure can be estimated by knowing the levels of these chemicals in human body fluids such as blood and milk. To provide exposure data to support the health risk assessments, measurements were made of several flame retardants in the maternal blood and milk of about 100 Canadian women. The results revealed the presence of flame retardants in Canadian women, with three flame retardants (Dechlorane 602, Dechlorane 603, and hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO)) being detected in more than 60% of biological samples. This work provided the first Canadian human exposure data for the three flame retardants. Health Canada will use the results of this study to fill gaps in knowledge that will help more fully assess the potential health risks of flame retardants. Measurements of levels in both blood and milk also provided scientific information of the partitioning of these flame retardants in the two very important human biomonitoring matrices, which also will help in the design of more effective human biomonitoring programs in future. This study was conducted in collaboration with the Department of Pediatrics of the University of Sherbrooke and was published in Environment International, 2014, 66:11-17.
Thyroid Hormone Response Element Half-Site Organization and its Effect on Thyroid Hormone Mediated Transcription
Health Canada is responsible for the assessment and management of health risks to Canadians associated with exposure to products and chemicals in the environment. The development of rapid tests to identify environmental chemicals that disrupt thyroid hormone (TH) action is important since growth and development of the body, particularly the brain and sensory organs, is dependent on the action of TH. Interference with TH production or action, whether by chemical toxicity or dietary deficiency, can impair these processes causing long-term deficiencies in intelligence, among other adverse health outcomes. Although the effects of TH within cells are mediated by a complex series of biological events, these processes are not well understood. Developing a better understanding of these variables is required to interpret the effects of TH disruption. This knowledge would also be beneficial in the development of rapid tests to identify environmental chemicals that disrupt TH action. In this study, Health Canada investigated the complex molecular biology underlying TH interactions in cultured cells. It was found that there are fundamental differences between various DNA sequences that direct how genes respond to TH. These differences will need to be considered in developing chemical toxicity screening tools. These data are being used by Health Canada to develop a novel set of tests that can be used to evaluate the ability of environmental chemicals to interfere with TH action. Results of this research are published in PLoS ONE, 2014, 9(6), e101155.
Bromodeoxyuridine (BrdU) Treatment to Measure Hepatocellular Proliferation Does Not Mask Furan-Induced Gene Expression Changes in Mouse Liver
Health Canada is responsible for the assessment and management of health risks to Canadians associated with exposure to products and chemicals in the environment. In order to evaluate the potential of chemicals to cause health risks to Canadians, Health Canada scientists must often rely on data produced from animal toxicity studies. However, these studies are typically expensive, time consuming, and raise animal welfare concerns that warrant the consideration of alternative approaches. Such alternative approaches may be aimed at avoiding or replacing the use of animals, reducing the numbers of animals used in each test, or refining methods to minimize animal suffering and improve their welfare. This study was undertaken to explore ways in which the number of animals required for toxicity testing could be reduced; more specifically, to determine whether rodent tissues derived from a toxicity test for liver cell proliferation can also be used for a second test to study how gene expression responds to the treatment. In this experiment, Health Canada evaluated whether treatment with the chemical bromodeoxyuridine (BrdU), used to detect liver cell proliferation, impacts gene expression in the livers of mice exposed to the model chemical furan, a known liver carcinogen. It was observed that BrdU does not appreciably impact gene expression. Indeed, furan-induced changes in gene expression were similar in BrdU and non-BrdU treated mice. This study demonstrated that treatment with BrdU is not appreciably in conflict with gene expression measurement. In such a case, it may be possible to reduce by half the number of experimental animals used in this type of study. This finding is an important first step towards the reduction of experimental animals used in this type of toxicity testing, but will need to be confirmed with several more chemicals before gene expression profiling of BrdU-treated samples becomes commonplace. Health Canada will use the results of this study to develop strategies to reduce the number of experimental animals required for chemical toxicity testing. Results of this research are published in Toxicology, 2014, 323, pp. 26-31.
Differential Expression of Long Noncoding RNAs in the Livers of Female B6C3F1 Mice Exposed to the Carcinogen Furan
Health Canada is responsible for helping to protect Canadians from exposure to potentially harmful chemicals (e.g. cancer causing chemicals). In this study, Health Canada, in collaboration with scientists from Integrated Laboratory Systems Inc., sought to develop stronger test methods to identify chemicals that may cause cancer in humans. The purpose of the research was to identify the types of biological processes that are affected early on by following exposure of rodent models to cancer-causing chemicals. Gene expression profiling is a method used to identify what genes are turned off and on in response to an exposure. This technology is providing increased insight into how chemicals cause adverse health effects. This study investigated the effects on gene functioning of the chemical furan, a known mouse liver carcinogen. In contrast to genes, which encode proteins that carry out cell functions, long non-coding RNAs (lncRNAs) have no protein products. LncRNAs are not well understood, but are thought to be important regulators of gene function and chromosome structure. Mice exposed to furan for 21 days exhibited very large changes in numerous lncRNAs. Similar effects were found in mice exposed for 28 days to a different carcinogen, benzo(a)pyrene, which suggests that changes in lncRNAs are not specific to furan, and that lncRNAs may be broadly important in response to carcinogens. It is not clear what the effects of lncRNA changes are on the health of the animals. This is the first work to suggest that lncRNAs might be important regulators of cell processes involved in chemical-induced cancer and more research is needed to clearly define the biological role of IncRNAs. Development of this test method will support Health Canada in testing for changes in lncRNAs following exposure to other carcinogenic and non-carcinogenic chemicals to determine what lncRNAs may be most predictive of the hazards posed by chemical exposures. Results of this research are published in Toxicological Sciences, 2013,135(2), 369-379.
Hepatic mRNA, microRNA, and miR-34a-Target Responses in Mice After 28 Days Exposure to Doses of Benzo(a)pyrene that Elicit DNA Damage and Mutation
Health Canada conducts research on chemicals in support of its mandate to assess the potential health risks of various substances to Canadians. In this study, Health Canada sought to develop a better understanding of the toxicology of Benzo(a)pyrene (BaP), and to explore the potential application of toxicogenomics to the risk assessment of BaP. BaP is an environmental toxin that has been shown to cause cancer and DNA mutation in laboratory animals. Because of the extensive published information available on the effects of BaP, it also serves as an excellent model for the development of new methodologies to study toxicity, allowing new and existing methods to be directly compared. Toxicogenomics is a relatively new discipline that investigates the effects of exposure to chemicals on all of the genes within an organism by examining what genes are turned on and off by a given chemical. By capturing effects across the whole genome, this approach enables an assessment of a large and diverse array of potential toxicological effects within a single experiment, reducing the cost and time associated with toxicity testing. In this study, groups of mice were treated with various concentrations of BaP for 28 days, which resulted in 134 genes (of 40,000) that were statistically significantly altered in the liver. These genes were primarily involved in the metabolism of BaP, the response to DNA damage, and how cells divide and replicate. The results provided Health Canada with important information on the genes and mechanisms involved in the response of the liver to BaP exposure across a range of doses. The gene changes measured are highly aligned with findings from existing methods, supporting the use of toxicogenomics as a tool to predict toxicity. Health Canada will use the results of this study to help determine how toxicogenomics data can best support future risk assessments. Results of this research are published in Environmental and Molecular Mutagenesis, 2012, 53(1), 10-21.
Identification of Thyroid Hormone Receptor Binding Sites in Developing Mouse Cerebellum
Health Canada conducts research and assessments of chemicals in order to protect Canadians from the potential health risks of various substances. Thyroid hormone (TH), produced by the thyroid gland, is essential for growth, development and metabolism; therefore, alterations in normal TH levels can lead to adverse health outcomes. In order for Health Canada to assess the risk of environmental chemicals affecting TH, it is important to understand the biological mechanisms involved. In this study, Health Canada, in collaboration with Carleton University, was looking to develop improved methods to identify chemicals that exert their adverse effects through disruption of TH. More specifically, this study aimed to develop computer data analytical approaches to identify which DNA sequences interact with TH, to better define the biological processes involved. By applying these new analytical approaches, 230 DNA sequences that interacted with TH were identified in rodents. Identifying and characterizing these sequences will help Health Canada to develop screening tools to evaluate the potential effects on cells and tissues when TH levels are altered, which can be used to inform future toxicological risk assessments. The results of this study are published in the journal BioMed Central (BMC) Genomics, 2013, 14(1), 341.
Determination of Selected Perfluorinated Compounds and Polyfluoroalkyl Phosphate Surfactants in Human Milk
Health Canada is responsible for the assessment and management of health risks associated with exposure to products and chemicals in the environment. Industrial surfactant products called polyfluoroalkyl phosphates, which are used in the production of food contact paper to impart oil/grease resistance, have been shown to migrate into food. Polyfluoroalkyl phosphate surfactants are emerging as ubiquitous contaminants that have been detected in human blood, although at very low concentration levels. In this study, a new method was developed to determine the levels of selected polyfluoroalkyl phosphate surfactants in human milk. As a result, four polyfluorinated disubstituted phosphate surfactants and perfluorooctanoic acid were detected and quantified in human milk samples at trace levels (parts per billion). Additional work which applies the developed methods to a larger population is required, in order to more fully investigate the potential correlation between the levels of polyfluoroalkyl phosphate surfactants and perfluorooctanoic acid levels in humans. The results of this study will be used by Health Canada to further assess the exposure and risks posed by these compounds to humans. Results of this research are published in Chemosphere, 2013, 91(6), 771-777.
Effects of Lactational and/or In Utero Exposure to Environmental Contaminants on the Glucocorticoid Stress-Response and DNA Methylation of the Glucocorticoid Receptor Promoter in Male Rats
Health Canada is responsible for the assessment and management of potential health risks to Canadians associated with exposure to chemicals in the environment. In general, chemicals are usually assessed on a one-by-one basis; however, exposures to mixtures of environmental contaminants are important because they may be more representative of natural conditions. In this study, Health Canada compared the effects of in utero exposure, lactational exposure, or exposure during both periods of development in rats to chemical mixtures of polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polychlorinated biphenyls, organochlorine pesticides and methylmercury. Exposure to some of the mixtures during the period of lactation, or during both periods of development induced an abnormal hormonal response to stress in the male rats when they reached adulthood. While exposure during the lactational period was sufficient to induce significant effects, exposure during the in utero period did not induce significant effects. Given that abnormal hormonal stress responses are associated with metabolic and mental health issues, these results support further investigation of the influence of developmental exposures to environmental contaminants and pre-disposition to stress-induced diseases. The results of this study will help Health Canada to better understand the health risks associated with exposure to these chemical mixtures. Results of this research are published in Toxicology, 2013, 308, 20-33.
Cohort Profile: The Maternal-Infant Research on Environmental Chemicals (MIREC) Research Platform
The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain national-level biomonitoring data for pregnant women and their infants and to examine potential adverse health effects of prenatal exposure to environmental chemicals on pregnancy and infant health. Biomonitoring is the measurement of a chemical substance (or break-down products of that substance) in human tissues or fluids. Measurements are usually taken in blood and urine, and sometimes in hair, saliva, or breast milk. In this study Health Canada researchers participated in the recruitment and analysis of samples from approximately 2000 women during their first trimester of pregnancy from 10 sites across Canada and followed through to delivery. Questionnaires administered during pregnancy and post-delivery collected information on occupation, lifestyle, medical history, environmental exposures and diet. Information on the pregnancy and the infant were collected from medical charts. Maternal blood, urine, hair and breast milk as well as cord blood and infant meconium were collected and analysed for several environmental chemicals and nutrients. Additional samples were stored in the study's biobank. MIREC participants tended to smoke less, be older and have a higher education level than national averages. The MIREC study, while smaller in number of participants than several international studies, has one of the most extensive datasets on prenatal exposure to multiple environmental chemicals in the world. The data, samples collected, and follow-up studies will make the MIREC research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals. Additionally, Health Canada will use the results of this study to inform future risk assessments and risk management of environmental chemicals, especially regarding exposures during pregnancy. Results of this research are published in the journal Paediatric and Perinatal Epidemiology (2013 Jul; 27(4):415-25).
Phthalates in Cosmetic and Personal Care Products: Concentrations and Possible Dermal Exposure
Phthalates are a group of compounds widely used to make plastics more flexible in consumer products, cosmetics, pharmaceuticals, medical devices, and food packaging. Certain phthalates are the subject of concern as they are suspected as having negative effects on reproduction and development. However, most of the research done on phthalates focuses on animal studies, and how this relates to human health is still unclear.
This study measured concentrations of 18 different phthalates in cosmetics and personal care products sold in Canada. Over 250 products (including 98 children products) were analyzed. Results were as follows:
|Phthalate Detected||Detection frequencyTable 1 Footnote 1||Concentration Range (%)|
Table 1 footnotes
|dimethyl phthalate (DMP)||1/252||0.0072|
|diethyl phthalate (DEP)||103/252||0.0015 - 2.5|
|diisobutyl phthalate (DiBP)||9/252||0.0002 - 0.0015|
|di-n-butyl phthalate (DnBP)||15/252||0.0002 - 2.43|
|di (2-ethylhexyl) phthalate (DEHP)||8/252||0.0002 - 0.1045|
The above results suggest that only DEP and DnBP are present in significant quantity in the test products. From their levels in products and product use patterns, daily exposures in adolescent women were estimated at 0.03, 78, 0.36 and 0.82 for DMP, DEP, DnBP, DEHP, respectively. Toddlers (0.5-4 years) and infants (0-6 months) were exposed to DEP only at 20 and 42 micrograms/kilogram of body weight/day (μg/kg bw/d), respectively.
The overall exposure to phthalates from the use of cosmetic and personal care products was low and, therefore, unlikely to pose health risks to Canadian consumers. Health Canada continues to monitor the research on phthalates, and has put regulations in place to limit exposure. DEHP is listed on Health Canada's Cosmetic Ingredient Hotlist as a prohibited ingredient in cosmetics. In addition, Health Canada has restricted the use of three phthalates (DEHP, DnBP and BBP) in children's toys and child care articles, and three others (DINP, DIDP and DnOP) in those children's products that might be placed in the mouth. Results of the research have been published in the Journal of Environmental Research, 2011 Apr;111(3):329-36.
Thyroid Hormone-Regulated Gene Expression in Juvenile Mouse Liver: Identification of Thyroid Response Elements Using Microarray Profiling and in Silico Analyses
Thyroid hormone (TH), produced by the thyroid gland, is essential for growth, development and metabolism, and alterations in normal TH levels can lead to adverse health outcomes. By understanding the biological mechanisms that are involved when TH is affected by environmental chemicals, Health Canada will be better able to fulfill its mandate to assess health risks from chemical substances. In this study, the effects of changes in TH concentrations on gene expression during liver development were examined using mice as a model. Juvenile mice were treated with chemicals that caused low TH levels, whereas a control group of mice was given TH directly, resulting in high TH levels. By comparing gene expression in the different groups of mice, genes were identified that appeared to be directly responsive to changes in TH. Collectively, these results substantially increase knowledge of the genes directly controlled by TH and could ultimately serve as early indicators of exposure to chemicals that alter TH balance for use in toxicological risk assessment. This study was published in BMC Genomics (2011 Dec 29),12(1):634.
Simultaneous Measurement of Benzo[A]Pyrene-Induced Pig-A and Lacz Mutations, Micronuclei And DNA Adducts in Muta Mouse
Health Canada uses a variety of tests to evaluate the health effects of chemicals present in the environment, and is constantly striving to develop and validate new, more efficient and useful tools for this purpose. Measuring DNA damage is a common and useful way of evaluating exposure to harmful chemicals, and it can often signal the possibility of an increased risk for cancer. The tests that are currently available for measuring DNA damage can be expensive and time-consuming, and Health Canada is currently investigating the use of more efficient and quicker tests. A new test to measure DNA damage directly from blood samples was recently developed; however, it is still in the early stages of validation. The performance of this new test was studied, using a chemical commonly found in the environment (benzo[a]pyrene (BaP)) that is known to cause DNA damage and cancer. BaP is found in cigarette smoke and diesel exhaust emissions, and its health effects have been well studied. The amount of DNA damage detected with the new test was found to be extremely comparable to responses measured using older, more traditional tests. Routine use of this test could lead to a more cost-effective and efficient method for screening chemicals for their ability to produce DNA damage and their potential to cause cancer, applicable for use in toxicological risk assessment. This study was conducted in collaboration with Litron Laboratories and the Institute of Cancer Research, and was published in Environmental and Molecular Mutagenesis (2011 Dec), 52(9):756-765.
Barhl1 is directly Regulated by Thyroid Hormone in the Developing Cerebellum of Mice
Health Canada conducts research on thyroid hormone disruption in support of its mandate to assess the health risks to Canadians of various chemicals that it is responsible for regulating. Thyroid hormones are essential for the development of the brain and auditory system. Exposure to some environmental chemicals during pregnancy may interfere with the normal thyroid hormone balance and lead to abnormally low thyroid hormone levels in the offspring. In humans, this leads to a lower intelligence quotient if diagnosis and treatment is not initiated at an early stage. In support of its mandate to assess the risks of various substances to the health of Canadians, Health Canada initiated this study, using animal models, to clarify how thyroid hormones control gene expression during development in order to understand the potential mechanisms involved and the possible involvement of environmental chemicals in this process, as well as to help develop new tools to identify chemicals that exert effects on thyroid hormone. The results of this study suggest that thyroid hormone deficiency, resulting in impaired brain development, may be caused in part through changes in the gene Barhl1. This gene is potentially a key component of the biological processes that play a role in the health effects resulting from a thyroid hormone deficiency at birth. Further work will help to determine whether Barhl1 levels could be used as a biomarker for exposure to environmental chemicals that alter thyroid hormone levels. This study was published in Biochemical and Biophysical Research Communications (2011 Nov), 415(1):157-162.
Pulmonary Gene and Microrna Expression Changes in Mice Exposed to Benzo(A)Pyrene by Oral Gavage
Health Canada is responsible for the assessment and management of health risks to Canadians associated with exposure to products and chemicals in the environment. Benzo[a]pyrene (BaP) is a chemical produced during the incomplete burning of organic material and is also a component of tobacco smoke. BaP is known to cause tumours in experimental animals, and there is also evidence to support an association between BaP exposure and cancer in humans. Chemical reactions that activate BaP into a form that causes cancer occur in both the lung and liver; however, the lung is the tissue where tumours form, suggesting the response to BaP in lung and liver tissues involves different biological processes. Health Canada conducted this study to understand why the lungs are more susceptible to cancer than the liver by studying how genes respond in mice exposed to BaP. The results revealed that some of the differences in cancer susceptibility between the liver and lungs may be due to effects on immune responses in the lung that do not occur in the liver. This study also suggests that it is also prudent to consider tissues that are not the usual targets of direct exposure to chemicals when assessing their health risks. These results will be used to fill gaps in knowledge that will help more fully assess the health risks of this priority chemical and mixtures containing this chemical. This study was conducted in collaboration with the Nutrition and Toxicology Research Institute at Maastricht University and was published in Toxicology (2011 Jul 29), 285(3):133-141.
Assessment of Subclinical, Toxicant-Induced Hepatic Gene Expression Profiles after Low-Dose, Short-Term Exposures in Mice
Health Canada is responsible for assessing chemicals used in Canada for their potential impacts on human health. Determining the responses of all the genes within an organism to chemical exposures is becoming a powerful means to improve the evaluation of potential hazards of chemicals by allowing signatures of toxicity to be developed faster and at a lower cost than when using traditional approaches. To advance the use of this approach, called toxicogenomics, within a risk assessment context, Health Canada conducted this study to examine responses to four chemicals (PCB126, phenobarbital, isoproterenol and lead acetate) given orally to mice in a descending series of doses, the highest of which was minimally toxic by standard clinical measures. The results of this study support using changes in genes as early indicators of toxicity, and the use of toxicogenomics data by Health Canada to reduce uncertainties in risk assessment as well as an aide in the design of longer-term toxicity studies of compounds with unknown toxicity. This study was published in Regulatory Toxicology and Pharmacology (2011 Jun 1), 60(1):54-72.
Polychlorinated Biphenyls (PCBS) Contamination and Aryl Hydrocarbon Receptor (AHR) Agonist Activity of Omega-3 Polyunsaturated Fatty Acid Supplements: Implications for Daily Intake of Dioxins and PCBS
Omega-3 polyunsaturated fatty acid (n-3 PUFA) rich oils are derived from fish and other organisms (e.g., seal, crustacean and flax), and are frequently consumed as nutritional supplements. Oil derived from fatty fish has been shown to provide substantial health benefits, especially in the prevention of coronary heart disease. However, these oils are often derived from organisms that are exposed to persistent organic pollutants, including polychlorinated biphenyls (PCBs), dioxins, and dioxin-like compounds. These compounds are preferentially stored in fatty tissue and accumulate in organisms over time. Therefore, it is possible that n-3 PUFA supplements could contain a significant amount of these compounds. To determine levels of two types of contaminants, seventeen oils available throughout Canada purchased from retailers in 2006 or 2007, were analyzed for PCBs and dioxin-like activity. When consumed at the recommended doses as a supplement to a typical Canadian diet, the tested seal-derived oil was shown to contribute to exceeding the tolerable daily intake for PCBs, and salmon-, tuna-, and sea herring-derived oils were shown to contribute to exceeding the tolerable daily intake of dioxin-like compounds. The beneficial properties of fish and n-3 PUFA supplements are noteworthy and well documented; however, the results of this study suggest that it is prudent to consume supplements derived from small, cold-water fatty fish. Further investigations on additional products and multiple sample lots would be necessary to draw firm conclusions about contamination of products available in Canada in order to inform risk management approaches. This study was conducted in collaboration with the University of Ottawa and was published in Food and Chemical Toxicology (2010 Nov),48(11):3093-3097.
A Survey of the Traditional Food Consumption that may Contribute to Enhanced Soil Ingestion in a Canadian First Nation Community
The inadvertent ingestion of soil is the major pathway for human exposures to non-volatile pollutants in contaminated soils. Health Canada has an interest in quantifying how much soil people ingest under various circumstances in order to more accurately assess the levels of contaminants that could be ingested through soil; this, in turn, helps to identify the criteria for contaminated site remediation and rehabilitation. Qualitative soil exposure assessments of people following traditional lifestyles typical of rural or wilderness areas near contaminated sites have proposed soil ingestion rates in the hundreds of milligrams per day. This study, which is a companion to a human soil ingestion study based on elemental tracers such as aluminum, examined and documented the traditional food consumption activities practiced by an Aboriginal community in the Nemiah Valley of British Columbia. The survey concluded that a significant portion of the community practiced a lifestyle that may lead to enhanced soil exposure. The assessment also concluded that some foods, specifically roots, may have substantial amounts of soil adhering to them that would result in ingestion of approximately 33 mg of soil per 100 g serving. The results of the study will be useful for the exposure assessment portion of human health risk assessments for contaminated sites located in rural or wilderness areas of Canada. This study was a collaboration with the University of Ottawa and was published in Science of the Total Environment (2012 May 1), 424:104-109.
A Soil Ingestion Pilot Study of a Population Following a Traditional Lifestyle Typical of Rural or Wilderness Areas
The inadvertent ingestion of soil particles is the major pathway for human exposure to non-volatile pollutants at contaminated sites. Health Canada has been working to understand how much soil people ingest under different circumstances in order to better identify effective site remediation and rehabilitation criteria. This study assessed soil ingestion in First Nations' individuals who practice traditional lifestyles in a wilderness area of Canada. There have been no quantitative studies to determine soil ingestion in these populations to date; however, qualitative assessments have proposed ingestion rates in the hundreds of milligrams per day for people following traditional lifestyles typical of rural or wilderness areas. By measuring fecal levels of elements normally found in soil, the study calculated daily soil ingestion rates for 7 adult subjects living in the Nemiah Valley of British Columbia. The measured soil ingestion rates were higher than those for previous studies of adults living in urban or suburban environments, but lower than the ingestion rates proposed in the aforementioned qualitative studies. The results of this research will enhance Health Canada's ability to critically evaluate current regulatory guidelines for contaminated sites, and their applications to people living in rural or wilderness areas of Canada. This study was conducted in collaboration with the University of Ottawa and the University of Northern British Columbia and was published in the journal Science of the Total Environment (2012 May 1), 424:110-120.
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