Novel halogenated flame retardants in Canadian human milk from the MIREC study (2008-2011).

Novel halogenated flame retardants (NHFRs) have been developed to replace those brominated flame retardants that have been restricted due to their persistence, bioaccumulation potential and toxicity, therefore, it is important to determine whether these replacement products are present at detectable concentrations in Canadians. NHFRs were measured in human milk samples (n = 541) collected from across Canada between 2008 and 2011, which is the first pan-Canadian dataset for these chemicals in human milk. Among the 15 measured NHFRs and eight methoxy-polybrominated diphenyl ethers (MeO-PBDEs), nine NHFRs and two MeO-PBDEs (6-MeO-PBDE 47 and 2-MeO-PBDE 68) were detected at a frequency of more than 9%. Despite benzene, 1,1'-(1,2-ethanediyl)bis [2,3,4,5,6-pentabromo-]/decabromodiphenylethane [DBDPE] being detected less frequently than the other observed NHFRs, its relative contribution to the sum of nine NHFRs was important when it was present. The maximum ΣNHFR concentration in Canadian human milk was 6930 pg g-1 lipid while the maximum ΣMeO-PBDEs was 1600 pg g-1 lipid. While most NHFR concentrations were significantly correlated with each other, no relationships between maternal age, parity or pre-pregnancy BMI were identified with ΣNHFR concentrations in the milk. In contrast, maternal age was significantly correlated with ΣMeO-PBDE concentrations (r = 0.237, p < 0.001). ΣNHFR concentrations were similarly not related to maternal education, although ΣMeO-PBDE concentrations were found to be higher in milk from women who had graduated from trade schools relative to the other education levels considered. NHFR detection frequency and concentrations observed in the Canadian human milk seem to align well with Europe.

Differences in mirex [dechlorane] and dechlorane plus [syn- and anti-] concentrations observed in Canadian human milk.

As part of the pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study, human milk samples were collected between 2008 and 2011, and analyzed for mirex, an organochlorine insecticide and flame retardant, in addition to dechlorane plus (syn- and anti-DDC-CO), the flame retardant replacement for mirex. Mirex was analyzed separately, using a method for the analysis of existing organochlorine insecticides, while the presence of DDC-CO isomers was determined using a method developed for the detection of emerging flame retardants. Mirex was detected in all samples analyzed (n = 298), while syn- and anti-DDC-CO were present in 61.0% and 79.5% of the samples, respectively (n = 541). Mirex concentrations have declined in human milk since the 1990s. Since this is the first pan-Canadian dataset reporting DDC-CO concentrations in human milk, no temporal comparisons can be made. Maternal age was correlated with concentrations of both compounds although parity did not impact concentrations of either analyte. Given the presence of this relatively recently identified flame retardant (DDC-CO) in human milk from women across Canada, studies to identify dominant sources of this compound are critical. Despite low concentrations of environmental chemicals in human milk from Canadian women, Health Canada supports breastfeeding of infants because of the important health benefits to both the mothers and their infants.

Occurrence of glycidyl esters in infant formula products on the Canadian market between 2015 and 2019.

Glycidyl fatty acid esters (GEs) are processing contaminants formed during refining steps of vegetable oils. 'In vivo' hydrolysis of GEs releases potentially carcinogenic and genotoxic glycidol (2,3-epoxy-1-propanol). Occurrence of GEs in vegetable oils used for infant formula manufacturing may pose a potential health concern for formula-fed infants. Refined oils are commonly used as the main fat ingredient in formula manufacturing. For this study, different infant formula products (powders, concentrates and ready-to-feed formula products) were purchased and analysed in 2015 (35 samples) and 2019 (33 samples). Seven individual GEs were analysed by LC-MS/MS via direct approach by stable isotope dilution analysis, and total bound glycidol concentrations were calculated. Concentrations of bound glycidol in reconstituted formula reached maxima of 40.3 ng/g in the 2015 samples and 31.5 ng/g in the samples collected in 2019, with respective means of 8.7 ng/g and 6.7 ng/g. The analysed bound glycidol concentrations are comparable with concentration ranges from other studies, but are higher than observed in studies from the European market. Temporal trend data show a reduction of bound glycidol concentrations in 2019. GE concentrations were compared across different manufacturers.

Occurrence of 2- and 3-monochloropropanediol esters (MCPDE) in infant formula products on the Canadian market between 2015 and 2019.

2- and 3-monochloropropanediol esters (MCPDEs) are most commonly formed as process-induced contaminants during the refinement of vegetable oils used for food production. 'In vivo' hydrolysis of 3-MCPDEs releases the potential carcinogen 3-monochloropropanediol (3-MCPD). Levels of MCPDEs in infant formula are of particular concern, as refined oils are commonly used as main fat ingredients. For this study, infant formula samples (powders, liquid concentrates and ready-to-feed infant formula samples) from the Canadian market were purchased and analysed in 2015 (35 samples) and 2019 (33 samples). MCPDE concentrations (expressed as free MCPD equivalents) were examined through an indirect analytical approach, applying acid-catalysed ester cleavage and using cyclohexanone as derivatising agent. Labelled diesters were used as internal standards. 2015 Survey data were analysed by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring mode (SIM). 2019 Survey data were analysed with an updated method using GC-MS/MS in multiple reaction monitoring modes (MRM). In 2015, levels in reconstituted formula ranging from 3.7 ng/g to 111 ng/g for 3-MCPD and 2.2 ng/g to 56.2 ng/g for 2-MCPD were found. In 2019, levels ranging from 3.9 ng/g to 74.8 ng/g for 3-MCPD and 1.0 ng/g to 33.9 ng/g for 2-MCPD were found. A significantly reduced mean of combined MCPDEs was observed between 2015 and 2019 data (64.5 ng/g, standard deviation (SD) 8.6 ng/g in 2015 to 31.8 ng/g, SD 5.6 ng/g in 2019, p-value = 0.024). For the majority of manufacturers, the data comparison among brand products over time shows decreased levels of MCPDEs. Occurrence data of MCPDEs, including data from previously published surveys (2012/2013), were also compared and a temporal trend was established.

Perfluorinated alkyl substances in Canadian human milk as part of the Maternal-Infant Research on Environmental Chemicals (MIREC) study.

Perfluorinated alkyl substances (PFAS) were determined in human milk samples (n = 664) from participants in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. ΣPFAS concentrations (sum of seven PFAS) ranged from 3.1 ng L-1 to 603 ng L-1, with a median concentration of 106 ng L-1 in the Canadian mothers' milk analyzed. These data comprise the first pan-Canadian dataset of PFAS in human milk. Perfluorooctanoic acid (PFOA) and linear perfluorooctanesulfonate (L-PFOS) were the dominant contributors to ΣPFAS in human milk samples. An inverse relationship between ΣPFAS concentrations and age was observed (Spearman correlation - 0.184). Primiparous women had elevated PFAS concentrations in milk relative to women who had children previously (p < 0.001). In contrast, the region of maternal birth did not influence ΣPFAS concentrations (p = 0.156). Although China and Norway have observed consistently detectable levels of perfluoroundecanoic acid (PFUdA) in human milk, PFAS with long carbon chains (n ≥ 11) were not present above method detection limits in Canadian human milk samples analyzed as part of the MIREC study. In conclusion, despite the presence of low levels of environmental contaminants in human milk, Health Canada supports breastfeeding due to the benefits to both infants and mothers.

Method development and evaluation for the determination of perfluoroalkyl and polyfluoroalkyl substances in multiple food matrices.

A method for the determination of 21 perfluorinated and 10 polyfluorinated alkyl substances (PFAS) was developed for application in different food matrices. Acetonitrile was used as the extraction solvent with solid phase extraction weak anion-exchange (SPE-WAX) clean up, with LC-MS/MS analysis using both surrogate and performance standards to correct for losses during sample preparation and matrix effects. The method has been evaluated in four different matrices (fish, pizza, chicken nuggets and spinach). Originally, the focus was to develop a method for foods commonly thought to be a source of PFASs (e.g. fish). It was expanded to include foods where PFAS exposure would be possible through their presence in grease-proof food packaging (e.g. pizza, chicken nuggets). Vegetables (lettuce) and fruit (tomato) have recently been considered as part of proficiency testing programmes, so the inclusion of some testing in a vegetable matrix (i.e. spinach) was also added to the testing. Limits of quantification ranged from 0.018 ng g-1 (L-PFDS) to 5.28 ng g-1 (FHEA), although method quantification limits for PFBA (12.4 ng g-1), 6:2 PAP (8.96 ng g-1) and 8:2 PAP (3.49 ng g-1) were elevated above instrumental limits owing to their consistent detection in reagent blank samples. PFAS analyses were strongly impacted by matrix, therefore the use of isotopically labelled internal standards was critical to the development of accurate results. The accuracy of the method using numerous proficiency testing schemes or interlaboratory comparison studies has shown the developed method to be successful with z-scores for all concerned analytes in all test matrices remaining within ±2.0, with the exception of PFBA in wheat flour which was -2.4.

Polybrominated Diphenyl Ethers in Human Follicular Fluid Dysregulate Mural and Cumulus Granulosa Cell Gene Expression.

Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants incorporated into numerous consumer products, leach out into dust resulting in widespread exposure. There is evidence from in vitro and in vivo animal studies that PBDEs affect ovarian granulosa cell function and follicular development, yet human studies of their association with female infertility are inconclusive. Here, we tested the hypothesis that exposure to the PBDEs in follicular fluid is associated with dysregulation of gene expression in the mural and cumulus granulosa cells collected from women undergoing in vitro fertilization by intracytoplasmic sperm injection. The median concentration of the ∑ 10PBDEs detected in the follicular fluid samples (n = 37) was 15.04 pg/g wet weight. RNA microarray analyses revealed that many genes were differentially expressed in mural and cumulus granulosa cells. Highest vs lowest quartile exposure to the Σ 10PBDEs or to 2 predominant PBDE congeners, BDE-47 or BDE-153, was associated with significant effects on gene expression in both cell types. Mural granulosa cells were generally more sensitive to PBDE exposure compared to cumulus cells. Overall, gene expression changes associated with BDE-47 exposure were similar to those for ∑ 10PBDEs but distinct from those associated with BDE-153 exposure. Interestingly, exposure to BDE-47 and ∑ 10PBDEs activated the expression of genes in pathways that are important in innate immunity and inflammation. To the best of our knowledge, this is the first demonstration that exposure to these environmental chemicals is associated with the dysregulation of pathways that play an essential role in ovulation.

Polychlorinated Biphenyls and Polychlorinated Dioxins-Furans in Lake Trout and Whitefish Composite Samples from Commercial Fisheries in Lakes Erie, Huron, and Superior.

Polychlorinated biphenyls (PCBs; sum of 36 congeners) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs; sum of 17 2,3,7,8-substituted congeners) were measured in 93 composite samples prepared from individual lake trout (Salvelinus namaycush) and whitefish (Coregonus clupeaformis) samples collected from Lake Erie, Lake Huron, and Lake Superior. All samples had detectable concentrations of PCBs and PCDD/Fs; maximum PCB concentrations in both trout (750 ng g-1 whole weight [ww]) and whitefish (210 ng g-1 ww) were found in composites from fish collected from Lake Huron. The maximum toxic equivalent concentration was found in a lake trout composite sample from Lake Huron (53 pg g-1 ww). PCB and PCDD/F congener profiles were comparable to patterns observed in fishes collected from other regions of Canada, although concentrations were above those found in other regions. A positive correlation was found between PCB concentrations determined using the historical Aroclor equivalency method and those determined using the sum of the congeners measured (r2 = 0.871; Spearman correlation r = 0.917) or using the six indicator PCB congeners (28, 52, 101, 138, 153, and 180; r2 = 0.850; Spearman correlation r = 0.935). PCBs were the dominant contributor to the overall toxic equivalent concentrations in the fish composite samples tested. These findings provide insight into PCB and PCDD/F concentrations in two commercially important fish species over a discrete time period.

Dioxins/furans and PCBs in Canadian human milk: 2008-2011.

Human milk was collected between 2008 and 2011 as part of the Maternal - Infant Research on Environmental Chemicals (MIREC) study that was initiated to establish Canadian national estimates of maternal and infant exposure to a broad suite of environmental contaminants (e.g., persistent organic pollutants [POPs], trace elements, phthalates, etc.). Among the 1017 human milk samples collected, 298 were analysed for polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs). World Health Organization (WHO) toxic equivalency concentrations (WHO TEQ2005) for PCDD/F+dioxin-like (DL) PCB ranged from 2.2pg TEQ2005 g-1 lipid to 27pg TEQ2005 g-1 lipid. The relative contribution of PCDDs to the overall WHO TEQ2005 (PCDD/F+DL PCB) has decreased from earlier investigations into POP levels in Canadian human milk. Significantly higher PCB concentrations were observed in milk from women born in Europe relative to those born in Canada (p<0.001), in contrast to results for the PCDD/Fs (p=0.496). Age was found to significantly impact milk ∑PCB concentrations (p=0.018), with elevated concentrations observed in milk from women >30years relative to those <30years of age. While this trend was also observed for the PCDD/Fs, this relationship was impacted by parity. WHO TEQ2005 concentrations were significantly higher in milk from primiparous women (p=0.019) and those >30years relative to those <30years of age (p<0.001). No significant differences were associated with education level or pre-pregnancy body mass index. PCB and PCDD/F concentrations have continued to decline in Canadian human milk since the last sampling of human milk was performed.

Toxicologic effects of 28-day dietary exposure to the flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH) in F344 rats.

The brominated flame retardant TBECH is used as an additive to delay ignition and inhibit fires in construction materials and consumer goods. Trends in human exposure are not clear, although humans may be exposed to TBECH via indoor dust and air. In birds and fish there is some evidence of disruption in endocrine and reproductive parameters due to TBECH. In vitro studies indicate that TBECH is an androgen receptor agonist. In this study rats were exposed to 0, 10, 50, 250, 1250 or 5000mg/kg technical TBECH for 28days in diet, corresponding to 0, 0.9, 4.2, 21.3, 98.0 or 328.9mg TBECH/kg bw/d in males and 0, 0.8, 3.9, 19.4, 91.7 or 321.4mg TBECH/kg bw/d in females. Dose-dependent increases in α- and ß- TBECH were detected in serum, liver and adipose. Rats in the 5000mg/kg group lost weight rapidly and were euthanized after 15-18days. At study termination rats displayed dose-dependent clinical and histopathological changes consistent with mild hepatic and renal inflammation. In male rats, evidence of gender-specific alpha2u-globulin nephropathy was not considered predictive of renal toxicity in humans. Frank immunosuppression or inappropriate immunostimulation were not apparent, nor was there a primary effect of TBECH on adaptive immunity. Some evidence of hormone disruption was observed, including changes in serum testosterone levels in males and changes in serum T3 and T4 levels in females. Apparent increases in thyroid follicular cell hypertrophy and hyperplasia in male and female rats were not statistically significant. Benchmark dose (BMD) modelling indicated that clinical changes indicative of mild nephrotoxicity and increased blood monocyte numbers indicative of inflammation and tissue damage were the most sensitive outcomes of TBECH exposure that could be modelled. Preliminary evidence of hormone disruption supports the need for rodent studies using more sensitive models of growth, development and reproduction.

A method for the analysis of multiple novel halogenated flame retardants in cow's milk.

A method was developed for the extraction and analysis of cow's milk to measure 21 halogenated flame retardants (FRs), including individual isomers plus eight methoxy-polybrominated diphenyl ethers (MeO-PBDEs). Extraction was performed using homogenisation with acetone:hexane with size exclusion chromatography followed by adsorption chromatography clean-up. Analysis was undertaken using gas chromatography high-resolution mass spectrometry. The method was validated in fortified cow's milk with FRs and 2-methoxy-PBDE 68 at three levels (low [12.5-1250 pg g(-)(1)], mid [37.5-5000 pg g(-)(1)] and high [400-10 000 pg g(-)(1)]). Additional methoxy-PBDEs were tested at two fortification levels. Isotope dilution was used to correct for losses during sample preparation and average recoveries ranged from 58% (allyl 2,4,6-tribromophenyl ether [ATE]) to 121% (γ-tetrabromoethylcyclohexane (γ-TBECH)). Limits of detection ranged from 0.055 pg g(-)(1) (6-methoxy-PBDE 47) to 38.9 pg g(-)(1) (decabromodiphenylethane (DBDPE)). Matrix effects were overcome through the use of surrogate and performance standards. A single FR (1-bromomethyl-2,3,4,5,6-pentabromobenzene [PBBB]) and two methoxy-PBDEs were detected in commercially available cow's milk collected from local supermarkets in Ottawa, ON, Canada. Detection frequency was < 25% for these compounds and, where present, concentrations were low.

Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations.

Brominated flame retardants (BFRs) are stable environmental contaminants known to exert endocrine-disrupting effects. Developmental exposure to polybrominated diphenyl ethers (PBDEs) is correlated with impaired thyroid hormone signaling, as well as estrogenic and anti-androgenic effects. As previous studies have focused on a single congener or technical mixture, the purpose of the current study was to examine the effects of gestational and early postnatal exposure to an environmentally relevant mixture of BFRs designed to reflect house dust levels of PBDEs and hexabromocyclododecane on postnatal developmental outcomes. Pregnant Sprague-Dawley rats were exposed to the PBDE mixture from preconception to weaning (PND 21) through the diet containing 0, 0.75, 250, and 750 mg mixture/kg diet. BFR exposure induced transient reductions in body weight at PND 35 in male and from PND 30-45 in female offspring (250 and 750 mg/kg). Liver weights (PND 21) and xenobiotic metabolizing enzyme activities (PND 21 and 46) were increased in both male and female offspring exposed to 250 and 750 mg/kg diets. Furthermore, serum T4 levels were reduced at PND 21 in both,male and female offspring (250 and 750 mg/kg). At PND 21, Serum alkaline phosphatase (ALP) was decreased in males exposed to 750 mg/kg dietat, and females exposed to 250 and 750 mg/kg diets. At PND 46 ALP was significantly elevated in males (250 and 750 mg/kg). Variations in the cervical vertebrae and phalanges were observed in pups at PND 4 (250 and 750 mg/kg). Therefore, BFR exposure during gestation through to weaning alters developmental programming in the offspring. The persistence of BFRs in the environment remains a cause for concern with regards to developmental toxicity.

Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.

Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis.

Inhalation and dietary exposure to PCBs in urban and rural cohorts via congener-specific measurements.

Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological, and respiratory toxicities are expansive and growing. However, PCB inhalation exposure assessments have been lacking for North American ambient conditions and lower-chlorinated congeners. We assessed congener-specific inhalation and dietary exposure for 78 adolescent children and their mothers (n = 68) in the Airborne Exposure to Semi-volatile Organic Pollutants (AESOP) Study. Congener-specific PCB inhalation exposure was modeled using 293 measurements of indoor and outdoor airborne PCB concentrations at homes and schools, analyzed via tandem quadrupole GS-MS/MS, combined with questionnaire data from the AESOP Study. Dietary exposure was modeled using Canadian Total Diet Survey PCB concentrations and National Health and Nutrition Examination Survey (NHANES) food ingestion rates. For ∑PCB, dietary exposure dominates. For individual lower-chlorinated congeners (e.g., PCBs 40+41+71, 52), inhalation exposure was as high as one-third of the total (dietary+inhalation) exposure. ∑PCB inhalation (geometric mean (SE)) was greater for urban mothers (7.1 (1.2) µg yr(­1)) and children (12.0 (1.2) µg yr(­1)) than for rural mothers (2.4 (0.4) µg yr(­1)) and children (8.9 (0.3) µg yr(­1)). Schools attended by AESOP Study children had higher indoor PCB concentrations than did homes, and account for the majority of children's inhalation exposure.

Hair as a biomarker of systemic exposure to polybrominated diphenyl ethers.

The efficacy of using hair as a biomarker for exposure to polybrominated diphenyl ether (PBDE) flame retardants was assessed in humans and an animal model. Paired human hair and serum samples were obtained from adult men and women (n = 50). In parallel, hair, serum, liver, and fat were collected from adult male Sprague-Dawley rats exposed to increasing doses of the PBDE mixture found in house dust for 70 days via the diet. All samples were analyzed by GC-MS for eight common PBDEs: BDE-28, -47, -99, -100, -153, -154, -183, and -209. Paired human hair and serum samples had five congeners (BDE-28, -47, -99, -100, and -154) with significant individual correlations (0.345-0.566). In rat samples, BDE-28 and BDE-183 were frequently below the level of detection. Significant correlations were observed for BDE-47, -99, -100, -153, -154, and -209 in rat hair, serum, liver, and fat across doses, with r values ranging from 0.803 to 0.988; weaker correlations were observed between hair and other tissues when data from the lowest dose group or for BDE-209 were analyzed. Thus, human and rat hair PBDE measurements correlate strongly with those in alternative matrices, validating the use of hair as a noninvasive biomarker of long-term PBDE exposure.

Polybrominated diphenyl ether (DE-71) interferes with thyroid hormone action independent of effects on circulating levels of thyroid hormone in male rats.

Polybrominated diphenyl ethers (PBDEs) are routinely found in human tissues including cord blood and breast milk. PBDEs may interfere with thyroid hormone (TH) during development, which could produce neurobehavioral deficits. An assumption in experimental and epidemiological studies is that PBDE effects on serum TH levels will reflect PBDE effects on TH action in tissues. To test whether this assumption is correct, we performed the following experiments. First, five concentrations of diphenyl ether (0-30 mg/kg) were fed daily to pregnant rats to postnatal day 21. PBDEs were measured in dam liver and heart to estimate internal dose. The results were compared with a separate study in which four concentrations of propylthiouracil (PTU; 0, 1, 2, and 3 ppm) was provided to pregnant rats in drinking water for the same duration as for diphenyl ether. PBDE exposure reduced serum T4 similar in magnitude to PTU, but serum TSH was not elevated by PBDE. PBDE treatment did not affect the expression of TH response genes in the liver or heart as did PTU treatment. PTU treatment reduced T4 in liver and heart, but PBDE treatment reduced T4 only in the heart. Tissue PBDEs were in the micrograms per gram lipid range, only slightly higher than observed in human fetal tissues. Thus, PBDE exposure reduces serum T4 but does not produce effects on tissues typical of low TH produced by PTU, demonstrating that the effects of chemical exposure on serum T4 levels may not always be a faithful proxy measure of chemical effects on the ability of thyroid hormone to regulate development and adult physiology.

The brominated flame retardants, PBDEs and HBCD, in Canadian human milk samples collected from 1992 to 2005; concentrations and trends.

Human milk samples were collected from individuals residing in various regions across Canada mostly in the years 1992 to 2005. These included five large cities in southern Canada as well as samples from Nunavik in northern Quebec. Comparative samples were also collected from residents of Austin, Texas, USA in 2002 and 2004. More than 300 milk samples were analysed for the brominated flame retardants (BFRs), PBDEs and HBCD, by extraction, purification and quantification using either isotope dilution gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-MS. The Canadian total PBDE values in the years 2002-2005 show median levels of about 20µg/kg on a lipid basis; a value significantly higher than in the 1980s and 1990s. Milk samples from Inuit donors in the northern region of Nunavik were slightly lower in PBDE concentrations than those from populated regions in the south of Quebec. Milk samples from Ontario contained slightly lower amounts of PBDEs in two time periods than those from Texas. HBCD levels in most milk samples were usually less than 1ppb milk lipid and dominated by the α-isomer. This large data set of BFRs in Canadian human milk demonstrates an increase in the last few decades in human exposure to BFRs which now appears to have stabilized.

Exposure to an environmentally relevant mixture of brominated flame retardants affects fetal development in Sprague-Dawley rats.

Brominated flame retardants are incorporated into a wide variety of consumer products and are known to enter into the surrounding environment, leading to human exposure. There is accumulating evidence that these compounds have adverse effects on reproduction and development in humans and animal models. Animal studies have generally characterized the outcome of exposure to a single technical mixture or congener. Here, we determined the impact of exposure of rats prior to mating and during gestation to a mixture representative of congener levels found in North American household dust. Adult female Sprague-Dawley rats were fed a diet containing 0, 0.75, 250 or 750mg/kg of a mixture of flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane) from two weeks prior to mating to gestation day 20. This formulation delivered nominal doses of 0, 0.06, 20 and 60mg/kg body weight/day. The lowest dose approximates high human exposures based on house dust levels and the dust ingestion rates of toddlers. Litter size and resorption sites were counted and fetal development evaluated. No effects on maternal health, litter size, fetal viability, weights, crown rump lengths or sex ratios were detected. The proportion of litters with fetuses with anomalies of the digits (soft tissue syndactyly or malposition of the distal phalanges) was increased significantly in the low (0.06mg/kg/day) dose group. Skeletal analysis revealed a decreased ossification of the sixth sternebra at all exposure levels. Thus, exposure to an environmentally relevant mixture of brominated flame retardants results in developmental abnormalities in the absence of apparent maternal toxicity. The relevance of these findings for predicting human risk is yet to be determined.

Polychlorinated dioxins, furans (PCDD/Fs), and polychlorinated biphenyls (PCBs) and their trends in Canadian human milk from 1992 to 2005.

More than 300 samples of human milk were collected from individuals residing in various regions across Canada in the years 1992 to 2005. The milks were taken from the main populated areas east to west in southern Canada as well as from the region of Nunavik in northern Quebec and analysed for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). The concentrations, expressed in ng kg(-1) milk lipid, show an overall decrease of virtually all compounds examined including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), World Health Organization 2005 toxic equivalents (WHO2005-TEQ) PCDD/PCDFs, WHO2005-TEQ dioxin-like PCBs (dl-PCBs), and total PCBs. Median values of 2,3,7,8-TCDD changed from about 1.5 ng kg(-1) milk lipid in 1992 to 0.8 ng kg(-1) in 2005 while the median WHO2005-TEQ PCDD/F fell from about 14-7 ng kg(-1) milk lipid in the same period. The concentrations of PCDD/Fs and PCBs in samples from Nunavik, which is in Arctic Quebec, were higher than those observed in milk from southern Quebec although this difference was not large. Over two time periods, milk samples from Hamilton, Ontario showed slightly higher levels of PCBs than Austin, Texas, USA--a North American city of similar size and development but with more than twice the PBDE exposure. When compared with earlier human milk data going back to the early 1980s, this large data set shows a steady decline of human exposure to POPs in Canada by a factor of about four times.

Hexabromocyclododecane concentrations in Canadian human fetal liver and placental tissues.

Detectable concentrations of the flame retardant hexabromocyclododecane (HBCD) have been reported in human tissues worldwide, but investigations to determine fetal exposure to this brominated flame retardant are lacking. This study was undertaken to determine the concentrations of α-, ß- and γ-HBCD in human tissues (fetal liver and placenta) from Canada. Tissue samples were collected over a thirteen year period following elective pregnancy terminations in Montreal, Quebec, Canada. Samples were extracted using homogenisation with solvent, cleaned up using adsorption chromatography and analysis was performed with liquid chromatography-tandem mass spectrometry. Total HBCD concentrations ranged from below the limit of detection (