Legacy halogenated flame retardants in Canadian human milk from the maternal-infant research on environmental chemicals study
Abstract
Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) were measured in 298 human milk samples collected from across Canada between 2008 and 2011 as part of the Maternal-Infant Research on Environmental Chemicals study. PBDEs were detected in 100% of the samples analyzed and concentrations ranged from 0.071 to 267 ng·g-1 lipid (median 15.6 ng·g-1 lipid). The dominant contributors to ΣPBDEs (Σ15, 17, 28, 37, 47, 66, 71, 75, 77, 85, 99, 100, 119, 138, 153, 154, 160, 183, 190, 209) were PBDE 47 > PBDE 153 > PBDE 99 > PBDE 100 > PBDE 28 > PBDE 209. Previously, PBDE 209 was considered to be a minor contributor to ΣPBDE concentrations in Canadian human milk and, therefore, not reported by our lab. This study showed that when present, PBDE 209 can be an important contributor to ΣPBDEs (range: below detection - 85.3 ng·g-1 lipid; median - 0.083 ng·g-1 lipid).
Keywords
INTRODUCTION
Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) are both additive brominated flame retardants (BFRs) that are mixed with polymers present in consumer products (e.g., textiles, electronics, etc.) to reduce flammability[1]. By being added and mixed with the polymers, rather than chemically bonded, they are more readily released to the environment throughout their lifecycle. PBDEs were produced as three mixtures named according to the dominant contributors to the total PBDE concentration: the penta-mix, dominated by the penta- and tetra-brominated congeners; the octa-mix, which encompasses significant levels of the octa-, nona- and decabrominated congeners, and the deca-mix, reported to comprise 92%-97% decabromodiphenyl ether (PBDE 209)[2]. The penta-mix and octa-mix were used in different applications (e.g., penta-mix - polyvinylchloride, unsaturated polyesters, rubber, paints, lacquers, and textiles; octa-mix - acrylonitrile butadiene styrene, polyamide, poly butylene terephthalate, polystyrene/high impact polystyrene). While the deca-mix was used for most purposes identified for the other mixtures, it was also used in polyethylene cross-linked polyethylene, polyethylene terephthalate, and polypropylene[3]. The inclusion of PBDEs in these chemicals resulted in their presence in a wide variety of consumer products such as televisions, computers, appliances, smoke detectors, conveyor belts, carpets, textiles, furniture, and the seating upholstery in vehicles[3]. HBCD was used as a replacement for PBDEs[4] primarily in building insulation (expanded and extruded polystyrene), although it was also used to a minor extent in textiles[5].
Although persistence is a desirable quality for flame retardants in consumer products, this characteristic, coupled with their application as additive BFRs, has contributed to their release into the environment during product lifecycles and following disposal[6-8]. Given that many of the products containing PBDEs and HBCD are present within homes and workplaces, they are detected at elevated concentrations in indoor dust and air relative to outdoor environments in global regions free of outdoor sources[9,10]. In addition, BFR levels in the air and dust in offices have been related to the number of electronic devices present[6]. Subsequently, the release of BFRs during recycling of electronic/electrical waste and repair of electronic equipment has been documented as leading to their elevated levels in air and dust where this activity is performed[11,12].
While both of these classes of BFRs are known to be persistent, they also accumulate in the tissues of living organisms, particularly in the lipid tissues[13]. As a result of the bioaccumulation potential, PBDEs and HBCD have been monitored in many different organisms globally, and studies have shown that both of these BFRs biomagnify through food webs[14-22]. In addition, PBDEs and HBCD have been reported in human tissues/fluids throughout the world (e.g., serum, milk) for more than a decade[23-33]. Human milk collected in Sweden over a period of 25 years (1972 to 1997) was analyzed to measure PBDEs and highlighted a dramatic increase in ΣPBDE (Σ of PBDE 28, 47, 66, 85, 99, 100, 153, 154) concentration, from < 0.1 ng·g-1 lipid in 1972 to ~4 ng·g-1 lipid in 1997[34,35]. Following this study, the same group analyzed a limited number of human milk samples (n = 15) collected in 2000-2001 and found ΣPBDE concentrations ranged from 0.56 to 7.72 ng·g-1 lipid, which shows that concentrations continued to increase into the early 2000s, prior to regulatory action being taken on these chemicals[36]. North American studies measuring PBDEs (consistently including Σ28, 47, 99, 100, 153) in human milk during the early to mid-2000s found concentrations to be higher than observed in Europe during a similar period (range 0.1-2,010 ng·g-1 lipid)[37]. Since HBCD has not been as widely studied as PBDEs, temporal trends were not readily established in human milk globally[38,39]. In addition to differences in temporal patterns, concentrations of these legacy BFRs vary among countries and regions.
The determination of PBDEs and HBCD in human milk is important because these data allow researchers to determine maternal exposure via their milk concentrations. Additionally, human milk is often the sole source of nutrition for infants and very young children, which means it represents an important dietary exposure to BFRs for this demographic. Owing to the fact that infants and very young children are growing and changing rapidly, BFR exposure during this phase of life may impact their development since these compounds are associated with impacts on endocrine function and frequently related to thyroid function disruption[13,40,41]. Although exposure at critical developmental stages may not result in immediate impacts, PBDE exposure can lead to increased risk of disease at later life stages (e.g., diabetes, cancer, neurobehavioural effects)[41-43], and HBCD has also been associated with neurobehavioural impacts and changes in sex-related hormones[40], resulting in effects on behaviour and memory[13].
Despite the presence of persistent organic contaminants, including BFRs, in human milk, the World Health Organization (WHO) recommends that mothers feed children human milk exclusively for the first six months, because of the presence of important nutritional constituents and positive health effects for the mothers and their babies[44]. In addition, breastfed infants are reported to have a lower incidence of obesity later in life[45].
The present study, known as the Maternal-Infant Research on Environmental Chemicals (MIREC) study, was undertaken across Canada between 2008 and 2011 to measure maternal concentrations of environmental chemicals during pregnancy and in the milk following the birth of their babies[46]. The work described herein is focused on the measurement of PBDEs and HBCD in human milk.
EXPERIMENTAL
Study population and sampling
Participants for the MIREC study were recruited from across Canada to allow for a pan-Canadian perspective on maternal environmental chemical concentrations. In addition to providing biomonitoring data on the participants, this work supported the determination of infant dietary exposure via human milk sampling. Research centres were identified as possible recruitment sites if it was determined that existing frameworks for clinical obstetric research were in place prior to being associated with the MIREC study. In advance of confirming any clinic as a MIREC recruitment site or study centre, each clinic was required to obtain ethics board approval from their own research centre, Health Canada’s ethics board, and the ethics board of the MIREC coordination centre in CHU Sainte Justine, Québec. Once a clinic was confirmed to be a MIREC study centre, recruitment was undertaken during prenatal clinics[46]. Study centres were established in 10 cities (from six provinces) across southern Canada, from west to east: Vancouver (British Columbia); Edmonton (Alberta); Winnipeg (Manitoba); Hamilton, Kingston, Ottawa, Sudbury and Toronto (Ontario); Montréal (Québec) and Halifax (Nova Scotia).
Eligibility requirements were limited to women aged 18 or above, in the first 14 weeks of gestation, and capable of communicating in either English or French[46]. Among the women approached regarding the study, 2,001 agreed to participate. As part of the requirement, participants were given lifestyle and demographic questionnaires during each of the first and third trimesters for their completion and approximately 50% (n = 1,017) of the recruited participants provided samples of their milk for analysis of multiple classes of chemicals (e.g., persistent organic pollutants, metals, bisphenol-A).
Health Canada analytical laboratories involved in the human milk analyses did not have the capacity to analyze all of the samples collected as part of the current study. As a result, a plan to distribute the milk samples among analytical laboratories was established for all analytes to ensure that samples from across all sampling sites were analyzed for each class of analyte. Data from the Canadian Community Health Survey (CCHS)[47] and estimates of the number of women who would continue to breastfeed for a period extending beyond two weeks of the birth of their babies were considered as part of the framework. This information was coupled with the number of participants from each of the research centres to enable the development of an estimate of samples available for distribution between laboratories. Statisticians then prepared a sample distribution framework to randomly select samples from each location to be analyzed by each of the laboratories. Factors considered while developing the sampling plan included the number of samples able to be handled by each lab, to reach a target of 300 total samples for legacy persistent organic pollutants (e.g., PBDEs and HBCD), and a representative distribution of ages and number of previous pregnancies/births by participant [Table 1]. The plan was developed in advance of all samples being received, and given that sample collection took place from 2008 until 2011, the plan had to allow for flexibility and to ensure that the pan-Canadian situation would be captured by each laboratory analyzing a subset of the samples. Among the 1,017 participants providing milk, 298 were identified and analyzed for PBDEs and HBCD in the Health Canada laboratory [Figure 1].
Figure 1. MIREC participant population and samples used for PBDE/HBCD analysis. MIREC: Maternal-Infant Research on Environmental Chemicals; PBDE: polybrominated diphenyl ether; HBCD: hexabromocyclododecane.
Participant summary information corresponding to the PBDE and HBCD analysis
| Characteristic | Minimum | Maximum | Mean | Median |
| n = 298 | ||||
| Born in Canada - 84.6% | ||||
| Age (years) | 21 | 46 | 33.6 | 34 |
| Parity | 1 | 5 | - | 2 |
| Pre-pregnancy body mass index | 16.6 | 48.6 | 24.6 | 23.1 |
| Education level | ||||
| Some or all high school | 18 | |||
| Some college | 9 | |||
| College or trade school completed | 53 | |||
| Undergraduate university completed | 125 | |||
| Graduate degree completed | 93 | |||
Consistent with previous Canadian studies, milk was collected by the study participants, who were asked to hand express their milk (fore- and hindmilk). If participants experienced difficulty with hand expression, a Medela® (Medela International, Zug, Switzerland) manual breast pump was provided, along with instructions for either manually expressing or using the breast pump to collect the milk. Milk samples were collected between two and 10 weeks following delivery of the babies, recognizing that milk was to be analyzed for a variety of different analytes/classes of compounds, 250 mL were requested of participants (125 mL in glass containers, 125 mL in plastic containers). In general, 250 mL were received from participants, although occasionally, the volumes received were lower. Aliquots of the samples for PBDE/HBCD analysis were collected into 500 mL wide-mouth amber I-CHEM® glass jars with fluoropolymer resin-liner polypropylene closure (Thermo Fisher Scientific, Rockwood, TN, USA). Participant instructions for collection allowed for them to express the milk over a period of time, and keep it in their refrigerator
Extraction and clean-up
Sample preparation followed the protocol for analysis of PBDEs and HBCD described previously for the other persistent organics (e.g., polychlorinated biphenyls)[48]. Briefly, samples (~25 g) were transferred into Erlenmeyer flasks and surrogate standards were added to the samples (13C PBDEs 15, 28, 47, 99, 153, 154, 183 and 209; 13C α-, β- and γ-HBCD) (Cambridge Isotope Laboratories, Andover, MA, USA). An aliquot of each sample (5%) was taken for gravimetric determination of lipid content in each sample. Prior to extraction by homogenizing in 2:1 (v/v) acetone: hexane (Residue analysis grade, EMD; Ottawa, ON, Canada), the samples were set aside on the lab bench for approximately 30 min following the addition of surrogate standards. Lipids present were digested by washing extracts with sequential aliquots of concentrated sulphuric acid (ACS grade, EMD; Ottawa, ON, Canada), followed by drying the extracts by passing them through anhydrous sodium sulphate. Column chromatography was performed using activated acidified silica gel, activated Florisil (60-100 mesh) (Fisher Scientific; Ottawa, ON, Canada), and carbon {Carbopack C (60-80 mesh) [Supelco (Bellefonte, PA)]} in series to clean up and fractionate the extracts[21]. Following clean-up, the extracts were evaporated just to dryness, reconstituted in 10 µL of the performance standard and placed into v-vials for gas chromatographic-high resolution mass spectrometric analysis of PBDEs.
Once PBDE analyses were completed, sample extracts were concentrated just to dryness using a gentle stream of nitrogen and diluted with the performance standard, deuterated d18 HBCD (α-, β- and γ-), in
Analysis
PBDE analysis
A Waters Autospec Ultima high resolution mass spectrometer (Waters Corporation, Mississauga, ON) operating at 10,000 resolution, coupled to an Agilent 6890 gas chromatograph (Agilent Technologies, Mississauga, ON), was used for all PBDE analyses (15, 17, 28, 37, 47, 66, 71, 75, 77, 85, 99, 100, 119, 126, 138, 153, 154, 160, 181, 183, 190, 205, 209). Separation of 23 congeners was achieved using a DB-5MS column
HBCD analysis
HBCD analyses were performed using a Waters Acquity ultra-high pressure liquid chromatograph I-Class coupled to a Waters Xevo TQ-XS triple quadrupole mass spectrometer with electrospray ionization operating in the negative ion detection mode. A 2.1 mm × 150 mm Kinetex C18, 2.6 µm column (Phenomenex, USA) was used to separate the three HBCD isomers considered. Mobile phase A (water) and acetonitrile: methanol (2:1) (mobile phase B) were used to separate α-, β- and γ-HBCD using gradient elution, starting with 60% mobile phase B for 1 min, transitioning to 80% mobile phase B by 4 min, holding until 11 min and increasing to 85% mobile phase B by 14 min and remaining there until 16 min, before returning to the starting conditions by 16.1 min, where it was allowed to stabilize until 22 min. The flow rate was 0.175 mL·min-1 and the column temperature was set to 25 °C to support complete resolution of the d18, 13C- and native HBCD isomers. The capillary and cone voltage were -2.5 kV and 20 V, respectively. The source temperature was set to 150 °C, while the desolvation temperature was 400 °C. The desolvation gas flow was 1,000 L·h-1, with the cone gas flow set to 170 L·h-1. Argon was used as the collision gas at a flow rate of 0.15 mL·min-1. The transitions monitored for native, 13C, and d18 HBCD isomers were: 639 → 79, 641 → 79, 641 → 81, and 643 → 81 (native); 651 → 79, 653 → 79, 653 → 81, and 655 → 81 (13C surrogates); and
Quality assurance/quality control
Two method blanks prepared using reagents alone, following the same protocol as for the unknown samples, were included with each set of samples to allow for the removal of laboratory background concentrations. Additionally, either one or two standard reference materials of human milk containing known concentrations of PBDEs [standard reference material (SRM) 1953 (unfortified), SRM 1954 (fortified)] were included with each set of samples prepared for analysis. For those sets where a single SRM was included, an internal sample of human milk that has been used in the laboratory as an internal quality control (QC) over time was also included. PBDE concentrations and patterns determined in the SRMs were as anticipated, with concentrations generally within two standard deviations of the expected values. The internal QC sample PBDE concentrations were generally within one standard deviation of the mean values.
Although similar certified reference materials with known HBCD concentrations were not available during the work, the HBCD concentrations in the SRMs were determined. Only α-HBCD was frequently detected in both the unfortified and fortified milk, with β- and γ-HBCD generally present below the limits of detection. Concentrations of α-HBCD in the SRMs were within two standard deviations of the mean concentration, similar to the results from testing the laboratory internal QC sample.
Average surrogate recoveries ranged from 35.0% (13C PBDE 15) to 93.3% (13C PBDE 100) in the human milk samples analyzed. HBCD average surrogate recoveries ranged from 68.8% to 83.5% (β-HBCD and γ-HBCD, respectively), while the average α-HBCD recovery was 77.1%. All concentrations in the samples were corrected for recovery.
In addition, representative breast pumps, similar to those sent to participants were examined for background PBDE and HBCD levels. Testing was performed by rinsing the pumps with purified water and the rinse water was prepared for analysis as samples alongside samples of purified water. Any detectable concentrations observed in the pump rinses were considered to be a result of the water used for this testing.
Limits of detection
Instrumental limits of detection (LOD) were determined for each PBDE based on a 3:1 signal to background noise ratio for each sample individually and method detection limits (MDLs) were then calculated to account for variation in instrument sensitivity and sample sizes. Average PBDE MDLs ranged from
Statistical analysis
Statistical analyses were performed using SigmaPlot 12.5 (Systat Software Inc.). For those compounds below the MDL in any sample, the analyte concentrations were adjusted to 1/2 MDL (i.e., MDL/2) established for the samples prior to initiating data summary and statistical analysis. In addition to developing descriptive statistics of these data, they were also studied to consider whether concentrations were related to some of the personal characteristics of the participants (e.g., age, number of children the participant had prior to this pregnancy/parity). The concentration data were not normally distributed; therefore, one-way analysis of variance (ANOVA) tests were performed using Kruskal-Wallis ANOVA on ranks. Relationships were considered statistically significant if the P-value was less than 0.05.
RESULTS AND DISCUSSION
The lipid content determined in the human milk samples ranged from 0.75% to 7.84%, with mean and median lipid concentrations of 3.26% and 3.22%, respectively. PBDEs and HBCD are lipophilic compounds; therefore, results are reported on a lipid-adjusted basis throughout this manuscript. While PBDEs were detected in all 298 of the milk samples collected from across Canada, HBCD was detected in 94.0% (n = 280) of the samples. PBDE 47 was the dominant contributor to ΣPBDE concentrations, followed by 153 > 99 > 100 > 28 > 209. Consistent with previous HBCD concentrations determined in Canadian serum[30], α-HBCD was the predominant isomer (93.3%) in human milk samples, with β-HBCD and γ-HBCD detected in 9.7% and 28.5% of the samples, respectively.
Concentrations
Although PBDEs were present at detectable concentrations in all 298 of the Canadian human milk samples analyzed, three congeners were observed in relatively few samples. PBDEs 126 and 205 were observed in only two samples (< 1%), while PBDE 181 was present at detectable concentrations in 22 samples (7.4%). As a result of the very low detection rate of these three congeners, they have been removed from the data analysis and calculation of total PBDE concentrations.
ΣPBDE (Σ of 20 congeners: 15, 17, 28, 37, 47, 66, 71, 75, 77, 85, 99, 100, 119, 138, 153, 154, 160, 183, 190 and 209) concentrations ranged from 0.071 to 267 ng·g-1 lipid in the human milk from the MIREC study
Figure 2. Selected PBDE congeners and ΣPBDE (Σ20 congeners) concentrations (ng·g-1 lipid) in human milk from the MIREC study (n = 298). Box indicates 25th, 50th (median), and 75th percentiles. Points indicate data outside of the 10th and 90th percentiles. PBDE: Polybrominated diphenyl ether; MIREC: Maternal-Infant Research on Environmental Chemicals.
Figure 3. α-, β- γ-HBCD and Σ(α-, β-, γ-) HBCD concentrations (ng·g-1 lipid) in human milk samples. Box indicates 25th, 50th (median), and 75th percentiles. Points indicate data outside of the 10th and 90th percentiles. HBCD: Hexabromocyclododecane.
Concentrations (ng·g-1 lipid) of selected PBDE congeners, total PBDEs (Σ20 congeners) and α-, β- and γ-HBCD and Σ (α-, β-, γ-) HBCD in human milk (2008-2011)
| Congener | Detection frequency (%) | Minimum | Maximum | Median | Geometric mean | Arithmetic mean | Standard deviation |
| PBDE 28 | 100 | 0.0001 | 7.45 | 0.550 | 0.566 | 0.835 | 0.901 |
| PBDE 47 | 100 | 0.005 | 145 | 7.44 | 7.97 | 13.6 | 19.6 |
| PBDE 99 | 100 | 0.006 | 55.6 | 1.09 | 1.28 | 2.83 | 6.14 |
| PBDE 100 | 100 | 0.001 | 20.3 | 1.17 | 1.27 | 2.29 | 3.17 |
| PBDE 153 | 99.3 | < MDL (0.004) | 57.5 | 2.01 | 2.41 | 5.03 | 8.22 |
| PBDE 154 | 99.3 | < MDL (0.003) | 1.93 | 0.077 | 0.084 | 0.157 | 0.264 |
| PBDE 183 | 98.0 | < MDL (0.001) | 2.78 | 0.043 | 0.043 | 0.082 | 0.201 |
| PBDE 209 | 70.5 | < MDL (0.001) | 85.3 | 0.083 | 0.071 | 0.635 | 5.08 |
| ΣPBDE1 | 100 | 0.071 | 267 | 15.6 | 16.8 | 26.5 | 33.2 |
| α-HBCD | 93.3 | < MDL (0.004) | 7.26 | 0.271 | 0.247 | 0.425 | 0.655 |
| β-HBCD | 9.7 | < MDL (0.001) | 0.801 | 0.006 | 0.008 | 0.024 | 0.084 |
| γ-HBCD | 28.5 | < MDL (0.001) | 6.39 | 0.010 | 0.012 | 0.097 | 0.454 |
| ΣHBCD2 | 94.0 | < MDL (0.010) | 7.66 | 0.303 | 0.316 | 0.547 | 0.871 |
PBDE 209 was observed in the serum of Canadian women of childbearing age as part of the CHMS work, although it had not been reported by our laboratory in human samples prior to that time. Although PBDE 209 was detected in 70.5% of the samples measured, the maximum PBDE 209 concentration observed in this work (85.3 ng·g-1 lipid) exceeded the maximum concentration of other congeners that generally contributed more to ΣPBDE concentrations (e.g., 99, 100, Table 2). PBDE 209 was not detected in all of the milk samples as part of the present study; when present, it contributed ≈ 3.3% to ΣPBDE concentrations.
Relationships between compounds
Strong Spearman correlations were found between the concentrations of each of the dominant, lower brominated PBDE congeners (tri- through penta-: 28, 47, 99 and 100) observed in Canadian human milk. While the concentrations of these lower brominated congeners were strongly correlated with each other
Spearman correlations between individual predominant contributing PBDE congeners in Canadian human milk (P values < 0.001 unless indicated)
| Congener | 47 | 99 | 100 | 153 | 209 |
| PBDE 28 | 0.922 | 0.791 | 0.832 | 0.353 | 0.074; P = 0.200 |
| PBDE 47 | 0.920 | 0.907 | 0.389 | 0.061; P = 0.292 | |
| PBDE 99 | 0.858 | 0.401 | 0.075; P = 0.197 | ||
| PBDE 100 | 0.592 | 0.085; P = 0.142 | |||
| PBDE 153 | 0.039; P = 0.503 |
ΣHBCD concentrations in the human milk analyzed were not correlated with ΣPBDE concentrations (r = 0.051, P = 0.377). This observation may be a result of HBCD being used primarily in insulation for buildings (e.g., polystyrene)[5], rather than in electronics and other consumer products.
Impact of maternal characteristics
Neither ΣPBDE (r = 0.019, P = 0.739) nor ΣHBCD (r = 0.084, P = 0.148) concentrations were correlated with maternal age in the human milk samples analyzed. This differs from legacy polychlorinated biphenyls (PCBs), where relationships between maternal age and chemical concentration in human milk (r = 0.385,
An ANOVA was performed to examine the relationship between ΣPBDE and ΣHBCD concentrations with characteristics of the participants who provided milk for these analyses [e.g., parity, pre-pregnancy body mass index (BMI), and education level]. A woman’s parity (1, 2, 3, 4+) impacted neither median ΣPBDE concentrations (P = 0.483) nor ΣHBCD concentrations (P = 0.366). This lack of relationship between parity and median concentrations is similarly consistent with the results of the NHFR concentrations in samples from this cohort (P = 0.777)[49]. Pre-pregnancy BMI (< 20, 20-25, > 25-30, > 30-35, > 35, no information provided) was not a factor that impacted ΣPBDE (P = 0.372) or ΣHBCD (P = 0.073) concentrations. The education level of the participants was broken down into a variety of categories [having some/completing high school, having earned the diploma, having taken some college classes, having earned college or trade school diploma, having earned an undergraduate university degree, and having earned a graduate degree (Master, Ph.D.)]. The ΣPBDE and ΣHBCD concentrations were not significantly impacted by this factor
Temporal trends
Both of the BFRs examined in the present study have been previously measured in Canadian human milk. The prior work from our laboratory did not include PBDE 209 because it was not consistently present and, at the time, it was thought to be a minor contributor to overall PBDE concentrations[28]. Total PBDE concentrations previously were reported as a total of seven congeners (Σ28, 47, 99, 100, 153, 154, 183) with concentrations ranging from 0.552 to 596 ng·g-1 lipid (median 2.99 ng·g-1 lipid; geometric mean 3.54 ng·g-1 lipid) for samples collected from across southern Canada in 1992 and from 0.841 to 956 ng·g-1 lipid (median 22.1 ng·g-1 lipid; geometric mean 25.2 ng·g-1 lipid) for the 2002 collection[28]. Median/geometric mean ΣPBDE concentrations (19.9 and 21.1 ng·g-1 lipid, respectively) in human milk collected from Hamilton, Ontario, in 2005 indicated that PBDE concentrations had stabilized[28]. The sum of concentrations for these same seven congeners in the present study, 2008-2011 collection, as part of the MIREC study, ranged from 0.473 to
While ΣPBDE concentrations appear to be declining, not all individual congeners follow this trend. A comparison of the previous data from our laboratory (1992, 2002 and 2005) with the data from the present work does show similar patterns for several of the congeners considered. The lowest median concentrations of PBDE 47, 99, 100, and 154 were observed in 1992, followed by increased concentrations in 2002, and appeared to stabilize by 2005, followed by a decline observed in the present work [Table 4]. Median PBDE 28 concentrations increased between 1992 and 2002, reaching the highest concentration observed in 2005, followed by a decline, while a comparison of the median PBDE 183 concentrations over time did not show a clear trend. In contrast to the other congeners investigated, the median PBDE 153 concentration determined in human milk from the present study was higher than the values reported in 1992, 2002 or 2005, although the results from 2002 and 2005 suggested the beginning of a decline [Table 4]. This variability in temporal trends among PBDE congeners is consistent with what has been reported for human milk collected in Sweden[50], although the pattern observed is similar to that observed in the serum of Swedish mothers where a decrease in PBDEs 47, 99, and 100 was observed and an increase in PBDE 153 was determined[51].
Median PBDE concentrations of select individual congeners in Canadian human milk over time, previous data taken from Ryan and Rawn (2014)[28]
| Compound | Median concentration (ng·g-1 lipid) | |||
| 1992 | 2002 | 2005 | Present study | |
| PBDE 28 | 0.108 | 0.948 | 1.40 | 0.550 |
| PBDE 47 | 1.42 | 12.9 | 12.1 | 7.44 |
| PBDE 99 | 0.507 | 3.30 | 2.55 | 1.09 |
| PBDE 100 | 0.228 | 1.91 | 1.52 | 1.17 |
| PBDE 153 | 0.304 | 1.32 | 1.11 | 2.01 |
| PBDE 154 | 0.042 | 0.174 | 0.147 | 0.077 |
| PBDE 183 | 0.173 | 0.121 | 0.172 | 0.043 |
An additional study that measured PBDE concentrations (Σ four congeners: 47, 99, 100, and 153) in human milk from two discrete communities in Canada (Kingston, Ontario in 2003/2004 and Sherbrooke, Québec in 2008/2009) has also been reported[52]. PBDE concentrations ranged from 2.7 to 108 ng·g-1 lipid and 2.9 to
HBCD was determined previously in human milk from one community in northern Canada (Nunavik) at two time points (1989-1991 and 1996-1999) and one location in southern Canada (Hamilton, Ontario) in 2005[28]. The early HBCD analysis of milk from Nunavik measured α-HBCD alone [0.1-0.6 ng·g-1 lipid (1989-1991) and 0.1-13.3 ng·g-1 lipid (1996-1999)][28]. In contrast, the analysis of samples collected from Hamilton in 2005 involved the determination of α-, β- and γ- isomers. ΣHBCD concentrations in those samples ranged from 0.1-28.2 ng·g-1 lipid, with median and geometric mean concentrations of 0.7 and 0.6 ng·g-1 lipid, respectively. The results of the pan-Canadian samples collected in the present study ranged from below the method detection limits to 7.66 ng·g-1 lipid [median 0.303 ng·g-1 lipid (303 pg·g-1 lipid)]. These data suggest that HBCD concentrations declined in Canadian human milk from the early investigations into HBCD concentration to the collection period covered in the present study, similar to the declining temporal trend for PBDEs.
Comparison with international studies
PBDE concentrations remained elevated in Canadian human milk relative to other countries during the sample collection period. This observation is consistent with the conclusions of a systematic review of global data for these compounds in human milk collected between 2000 and 2012[54]. European countries continue to have lower PBDE concentrations in human milk [Table 5] in comparison to Canadian results. South American PBDE concentrations are similarly low relative to the concentrations reported in North America [Table 5]. The selection of representative congeners used for the determination of ΣPBDE concentrations, however, makes the direct comparison between regions challenging. While some areas of Asia have lower PBDE concentrations in human milk relative to Canada, other regions show elevated levels. HBCD concentrations in Canadian human milk seem to be within the range reported internationally [Table 6]. In contrast to the PBDEs, HBCD concentrations in human milk collected from some European countries are elevated over concentrations reported in the present study, where collection occurred between 2008-2011.
International PBDE concentrations (ng·g-1 lipid) reported in human milk
| Country | n | Range | Median | Congeners included | Year(s) of collection | Ref. |
| North America | ||||||
| Canada | 298 | 0.473-257 | 14.6 | 28, 47, 99, 100, 153, 154, 183 | 2008-2011 | Current study |
| Canada | 298 | 0.071-267 | 15.6 | Σ20 PBDE congeners | 2008-2011 | Current study |
| USA | 31 | 4.79-18.6 | 15, 28, 47, 99, 153 | 2016-2020 | Jung et al., 2023[55] | |
| 10 | 8.78 (non-firefighters) | |||||
| 21 | 9.89 (firefighters) | |||||
| USA | 50 | 1.46-1,170 | 15.0 | 28, 47, 85, 99, 100, 139, 153, 154, 183 | 2019 | Schreder et al., 2023[56] |
| South America | ||||||
| Brazil | 200 | 0.14-6.5 (wet weight, ww) | 2.33 (geometric mean, ww) | 28, 47, 99, 100, 153, 154, 183 | 2019-2020 | Souza et al., 2022[57] |
| Colombia | 60 | 0.33-16.4 | 1.28 | 28, 47, 99, 100, 153, 154, 183 | 2014-2015 | Torres-Moreno et al., 2023[58] |
| Europe Scandinavia | ||||||
| Denmark | 438 | 1.22-111 | 4.90 | 28, 47, 99, 100, 153, 154, 183 | 1997-2002 | Antignac et al., 2016[31] |
| Finland | 22 | 1.47-19.0 | 5.19 | 28, 47, 99, 100, 153, 154, 183 | 1997-2002 | Antignac et al., 2016[31] |
| Sweden | 198 | 0.33-73 | 1.2; 1.3; 1.4; 1.8 (different locations) | 47 99 100 153 | 2000-2004 | Glynn et al., 2011[25] |
| < 0.1-17 | 0.3, 0.2, 0.2, 0.5 | |||||
| < 0.08-18 | 0.3, 0.2, 0.3, 0.4 | |||||
| 0.2-8.0 | 0.6, 0.5, 0.6, 0.7 | |||||
| Other | ||||||
| Czech Republic | 231 | 0.05-0.99 (PBDE 47) 0.15-1.31 (PBDE 99) 0.15-0.79 (PBDE 153) (5-95 percentile) | 0.15, 0.19 (2 locations, PBDE 47) Not calculated (PBDE 99) 0.32 (1 location only calculated, PBDE 153) | 47, 99, 153 individually | 2019-2021 | Parizek et al., 2023[59] |
| France | 96 | 0.45-15.3 | 1.47 | 28, 47, 99, 100, 153, 154, 183 | 2011-2014 | Antignac et al., 2016[31] |
| Ireland | 161 | 1.7-24 | 2.5 | 28, 47, 99, 100, 153, 154, 183, 209 | 2016-2018 | Wemken et al., 2020[32] |
| Asia | ||||||
| China (Shanghai) | 36 | 7.9-2,980 (pg·g-1 ww) | 32 pg·g-1 ww | 28, 47, 99, 100, 153, 154, 183, 209 | 2018-2019 | Lin et al., 2022[60] |
| China | 105 | 0.458-157 | 1.1 | 28, 47, 99, 100, 153, 154, 183, 209 | 2018 | Zhao and Shi, 2021[33] |
| Japan | 40 | < 0.2-69 | 1.5 | 28, 47, 99, 100, 153, 154 | 2005-2006 | Fujii et al., 2012[61] |
| Philippines | 30 | 0.61-11 | 2.6 | 15, 28, 47, 99, 100, 153, 154, 183, 196, 197, 207, 209 | 2008 | Malarvannan et al., 2013b[26] |
| Vietnam | 33 | 0.24-250 | 0.57, 0.73, 2.3, 3.2, 84 (by site) | 15, 28, 47, 99, 100, 153, 154, 183, 196, 197, 206, 207, 209 | 2007 | Tue et al., 2010[23] |
| Middle East | ||||||
| Saudi Arabia | 75 | 0.2-3.6 | 2.8 (quartile 1-3) | 47, 99, 153, 209, identified | Not specified | Yakout et al., 2023[62] |
International HBCD concentrations (ng·g-1 lipid) reported in human milk
| Country | n | Range | Median | HBCD isomers included | Year(s) of Collection | Ref. |
| North America | ||||||
| Canada | 298 | 0.010-7.66 | 0.303 | Σα-, β-, γ- | 2008-2011 | Current study |
| Europe Scandinavia | ||||||
| Denmark | 435 | 0.02-28.7 | 0.31 | α- | 1997-2002 | Antignac et al., 2016[31] |
| Finland | 22 | 0.03-2.19 | 0.31 | α- | 1997-2002 | Antignac et al., 2016[31] |
| Sweden | 178 | 0.09-10 | 0.3, < 0.4, 0.4, 0.4 (by region) | Not specified (GC-MS analysis) | 2000-2004 | Glynn et al., 2011[25] |
| Other | ||||||
| Czech Republic | 231 | 0.25-17.1 (ng·mL-1) | Not calculated | α- | 2019-2021 | Parizek et al., 2023[59] |
| France | 41 | 0.22-4.21 | 0.56 | α- | 2011-2014 | Antignac et al., 2016[31] |
| Ireland | 161 | 0.83-3.6 | 1.8 | Σα-, β-, γ- | 2016-2018 | Wemken et al., 2020[32] |
| Asia | ||||||
| China | 105 | 2.84-196 | 7.64 | Σα-, β-, γ- | 2018 | Zhao and Shi, 2021[33] |
| Philippines | 30 | < 0.01-0.91 | 0.19 | Σα-, β-, γ- | 2008 | Malarvannan et al., 2013b[26] |
| Vietnam, some individuals involved in recycling | 33 | 0.07-7.6 | 0.33, 0.42, 0.38, 0.36, 2.0 (by site) | Σα-, β-, γ- | 2007 | Tue et al., 2021[23] |
CONCLUSIONS
PBDE concentrations declined in Canadian human milk between the early 2000s and the collection period of the present study (2008-2011). Maximum HBCD concentrations determined in the present study were lower than the previous maximum values measured in Canadian human milk. Concentrations of these BFRs in human milk were not correlated with maternal age. Parity (1, 2, 3, 4+) and pre-pregnancy BMI (< 20, 20-25, > 25-30, > 30-35, > 35) did not significantly impact PBDE levels (P = 0.483, P = 0.372, parity and pre-pregnancy BMI, respectively) or HBCD concentrations (P = 0.366, P = 0.073, parity and pre-pregnancy BMI, respectively). Maternal education level similarly did not affect PBDE (P = 0.878) or HBCD (P = 0.745) concentrations in the human milk from the MIREC study. Ongoing monitoring of these BFRs is required to establish whether a continued decrease in concentration over time is occurring in Canadian human milk, following regulatory action on a global scale.
DECLARATIONS
Acknowledgements
The authors thank the participants in the study and their families. The authors also acknowledge the MIREC Study Group, in particular the site investigators, in addition to their field staff and the coordinating centre. The authors thank Sue Quade for carefully reviewing the manuscript and tracking reference formatting.
Authors’ contributions
Made substantial contributions to the conception and design of the study and performed data analysis and interpretation: Rawn DFK, Arbuckle TE
Performed data acquisition, as well as providing administrative, technical, and material support: Sadler AR, Casey VA, Breton F, Sun WF, Feng SY
Availability of data and materials
The data that has been used is confidential.
Financial support and sponsorship
MIREC was funded by Health Canada’s Chemicals Management Plan, the Canadian Institute of Health Research (grant MOP-81285), and the Ontario Ministry of the Environment.
Conflicts of interest
All authors declared that there are no conflicts of interest.
Ethical approval and consent to participate
Participants consented to participate in the study and ethics Board approval was obtained from Health Canada’s ethics board, the ethics board of the MIREC coordination centre at CHU Sainte Justine, Québec, and the ethics board at each of the research centres (Vancouver, Edmonton, Winnipeg, Hamilton, Kingston, Ottawa, Sudbury, Toronto, Montréal and Halifax) (REB 2006-027H).
Consent for publication
Not applicable.
Copyright
© The Author(s) 2024.
REFERENCES
1. Alaee M, Arias P, Sjödin A, Bergman A. An overview of commercially used brominated flame retardants, their applications, their use patterns in different countries/regions and possible modes of release. Environ Int 2003;29:683-9.
2. Guardia MJ, Hale RC, Harvey E. Detailed polybrominated diphenyl ether (PBDE) congener composition of the widely used penta-, octa-, and deca-PBDE technical flame-retardant mixtures. Environ Sci Technol 2006;40:6247-54.
3. Rahman F, Langford KH, Scrimshaw MD, Lester JN. Polybrominated diphenyl ether (PBDE) flame retardants. Sci Total Environ 2001;275:1-17.
5. Alshemmari H. Inventories and assessment of POPs in the State of Kuwait as a basis for Stockholm Convention implementation. Emerg Contam 2021;7:88-98.
6. Li Y, Chen L, Wen ZH, et al. Characterizing distribution, sources, and potential health risk of polybrominated diphenyl ethers (PBDEs) in office environment. Environ Pollut 2015;198:25-31.
7. Sun J, Wang Q, Zhuang S, Zhang A. Occurrence of polybrominated diphenyl ethers in indoor air and dust in Hangzhou, China: level, role of electric appliances, and human exposure. Environ Pollut 2016;218:942-9.
8. Betts KS. Hand-me-down hazard: flame retardants in discarded foam products. Environ Health Perspect 2015;123:A56-63.
9. Cao Z, Xu F, Li W, et al. Seasonal and particle size-dependent variations of hexabromocyclododecanes in settled dust: implications for sampling. Environ Sci Technol 2015;49:11151-7.
10. Ding N, Wang T, Chen SJ, et al. Brominated flame retardants (BFRs) in indoor and outdoor air in a community in Guangzhou, a megacity of southern China. Environ Pollut 2016;212:457-63.
11. Zheng X, Xu F, Chen K, et al. Flame retardants and organochlorines in indoor dust from several e-waste recycling sites in South China: composition variations and implications for human exposure. Environ Int 2015;78:1-7.
12. Iwegbue CM, Eyengho SB, Egobueze FE, et al. Polybrominated diphenyl ethers and polychlorinated biphenyls in indoor dust from electronic repair workshops in southern Nigeria: implications for onsite human exposure. Sci Total Environ 2019;671:914-27.
13. Birnbaum LS, Staskal DF. Brominated flame retardants: cause for concern? Environ Health Perspect 2004;112:9-17.
14. Jaspers V, Covaci A, Maervoet J, et al. Brominated flame retardants and organochlorine pollutants in eggs of little owls (Athene noctua) from Belgium. Environ Pollut 2005;136:81-8.
15. Law K, Halldorson T, Danell R, et al. Bioaccumulation and trophic transfer of some brominated flame retardants in a Lake Winnipeg (Canada) food web. Environ Toxicol Chem 2006;25:2177-86.
16. Ueno D, Isobe T, Ramu K, et al. Spatial distribution of hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs) and organochlorines in bivalves from Japanese coastal waters. Chemosphere 2010;78:1213-9.
17. Polder A, Venter B, Skaare JU, Bouwman H. Polybrominated diphenyl ethers and HBCD in bird eggs of South Africa. Chemosphere 2008;73:148-54.
18. Shaw SD, Berger ML, Brenner D, Kannan K, Lohmann N, Päpke O. Bioaccumulation of polybrominated diphenyl ethers and hexabromocyclododecane in the northwest Atlantic marine food web. Sci Total Environ 2009;407:3323-9.
19. McKinney MA, Letcher RJ, Aars J, et al. Flame retardants and legacy contaminants in polar bears from Alaska, Canada, East Greenland and Svalbard, 2005-2008. Environ Int 2011;37:365-74.
20. Vorkamp K, Rigét FF, Bossi R, Dietz R. Temporal trends of hexabromocyclododecane, polybrominated diphenyl ethers and polychlorinated biphenyls in ringed seals from East Greenland. Environ Sci Technol 2011;45:1243-9.
21. Rawn DF, Sadler A, Quade SC, et al. Brominated flame retardants in Canadian chicken egg yolks. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2011;28:807-15.
22. Sørmo EG, Salmer MP, Jenssen BM, et al. Biomagnification of polybrominated diphenyl ether and hexabromocyclododecane flame retardants in the polar bear food chain in Svalbard, Norway. Environ Toxicol Chem 2006;25:2502-11.
23. Tue NM, Sudaryanto A, Minh TB, et al. Accumulation of polychlorinated biphenyls and brominated flame retardants in breast milk from women living in Vietnamese e-waste recycling sites. Sci Total Environ 2010;408:2155-62.
24. Kalantzi OI, Geens T, Covaci A, Siskos PA. Distribution of polybrominated diphenyl ethers (PBDEs) and other persistent organic pollutants in human serum from Greece. Environ Int 2011;37:349-53.
25. Glynn A, Lignell S, Darnerud PO, et al. Regional differences in levels of chlorinated and brominated pollutants in mother’s milk from primiparous women in Sweden. Environ Int 2011;37:71-9.
26. Malarvannan G, Isobe T, Covaci A, Prudente M, Tanabe S. Accumulation of brominated flame retardants and polychlorinated biphenyls in human breast milk and scalp hair from the Philippines: levels, distribution and profiles. Sci Total Environ 2013;442:366-79.
27. Malarvannan G, Dirinck E, Dirtu AC, et al. Distribution of persistent organic pollutants in two different fat compartments from obese individuals. Environ Int 2013;55:33-42.
28. Ryan JJ, Rawn DF. The brominated flame retardants, PBDEs and HBCD, in Canadian human milk samples collected from 1992 to 2005; concentrations and trends. Environ Int 2014;70:1-8.
29. Rawn DF, Gaertner DW, Weber D, Curran IH, Cooke GM, Goodyer CG. Hexabromocyclododecane concentrations in Canadian human fetal liver and placental tissues. Sci Total Environ 2014;468-9:622-9.
30. Rawn DFK, Ryan JJ, Sadler AR, et al. Brominated flame retardant concentrations in sera from the Canadian Health Measures Survey (CHMS) from 2007 to 2009. Environ Int 2014;63:26-34.
31. Antignac JP, Main KM, Virtanen HE, et al. Country-specific chemical signatures of persistent organic pollutants (POPs) in breast milk of French, Danish and Finnish women. Environ Pollut 2016;218:728-38.
32. Wemken N, Drage DS, Cellarius C, et al. Emerging and legacy brominated flame retardants in the breast milk of first time Irish mothers suggest positive response to restrictions on use of HBCDD and Penta- and Octa-BDE formulations. Environ Res 2020;180:108805.
33. Zhao X, Shi Z. Legacy brominated flame retardants in human milk from the general population in Beijing, China: biomonitoring, temporal trends from 2011 to 2018, and nursing infant’s exposure assessment. Chemosphere 2021;285:131533.
34. Meironyté D, Norén K, Bergman A. Analysis of polybrominated diphenyl ethers in Swedish human milk. a time-related trend study, 1972-1997. J Toxicol Environ Health A 1999;58:329-41.
35. Norén K, Meironyté D. Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20-30 years. Chemosphere 2000;40:1111-23.
36. Meironyté Guvenius D, Aronsson A, Ekman-Ordeberg G, Bergman A, Norén K. Human prenatal and postnatal exposure to polybrominated diphenyl ethers, polychlorinated biphenyls, polychlorobiphenylols, and pentachlorophenol. Environ Health Perspect 2003;111:1235-41.
37. Daniels JL, Pan IJ, Jones R, et al. Individual characteristics associated with PBDE levels in U.S. human milk samples. Environ Health Perspect 2010;118:155-60.
38. Toms LML, Guerra P, Eljarrat E, et al. Brominated flame retardants in the Australian population: 1993-2009. Chemosphere 2012;89:398-403.
39. Law RJ, Covaci A, Harrad S, et al. Levels and trends of PBDEs and HBCDs in the global environment: status at the end of 2012. Environ Int 2014;65:147-58.
40. Feiteiro J, Mariana M, Cairrão E. Health toxicity effects of brominated flame retardants: from environmental to human exposure. Environ Pollut 2021;285:117475.
41. Renzelli V, Gallo M, Morviducci L, et al. Polybrominated diphenyl ethers (PBDEs) and human health: effects on metabolism, diabetes and cancer. Cancers 2023;15:4237.
42. Darnerud PO, Eriksen GS, Jóhannesson T, Larsen PB, Viluksela M. Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology. Environ Health Perspect 2001;109 Suppl 1:49-68.
44. World Health Organization. Infant and young child feeding. 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/infant-and-young-child-feeding. [Last accessed on 5 Jun 2024].
45. Victora CG, Bahl R, Barros AJD, et al; Lancet Breastfeeding Series Group. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet 2016;387:475-90.
46. Arbuckle TE, Fraser WD, Fisher M, et al. Cohort profile: the maternal-infant research on environmental chemicals research platform. Paediatr Perinat Epidemiol 2013;27:415-25.
47. Statistics Canada. Canadian Community Health Survey - annual component (CCHS). Available from: https://www23.statcan.gc.ca/imdb/p2SV.pl?Function=getSurvey&Id=144170#a2. [Last accessed on 5 Jun 2024].
48. Rawn DFK, Sadler AR, Casey VA, et al. Dioxins/furans and PCBs in Canadian human milk: 2008-2011. Sci Total Environ 2017;595:269-78.
49. Rawn DFK, Corrigan C, Ménard C, Sun WF, Breton F, Arbuckle TE. Novel halogenated flame retardants in Canadian human milk from the MIREC study (2008-2011). Chemosphere 2024;350:141065.
50. Lignell S, Aune M, Darnerud PO, Cnattingius S, Glynn A. Persistent organochlorine and organobromine compounds in mother’s milk from Sweden 1996-2006: compound-specific temporal trends. Environ Res 2009;109:760-7.
51. Darnerud PO, Lignell S, Aune M, et al. Time trends of polybrominated diphenylether (PBDE) congeners in serum of Swedish mothers and comparisons to breast milk data. Environ Res 2015;138:352-60.
52. Siddique S, Xian Q, Abdelouahab N, et al. Levels of dechlorane plus and polybrominated diphenylethers in human milk in two Canadian cities. Environ Int 2012;39:50-5.
53. Secretariat of the Stockholm Convention. The 12 initial POPs under the Stockholm Convention. Available from: http://chm.pops.int/TheConvention/ThePOPs/The12InitialPOPs/tabid/296/Default.aspx. [Last accessed on 5 Jun 2024].
54. Zhang J, Chen L, Xiao L, Ouyang F, Zhang QY, Luo ZC. Polybrominated diphenyl ether concentrations in human breast milk specimens worldwide. Epidemiology 2017;28 Suppl 1:S89-97.
55. Jung AM, Beitel SC, Gutenkunst SL, et al. Excretion of polybrominated diphenyl ethers and AhR activation in breastmilk among firefighters. Toxicol Sci 2023;192:223-32.
56. Schreder E, Zheng G, Sathyanarayana S, Gunaje N, Hu M, Salamova A. Brominated flame retardants in breast milk from the United States: first detection of bromophenols in U.S. breast milk. Environ Pollut 2023;334:122028.
57. Souza MCO, Devóz PP, Ximenez JPB, Bocato MZ, Rocha BA, Barbosa F. Potential health risk to Brazilian infants by polybrominated diphenyl ethers exposure via breast milk intake. Int J Environ Res Public Health 2022;19:11138.
58. Torres-Moreno AC, Mejia-Grau K, Puente-DelaCruz L, et al. Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) in human breast milk from Colombia: a probabilistic risk assessment approach. Chemosphere 2023;339:139597.
59. Parizek O, Gramblicka T, Parizkova D, et al. Assessment of organohalogenated pollutants in breast milk from the Czech Republic. Sci Total Environ 2023;871:161938.
60. Lin Y, Feng C, Le S, et al. Infant exposure to PCBs and PBDEs revealed by hair and human milk analysis: evaluation of hair as an alternative biomatrix. Environ Sci Technol 2022;56:15912-9.
61. Fujii Y, Ito Y, Harada KH, Hitomi T, Koizumi A, Haraguchi K. Regional variation and possible sources of brominated contaminants in breast milk from Japan. Environ Pollut 2012;162:269-74.
Cite This Article
Open AccessHow to Cite
Rawn, D. F. K.; Sadler, A. R.; Casey, V. A.; Breton, F.; Sun, W. F.; Feng, S. Y.; Arbuckle, T. E. Legacy halogenated flame retardants in Canadian human milk from the maternal-infant research on environmental chemicals study. J. Environ. Expo. Assess. 2024, 3, 16. http://dx.doi.org/10.20517/jeea.2024.04
Download Citation
Export Citation File:
Type of Import
Tips on Downloading Citation
Citation Manager File Format
Type of Import
Direct Import: When the Direct Import option is selected (the default state), a dialogue box will give you the option to Save or Open the downloaded citation data. Choosing Open will either launch your citation manager or give you a choice of applications with which to use the metadata. The Save option saves the file locally for later use.
Indirect Import: When the Indirect Import option is selected, the metadata is displayed and may be copied and pasted as needed.
About This Article
Special Issue
Copyright
Comments
Comments must be written in English. Spam, offensive content, impersonation, and private information will not be permitted. If any comment is reported and identified as inappropriate content by OAE staff, the comment will be removed without notice. If you have any queries or need any help, please contact us at support@oaepublish.com.