Plasma Polybrominated Diphenyl Ethers Research Articles

Racial and ethnic disparities in preterm birth: a mediation analysis incorporating mixtures of polybrominated diphenyl ethers.

Racial and ethnic disparities persist in preterm birth (PTB) and gestational age (GA) at delivery in the United States. It remains unclear whether exposure to environmental chemicals contributes to these disparities. We applied recent methodologies incorporating environmental mixtures as mediators in causal mediation analysis to examine whether racial and ethnic disparities in GA at delivery and PTB may be partially explained by exposures to polybrominated diphenyl ethers (PBDEs), a class of chemicals used as flame retardants in the United States. Data from a multiracial/ethnic US cohort of 2008 individuals with low-risk singleton pregnancies were utilized, with plasma PBDE concentrations measured during early pregnancy. We performed mediation analyses incorporating three forms of mediators: (1) reducing all PBDEs to a weighted index, (2) selecting a PBDE congener, or (3) including all congeners simultaneously as multiple mediators, to evaluate whether PBDEs may contribute to the racial and ethnic disparities in PTB and GA at delivery, adjusted for potential confounders. Among the 2008 participants, 552 self-identified as non-Hispanic White, 504 self-identified as non-Hispanic Black, 568 self-identified as Hispanic, and 384 self-identified as Asian/Pacific Islander. The non-Hispanic Black individuals had the highest mean ∑PBDEs, the shortest mean GA at delivery, and the highest rate of PTB. Overall, the difference in GA at delivery comparing non-Hispanic Black to non-Hispanic White women was -0.30 (95% CI: -0.54, -0.05) weeks. This disparity reduced to -0.23 (95% CI: -0.49, 0.02) and -0.18 (95% CI: -0.46, 0.10) weeks if fixing everyone's weighted index of PBDEs to the median and the 25th percentile levels, respectively. The proportion of disparity mediated by the weighted index of PBDEs was 11.8%. No statistically significant mediation was found for PTB, other forms of mediator(s), or other racial and ethnic groups. PBDE mixtures may partially mediate the Black vs. White disparity in GA at delivery. While further validations are needed, lowering the PBDEs at the population level might help reduce this disparity.

Higher HDL-C levels attenuated the association of plasma polybrominated diphenyl ethers with prediabetes and type 2 diabetes mellitus in rural Chinese adults

BackgroundPlasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. MethodsIn this study, a total of 2607 subjects aged 18–79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. ResultsThe geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high‐density lipoprotein cholesterol (HDL-C) levels increased. ConclusionsOur findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.

Prenatal exposure to polybrominated diphenyl ethers and inattention/hyperactivity symptoms in mid to late adolescents.

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with increased symptoms of attention deficit/hyperactivity disorder (ADHD) in early to middle childhood, as well as early adolescence. However, data are limited for the long-lasting impact of exposure on outcomes assessed across the entire adolescent period and the sex-specificity of such associations. We investigated the association between continuous natural-log-transformed cord plasma PBDE concentrations and ADHD rating scale 4th edition (ADHD-RS-IV) score from mid adolescence (approximately 11 years old) to late adolescence (approximately 17 years old). The study sample includes a subset (n = 219) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used generalized estimating equations to account for the repeated measure of ADHD-RS scores. We examined interactions between exposure to PBDE and sex using cross-product terms and sex-stratified models. In addition, we used linear regression using an age-stratified sample as a sensitivity analysis. Associations between prenatal exposure and parents' reports of ADHD symptoms varied by sex (p-interaction <0.20), with positive relationships observed among girls but not boys from sex-stratified models. Our finding suggests prenatal exposure to PBDE may affect ADHD symptoms assessed during middle to late adolescence and the sex-specificity of such impact. Our results can be confirmed by future studies with larger and more diverse samples.

Polybrominated diphenyl ethers in early pregnancy and preterm birth: Findings from the NICHD Fetal Growth Studies.

Studies suggest associations between exposure to individual polybrominated diphenyl ethers (PBDEs) with preterm birth (PTB) and shorter gestational age. Little is known about exposure to PBDE mixtures and these outcomes. We evaluated associations of multiple PBDEs in early pregnancy with gestational age at delivery and PTB. Data were collected from 2046 women without obesity and 396 women with obesity from the NICHD Fetal Growth Studies, who had early pregnancy plasma PBDEs concentrations and gestational age at delivery. PTB was defined as < 37 weeks of gestation at delivery and further categorized into subtypes (late or very early/moderate; spontaneous or medically indicated). We applied (1) generalized linear models (GLM); (2) principal component analysis (PCA); and (3) Bayesian Kernel Machine Regression (BKMR) to evaluate the individual and joint associations of log-transformed PBDE concentrations with gestational age at delivery and PTB, adjusting for potential confounders and evaluating effect modifiers. In GLM analyses, a 1-standard deviation (SD) increase in log-PBDE 153 was associated with shorter gestational age at delivery [adjusted β (95% CI)=-0.19 (-0.31, -0.06) weeks] among women without obesity. In PCA analyses, 1-SD increase in the principal component summarizing most of PBDE 153 variability was associated with shorter gestational age at delivery [adjusted β (95% CI)=-0.18 (-0.30, -0.06) weeks], very early/moderate PTB [adjusted OR (95% CI)=1.91 (1.19, 3.07)], and spontaneous PTB [adjusted OR (95% CI)=1.34 (1.00, 1.80)] among women without obesity. Associations were stronger among non-Hispanic Black women, women with BMI ranging between 25 and 30kg/m2, and women who were ≥35 years old among those without obesity. In BKMR analyses, a suggestive inverse association between PBDE 153 and gestational age at delivery, and an inverse U-shaped association between PBDE 154 and gestational age at delivery were observed in women without obesity. No statistically significant association of PBDEs and gestational age or PTB was observed among women with obesity. PBDEs, specifically PBDE 153, were associated with shorter gestation and higher risk of certain PTB subtypes among pregnant women without obesity.

Thyroid hormones in relation to polybrominated diphenyl ether and metals exposure among rural adult residents along the Yangtze River, China.

Although several studies indicate that exposure to polybrominated diphenyl ethers (PBDEs) and metals may influence thyroid function, the evidence is limited and inconsistent in general population. The current study was conducted to determine the levels of plasma PBDEs and urinary metals and evaluate the associations of co-exposure to both with thyroid hormones (THs) among rural adult residents along the Yangtze River, China. A total of 329 subjects were included in current analyses, and 8 PBDEs congeners and 14 urinary metals were measured to reflect the levels of environmental exposure. Multiple linear regression models were used to evaluate the association between PBDEs, metals and THs levels. Bayesian Kernel Machine Regression (BKMR) was used to examine PBDEs and metals mixtures in relation to THs. The geometric mean (GM) and 95% confidence interval (CI) of total measured PBDEs was 65.10 (59.96, 70.68) ng/g lipid weights (lw). BDE-209 was the most abundant congener, with a GM (95% CI) of 47.91 (42.95, 53.26) ng/g lw, accounting for 73.6% of the total PBDEs. Free thyroxine (FT4) was significantly negatively associated with BDE-28, 47, 99, 100, 154, and 183, and urinary strontium [β (95% CI): -0.04 (-0.07, -0.02)], but positively associated with selenium [β (95% CI): 0.04 (0.02, 0.06)]. Free triiodothyronine (FT3) was negatively associated with BDE-28 [β (95% CI): -0.03 (-0.05, -0.01)] and urinary arsenic [β (95% CI): -0.01 (-0.02, -0.001)]. The current study did not observe a statistically significant association of thyroid-stimulating hormone (TSH) with PBDEs and urinary metals. BKMR analyses showed similar trends when these chemicals were taken into consideration simultaneously. We found no significant interaction in the association between individual chemical at the 25th versus 75th percentiles and THs estimates, comparing the results when other chemicals were set at their 10th, 50th, and 90th percentile levels. Further study is required to confirm these findings and determine potential mechanisms.

Plasma polybrominated diphenyl ethers, urinary heavy metals and the risk of thyroid cancer: A case-control study in China.

The incidence of thyroid cancer (TC) has increased rapidly worldwide in recent years. Exposure to endocrine disruptors can affect thyroid hormones and is probably carcinogenic to humans. The effects of polybrominated diphenyl ethers (PBDEs), some heavy metals (Cd, Pb, As and Hg) on risk of TC have been rarely reported. Hence, we aimed to examine the associations of TC risk with exposure to PBDEs and four heavy metals. This case-control study involved 308TC cases and 308 age- and sex-matched controls. Plasma PBDEs concentrations were determined by gas chromatograph-mass spectrometry. Concentrations of heavy metals concentrations in urine specimens were detected by graphite furnace atomic absorption spectrometry or inductively coupled plasma optical emission spectrometry. Conditional logistic regression models were used to explore associations of PBDEs and 4 heavy metals exposures with TC risk. A joint-effect interaction term was inserted into the logistic regression models to assess the multiplicative interaction effects of PBDEs-heavy metals on TC risk. Some PBDE congeners (BDE-028, -047,-099,-183,-209) were positively correlated with TC risk. As and Hg were also associated with the increased TC risk. Compared with low exposure levels, participants with high exposure levels of As and Hg were 5.35 and 2.98 times more likely to have TC, respectively. Co-exposure to BDE-209 and Pb had a negative interaction effect on TC risk. Some PBDE congeners (e.g. BDE-028, -047,-209) and Hg had a significant positive interaction effect on the risk of TC. The joint exposure of BDE-183 and Hg showed a negative interaction effect on TC risk, but the corresponding OR value was still statistically significant. Exposure to PBDEs, As and Hg may be associated with TC development. Joint exposure to PBDEs and Pb or Hg has interaction effects on TC risk. Further prospective research with large sample is required to confirm these findings.

Association between exposure to persistent organic pollutants and mercury, and glucose metabolism in two Canadian Indigenous populations

BackgroundThe body burden of metals and persistent organic pollutants (POPs) is particularly high in populations that rely on fish and other marine species for sustenance. This exposure has been associated with an increased risk of type 2 diabetes, but results remain contrasted. ObjectiveWe studied this association in two Indigenous populations of northern Québec (Canada) with markedly different prevalences of diabetes and levels of exposure to POPs and mercury. MethodsAs part of health surveys conducted in 2004–2009, diabetes prevalence and glucose metabolism (glucose, insulin, HOMA-IR, HOMA-B) in non-diabetic fasting adults were assessed using similar protocols in two populations: Inuit from Nunavik (n = 877) and Cree from Eeyou Istchee territory (n = 780). Blood mercury, plasma polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides/metabolites and polybrominated diphenylethers (PBDEs) levels were measured in samples collected at the time of examination. Logistic and linear regressions and restricted cubic splines analyses were conducted adjusting for sex, age, waist circumference, smoking and omega-3 fatty acid content in plasma phospholipids. ResultsDiabetes prevalence was higher in Cree (20%) than in Inuit (7%), whereas environmental exposure was 2 to 3-fold greater in Inuit than in Cree participants. In the range of exposure common to the two populations, we observed similar linear increases in the risk of diabetes with increasing contaminant exposure. Among Cree participants, fasting glucose was positively associated with plasma PBDE level, and HOMA-B negatively associated with concentrations of ∑PCBs, dichlorodiphenyldichloroethylene, PBDEs and ∑OC pesticides. Among Inuit participants, a trend towards reduced insulin secretion was observed in association with most contaminants, but the relation was nonlinear (greater reduction at intermediate levels of exposure). A significant increase in fasting glucose levels was observed at elevated blood mercury levels (>16 μg/L). ConclusionThe observed association between POPs exposure and diabetes risk in the two populations studied should be confirmed using prospective design. Our results suggest the need for additional research on the physiopathological process through which POPs exposure may induce type 2 diabetes in these Indigenous populations.

Temporal trends and developmental patterns of plasmapolybrominated diphenyl ether concentrations over a 15-year period between 1998 and 2013.

Polybrominated diphenyl ethers (PBDEs) were used extensively as flame retardants in furniture containing polyurethane foam until they were phased out of use, beginning in 2004. We examined temporal changes in PBDE concentrations from 1998 to 2013 and characterized patterns of exposure over the early lifecourse among 334 children (903 samples) between birth and 9 years. We examined time trends by regressing PBDE concentration on year of sample collection in age-adjusted models and characterized developmental trajectories using latent class growth analysis (LCGA). Controlling for age, BDE-47 concentrations decreased 5% (95% confidence interval (CI): −9, −2) per year between 1998 and 2013. When considering only postnatal samples, this reduction strengthened to 13% (95% CI: −19, −9). Findings for BDEs-99, 100 and 153 were similar, except that BDE-153 decreased to a lesser extent when both prenatal and postnatal samples were considered (−2%, 95% CI: −7, 0). These findings suggest that, on average, pentaBDE body burdens have decreased since the 2004 phase-out of these chemicals. When examining developmental period, PBDE concentrations peaked during toddler years for the majority of children, however, our observation of several unique trajectories suggests that a single measure may not accurately reflect exposure to PBDEs throughout early life.

Exposure to Polybrominated Diphenyl Ethers (PBDEs) and Hypothyroidism in Canadian Women.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a wide range of products, resulting in widespread human exposure. Epidemiological studies in some populations reported exposure to PBDEs and thyroid hormone levels but little epidemiological data are available among women from the general population. The objective of the study was to examine the association of PBDEs with hypothyroidism. This was a cross-sectional analysis of the 2007-2009 Canadian Health Measures Survey. A total of 745 women representative of Canadian women aged 30-79 years participated in the study. Main Outcome and Methods: We estimated the prevalence ratios (PRs) for hypothyroidism in relation to plasma concentrations of BDE-47, -99, -100, and -153 and their sum (ΣPBDEs). Women were identified as cases if they reported a doctor-diagnosed thyroid condition and underwent thyroid hormone replacement therapy (n = 90). Higher plasma levels of brominated diphenyl ether (BDE)-47 and -100 and ΣPBDEs were associated with an increased prevalence of hypothyroidism. The PR for a 10-fold increase in ΣPBDEs was 1.7 (95% confidence interval [CI] 1.0, 3.0). Associations were consistently higher among women aged 30-50 years than among those 51-79 years for ΣPBDEs and the other PBDE congeners, although the interaction was significant only for BDE-100. For instance, in the younger age group, women with detectable levels of BDE-100 had a PR of 3.8 (95% CI 1.2, 12.3) compared with women with undetectable levels; the corresponding PR in the older age group was 1.2 (95% CI 0.6, 2.3). No association was observed for BDE-99 and -153. Plasma PBDE levels were associated with an increased prevalence of hypothyroidism in Canadian women aged 30-50 years. Although the cross-sectional design of the study limits inferences of causality, these findings have important implications, given the key role of thyroid hormones in several biological mechanisms during reproductive age.

Levels of PBDEs in plasma of juvenile starlings (Sturnus vulgaris) from British Columbia, Canada and assessment of PBDE metabolism by avian liver microsomes

In this study, the levels of polybrominated diphenyl ethers (PBDEs), HO-PBDEs, and bromophenols were monitored in starling chick plasma samples collected in Delta (British Columbia, Canada) close to the Vancouver municipal landfill and in Glen Valley, a rural area in British Columbia. The in vitro formation of hydroxylated metabolites of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and 2,2′,4,4′,5-pentabromodiphenyl ether (BDE-99) was also investigated using starling chick liver microsomes. Total PBDE plasma levels were approximately 60 times higher in starling chicks from Delta than from Glen Valley, suggesting that the Delta site is a major source of PBDEs for the local population of starlings and that PBDEs previously measured in starling eggs are bioavailable to chicks. In both locations, BDE-47 and BDE-99 were the two major congeners present at similar concentrations, suggesting contamination with the Penta-BDE mixture. Among the several possible hydroxylated metabolites of PBDEs monitored in starling plasma, only 2,4,5-tribromophenol was detected and its levels did not exceed 18±7pg/mL. Also, several hydroxylated metabolites of BDE-47 and BDE-99 were formed by starling chick liver microsomes, but in low amounts. Therefore, our data consistently suggest that oxidative metabolism of PBDEs in starling chicks proceeds at low rate in vivo and in vitro. In conclusion, the landfill located in Delta is a relevant source of bioavailable PBDEs for the local starling population. Because of the limited ability of starling chicks to metabolize PBDEs, these compounds are likely to bioaccumulate in starlings over time. The possible toxicological implications of PBDEs bioaccumulation in starlings are currently unknown and require further research.

Invited Commentary: Maternal Plasma Polybrominated Diphenyl Ethers and Thyroid Hormones--Challenges and Opportunities

Thyroid hormones play a fundamental role in fetal and child development. While iodine deficiency-related maternal and child hypothyroidism may cause severe mental retardation, recent evidence suggests that milder forms of maternal hypothyroidism and hypothyroxinemia during pregnancy are also associated with altered neurodevelopment. On the other hand, hyperthyroidism during pregnancy has been associated with adverse fetal outcomes. Findings published by Abdelouahab et al. in the American Journal of Epidemiology (Am J Epidemiol. 2013;178(5):701-713) suggest that plasma concentrations of maternal polybrominated diphenyl ethers (PBDEs), which were used as flame retardants until recently and are detected in the tissues of virtually every North American, are associated with umbilical cord and maternal thyroid hormone levels during pregnancy. Although PBDEs have been consistently shown to reduce levels of free and total thyroxine in experimental animal studies, the direction of associations in human studies has been inconsistent. In this commentary, I discuss challenges beyond the factors often cited in the epidemiologic literature to explain inconsistent findings which more specifically apply to the study of PBDEs and thyroid hormones. These include the determination of iodine intake status, the method used to adjust for blood lipid concentrations, the measurement of free thyroid hormone levels, the possible effect of PBDE metabolites, and the potential for reverse causality.

Oral Argument: Sublingual Findings Challenge Key Assumptions about BPA Exposure

Key assumptions about bisphenol A (BPA) exposure and bioavailability may be off base, according to a new report in EHP that questions the traditional interpretation of biomonitoring data underlying current risk assessments of the chemical.1 Laboratory research suggests that BPA, a widely used chemical for polycarbonate plastics and other products, is an endocrine disruptor with potential adverse health effects involving reproduction, metabolism, and cancer.2,3 Median daily intake of the chemical through the diet is estimated to be 0.01–0.12 µg/kg body weight, based on urinary concentrations of BPA metabolites.4 These metabolites, particularly BPA glucuronide (BPAG), are not biologically active like the parent compound. Nearly all ingested BPA has been thought to be absorbed in the small intestine and rapidly converted to BPAG in the liver prior to bodywide distribution.5,6 Given the estimated daily intake and assumption of rapid conversion, the European Food Safety Authority set a tolerable daily intake of BPA at 0.05 mg/kg.1 However, the current study indicates that BPA can be completely absorbed directly into the bloodstream from the mouth, thus bypassing early rapid metabolism and remaining biologically active for an extended period of time. “Most previous studies have relied on the gavage method, where BPA is distributed directly into the gut,” says Laura Vandenberg, a postdoctoral fellow at the Tufts University Center for Regenerative and Developmental Biology, who was not involved in the study. “This isn’t how food actually enters our bodies. We chew it, move it around in our mouths, and it interacts with numerous surfaces—our tongue, cheeks, etc.—before it enters the stomach.” Gavage studies suggest there should not be detectable levels of unmetabolized BPA in the blood after exposure, yet dozens of other studies report otherwise, she says. The researchers compared the bioavailability of BPA given sublingually (under the tongue) versus intravenously or by gavage. In one experiment 6 dogs received a dose of 5 mg/kg first intravenously, then a week later sublingually either all at once or one drop at a time. In another experiment, conducted in three parts, the same dogs received a dose of 0.05 mg/kg first intravenously, then sublingually, and finally a 20-mg/kg dose delivered by gavage. After each administration, blood samples were collected to measure BPA and BPAG and calculate various parameters such as maximum concentration, time to maximum concentration, and mean residence time.1 BPA was readily absorbed from both the mouth and the gut, but bioavailability throughout the body differed significantly depending on the absorption site. Over the 2 hours following dosing, 5 mg/g and 0.05 mg/kg sublingual BPA yielded ratios of biologically inactive BPAG to biologically active BPA of 1:1–13:1 and 1:1–6:1, respectively, compared with 237:1–634:1 for the dose placed directly in the stomach.1 If confirmed, new findings on sublingual BPA dosing could have important implications for human exposures to BPA. “The sublingual route is a rather well-known route of absorption for those who are involved in the development of drugs but not for those working with contaminants in general and BPA in particular,” says study coauthor Pierre-Louis Toutain, a professor of physiology and therapeutics at the National Veterinary School of Toulouse, France. He says dogs were chosen as the study animals because their oral tissue closely resembles that of humans. The sublingual dosing used in the study may present different conditions from the exposure that occurs while eating or drinking. It also does not reflect potential nonfood exposures from sources such as dust, cigarette filters, thermal papers, and dental sealants that previous research has suggested occur.7 However, “the authors have shown very clearly that when BPA comes into contact with the mucosa under the tongue, it can be rapidly absorbed into the bloodstream. When this happens, it enters the bloodstream without being metabolized,” says Vandenberg. Additionally, this study may explain previous biomonitoring reports of plasma BPA levels deemed impossible or incorrect based on assumptions about gut-only absorption. This is important because plasma levels found in biomonitoring studies are similar to those found to cause adverse health effects in animal studies.7 Urinary BPAG serves as an index of external BPA exposure in biomonitoring studies, but it tells us nothing about the route of absorption, says Toutain. Given the researchers’ findings, he says it would be unacceptable to assume that only a negligible fraction of BPAG circulated as active BPA before it was converted to the inactive form measured in urine. He says, “It is clear that our data suggesting that BPA bioavailability can be high should raise some questions and possibly lead some agencies to reconsider their risk analysis on BPA.”

Polybrominated diphenyl ethers in relation to autism and developmental delay: a case-control study

BackgroundPolybrominated diphenyl ethers (PBDEs) are flame retardants used widely and in increasing amounts in the U.S. over the last few decades. PBDEs and their metabolites cross the placenta and studies in rodents demonstrate neurodevelopmental toxicity from prenatal exposures. PBDE exposures occur both via breastfeeding and hand-to-mouth activities in small children.MethodsParticipants were 100 children from the CHARGE (CHildhood Autism Risk from Genetics and the Environment) Study, a case-control epidemiologic investigation of children with autism/autism spectrum disorder, with developmental delay and from the general population. Diagnoses of autism were confirmed by the Autism Diagnostic Observation Schedule and Autism Diagnostic Inventory-Revised, and of developmental delay using the Mullen's Scales of Early Learning and the Vineland Adaptive Behavior Scales. Typically developing controls were those with no evidence of delay, autism, or autism spectrum disorder. Eleven PBDE congeners were measured by gas chromatography/mass spectrometry from serum specimens collected after children were assessed. Logistic regression was used to evaluate the association between plasma PBDEs and autism.ResultsChildren with autism/autism spectrum disorder and developmental delay were similar to typically developing controls for all PBDE congeners, but levels were high for all three groups.ConclusionsPlasma samples collected post-diagnosis in this study may not represent early life exposures due to changes in diet and introduction of new household products containing PBDEs. Studies with direct measurements of prenatal or infant exposures are needed to assess the possible causal role for these compounds in autism spectrum disorders.

Plasma PBDE and thyroxine levels in rats exposed to Bromkal or BDE-47

In experimental models, polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants, have caused effects in a number of biological end-points, including neurobehavioural effects, disturbances in thyroid and steroid hormone homeostasis, and other steroid-related effects. Almost exclusively, only external dose metrics (dose per body weight basis) have been studied in connection to the observed effects. In this study we report on new analyses of plasma PBDE levels in surplus samples from earlier studies on thyroid hormones (TH) in exposed rodents. Female, 7-week old Sprague-Dawley rats were given either Bromkal 70-5 DE (Study I; 18 or 36 mg/kg bw/day) or BDE-47 (Study II; 1, 6 or 18 mg/kg bw/day) daily by gavage for two weeks. At an external dose of 18 mg/kg bw/day significant TH effects (decreased plasma free thyroxin levels) were observed in both studies, corresponding to an internal (plasma) dose of 463 microg sumPBDE/g lipid (Study I) or 421 microg BDE-47/g lipid (Study II). If we compare the contribution of different BDE congeners to the total BDE level in rat plasma after Bromkal exposure (Study II), and in the Bromkal mixture itself, the most important congener in the Bromkal mixture were also found in plasma. However, the relative concentration of BDE-99 was lower, and that of BDE-153 was higher, than that of the mixture, indicating selectivity in uptake, metabolism and/or excretion of the individual BDE congeners. Explicitly, the possible in vivo conversion of BDE-99 to BDE-47, and of BDE-154 to BDE-153 could not be excluded. The internal dose in the present rat study could be compared to reported human serum doses of PBDE. Human serum/blood levels have a wide range, from 3 to 6 ng sumPBDE/g lipid in background samples from Europe, about 10 times higher in US sample, and up to 100 times higher (300-600 ng/g lipid) in upper-end levels in collected samples from USA. As a consequence, the margin between effects levels in the rat and exposure levels in man varies widely, with a quotient roughly from 1000 to 100,000. Generally, it could be expected that this margin is lower than if external dose metrics would be used. An even lower margin could be expected as recent studies have shown effects in offspring at lower doses than those giving effects in our studies. Lastly, it should be noted that humans are already exposed to a mixture of chemicals in daily life, a fact that complicates this kind of comparison.

Dietary intake of differently fed salmon: a preliminary study on contaminants

In a previous study, a group of coronary heart disease (CHD) patients exhibited positive cardioprotective effects of fatty acids derived from a diet of farmed Atlantic salmon fed fish oil (Seierstad et al. 2005). This follow-up study examines these patients for plasma exposure to selected organic and inorganic contaminants found in seafood that may detract from the benefits of eating oily fish. The study design was from Seierstad et al. (2005), where 58 patients were allocated into three groups consuming 700 g week(-1) of differently fed Atlantic salmon (Salmo salar) fillets for 6 weeks: 100% fish oil (FO), 100% rapeseed oil (RO), or 50% of each (FO/RO). Different fillets showed graded levels (FO > FO/RO > RO) of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DLPCBs), indicator PCBs, polybrominated diphenyl ethers (PBDEs), and arsenic (As). Mercury (Hg) and lead (Pb) levels were similar across the three types of fillets. After 6 weeks of consumption, patient levels of PCDDs, DLPCBs, and PCBs in plasma decreased as the dietary intake of these contaminants increased. Plasma PBDEs only showed increases for the FO patients. Levels of inorganic contaminants in plasma showed only slight changes over the study period. These results show a reduction in the use of marine oils in fish feed reduces organic contaminant levels in farmed salmon while still providing a good dietary source of marine fatty acids.

Comparing electron ionization high-resolution and electron capture low-resolution mass spectrometric determination of polybrominated diphenyl ethers in plasma, serum and milk

Gas chromatography coupled to low-resolution mass spectrometry with electron capture negative ionization as detection mode (GC-LRMS (ECNI)) has been compared to gas chromatography coupled to high-resolution mass spectrometry using electron ionization as detection mode (GC-HRMS (EI)) for determination of polybrominated diphenyl ethers (PBDEs) in biological samples. Extracts of 5.0 g plasma, serum and milk samples were analyzed using both methods. The GC-LRMS (ECNI) and GC-HRMS (EI) systems were found to be equally well suited for determination of PBDEs in the biological samples, as well as in standard solutions, with respect to response, detection limits and repeatability at the pg-level. The estimated limits of detection (LOD) in milk extracts ranged from 0.3–0.6 pg PBDE/g milk and 0.4–0.7 pg PBDE/g milk, for the GC-LRMS (ECNI) and GC-HRMS (EI) systems, respectively. The method repeatability including sample preparation was in the range 4.7–8.4% and 0.6–10% relative standard deviation (RSD) for the GC-LRMS (ECNI) and GC-HRMS (EI) systems, respectively.