Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

Background

Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy.

Objectives

Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women.

Methods

We measured the concentration of 10 PBDE congeners, free thyroxine (T₄), total T_4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation.

Results

Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (∑PBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), −20.6 to 0.0] and 18.7% (95% CI, −29.2 to −4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T₄) were also significantly elevated in participants in the highest quartile of ∑PBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T₄ were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ∑PBDEs.

Conclusions

Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development.     

Diet Contributes Significantly to the Body Burden of PBDEs in the General U.S. Population

Background

Exposure of the U.S. population to polybrominated diphenyl ethers (PBDEs) is thought to be via exposure to dust and diet. However, little work has been done to empirically link body burdens of these compounds to either route of exposure.

Objectives

The primary goal of this research was to evaluate the dietary contribution to PBDE body burdens in the United States by linking serum levels to food intake.

Methods

We used two dietary instruments—a 24-hr food recall (24FR) and a 1-year food frequency questionnaire (FFQ)—to examine food intake among participants of the 2003–2004 National Health and Nutrition Examination Survey. We regressed serum concentrations of five PBDEs (BDE congeners 28, 47, 99, 100, and 153) and their sum (∑PBDE) against diet variables while adjusting for age, sex, race/ethnicity, income, and body mass index.

Results

∑PBDE serum concentrations among vegetarians were 23% (p = 0.006) and 27% (p = 0.009) lower than among omnivores for 24FR and 1-year FFQ, respectively. Serum levels of five PBDE congeners were associated with consumption of poultry fat: Low, medium, and high intake corresponded to geometric mean ∑PBDE concentrations of 40.6, 41.9, and 48.3 ng/g lipid, respectively (p = 0.0005). We observed similar trends for red meat fat, which were statistically significant for BDE-100 and BDE-153. No association was observed between serum PBDEs and consumption of dairy or fish. Results were similar for both dietary instruments but were more robust using 24FR.

Conclusions

Intake of contaminated poultry and red meat contributes significantly to PBDE body burdens in the United States.     

Serum Polybrominated Diphenyl Ether (PBDE) Levels Are Higher in Children (2–5 Years of Age) than in Infants and Adults

Background

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many products and have been detected in human samples worldwide. Limited data show that concentrations are elevated in young children.

Objectives

We investigated the association between PBDEs and age with an emphasis on young children from Australia in 2006–2007.

Methods

We collected human blood serum samples (n = 2,420), which we stratified by age and sex and pooled for analysis of PBDEs.

Results

The sum of BDE-47, -99, -100, and -153 concentrations (∑₄PBDE) increased from 0–0.5 years (mean ± SD, 14 ± 3.4 ng/g lipid) to peak at 2.6–3 years (51 ± 36 ng/g lipid; p < 0.001) and then decreased until 31–45 years (9.9 ± 1.6 ng/g lipid). We observed no further significant decrease among ages 31–45, 45–60 (p = 0.964), or > 60 years (p = 0.894). The mean ∑₄PBDE concentration in cord blood (24 ± 14 ng/g lipid) did not differ significantly from that in adult serum at ages 15–30 (p = 0.198) or 31–45 years (p = 0.140). We found no temporal trend when we compared the present results with Australian PBDE data from 2002–2005. PBDE concentrations were higher in males than in females; however, this difference reached statistical significance only for BDE-153 (p = 0.05).

Conclusions

The observed peak concentration at 2.6–3 years of age is later than the period when breast-feeding is typically ceased. This suggests that in addition to the exposure via human milk, young children have higher exposure to these chemicals and/or a lower capacity to eliminate them.     

Insights into PBDE Uptake,Body Burden,and Elimination Gained from Australian Age–Concentration Trends Observed Shortly after Peak Exposure

Background

Population pharmacokinetic models combined with multiple sets of age–concentration biomonitoring data facilitate back-calculation of chemical uptake rates from biomonitoring data.

Objectives

We back-calculated uptake rates of PBDEs for the Australian population from multiple biomonitoring surveys (top-down) and compared them with uptake rates calculated from dietary intake estimates of PBDEs and PBDE concentrations in dust (bottom-up).

Methods

Using three sets of PBDE elimination half-lives, we applied a population pharmacokinetic model to the PBDE biomonitoring data measured between 2002–2003 and 2010–2011 to derive the top-down uptake rates of four key PBDE congeners and six age groups. For the bottom-up approach, we used PBDE concentrations measured around 2005.

Results

Top-down uptake rates of Σ₄BDE (the sum of BDEs 47, 99, 100, and 153) varied from 7.9 to 19 ng/kg/day for toddlers and from 1.2 to 3.0 ng/kg/day for adults; in most cases, they were—for all age groups—higher than the bottom-up uptake rates. The discrepancy was largest for toddlers with factors up to 7–15 depending on the congener. Despite different elimination half-lives of the four congeners, the age–concentration trends showed no increase in concentration with age and were similar for all congeners.

Conclusions

In the bottom-up approach, PBDE uptake is underestimated; currently known pathways are not sufficient to explain measured PBDE concentrations, especially in young children. Although PBDE exposure of toddlers has declined in the past years, pre- and postnatal exposure to PBDEs has remained almost constant because the mothers’ PBDE body burden has not yet decreased substantially.

Citation

Gyalpo T, Toms LM, Mueller JF, Harden FA, Scheringer M, Hungerbühler K. 2015. Insights into PBDE uptake, body burden, and elimination gained from Australian age–concentration trends observed shortly after peak exposure. Environ Health Perspect 123:978–984; http://dx.doi.org/10.1289/ehp.1408960     

Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Thyroid Hormones in Maternal and Cord Sera: The HOME Study,Cincinnati, USA

Background

Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants.

Objectives

We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera.

Methods

We used data from the Health Outcomes and Measures of the Environment (HOME)Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ± 3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256).

Results

Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT₄), respectively. Both congeners were also positively associated with maternal free thyroxine (FT₄). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT₃ and FT₃). A 10-fold increase in BDE-28 was associated with elevated FT₃ concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum.

Conclusions

These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T₄ and T₃ during pregnancy.

Citation

Vuong AM, Webster GM, Romano ME, Braun JM, Zoeller RT, Hoofnagle AN, Sjödin A, Yolton K, Lanphear BP, Chen A. 2015. Maternal polybrominated diphenyl ether (PBDE) exposure and thyroid hormones in maternal and cord sera: the HOME Study, Cincinnati, USA. Environ Health Perspect 123:1079–1085; http://dx.doi.org/10.1289/ehp.1408996     

Hydroxylated Metabolites of Polybrominated Diphenyl Ethers in Human Blood Samples from the United States

Background

A previous study from our laboratory showed that polybrominated diphenyl ethers (PBDEs) were metabolized to hydroxylated PBDEs (HO-PBDEs) in mice and that para-HO-PBDEs were the most abundant and, potentially, the most toxic metabolites.

Objective

The goal of this study was to determine the concentrations of HO-PBDEs in blood from pregnant women, who had not been intentionally or occupationally exposed to these flame retardants, and from their newborn babies.

Methods

Twenty human blood samples were obtained from a hospital in Indianapolis, Indiana, and analyzed for both PBDEs and HO-PBDEs using electron-capture negative-ionization gas chromatographic mass spectrometry.

Results

The metabolite pattern of HO-PBDEs in human blood was quite different from that found in mice; 5-HO-BDE-47 and 6-HO-BDE-47 were the most abundant metabolites of BDE-47, and 5′-HO-BDE-99 and 6′-HO-BDE-99 were the most abundant metabolites of BDE-99. The relative concentrations between precursor and corresponding metabolites indicated that BDE-99 was more likely to be metabolized than BDE-47 and BDE-100. In addition, three bromophenols were also detected as products of the cleavage of the diphenyl ether bond. The ratio of total hydroxylated metabolites relative to their PBDE precursors ranged from 0.10 to 2.8, indicating that hydroxylated metabolites of PBDEs were accumulated in human blood.

Conclusions

The quite different PBDE metabolite pattern observed in humans versus mice indicates that different enzymes might be involved in the metabolic process. Although the levels of HO-PBDE metabolites found in human blood were low, these metabolites seemed to be accumulating.     

Contamination of U.S. butter with polybrominated diphenyl ethers from wrapping paper

Objectives

Our aim was to report the first known incidence of U.S. butter contamination with extremely high levels of polybrominated diphenyl ethers (PBDEs).

Methods

Ten butter samples were individually analyzed for PBDEs. One of the samples and its paper wrapper contained very high levels of higher-brominated PBDEs. Dietary estimates were calculated using the 2007 U.S. Department of Agriculture Loss-Adjusted Food Availability data, excluding the elevated sample.

Results

The highly contaminated butter sample had a total upper bound PBDE level of 42,252 pg/g wet weight (ww). Levels of brominated diphenyl ether (BDE)-206, -207, and -209 were 2,000, 2,290, and 37,600 pg/g ww, respectively. Its wrapping paper contained a total upper-bound PBDE concentration of 804,751 pg/g ww, with levels of BDE-206, -207, and -209 of 51,000, 11,700, and 614,000 pg/g, respectively. Total PBDE levels in the remaining nine butter samples ranged from 180 to 1,212 pg/g, with geometric mean of 483 and median of 284 pg/g. Excluding the outlier, total PBDE daily intake from all food was 22,764 pg/day, lower than some previous U.S. dietary intake estimates.

Conclusion

Higher-brominated PBDE congeners were likely transferred from contaminated wrapping paper to butter. A larger representative survey may help determine how frequently PBDE contamination occurs. Sampling at various stages in food production may identify contamination sources and reduce risk.     

Persistent Organic Pollutant Residues in Human Fetal Liver and Placenta from Greater Montreal,Quebec: A Longitudinal Study from 1998 through 2006

Background

There is general concern that persistent organic pollutants (POPs) found in the environment, wildlife, food, water, house dust, human tissues, and fluids may alter normal human physiologic activities (e.g., fetal development, immune and endocrine systems). Although the levels of some POPs [polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs)] in these matrices have decreased after their ban, others [polybrominated diphenyl ethers (PBDEs)] have increased in recent years.

Objective

To determine the longitudinal trend of specific POPs in human fetal tissues for risk assessment purposes.

Methods

We analyzed early to mid-gestation fetal liver (n = 52) and placental (n = 60) tissues, obtained after elective abortions during 1998–2006, for selected PBDEs, PCBs, and OCs using gas chromatography–mass spectroscopy.

Results

Total PBDEs in fetal liver increased over time (mean ± SE: 1998, 284.4 ± 229.8 ng/g lipid; 2006, 1,607.7 ± 605.9; p < 0.03), whereas placental levels were generally lower, with no clear trend. Low levels of PCBs and OCs varied yearly, with no evident trend. The major analytes in 1998 were OCs (liver, 49%; placenta, 71%), whereas the major analytes in 2006 were PBDEs (liver, 89%; placenta, 98%). The 1998–2006 tissue PBDE congener profile is similar to that of DE-71, a commercial primarily pentabrominated diphenyl ether mixture manufactured in North America.

Conclusions

Although commercial production of penta- and octa-brominated diphenyl ethers in North America was halted in 2004, their concentrations in fetal liver and placenta are now greater than the tissue burdens for the analyzed OCs and PCBs. Our findings also demonstrate that PBDEs accumulate within the fetal compartment at a very early stage in gestation.     

Exposure to Hexabromocyclododecanes (HBCDs) via Dust Ingestion,but Not Diet,Correlates with Concentrations in Human Serum: Preliminary Results

Background

Hexabromocyclododecane (HBCD) is a high-production-volume chemical used as flame retardant in polystyrene insulation and textiles. Because it is not chemically bound to the polymer, HBCD can migrate into the environment, contaminating indoor dust and foodstuff.

Objectives

We examined for the first time the relationship between combined exposure to three HBCD isomers (∑HBCDs) via ingestion of food (duplicate diets) and indoor dust and HBCD concentrations in serum for 16 Belgian adults (20–25 years of age). We also determined the chiral signatures of HBCDs to advance understanding of source-to-human enantioselective degradation and/or metabolism.

Methods

Concentrations and chiral signatures of α-, β-, and γ-HBCD in duplicate diets, dust, and serum were measured by liquid chromatography/tandem mass spectrometry.

Results

Dietary intakes of ∑HBCDs were 1.2–20 ng/day (average, 7.2 ng/day), whereas those estimated under average (20 mg dust/day) and high (50 mg dust/day) dust ingestion scenarios were 1.1–15 ng/day (average intake, 3.2 ng/day) and 2.8–38 ng/day (average intake, 8.0 ng/day), respectively. Concentrations of ∑HBCDs measured in blood serum were < 0.5 to 11 ng/g lipid weight (lw) (average, 2.9 ng/g lw). γ-HBCD dominated in food, whereas α-HBCD dominated in dust and was the sole isomer in serum. Although exposure via dust ingestion correlated significantly (p < 0.01) with concentrations in serum, no such correlation was evident with dietary exposure (p > 0.1). Although no enantioselective enrichment was detected in either dust or diet, substantial enrichment of (−)α-HBCD was observed in serum.

Conclusions

Serum concentrations of HBCDs were correlated with the exposure via dust, but not via dietary ingestion. The enrichment of the (−)α-HBCD enantiomer in humans appears to be due to in vivo enantioselective metabolism/excretion rather than ingestion of dust or diet.     

Do Human Milk Concentrations of Persistent Organic Chemicals Really Decline During Lactation? Chemical Concentrations During Lactation and Milk/Serum Partitioning

Background

Conventional wisdom regarding exposures to persistent organic chemicals via breast-feeding assumes that concentrations decline over the course of lactation and that the mother’s body burden reflects her cumulative lifetime exposure. Two important implications stemming from these lines of thought are, first, that assessments of early childhood exposures should incorporate decreasing breast milk concentrations over lactation; and, second, that there is little a breast-feeding mother can do to reduce her infant’s exposures via breast-feeding because of the cumulative nature of these chemicals.

Objectives

We examined rates of elimination and milk/serum partition coefficients for several groups of persistent organic chemicals.

Methods

We collected simultaneous milk and blood samples of 10 women at two times postpartum and additional milk samples without matching blood samples.

Results

Contrary to earlier research, we found that lipid-adjusted concentrations of polybrominated diphenyl ethers, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and furans, and organochlorine pesticides in serum and milk do not consistently decrease during lactation and can increase for some women. Published research has also suggested an approximate 1:1 milk/serum relationship (lipid adjusted) on a population basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin; however, our results suggest a more complex relationship for persistent, lipophilic chemicals with the milk/serum relationship dependent on chemical class.

Conclusions

Decreases in concentration of lipophilic chemicals on a lipid-adjusted basis during lactation should no longer be assumed. Thus, the concept of pumping and discarding early milk as means of reducing infant exposure is not supported. The hypothesis that persistent lipophilic chemicals, on a lipid-adjusted basis, have consistent concentrations across matrices is likely too simplistic.     

Concentrations of Phthalate Metabolites in Milk,Urine, Saliva,and Serum of Lactating North Carolina Women

Background

Phthalates are ubiquitous in the environment, but concentrations in multiple media from breast-feeding U.S. women have not been evaluated.

Objectives

The objective of this study was to accurately measure and compare the concentrations of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women.

Methods

We analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters.

Results

We detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3–22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concentration in urine. Metabolite concentrations differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride levels were increased among women with higher concentrations of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concentrations.

Conclusions

Our data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concentrations reflect maternal exposure and do not represent the concentrations of oxidative metabolites in other body fluids, especially milk.     

Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in Relation to Timing of Puberty in a Longitudinal Study of Girls

Background

Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program.

Objectives

Our goal was to examine persistent organic pollutants (POPs) in relation to pubertal onset.

Methods

Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1–4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling.

Results

Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ΣPBDE = 1.05; 95% CI: 1.02, 1.08, for ΣPCB = 1.05; 95% CI: 1.01, 1.08, and for ΣOCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs.

Conclusions

This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.

Citation

Windham GC, Pinney SM, Voss RW, SjÖdin A, Biro FM, Greenspan LC, Stewart S, Hiatt RA, Kushi LH. 2015. Brominated flame retardants and other persistent organohalogenated compounds in relation to timing of puberty in a longitudinal study of girls. Environ Health Perspect 123:1046–1052; http://dx.doi.org/10.1289/ehp.1408778     

Serum Concentrations of Antibodies Against Vaccine Toxoids in Children Exposed Perinatally to Immunotoxicants

Background

Polychlorinated biphenyls (PCBs) may cause immunotoxic effects, but the detailed dose–response relationship and possible vulnerable time windows of exposure are uncertain. In this study we applied serum concentrations of specific antibodies against childhood vaccines as sentinels of immunotoxicity.

Objectives

The main objective was to assess the possible dependence of antibody concentrations against diphtheria and tetanus toxoids in children with regard to prenatal and postnatal PCB exposures.

Methods

From a cohort of 656 singleton births formed in the Faroe Islands during 1999–2001, children were invited for examination with assessment of serum antibody concentrations at 5 years (before and after a booster vaccination) and at 7 years of age. Total PCB concentrations were determined in serum from ages 5 and 7 years, and data were also available on PCB concentrations in maternal pregnancy serum, maternal milk, and, for a subgroup, the child’s serum at 18 months of age.

Results

A total of 587 children participated in the examinations at ages 5 and/or 7 years. At age 5 years, before the booster vaccination, the antidiphtheria antibody concentration was inversely associated with PCB concentrations in milk and 18-month serum. Results obtained 2 years later showed an inverse association of concentrations of antibodies against both toxoids with PCB concentrations at 18 months of age. The strongest associations suggested a decrease in the antibody concentration by about 20% for each doubling in PCB exposure. At age 5 years, the odds of an antidiphtheria antibody concentration below a clinically protective level of 0.1 IU/L increased by about 30% for a doubling in PCB in milk and 18-month serum.

Conclusions

Developmental PCB exposure is associated with immunotoxic effects on serum concentrations of specific antibodies against diphtheria and tetanus vaccinations. The immune system development during the first years of life appears to be particularly vulnerable to this exposure.     

Hydroxylated metabolites of the polybrominated diphenyl ether mixture DE-71 are weak estrogen receptor-alpha ligands

Background

Polybrominated diphenyl ethers (PBDEs) are widely found in the environment and are suspected endocrine disruptors. We previously identified six hydroxylated metabolites of PBDE (OH-PBDEs) in treated mice.

Objective

We tested the hypothesis that OH-PBDEs would interact with and alter activity of estrogen receptor-α (ER-α).

Methods

We tested estrogenicity using two assays: ³H-estradiol (³H-E₂) displacement from recombinant ER-α and induction of reporter gene (ERE-luciferase) in cultured cells. We incubated the PBDE mixture DE-71 with rat liver microsomes and tested the resultant metabolite mixture for estrogenic activity. We also determined relative estrogenic potential of individual hydroxylated PBDE congeners.

Results

Reporter gene activity was increased by DE-71 that had been subjected to microsomal metabolism. DE-71 did not displace E₂ from ER-α, but all six of the OH-PBDE metabolites did. para-Hydroxylated metabolites displayed a 10- to 30-fold higher affinity for ER-α compared with ortho-hydroxylated PBDEs, and one produced a maximal effect 30% higher than that produced by E₂. Coadministration of E₂ and DE-71, or certain of its metabolites, yielded reporter activity greater than either chemical alone. Two ortho-OH-PBDEs were antiestrogenic in the reporter assay.

Conclusions

The observations—that the DE-71 mixture did not displace ³H-E₂ from ER-α while the hydroxylated metabolites did—suggest that the weak estrogenic effects of DE-71 are due to metabolic activation of individual congeners. However, the behavior of DE-71 and its metabolites, when co-administered with E₂, suggest a secondary, undetermined mechanism from classical ER-α activation.     

Chemical Contamination of Green Turtle (Chelonia mydas) Eggs in Peninsular Malaysia: Implications for Conservation and Public Health

Background

Persistent organic pollutants (POPs)—such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)—and heavy metals have been reported in sea turtles at various stages of their life cycle. These chemicals can disrupt development and function of wildlife. Furthermore, in areas such as Peninsular Malaysia, where the human consumption of sea turtle eggs is prevalent, egg contamination may also have public health implications.

Objective

In the present study we investigated conservation and human health risks associated with the chemical contamination of green turtle (Chelonia mydas) eggs in Peninsular Malaysia.

Methods

Fifty-five C. mydas eggs were collected from markets in Peninsular Malaysia and analyzed for POPs and heavy metals. We conducted screening risk assessments (SRAs) and calculated the percent of acceptable daily intake (ADI) for POPs and metals to assess conservation and human health risks associated with egg contamination.

Results

C. mydas eggs were available in 9 of the 33 markets visited. These eggs came from seven nesting areas from as far away as Borneo Malaysia. SRAs indicated a significant risk to embryonic development associated with the observed arsenic concentrations. Furthermore, the concentrations of coplanar PCBs represented 3 300 times the ADI values set by the World Health Organization.

Conclusions

The concentrations of POPs and heavy metals reported in C. mydas eggs from markets in Peninsular Malaysia pose considerable risks to sea turtle conservation and human health.     

Para- and ortho-substitutions are key determinants of polybrominated diphenyl ether activity toward ryanodine receptors and neurotoxicity

Background

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants that bioaccumulate in human tissues. Their neurotoxicity involves dysregulation of calcium ion (Ca²⁺) signaling; however, specific mechanisms have yet to be defined.

Objective

We aimed to define the structure–activity relationship (SAR) for PBDEs and their metabolites toward ryanodine receptors type 1 (RyR1) and type 2 (RyR2) and to determine whether it predicts neurotoxicity.

Methods

We analyzed [³H]ryanodine binding, microsomal Ca²⁺ fluxes, cellular measurements of Ca²⁺ homeostasis, and neurotoxicity to define mechanisms and specificity of PBDE-mediated Ca²⁺ dysregulation.

Results

PBDEs possessing two ortho-bromine substituents and lacking at least one para-bromine substituent (e.g., BDE-49) activate RyR1 and RyR2 with greater efficacy than corresponding congeners with two para-bromine substitutions (e.g., BDE-47). Addition of a methoxy group in the free para position reduces the activity of parent PBDEs. The hydroxylated BDEs 6-OH-BDE-47 and 4′-OH-BDE-49 are biphasic RyR modulators. Pretreatment of HEK293 cells (derived from human embryonic kidney cells) expressing either RyR1 or RyR2 with BDE-49 (250 nM) sensitized Ca²⁺ flux triggered by RyR agonists, whereas BDE-47 (250 nM) had negligible activity. The divergent activity of BDE-49, BDE-47, and 6-OH-BDE-47 toward RyRs predicted neurotoxicity in cultures of cortical neurons.

Conclusions

We found that PBDEs are potent modulators of RyR1 and RyR2. A stringent SAR at the ortho and para position determined whether a congener enhanced, inhibited, or exerted nonmonotonic actions toward RyRs. These results identify a convergent molecular target of PBDEs previously identified for noncoplanar polychlorinated biphenyls (PCBs) that predicts their cellular neurotoxicity and therefore could be a useful tool in risk assessment of PBDEs and related compounds.     

Birth delivery mode modifies the associations between prenatal polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels

Background

Developing infants may be especially sensitive to hormone disruption from chemicals including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs).

Objective

We investigated relationships between cord serum levels of PCBs and PBDEs and thyroid hormones measured in cord blood serum and neonatal blood spots.

Methods

We measured PCBs and PBDEs, thyrotropin (TSH), thyroxine (T₄) and free T₄ (FT₄) in cord blood serum from 297 infants who were delivered at the Johns Hopkins Hospital in 2004–2005. We abstracted results of total T₄ (TT₄) measured in blood spots collected in the hospital and at neonatal visits. We used delivery mode (augmented vaginal deliveries and nonelective cesarean deliveries) as a surrogate for intrapartum stress, which is known to alter cord blood thyroid hormones.

Results

In the full study population, no compounds were associated with a change in average TSH, FT₄, or TT₄. BDE-100 was associated with increased odds of low cord TT₄, BDE-153 with increased odds of low cord TT₄ and FT₄, and no compounds were associated with increased odds of high TSH. For infants born by spontaneous, vaginal, unassisted deliveries, PCBs were associated with lower cord TT₄ and FT₄ and lower TT₄ measured in neonatal blood spots. PBDEs showed consistent but mainly nonsignificant negative associations with TT₄ and FT₄ measurements.

Conclusions

Prenatal PCB and PBDE exposures were associated with reduced TT₄ and FT₄ levels among infants born by spontaneous, unassisted vaginal delivery. Intrapartum stress associated with delivery mode may mask hormonal effects of PCBs and PBDEs.