New insights into the endocrine disrupting effects of brominated flame retardants

The objective of this review is to provide an overview of recent studies demonstrating the endocrine disrupting (ED) effects of brominated flame retardants (BFRs), while highlighting interesting data presented at the recent international BFR workshop in Amsterdam in April, 2007. A review written in 2002 was used as a starting point and about 60 publications published since 2003 were reviewed. New insights into the in vivo effects of BFRs on thyroid hormone, estrogen and androgen pathways in both mammalian and non-mammalian models are provided, and novel (in vitro) findings on the mechanisms underlying ED effects are highlighted. Special attention is also given to reports on neurotoxicological effects at relatively low doses of BFRs, although an endocrine-related mechanism is disputable. Convincing evidence has been published showing that BFRs and importantly, BFR metabolites, have the potential to disrupt endocrine systems at multiple target sites. While some studies suggest a wide margin of safety between effect concentrations in rodent models and levels encountered in humans and the environment, other studies demonstrate that exposure to low doses relevant for humans and wildlife at critical time points in development can result in profound effects on both endocrine pathways and (neuro)development.     

Levels and sources of brominated flame retardants in human hair from urban, e-waste, and rural areas in South China

Human hair and indoor dust from urban, e-waste, and rural areas in south China were collected and analyzed for brominated flame retardants (BFRs). BFRs concentrations in hair from occupational e-waste recycling workers were higher than those from non-occupational exposed residents in other sampling areas. Polybrominated diphenyl ethers (PBDEs) and decabromodiphenyl ethane (DBDPE) are two major BFRs in hair samples. The PBDE congener profiles in hair from the e-waste area are different from those from urban and rural areas with relatively higher contribution of lower brominated congeners. DBDPE, instead of BDE209, has become the major BFR in non-e-waste recycling areas. Significant correlations were found between hair level and dust level for DBDPE and BTBPE but not for PBDEs. The different PBDE congener profiles between dust and hair may suggest that exogenous exposure to the PBDE adsorbed on dust is not a major source of hair PBDEs.     

Brominated flame retardants in the hair and serum samples from an e-waste recycling area in southeastern China: the possibility of using hair for biomonitoring

Hair samples and paired serum samples were collected from e-waste and urban areas in Wenling of Zhejiang Province, China. The PBDE and DBDPE concentrations in hair and serum samples from e-waste workers were significantly higher than those of non-occupational residents and urban residents. BDE209 was the dominating BFRs in hair and serum samples from the e-waste area, while DBDPE was the major BFRs from the urban area. Statistically significant correlations were observed between hair level and serum level for some substances (BDE209, DBDPE, BDE99, BDE47, BDE28, and BDE17), although the PBDE congener profiles in hair were different from those in the serum. A statistically significant positive correlation between the PBDE concentrations and the working age, as well as gender difference, was observed in e-waste workers. Different sources of PBDEs and DBDPE in three groups were identified by principal component analysis and spearman correlation coefficient. Hair is suggested to be a useful matrix for biomonitoring the PBDE exposure in humans.     

Hazardous substances in indoor dust emitted from waste TV recycling facility

Various hazardous substances contained in waste TV sets might be released into environment via dust during recycling activities. Two brominated flame retardants (BFRs), polybrominated diphenyl ethers (PBDEs), and tetrabromobisphenol A (TBBPA), and five kinds of heavy metals (Cu, Pb, Cd, Cr, and Ni) were detected in indoor dust collected from two workshops (TV dismantling workshop and subsequent recycling workshop). PBDEs concentrations in dust from waste wires recycling line (722,000 ng/g) were the highest among the studied sites, followed by those in manual dismantling–sorting line (117,000 ng/g), whereas TBBPA concentrations were the highest in manual dismantling–sorting line (557 ng/g) and printed circuit board (PCB) recycling line (428 ng/g). For heavy metals, Cu and Pb were the most enriched metals in all dust samples. The highest concentration of Pb (22,900 mg/kg) was found in TV dismantling workshop-floor dust. Meanwhile, Cu was the predominant metal in dust from the PCB recycling line, especially in dust collected from electrostatic separation area (42,700 mg/kg). Occupational exposure assessment results showed that workers were the most exposed to BDE-209 among the four PBDE congeners (BDE-47, BDE-99, BDE-153, and BDE-209) in both workshops. The hazard quotient (HQ) indicated that noncancerous effects were unlikely for both BFRs and heavy metals (HQ?<?1), and carcinogenic risks for Cd, Cr, and Ni (risk?<?10^?6) on workers in two workshops were relatively low.     

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.     

Brominated flame retardant concentrations and trends in abiotic media

BFR burdens in abiotic media have been less studied than in biota, despite their essential value as an aide to identifying sources, temporal and geographic trends and exposure routes. Many polymer products consist of several percent by weight of BFRs. Global trade in these can result in rapid and wholesale BFR movement. Loss from in-use products of nonreactive BFRs may be important, particularly in respect to indoor exposure. In the case of BDE-209, discharges from publicly owned treatment works may be substantial. BFR burdens in air, water and sewage sludge respond rapidly to changes in environmental BFR inputs. PBDEs have been the most widely studied. In many locales PBDE burdens in these media now surpass those of PCBs. Air and water near sources and urban areas are typically enriched relative to rural locales. The more volatile PBDEs dominate in the vapor phase, while BDE-209 typically predominates on particulates. Evidence exists for long-range transport of the more volatile PBDEs. A greater diversity of BFRs (mostly PBDEs, HBCD and TBBP-A) has been detected in sewage sludges. Land application of these sludges on agricultural fields is one conduit for soil contamination. In general, environmental concentrations of BDE-209 appear to be increasing, while penta-BDE burdens in Europe may have peaked. Sediments function as longer-term integrators of environmental burdens. Concentrations of common BFRs therein may be substantial near point sources. Evidence for debromination in the environment has been limited to date. However, some laboratory and field observations suggest it is possible to a limited extent.     

Effects of acute postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl on sperm function and hormone levels in adult rats

Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'-tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.     

Perinatal dioxin exposure, cytochrome P-450 activity, liver functions and thyroid hormones at follow-up after 7-12 years

OBJECTIVES: Prenatal and lactational exposure to Dutch "background" dioxin levels may cause health effects spanning many years. In addition, perinatal studies have shown a relationship between dioxin exposure and thyroid disturbance. To assess the later health effects of prenatal and lactational dioxin exposure on liver function we measured plasma ALAT and ASAT levels amongst our longitudinal cohort, as was done perinatally and at 2(1/2) years. The children underwent a caffeine loading test to determine CYP1A2 activity. To assess the later effects on thyroid function we measured plasma TSH and FT4. STUDY DESIGN: A longitudinal cohort of 37 healthy children (age 7-12, mean 8.2 years), with documented prenatal and lactational dioxin exposure, ingested 3mg caffeine/kg BW 6h prior to blood withdrawal. Paraxanthine/caffeine molar ratio, ALAT, ASAT, TSH and FT4 were determined in venous blood. RESULTS: Linear regression of ASAT and ALAT revealed no relation with prenatal and lactational dioxin exposure. No correlation was found between the paraxanthine/caffeine molar ratio and prenatal and lactational dioxin exposure. Linear regression of TSH and FT4 revealed no relation with prenatal and lactational dioxin exposure. CONCLUSION: This follow-up has shown a normalisation of previously abnormal ALAT and ASAT levels, indicating a transient effect. CYP1A2 activity, measured by means of a caffeine-loading test, revealed no correlation with the prenatal and lactational exposures. A normalisation of previously abnormal thyroid hormone homeostasis was seen, also possibly indicating a transient effect. This study provides new data on long-term follow-up after perinatal dioxin exposure to background levels of dioxins.     

Toxicity of analytically cleaned pentabromodiphenylether after prolonged exposure in estuarine European flounder (Platichthys flesus), and partial life-cycle exposure in fresh water zebrafish (Danio rerio)

Residues of polybrominated diphenylethers (PBDEs), extensively applied as flame retardants, are widely spread in the aquatic environment and biota. The present study investigates effects of the environmentally relevant lower brominated diphenylethers in two fish species in vivo under controlled laboratory conditions. Euryhaline flounder (Platichthys flesus) and freshwater zebrafish (Danio rerio) were exposed to a range of concentrations of a commercial pentabromodiphenylether mixture, DE-71. Chemical analysis of exposed fish showed a pattern of PBDE congeners that was very similar to that in wild fish. The resulting range included environmentally relevant, as well as higher levels. Animals were investigated histopathologically with emphasis on endocrine and reproductive organs. In zebrafish, hatching of embryos and larval development were assessed. Biochemical parameters were investigated in flounder as markers for suggested dioxin-like activity (ethoxyresorufin-O-deethylase=EROD), and activation of endogenous estrogen synthesis (gonad aromatase activity). Thyroid hormones were analyzed in plasma in both species. Benchmark analysis using internal PBDE concentrations showed a mild dose-dependent decrease of hepatic EROD and ovarian aromatase activities, and plasma thyroxin levels in flounder, and an increase of plasma thyroid hormone levels in zebrafish. These trends did not result in statistically significant differences from control fish, and major histopathological changes were not observed. Reproduction in zebrafish appeared to be the most sensitive parameter with statistically significantly reduced larval survival and non-significant indications for decreased egg production at internal levels that were more than 55 times the highest environmental recordings. The present results indicate limited risk for endocrine or reproductive effects of current environmental PBDE contamination in fish.     

Effects of in utero di-butyl phthalate and butyl benzyl phthalate exposure on offspring development and male reproduction of rat

The study was conducted to assess the effects of in utero di-butyl phthalate (DBP) and butyl benzyl phthalate (BBP) exposure during late gestation on offspring’s development and reproductive system of male rats. Pregnant rats were treated orally with DBP (2, 10, 50 mg/kg), BBP (4, 20, 100 mg/kg), and diethylstilbestrol (DES) 6 μg/kg (positive control) from GD14 to parturition. A significant reduction in dams’ body weight on GD21 in DBP-, BBP-, and DES-treated groups was observed. The gestation length was considerably elevated in the treated groups. Decline in male pups’ body weight was significant at PND75 in DBP- (50 mg/kg), BBP- (20,100 mg/kg), and DES-treated groups. The weight of most of the reproductive organs and sperm quality parameters was impaired significantly in DBP- (50 mg/kg) and BBP- (100 mg/kg) treated groups. Further, a non-significant decline in testicular spermatid count and daily sperm production was also monitored in treated groups. A significant reduction in serum testosterone level in BBP (100 mg/kg), whereas the testicular activity of 17β-HSD was declined non-significantly in the treated groups with respect to control. The data suggests that DBP and BBP exposure during late gestation period might have adverse effects on offspring’s development, spermatogenesis, and steroidogenesis in adult rats.     

A synchronized amphibian metamorphosis assay as an improved tool to detect thyroid hormone disturbance by endocrine disruptors and apolar sediment extracts

Amphibian metamorphosis assays are used to evaluate potential effects of endocrine disrupting compounds on the thyroid hormone axis. In this study, Xenopus laevis tadpoles are kept in a solution of 0.2% thiourea (TU) to arrest and synchronise them in their development. The advantage of this synchronized amphibian metamorphosis assays is that synchronised tadpoles are available at any time to start metamorphosis experiments, and experimental groups are much more homogenous at the start of experimental exposure compared with groups selected from an untreated pool of animals. The water volume per animal was kept constant throughout the experimental period to overcome the influence of declining numbers of animals per aquarium due to metamorphosis and mortality on the density dependent development of the remaining tadpoles. Clophen A50 (a technical PCB mixture), the single congener 3,3',4,4'-tetrachlorobiphenyl (PCB 77) and apolar sediment extracts that were previously tested positive in the T-Screen, an in vitro proliferation assay for thyroid hormone disruption, were tested in the Synchronized Amphibian Metamorphosis Assay. Endpoints studied were mortality, malformations, body weight, and percentage of metamorphosed froglets at the end of the 60-day experimental period, percentage of tadpoles in different developmental stages, and developmental stage-dependent awarded penalty points. Dietary exposure to Clophen A50 (0.2-50mg/kg food) resulted in a significant increased percentage of tadpoles that did not pass metamorphosis at concentrations higher than 2mg/kg food. Time until metamorphosis in those animals that were able to metamorphose after the 60-days experimental period was significantly decreased. Dietary exposure to PCB 77, a congener that can be readily metabolised, did not result in significant effects in any exposure group (2-500 microg/kg food). Apolar sediment extracts from two of the three sites that are contaminated with a wide variety of chemicals significantly decreased the percentage of metamorphosed animals and significantly increased the number of tadpoles that remained in early and late metamorphic stages. These effects already occurred when the extracts where diluted more than 1000 times (on an organic carbon base) compared to environmental concentrations. The rank of potency was comparable to results obtained with the T-screen. This suggests the presence of thyroid hormone disrupting compounds in the aquatic environment and possible effects of such compounds on animal development in the wild.     

Polychlorinated biphenyls, sex steroid hormones and liver retinoids in adult male European common frogs Rana temporaria

Declines in amphibian populations and species biodiversity during the last decades has called for an assessment of possible threats to these animals. Polychlorinated biphenyls (PCBs) are known endocrine disrupting contaminants and are found in high levels in some populations of wild living amphibians. To evaluate the endocrine disrupting potential of PCBs in adult frogs, Aroclor 1,254 were subcutaneously injected into male European common frogs Rana temporaria. The injected doses ranged from 0.01 to 100 mg/kg body mass, resulting in liver concentrations between 74 and 133,619 microg/kg ww. After 14 days, serum testosterone (T), estradiol (E) and hepatic retinol (R) and retinylpalmitate (RP) were easured. No dose dependent effects were found on levels of hormones or retinoids. However, a significantly higher within-group variation in the E-T ratio in the exposed groups may indicate that the sex-hormone homeostasis of male R. temporaria is affected by PCBs shortly after arousal from hibernation, but that the effects are subtle and that several different mechanisms are involved. The lack of direct effect on T, E, R and RP may be due to the timing of exposure (shortly after arousal from hibernation), or due to a relatively short exposure time to Aroclor 1,254. Based on the results, we propose that future research should focus on effects of PCBs in relation to the different physiological phases frogs experience throughout the year (hibernation, reproduction etc.).     

Effect of long-term dietary lead exposure on some maturation and reproductive parameters of a female Prussian carp (Carassius gibelio B.)

Lead is reported to be an endocrine disruptor. In the current study, we exposed female Prussian carp to artificial feed, supplemented with five doses of dietary Pb (0, 1 (control), 8, 13, 24, and 49 mg/kg) over either a 24-month period or a 12-month period, followed by further 12 months where the fish were fed the control diet. Periodically, oocyte maturation, gonadosomatic index (GSI), ability to secret luteinizing hormone (LH) as well as gonad Pb concentrations were measured. It was found that the reproductive system of the female Prussian carp is not indifferent to chronic exposure to lead. The negative effect was manifested by a decrease in the GSI after 12 months despite the fact that a higher proportion of oocytes at more advanced maturity stages were concurrently observed. After 12 months of exposure, the effect on LH secretion varied according to the dose. In the group exposed to the lowest dose (8 mg/kg), LH decreased spontaneously, and in the groups exposed to the highest two doses (24 and 48 mg/kg), a significantly higher LHRH-A-stimulated LH secretion was observed. After 24 months of lead exposure, the effects on oocyte maturation and size and on GSI values were not pronounced. Analysis of the effect of lead exposure on LH secretion showed that the relationships were similar to those observed after 12 months but nonsignificant. During chronic a 24-month period exposure to Pb, Prussian carp female appears to acclimate to Pb doses used in the experiment. After 12 months of exposure and 12 months of depuration, the levels of spontaneous and stimulated LH secretion observed in all the groups were similar to the control, which is evidence that depuration eliminates the previously observed effects of exposure to lead. Lead is easily accumulated in the ovary, reaching a fivefold higher level (0.8 mg/kg tissue) compared to the control (0.15 mg/kg tissue), but after discontinuation of exposure, this organ is quickly depurated. The results indicate that environmental Pb can be a potent endocrine disruptor affecting ovarian steroidogenesis, gametogenesis, and ovulation, which may lead to adverse impacts on fish reproduction and population density and that female Prussian carp become resistant to the negative effects of lead with advancing age, and their organs cope by reaching a state of homeostasis.     

Monitoring of PBDEs concentration in umbilical cord blood and breast milk from Korean population and estimating the effects of various parameters on accumulation in humans

In this study, we investigated concentration, congener distribution pattern, and effects of potential environmental factors that affect PBDE accumulation. We also estimated correlation between PBDE concentration and health status or thyroid function by analyzing 90 cord blood and 21 breast milk samples obtained from Korean population. Seven from tri- to hepta-BDEs were analyzed by solid phase extraction-high-resolution gas chromatography/high-resolution mass spectrometry (SPE-HRGC/HRMS). The total concentration of 7 PBDEs in cord blood was 2.786-94.64 ng g(-1) lipid and that in breast milk was 1.076-8.664 ng g(-1) lipid. Tetra-BDE (#47) was the predominant type of PBDE and was present at concentrations of over 40% in both sample types. A weak correlation was observed between the concentration of BDE28 and 153 and thyroid hormone concentration only in the breast milk samples. In children, a weak negative correlation was observed between free thyroxine (FT4) concentration and BDE28 concentration (0.302, p<0.05), while in mothers, a weak positive correlation was observed between thyroid hormone concentration and BDE153 concentration (0.403, p<0.05). No significant correlations between PBDE concentration and work and residential environments were found in this study, but a weak correlation between BDE concentration in cord blood and potential PBDE sources was confirmed by investigating the frequency of oil paint usage (0.510, p<0.001). A weak correlation was also found between PBDE concentration in breast milk during pregnancy and dietary habits such as green tea drinking (0.541, p=0.025) and Trichiuridae intake (0.565, p=0.015).     

Low hepatic 7-ethoxyresorufin-O-deethylase (EROD) activity and minor alterations in retinoid and thyroid hormone levels in flounder (Platichthys flesus) exposed to the polychlorinated biphenyl (PCB) mixture, Clophen A50

The effect of the polychlorinated biphenyl (PCB) mixture Clophen A50 on hepatic cytochrome P4501A1 dependent EROD (7-ethoxyresorufin-O-deethylase) activity, plasma thyroid hormone levels and plasma, kidney and liver retinoid concentrations of the euryhaline flatfish flounder (Platichthys flesus) was determined 2 and 10 days after i.p. (intraperitoneal) injection with 20, 100 and 500 mg Clophen A50/kg body weight. No effect of Clophen A50 on total cytochrome P450 content in flounder liver was observed at both time points. A six-fold, dose-dependent, significant increase in EROD activity was found at exposure day 10 in flounder receiving 100 or 500 mg Clophen A50/kg body weight. Plasma retinol concentrations were not altered at both time points after Clophen A50 administration, whereas renal retinol levels showed a minor dose-related increase at day 2 and day 10 of exposure. Significant alterations in hepatic retinoid concentrations were observed, which were not dependent on the dose of PCB administered. In addition Clophen A50 administration did not result in a dose-related alteration of total T4 concentrations in plasma. Total T3 concentrations in plasma were only significantly increased at day 2 after exposure, whereas free T4 concentrations were increased at both time points after Clophen A50 administration. These data indicate that with regard to the parameters investigated and in contrast to other fish species studied, the flounder is not a sensitive species to PCB exposure.     

Physical and motor development in male and female rat offspring prenatally exposed to gamma radiation

Abstract

The effects of radiation on physical and motor development of male and female rats exposed to ionizing radiation in utero were studied. Rats were exposed to three different doses of radiation (150 rad, 15 rad and 6.8 rad, considered as high, moderate and low doses of radiation respectively) on the 20th day of prenatal life. Exposure to 150 rad contributed to significantly lower body weights of both male and female rat offspring. Upper jaw tooth eruption was delayed in 150 rad treated male offspring, as well as in 15 rad and 150 rad treated female offspring. Cliff‐avoidance response was delayed in 6.8 rad, 15 rad, and 150 rad treated male offspring; and 150 rad treated female offspring. Lower jaw tooth eruption, eye opening, and crawling were not affected by radiation in male or female animals. Results indicate that radiation affected the developmental parameters of both male and female rat offspring, and sex of the offspring played no role in the magnitude of radiation induced damages.     

Polybrominated diphenyl ether exposure to electronics recycling workers--a follow up study

Workers at an electronics recycling plant have previously been shown to have elevated serum levels of polybrominated diphenyl ethers (PBDEs) compared to referents without occupational PBDE exposure. Subsequent structural changes and industrial hygiene measures at the plant were applied to improve the work environment. The present study aims to assess the impact of these work environment changes on the occupational exposure to PBDEs.

Blood were drawn from the workers and analyzed at two different laboratories, and serum concentrations of several PBDE congeners were determined by GC/MS or GC/HRMS. Cross-sectional studies were performed prior to (in 1997; N = 19) and after (in 2000; N = 27) workplace improvements. Longitudinal studies were performed on twelve of the workers that were sampled at both occasions.

Even though the amount of processed goods had doubled in 2000 as compared to 1997, there was a significant decrease in the serum levels of BDE-183 and BDE-209. For BDE-209 the levels observed in year 2000 were even lower than in referents with no occupational exposure. In contrast to the decrease of higher brominated diphenyl ethers, the concentrations of BDE-47 did not significantly change. For BDE-153, the cross-sectional study indicated no change, whereas the longitudinal follow up indicated a significant increase.

This study shows that the industrial hygiene improvements clearly reduced the occupational exposure to BDE-183 and BDE-209 at the plant. Still, the levels of hexa- to nonaBDEs but not BDE-209 were elevated, compared to referents with no occupational exposure.     

Maternal transfer of brominated flame retardants in zebrafish (Danio rerio)

In many species reproduction and embryonic development have been shown to be sensitive to environmental contaminants. Understanding embryonic exposure to environmental contaminants is thus highly important. In this study concentrations of brominated flame retardants (BFRs) were measured in zebrafish eggs after parental exposure for 42 days via the diet. Zebrafish were exposed to two doses of eleven structurally-diverse BFRs. Eight BFRs were detected in the female zebrafish and maternal transfer to eggs was evident for all eight compounds. The highest concentrations in eggs were observed for hexabromocyclododecane (HBCD) and 2,4,4'-tribromodiphenyl ether (BDE 28), followed by 2,2',3,4,4',5',6-heptabromodiphenyl ether (BDE 183) and tetrabromobisphenol A 2,3-dibromopropyl ether (TBBPA DBPE). Five potential BFR metabolites were tentatively identified in female fish and maternal transfer was observed also for these compounds. The lipid adjusted concentrations in eggs were significantly higher than the concentrations in female fish for several of the BFRs. Further, the results showed a generally higher transfer in the lower exposure level and also indicated a dependency on the physico-chemical properties of the compounds.     

Levels and distribution of polybrominated diphenyl ethers in various tissues of birds of prey

In the present study, concentrations and tissue distribution of polybrominated diphenyl ethers (PBDEs; IUPAC # 28, 47, 99, 100, 153, 154, 183, and 209) were examined in brain, adipose tissue, liver, muscle, and serum of birds of prey. Median SigmaPBDE levels (BDE 28-183) in the tissues of sparrowhawks ranged from 360 to 1900 ng/g lipid weight (lw), which was in general one order of magnitude higher than in the tissues of common buzzards (26-130 ng/g lw). There were no differences in PBDE congener patterns between the various tissues within individuals of a certain species. Inter-species differences in PBDE patterns and in particular the percentage of BDE 99, 100 and 153 were, however, pronounced between sparrowhawk and common buzzard. BDE 209 was detected in nearly all serum and in some liver samples, but not in any other tissues. This observation suggests that exposure to BDE 209 is low or that this congener is poorly accumulated. Passive (lipid content related) diffusion could not completely describe the PBDE tissue distribution, e.g. the lowest PBDE-load was measured in brain, a fairly lipid rich tissue.     

Effects of perinatal exposure to bisphenol A and di(2-ethylhexyl)-phthalate on gonadal development of male mice

Purpose

In this study, we investigated the effects of maternal transfer of bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP) during gestational and weaning periods on gonadal development of male offspring.

Methods

Pregnant CD-1 mice were administered by gavages in corn oil with 0.1, 1, or 10 mg/kg/day of BPA and DEHP from gestational days (GD1?C21) to the weaning period (postnatal days (PND) 1?C21).

Results

Our data indicated that the exposure significantly reduced the male-to-female sex ratio and the sizes of the gonads of male pups as recorded at PND15. The testes of the perinatally exposed male pups were developed less and the expression levels of testicular anti-mullerian hormone, androgen receptor, cyclin A, and StAR were significantly lesser than the control male pups. The less developed testes were accompanied with significant reductions in the expression levels of Gnrh and Fsh at the hypothalamic?Cpituitary levels. The negative effects were found to be persistent in the sexually mature pups at PND42.

Conclusion

Our data reveal that the maternal transfer of BPA and DEHP may impose negative influence on the development and functions of the reproductive system of male pups.