Eleven recently completed toxicological studies were critically reviewed to identify toxicologically significant endpoints and dose-response information. Dose-response data were compiled and entered into the USEPA's benchmark dose software (BMDS) for calculation of a benchmark dose (BMD) and a benchmark dose low (BMDL). After assessing 91 endpoints across the nine studies, a total of 23 of these endpoints were identified for BMD modeling, and BMDL estimates corresponding to various dose-response models were compiled for these separate endpoints. Thyroid, neurobehavior and reproductive endpoints for BDE-47, -99, -209 were quantitatively evaluated. According to methods and feature of each study, different uncertainty factor (UF) value was decided and subsequently reference doses (RfDs) were proposed. Consistent with USEPA, the lowest BMDLs of 2.10, 81.77, and 1698 µg/kg were used to develop RfDs for BDE-47, -99, and -209, respectively. RfDs for BDE-99 and BDE-209 were comparable to EPA results, and however, RfD of BDE-47 was much lower than that of EPA, which may result from that reproductive/developmental proves to be more sensitive than neurobehavior for BDE-47 and the principal study uses very-low-dose exposure.
Animals ; Female ; Halogenated Diphenyl Ethers ; toxicity ; Male ; Mice ; Rats ; Reference Standards ; Toxicity Tests

Objective To discuss the effects of polybrominated diphenyl ethers （PBDEs） exposure in e-waste dismantling region on the human body and provide data support for the identification of environmental health damage to residents in the e-waste dismantling region. Methods Adults in an e-waste dismantling region （exposed group, 54 participants） and a control region （control group, 58 participants） were selected, questionnaires were carried out and blood and urine samples were collected. Blood PBDEs, blood lipids, blood routine, blood lead, urine cadmium, urine chromium and urine nickel were detected. T-test was utilized to compare the differences of PBDEs between the two groups. Multivariate analysis were utilized to compare the differences between the two groups in blood routine indexes. Linear regression was used to analyze the relationship between PBDEs and blood routine. Results Exposure levels of PBDEs were significantly higher in the exposed group （240.00 ng/g, adjusted mass fraction of blood lipids, thereafter） than in the control group （93.00 ng/g, P<0.05）. There was no statistical significance in the differences in most blood routine indexes of the two groups （ P>0.05）, and their reference values were all within normal ranges. Mean platelet volume, plateletcrit, basophils percentage, absolute value of basophils, and mean corpuscular hemoglobin concentration were higher in the exposed group than in the control group （P<0.05）. Platelet distribution widths were lower in the exposed group than in the control group and below the normal reference range （P<0.05）. Conclusion PBDEs exposure in e-waste dismantling region tend to change platelet morphology, the number of basophils, and mean corpuscular hemoglobin concentration, and may pose potential health hazards to local residents.
Adult ; China ; Electronic Waste/analysis* ; Environmental Monitoring ; Halogenated Diphenyl Ethers/toxicity* ; Human Body ; Humans

Animals ; Female ; Halogenated Diphenyl Ethers ; Herbicides ; toxicity ; Male ; Mice ; Mice, Inbred Strains ; Mutagenicity Tests ; Phenyl Ethers ; toxicity

OBJECTIVETo investigate the effect of maternal decabromodiphenyl ether (BDE-209) exposure on the sexual development in male offspring rats.

METHODSTwenty-four pregnant Sprague-Dawley rats were randomly divided into three BDE-209 exposure groups and one control group. The three BDE-209 exposure groups were given BDE-209 (100, 300, and 900 mg/kg) by gavage on gestational days 12∼18, and the control group was given corn oil. The body weight and body length of each newborn male rat was measured at postnatal days 4, 10, 16, and 21. Twelve newborn male rats were randomly selected from each group; anogenital distance was measured at postnatal day 21, serum testosterone was measured, and the organ coefficient of testis was calculated.

RESULTSThe newborn male rats in all exposure groups showed declining trends in body weight and body length compared with those in the control group, and the 900 mg/kg BDE-209 exposure group had significantly lower body weight and body length than the control group at postnatal days 4, 10,16, and 21 (P < 0.01). At postnatal day 21, the 100, 300, and 900 mg/kg BDE-209 exposure groups had anogenital distances of 17.82±2.35 mm, 16.32±1.66 mm, and 15.80±1.34 mm, respectively, demonstrating a significant decrease with increased exposure dose (P < 0.05), but no significant difference was found when comparing these values with that of the control group (16.64±2.38 mm) (P > 0.05). There were no significant differences in serum testosterone and organ coefficients of testis and epididymis between the control group and BDE-209 exposure groups (P > 0.05).

CONCLUSIONMaternal exposure to BDE-209 has adverse effect on the growth of male offspring rats, but it leads to no significant changes in sexual development.

Animals ; Female ; Halogenated Diphenyl Ethers ; toxicity ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Sexual Development ; drug effects

OBJECTIVETo study the oxidative stress induced by decabromodiphenylether (PBDE-209) in the cerebral cortex, hippocampus, cerebellum and striatum of mice.

METHODSTwenty-eight male BALB/c mice were randomized divided into four groups with seven mice in each: solvent control, blank control, low (200 mg/kg) and high (500 mg/kg) dose groups. Test substances were administered by gavage and mice were sacrificed 6 weeks after treatment. Malonyldialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) in cerebral cortex, hippocampus, cerebellum and striatum were examined.

RESULTSThe content of MDA in cerebral cortex, cerebellum, striatum and hippocampus in high dose group was (92.25 ± 36.64), (4.24 ± 1.15), (12.92 ± 4.30), (12.12 ± 6.39) nmol/mg pro respectively, higher than that in blank group [(56.713 ± 6.44), (2.42 ± 1.41), (4.05 ± 2.23), (4.91 ± 1.60) nmol/mg pro] and the difference was statistically significant (P < 0.05); T-SOD activity in cerebral cortex, cerebellum and striatum in low dose group was (182.48 ± 11.59), (6.67 ± 1.56), (35.48 ± 21.98) U/mg pro respectively, lower than that in blank group [(277.76 ± 106.70), (18.02 ± 16.40), (63.57 ± 20.83) U/mg pro] and the difference was statistically significant (P < 0.05); in high dose group the T-SOD activity in hippocampus was(59.26 ± 37.09) U/mg pro, lower than that in blank group [(93.28 ± 21.75) U/mg pro] and the difference was statistically significant (P < 0.05); The content of GSH in cerebral cortex, cerebellum and striatum in high dose group was (40.98 ± 13.19), (3.55 ± 1.55), (24.46 ± 11.30) mg/g pro respectively, lower than that in blank group [(75.79 ± 26.51), (8.01 ± 3.23), (44.52 ± 13.15) mg/g pro and the difference was statistically significant (P < 0.05); while the content of GSH in hippocampus was not decreased significantly compared with the blank group (P > 0.05).

CONCLUSIONPBDE-209 could induce oxidative stress in nervous tissue. The tissue oxidative damage might be one of the primary mechanisms of neurotoxicity of PBDE-209.

Animals ; Brain ; drug effects ; metabolism ; Halogenated Diphenyl Ethers ; toxicity ; Male ; Mice ; Mice, Inbred BALB C ; Oxidative Stress ; drug effects

OBJECTIVETo assess the DNA damage in mouse sperms induced by exogenous BDE-209 and explore the possible mechanism of BDE-209 in affecting normal zygote development.

METHODSMouse sperms were harvested from the epididymal tail and suspended in HTF medium for a 90-min exposure to BDE-209 at varied concentrations of 0, 2.5, 5.0, 10, and 20 µg/ml (groups A-E, respectively). After the exposure, the sperms were subjected to single-cell gel electrophoresis (SCGE) to assess the DNA damage.

RESULTSThe tail length of the sperms averaged 1.15 ∓ 1.27 µm in group A. Exposure to 10 and 20 µg/ml BDE-209 resulted in a significant lengthening of the sperm tails (2.13 ∓ 1.29 µm and 2.83 ∓ 2.46 µm, respectively, P<0.01) as well as increased DNA content in the tail of the cells (P<0.01). The Olive tail moment in group A was 0.270 ∓ 0.322, and increased after BDE-209 exposure to 0.453 ∓ 0.375 and 808 ∓ 0.822 in groups D and E, respectively. The tail/head length ratio in groups C, D, and E (0.077 ∓ 0.093, 0.112 ∓ 0.068, and 0.191 ∓ 0.207) were significantly greater than that in group A (0.045 ∓ 0.049). The DNA damage of the mouse sperms was directly correlated to the concentrations of BDE-209, with correlation coefficients all above 0.9.

CONCLUSIONSExogenous BDE-209 can cause mouse sperm DNA damage and lead to sperm DNA chain breakage, and this effect shows an obvious dose dependence.

Animals ; Cells, Cultured ; DNA Damage ; drug effects ; Dose-Response Relationship, Drug ; Flame Retardants ; toxicity ; Halogenated Diphenyl Ethers ; toxicity ; Male ; Mice ; Spermatozoa ; drug effects ; metabolism

OBJECTIVETo investigate the effects of exposure to decabrominated diphenyl ether (PBDE-209) on learning and memory of BALB/c mice.

METHODSEighteen female BALB/c mice were randomized divided into 3 groups and gavaged with peanut oil in the control groups and 300, 1500 mg x kg(-1)xd(-1) PBDE-209 in peanut oil daily in two exposed groups respectively for 4 weeks. The learning and memory ability of mice were tested by the Morris water maze and the shuttling box respectively. The body weight and organs index were measured and the acetylcholinesterase and butyrylcholinesterase activity in brain were determined. The liver histopathological examination was performed.

RESULTSThe heart index in high dose PBDE-209 group was higher than that of the low dose PBDE-209 group (P < 0.05). The results of Morris water maze showed that escape latency period was significantly shorter than the control group (F = 3.134, P < 0.05). The swimming time in the second quadrant of low dose PBDE-209 group was (15.78 +/- 10.92) s, significantly shorter compared with the swimming time in the second quadrant of the control group's [(28.80 +/- 8.67) s] (P < 0.05). There was no significant difference in the times of active avoidance in the shuttling between three groups (F = 3.423, P = 0.06). There were no significant differences in acetylcholinesterase and butyrylcholinesterase activity in brain of PBDE-209 groups compared with the control group (P > 0.05). Histologically liver damages in structure such as adipose degeneration and swelling were observed in PBDE groups.

CONCLUSIONExposure to PBDE-209 slightly impairs the space learning and memory ability of BALB/c mice, and it has some hepatotoxicity.

Animals ; Behavior, Animal ; Dose-Response Relationship, Drug ; Female ; Halogenated Diphenyl Ethers ; toxicity ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred BALB C ; Toxicity Tests

OBJECTIVETo investigate the cyto-genotoxicity of 2, 2', 4, 4'-tetrabromodiphenyl ethers (PBDE-47) combined with 2, 2', 4, 4', 5-hexachlorobiphenyl (PCB153) treatment in SH-SY5Y cells.

METHODSExponentially growing SH-SY5Y cells were exposed to different concentrations of PBDE-47 or/and PCB153 for 24 h in vitro. Cell viability, DNA damage, chromosome abnormalities, and DNA-protein crosslinks (DPC) were measured using MTT, comet assay, cytokinesis-block micronucleus (CBMN) test, and SDS-KCl assay respectively.

RESULTSCompared to the each single PBDE-47 groups, the nuclear division index (NDI) was significantly lower (P < 0.05) and the frequencies of micronuclei (MNI), percentage of DNA in the tail, Olive tail moment and DPC were significantly increased (P < 0.05) in the PBDE-47 combined with PCB153 groups. There was a statistical decrease in cell viability in groups of 4 micromol/L PBDE-47 and above combined with PCB153 than that in contrast to the same dose of PBDE-47 group or PCB153 alone (P < 0.05). Significant increase was found in MNI frequency and DPC in 2 micromol/L PBDE-47 and above combined with PCB153 than those in the single PCB153 group (P < 0.05). In the groups of 4 micromol/L PBDE-47 and above combined with PCB153, the cell NDI were significantly lower than that of the single PCB153 group (P < 0.05). Compared to the single PCB153 group, the percentage of DNA in the tail and Olive tail moment was significantly increased in the 8 micromol/L PBDE-47 combined with 5 micromol/L PCB153. Factorial analysis showed that interactions between PBDE-47 and PCB153 existed in inhibiting cell viability, inducing DNA damage, MNI, and DPC formation (P < 0.01), and possessing synergistic effects.

CONCLUSIONSome dose of PBDE-47 combined with PCB153 can inhibit cell viability, induce DNA damage, DPC formation, and chromosome abnormalities. The pattern of the combined effect is synergistic in cyto-genotoxicity.

Cell Line, Tumor ; Cell Survival ; drug effects ; Comet Assay ; DNA Damage ; drug effects ; Drug Synergism ; Halogenated Diphenyl Ethers ; toxicity ; Humans ; Micronucleus Tests ; Neuroblastoma ; genetics ; pathology ; Polychlorinated Biphenyls ; toxicity

OBJECTIVETo explore the lipid peroxidation and the testicular morphological change induced by decabrominated diphenyl ether (BDE-209) in male BALB/c mice.

METHODSTwenty one male BALB/c mice were randomly divided into three groups: the high exposure group (500 mg/kg BDE-209), the low exposure group (200 mg/kg BDE-20) and control group (normal saline). The mice were exposed by gavage one time a day for 6 weeks, then were sacrificed. Body weight, testis weight, malonyldialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) in testis were examined. The morphological alteration of testis was observed. TUNEL assay was used to detect the apoptosis in testicular cells.

RESULTSBody weight and testis weight in high and low exposure groups were (21.6140 +/- 2.3550) g, (20.8000 +/- 1.7630) g and (0.1859 +/- 0.0349) g, (0.1718 +/- 0.0266) g, respectively, which were significantly lower than those (27.7570 +/- 1.2880) g and (0.2302 +/- 0.0335) g in the control group (P < 0.05); the testis coefficient in high exposure group was (0.8640% +/- 0.1706%), which was significantly higher than that (0.8329 +/- 0.1386%) in the control group (P < 0.05). The GSH level and SOD activities of testis in 2 BDE-209 groups were 0.044 +/- 0.006, 0.039 +/- 0.005 nmol/mg prot, and 0.735 +/- 0.179, 0.907 +/- 0.198 U/mg prot, respectively, which were significantly lower than those (0.052 +/- 0.067) mol/mg and (1.161 +/- 0.188) U/mg in the control group (P < 0.05). The levels of MDA in 2 BDE-209 groups were (2.365 +/- 0.339) and (1.752 +/- 0.366) nmol/mg prot, which were significantly higher than that (1.173 +/- 0.232 nmol/mg prot) in control group (P < 0.05). there were significant differences of SOD and MDA levels between high exposure group and low exposure group (P < 0.05). Histological examination showed that the number of spermatogenic cells and layer were decreased significantly in 2 exposure groups as compared with control group. TUNEL assay showed that apoptosis cells appeared in 2 exposure groups.

CONCLUSIONBDE-209 changed lipid peroxidation in male BALB/c mice testis and caused toxic effects on the testis.

Animals ; Apoptosis ; Halogenated Diphenyl Ethers ; toxicity ; Lipid Peroxidation ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mutagenicity Tests ; Testis ; drug effects ; metabolism ; pathology

OBJECTIVETo evaluate the effect of prenatal and lactational exposure to brominated diphenyl ethers-209 (BDE-209) on the expression of growth associated protein-43 (GAP-43) and brain-derived neurotrophic factors (BDNF) in the hippocampus of the offspring rats.

METHODSPeanut oil suspensions of commercial BDE-209 were administered daily at doses of 100, 300, 600, and 1200 mg/kg by oral gavage in pregnant Wistar rats (groups A, B, C, and D, respectively). The control group (E) only received peanut oil of an equivalent volume. The hippocampus was isolated from 10 offspring rats in each group to determine the expression of GAP-43 and BDNF using immunohistochemistry.

RESULTSThe GAP-43 in the BDE-209-treated groups were lower than that of the control group, and decreased with the increase of the dose of BDE-209 exposure. The groups C and D (P=0.013, P=0.000), but not the groups A and B (P=0.177, P=0.093), showed significant difference from the control group in GAP-43 expression. The positive expression of BDNF in the hippocampus was decreased as the exposure dose to BDE-209 increased, and significant differences were found between the groups B, C, D and the control group (P=0.033, P=0.005, P=0.001, respectively), but not between group A and the control group (P=0.066).

CONCLUSIONSMaternal BDE-209 exposure can decrease the expression of GAP-43 and BDNF in the hippocampus of offspring rats, which may affect the axonal plasticity and regeneration of the neurons.

Animals ; Brain-Derived Neurotrophic Factor ; biosynthesis ; Female ; GAP-43 Protein ; biosynthesis ; Halogenated Diphenyl Ethers ; toxicity ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Male ; Maternal Exposure ; Maternal-Fetal Exchange ; Pregnancy ; Prenatal Exposure Delayed Effects ; Random Allocation ; Rats ; Rats, Wistar