During the past decades, advancement in pubertal onset especially in girls has been noticed worldwide. Genetic factors and increasing prevalence of adiposity may contribute, however ubiquitous presence of endocrine disrupting chemicals (EDCs) is suspected to be involved in the trend of earlier pubertal onset. Most of known EDCs have estrogenic and/or anti-androgenic actions and few have androgenic or anti-estrogenic effects. Some studies reported earlier age at menarche after exposure to polycholorinated biphenyls (PCBs), polybrominated biphenyls, dicholordiphenyltrichloroethane, phthalate esters, while several other studies found no effect of these compounds on Tanner stages or age at menarche in girls. Limited studies reported an association of delayed puberty in boys and exposure to PCBs or the pesticide endosulfan. However, epidemiological research on the effects of EDCs on sexual maturation is hampered by many pitfalls, such as the mixture of many chemicals with different effects in environment, unidentified critical window of exposure, and limited knowledge about the time lag between exposure and effect. In this paper, we reviewed possible mode of actions of different chemical compounds, and summarized animal/human studies shown the effects of EDCs on the pubertal development.
Adiposity ; Endocrine Disruptors ; Endosulfan ; Esters ; Estrogen Receptor Modulators ; Estrogens ; Female ; Menarche ; Phthalic Acids ; Polybrominated Biphenyls ; Polychlorinated Biphenyls ; Prevalence ; Puberty ; Puberty, Delayed ; Sexual Maturation

OBJECTIVETo explore the concentration of polybrominated diphenyl ethers (PBDEs) in umbilical cord serum and analyze the influence of exposure to PBDEs during fetal stage on newborn birth outcomes in Shanghai.

METHODSFifty delivery women in a Shanghai hospital were surveyed by questionnaire, and the umbilical cord serum were collected from September 2006 to April 2007. All the delivery women were singleton pregnancies, excluding high blood pressure, diabetes, HIV infection and adverse medical history. Seven congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154 and BDE-183) were measured by gas chromatography-negative chemical ionization-mass spectrometry and the influencing factors were analyzed.

RESULTSNewborns' length, weight, chest circumference, head circumference and body mass index (BMI) were (50.15 ± 0.75) cm, (3.49 ± 0.42) kg, (34.76 ± 1.51) cm, (35.03 ± 1.40) cm, (13.76 ± 1.36) kg/m(2), respectively. The median of Σ(7PBDEs) concentration in umbilical cord serum was 14.06 (1.03 - 379.73) ng/g lipid weight (lw). The detection rate of BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154 and BDE-183 were 22% (11/50), 22% (11/50), 98% (49/50), 72% (36/50), 76% (38/50), 90% (45/50) and 14% (7/50), respectively. The median (range) of PBDEs (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183) congeners were < LOD (< LOD-137.20 ng/g lw), < LOD (< LOD-33.17 ng/g lw), 7.54 ng/g lw (< LOD-94.01 ng/g lw), 1.57 ng/g lw (< LOD-46.95 ng/g lw), 0.63 ng/g lw (< LOD-79.08 ng/g lw), 0.63 ng/g lw (< LOD-22.30 ng/g lw) and < LOD (< LOD-21.63 ng/g lw), respectively. The newborns' BMI showed a negative correlation with BDE-99 (r = -0.347, P < 0.05) and BDE-154 (r = -0.292, P < 0.05). BDE-99 in low-length group (≤ 50 cm, 10.59 ng/g lw) was significantly higher (t = 2.32, P = 0.03) than that in high-length group (> 50 cm, 3.60 ng/g lw).

CONCLUSIONPBDEs were commonly detected in newborns' umbilical cord serum in this study. Our findings indicated that exposure to PBDEs adversely affected the development of the newborns.

China ; Female ; Fetal Blood ; chemistry ; Humans ; Infant, Newborn ; Maternal Exposure ; Polybrominated Biphenyls ; blood ; Pregnancy ; Prenatal Exposure Delayed Effects ; Surveys and Questionnaires

The present study determined the thyroid hormone interference of tetrabromobisphenol A (TBBPA) in Sprague-Dawley (SD) rats, and the derived-reference dose (RfD) of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.
Animals ; Dose-Response Relationship, Drug ; Female ; Male ; Polybrominated Biphenyls ; toxicity ; Rats ; Rats, Sprague-Dawley ; Thyroid Hormones ; metabolism ; Thyrotropin ; metabolism ; Thyroxine ; metabolism ; Triiodothyronine ; metabolism

OBJECTIVETo investigate the effects of polybrominated diphenyl ether-153 (BDE-153) exposure during lactation period on the calcium ion (Ca(2+)) concentration and calcium-activated enzyme levels in cerebral cortical cells among adult rats and to provide a scientific basis for the study on the developmental neurotoxicity of BDE-153.

METHODSForty newborn male rats were randomly and equally divided into four groups according to their body weights and litters: 1, 5, and 10 mg/kg BDE-153 groups and olive oil solvent control group. On postnatal day 10 (PND 10), the BDE-153 groups were administrated BDE-153 (0.1 ml/10 g body weight) by intraperitoneal injection, while the olive oil solvent control group was given an equal volume of olive oil. Two months later, these rats were decapitated, and the cerebral cortex was separated quickly on an ice-cold dish. The Ca(2+) concentration in cerebral cortical cells was measured by flow cytometry. The activities of calcineurin (CaN) and Ca(2+)-Mg(2+)-ATP enzyme were determined by colorimetric method. The mRNA and protein expression of calpain-1 and calpain-2 was measured by real-time quantitative PCR and Western blot.

RESULTSThe mean fluorescence intensities of intracellular Ca(2+) in control group and 1, 5, and 10 mg/kg BDE-153 groups were 10.83, 1.48, 1.93, and 0.62, respectively; the 1, 5, and 10 mg/kg BDE-153 groups had significantly lower intercellular Ca(2+) concentrations than the control group (P < 0.05). The activities of CaN and Ca(2+)-Mg(2+)-ATP enzyme and mRNA and protein expression of calpain-1 showed no significant differences between the 1, 5, and 10 mg/kg BDE-153 groups and control group (P > 0.05). The protein expression of calpain-2 increased as the dose of BDE-153 rose. Compared with the control group (mRNA: 0.81±0.26; protein: 0.15±0.07), the 5 and 10 mg/kg BDE-153 groups had significantly higher mRNA expression of calpain-2 (5 mg/kg BDE-153 group: 1.16±0.52; 10 mg/kg BDE-153 group: 1.32±0.23) and significantly higher protein expression of calpain-2 (5 mg/kg BDE-153 group: 0.31±0.07; 10 mg/kg BDE-153 group: 0.37±0.06) (P < 0.05). The 10 mg/kg BDE-153 group had significantly higher protein expression of calpain-2 than the 1 mg/kg BDE-153 group (0.37±0.06 vs 0.22±0.07, P < 0.05).

CONCLUSIONCa(2+-) mediated calpain-2 activation may be one of the main mechanisms of BDE-153 neurotoxicity.

Animals ; Animals, Newborn ; Ca(2+) Mg(2+)-ATPase ; metabolism ; Calcineurin ; metabolism ; Calcium ; metabolism ; Calpain ; metabolism ; Cerebral Cortex ; metabolism ; Male ; Polybrominated Biphenyls ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo assess the potential hazard of environmental deca-brominated diphenyl ether (PBDE-209) exposure to the immune function of the offspring rats.

METHODSThe parental Wistar rats were exposed to PBDE-209 administered intragastrically during pregnancy and lactation, and the development of the immune organs and changes in T lymphocyte subset and their proliferation, NK cell surface markers CD161 and serum immunoglobulins (IgM and IgG) were observed.

RESULTSSignificant differences in the weight of the immune organs were noted between the exposure group and control group. In the exposure group, the percentage of T lymphocyte subset CD3(+), CD4(+), CD8(+), CD4(+)CD8(+), the percentage of NK cell surface markers CD16 1 and CD4(+)/CD8(+) ratio were lowered, while the percentage of CD4(-)CD8(-) cells increased. T lymphocyte subset proliferation in the exposure group did not show obviously changes, but compared with the control group, the IgM level in the exposure group was significantly lowered. No significant differences were observed in IgG levels between the exposure and control groups.

CONCLUSIONContinuous exposure to high-dose PBDE-209 in female rats during pregnancy and lactation results in possible adverse effect on the immune function of the offspring rats.

Animals ; CD4-CD8 Ratio ; Female ; Flame Retardants ; toxicity ; Halogenated Diphenyl Ethers ; Killer Cells, Natural ; drug effects ; immunology ; Lactation ; Male ; Maternal Exposure ; Phenyl Ethers ; toxicity ; Polybrominated Biphenyls ; toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar ; T-Lymphocyte Subsets ; drug effects ; immunology