Environmental Pollutants ; Flame Retardants ; Hydrocarbons, Brominated

OBJECTIVETo investigate the occurrence and concentrations of melamine and its analogues in tainted infant formula and to identify the etiologic factors for the urinary stones epidemic in infants and young children in China in 2008.

METHODSSanlu infant formula samples were collected from families of the affected children in Gansu province, and markets in Gansu and Hebei provinces and Beijing city. Melamine and its analogues, including cyanuric acid, ammeline, and ammelide were measured by gas chromatography/tandem mass spectrometry.

RESULTSHigh prevalence and concentrations of melamine were found in Sanlu infant formula samples, with low concentrations of cyanuric acid, ammeline and ammelide. Melamine were detected in 87 out of 111 Sanlu infant formula samples with a range of 118 to 4,700 mg/kg.

CONCLUSIONThe results provide strong evidence for melamine as the etiological factor for the urinary stones epidemic in infants and young children in China in 2008.

China ; Flame Retardants ; analysis ; Food Contamination ; Humans ; Infant ; Infant Formula ; chemistry ; Triazines ; chemistry

OBJECTIVETo estimate the dietary melamine exposure in Chinese infants and young children from the consumption of melamine adulterated Sanlu infant formula.

METHODSFour age groups of infants and young children (3, 6, 12, and 24 months) were chosen as the assessed subjects and the maximum amount of infant formula consumption was estimated based on the recommended usage level in the package insert of Sanlu infant formula and other brands. Melamine was analyzed in 111 Sanlu infant formula samples collected from the markets in Beijing and Gansu province using the LC-MS-MS with a limit of quantification of 0.05 mg/kg. Four levels of melamine concentration were chosen to estimate the dietary intakes, including the mean, median, 90th percentile, and maximum.

RESULTSThe infants of 3 months had the highest intake of melamine, and with the increase of the age (month), the intake decreased. Based on the median melamine concentration (1,000 mg/kg) as an example, the melamine intakes for the infants of 3, 6, 12, and 24 months were 23.4, 21.4, 15.0, and 8.6 mg/kg bw/d, respectively.

CONCLUSIONDietary melamine intakes from tainted Sanlu infant formula significantly exceeded the TDI level (0.2 mg/kg bw/d) recommended by the WHO Expert Meeting in 2008. However, the present assessment has some limitations including the poor representative samples, the varied melamine concentrations in the adulterated Sanlu infant formula, and other brand infant formula possibly consumed by these infants.

China ; Diet ; Eating ; Female ; Flame Retardants ; analysis ; metabolism ; Food Contamination ; Humans ; Infant ; Infant Formula ; chemistry ; Male ; Triazines ; chemistry ; metabolism

Information regarding decabromodiphenyl ethane (DBDPE) effects on hepatotoxicity and metabolism is limited. In the present study, Wistar rats were given oral DBDPE at different doses. DBDPE induced oxidative stress, elevated blood glucose levels, increased CYP2B2 mRNA, CYP2B1/2 protein, 7-pentoxyresorufin O-depentylase (PROD) activity, and induced CYP3A2 mRNA, CYP3A2 protein, and luciferin benzylether debenzylase (LBD) activity. UDPGT activity increased with its increasing exposure levels, suggesting that oral DBDPE exposure induces drug-metabolizing enzymes in rats via the CAR/PXR signaling pathway. The induction of CYPs and co-regulated enzymes of phase II biotransformation may affect the homeostasis of endogenous substrates, including thyroid hormones, which may, in turn, alter glucose metabolism.
Animals ; Bromobenzenes ; toxicity ; Chemical and Drug Induced Liver Injury ; enzymology ; etiology ; Female ; Flame Retardants ; toxicity ; Liver ; drug effects ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Toxicity Tests

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 develop an analytical method for simultaneously qualitative and quantitative determination of melamine and triazine-related by-products including ammelide, ammeline, and cyanuric acid in milk and milk products by gas chromatography-tandem mass spectrometry (GC-MS/MS).

METHODSMelamine and triazine-related by-products namely ammelide, ammeline and cyanuric acid in the samples were extracted in a solvent mixture of diethylamine, water, and acetonitrile (10:40:50, V/V/V). After centrifugation, an aliquot of the supernatant was evaporated to dryness under a gentle stream of nitrogen gas, and then melamine and triazine-related by-products were derivatized using BSTFA with 1% TMCS. The derivatives of melamine and its analogues were determined by gas chromatography/tandem mass spectrometry using multiple reactional monitoring (MRM) with 2, 6-Diamino-4-chloropyrimidine (DACP) being used as an internal standard.

RESULTSThe linear detectable ranges were from 0.004 mg/kg to 1.6 mg/kg for melamine, ammelide, ammeline, and cyanuric acid with a correlation coefficient no less than 0.999. The recovery rates of the four compounds in spiked blank milk powder at concentrations 0.5, 1, 2 mg/kg were between 61.4%-117.2%, and the relative standard deviation was no more than 11.5% (n=6). The detection limits of melamine, ammelide, ammeline and cyanuric acid in milk powder were 0.002 mg/kg with a ratio of signal to noise of 3.

CONCLUSIONThis GC-MS/MS method for simultaneous determination of melamine, ammelide, ammeline, and cyanuric acid in milk and milk products is sensitive and specific.

Animals ; Cattle ; Chromatography, Gas ; Flame Retardants ; analysis ; Food Contamination ; Milk ; chemistry ; Molecular Sequence Data ; Sensitivity and Specificity ; Tandem Mass Spectrometry ; Triazines ; chemistry

To investigate the genotoxicity and reveal the potential toxicological mechanisms of Hexabromocyclododecane (HBCD), human breast cells HBL-100 were exposed to a sequence of HBCD concentrations (0, 5, 10, and 50 mg/L) for 24 h. With a series of zymology and molecular biology methods, we found that HBCD induced dose-dependent oxidative stress on HBL-100 DNA. As revealed in qRT-PCR, activated prognostic factor ATM down-regulated tumor suppressor gene BRCA1 and prompted DNA repair genes hOGG1 and hMTH1 expression in lower concentrations of HBCD (< 10 mg/L). However, DNA repair were inhibited as well as cell proliferation rate by higher concentrations of HBCD (50 mg/L). The results inferred that the genotoxicity of HBCD was dose-dependent and related to DNA repair pathway.
Breast Neoplasms ; chemically induced ; genetics ; Cell Line, Tumor ; DNA Damage ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; Female ; Flame Retardants ; toxicity ; Humans ; Hydrocarbons, Brominated ; toxicity ; Oxidative Stress ; Random Allocation

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