Extraction and cleanup methods for analysis of phenolic and neutral organohalogens in plasma.

A method for the analysis of potential endocrine-disrupting compounds, such as phenolic halogenated compounds (e.g., chlorinated and brominated phenols) and hydroxylated PCBs, in blood plasma is presented. Neutral halogenated compounds, specifically brominated diphenyl ethers and PCBs, are also included in the evaluation. An efficient denaturation and extraction step is described, and three methods for lipid removal are evaluated. The latter includes a nondestructive method based on high-resolution gel permeation chromatography (HR-GPC), a newly developed silica gel/sulfuric acid column, and lipid removal by sulfuric acid treatment. Recoveries, based on gas chromatography with an electron capture detector (GC-ECD), were between 70 and 90% for most of the studied compounds. The recoveries of phenolic compounds were generally slightly lower than those of the neutral compounds. The sulfuric acid treatment and silica gel/sulfuric acid column gave the highest yields for acid stable compounds, although a few target compounds were lost during that treatment and all compounds were recovered with the HR-GPC method.

Reproductive toxicity in mink (Mustela vison) chronically exposed to environmentally relevant polychlorinated biphenyl concentrations.

Female mink were exposed to a technical polychlorinated biphenyl (PCB) preparation (Clophen A50 [A50]; 0.1 or 0.3 mg/animal/d), one fraction of A50 containing the non- and mono-ortho-chlorinated congeners (0-1-ortho-chlorobiphenyls [CBs]), another fraction of A50 containing the congeners with two to four ortho-chlorines (2-4-ortho-CBs), or an organic extract from Baltic gray seal blubber. The animals were exposed for 18 months, including two reproduction seasons. Among the animals given the highest dose of A50, the whelping frequency was reduced in the second reproductive season, and all kits died within 24 h of birth. Reproduction was also impaired by the lower dose of A50. Daily exposure to the 0-1-ortho-CBs separated from 0.3 mg A50 severely reduced kit survival. Reproduction was not significantly impaired by daily exposure to the 2-4-ortho-CBs separated from 0.3 mg A50 or by exposure to the blubber extract. We conclude that the reproductive toxicity in chronically PCB-exposed mink is caused by the aryl hydrocarbon (Ah) receptor agonists. The lowest-observed-effect level for reproductive impairment was 2.4 ng 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) per kilogram body weight and day (22 pg TEQs/g feed). Ethoxyresorufin-O-dealkylase (EROD) was strongly induced by the 0-1-ortho-CBs and pentoxyresorufin-O-dealkylase by the 2-4-ortho-CBs. High EROD activity was correlated with low kit production, and consequently EROD may serve as a marker for reproductive toxicity by Ah receptor agonists in mink.

Polybrominated diphenyl ethers in maternal serum, umbilical cord serum, colostrum and mature breast milk. Insights from a pilot study and the literature.

Human serum and mother's milk are frequently used to assess exposure to polybrominated diphenyl ethers (PBDEs), including transplacental transfer to the foetus. However, little is known about the kinetics of PBDEs, especially the highly brominated BDE congeners. In this pilot study, maternal serum samples were collected from 10 women at delivery and five to six weeks post partum. Umbilical serum was also obtained. Milk was donated two to five days, and five to six weeks after delivery. The amount of PBDEs in these samples was determined using liquid-liquid extraction and GC/MS. Low, moderately and highly brominated diphenyl ethers were present in umbilical cord serum, indicating placental transfer. The lipid-adjusted levels of BDE-47, BDE-207 and BDE-209 were similar in maternal and umbilical cord serum, whereas the cord serum levels for the penta- to octa-BDEs quantified were lower than in maternal serum. Marked changes were seen in the congener pattern in breast milk during the first month of lactation, whereas maternal serum levels did not change significantly. The general pattern was an enrichment of low to moderately brominated congeners (i.e. from BDE-17 to BDE-154, with the exception of BDE-28) in colostrum compared with maternal serum. In contrast, more highly brominated congeners were found at similar, or lower levels in colostrum than in maternal serum. After the transition from colostrum to mature milk, the levels of BDE-153 and BDE-209 were substantially reduced, and BDE-209 was below the limit of detection in 6 out of 9 samples. A literature review on the design and reporting of studies on the transfer of PBDEs from mother to infant revealed a lack of transparency in many cases. The use of the recently published STROBE-ME guidelines is therefore recommended.

Management of radiation-induced sarcomas in a tertiary referral centre: a review of 25 cases.

INTRODUCTION: Radiation-induced sarcomas are a rare and late complication of radiotherapy for breast carcinoma which often have poor prognosis. METHODS: This study is a retrospective review of 25 patients referred to a regional sarcoma unit between 1978 and 2009. RESULTS: Radiation-induced sarcoma following the diagnosis and treatment of breast cancer occurred after a mean period of 156 months. Anatomical sites involved were the breast, chest wall, clavicle, scapula, humerus and axilla. Twenty one patients had wide local excision followed by chest wall reconstruction, latissimus dorsi flap cover or limb amputation. The estimated five years survival following the diagnosis of the radiation-induced sarcoma was 27% and the local recurrence rate 52%. CONCLUSION: Radiation-induced sarcoma following breast cancer has high local recurrence rate and poor prognosis. They should be managed in a multi-disciplinary setting. Long-term follow-up of patients treated with radiotherapy for breast cancer is therefore advisable.

Persistent organohalogen contaminants in plasma from groups of humans with different occupations in Bangladesh.

The present study is aimed to assess persistent organic halogenated pollutants in humans living in Bangladesh. The results are compared to other similar studies in the region and globally. Human blood plasma were collected from groups of men and women with different occupations, i.e. being students, garment industry workers, employees at the Power Development Board (PDB), all groups in Dhaka, fishermen and fishermen wife's from Dhaka and another group from Barisal district. The plasma was analysed for hexachlorobenzene (HCB), the hexachlorocyclohexane isomers, alpha-HCH, beta-HCH, gamma-HCH and delta-HCH, the DDT group of chemicals, chlordane compounds, trans-chlordane, cis-chlordane, oxychlordane, trans-nonachlor, trans-heptachlorepoxide, methoxychlor and mirex. The most abundant contaminant, in all groups studied, p,p'-DDE is dominating, with p,p'-DDT/Sigma DDT ratios indicating recent and ongoing DDT exposure. Among the other pesticides analysed beta-HCH is the most abundant indicating the use of technical HCH products instead of Lindane (gamma-HCH). While the Sigma DDT is present in the low ppm range the beta-HCH is detected in up to approx. 400 ppb, lipid basis. The beta-HCH is most abundant in the groups of students. In contrast to the pesticides analysed very low concentrations of polychlorinated biphenyls (PCB) are present in all study groups, with e.g. CB-153 in the range of 5-30 ng g(-1) fat. The concentrations of the DDT group of chemical differ significantly between fishermen and fishermen's wives living and working in the Dhaka area versus those living and working in Barisal. Also, fishermen and their wives had significantly different concentrations of DDT compared to garment industry workers.

Tumour marker prescriptions for cancer screening in the Hellenic primary care.

Tumour markers are neither sensitive nor specific enough for cancer screening. Despite established guidelines, tumour marker 'screening myth' may be alive among physicians, but no study has analysed the phenomenon. This study aims to investigate tumour marker recommendation for screening purposes in primary care setting. A total of 209 Hellenic physicians were surveyed for screening activities by a multiple-choice questionnaire. Data were abstracted for the following tumour marker recommendations: carcinoembryonic antigen (CEA); cancer antigens 19.9, 125 and 15.3; alpha-fetoprotein and beta-human chorionic gonadotropin (beta-HCG). A high rate of physicians advocate that tumour markers in cancer screening (range from 24% for beta-HCG to 46% for CEA). This phenomenon is not related to age, sex, type and level of physicians' specialization. In conclusion, many physicians recommend tumour markers for screening purposes. This may be harmful, since their prescriptions unnecessarily burden health economics, and further evaluation of false-positive findings might be associated with increased costs and risk from additional diagnostic/therapeutic interventions.

Identification of hydroxylated PCB metabolites and other phenolic halogenated pollutants in human blood plasma.

A growing number of studies have reported phenolic halogenated compounds (PHCs) that are retained in the blood of humans and wildlife. These PHCs may be industrial chemicals; metabolites thereof, as in the case with polychlorobiphenylols (OH-PCBs); or of natural origin. The present study was aimed to identify hitherto unknown PHCs in human plasma with chemical structures that are consistent to PHCs known to possess endocrine-disrupting activity. For this purpose, samples of blood plasma from 10 randomly selected male blood donors from Sweden were pooled and analyzed by GC/ECD and GC/MS. Brominated, bromochlorinated, and chlorinated methyl derivatives of phenols and OH-PCBs were synthesized to be used as authentic reference standards. More than 100 PHCs were indicated in the plasma, and among those a total of 9 monocyclic brominated or chlorinated phenol-, guaiacol-, and/or catechol-type compounds were identified as their methylated derivatives. The two major compounds were 2,4,6-tribromophenol and pentachlorophenol. Thirty-eight OH-PCB congeners were structurally identified on two GC columns of different polarity. The origin of the OH-PCB metabolites in the context of their parent PCB congeners are suggested. Other PHCs identified in the male plasma were Triclosan (5-chloro-2-[2,4-dichlorophenoxy] phenol), a common bactericide; 4-hydroxy-heptachlorostyrene, a metabolite of octachlorostyrene; and 3,5-dibromo-2-(2,4-dibromophenoxy)phenol, a natural compound and a potential metabolite of polybrominated diphenyl ethers.