The long-term effect of job mobility on workers' mental health: a propensity score analysis.

OBJECTIVES: The main purpose of this longitudinal study was to elucidate the impact of external job mobility, due to a change of employer, on mental health. METHODS: A cohort of Belgian employees from the IDEWE occupational medicine registry was followed-up for twenty-seven years, from 1993 to 2019. The use of drugs for neuropsychological diseases was considered as an objective indicator of mental health. The covariates were related to demographic, physical, behavioural characteristics, occupational and work-related risks. Propensity scores were calculated with a Cox regression model with time-varying covariates. The PS matching was used to eliminate the systematic differences in subjects' characteristics and to balance the covariates' distribution at every time point. RESULTS: The unmatched sample included 11,246 subjects, with 368 (3.3%) that changed their job during the baseline year and 922 (8.2%) workers that left their employer during the follow-up. More than half of the matched sample were males, were aged less than 38 years old, did not smoke, were physically active, and normal weighted, were not exposed to shift-work, noise, job strain or physical load. A strong association between job mobility and neuropsychological treatment was found in the matched analysis (HR = 2.065, 95%CI = 1.397-3.052, P-value < 0.001) and confirmed in the sensitivity analysis (HR of 2.012, 95%CI = 1.359-2.979, P-value < 0.001). Furthermore, it was found a protective role of physical activity and a harmful role of job strain on neuropsychological treatment. CONCLUSIONS: Our study found that workers with external job mobility have a doubled risk of treatment with neuropsychological medication, compared to workers without job mobility.

The Impact of a Change in Employment on Three Work-Related Diseases: A Retrospective Longitudinal Study of 10,530 Belgian Employees.

BACKGROUND: The literature that has investigated to what extent a change in employment contributes to good health is contradictory or shows inconsistent results. The aim of this study was to investigate whether an association exists between a change in employment and cardiovascular, musculoskeletal and neuropsychological diseases in a sample of 10,530 Belgian workers in a seven-year follow-up study period. METHODS: The following factors were analysed: Demographic variables, a change in employment and the work-related risks. Individuals being on medication for cardiovascular, musculoskeletal, and neuropsychological diseases were used as proxies for the three health issues. Logistic regression models for autocorrelated data with repeated measures were used to examine each medication type. RESULTS: A change in employment and psychosocial load can have an important effect on the health of cardiovascular employees. Demographic variables, such as BMI and age, are risk factors for all three medications. Repetitive, manual tasks, handling static, exposure to noise levels of 87 dB, mechanical and/or manual handling with loads, and shift work were found to be positively associated with medications taken for musculoskeletal diseases. Exposure to noise 80 dB(A), managing physical loads and night work were found to be associated with being on medication for neuropsychological diseases. Physical activity and skill levels were considered to be protective factors for being on medication for neuropsychological diseases. CONCLUSIONS: Change in employment and psychosocial load were found as two important risk factors for being on medication for cardiovascular (CVD). Dealing with loads, doing shift work and being daily exposed to the noise of 87 dB correlated with being on medication for musculoskeletal (MSD). Dealing with physical loads, doing night work and being exposed to the noise of 80 dB were risk factors for being on medication for neuropsychological (NPD). While doing physical activity and reporting higher skill levels were found to be protective factors for NPD.

Sacrospinous hysteropexy versus vaginal hysterectomy with suspension of the uterosacral ligaments in women with uterine prolapse stage 2 or higher: multicentre randomised non-inferiority trial.

OBJECTIVE: To investigate whether uterus preserving vaginal sacrospinous hysteropexy is non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments in the surgical treatment of uterine prolapse. DESIGN: Multicentre randomised controlled non-blinded non-inferiority trial. SETTING: 4 non-university teaching hospitals, the Netherlands. PARTICIPANTS: 208 healthy women with uterine prolapse stage 2 or higher requiring surgery and no history of pelvic floor surgery. INTERVENTIONS: Treatment with sacrospinous hysteropexy or vaginal hysterectomy with suspension of the uterosacral ligaments. The predefined non-inferiority margin was an increase in surgical failure rate of 7%. MAIN OUTCOME MEASURES: Primary outcome was recurrent prolapse stage 2 or higher of the uterus or vaginal vault (apical compartment) evaluated by the pelvic organ prolapse quantification system in combination with bothersome bulge symptoms or repeat surgery for recurrent apical prolapse at 12 months' follow-up. Secondary outcomes were overall anatomical recurrences, including recurrent anterior compartment (bladder) and/or posterior compartment (bowel) prolapse, functional outcome, complications, hospital stay, postoperative recovery, and sexual functioning. RESULTS: Sacrospinous hysteropexy was non-inferior for anatomical recurrence of the apical compartment with bothersome bulge symptoms or repeat surgery (n=0, 0%) compared with vaginal hysterectomy with suspension of the uterosacral ligaments (n=4, 4.0%, difference -3.9%, 95% confidence interval for difference -8.6% to 0.7%). At 12 months, overall anatomical recurrences, functional outcome, quality of life, complications, hospital stay, measures on postoperative recovery, and sexual functioning did not differ between the two groups. Five serious adverse events were reported during hospital stay. None was considered to be related to the type of surgery. CONCLUSIONS: Uterus preservation by sacrospinous hysteropexy was non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments for surgical failure of the apical compartment at 12 months' follow-up. TRIAL REGISTRATION: trialregister.nl NTR1866.

Hysteropexy in the treatment of uterine prolapse stage 2 or higher: a multicenter randomized controlled non-inferiority trial comparing laparoscopic sacrohysteropexy with vaginal sacrospinous hysteropexy (LAVA-trial, study protocol).

BACKGROUND: Pelvic organ prolapse is a common health problem: the lifetime risk of undergoing surgery for pelvic organ prolapse by the age of 85 years is 19%. Pelvic organ prolapse has significant negative effects on a woman's quality of life. Worldwide, vaginal hysterectomy is the leading treatment method for patients with symptomatic uterovaginal prolapse. Several studies have shown that vaginal sacrospinous hysteropexy and laparoscopic sacrohysteropexy are safe and effective alternatives in treating uterine descent. To date, it is unclear which of these techniques leads to the best operative result and the highest patient satisfaction. Therefore, we conducted the LAVA trial. METHODS: The LAVA trial is a randomized controlled multicenter non-inferiority trial. The study compares laparoscopic sacrohysteropexy with vaginal sacrospinous hysteropexy in women with uterine prolapse stage 2 or higher. The primary outcome of this study is surgical success of the apical compartment at 1 and 5 years follow-up. Secondary outcomes are subjective improvement on urogenital symptoms and quality of life (assessed by disease-specific and general quality of life questionnaires), complications following surgery, hospital stay, post-operative recovery, sexual functioning and costs-effectiveness. Evaluation will take place pre-operatively, and 6 weeks, 6 months, 12 months and annually till 60 months after surgery. Validated questionnaires will be used.Analysis will be performed according to the intention to treat principle. Based on comparable recurrence rates of 3% and a non-inferiority margin of 10%, 62 patients are needed in each arm to prove the hypothesis with a 95% confidence interval. DISCUSSION: The LAVA trial is a randomized controlled multicenter non-inferiority trial that will provide evidence whether the efficacy of laparoscopic sacrohysteropexy is non-inferior to vaginal sacrospinous hysteropexy in women with symptomatic uterine prolapse stage 2 or higher. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR4029.

The challenge of implementing laparoscopic sacrocolpopexy.

Vaginal-vault prolapse is effectively treated using sacrocolpopexy (SCP). A randomized trial demonstrated that it can be performed as effectively via laparoscopy (LSCP) as via laparotomy and with less morbidity. This evidence begs the question of how units offering abdominal sacrocolpopexy will implement LSCP. Several limitations need to be overcome. LSCP initially requires longer operating time; however, that decreases with surgeon experience. To decrease operation time, suture training can be implemented ahead. Following a 15-h suturing lab, trainees achieved comparable operation times after 30 cases. Dissection is another critical time-consuming step and is difficult to model. Proficiency is more dependent on patient characteristics, though this component is poorly studied. One experience showed it takes 60 procedures to effectively limit complications. The large number of patients required for surgeon training for this relative infrequent operation creates a problem, thus limiting the number of centers available for training surgeons within a reasonable period.

Value of urodynamics before stress urinary incontinence surgery: a randomized controlled trial.

OBJECTIVE: To estimate whether a strategy of immediate surgery was noninferior to a strategy based on discordant urodynamic findings followed by individually tailored therapy in women with stress urinary incontinence (SUI). METHODS: A multicenter diagnostic cohort study with an embedded noninferiority randomized controlled trial was conducted in six academic and 24 nonacademic Dutch hospitals. Women with predominant SUI eligible for surgical treatment based on clinical assessment were included between January 2009 and November 2010. All patients underwent urodynamics. In patients in whom urodynamics were discordant with clinical assessment, participants were randomly allocated to receive either immediate surgery or individually tailored therapy based on urodynamics. The primary outcome was clinical improvement assessed by the Urogenital Distress Inventory 12 months after baseline. Analysis was by intention to treat; a difference in mean improvement of 5 points or less was considered noninferior. RESULTS: Five hundred seventy-eight women with SUI were studied, of whom 268 (46%) had discordant findings. One hundred twenty-six patients gave informed consent for randomization and were allocated to receive immediate surgery (n=64) or individually tailored therapy (n=62). The mean improvement measured with the Urogenital Distress Inventory after 1 year was 44 points (±24) in the group receiving immediate surgery and 39 (±25) points in the group receiving individually tailored treatment. The difference in mean improvement was 5 points in favor of the group receiving immediate surgery (95% confidence interval -∞ to 5). There were no differences with respect to cure or complication rate. CONCLUSION: In women with uncomplicated SUI, an immediate midurethral sling operation is not inferior to individually tailored treatment based on urodynamic findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00814749. LEVEL OF EVIDENCE: I.

Clomipramine concentration and withdrawal symptoms in 10 neonates.

AIM: After in utero exposure to tricyclic antidepressants, neonatal withdrawal symptoms have been reported with an estimated incidence between 20 and 50%; however, few data are available for clomipramine. This could also be the case for neonatal pharmacokinetic clomipramine parameters and so this study was set up. METHODS: Babies exposed to clomipramine in utero were included in an observational study, approved by the local ethics committee, after written informed consent. Withdrawal symptoms were scored at 12, 24 and 48 h after birth using the Finnegan score. Plasma concentrations were determined using an in-house-developed, validated liquid chromatography with mass detection (LC-MSMS) method at 0, 12, 24 and 48 h after birth. RESULTS: We found that three of 11 pregnancies were complicated with pre-eclampsia. Ten neonates were observed for clomipramine withdrawal symptoms. The observed withdrawal symptoms were too short a period of sleep after feeding (6), poor feeding (3), mild to severe tremors (6), hyperactive Moro reflex (3) and respiratory rate >60 breaths min(-1). Serious withdrawal reactions, such as tachycardia and cyanosis, were seen. We calculated a half-life value of 42 ± 16 h for clomipramine in neonates. Only a weak correlation was found between withdrawal reactions and clomipramine plasma concentration or desmethylclomipramine plasma concentration. CONCLUSIONS: In neonates, clomipramine is eliminated with a half-life value of 42 h, compared with 20 h in adults. In two of 10 neonates, tachycardia and cyanosis were seen as serious withdrawal symptoms after maternal use of clomipramine.

[Uterus preserving surgery versus vaginal hysterectomy in treatment of uterine descent: a systematic review]. / Uterussparende chirurgie versus vaginale hysterectomie als behandeling van descensus uteri.

OBJECTIVE: To compare the outcomes of uterus preserving procedures and vaginal hysterectomy in treatment of uterine prolapse. DESIGN: Systematic review. METHOD: We searched in Pubmed, Embase, the Cochrane Library and the reference lists of relevant publications for articles comparing uterus preserving procedures with vaginal hysterectomy. The following outcome measures were studied: anatomical result, subjective outcome regarding prolapse symptoms, micturition, defecation and sexual function, quality of life, duration of surgery, duration of hospital stay, amount of blood loss, complications and postoperative recovery. RESULTS: We found one systematic review, one randomised trial and five cohort studies, from which eight comparative studies were selected for review. There was no difference in subjective outcome after sacrospinous fixation, Manchester Fothergill procedure, abdominal hysteropexy and intravaginal slingplasty on comparison with vaginal hysterectomy. All procedures, except for sacrospinous ligament fixation, had similar anatomical outcomes to vaginal hysterectomy. With the exception of Manchester Fothergill procedure hospital stay was shorter after uterus preservation. The quality of most of the studies was poor, with only small numbers of patients included and short-term follow up. CONCLUSIONS: Although some uterus preserving procedures are associated with shorter operation time, shorter duration of hospital stay and less blood loss than vaginal hysterectomy, based on the current literature there is no clear preference for either uterus preserving surgery or hysterectomy in surgical treatment of uterine descent, since randomised trials of sufficient quality are lacking. Prospective clinical randomised trials with long term follow-up are needed to investigate the value of uterine preserving procedures.

One-day versus 3-day suprapubic catheterization after vaginal prolapse surgery: a prospective randomized trial.

INTRODUCTION AND HYPOTHESIS: For prolonged catheterization after vaginal prolapse surgery with anterior colporrhaphy, the optimal duration to prevent overdistention of the bladder remains unknown. We designed this study to determine the optimal length of catheterization. METHODS: We conducted a prospective randomized trial in which 179 women were allocated to 1-day or 3-day suprapubic catheterization. The primary outcome was the duration of catheterization. RESULTS: Mean duration of catheterization and hospital stay was significantly shorter in the 1-day catheterization group. The number of successful voiding trials was higher in the 3-day catheterization group (90.9% versus 79.3%), but this did not reach statistical significance. The percentage of urinary tract infection did not differ significantly between the groups (4.5% versus 2.4%). CONCLUSION: Starting a voiding trial 1 day after vaginal prolapse surgery leads to shorter duration of catheterization and hospital stay.

Treatment of uterine prolapse stage 2 or higher: a randomized multicenter trial comparing sacrospinous fixation with vaginal hysterectomy (SAVE U trial).

BACKGROUND: Pelvic organ prolapse is a common health problem, affecting up to 40% of parous women over 50 years old, with significant negative influence on quality of life. Vaginal hysterectomy is currently the leading treatment method for patients with symptomatic uterine prolapse. Several studies have shown that sacrospinous fixation in case of uterine prolapse is a safe and effective alternative to vaginal hysterectomy. However, no large randomized trials with long-term follow-up have been performed to compare efficacy and quality of life between both techniques.The SAVE U trial is designed to compare sacrospinous fixation with vaginal hysterectomy in the treatment of uterine prolapse stage 2 or higher in terms of prolapse recurrence, quality of life, complications, hospital stay, post-operative recovery and sexual functioning. METHODS/DESIGN: The SAVE U trial is a randomized controlled multi-center non-inferiority trial. The study compares sacrospinous fixation with vaginal hysterectomy in women with uterine prolapse stage 2 or higher. The primary outcome measure is recurrence of uterine prolapse defined as: uterine descent stage 2 or more assessed by pelvic organ prolapse quantification examination and prolapse complaints and/or redo surgery at 12 months follow-up. Secondary outcomes are subjective improvement in quality of life measured by generic (Short Form 36 and Euroqol 5D) and disease-specific (Urogenital Distress Inventory, Defecatory Distress Inventory and Incontinence Impact Questionnaire) quality of life instruments, complications following surgery, hospital stay, post-operative recovery and sexual functioning (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire). Analysis will be performed according to the intention to treat principle. Based on comparable recurrence rates of 3% and considering an upper-limit of 7% to be non-inferior (beta 0.2 and one sided alpha 0.025), 104 patients are needed per group. DISCUSSION: The SAVE U trial is a randomized multicenter trial that will provide evidence whether the efficacy of sacrospinous fixation is similar to vaginal hysterectomy in women with uterine prolapse stage 2 or higher. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1866.

A randomized, controlled trial comparing an innovative single incision sling with an established transobturator sling to treat female stress urinary incontinence.

PURPOSE: Mid urethral sling procedures have become the surgical treatment of choice for female stress urinary incontinence. Innovative modifications of mid urethral sling procedures were recently introduced with the claim of offering similar efficacy and decreased morbidity. We compared the efficacy and morbidity of an innovative single incision mid urethral tape and an established transobturator procedure. MATERIALS AND METHODS: We performed a prospective, randomized, controlled trial in 6 teaching hospitals in Belgium and The Netherlands between 2007 and 2009. A total of 96 patients received a TVT Secur™ single incision sling and 98 received a TVT™ Obturator System. We collected data on patient characteristics, surgery related parameters, adverse events, clinical followup, Urogenital Distress Inventory and SF-36® scores, validated questionnaires on daily life activities and visual analog scores objectifying pain. Followup was 1 year. RESULTS: One-year followup was available for 75 single incision sling and 85 obturator system cases. Stress urinary incontinence could be objectified in 16.4% of the patients with a single incision sling and in 2.4% with an obturator system (p <0.05). Stress urinary incontinence was subjectively reported by 24% of single incision sling and 8% of obturator system patients (p <0.05). One year after surgery the mean ± SD UDI incontinence domain score in the single incision sling and obturator system groups was 21 ± 24 and 13 ± 21, respectively (p <0.01). Patients with a single incision sling experienced significantly less pain during the first 2 weeks after surgery (p <0.05) and returned significantly earlier to normal daily activity. The OR of re-intervention for stress urinary incontinence 1 year after receiving a single incision sling vs an obturator system was 2.3 (95% CI 1.9-2.7). CONCLUSIONS: The single incision sling procedure is associated with less postoperative pain and a lower objective cure rate than the obturator system procedure.

Trocar-guided mesh compared with conventional vaginal repair in recurrent prolapse: a randomized controlled trial.

OBJECTIVE: To compare efficacy and safety of trocar-guided tension-free vaginal mesh insertion with conventional vaginal prolapse repair in patients with recurrent pelvic organ prolapse. METHODS: Patients with recurrent pelvic organ prolapse stage II or higher were randomly assigned to either conventional vaginal prolapse surgery or polypropylene mesh insertion. Primary outcome was anatomic failure (pelvic organ prolapse stage II or higher) in the treated vaginal compartments. Secondary outcomes were subjective improvement, effects on bother, quality of life, and adverse events. Questionnaires such as the Incontinence Impact Questionnaire and Urogenital Distress Inventory were administered at baseline, 6 months, and 12 months. Anatomic outcomes were assessed by an unblinded surgeon. Power calculation with α=0.05 and ß=0.80 indicated that 194 patients were needed. RESULTS: Ninety-seven women underwent conventional repair and 93 mesh repair. The follow-up rate after 12 months was 186 of 190 patients (98%). Twelve months postsurgery, anatomic failure in the treated compartment was observed in 38 of 84 patients (45.2%) in the conventional group and in eight of 83 patients (9.6%) in the mesh group (P<.001; odds ratio, 7.7; 95% confidence interval, 3.3-18). Patients in either group reported less bulge and overactive bladder symptoms. Subjective improvement was reported by 64 of 80 patients (80%) in the conventional group compared with 63 of 78 patients (81%) in the mesh group. Mesh exposure was detected in 14 of 83 patients (16.9%). CONCLUSION: At 12 months, the number of anatomic failures observed after tension-free vaginal mesh insertion was less than after conventional vaginal prolapse repair. Symptom decrease and improvement of quality of life were equal in both groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00372190. LEVEL OF EVIDENCE: I.

Protocol for the value of urodynamics prior to stress incontinence surgery (VUSIS) study: a multicenter randomized controlled trial to assess the cost effectiveness of urodynamics in women with symptoms of stress urinary incontinence in whom surgical treatment is considered.

BACKGROUND: Stress urinary incontinence (SUI) is a common problem. In the Netherlands, yearly 64.000 new patients, of whom 96% are women, consult their general practitioner because of urinary incontinence. Approximately 7500 urodynamic evaluations and approximately 5000 operations for SUI are performed every year. In all major national and international guidelines from both gynaecological and urological scientific societies, it is advised to perform urodynamics prior to invasive treatment for SUI, but neither its effectiveness nor its cost-effectiveness has been assessed in a randomized setting. The Value of Urodynamics prior to Stress Incontinence Surgery (VUSIS) study evaluates the positive and negative effects with regard to outcome, as well as the costs of urodynamics, in women with symptoms of SUI in whom surgical treatment is considered. METHODS/DESIGN: A multicentre diagnostic cohort study will be performed with an embedded randomized controlled trial among women presenting with symptoms of (predominant) SUI. Urinary incontinence has to be demonstrated on clinical examination and/or voiding diary. Physiotherapy must have failed and surgical treatment needs to be under consideration. Patients will be excluded in case of previous incontinence surgery, in case of pelvic organ prolapse more than 1 centimeter beyond the hymen and/or in case of residual bladder volume of more than 150 milliliter on ultrasound or catheterisation. Patients with discordant findings between the diagnosis based on urodynamic investigation and the diagnosis based on their history, clinical examination and/or micturition diary will be randomized to operative therapy or individually tailored therapy based on all available information. Patients will be followed for two years after treatment by their attending urologist or gynaecologist, in combination with the completion of questionnaires. Six hundred female patients will be recruited for registration from approximately twenty-seven hospitals in the Netherlands. We aspect that one hundred and two women with discordant findings will be randomized. The primary outcome of this study is clinical improvement of incontinence as measured with the validated Dutch version of the Urinary Distress Inventory (UDI). Secondary outcomes of this study include costs, cure of incontinence as measured by voiding diary parameters, complications related to the intervention, re-interventions, and generic quality of life changes. TRIAL REGISTRATION: Clinical Trials NCT00814749.

Variations in spatial and temporal distribution of Archaea in the North Sea in relation to environmental variables.

The spatial and temporal distribution of pelagic Archaea was studied in the southern North Sea by rRNA hybridization, sequencing and quantification of 16S rRNA gene and membrane lipid analyses and related to physical, chemical and biological parameters to determine the factors influencing archaeal biogeography. A clear temporal variability was observed, with marine Crenarchaeota (Group I.1a) being relatively more abundant in winter and Euryarchaeota dominating the archaeal assemblage in spring and summer. Spatial differences in the lateral distribution of Crenarchaeota were also evident. In fact, their abundance was positively correlated with the copy number of the gene encoding the alpha subunit of crenarchaeotal ammonia monooxygenase (amoA) and with concentrations of ammonia, nitrate, nitrite and phosphorus. This suggests that most Crenarchaeota in the North Sea are nitrifiers and that their distribution is determined by nutrient concentrations. However, Crenarchaeota were not abundant when larger phytoplankton (>3 microm) dominated the algal population. It is hypothesized that together with nutrient concentration, phytoplankton biomass and community structure can predict crenarchaeotal abundance in the southern North Sea. Euryarchaeotal abundance was positively correlated with chlorophyll a concentrations, but not with phytoplankton community structure. Whether this is related to the potential of Euryarchaeota to perform aerobic anoxygenic phototrophy remains to be shown, but the conspicuous seasonal distribution pattern of Crenarchaeota and Euryarchaeota suggests that they occupy a different ecological niche.

Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants.

In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure-activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecularproperties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200-320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure-activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.

Levels of hexabromocyclododecane in harbor porpoises and common dolphins from western European seas, with evidence for stereoisomer-specific biotransformation by cytochrome p450.

Commercial hexabromocyclododecane (HBCD) is a high-production-volume flame-retardant applied in polystyrene foams. It contains three stereoisomers, of which gamma-HBCD always dominates. Here we report on the levels of HBCD in blubber of harbor porpoise and common dolphin from different European seas. The highest total (sigma)-HBCD levels were measured in harbor porpoises stranded on the Irish and Scottish coasts of the Irish Sea (median concentration 2.9 microg (g of lipid)(-1)) and the northwest coast of Scotland (median concentration 5.1 microg (g of lipid)(-1)). The median levels in other areas were, for the harbor porpoise south coast of Ireland, 1.2 microg (g of lipid)(-1), for the coasts of The Netherlands, Belgium, and France north of Calais (southern North Sea), 1.1 microg (g of lipid)(-1), for the east coast of Scotland (northern North Sea), 0.77 microg (g of lipid)(-1), and, for Galicia (Spain), 0.1 microg (g of lipid)(-1). The median levels for the common dolphin were, for west coast of Ireland, 0.9 microg (g of lipid)(-1), for the French coast of the English Channel between Normandy and Brest, 0.4 microg (g of lipid)(-1), and, for Galicia, 0.2 microg (g of lipid)(-1). A subset of 10 harbor porpoise and 9 common dolphin blubber samples representing all areas were analyzed by LC/MS to determine the diastereomeric composition of their HBCD residues. All samples showed exclusively the peak of alpha-HBCD. To test if biotransformation by the cytochrome P450 system could explain the observed compositional difference with technical HBCD mixtures, a number of in vitro assays with microsomal preparations of liver were carried out. We had to revert to material stored at -80 degrees C from laboratory rats and a fresh harbor seal found dead in the Dutch Wadden Sea, since such liver samples of cetaceans were not in our possession. The in vitro assays showed that beta- and gamma-HBCDs were indeed significantly metabolized when incubated in the presence of NADPH as electron donor, compared to a set of reference samples which were identical except for the addition of NADPH. In contrast, the peak of alpha-HBCD did not decrease significantly in the presence of NADPH. In separate microsomal assays with beta- and gamma-HBCDs, new peaks of brominated compounds (signal at m/z = 79 or 81) with masses of [M + 0] were formed only when NADPH was added. This confirms the process of cytochrome P450 mediated biotransformation. Although rat and harbor seal belong to different families of the mammalia than the cetaceans, we propose that biotransformation by the cytochrome P450 system is also the most likely process to explain the exclusive accumulation of alpha-HBCD in harbor porpoise and common dolphin.

Distribution and fate of HBCD and TBBPA brominated flame retardants in North Sea estuaries and aquatic food webs.

Tetrabromobisphenol A (TBBPA) and hexabromocyclododecane diastereoisomers (alpha-, beta/-, and gamma-HBCD) were investigated in effluents from sewage treatment works, landfill leachates, sediments, and food web organisms of the North Sea basin. Residues were quantified by liquid chromatography-mass spectrometry. Both flame retardants were enriched in sewage sludges, where a maximum total (sigma) HBCD concentration of 9.1 mg/kg (dry weight; d.w.) was found; TBBPA was at levels of 102 microg/kg. Landfill leachates from The Netherlands showed up to 36 mg (sigmaHBCD)/ kg (d.w.). gamma-HBCD dominated isomeric profiles in sediments, and concentrations were elevated near to a site of HBCD manufacture. alpha-HBCD was the primary congener detected in marine mammals; however, very few samples exhibited TBBPA. sigmaHBCD ranged from 2.1 to 6.8 mg/kg (lipid weight; l.w.) in liver and blubber of harbor porpoises (Phocoena phocoena) and seals (Phoca vitulina). TBBPA levels in cormorant (Phalacrocorax carbo) livers were up to 1 order of magnitude lower compared to sigmaHBCD. HBCD in eels (Anguilla anguilla) from the Scheldt basin (Belgium) reflected the spatial distribution of concentrations in local sediments. This study shows evidence of HBCD bioaccumulation at the trophic level and biomagnification in the ascending aquatic food chain, and these findings justify risk assessment studies at the ecosystem level.

Atmospheric transport of polybrominated diphenyl ethers and polychlorinated biphenyls to the Baltic Sea.

The atmospheric transport of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) was compared by measuring concentrations in air and deposition on an island located in the central basin of the Baltic Sea. Median sigmaPBDE and sigmaPCB concentrations (gaseous + particle) were 8.6 and 7.4 pg m(-3), respectively. Airborne PCBs were mainly found in the gaseous phase, while most of the PBDEs were detected on particles, which agrees with predicted particle/gas distributions. SigmaPBDE levels were dominated by the decabrominated BDE209 followed bythe tetrabrominated BDE47 and pentabrominated BDE99. BDE209 is a marker for the environmental distribution of the commercial deca-BDE formulation (>99.5% BDE209), whereas BDE47 and BDE99 are markers for the commercial penta-BDE mixture. General correlations between PBDEs and PCBs suggested similarities in sources and transport mechanism, while more detailed examination of the data identified notable behaviors and exceptions. Differences in regression slopes among tetra-, penta-, and decabrominated PBDEs may reflect different transport processes and the change in usage pattern. Tetra- and pentabrominated PBDEs may originate from secondary sources such as air surface exchange in a manner similar to that of the PCBs, while the deca-BDE209 formulation still has primary sources. The tribrominated BDE17 was also detected and is proposed to be a breakdown product due to atmospheric debromination processes. PBDEs had higher washout ratios than PCBs, explaining their higher concentrations compared to PCBs in precipitation (median of 6.0 and 0.5 ng L(-1) for sigmaBDE and sigmaPCB concentrations ("dissolved" + particle), respectively) than in air. The calculated yearly deposition of PBDEs and PCBs indicated that the atmospheric input of PBDEs to the Baltic Proper is currently exceeding that of the PCBs by a factor of 40, while that of the PCBs is decreasing.

Levels of polybrominated diphenyl ether flame retardants in sediment cores from Western Europe.

The levels of 14 brominated diphenyl ether (BDE)-congeners in sediment cores from three locations in Western Europe have been determined by GC/MS (negative chemical ionization mode). Sediments from the Drammenfjord (Norway), the western Wadden Sea (The Netherlands), and the freshwater Lake Woserin (Mecklenburg-Vorpommern, Germany) showed a time-dependent pattern in the distribution of BDEs since the beginning of the industrial production of polybrominated diphenyl ether (PBDE) formulations. Two out of three commercially available PBDE formulations could be distinguished. Starting from the beginning of the 1970s, the penta-mix formulation is clearly present, but the deca-mix formulation is only present since the late 1970s. The octa-mix formulation appeared to be still absent in these sediments, as its marker-congener, BDE183, was never detected. In the cores from the western Wadden Sea and Lake Woserin, all TOC-normalized concentrations of the penta-BDE-derived congeners were leveling off in the most recent sediment layers representing 1995 and 1997, whereas those in the Drammenfjord were still increasing in 1999. The levels of BDE209, however, decreased in the most recent layer of all three cores. In Lake Woserin, the concentrations of BDE209 were much less elevated above those of the tri- to hexa-BDEs than in the other the two areas. This might be due to the absence of a significant PBDE input from sources other than the atmosphere to this rural lake. The absence of all PBDE congeners in the older layers of the three sediment cores, as well as in several 100-150-My-old layers from an extremely organic-rich marine sediment from the Kimmeridge clay formation in Dorset (UK), indicated the absence of natural production of the BDE congeners analyzed.

Levels and trends of polybrominated diphenylethers and other brominated flame retardants in wildlife.

In this paper, we review the available data for polybrominated diphenylethers (PBDEs) and other flame retardants in wildlife, with the exception of fishes from Europe and North America which are covered in more detail elsewhere. More data are available for PBDEs than for other compounds, and these show that some of these compounds have become widely distributed in the environment, being found in samples from Europe, Australia, Azerbaijan, North America and the Arctic. Most available data relate to birds and their eggs and marine mammals, but the results of two food web studies are also included. The detection of PBDEs in pelagic marine mammals which feed in deep offshore waters, including baleen whales, indicate that these compounds have found their way into deep-water, oceanic food webs as well as the coastal/shallow sea examples described in detail. In the North Sea study, the most marked increase in lipid-normalised concentrations of six BDE congeners occurred during transfer from predatory fish to marine mammals. In the St. Lawrence Estuary study, marked differences in the ratios observed between species suggested that some fish species may be able to metabolise BDE99.A number of time trend studies have also been conducted, notably in guillemot eggs from Sweden (1969-2000), beluga whales from the Canadian Arctic (1982-1997 and 1989-2001) and from the St. Lawrence Estuary (1988-1999), and ringed seals from the Canadian Arctic (1981-2000). In the temperate latitudes, from these and other studies (e.g. in dated sediment cores), PBDE concentrations began to rise earlier than in those from high latitudes, in line with data for production and use. These trends have now slowed in many cases. Declines could be expected in Europe for many congeners following the cessation of manufacture and use of the penta-mix formulation in the EU, though these are not yet apparent in environmental samples. In Arctic biota, however, the rapidly rising concentrations seen currently in Canada could be expected to continue for some time, reflecting continued production and use of the penta-mix formulation in North America (>95% of the world total) and the impact of long-range atmospheric transport.