Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019.

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age, yet US incidence estimates do not exist, and prevalence estimates vary widely. OBJECTIVE: A population-based US study estimated the incidence, prevalence, and trends of polycystic ovary syndrome by age, race and ethnicity, and diagnosing provider type. STUDY DESIGN: A retrospective cohort study of patients enrolled in Kaiser Permanente Washington from 2006 to 2019 was conducted. All members identified as female, aged 16 to 40 years with at least 3 years of enrollment and at least 1 healthcare encounter during that time, were eligible for inclusion. Individuals were excluded if they had a history of oophorectomy or hysterectomy. Polycystic ovary syndrome cases were identified using the International Classification of Diseases diagnosis codes (International Classification of Diseases, Ninth Revision, 256.4 or International Classification of Diseases, Tenth Revision, E28.2). Individuals with a polycystic ovary syndrome diagnosis before study entry were excluded from incidence rate estimations. The incidence rates were adjusted by age using direct standardization to the 2010 US census data. Temporal trends in incidence were assessed using weighted linear regression (overall) and Poisson regression (by age, race and ethnicity, and provider type). Prevalent cases were defined as patients with a polycystic ovary syndrome diagnosis at any time before the end of 2019. Medical record review of 700 incident cases diagnosed in 2011-2019 was performed to validate incident cases identified by International Classification of Diseases codes using the Rotterdam criteria. RESULTS: Among 177,527 eligible patients who contributed 586,470 person-years, 2491 incident polycystic ovary syndrome cases were identified. The mean age at diagnosis was 26.9 years, and the mean body mass index was 31.6 kg/m2. Overall incidence was 42.5 per 10,000 person-years; the rates were similar over time but increased in individuals aged 16 to 20 years from 31.0 to 51.9 per 10,000 person-years (P=.01) and decreased among those aged 26 to 30 years from 82.8 to 45.0 per 10,000 person-years (P=.02). A small decreasing temporal trend in incidence rates was only observed among non-Hispanic White individuals (P=.01). The incidence rates by diagnosing provider type varied little over time. Among the 58,241 patients who contributed person-time in 2019, 3036 (5.2%) had a polycystic ovary syndrome International Classification of Diseases diagnosis code; the prevalence was the highest among the Hawaiian and Pacific Islander group (7.6%) followed by Native American and Hispanic groups. Medical record review classified 60% as definite or probable incident, 14% as possible incident, and 17% as prevalent polycystic ovary syndrome. The overall positive predictive value of polycystic ovary syndrome International Classification of Diseases diagnosis code for identifying definite, probable, or possible incident polycystic ovary syndrome was 76% (95% confidence interval, 72%-79%). CONCLUSION: Among a cohort of nonselected females in the United States, we observed stable rates of incident polycystic ovary syndrome diagnoses over time. The incidence of polycystic ovary syndrome was 4- to 5-fold greater than reported for the United Kingdom. The prevalence of polycystic ovary syndrome (5.2%) was almost double before the published US estimates (2.9%) based on the International Classification of Diseases codes. Race and ethnicity and provider type did not seem to have a major impact on temporal rates. Incident diagnoses increased over time in younger and decreased in older age groups, perhaps related to shifting practice patterns with greater awareness among practitioners of the impact of polycystic ovary syndrome on long-term health outcomes and improved prevention efforts. Moreover, increasing obesity rates may be a factor driving the earlier ages at diagnosis.

Is there synergistic interaction between fungicides inhibiting different enzymes in the ergosterol biosynthesis pathway in toxicity tests with the green alga Raphidocelis subcapitata?

Products used for plant protection or as biocides often contain more than one active substance together with numerous formulation additives. The environmental risk assessment for such commercial mixtures applies as default the concept of concentration addition. There is remaining regulatory concern, however, that underestimation of risks can occur if components in the mixture interact synergistically, i.e., elicit effects greater than those predicted by concentration addition. While cases of true synergism appear to be rare, the combination of substances targeting different steps in the same biosynthesis pathway was pointed out as one potential case of synergistic interaction although mechanistic explanations are lacking. The present study aimed to verify this hypothesis using the green alga Raphidocelis subcapitata as the regulatory standard test organism for which such synergism had been indicated earlier. Algal growth inhibition tests were conducted with mixtures of ergosterol biosynthesis inhibitors (tebuconazole, fenpropidin, and fenpropimorph). The fungicides were first tested individually to derive reliable data for a mixture toxicity prediction. The here determined toxicity estimates for two of the fungicides were considerably lower than the endpoints in the regulatory dossiers, which had been used for earlier mixture toxicity predictions. Experimentally observed toxicity estimates for the mixtures deviated <2.6-fold from the predicted values. Hence, the hypothesis of synergistic interaction between fungicides targeting different enzymes in the ergosterol biosynthesis was clearly not confirmed for the green alga R. subcapitata. Overall, the present study demonstrates the importance of reliable and correct input data for mixture toxicity predictions in order to avoid erroneous conclusions on non-additive (synergistic) interactions.

A sensitive multi-residue method for the determination of 35 micropollutants including pharmaceuticals, iodinated contrast media and pesticides in water.

A sensitive, multi-residue method using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to determine a representative group of 35 analytes, including corrosion inhibitors, pesticides and pharmaceuticals such as analgesic and anti-inflammatory drugs, five iodinated contrast media, ß-blockers and some of their metabolites and transformation products in water samples. Few other methods are capable of determining such a broad range of contrast media together with other analytes. We studied the parameters affecting the extraction of the target analytes, including sorbent selection and extraction conditions, their chromatographic separation (mobile phase composition and column) and detection conditions using two ionisation sources: electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI). In order to correct matrix effects, a total of 20 surrogate/internal standards were used. ESI was found to have better sensitivity than APCI. Recoveries ranging from 79 to 134 % for tap water and 66 to 144 % for surface water were obtained. Intra-day precision, calculated as relative standard deviation, was below 34 % for tap water and below 21 % for surface water, groundwater and effluent wastewater. Method quantification limits (MQL) were in the low ng L(-1) range, except for the contrast agents iomeprol, amidotrizoic acid and iohexol (22, 25.5 and 17.9 ng L(-1), respectively). Finally, the method was applied to the analysis of 56 real water samples as part of the validation procedure. All of the compounds were detected in at least some of the water samples analysed. Graphical Abstract Multi-residue method for the determination of micropollutants including pharmaceuticals, iodinated contrast media and pesticides in waters by LC-MS/MS.

Electrochemical decomposition of fluorinated wetting agents in plating industry waste water.

Electrochemical decomposition of fluorinated surfactants (PFAS, perfluorinated alkyl substances) used in the plating industry was analyzed and the decomposition process parameters optimized at the laboratory scale and production scale of a 500-liter reactor using lead electrodes. The method and system was successfully demonstrated under production conditions to treat PFAS) with up to 99% efficiency in the concentration range of 1,000-20,000 µg/l (1 ppm-20 ppm). The treatment also reduced hexavalent chromium (Cr(6+)) ions to trivalent chromium (Cr(3+)) ions in the wastewater. If the PFAS-containing wastewater is mixed with other wastewater streams, specifically from nickel plating drag out solution or when pH values >5, the treatment process is ineffective. For the short chain PFAS, (perfluorobutylsulfonate) the process was less efficient than C6-C8 PFAS. The process is automated and has safety procedures and controls to prevent hazards. The PFAS were decomposed to hydrogen fluoride (HF) under the strong acid electrochemical operating conditions. Analytical tests showed no evidence of organic waste products remaining from the process. Conventional alternative PFAS removal systems were tested on the waste streams and compared with each other and with the-E-destruct (electrochemical oxidation) process. For example, ion exchange resin (IX resin) treatment of wastewater to complex and remove PFAS was found to be seven times more efficient when compared to the conventional activated carbon absorption (C-treat) process. However, the E-destruct process is higher in capacity, exhibits longer service life and lower operating costs than either IX or C-treat methods for elimination of PFAS from these electroplating waste streams.

Characterization of anastrozole effects, delivered by an intravaginal ring in cynomolgus monkeys.

STUDY QUESTION: Is it feasible to deliver anastrozole (ATZ), an aromatase inhibitor (AI), by a vaginal polymer-based drug delivery system in the cynomolgus monkey (Macaca fascicularis) to describe the pharmacokinetic profile? SUMMARY ANSWER: The present study showed the effective release of ATZ into the systemic circulation from intravaginal rings in cynomolgus monkeys. WHAT IS KNOWN ALREADY: ATZ is a marketed drug with well documented pharmacological and safety profiles for oral administration. Aromatase is the key enzyme catalyzing estrogen biosynthesis and is overexpressed in endometriotic lesions. AIs show therapeutic efficacy in endometriosis in exploratory clinical trials. STUDY DESIGN, SIZE, DURATION: The pharmacokinetics of the in vivo release and the pharmacodynamic activity of ATZ released by intravaginal rings (IVR) were investigated in healthy cycling female cynomolgus monkeys in three different dose groups (n = 5) for one menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: IVRs for the cynomolgus monkey, releasing three different doses of ATZ were designed and tested for in vitro/in vivo release for up to 42 days. For pharmacokinetic and pharmacodynamic evaluation, plasma samples were taken once daily from Day 1 to 3 and then every third day until menses occurred (17-42 days). MAIN RESULTS AND THE ROLE OF CHANCE: ATZ was shown to be compatible with the IVR drug delivery system. An average in vivo release of 277 µg/day/animal of ATZ for one menstrual cycle was effective in causing a decrease of systemic estradiol (E2) levels by ∼30% without inducing counter regulation such as the elevation of FSH or the formation of ovarian cysts. LIMITATIONS, REASONS FOR CAUTION: The study was limited to three dose groups in which only the highest dose decreased the E2 level. Hence, additional research with IVRs releasing higher amounts of ATZ is required to define the threshold for an ATZ-dependent ovarian stimulation in cynomolgus monkeys. WIDER IMPLICATIONS OF THE FINDINGS: The release rate administered from IVRs is sufficient and in a range that supports feasibility of IVR administration of ATZ as a new approach for long-term therapy of estrogen-dependent diseases such as endometriosis in human.

Risk Factors for Incident Polycystic Ovary Syndrome Diagnosis.

Objective: While highly prevalent, risk factors for incident polycystic ovary syndrome (PCOS) are poorly delineated. Using a population-based cohort, we sought to identify predictors of incident PCOS diagnosis. Materials and Methods: A matched case-control analysis was completed utilizing patients enrolled in Kaiser Permanente Washington from 2006 to 2019. Inclusion criteria included female sex, age 16-40 years, and ≥3 years of prior enrollment with ≥1 health care encounter. PCOS cases were identified using International Classification of Diseases codes. For each incident case (n = 2,491), 5 patients without PCOS (n = 12,455) were matched based on birth year and enrollment status. Potential risk factors preceding diagnosis included family history of PCOS, premature menarche, parity, race, weight gain, obesity, valproate use, metabolic syndrome, epilepsy, prediabetes, and types 1 and 2 diabetes. Potential risk factors for incident PCOS diagnosis were assessed with univariate and multivariable conditional logistic regressions. Results: Mean age of PCOS cases was 26.9 years (SD 6.8). PCOS cases, compared with non-PCOS, were more frequently nulliparous (70.9% versus 62.4%) and in the 3 years prior to index date were more likely to have obesity (53.8% versus 20.7%), metabolic syndrome (14.5% versus 4.3%), prediabetes (7.4% versus 1.6%), and type 2 diabetes (4.1% versus 1.7%) (p < 0.001 for all comparisons). In multivariable models, factors associated with higher risk for incident PCOS included the following: obesity (compared with nonobese) Class I-II (body-mass index [BMI], 30-40 kg/m2; odds ratio [OR], 3.8; 95% confidence interval [CI], 3.4-4.2), Class III (BMI > 40 kg/m2; OR, 7.5, 95% CI, 6.5-8.7), weight gain (compared with weight loss or maintenance) of 1-10% (OR, 1.7, 95% CI, 1.3-2.1), 10-20% (OR, 1.9; 95% CI, 1.5-2.4), and >20% (OR, 2.6; 95% CI, 1.9-3.6), prediabetes (OR, 2.7; 95% CI, 2.1-3.4), and metabolic syndrome (OR, 1.8: 95% CI, 1.5-2.1). Conclusion: Excess weight gain, obesity, and metabolic dysfunction may play a key role in the ensuing phenotypic expression of PCOS. Treatment and prevention strategies targeted at preventing weight gain in early reproductive years may help reduce the risk of this syndrome.

Water quality of The Gambia River: A prospective drinking water supply.

Drinking water in The Gambia is mostly derived from boreholes that could potentially be contaminated. The Gambia River, a major river in West Africa that covers 12 % of the country's area, could be more exploited for drinking water supply. During the dry season, the total dissolved solids (TDS), ranging from 0.02 to 33 g/L in The Gambia River, decreases with the distance to the river mouth with no major inorganic contamination. The freshwater (<0.8 g/L TDS) starts from Jasobo at approximately 120 km from the river mouth and extends by about 350 km to the eastern border of The Gambia. With a dissolved organic carbon (DOC) ranging from 2 to 15 mgC/L, the natural organic matter (NOM) of The Gambia River was characterised by 40-60 % humic substances of paedogenic origin. With such characteristics, unknown disinfection by-products could be formed if chemical disinfection, such as chlorination, was implemented during treatment. Out of 103 types of micropollutants, 21 were detected (4 pesticides, 10 pharmaceuticals, 7 per- and polyfluoroalkyl substances (PFAS)) with concentrations ranging from 0.1 to 1500 ng/L. Pesticides, bisphenol A and PFAS concentrations were below the stricter EU guidelines set for drinking water. These were mainly confined to the urban area of high population density near the river mouth, while the quality of the freshwater region of low population density was surprisingly pristine. These results indicate that The Gambia River, especially in its upper regions, would be well suited as a drinking water supply when using decentralised ultrafiltration treatment for the removal of turbidity, as well as, depending on pore size, to a certain extent microorganisms and DOC.

Up-to-date monitoring data of wastewater and stormwater quality in Germany.

A comprehensive dataset of pollutant concentrations in German urban wastewater systems is available from recently completed monitoring projects. It contains up to 1000 concentration values for each of 79 substances in wastewater treatment plant (WWTP) effluents from 49 sites, and up to 157 values for each of 95 substances in combined sewer overflows (CSOs) from 12 sites. WWTP influents and stormwater outfalls were sampled to a lesser extent. All sampling methods were harmonised and aimed at collecting event or multi-day composite samples over periods of ≥1 year. Among the substances analysed were biocides and pesticides, polycyclic aromatic hydrocarbons, perfluorinated alkyl substances, metals, pharmaceuticals, benzotriazoles, phenols, acesulfame, di-(2-ethylhexyl)phthalate, and hexabromocyclododecanes. Occurrence, concentration ranges, and removal rates of selected WWTPs are presented. CSOs can be confirmed as an important pathway of metals and PAH to receiving waters when compared to WWTPs on the basis of annual per capita loads. The derived volume-weighted site mean concentrations are qualified to be used as representative input data for estimation of average substance emissions in large areas, e.g. on river basin scale, if no site-specific data are available. As such, they will contribute to the development of strategies to reduce substance emissions, taking into account not only WWTPs but also stormwater-related discharges.

Removal of Trace Organic Contaminants by Parallel Operation of Reverse Osmosis and Granular Activated Carbon for Drinking Water Treatment.

In response to increasingly stringent restrictions for drinking water quality, a parallel operation of two common technologies, low-pressure reverse osmosis (LPRO) and activated carbon filtration (ACF), was investigated in a comprehensive five-month pilot study for the removal of 32 typical trace organic contaminants (TrOCs) from Rhine bank filtrates employing a semi- technical plant. TrOCs have been divided into three groups: polyfluorinated aliphatic compounds; pharmaceuticals, pesticides and metabolites; in addition to volatiles, nitrosamines and aminopolycarboxylic acids, which were also examined. The net pressure behavior, normalized salt passage and rejection of TrOCs by LPRO were investigated and compared with ACF operation. In addition, autopsies from the leading and last membrane modules were performed using adenosine triphosphate (ATP), total organic carbon (TOC), ICP-OES and SEM-EDX techniques. Generally, rather stable LPRO membrane performance with limited membrane fouling was observed. TrOCs with a molecular weight of ≥ 150 Da were completely retained by LPRO, while the rejection of di- and trichloro compounds improved as the filtration progressed. ACF also showed significant removal for most of the TrOCs, but without desalination. Accordingly, the ACF and LPRO can be operated in parallel such that the LPRO permeate and the ACF-treated bypass can be mixed to produce drinking water with adjustable hardness and significantly reduced TrOCs.

Gene expression analysis in zebrafish embryos: a potential approach to predict effect concentrations in the fish early life stage test.

Based on the hypothesis that analysis of gene expression could be used to predict chronic fish toxicity, the zebrafish (Danio rerio) embryo test (DarT), developed as a replacement method for the acute fish test, was expanded to a gene expression D. rerio embryo test (Gene-DarT). The effects of 14 substances on lethal and sublethal endpoints of the DarT and on expression of potential marker genes were investigated: the aryl hydrocarbon receptor 2, cytochrome P450 1A (cypla), heat shock protein 70, fizzy-related protein 1, the transcription factors v-maf musculoaponeurotic fibrosarcoma oncogene family protein g (avian) 1 and NF-E2-p45-related factor, and heme oxygenase 1 (hmox1). After exposure of zebrafish embryos for 48 h, differential gene expression was evaluated using reverse transcriptase-polymerase chain reaction, gel electrophoresis, and densitometric analysis of the gels. All tested compounds significantly affected the expression of at least one potential marker gene, with cyp1a and hmox1 being most sensitive. Lowest-observed-effect concentrations (LOECs) for gene expression were below concentrations resulting in 10% lethal effects in the DarT. For 10 (3,4- and 3,5-dichloroaniline, 1,4-dichlorobenzene, 2,4-dinitrophenol, atrazine, parathion-ethyl, chlorotoluron, genistein, 4-nitroquinoline-1-oxide, and cadmium) out of the 14 tested substances, LOEC values derived with the Gene-DarT differ by a factor of less than 10 from LOEC values of fish early life stage tests with zebrafish. For pentachloroaniline and pentachlorobenzene, the Gene-DarT showed a 23- and 153-fold higher sensitivity, respectively, while for lindane, it showed a 13-fold lower sensitivity. For ivermectin, the Gene-DarT was by a factor of more than 1,000 less sensitive than the acute fish test. The results of the present study indicate that gene expression analysis in zebrafish embryos could principally be used to predict effect concentrations in the fish early life stage test.

Occurrence of the antidiabetic drug metformin in sewage and surface waters in Germany.

The antidiabetic drug metformin is among the pharmaceuticals with the highest production numbers world-wide. This paper presents first data on the occurrence of metformin in sewage and surface waters in Germany. Analysis of metformin is based on pre-concentration of the analyte onto a polymeric solid-phase material and subsequent determination by liquid chromatography and tandem mass spectrometry. Applying the method to sewage and surface waters, recoveries >90% and limits of detection of 10 ng L(-1) could be achieved by pre-concentration of a sample volume of only 10 mL. Measurements in sewage and surface waters showed an almost ubiquitous presence of metformin in the aquatic environment. The measured concentration levels in sewage treatment plant influents correlate nicely to the prescription numbers for metformin in Germany. During sewage treatment a significant reduction of metformin concentrations was observed which seems to be mainly due to microbial degradation. Despite this significant elimination during sewage treatment, metformin was found in all river waters under investigation. Concentration levels depend on the sewage fraction of the receiving waters and for most rivers are in the range of several 100 ng L(-1), i.e. in the same order of magnitude or even higher than for other relevant pharmaceutical residues.

Determination of monochloramine dissipation kinetics in various surface water qualities under relevant environmental conditions - Consequences regarding environmental risk assessment.

A total 190 experiments were performed to study the dissipation kinetics of monochloramine (NH2Cl, CAS no 10599-90-3) in surface water samples from six rivers (Loire, Rhône, Meuse, Garonne, Seine and Moselle) and an artificial reservoir (Mirgenbach), all located in France. Experiments were conducted in an open reactor, under relevant controlled environmental conditions. The impact of various parameters such as initial NH2Cl concentration, temperature, pH, presence of sediments, sampling site and collection period was investigated. It was found that NH2Cl dissipated rapidly without any lag phase, and that decay follows an apparent first-order kinetics (r2 > 0.99). Presence of sediment greatly accelerated decay. Half-lives were generally <1 h in river water in presence of natural sediment, but of several hours without sediment. The impact of pH was low for the normal river water pH range. However, increase in temperature significantly accelerated decay. The combination of high initial NH2Cl concentrations and elevated temperatures generally gives half-lives similar to those obtained at lower temperatures and lower concentrations. Short half-lives (0.06 to 1.50 h) were found in all the surface waters examined, regardless of geographic location of sampling site or collection period, indicating no temporal or site-specific effects on NH2Cl dissipation. Decay was slightly faster at lower initial concentrations, which supports extrapolation of half-lives measured in this study to a wide range of environmental concentrations. It can thus be assumed that NH2Cl degradation in river and reservoir waters is mainly determined by presence of sediments and temperature.

Environmental risk assessment of biocidal products: identification of relevant components and reliability of a component-based mixture assessment.

BACKGROUND: Biocidal products are mixtures of one or more active substances (a.s.) and a broad range of formulation additives. There is regulatory guidance currently under development that will specify how the combined effects of the a.s. and any relevant formulation additives shall be considered in the environmental risk assessment of biocidal products. The default option is a component-based approach (CBA) by which the toxicity of the product is predicted from the toxicity of 'relevant' components using concentration addition. Hence, unequivocal and practicable criteria are required for identifying the 'relevant' components to ensure protectiveness of the CBA, while avoiding unnecessary workload resulting from including by default components that do not significantly contribute to the product toxicity. The present study evaluated a set of different criteria for identifying 'relevant' components using confidential information on the composition of 21 wood preservative products. Theoretical approaches were complemented by experimentally testing the aquatic toxicity of seven selected products. RESULTS: For three of the seven tested products, the toxicity was underestimated for the most sensitive endpoint (green algae) by more than factor 2 if only the a.s. were considered in the CBA. This illustrated the necessity of including at least some additives along with the a.s. Considering additives that were deemed 'relevant' by the tentatively established criteria reduced the underestimation of toxicity for two of the three products. A lack of data for one specific additive was identified as the most likely reason for the remaining toxicity underestimation of the third product. In three other products, toxicity was overestimated by more than factor 2, while prediction and observation fitted well for the seventh product. Considering all additives in the prediction increased only the degree of overestimation. CONCLUSIONS: Supported by theoretical calculations and experimental verifications, the present study developed criteria for the identification of CBA-relevant components in a biocidal product. These criteria are based on existing criteria stated in the regulation for classification, labelling and packaging of substances. The CBA was found sufficiently protective and reliable for the tested products when applying the here recommended criteria. The lack of available aquatic toxicity data for some of the identified relevant components was the main reason for underestimation of product toxicity.

Prospective environmental risk assessment of mixtures in wastewater treatment plant effluents - Theoretical considerations and experimental verification.

The aquatic environment is continually exposed to a complex mixture of chemicals, whereby effluents of wastewater treatment plants (WWTPs) are one key source. The aim of the present study was to investigate whether environmental risk assessments (ERAs) addressing individual substances are sufficiently protective for such coincidental mixtures. Based on a literature review of chemicals reported to occur in municipal WWTP effluents and mode-of-action considerations, four different types of mixtures were composed containing human pharmaceuticals, pesticides, and chemicals regulated under REACH. The experimentally determined chronic aquatic toxicity of these mixtures towards primary producers and the invertebrate Daphnia magna could be adequately predicted by the concept of concentration addition, with up to 5-fold overestimation and less than 3-fold underestimation of mixture toxicity. Effluents of a municipal WWTP had no impact on the predictability of mixture toxicity and showed no adverse effects on the test organisms. Predictive ERAs for the individual mixture components based on here derived predicted no effect concentrations (PNECs) and median measured concentrations in WWTP effluents (MCeff) indicated no unacceptable risk for any of the individual chemicals, while MCeff/PNEC summation indicated a possible risk for multi-component mixtures. However, a refined mixture assessment based on the sum of toxic units at species level indicated no unacceptable risks, and allowed for a safety margin of more than factor 10, not taking into account any dilution of WWTP effluents by surface waters. Individual substances, namely climbazole, fenofibric acid and fluoxetine, were dominating the risks of the investigated mixtures, while added risk due to the mixture was found to be low with the risk quotient being increased by less than factor 2. Yet, uncertainty remains regarding chronic mixture toxicity in fish, which was not included in the present study. The number and identity of substances composing environmental mixtures such as WWTP effluents is typically unknown. Therefore, a mixture assessment factor is discussed as an option for a prospective ERA of mixtures of unknown composition.

Analysis of isothiazolinones in environmental waters by gas chromatography-mass spectrometry.

This paper describes an analytical method for the determination of five biocides of isothiazolinone type (2-methyl-3-isothiazolinone (MI), 5-chloro-2-methyl-3-isothiazolinone (CMI), 1,2-benzisothiazolinone (BIT), 2-octyl-3-isothiazolinone (OI), 4,5-dichloro-2-octyl-3-isothiazolinone (DCOI)) in environmental waters. The method is based on pre-concentration of the analytes by solid-phase extraction onto a mixture of a polymeric material and RP-C18 material and subsequent determination by gas chromatography-mass spectrometry (GC-MS). One of the target compounds (BIT) is derivatised with diazomethane after pre-concentration to improve its chromatographic performance. The method was optimised with respect to pre-concentration conditions (liquid-liquid extraction versus solid-phase extraction, solid-phase material, elution solvent and volume) and extensively validated. Applying the method to surface waters, groundwaters, and drinking waters, limits of detection between 0.01 and 0.1 microg/l could be achieved and the repeatability was below 10% for all compounds except for MI. Additional investigations showed that the stability of the isothiazolinones in environmental waters is limited and sample storage at 4 degrees C is mandatory to preserve the target biocides. First investigations of influents and effluents of a wastewater treatment plant showed that conventional wastewater treatment exhibits a high efficiency for removal of the isothiazolinones. In river waters, the target isothiazolinones could not be detected.

Occurrence and fate of nitrification and urease inhibitors in the aquatic environment.

Nitrification and urease inhibitors (NUIs) decelerate the bacterial oxidation of nitrogen species by suppressing the activity of soil microorganisms. Thus, nitrogen losses can be limited and the efficiency of nitrogen fertilizers can be increased. After application NUI transfers to surface water may occur through leaching or surface run-off. In order to assess the occurrence of nitrification and urease inhibitors in the aquatic environment a multi-analyte high-performance liquid chromatography-mass spectrometry method was developed. 1H-1,2,4-Triazole and dicyandiamide (DCD) were detected for the first time in German surface waters. Only at a few sites 1H-1,2,4-triazole has been episodically detected with concentrations up to the µg L(-1)-range. DCD was ubiquitously present in German surface waters. An industrial site was identified as the point source of DCD being responsible for exceptionally high DCD concentrations of up to 7.2 mg L(-1) in close proximity to the point of discharge. Both compounds were also detected in at least one wastewater treatment plant effluent, but their concentrations in surface waters did not correlate with those of typical markers for domestic wastewater. Other NUIs were not detected in any of the samples. Laboratory-scale batch tests proved that 1H-1,2,4-triazole and DCD are not readily biodegradable, are not prone to hydrolysis and do not tend to adsorb onto soil particles. Ozonation and activated carbon filtration proved to be ineffective for their removal.

Automated water analyser computer supported system (AWACSS) Part I: Project objectives, basic technology, immunoassay development, software design and networking.

A novel analytical system AWACSS (automated water analyser computer-supported system) based on immunochemical technology has been developed that can measure several organic pollutants at low nanogram per litre level in a single few-minutes analysis without any prior sample pre-concentration nor pre-treatment steps. Having in mind actual needs of water-sector managers related to the implementation of the Drinking Water Directive (DWD) (98/83/EC, 1998) and Water Framework Directive WFD (2000/60/EC, 2000), drinking, ground, surface, and waste waters were major media used for the evaluation of the system performance. The instrument was equipped with remote control and surveillance facilities. The system's software allows for the internet-based networking between the measurement and control stations, global management, trend analysis, and early-warning applications. The experience of water laboratories has been utilised at the design of the instrument's hardware and software in order to make the system rugged and user-friendly. Several market surveys were conducted during the project to assess the applicability of the final system. A web-based AWACSS database was created for automated evaluation and storage of the obtained data in a format compatible with major databases of environmental organic pollutants in Europe. This first part article gives the reader an overview of the aims and scope of the AWACSS project as well as details about basic technology, immunoassays, software, and networking developed and utilised within the research project. The second part article reports on the system performance, first real sample measurements, and an international collaborative trial (inter-laboratory tests) to compare the biosensor with conventional anayltical methods.

Automated Water Analyser Computer Supported System (AWACSS) Part II: Intelligent, remote-controlled, cost-effective, on-line, water-monitoring measurement system.

A novel analytical system AWACSS (Automated Water Analyser Computer Supported System) based on immunochemical technology has been evaluated that can measure several organic pollutants at low nanogram per litre level in a single few-minutes analysis without any prior sample pre-concentration or pre-treatment steps. Having in mind actual needs of water-sector managers related to the implementation of the Drinking Water Directive (DWD) [98/83/EC, 1998. Council Directive (98/83/EC) of 3 November 1998 relating to the quality of water intended for human consumption. Off. J. Eur. Commun. L330, 32-54] and Water Framework Directive (WFD) [2000/60/EC, 2000. Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a framework for Community action in the field of water policy. Off. J. Eur. Commun. L327, 1-72], drinking, ground, surface, and waste waters were major media used for the evaluation of the system performance. The first part article gave the reader an overview of the aims and scope of the AWACSS project as well as details about basic technology, immunoassays, software, and networking developed and utilised within the research project. The second part reports on the system performance, first real sample measurements, and an international collaborative trial (inter-laboratory tests) to compare the biosensor with conventional anayltical methods. The systems' capability for analysing a wide range of environmental organic micro-pollutants, such as modern pesticides, endocrine disrupting compounds and pharmaceuticals in surface, ground, drinking and waste water is shown. In addition, a protocol using reconstitution of extracts of solid samples, developed and applied for analysis of river sediments and food samples, is presented. Finally, the overall performance of the AWACSS system in comparison to the conventional analytical techniques, which included liquid and gas chromatographic systems with diode-array UV and mass spectrometric detectors, was successfully tested in an inter-laboratory collaborative trial among six project partners.

Analysis of iodinated X-ray contrast agents in water samples by ion chromatography and inductively-coupled plasma mass spectrometry.

In this paper, an analytical method for the determination of six iodinated X-ray contrast agents (amidotrizoic acid, iohexol, iomeprol, iopamidol, iopromide, and ioxitalamic acid), iodide, and iodate in water samples is presented. The method is based on a separation of the analytes by ion chromatography (IC) and a subsequent detection by inductively-coupled plasma mass spectrometry (ICP-MS). The method was optimised with respect to separation conditions (column type and eluent composition) and extensively validated. Without pre-concentration of the samples, limits of detection below 0.2 microg/l could be achieved whereby reproducibility was below 6% for all compounds under investigation.