Validation of a method to determine transformation of chemicals in anaerobic liquid pig and cattle manure for the OECD test guideline programme.

Manure is widely used as a fertilizer and applied to agricultural land. It may contain highly active chemicals like veterinary medicinal products or biocides, which enter into the environment by this pathway. This is recognized by several regulatory frameworks, however, a detailed method for examining the transformation of chemicals in manure was lacking. This article describes the validation of a method for studying the anaerobic transformation of chemicals in pig and cattle liquid manure. Different steps are covered with an emphasis on the validation ring test and the OECD (Organisation for Economic Cooperation and Development) process that led to the recent adoption of the method as OECD Test Guideline (TG) 320.

Enhanced ready biodegradability screening tests for the evaluation of potential PBT substances.

In persistence assessment enhanced ready biodegradation tests (eRBT) are aimed to close the gap between screening tests and complex simulation tests. However, only few data from these tests are available and neither guidance on the design and interpretation of eRBTs, nor suitable validity criteria have been established so far. In a practical testing programme 5 compounds with controversial degradation data have been tested in 4 test series including prolongation to 60 days and use of different inocula (activated sludge, final effluent from a STP), flask sizes, and endpoints (CO2, O2, DOC). The drug ibuprofen and the intermediate 4-fluorophenol were biodegraded by >60% within 28 days within a 10-day-window and therefore are considered as readily biodegradable and in conclusion fulfilling the criteria for "not persistent". The mean mineralization of the pesticide synergist piperonylbutoxide and the antioxidant octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate achieved 20%-50% (="potentially P"). The mineralization of the cosmetic ingredient cis-13-docosenonamide (Erucamide) was between 36%-64% after 60 days with activated sludge and 21% with the effluent from the STP. Diethylene glycol reached the pass level of 60% mineralization within 28 days in all test series without always meeting the 10-day window, and thus proved to be a suitable reference substance for eRBTs. Based on the results of the study several recommendations for the test design, the evaluation and the interpretation of eRBTs are made. However, a broader data set is required and further enhancements such as the quality and amount of the inoculum should also be considered in future research.

Review of the environmental fate and effects of two UV filter substances used in cosmetic products.

Sunscreens containing UV filters, such as octocrylene (OCR) and butyl-methoxydibenzoylmethane (BMDBM), have been increasingly used to protect human skin against UV radiation. Both substances have been detected in monitoring studies in the freshwater and marine environment, and there has been concern about potential effects on aquatic organisms. In the present work, the environmental fate and occurrence, bioaccumulation and ecotoxicity including endocrine effects of OCR and BMDBM are reviewed focusing on the aquatic environment. The two UV filters have low water solubilities and a high sorption potential. The available data indicate that OCR is poorly biodegradable. BMDBM lacks anaerobic and inherent biodegradability. However, it was biodegraded to variable degrees in simulation studies. Measured concentrations in the freshwater and marine environment were found to vary considerably between sites, depending on the extent of recreational activities or wastewater discharges. While the bioconcentration factor of OCR in fish is below the threshold value for bioaccumulation according to EU REACH, the available data for BMDBM do not allow a definitive conclusion on its bioaccumulation potential. Analysis of the aquatic toxicity data showed that data quality was often limited, e.g. in the case of effect concentrations substantially exceeding maximum achievable dissolved concentrations. Up to their limit of water solubility, OCR and BMDBM showed no toxicity to microorganisms, algae, and corals, and no acute toxicity to daphnids and fish. In chronic daphnid tests, OCR was highly toxic, whereas BMDBM lacked toxicity. Reliable water-sediment toxicity tests are required to further evaluate possible effects on benthic invertebrates. The available data do not provide evidence for endocrine effects of the two UV filters on fish. In order to assess potential environmental risks caused by OCR and BMDBM, a validated exposure model for estimating direct emission of UV filters into the aquatic environment and data from systematic, longer-term monitoring studies are needed.

Compartment-Specific Screening Tools for Persistence: Potential Role and Application in the Regulatory Context.

The persistence assessment under the European Union regulation Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) relies on compartment-specific degradation half-lives derived from laboratory simulation studies with surface water, aquatic sediment, or soil. Although these data are given priority, they are not available for most of the compounds. Therefore, according to the Integrated Assessment and Testing Strategy (ITS) for persistence assessment, results from ready biodegradability tests (RBTs) are used within a persistence screening to decide whether a substance is considered as "not persistent" or "potentially persistent." However, ready biodegradability is currently tested only in water. Consequently, there is a lack of approaches that include the soil and sediment compartments for persistence assessment at the screening level. In previous studies, compartment-specific screening tools for water-sediment (Water-Sediment Screening Tool [WSST]) and soil (Soil Screening Tool [SST]) were developed based on the existing test guideline Organisation for Economic Development and Co-operation (OECD TG 301C [MITI (Ministry of International Trade and Industry, Japan) test]). The test systems MITI, WSST, and SST were successfully applied to determine sound and reliable biodegradation data for 15 test compounds. In the present study, these results are used within the scope of a new alternative persistence screening approach, the Compartment-Specific Persistence Screening (CSPS). Compared to the persistence screening under REACH, the CSPS is a more conservative approach that provides additional reasonable results, particularly for compounds that sorb to sediment and soil, and for which the current standard persistence screening might be insufficient. Thus, the CSPS can be used to identify potentially persistent and nonpersistent compounds in the regulatory context by a comprehensive assessment that includes water, soil, and sediment. Moreover, experimentally determined half-lives from the compartment-specific screening tools can be used as input for multimedia models that estimate, for example, overall persistence (Pov ). The application of fixed half-life factors to extrapolate from water to soil and sediment, which is here demonstrated to be inappropriate, can thereby be avoided. Integr Environ Assess Manag 2019;00:000-000. © 2019 SETAC.

Occurrence and transformation of veterinary pharmaceuticals and biocides in manure: a literature review.

The spread of veterinary medicinal products (VMPs) and biocides via manure onto agriculturally used areas represents a very important emission into the environment for these product groups. Within this literature study, publicly available transformation studies with liquid manure are summarized. Transformation studies were evaluated regarding the transformation fate of tested substances, the origin and characteristics of used manure, the experimental setup, and the measured parameters. As main topics within the 42 evaluated transformation studies, the high dependency of transformation on temperature, redox potential, dry matter content, and other parameters is reported. Test duration throughout the studies ranged from 2 to 374 days and study temperature ranged from 5 to 55 °C. Only seven publications gave information on the redox potential of the manure. Further, the characterization of the matrix in many cases was inadequate due to missing parameters such as dry matter content or pH. Only three publications studied transformation of biocides. To allow for a consistent assessment of studies within the registration process, a harmonized internationally accepted and validated test method is needed. Additionally, monitoring data of VMPs in manure were collected from literature and evaluated regarding the origin and characteristics of the manure, the minimum/maximum found concentrations, and the percentage of identified compounds. Within the 27 evaluated publications, 1568 manure samples were analyzed and 39 different active substances for VMPs and 11 metabolites and transformation products of VMPs could be found in manure. Most often, the samples were analyzed for sulfonamides, tetracyclines, and fluoroquinolones. Not one study searched for biocides or worked with a non-target approach. For sulfadiazine and chlortetracycline, concentrations exceeding the predicted environmental concentrations were found.

Simulation Studies to Explore Biodegradation in Water-Sediment Systems: From OECD 308 to OECD 309.

Studies according to OECD 308 and OECD 309 are performed to simulate the biodegradation of chemicals in water-sediment systems in support of persistence assessment and exposure modeling. However, several shortcomings of OECD 308 have been identified that hamper data evaluation and interpretation, and its relation to OECD 309 is still unclear. The present study systematically compares OECD 308 and OECD 309 and two variants thereof to derive recommendations on how to experimentally address any shortcomings and improve data for persistence and risk assessment. To this end, four (14)C-labeled compounds with different biodegradation and sorption behavior were tested across standard OECD 308 and 309 test systems and two modified versions thereof. The well-degradable compounds showed slow equilibration and the least mineralization in OECD 308, whereas the modified systems provided the highest degree of mineralization. Different lines of evidence suggest that this was due to increased oxygenation of the sediment in the modified systems. Particularly for rapidly degrading compounds, non-extractable residue formation was in line with degradation and did not follow the sediment-water ratio. For the two more slowly degrading compounds, sorption in OECD 309 (standard and modified) increased with time beyond levels proposed by equilibrium partitioning, which could be attributed to the grinding of the sediment through the stirring of the sediment suspension. Overall, the large differences in degradation observed across the four test systems suggest that refined specifications in test guidelines are required to reduce variability in test outcomes. At the same time, the amount of sediment and its degree of oxygenation emerged as drivers across all test systems. This suggests that a unified description of the systems was possible and would pave the way toward a more consistent consideration of degradation in the water-sediment systems across different exposure situations and regulatory frameworks.

Bridging across OECD 308 and 309 Data in Search of a Robust Biotransformation Indicator.

The OECD guidelines 308 and 309 define simulation tests aimed at assessing biotransformation of chemicals in water-sediment systems. They should serve the estimation of persistence indicators for hazard assessment and half-lives for exposure modeling. Although dissipation half-lives of the parent compound are directly extractable from OECD 308 data, they are system-specific and mix up phase transfer with biotransformation. In contrast, aerobic biotransformation half-lives should be easier to extract from OECD 309 experiments with suspended sediments. Therefore, there is scope for OECD 309 tests with suspended sediment to serve as a proxy for degradation in the aerobic phase of the more complicated OECD 308 test, but that correspondence has remained untested so far. Our aim was to find a way to extract biotransformation rate constants that are universally valid across variants of water-sediment systems and, hence, provide a more general description of the compound's behavior in the environment. We developed a unified model that was able to simulate four experimental types (two variants of OECD 308 and two variants of OECD 309) for three compounds by using a biomass-corrected, generalized aerobic biotransformation parameter (k'bio). We used Bayesian calibration and uncertainty assessment to calibrate the models for individual experimental types separately and for combinations of experimental types. The results suggested that k'bio was a generally valid parameter for quantifying biotransformation across systems. However, its uncertainty remained significant when calibrated on individual systems alone. Using at least two different experimental types for the calibration of k'bio increased its robustness by clearly separating degradation from the phase-transfer processes taking place in the individual systems. Overall, k'bio has the potential to serve as a system-independent descriptor of aerobic biotransformation at the water-sediment interface that is equally and consistently applicable for both persistence and exposure assessment purposes.

Development and application of screening tools for biodegradation in water-sediment systems and soil.

Two new screening-test systems for biodegradation in water-sediment systems (WSST; Water-Sediment Screening Tool) and soil (SST; Soil Screening Tool) were developed in analogy with the water-only test system OECD 301C (MITI-test). The test systems could be applied successfully to determine reproducible experimental mineralization rates and kinetics on the screening-test level for fifteen organic chemicals in water (MITI), water-sediment (WSST) and soil (SST). Substance-specific differences were observed for mineralization compared among the three test systems. Based on mineralization rate and mineralization half-life, the fifteen compounds could be grouped into four biodegradation categories: substances with high mineralization and a half-life <28 days in (1) all three test systems, (2) only in the MITI test and in the WSST, (3) only in the SST, and (4) none of the test systems. The observed differences between the MITI results and the WSST and SST biodegradation rates of the compounds do not reflect their (reversible) sorption into organic matter in terms of experimental K(oc) values and log D values for the relevant pH range. Regarding mineralization kinetics we recommend to determine the lag-phase, mineralization half-life and mineralization rate using a 5-parameter logistic regression for degradation curves with and without lag-phase. Experimental data obtained with the WSST and the SST could be verified by showing good agreement with biodegradation data from databases and literature for the majority of compounds tested. Thus, these new screening-tools for water-sediment and soil are considered suitable to determine sound and reliable quantitative mineralization data including mineralization kinetics in addition to the water-only ready biodegradability tests according to OECD 301.

A water-sediment screening tool for measuring biodegradation of organic chemicals.

A water-sediment screening tool (WSST) was developed based on OECD guideline 301 C (MITI I; Ministry of International Trade and Industry, Japan) to generate biodegradation data. The WSST and experimental procedures were tested and validated using aniline (CAS No. 62-53-3) and benzoic acid (CAS No. 65-85-0) as reference substances. In the presence of sediment components a higher endogenous respiration rate in the control vessels without test substance was measured compared to the water-only MITI test system, particularly due to organic constituents. However, it could be demonstrated that a distinct biodegradation in the presence of sediment can be determined and that there is no influence of the sediment pre-treatment on the biological oxygen demand in the WSST. Experiments resulted in biodegradation rates >60% after approximately six days for both compounds. However, degradation of benzoic acid resulted in a shorter lag-phase and a higher degree of degradation compared to aniline. Differences in results between the MITI test system and the WSST observed for aniline can be explained by adsorption to constituents of the sediment and assimilation by activated sludge. In comparison with literature data the results obtained for aniline in the MITI test system and the WSST showed reproducibility and were within the expected range. In conclusion, the WSST is a suitable screening tool to determine kinetic biodegradation data required to predict the biodegradation behaviour of organic chemicals in water-sediment systems and the data might be used to improve quantitative structure-property relationships (QSPRs).

Effects of the parasiticide ivermectin on the cladoceran Daphnia magna and the green alga Pseudokirchneriella subcapitata.

Although widely used for the treatment of endo- and ectoparasites in livestock and pets, very few data on chronic effects on aquatic organisms are available for the parasiticide ivermectin. In the present study, toxicity of ivermectin to two freshwater organisms, the cladoceran Daphnia magna and the green alga Pseudokirchneriella subcapitata was investigated. For D. magna, a mean LC(50) 48 h of 5.7 ngl(-1) was derived from 10 acute tests. Chronic toxicity of ivermectin to D. magna was extremely high: with 0.001 and 0.0003 ngl(-1), respectively, nominal LOEC and NOEC based on growth and reproduction were far below the analytical limit of detection for this compound. P. subcapitata was considerably less sensitive to ivermectin than D. magna. For both growth rate and yield, EC(50) was >4,000 microgl(-1), LOEC was 1,250 microgl(-1) and NOEC 391microgl(-1). In view of the high toxicity to D. magna, the use of ivermectin might pose a risk to local aquatic ecosystems. Further studies should be carried out to investigate the effects of ivermectin and its degradation products on pelagic and benthic freshwater invertebrates.

Improvement of the applicability of ecotoxicological tests with earthworms, springtails, and plants for the assessment of metals in natural soils.

The environmental risk assessment of metals in the soil compartment is based mainly on tests performed in Organization for Economic Cooperation and Development (OECD) artificial soil, but ecologically, the use of natural soils would be more relevant. In this contribution, the reproduction and growth of three standard species (an earthworm, a collembolan, and a dicotyledonous plant, respectively) was evaluated in nine natural soils (covering a wide range of pH values, organic matter content, texture, and so on) and in OECD artificial soil. Afterward, the effects of the model chemical zinc nitrate were assessed in all soils that were identified as being suitable for these species. The test results indicate that the toxicity of zinc nitrate can be higher by a factor of approximately four compared to artificial soil for invertebrates (earthworms and collembolans), whereas plants are only slightly more sensitive in some natural soils than in artificial soil. When comparing the different endpoints, it could be confirmed that the median effective concentration (EC50) is the most robust compared to the highly uncertain 10% effective concentration. Decreasing toxicity of zinc nitrate to collembolans was significantly correlated with an increase in soil pH but not with cation exchange capacity (CEC) or organic carbon (OC) content. No significant correlation was found between the toxicity of zinc nitrate to earthworms or plants and soil pH, CEC, or OC content. Possible consequences of the results are discussed, such as the testing of natural soils in addition to the OECD artificial soil or the inclusion of an additional safety factor to use the EC50 in current risk assessment schemes focusing on no-observed-effect concentrations.

Biodegradability of 14C-labeled antibiotics in a modified laboratory scale sewage treatment plant at environmentally relevant concentrations.

For all new pharmaceuticals, an environmental risk assessment (ERA) has to be performed according to guidelines developed by the European Medicines Evaluation Agency. An important factor of this procedure is the assessment of the predicted environmental concentration in the aquatic environment, which is significantly influenced by the biodegradability of pharmaceuticals in sewage treatment plants. Established standardized methods for determining biodegradation under laboratory conditions apply to substance concentrations, which are much higherthan those expected in reality. Against this background, the laboratory scale sewage treatment plant (LSSTP), as described by the Organisation for Economic Cooperation and Development (OECD) Guideline No. 303A, was modified to construct a lossless system, which allows laboratory testing at realistic concentrations. To verify the experimental setup, the antibiotics benzylpenicillin, ceftriaxone, and trimethoprim were tested at low concentrations (microg/L) using 14C-labeled compounds. The results show that approximately 25% of benzylpenicillin was mineralized, whereas ceftriaxone and trimethoprim were not mineralized at all. Due to the high total recoveries of added radioactivity (> or =95%) and the fact that the findings comply with available literature data, the lossless operation of the test system could be proved. Consequently, the modified LSSTP is a suitable tool to determine more realistic biodegradation data required for the exposure assessment within the scope of an ERA for pharmaceuticals.

The influence of anthracycline therapy on cardiac function during anesthesia.

UNLABELLED: Cardiotoxicity is a well recognized complication of anthracycline (AC) therapy. Subtle abnormalities in myocardial function that become apparent only after exercise may exist in survivors of childhood cancer who have previously received AC, yet have normal resting cardiac function. To evaluate if anesthesia-induced changes in cardiac function differ in pediatric patients with previous AC therapy from healthy children and adolescents, we evaluated in a prospective study 43 patients, of whom 42 were analyzed. Twenty-one patients (AC-group), mean age 9.6 yr (range, 3-16 yr), who had received 193 (30-490) mg/m(2) of AC as a mean cumulative dose with normal resting cardiac function (shortening fraction [SF] 0.34, normal value > 0.30) underwent removal of a Hickman catheter under general anesthesia. Twenty-one patients, mean age 10.9 yr (range, 4-17 yr), who underwent placement of a Hickman catheter before chemotherapy served as the control. All children were premedicated with midazolam 0.5 mg/kg orally. Anesthesia was induced by sodium thiopental (5 mg/kg), fentanyl (3 micro g/kg), and rocuronium (0.6 mg/kg) and maintained with isoflurane (1 MAC) in N(2)O/O(2) (70/30). Before induction (baseline), 5 and 20 min after intubation (T1 and T2), and 20 min after extubation (control), cardiac function was assessed by transthoracic (baseline, control) and transesophageal (T1, T2) echocardiography. Compared with baseline (SF: 34.9 +/- 3.7 [AC], 34.1 +/- 3.7 [C] [not significant]; stroke volume index [SVI] 36 +/- 6 mL/m(2)[AC], 35 +/- 4 mL/m(2)[C] [not significant]; cardiac index [CI] 3.6 +/- 0.6 L/min/m(2)[AC], 3.2 +/- 0.5 L/min/m(2)[C] [not significant]), we found a significant decrease in SF and SVI in both groups at T1 (SF: 26.2 +/- 3.6 [AC] versus 28.6 +/- 3.6 [C] [P < 0.05]; SVI: 26 +/- 4 mL/m(2) [AC] versus 30 +/- 46 mL/m(2) [C] [P < 0.05]) and T2 (SF: 24.1 +/- 3.2 [AC] versus 28.2 +/- 2.5 [C] [P < 0.01], SVI: 26 +/- 6 mL/m(2) [AC] versus 31 +/- 5 mL/m(2) [C] [P < 0.01]), which was significantly greater in the AC group. There were no significant changes of variables of diastolic function (E/A ratio, isovolumetric relaxation time) between both groups. Previous treatment with AC may enhance the myocardial depressive effect of anesthetics even in patients with normal resting cardiac function. IMPLICATIONS: Previous treatment with anthracylines, a group of chemotherapeutic drugs in use for childhood cancer, may enhance the myocardial depressive effect of anesthetics even in children and adolescents with normal resting cardiac function.

[Anthropology and synthetic Darwinism in the Third Reich: The Evolution of Organisms (1943)]. / Anthropologie und synthetischer Darwinismus im Dritten Reich: Die Evolution der Organismen (1943).

This essay will analyse early attempts to base anthropology on the theoretical model provided by the emerging synthetic Darwinism of the 1940s. In the first section we will investigate the historical context of the publication of one of the central documents of synthetic Darwinism in Germany: Gerhard Heberer's Die Evolution der Organismen (1943). Anthropology was covered extensively in this book. The second section will give an impression of the live and work of the five anthropologists represented in Heberer's book: Christian von Krogh, Wilhelm Gieseler, Otto Reche, Hans Weinert, and Gerhard Heberer. The third part of our paper will clarify whether these anthropologists shared a common theoretical outlook with the founders of synthetic Darwinism, and to what degree they were committed to the racial ideas of the Third Reich.