Aquatic Toxicity Integrated Testing and Assessment Strategies (ITS) for Difficult Substances: Case Study With Thiochemicals

Background An Integrated Testing and Assessment Strategy (ITS) for aquatic toxicity of 16 thiochemicals to be registered under REACH revealed 12 data gaps, which had to be filled by experimental data. These test results are now available and offer the unique opportunity to subject previous estimates obtained by read-across (analogue and category approaches) to an external validation. The case study thiochemicals are so-called difficult substances due to instability and poor water solubility, challenging established ITS. Results The new experimental data confirm the previous predictions of acute aquatic toxicity with the new test results indicating a 2-5 times lower toxicity than previously predicted. The previous predictions thus are conservative and closer to the experimental results than expected. The good agreement can be attributed to the fact that we had limited the extrapolations to narrow chemical groups with similar SH-group reactivities. The new experimental data further strengthen and externally validate the existing trends based on similarity in chemical structures, mode of action (MoA), water solubility and stability of source and target compounds in aquatic media. Based on the new experimental data, reliable revised PNECs could be derived and the REACH requirements for these thiochemicals are largely fulfilled. Appropriately adapted ITS are therefore able to reduce in vivo tests with fish even for difficult substances and replace them with alternative information. Conclusions Both experimental and alternative information for difficult substances such as thiochemicals that are rapidly transformed in water are subject to considerable uncertainty. For example, the use of nominal, initial or time-weighted average concentrations, contribute variability in the determination of aquatic toxicity. The use of nominal concentrations is likely to be the most appropriate choice as it reflects realistic worst-case environmental conditions in these cases. In general, uncertainties in (historical) test results and alternative information (read-across) must be considered in terms of how much uncertainty is acceptable for environmental protection on the one hand and how much certainty is technically feasible on the other.

Canadian Regulatory Perspective on Next Generation Risk Assessments for Pest Control Products and Industrial Chemicals

In 2012, the Council of Canadian Academies published the expert panel on integrated testing of pesticide’s report titled: Integrating emerging technologies into chemical safety assessment. This report was prepared for the Government of Canada in response to a request from the Minister of Health and on behalf of the Pest Management Regulatory Agency. It examined the scientific status of the use of integrated testing strategies for the regulatory health risk assessment of pesticides while noting the data-rich/poor dichotomy that exists when comparing pesticide formulations to most industrial chemicals. It also noted that the adoption of integrated approaches to testing and assessment (IATA) strategies may refine and streamline testing of chemicals, as well as improve results in the future. Moreover, the experts expected to see an increase in the use of integrated testing strategies over the next decade, resulting in improved evidence-based decision-making. Subsequent to this report, there has been great advancements in IATA strategies, which includes the incorporation of adverse outcome pathways (AOPs) and new approach methodologies (NAMs). This perspective provides the first Canadian regulatory update on how Health Canada is also advancing the incorporation of alternative, non-animal strategies, using a weight of evidence approach, for the evaluation of pest control products and industrial chemicals. It will include specific initiatives and describe how this work is leading to the creation of next generation risk assessments. It also reflects Health Canada’s commitment towards implementing the 3Rs of animal testing: reduce, refine and replace the need for animal studies, whenever possible.

Increased integrated testing for HIV, hepatitis C and sexually transmitted infections in health care facilities: results from the INTEGRATE Joint Action pilots in Lithuania, Romania and Spain

Background Indicator condition guided HIV testing is a proven effective strategy for increasing HIV diagnosis in health care facilities. As part of the INTEGRATE Joint Action, we conducted four pilot studies, aiming to increase integrated testing for HIV/HCV/HBV and sexually transmitted infections, by introducing and expanding existing indicator condition guided HIV testing methods. Methods Pilot interventions included combined HIV/HCV testing in a dermatovenerology clinic and a clinic for addictive disorders in Lithuania; Increasing HIV testing rates in a tuberculosis clinic in Romania by introducing a patient information leaflet and offering testing for HIV/HCV/sexually transmitted infections to chemsex-users in Barcelona. Methods for implementing indicator condition guided HIV testing were adapted to include integrated testing. Testing data were collected retrospectively and prospectively. Staff were trained in all settings, Plan-do-study-act cycles frequently performed and barriers to implementation reported. Results In established indicator conditions, HIV absolute testing rates increased from 10.6 to 71% in the dermatovenerology clinic over an 18 months period. HIV testing rates improved from 67.4% at baseline to 94% in the tuberculosis clinic. HCV testing was added to all individuals in the dermatovenerology clinic, eight patients of 1701 tested positive (0.47%). HBV testing was added to individuals with sexually transmitted infections with a 0.44% positivity rate (2/452 tested positive). The Indicator condition guided HIV testing strategy was expanded to offer HIV/HCV testing to people with alcohol dependency and chemsex-users. 52% of chemsex-users tested positive for ≥ 1 sexually transmitted infection and among people with alcohol dependency 0.3 and 3.7% tested positive for HIV and HCV respectively. Conclusions The four pilot studies successfully increased integrated testing in health care settings, by introducing testing for HBV/HCV and sexually transmitted infections along with HIV testing for established indicator conditions and expanding the strategy to include new indicators; alcohol dependency and chemsex. HCV testing of individuals with alcohol abuse showed high positivity rates and calls for further implementation studies. Methods used for implementing indicator condition guided HIV Testing have proven transferable to implementation of integrated testing.

Increasing integrated testing in community settings through interventions for change, including the Spring European Testing Week

Background Maximising access to testing by targeting more than one infection is effective in identifying new infections in settings or populations. Within the EU funded Joint Action INTEGRATE, this paper examined the feasibility and impact of expanding integrated testing for HIV, hepatitis C (HCV), chlamydia, gonorrhoea and/or syphilis in four community-based pilots through targeted interventions in Croatia, Italy and Poland and the Spring European Testing Week since community settings are key in detecting new infections and reaching key populations. Methods Pilots led by local INTEGRATE partners prioritised testing for other infections or key populations. The Croatian pilot expanded testing for men who have sex with men to syphilis, chlamydia and gonorrhoea. Italian partners implemented a HIV and HCV testing/information event at a migrant centre. A second Italian pilot tested migrants for HIV and HCV through outreach and a low-threshold service for people who use drugs. Polish partners tested for HIV, HCV and syphilis among people who inject drugs in unstable housing via a mobile van. Pilots monitored the number of individuals tested for each infection and reactive results. The pilot Spring European Testing Week from 18 to 25 May 2018 was an INTEGRATE-driven initiative to create more testing awareness and opportunities throughout Europe. Results The Croatian pilot found a high prevalence for each syphilis, chlamydia and gonorrhoea respectively, 2.1%, 12.4% and 6.7%. The Italian migrant centre pilot found low proportions who were previously tested for HIV (24%) or HCV (11%) and the second Italian pilot found an HCV prevalence of 6.2%, with low proportions previously tested for HIV (33%) or HCV (31%). The Polish pilot found rates of being previously tested for HIV, HCV and syphilis at 39%, 37%, and 38%, respectively. Results from the Spring European Testing Week pilot showed it was acceptable with increased integrated testing, from 50% in 2018 to 71% in 2019 in participants. Conclusions Results show that integrated testing is feasible and effective in community settings, in reaching key populations and minimising missed testing opportunities, and the pilots made feasible because of the European collaboration and funding. For sustainability and expansion of integrated community testing across Europe, local government investment in legislation, financial and structural support are crucial.

Biotransformation of Silver Nanoparticles into Oro-Gastrointestinal Tract by Integrated In Vitro Testing Assay: Generation of Exposure-Dependent Physical Descriptors for Nanomaterial Grouping

Grouping approaches of nanomaterials have the potential to facilitate high throughput and cost effective nanomaterial screening. However, an effective grouping of nanomaterials hinges on the application of suitable physicochemical descriptors to identify similarities. To address the problem, we developed an integrated testing approach coupling acellular and cellular phases, to study the full life cycle of ingested silver nanoparticles (NPs) and silver salts in the oro-gastrointestinal (OGI) tract including their impact on cellular uptake and integrity. This approach enables the derivation of exposure-dependent physical descriptors (EDPDs) upon biotransformation of undigested nanoparticles, digested nanoparticles and digested silver salts. These descriptors are identified in: size, crystallinity, chemistry of the core material, dissolution, high and low molecular weight Ag-biomolecule soluble complexes, and are compared in terms of similarities in a grouping hypothesis. Experimental results indicate that digested silver nanoparticles are neither similar to pristine nanoparticles nor completely similar to digested silver salts, due to the presence of different chemical nanoforms (silver and silver chloride nanocrystals), which were characterized in terms of their interactions with the digestive matrices. Interestingly, the cellular responses observed in the cellular phase of the integrated assay (uptake and inflammation) are also similar for the digested samples, clearly indicating a possible role of the soluble fraction of silver complexes. This study highlights the importance of quantifying exposure-related physical descriptors to advance grouping of NPs based on structural similarities.

Integrated Testing of Building Fabric Thermal Performance for Calibration of Energy Models of Three Low-Energy Dwellings in the UK

This paper presents the methodology and results of in situ testing of building fabric thermal performance to calibrate as-built energy models of three low-energy dwellings in the UK, so as to examine the gap between as-designed and as-built energy performance. The in situ tests included repeat testing of air permeability (AP) integrated with thermal imaging survey and heat flux measurements of the building fabric elements, along with concurrent monitoring of indoor temperature during the pre-occupancy stage. Despite being designed to high thermal standards, wall and roof U-values were measured to be higher than expected. Thermal imaging surveys revealed air leakage pathways around door/window openings, penetrations and junctions between walls and ceilings, indicating poor detailing and workmanship. AP was found to have increased after the initial test due to post-completion alteration to the building fabric. Though the results did not meet design expectation, they were within the UK Building Regulations. Calibration of energy models with temperature monitoring provided a less extreme energy performance gap than simply replacing the designed values with test results. Insights from this study have reinforced the need for building regulations to require integrated testing of building fabric as part of housing delivery to ensure performance targets are realised.

Inline-fähige Prüftechnik von Lithium-Ionen-Batterien/Inline test systems for the electrode production of lithium-ion batteries

Bei der Fertigung von Batteriezellen in millionenfacher Anzahl ist eine gleichbleibend hohe Qualität von großer Bedeutung und die Sicherstellung eine ebensolche Herausforderung. Daneben sind Aspekte wie Kostenreduktion und Ressourcenschonung entscheidend für die zukünftige Verbreitung von Lithium-Ionen-Batterien für die Elektromobilität aber auch für den vermehrten Anwendungsfall der stationären Energiespeicherung. Produktionsintegrierte Prüfsysteme gekoppelt mit KI-basierten Datenkonzepten sind ein zentrales Element für eine effektive Qualitätssicherung und damit eine erhöhte Gesamtwirtschaftlichkeit in einer digitalen Batterieproduktion.   In battery cell production, it is of great importance and an equally great challenge to produce millions of units of consistently high quality. In addition, aspects such as cost reduction and resource conservation are crucial for the future spread of lithium-ion batteries for electromobility but also for the increased use in stationary energy storage. Production-integrated testing systems coupled with AI-based data concepts are a central element for effective quality assurance and thus increased overall cost-effectiveness in digital battery production.