A quantitative risk assessment for skin sensitizing plant protection products: Linking derived No-Effect levels (DNELs) with agricultural exposure models.

Chemical skin sensitizers produce allergic contact dermatitis, which is one of the most frequent occupational diseases associated with chemical exposures. Skin exposure is the major route of exposure when using plant protection products (PPPs). Therefore, skin sensitization is an important factor to be addressed during the regulatory risk assessment of PPPs. The main regulatory decision criterion considered when performing risk assessment for skin sensitizers is the dose applied. The equally important criteria "potency of the substance" is insufficiently considered by two potency categories as potency may vary up to five orders of magnitude. "Frequency of exposure" to the skin sensitizer is not considered at all. Consequently, an improved risk assessment methodology is essential to adequately assess health risks from skin sensitizers, especially for agricultural operators using PPPs. A quantitative risk assessment (QRA) approach for addressing PPPs sensitizing potential is proposed here. This QRA combines a methodology to derive a substance-specific threshold for skin sensitizers, a Derived No-Effect Level (DNEL), and an agricultural exposure model used for assessing chronic health risks of PPPs. The proposed QRA for skin sensitizing PPPs is a clear improvement over current risk assessment to ensure the safe use of skin sensitizers in an occupational context

Political mobilisation by minorities in Britain: negative feedback of ‘race relations'?

This article uses a political opportunity approach to study the relationship of minority groups to the political community in Britain. The main argument is that the British race relations approach established in the 1960s had an important effect that still shapes the patterns of political contention by different minority groups today. Original data on political claims-making by minorities demonstrate that British 'racialised' cultural pluralism has structured an inequality of opportunities for the two main groups, African-Caribbeans and Indian subcontinent minorities. African-Caribbeans mobilise along racial lines, use a strongly assimilative 'black' identity, conventional action forms, and target state institutions with demands for justice that are framed within the recognised framework of race relations. Conversely, a high proportion of the Indian subcontinent minority mobilisation is by Muslim groups, a non-assimilative religious identity. These are autonomously organised, but largely make public demands for extending the principle of racial equality to their non-racial group. Within the Indian subcontinent minorities, the relative absence of mobilisation by Indian, Sikh and Hindu minorities, who have achieved much better levels of socio-economic success than Pakistani and Bangladeshi Muslims, suggests that there is also a strong socioeconomic basis for shared experiences and grievances as Muslims in Britain. This relativises the notion that Muslim mobilisation is Britain is purely an expression of the right for cultural difference per se, and sees it as a product of the paradoxes of British race relations

Systems toxicology: real world applications and opportunities

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity

Establishing Lagrangian connections between observations within air masses crossing the Atlantic during the International Consortium for Atmospheric Research on Transport and Transformation experiment

The ITCT-Lagrangian-2K4 (Intercontinental Transport and Chemical Transformation) experiment was conceived with an aim to quantify the effects of photochemistry and mixing on the transformation of air masses in the free troposphere away from emissions. To this end, attempts were made to intercept and sample air masses several times during their journey across the North Atlantic using four aircraft based in New Hampshire (USA), Faial (Azores) and Creil (France). This article begins by describing forecasts from two Lagrangian models that were used to direct the aircraft into target air masses. A novel technique then identifies Lagrangian matches between flight segments. Two independent searches are conducted: for Lagrangian model matches and for pairs of whole air samples with matching hydrocarbon fingerprints. The information is filtered further by searching for matching hydrocarbon samples that are linked by matching trajectories. The quality of these "coincident matches'' is assessed using temperature, humidity and tracer observations. The technique pulls out five clear Lagrangian cases covering a variety of situations and these are examined in detail. The matching trajectories and hydrocarbon fingerprints are shown, and the downwind minus upwind differences in tracers are discussed

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially-driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a roadmap towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.JRC.I.5-Systems Toxicolog

Report of the 1st and 2nd Mystery of Reactive Oxygen Species Conferences

Non peer reviewe

Scientific opinion on the tolerable upper intake level for manganese

Funding Information: The Panel wishes to thank for their contribution to this output: the WG on Upper Levels: Peter Aggett, Brandy Beverly, Torsten Bohn, Julia Bornhorst, Marta Crous-Bou, Francesco Cubadda, Aymeric Dopter, Susan Fairweather-Tait, Rex FitzGerald, Susan Lanham New, Georg Lietz, Harry J McArdle, Anne Molloy, Giovanni Passeri, Kristina Pentieva, Marco Vinceti and Misha Vrolijk; hearing expert: Peter Willatts, individual scientific advisor (ISA) expert: Keyvin Darney and EFSA staff members: Constanza De Matteu Monteiro, Jean-Lou Dorne, Alessandra Giarola, Irene Muñoz Guajardo, Nena Karavasiloglou, Laura Ciccolallo, Roanne Marie Saad, Angeliki Sofroniou and Silvia Valtueña Martínez. The Panel also wishes to thank Carmen Peláez for her contribution as member of the NDA Panel until June 2023. The Panel acknowledges Thorhallur I Halldorsson, Bryndis Eva Birgisdottir, Anete Dudele, Jacob Juel Christensen and Birna Thorisdottir for the preparatory work as part of a procurement procedure. The Panel also wishes to acknowledge the contribution of all national institutions in European countries that provided consumption data for this scientific output. Publisher Copyright: © 2023 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority.Peer reviewe

Follow-up of the re-evaluation of sulfur dioxide (E 220), sodium sulfite (E 221), sodium bisulfite (E 222), sodium metabisulfite (E 223), potassium metabisulfite (E 224), calcium sulfite (E 226), calcium bisulfite (E 227) and potassium bisulfite (E 228)

Sulfur dioxide-sulfites (E 220-228) were re-evaluated in 2016, resulting in the setting of a temporary ADI of 0.7 mg SO2 equivalents/kg bw per day. Following a European Commission call for data, the present follow-up opinion assesses data provided by interested business operators (IBOs) and additional evidence identified in the publicly available literature. No new biological or toxicological data addressing the data gaps described in the re-evaluation were submitted by IBOs. Taking into account data identified from the literature search, the Panel concluded that there was no substantial reduction in the uncertainties previously identified in the re-evaluation. Therefore, the Panel considered that the available toxicity database was inadequate to derive an ADI and withdrew the current temporary group acceptable daily intake (ADI). A margin of exposure (MOE) approach was considered appropriate to assess the risk for these food additives. A lower confidence limit of the benchmark dose of 38 mg SO2 equivalents/kg bw per day, which is lower than the previous reference point of 70 mg SO2 equivalents/kg bw per day, was estimated based on prolonged visual evoked potential latency. An assessment factor of 80 was applied for the assessment of the MoE. At the estimated dietary exposures, when using a refined exposure scenario (Data set D), MOEs at the maximum of 95th percentile ranges were below 80 for all population groups except for adolescents. The dietary exposures estimated using the maximum permitted levels would result in MOEs below 80 in all population groups at the maximum of the ranges of the mean, and for most of the population groups at both minimum and maximum of the ranges at the 95th percentile. The Panel concluded that this raises a safety concern for both dietary exposure scenarios. The Panel also performed a risk assessment for toxic elements present in sulfur dioxide-sulfites (E 220-228), based on data submitted by IBOs, and concluded that the maximum limits in the EU specifications for arsenic, lead and mercury should be lowered and a maximum limit for cadmium should be introduced

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Re-evaluation of neohesperidine dihydrochalcone (E 959) as a food additive

The present opinion deals with the re-evaluation of neohesperidine dihydrochalcone (E 959) when used as a food additive. It is obtained by catalytic hydrogenation of a flavanone - neohesperidine - which is naturally occurring and thus isolated by alcohol extraction in bitter oranges (Citrus aurantium). Based on in vivo data in rat, neohesperidine dihydrochalcone is likely to be absorbed, also in humans, and to become systemically available. It does not raise a concern regarding genotoxicity. The toxicity data set consisted of studies on subchronic and prenatal developmental toxicity. No human studies were available. The data set was considered sufficient to derive a new acceptable daily intake (ADI). Based on the weight of evidence (WoE) analysis, the Panel considered unlikely that neohesperidine dihydrochalcone would lead to adverse effects on health in animals in the dose ranges tested. The Panel also considered that a carcinogenicity study was not warranted and that the lack of human data did not affect the overall confidence in the body of evidence. The Panel derived an ADI of 20 mg/kg bodyweight (bw) per day based on a no observed adverse effect level (NOAEL) of 4,000 mg/kg bw per day from a 13-week study in rat, applying the standard default factors of 100 for inter- and intraspecies differences and of 2 for extrapolation from subchronic to chronic exposure. For the refined brand-loyal exposure assessment scenario, considered to be the most appropriate for the risk assessment, the exposure estimates at the mean ranged from < 0.01 to 0.09 mg/kg bw per day and at the 95th percentile (P95) from 0.01 to 0.24 mg/kg bw per day. Considering the derived ADI of 20 mg/kg bw per day, the exposure estimates were below the reference value in all age groups. Therefore, the Panel concluded that dietary exposure to the food additive neohesperidine dihydrochalcone (E 959) at the reported uses and use levels would not raise a safety concern