Low molecular weight plasma antioxidants in healthy individuals and head and neck squamous cell carcinoma patients

Cand. Scient. Amrit Kaur Sakhi har i sin doktorgrad sett på en mulig sammenheng mellom nivået av antioksidanter i blod og overlevelsesprosent hos øre-nese-hals kreftpasienter. Øre-nese-hals kreft er den sjuende mest vanlige krefttype på verdens basis og selv om behandlingsmetodene er blitt bedre, har overlevelsesprosenten vært rundt 50 %. I sin avhandling Low molecular weight plasma antioxidants in healthy individuals and head and neck squamous cell carcinoma patients har Sakhi sett at øre-nese-hals kreftpasienter har lavere nivåer av antioksidanter sammenlignet med friske individer. I tillegg har pasienter med høyt nivå av karotenoider (en type antioksidanter som finnes i frukt og grønnsaker) både før og etter avsluttet strålebehandling bedre overlevelse enn de som har lave nivåer. Strålebehandling øker oksidativt stress i pasienter og de pasientene som har høyest økning i oksidativt stress under behandlingen har bedre overlevelse. Disse resultatene viser at det kan være gunstig å øke antioksidantnivået i øre-nese-hals kreftpasienter før og etter avsluttet strålebehandling. Derimot kan det være uheldig å øke pasientenes antioksidantnivå mens de får strålebehandling siden antioksidantene kan motvirke behandlingseffekten av stråling ved å dempe oksidativt stress. Vi konkluderer derfor med at optimalisering av antioksidantstatus i øre-nese-hals kreftpasienter er viktig for å forbedre deres overlevelse og bør studeres nærmere. Den siste rapporten fra World Cancer Research Fund har også vist at høyt inntak av frukt og grønt sannsynligvis minker risiko for å utvike denne krefttypen. Det er også viktig at forbedring av antioksidantstatus skjer ved å øke inntaket av frukt og grønt og ikke via antioksidanttilskudd, siden andre studier har vist ingen eller negative effekter av tilskudd. Sakhi´s arbeid har også vist at kaffe etterfulgt av frukt og bær er hovedkilder til antioksidanter i det norske kostholdet

Pulmonary phthalate exposure and asthma - is PPAR a plausible mechanistic link?

Due to their extensive use as plasticisers in numerous consumer products, phthalates have become ubiquitous environmental contaminants. An increasing number of epidemiological studies suggest that exposure to phthalates may be associated with worsening or development of airway diseases. Peroxisome Proliferation Activated Receptors (PPAR)s, identified as important targets for phthalates in early studies in rodent liver, have been suggested as a possible mechanistic link. In this review we discuss the likelihood of an involvement of PPARs in asthma development and exacerbation due to pulmonary phthalate exposure. First, we go through the literature on indoor air levels of phthalates and pulmonary phthalate kinetics. These data are then used to estimate the pulmonary phthalate levels due to inhalation exposure. Secondly, the literature on phthalate-induced activation or modulation of PPARs is summarized. Based on these data, we discuss whether pulmonary phthalate exposure is likely to cause PPAR activation, and if this is a plausible mechanism for adverse effects of phthalates in the lung. It is concluded that the pulmonary concentrations of some phthalates may be sufficient to cause a direct activation of PPARs. Since PPARs mainly mediate anti-inflammatory effects in the lungs, a direct activation is not a likely molecular mechanism for adverse effects of phthalates. However, possible modulatory effects of phthalates on PPARs deserve further investigation, including partial antagonist effects and/or cross talk with other signalling pathways. Moreover other mechanisms, including interactions between phthalates and other receptors, could also contribute to possible adverse pulmonary effects of phthalates

European interlaboratory comparison investigations (ICI) and external quality assurance schemes (EQUAS) for the analysis of bisphenol A, S and F in human urine: Results from the HBM4EU project

The Human Biomonitoring for Europe initiative (HBM4EU) aims to study the exposure of citizens to chemicals and potentially associated health effects. One objective of this project has been to build a network of laboratories able to answer to the requirements of European human biomonitoring studies. Within the HBM4EU quality assurance and quality control scheme (QA/QC), a number of interlaboratory comparison investigations (ICIs) and external quality assurance schemes (EQUASs) were organized to ensure data consistency, comparability and reliability. Bisphenols are among the prioritized substance groups in HBM4EU, including bisphenol A (BPA), bisphenol S (BPS) and bisphenol F (BPF) in human urine. In four rounds of ICI/EQUAS, two target concentration levels were considered, related to around P25 and P95 of the typical exposure distribution observed in the European general population. Special attention was paid to the conjugated phase II metabolites known to be most dominant in samples of environmentally exposed individuals, through the analysis of both native samples and samples fortified with glucuronide forms. For the low level, the average percentage of satisfactory results across the four rounds was 83% for BPA, 71% for BPS and 62% for BPF. For the high level, the percentages of satisfactory results increased to 93% for BPA, 89% for BPS and 86% for BPF. 24 out of 32 participating laboratories (75%) were approved for the analyses of BPA in the HBM4EU project according to the defined criterion of Z-scores for both low and high concentration levels in at least two ICI/EQUAS rounds. For BPS and BPF, the number of qualified laboratories was 18 out of 27 (67%) and 13 out of 28 (46%), respectively. These results demonstrate a strong analytical capability for BPA and BPS in Europe, while improvements may be needed for BPF.We gratefully acknowledge funding by the European Union's Horizon 2020 research and innovation programme under the grant agreement No. 733032 HBM4EU. The authors would like to thank the HBM4EU Secretariat at the German Environment Agency for administrative support. The authors acknowledge all the participating and expert laboratories (Table A1, SM) that made the HBM4EU QA/QC programme possible as well as the Management and Advisory Boards of HBM4EU.S

Proficiency and Interlaboratory Variability in the Determination of Phthalate and DINCH Biomarkers in Human Urine: Results from the HBM4EU Project

A quality assurance/quality control program was implemented in the framework of the EU project HBM4EU to assess and improve the comparability of biomarker analysis and to build a network of competent laboratories. Four rounds of proficiency tests were organized for 15 phthalate and two DINCH urinary biomarkers (0.2-138 ng/mL) over a period of 18 months, with the involvement of 28 laboratories. A substantial improvement in performance was observed after the first round in particular, and by the end of the program, an average satisfactory performance rate of 90% was achieved. The interlaboratory reproducibility as derived from the participants' results varied for the various biomarkers and rounds, with an average of 24% for the biomarkers of eight single-isomer phthalates (e.g., DnBP and DEHP) and 43% for the more challenging biomarkers of the mixed-isomer phthalates (DiNP, DiDP) and DINCH. When the reproducibility was based only on the laboratories that consistently achieved a satisfactory performance, this improved to 17% and 26%, respectively, clearly demonstrating the success of the QA/QC efforts. The program thus aided in building capacity and the establishment of a network of competent laboratories able to generate comparable and accurate HBM data for phthalate and DINCH biomarkers in 14 EU countries. In addition, global comparability was ensured by including external expert laboratories.This study was part of the HBM4EU project receiving funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032. Co-funding was received from the Dutch Ministry of Agriculture, Nature and Food Quality (project KB 37-002-014-001/002).S

From science to policy: How European HBM indicators help to answer policy questions related to phthalates and DINCH exposure

Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined

Chemical exposure via the environment : Report from a NEXPO Workshop on human exposure to chemicals via the environment

Humans are exposed directly to chemicals in occupational settings and as consumers, but also indirectly due to contamination of the environment through air, food and drinking water. The report is the final product of a workshop in Oslo 2017 organised by the Nordic Exposure Group (NEXPO) in close cooperation with the European Chemicals Agency (ECHA). The report includes a summary of the presentations given at the workshop, a list of available resources, the discussion points raised in the groups and plenary as well as the recommendations for improvements in guidance and tools for future assessments. The recommendations particularly point out a need for extending the ECHA guidance on Humans exposed indirectly via the environment