Addiotional Deliverable Report AD14.6. Report on the state of development of Task 14.3: Identification of needs for the implementation of both classical and new biomarkers of effect and decision criteria for their validation (original) (raw)

2020, Zenodo (CERN European Organization for Nuclear Research)

Background: WP14 is investigating the use and implementation of both classical and novel effect biomarkers that can address previous data gaps identified, providing an added value to HBM studies. Objective: The current deliverable aims to present the state of development of Task 14.3: "Identification of needs for the implementation of only new biomarkers of effect and decision criteria for their validation", consisting on the experimental work related to some of the new effect biomarkers undertaken in WP14 during 2019. Methods: Novel biomarkers (as brain-derived neurotrophic dactor, BDNF) were fine-tuned in order to investigate the appropriated quality and assessment conditions before its implementation in the HBM4EU aligned studies. Regarding biomarkers of combined activity to chemical mixtures, an effect-directed analysis identified the subfractions of the previously whole extracted alpha-fraction from placentas (D14.4 and AD14.4) with the highest antiandrogenic activity. Additionally, a method to isolate and assess xenoestrogenic combined activity of mixtures of PFAS compounds from the same placentas samples was developed. Results: The preliminary data with the INMA-Granada blood and serum samples shows the technical feasibility to implement novel biomarkers of brain function, as BDNF, at different levels of biological organisation, although at this stage, no conclusions for its applicability can be taken. Moreover, the use of cell-based bioassays may help to better understand how chemical mixtures contained in human samples may exert combined biological activities, allowing also identifying both known and new chemicals of concern in human tissues. Conclusions: The pilot study with INMA-Granada samples has demonstrated the technical feasibility to implement novel biomarkers of brain function such as BDNF, at different levels of biological organisation, in HBM4EU aligned studies. Moreover, the use of cell-based bioassays may help to better understand how specific chemical mixtures contained in human samples may exert combined hormonal activities. Finally, the development of chemical´s mixture isolation, such as PFAS, opens the possibility of assessing specific chemical families isolated from human samples, with potential implications for risk assessment and policy making. Future Steps: i) To implement novel biomarkers of brain function in the HBM4EU aligned studies based on the results obtained with the INMA-Granada pilot study; ii) To analyse and integrate all exposure, effect and outcome data available for neurodevelopment in the INMA-Granada study; iii) To identify the chemical profile of the placental subfractions showing the highest antiandrogenic activities, through the use of non-targeted chemical methods under the interaction with WP16 partners; iv) Further test other biological activities of the isolated mixture of PFAS from placenta samples, and explore the isolation of other chemical families in other more convenient biological samples for HBM studies such as blood and urine samples. AD14.6-Report on the state of development of Task 14.3: Identification of needs for the implementation of both classical and new biomarkers of effect and decision criteria for their validation Security: Public WP14-Effect Biomarkers Version: 1.