PARC Projects

Shift away from animal testing
Developing toxicity roadmaps
Health effects
Human health
NGRA
Time span
-
Potential impacts
  • Experience advantage through decreased reliance on improved regulation of hazardous substances.
  • Aid in the development of regulations for chemicals, plant protection products, biocides, cosmetics, and materials in contact with food.
  • Contribute to advancements in public health, by addressing gaps in our understanding through the adoption of regulatory measures based on the assays.
Partners involved
INSERM (FR)
SU (SE)
AU (DK)
AUTH (GR)
BfG (DE)
BPI (GR)
DTU (DK)
IISPV (ES)
IRSN (FR)
ISS (IT)
KI (SE)
KIT (DE)
LIST (LU)
MUI (AT)
NILU (NO)
NIPH (NO)
NCPHP (HU)
UG-PL (PL)
SDU (DK)
UGent (BE)
UOC (GR)
UIBK (AT)
UMIL (IT)
UNIVIE (AT)
WR (NL)
Contacts
Karine Audouze (INSERM)
karine.audouze [at] u-paris.fr
Birgit Mertens (Sciensano)
birgit.mertens [at] sciensano.be
Overview

New scientific methods, such as New Approach Methodologies (NAMs ↗), generate a large amount of valuable data, but using this for regulatory and toxicological purposes remains a challenge without a clear and integrated framework. Adverse Outcome Pathways (AOPs ↗) offer a promising solution. They are organised roadmaps that describe existing knowledge on how a chemical may cause harm – linking molecular initiating events that are triggered by chemicals - to biological changes and adverse health effects.

This project addresses current gaps by developing comprehensive AOPs for key regulatory concerns, including immune system toxicity ↗, neurotoxicity ↗, non-genetoxic carcinogenicity ↗, endocrine disruption ↗ and metabolic changes.

Teams of experts will identify existing AOPs, spot missing knowledge, and develop new AOPs using consistent, transparent methods.

The project will enhance tools, for examplebased on artificial intelligence, and methodologies for AOP construction. Four specialised teams have been established to identify potential biomarkers and develop corresponding AOPs that signal harmful effects.

By connecting mechanistic data with regulatory needs, this initiative will enhance how chemicals are assessed for safety. The outcomes will support the use of NAMs and integrated approaches (IATA ↗) in evaluating chemicals, plant protection products, biocides, cosmetics, and food-related substances. Ultimately, the project aims to contribute to safer products, informed policies and a healthier environment.

Policy relevance

AOPs provide a science-based framework that enhances the relevance and transparency of regulatory decisions by linking mechanistic data to adverse health outcomes.

P5.3.2.a_Y1_AOPDevelopment_Inserm

Related Publications

AOP-helpFinder 2.0: Integration of an event-event searches module
AOP-helpFinder 2.0: Integration of an event-event searches module copied to clipboard
Authors
Jaylet Thomas, Coustillet Thibaut, Jornod florence, Margaritte-Jeannin Patricia, Audouze Karine
Journal
Environment International
Vol. 177
108017
Keywords
Adverse outcome pathways, AOP, AOP-helpFinder, Text mining, Artificial intelligence, Toxicology
Date of publication
copied to clipboard
1/3

An updated version of AOP-helpFinder proposes novel functionalities, the main one being the implementation of an automatic screening of the abstracts from the PubMed database to identify and extract event-event associations.

2/3

A new scoring system was created to classify the identified co-occurred terms (stressor-event or event-event) to help prioritization and support the weight of evidence approach, allowing a global assessment of the strength and reliability of the AOP.

3/3

To facilitate interpretation of the results, visualization options are proposed.

1/1

AOP-helpFinder is complementary to existing toxicological models and very valuable for the toxicological and regulatory communities for risk assessment, gap identification and prioritization of future tests.

To support the use of alternative methods in regulatory assessment of chemical risks, the concept of adverse outcome pathway (AOP) constitutes an important toxicological tool. AOP represents a structured representation of existing knowledge, linking molecular initiating event (MIE) initiated by a prototypical stressor that leads to a cascade of biological key event (KE) to an adverse outcome (AO). Biological information to develop such AOP is very dispersed in various data sources. To increase the chance of capturing relevant existing data to develop a new AOP, the AOP-helpFinder tool was recently implemented to assist researchers to design new AOP. Here, an updated version of AOP-helpFinder proposes novel functionalities. The main one being the implementation of an automatic screening of the abstracts from the PubMed database to identify and extract event-event associations. In addition, a new scoring system was created to classify the identified co-occurred terms (stressor-event or event-event (which represent key event relationships) to help prioritization and support the weight of evidence approach, allowing a global assessment of the strength and reliability of the AOP. Moreover, to facilitate interpretation of the results, visualization options are also proposed. The AOP-helpFinder source code are fully accessible via GitHub, and searches can be performed via a web interface at http://aop-helpfinder-v2.u-paris-sciences.fr/.

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Environment
Health effects
Human health
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NGRA
Mixtures
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Workers
Streamlining data processing methods for suspect and non-target screening
Streamlining data processing methods for suspect and non-target screening

Developing toxicity roadmaps

Time span
-
Potential impacts
  • Experience advantage through decreased reliance on improved regulation of hazardous substances.
  • Aid in the development of regulations for chemicals, plant protection products, biocides, cosmetics, and materials in contact with food.
  • Contribute to advancements in public health, by addressing gaps in our understanding through the adoption of regulatory measures based on the assays.
INSERM (FR)
SU (SE)
AU (DK)
AUTH (GR)
BfG (DE)
BPI (GR)
DTU (DK)
IISPV (ES)
IRSN (FR)
ISS (IT)
KI (SE)
KIT (DE)
LIST (LU)
MUI (AT)
NILU (NO)
NIPH (NO)
NCPHP (HU)
UG-PL (PL)
SDU (DK)
UGent (BE)
UOC (GR)
UIBK (AT)
UMIL (IT)
UNIVIE (AT)
WR (NL)
Overview

New scientific methods, such as New Approach Methodologies (NAMs ↗), generate a large amount of valuable data, but using this for regulatory and toxicological purposes remains a challenge without a clear and integrated framework. Adverse Outcome Pathways (AOPs ↗) offer a promising solution. They are organised roadmaps that describe existing knowledge on how a chemical may cause harm – linking molecular initiating events that are triggered by chemicals - to biological changes and adverse health effects.

This project addresses current gaps by developing comprehensive AOPs for key regulatory concerns, including immune system toxicity ↗, neurotoxicity ↗, non-genetoxic carcinogenicity ↗, endocrine disruption ↗ and metabolic changes.

Teams of experts will identify existing AOPs, spot missing knowledge, and develop new AOPs using consistent, transparent methods.

The project will enhance tools, for examplebased on artificial intelligence, and methodologies for AOP construction. Four specialised teams have been established to identify potential biomarkers and develop corresponding AOPs that signal harmful effects.

By connecting mechanistic data with regulatory needs, this initiative will enhance how chemicals are assessed for safety. The outcomes will support the use of NAMs and integrated approaches (IATA ↗) in evaluating chemicals, plant protection products, biocides, cosmetics, and food-related substances. Ultimately, the project aims to contribute to safer products, informed policies and a healthier environment.

Policy relevance

AOPs provide a science-based framework that enhances the relevance and transparency of regulatory decisions by linking mechanistic data to adverse health outcomes.

Contacts
Karine Audouze (INSERM)
karine.audouze [at] u-paris.fr
Birgit Mertens (Sciensano)
birgit.mertens [at] sciensano.be
Topics
Shift away from animal testing
Keywords
Health effects
Human health
NGRA

Related Projects

Enhancing healthy and safe working conditions in hospitals
Human biomonitoring studies on the general population
Enhancing the risk assessment of chemical mixtures
Advancing endocrine disruptor assessment
New approaches to assess organ toxicity without animal testing
Developing toxicity roadmaps