A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe

Marx‐Stoelting, Philip; Rivière, Gilles; Luijten, Mirjam; Aiello-Holden, K; Bandow, Nicole; Baken, Kirsten; Cañas, Ana; Castaño, Argelia; Denys, Sébastien; Fillol, Clémence; Herzler, Matthias; Iavicoli, Ivo; Karakitsios, Spyros; Klánová, Jana; Kolossa-Gehring, Marike; Koutsodimou, A; Vicente, Joana Lobo; Lynch, Iseult; Namorado, Sónia; Nørager, S.; Pittman, Amelia; Rotter, Stefanie; Sarigiannis, Dimosthenis; Silva, M J; Theunis, Jan; Tralau, Tewes; Uhl, Maria; Klaveren, Jacob van; Wendt-Rasch, Lina; Westerholm, E; Rousselle, Christophe; Sanders, P.

doi:10.1007/s00204-022-03435-7

Cited by 57 publications

(28 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, studying effects of complex chemical mixtures still has many limitations such as accurate mixture reconstruction in laboratory testing (lack of standards, limited information on real-world compositions, complexity of exposure sequences, lack of suitable data exchange formats) and current frameworks for assessing risk, largely established in chemical and drug toxicity testing, lack additional information, for example, exposure route in pharmacokinetic models (e.g., dermal vs ingested, which impacts dose and elimination route). Coordinating, interlinking, and building on developments in toxicology (such as in ONTOX and PARC), may begin to allow for characterizing complex mixture effects in detail, particularly when coupled with advances in exposome characterization as discussed above. There are also opportunities to couple AOPs with aggregate exposure pathways (AEPs) to define the impacts of mixtures on shared molecular targets …”

Section: Developing Framework For Integrating Molecular Biology and E...mentioning

confidence: 99%

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Foreman,

Warth,

Hessel

et al. 2024

Environ. Sci. Technol.

View full text Add to dashboard Cite

Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

show abstract

Section: Developing Framework For Integrating Molecular Biology and E...mentioning

confidence: 99%

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Foreman,

Warth,

Hessel

et al. 2024

Environ. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…The European Partnership for the Assessment of Risks from Chemicals (PARC) aims to develop next-generation chemical hazard and risk assessment tools to better protect human health and the environment ( Marx-Stoelting et al, 2023 ). A major ambition of the project is to develop new approach methods (NAMs) for human health hazard assessment that covers developmental neurotoxicity (DNT), adult neurotoxicity (ANT), thyroid hormone disruption, immunotoxicity, and non-genotoxic carcinogens.…”

Section: The European Partnership For the Assessment Of Risks From Ch...mentioning

confidence: 99%

New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project

Tal,

Myhre,

Fritsche

et al. 2024

Front. Toxicol.

View full text Add to dashboard Cite

In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.

show abstract

“…And these efforts should leverage the knowledge we already possess to devise a broad NAM-based screening battery capable of identifying key events (KEs) of TH-mediated causal pathways. In this project, that we are performing under the European Union (EU)-funded Partnership for the Assessment of Risk from Chemicals ( PARC, 2023 ) programme ( Marx-Stoelting et al, 2023 ; PARC), we aim to provide both novel biological knowledge of how THs may regulate development and how TH system disruptors can perturb these processes, in order to establish and develop NAMs to be incorporated in regulatory decision making for the identification of TH system disruptors.…”

Section: Introductionmentioning

confidence: 99%

New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project

Ramhøj,

Axelstad,

Baert

et al. 2023

Front. Toxicol.

View full text Add to dashboard Cite

Current test strategies to identify thyroid hormone (TH) system disruptors are inadequate for conducting robust chemical risk assessment required for regulation. The tests rely heavily on histopathological changes in rodent thyroid glands or measuring changes in systemic TH levels, but they lack specific new approach methodologies (NAMs) that can adequately detect TH-mediated effects. Such alternative test methods are needed to infer a causal relationship between molecular initiating events and adverse outcomes such as perturbed brain development. Although some NAMs that are relevant for TH system disruption are available–and are currently in the process of regulatory validation–there is still a need to develop more extensive alternative test batteries to cover the range of potential key events along the causal pathway between initial chemical disruption and adverse outcomes in humans. This project, funded under the Partnership for the Assessment of Risk from Chemicals (PARC) initiative, aims to facilitate the development of NAMs that are specific for TH system disruption by characterizing in vivo mechanisms of action that can be targeted by in embryo/in vitro/in silico/in chemico testing strategies. We will develop and improve human-relevant in vitro test systems to capture effects on important areas of the TH system. Furthermore, we will elaborate on important species differences in TH system disruption by incorporating non-mammalian vertebrate test species alongside classical laboratory rat species and human-derived in vitro assays.

show abstract

A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe

Cited by 57 publications

References 25 publications

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project

New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project

Contact Info

Product

Resources

About