PARC Projects

Provide protection against most harmful chemicals
Shift away from animal testing
In vitro methods to assess respiratory uptake and toxicity
Human health
NGRA
Time span
-
Potential impacts
  • A guidance document on dosimetry and the use of respiratory in vitro models for uptake assessment;
  • Further development of a biokinetic model to determine respiratory uptake
  • Standardisation of methods to assess respiratory uptake with in vitro models
Partners involved
RIVM (NL)
INERIS (FR)
VITO (BE)
ENSP (PT)
LIST (LU)
IRFMN (IT)
STAMI (NO)
UG-PL (PL)
AUTH (GR)
WU-TOX (NL)
Contacts
Yvonne Staal (RIVM)
Yvonne.Staal [at] RIVM.nl
Tanja Hansen (Fraunhofer)
tanja.hansen [at] item.fraunhofer.de
Pierre-Andre Billat (INERIS)
Pierre-andre.BILLAT [at] ineris.fr
Overview

Inhalation is an important but often not assessed route of chemical exposure, alongside dermal and oral pathways. This project addresses the current gap by developing in vitro models to assess how chemicals are absorbed, accumulated, and transported through respiratory tissues.

The focus is on two key chemical groups pesticides (e.g. pyrethroids) and per- and polyfluoroalkyl substances (PFAS) that are commonly encountered in occupational settings. Using data-rich chemicals with existing human in vivo data, the project will generate in vitro respiratory uptake data, develop biokinetic and QSAR models ↗, and refine physiologically based kinetic (PBK) models to estimate respiratory uptake. In vitro to in vivo extrapolation (IVIVE) ↗ will translate laboratory findings into real-world exposure levels.

This work aims to standardise in vitro respiratory models and dosimetry methods, enabling accurate evaluation of systemic effects from inhalation exposure. These advances will support regulatory risk assessments under frameworks such as REACH ↗ and OSHA, while contributing to reduced reliance on animal testing.

The project supports several PARC activities, including PFAS ↗ assessment, NAM ↗ development, endocrine disruptor mixtures, chronic toxicity modelling and read-across strategies. By delivering reliable tools and data, this initiative strengthens safety evaluations and enhances human health protection in industrial and environmental contexts.

Achievements & Results

The project has started in May 2025, the first activity is to identify data daps on air-liquid interface models’ dosimetry, in vitro biokinetic approaches and permeability models.

Policy relevance

This project will:

  • provide guidance for assessment of respiratory uptake of airborne substances;
  • enable regulatory implementation of NAM-based approaches focusing on inhaled exposure.

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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

In vitro methods to assess respiratory uptake and toxicity

Time span
-
Potential impacts
  • A guidance document on dosimetry and the use of respiratory in vitro models for uptake assessment;
  • Further development of a biokinetic model to determine respiratory uptake
  • Standardisation of methods to assess respiratory uptake with in vitro models
RIVM (NL)
INERIS (FR)
VITO (BE)
ENSP (PT)
LIST (LU)
IRFMN (IT)
STAMI (NO)
UG-PL (PL)
AUTH (GR)
WU-TOX (NL)
Overview

Inhalation is an important but often not assessed route of chemical exposure, alongside dermal and oral pathways. This project addresses the current gap by developing in vitro models to assess how chemicals are absorbed, accumulated, and transported through respiratory tissues.

The focus is on two key chemical groups pesticides (e.g. pyrethroids) and per- and polyfluoroalkyl substances (PFAS) that are commonly encountered in occupational settings. Using data-rich chemicals with existing human in vivo data, the project will generate in vitro respiratory uptake data, develop biokinetic and QSAR models ↗, and refine physiologically based kinetic (PBK) models to estimate respiratory uptake. In vitro to in vivo extrapolation (IVIVE) ↗ will translate laboratory findings into real-world exposure levels.

This work aims to standardise in vitro respiratory models and dosimetry methods, enabling accurate evaluation of systemic effects from inhalation exposure. These advances will support regulatory risk assessments under frameworks such as REACH ↗ and OSHA, while contributing to reduced reliance on animal testing.

The project supports several PARC activities, including PFAS ↗ assessment, NAM ↗ development, endocrine disruptor mixtures, chronic toxicity modelling and read-across strategies. By delivering reliable tools and data, this initiative strengthens safety evaluations and enhances human health protection in industrial and environmental contexts.

Achievements & Results

The project has started in May 2025, the first activity is to identify data daps on air-liquid interface models’ dosimetry, in vitro biokinetic approaches and permeability models.

Policy relevance

This project will:

  • provide guidance for assessment of respiratory uptake of airborne substances;
  • enable regulatory implementation of NAM-based approaches focusing on inhaled exposure.
Contacts
Yvonne Staal (RIVM)
Yvonne.Staal [at] RIVM.nl
Tanja Hansen (Fraunhofer)
tanja.hansen [at] item.fraunhofer.de
Pierre-Andre Billat (INERIS)
Pierre-andre.BILLAT [at] ineris.fr
Topics
Provide protection against most harmful chemicals
Shift away from animal testing
Keywords
Human health
NGRA

Related Projects

Advancing chemical risk assessment for diverse populations