Toxicity reference values (TRVs)

The Agency’s work

As part of its missions and under the French National Environmental & Health Action Plan (2004-2008), the Agency began a national programme on TRVs in 2004 with the aim of building solid French expertise that could be shared by the various competent authorities in this area.

In response to a request by the Directorate General for Health and the Directorate General for Risk Prevention, the Agency set up an expert group dedicated to TRVs in 2008. Its aim is to establish TRVs for substances of interest and introduce the procedures for their support, the framework for their dissemination and use, and how they are to be monitored over time. This group also aims to develop and enhance methodological knowledge relating to TRVs.

How are TRVs developed?

Formulation of TRVs involves the following steps:

  • identifying and analysing the available toxicity data, based on epidemiological and/or experimental studies;
  • identifying the target organ(s) and critical effect;
  • identifying the assumption according to which it is established: with or without a threshold dose, depending on the substance’s mode of action;
  • choosing one (or more) key study of good scientific quality that can generally be used to establish a dose-response (or dose-effect) relationship;
  • defining a critical dose for humans or animals from this study, and if required, in the case of a critical dose obtained in animals, adjusting this dose to humans;
  • for a threshold TRV, applying uncertainty factors to this critical dose so as to derive a TRV that is applicable to the entire population;
  • for a non-threshold TRV, conducting a linear extrapolation from the origin in order to determine a potency factor.

The report entitled "Toxicity reference values - ANSES’s TRV development guide (PDF) (in French))" provides the main methodological elements useful for the establishment of TRVs (threshold or non-threshold).

After a review of existing methods for considering mixtures (report in French), Anses proposed a tiered approach to develop TRVs for a mixture of substances, considering either the whole mixture or each substances of the mixture. This approach was applied to the example of the BTEX mixture (benzene, toluene, ethylbenzene, xylenes) (report in French).


The work conducted by the Agency

So far, about a hundred substances TRVs have been formulated by the Agency for about sixty chemical substances.

See page "List of toxicity reference values (TRVs) established by ANSES"

ANSES has also compiled a database of around 500 TRVs that it has chosen to use for its own expert appraisal work. Making this database available facilitates access to the TRVs for all users, in particular the various public and private partners (consultancies, regional directorates for the environment, land planning & housing, regional health agencies, INERIS, etc.).

All the TRVs established or selected by ANSES in the context of collective expert appraisals carried out within the Agency are available from the Excel table below. This table lists:

  • the substance and its CAS number;
  • the year the TRV was established and by whom;
  • the TRV type (short, mid and long term);
  • the route of exposure;
  • the targeted population;
  • the value and unit of the TRV;
  • the expert appraisal during which the TRV was established or selected, as well as its year of publication, with a link to the report in pdf format.

Download the table of TRVs established or selected by ANSES (Excel) (in French)

The European reference values for active plant protection and biocidal substances are available from the following databases:

The reports describing the internal guide values derived in the European project HBM4EU (HBM-GV) for the general population or the occupational population are available via the following link: hbm4eu.eu/deliverables (Work Package 5: Translation of results into policy).

Which substances is ANSES currently examining?

The substances for which ANSES has been asked to develop TRVs, either through formal requests or internal requests (for risk assessment or related to work on  indoor air quality guidelines - IAQGs) or occupational exposure limits to chemicals - OELs)) or for establishing the development method, have been identified and included in the 2024 work programme: 

  • Aluminium (CAS 7429-90-5) (short- and long-term respiratory TRVs)
  • Benzene (CAS 71-43-2) (short, medium and long-term respiratory TRVs)
  • Black carbon (short- and long-term respiratory TRVs)
  • Dinitrotoluene and its isomers (CAS 25321-14-6, 602-01-7, 606-20-2, 610-39-9, long-term oral TRVs)
  • Isoflavones (oral TRV)
  • Particulate matter (respiratory TRV)
  • 21 Perfluorinated compounds (long-term oral TRVs)
  • Ultrafine particles (PUF) (short- and long-term respiratory TRVs)