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French Agency for Food, Environmental and Occupational Health & Safety

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Updated on 11/04/2019

Toxicity reference values (TRVs)

The Agency’s work

Keywords : Reference values (RVs)

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.

A toxicity reference value (TRV) is a toxicological index that, when compared with exposure, is used to qualify or quantify a risk to human health. The way in which TRVs are developed depends on available data on the substances' toxicological mechanisms of action and on commonly accepted assumptions: a distinction is therefore made between "TRVs without a threshold dose" and "TRVs with a threshold dose". They are widely used in quantitative health risk assessment, a decision-making process designed to provide the scientific evidence essential for proposing corrective measures for implementation by risk managers (ICPE regulations, prevention, local management of a degraded situation), etc. TRVs are developed according to a highly structured and rigorous approach involving collective assessments.

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. 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.

Two successive working groups were set up, enabling a reference method to be proposed for establishing TRVs, both for substances that are toxic to reproduction and development, and for carcinogens. This two-phased organisation has been able to meet expectations regarding establishment of TRVs for substances with and without a threshold dose, therefore covering all possible effects.

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 (in French)" provides the main methodological elements useful for the establishment of TRVs (threshold or non-threshold).

The work conducted by the Agency

So far, around 60 TRVs have been formulated by the Agency for nearly 40 chemical substances.

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 (acute, subchronic, chronic, carcinogen with/without a threshold, internal),
  • 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.

 

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

 

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 2018 work programme: 

  • Acrolein (CAS 107-02-8) (acute and chronic TRV by the respiratory route),
  • BTEX (benzene, toluene, ethylbenzene, xylene)
  • Cyclooctadiene-1,5 (CAS 111-78-4) (chronic TRV by orale and inhalation route),
  • Cyclododecatriene-1,5,9 (CAS 4904-61-4) (chronic TRV by orale and inhalation route),
  • Nitrogen dioxide (NO2) (CAS 10102-44-0) (acute and chronic TRV by the respiratory route),
  • Sodium valproate (CAS 1069-66-5) (chronic TRV by the respiratory route),
  • Zirconium (CAS 7440-67-7) (chronic TRV by oral route).