Human health REVERSIBILITY OF OCULAR EFFECTS PROJECT

Reversibility of eye effects – relevance for classification under CLP

Summary

An analysis of historical in vivo data identified key ocular effects that drive classification of mixtures as Category 1 (serious eye damage) or Category 2 (eye irritation). All in vivo data used were generated by industry well in excess of 10 years ago and no new in vivo data were generated to support this data analysis.

Background

Historically, the in vivo Draize eye test was used to classify chemicals and/or products for ocular effects as Category 1, Category 2 or No Category (not requiring classification for eye irritation or serious eye damage). A sound evaluation of existing in vivo data can help to understand the primary drivers of classification and the robustness of classifications under EU CLP regulation.

Furthermore, as in vitro test methods continue to gain regulatory acceptance, such an evaluation of historical in vivo data supports better understanding of the capabilities and applicability of the different in vitro test methods.

Outcome of research

Historical in vivo data for surfactant-based products and surfactants obtained from public and proprietary sources were evaluated in order to:

  • derive classifications using the EU CLP regulation (Regulation (EC) No 1272/2008) for each test material and
  • identify the key ocular effects that drive the classifications in order to better understand the basis on which Category 1 and Category 2 classifications were derived.

In vivo data from both the Draize eye test and Low Volume Eye Irritation Test [LVET] were incorporated into this analysis. A number of important findings resulted from the analysis of this in vivo dataset which are summarized as:

  1. The key ocular effect driving identification of Category 1 in both Draize and LVET was persistence of corneal opacity to Day 21 of a study;
  2. The proportion of studies identifying Category 1 based on persistence of corneal opacity was greater for LVET than for Draize;
  3. The proportion of studies identifying Category 1 based on severity of corneal opacity (as defined over days 1-3 of the study) was greater for Draize than for LVET; 
  4. In some cases, persistence of effects in the Draize and LVET were based on other ocular effects e.g. conjunctival redness which occurred in one or in a minority of the animals;
  5. Iris inflammation rarely drove classification of Category 1 in both Draize and LVET;
  6. A key driver of Category 2 classification when corneal opacity was not involved was conjunctival redness with the proportion of studies identifying Category 2 based on this driver being similar between the Draize eye test and LVET.


This analysis provides in-depth insight into the ocular effects that drive classification of surfactant-based products and surfactants which can be used to better understand appropriate classification of such materials within EU CLP regulation and for the applicability of different in vitro test methods/approaches for this purpose.