Registration Dossier

Administrative data

Description of key information

Skin irritancy: 3 studies all showing mild irritancy.

Eye irritancy: 3 studies, all showing moderate to severe and persistent irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritancy

In an old skin irritation study that pre-dates guidelines, rabbit skin was exposed to 2-(2-(2-butoxyethoxy)ethoxy)ethanol for a period of 20 hours . Both dorsal skin and ear tissue was exposed. The dorsal skin showed slight redness but full recovery was observed within 8 days. Whilst the study did not provide the normal level of detail required for comparison with the classification criteria, the level of response seen was sufficiently slight to be able to conclude with certainty that skin irritancy is not an important characteristic of this substance and that is does not meet the criteria for classification as a skin irritant either under the EU or GHS systems.

Eye irritancy

In a guideline OECD405 eye irritancy study, a test substance consisting substantially of 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol (70 -80%), with the balance its higher molecular weigh homologues produced marked eye irritation. The most severe reaction was conjunctival erythema, which averaged a response of 2.7 across all animals tested and the 24, 48 and 72 hour observations. This reaction is sufficiently severe to warrant classification as an eye irritant. Whilst the way the subsequent observations were reported is not entirely clear, it would appear that most effects had disappeared within 14 days apart from possibly slight conjunctival redness in one animal only. On the basis of these results, the substance does not warrant classification as a severe eye irritant. However, in another guideline (OECD 405) and GLP eye irritancy study, the same substance was found to be an irreversible eye irritant. Whilst the immediate acute irritancy response was sufficient to trigger classification as a reversible eye irritant, the lesions seen were particularly persistent and vascularisation in one animal did not fully reverse during the observation period. It should be noted that in this study eye washing was not carried out 24 hours after instillation as this was not permitted under the older guideline prevaling at the time.

In a guideline OECD405 eye irritancy study, a substance containing 65% TEGBE and ~35% TetraEGBE produced marked irritation in rabbit eyes. The most severe reaction was conjunctival erythema, which averaged a response of 2.7 across all animals tested and the 24, 48 and 72 hour observations. This reaction is sufficiently severe to warrant classification as an eye irritant. Whilst the way the subsequent observations were reported is not entirely clear, it would appear that most effects had disappeared within 14 days apart from possibly slight conjunctival redness in one animal only. On the basis of these results, the substance does not warrant classification as a severe eye irritant. It should be noted that in this study eye washing was carried out 24 hours after instillation as permitted under the guideline prevaling at the time.

In an old eye irritation study in rabbits for which only basic results are available, 2-(2-(2-butoxyethoxy)ethoxy)ethanol produced severe redness, edema and opacity which persisted for 8 days. After 8 days, scars were visible (eyelid vessels were considerably injected). Eye signs (redness, edema, opacity and scar) were scored from slight to very severe. These high scores suggest that the immediate acute response was probably strong enough to warrant classification as a severe eye irritant (R41 or H318), although the available data is not sufficiently detailed to enable this to be unequivocally determined. However, in a modern, in vitro eye irritancy test based on the HET-CAM assay, the same substance was judged to pose no risk of serious damage to eyes.

Justification for classification or non-classification

Based on the information available, skin irritancy does not appear to be a significant characteristic of this substance and therefore labelling is not required.

Information available for the eye irritancy properties of 2-(2-(2-butoxyethoxy)ethoxy)ethanol is clear in indicating that the acute response in terms of conjunctival effects and odema (chemosis) is sufficient to warrant classification as a causing eye irritation. However, the data suggests that even when the response is less severe, in the absence of washing after 24 hours, the lesions are very persistent and can take more than 21 days to resolve. On this basis, classification as causing eye damage is warranted. The human situation is better represented by washing at 24 hours and it is likely that the second study more accurately reflects the hazard to humans and that a category 2 classification is most appropriate. However, when the harmonised classification was agreed by the classification and labelling working group under the old directive 67/548, this second study was not available and a decision was therefore made to classify the substance as R41, which translates to category 1 (causes severe eye damage) under the CLP regulation.

It should also be noted however that available data on the eye irritancy of preparations containing this substance at lower percentages suggest that the effects consistently become reversible at concentrations below 30% and eye irritancy properties become quite mild at concentrations below this. On this basis, appropriate concentration limits for preparations are causes eye damage H318 (>30%) severe eye irritant H319 (20 -30%), not classified for eye irritancy (<20%). An attachment to the IUCLID record contains a submission made to the EU Classification and labelling working group in 2001. This includes eye irritation testing data on brake fluid formulations containing TEGBE (2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol) and was used by the working group to derive the classification limits in the existing harmonised classification. No new data has become available since this decision was made that would render it in valid - in fact the new data that is available would suggest that the pure substance should only be classified as category 2.