Reaction mass of 2-(2-(2-butoxyethoxy)ethoxy)ethanol and 3,6,9,12-tetraoxahexadecan-1-ol

Endpoint summary

Description of key information

Skin irritancy: not irritating

Eye irritancy: causes irreversible eye damage.

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 (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

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.

The skin irritation potential of the ethylene glycol ether butyl series decreases with increasing molecular weight as demonstrated by the data available on the first three members of the series. Therefore, TEGBE is expected to be more irritating than TetraEGBE and using data from a study using pure TEGBE to estimate the skin irritation potential of a multi-constituent substance of TEGBE-TetraEGBE will be a conservative approach. It seems reasonable to predict by extrapolation that TetraEGBE will have skin irritation potential no worse than TEGBE and therefore the multi-constituent substance TEGBE-TetraEGBE will also show minimal skin irritation potential and that classification is not warranted.

Eye irritancy

In another guideline (OECD 405) and GLP eye irritancy study, the 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. In another guideline OECD405 eye irritancy study, the substance 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 causing irreversible eye damage.

Data is also available for the main components in separate studies. 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. In a guideline OECD205 study, the substance tetrathylene glycol monobutyl ether was found cause slight corneal opacity that persistend for up to day 7. Moderate iritis was seen in one animal 72 hours after application only. Moderate or severe conjunctival redness was observed in all animals after 24 hours up to 72 hours and decreased to slight after 7 days. Moderate conjunctival chemosis was noted in all animals 24 hours after application, persisted in one animal up to 72 hours and decreased to slight after 7 days, whereas in the ether two animals chemosis decreased to slight after 48 up to 72 hours after application. Slight or moderate discharge was seen in all animals 24 hours after application. In addition small retraction in the eyelid, suppuratien, centracted pupil, discharge of blood, injected scleral vessels, circular or in a circumscribed area and marginal vascularization of the cornea in a circumscribed area were observed ever the study period.  The study was only continued for up to 14 days after which not all symptoms had reversed.

In an in vitro eye irritancy test based on the HET-CAM assay, the component TEGBE was judged to pose no risk of serious damage to eyes.

Effects on eye irritation: highly irritating

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.

For eye irritancy potential, from the data available it is clear that the acute response in terms of conjunctival effects and odema (chemosis) is sufficiently strong enough to warrant classification as a severe eye irritant (H318), although the available data is not sufficiently detailed to enable this to be unequivocally determined. However, there is also data to suggest that even when the response is less severe, the lesions are very persistent and can take more than 21 days to resolve. On this basis, classification as a severe eye irritant is warranted. It should 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. This data is appended to record .002 in chapter 7.3.2 of the IUCLID dosssier. On this basis, appropriate concentration limits for preparations are severe eye irritant (>30%, H318), eye irritant (20 -30%, H319), not classified for eye irritancy (<20%). Accordingly, this substance is classified as H318 with the indicated specific concentration limits according to Regulation Annex VI of EC1272/2008 (CLP).