Registration Dossier

Administrative data

Description of key information

Skin irritancy: 2 studies showing mild to negligible irritancy.

Eye irritancy:4 studies two showing marked persistent irritancy and two showing lower levels of irritancy.

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 a guideline (OECD 404) and GLP skin irritancy study, a substance meeting the description Poly(oxy-1,2,-ethanediyl), α-butyl, ω-hydroxyl was found to be a mild irritant to rabbit skin (PDII = 0.2) with all effects (mild erythema but no odema) fully reversible within 72 hours. In an old, well reported skin irritation study that followed the basic principles of the current OECD guideline, White Vienna rabbits were used. 2 animals were treated for 20 hours to the substance 3,6,9,12-tetraoxahexadecan-1-ol under occlusive conditions. No adverse skin reaction was seen.

Eye irritancy

In a guideline GLP eye irritation study, the substance 3,6,9,12-tetraoxahexadecan-1-ol was tested in rabbit eyes to assess the level of eye irritancy produced. Under the conditions of the test, moderate eye irritation was observed, the most acute response being moderate to severe conjunctival erythema. All symptoms disappeared within 14 days. In a guideline OECD405 eye irritancy study, a substance meeting the description "Ethanol, 2-butoxy- ,manufacture of, by-products from" (which is very similar in composition to the registered UCVB substance) produced marked irritation in rabbit eyes. The rabbit eyes were washed with water after 24 hours as permitted under the guideline. 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.

In both of the above studies, the rabbit eyes were washed after 24 hours as permitted under the guideline. This can be considered more representative of the hazard in man as humans have a lachrymatory response to irritants (a response lacking in rabbits.). A more severe reponse (or more correctly, a response that showed slower healing) was seen in two further studies that did not use washing after 24 hours. In a guideline (OECD 405) and GLP eye irritancy study, the substance "Ethanol, 2-butoxy- ,manufacture of, by-products from" (which is very similar in composition to the registered UCVB substance) was found to be an irreversible eye irritant (symptoms still present after 24 hours). Whilst the immediate acute irritancy response was sufficient to trigger classification as an eye irritant, the lesions seen were particularly persistent and vascularisation in one animal did not fully reverse during the observation period, which would suggest classification as a severe eye irritant is more appropriate. Information on preparations containing this substance consistently suggest that the effects become reversible at concentrations below 30%. In another similar guideline and GLP study, a substance meeting the description "Poly(oxy-1,2,-ethanediyl), α-butyl, ω-hydroxyl" was found to cause significant but reversible irritation to the rabbit eye. The substance met the criteria for classification as an eye irritant (R36 or H319).

In an in vitro assay designed to assess the irritation potential for severe eye damage, 3,6,9,12-tetraoxahexadecan-1-ol was testsed in the HET-CAM = (Hen Egg Test - Chorioallantoic Membrane) assay. The level of response seen was not indicative of a severe eye irritant.

Effects on eye irritation: 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.

The case for classification of this substance for eye irritancy is less clear cut. There is no doubt that the substance meets the criteria for classification as an eye irritant (R36 under directive 67/548 or H319 under regulation 1272/2008). However, some data suggests that classification for more severe effects (R41 or H318) may be more appropriate, primarily because of the persistency of lesions. In studies where washing was used, symptoms were more quickly reversed, usually within the 21 day observation period. However, in studies not using washing, lesions often persisted to the end of the 21 day observation period. Whilst studies using washing may be regarded as more representative of the human situation, a conservative interpretation of the data suggests that classification as a severe eye irritant is appropriate (R41, H318). Such a classification is consistent with one of the main components 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol. 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).