2-(2-(2-ethoxyethoxy)ethoxy)ethanol

Endpoint summary

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:

no adverse effect observed (not irritating)

Additional information

SKIN IRRITATION

There are no reliable skin irritancy studies available for the substance 2-(2-(2-ethoxyethoxy)ethoxy)ethanol. For this specific end point, Chapter 13 of the IUCLID dossier submitted by the lead registrant contains a full and detailed justification for using a category approach to fulfil the data requirements for glycol ethers and to specifically justify the use of read across for certain end points. Data is available for most of the important category members for the skin irritation end point and shows a clear trend of increasing skin irritancy with increasing chain length of the alcohol used and decreasing number of EO moieties present. In this case, interpolation between adjacent members of the category is used as a reliable and justified approach. This is shown in the diagram below:

Skin irritancy (XXXX = most irritating, Source A= least irritating)
Number of EO units	Alcohol chain length
	Methyl	Ethyl	Propyl	Butyl	Pentyl	Hexyl
Mono						XXXX
Di
Tri		Source B
Tetra	Source A	Target

 

Data for the two “source” substances are described below:

In a well reported skin irritancy study, the test substance 2-(2-(2-methoxyethoxy)ethoxy)ethanol was applied under occluded conditions to rabbit skin for exposure periods of up to 20 hours. The test substance was then washed before observing the animals for a period of up to 8 days. Mild erythema was seen in one of the two test animals but odema was not reported. Effects disappeared within 48 hours. On the basis of these results the substance is not regarded as a skin irritant.

In a well reported irritation study in White Vienna rabbits, 2 -(2-ethoxyethoxy)ethanol was applied to pairs of animals under occlusion. Exposure time was for 1, 5, 15mins and 20 hours. For the longest exposure, there was no sign of odema and mild erythema which disappeared in one animal by 72 hours and by 7 days in the second animal. In another skin irritation study in albino rabbits the same substance was applied to 6 animals on to abraded and intact skin under occlusion. The animals were restrained during a 24hr exposure at the end of which the patches were removed and the reactions scored for erythema and edema immediately and 72 hours afterward. The average primary irritation score was 0.5. The results from both these studies indicate that this substance does not warrant classification as a skin irritant.

It is reasonable to interpolate between these results to predict that 2-(2-(2-.ethoxyethoxy)ethoxy)ethanol would also not be irritating to skin.

EYE IRRITATION

There are no reliable eye irritancy studies available for the substance 2-(2-(2-ethoxyethoxy)ethoxy)ethanol. For this specific end point, Chapter 13 of the IUCLID dossier submitted by the lead registrant contains a full and detailed justification for using a category approach to fulfil the data requirements for glycol ethers and to specifically justify the use of read across for certain end points. Data is available for most of the important category members and shows a clear trend of increasing eye irritancy with increasing chain length of the alcohol used and increasing number of EO moieties present. It is of note that the alcohol used (length of alkyl chain) is the more important determinant or eye irritancy potential rather than the number of EO units so vertical extrapolation may be more valid than vertical. However, interpolation between adjacent members of the category can be considered the most reliable and justified approach. This is shown in the diagram below:

Skin irritancy (XXXX = most irritating,xxxx= least irritating)
Number of EO units	Alcohol chain length
	Methyl	Ethyl	Propyl	Butyl	Pentyl	Hexyl
Mono	xxxx
Di
Tri		Source B
Tetra	Source A	Target				XXXXX

 

Data for the two “source” substances are described below:

In an eye irritation study which broadly followed the OECD guideline but for which only comprehensive data was available for a single animals, 2 -(2 -(2 -methoxyethoxy)ethoxy)ethanol was instilled in the eyes of 2 rabbits, which were then observed for up to 8 days. No washout was used. Minimal effects were observed. No chemosis, corneal opacity or iritis was seen and only mild conjunctival odema which had certainly disappeared within 8 days and possibly sooner. On the basis of this information, this substance has a low potential for eye irritancy and does not warrant classification as an eye irritant.

A well reported study assessed the eye irritancy potential of 2 -(2 -ethoxyethoxy)ethanol. Even without a washing stage, the substance showed minimal iritis or corneal effects and minimal chemosis. Mild to moderate onjunctival effects were seen but insufficient to warrant classification. All significant effects appeared to reverse within 72 hours. The conclusion from this study is that this substance does not warrant classification as an eye irritant.

It is reasonable to interpolate between these results to predict that 2-(2-(2-.ethoxyethoxy)ethoxy)ethanol would also not be irritating to eyes. Analysis of the irritancy potential of (poly)ethylene glycol alkyl ethers shows that eye irritancy potential is mainly dominated by the length of the alkyl chain (with increasing irritancy potential as the alkyl chain increases.) On this basis, the substance 2 -(2 -ethoxyethoxy)ethanol is most likely to have similar irritation potential to TEGEE. This observation does not change the conclusions however.)

Justification for classification or non-classification

SKIN IRRITATION: Available data indicates that classification for skin irritation is not required.

EYE IRRITATION: Available data indicates that classification for skin irritation is not required.