Alcohols, C9-11, ethoxylated

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating 
Eye irritation (OECD 405): irritating

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)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

To cover the endpoint irritation of substance C9-11AE (CAS 68439-46-3), studies from similar substances were taken for a weight-of-evidence approach. Read-across is justified because the length of the alkyl chain does not exert any meaningful influence on skin irritation potential, whereas the degree of ethoxylation is of more importance. The irritation potential of AEs is decreasing with increasing ethoxylation degree. The lower ethoxylation level of EO 1 - 3, which includes all read-across substances, appeared to be more irritating (HERA, 2009).

Since the category chemicals differ mainly from each other only by the number of -CH2- units (except for the unsaturated group), the category is very homogenous and it is assumed that each category member exhibits the same toxic mode of action.

Based on weight of evidence and interpolation on the given study reports the following subcategories for skin irritation can be derived:

Class I:          short chain AEO (C6-11) → not classified for skin irritation 

Class II:         detergent grade AEO (C12-15) → not classified for skin irritation

Class III:        saturated long chain AEO (C16-18) → not classified for skin irritation

Class IV:        unsaturated long chain AEO (C16/18 and C18 unsatd.) → R38

For further details please refer to the category justification attached in IUCLID section 13.

Exemplary study summaries are provided to assess the skin and eye irritating potential of C9-11 AE.

 

For the endpoint skin irritation, the read-across substances C10-16 AE (CAS 68002-97-1), C6-12AE (CAS 68439-45-2) and C10AE (CAS 26183-52-8) were used to cover this endpoint.

The first study for the weight of evidence approach assessed the irritating potential to the skin with C10-16 AE (CAS 68002-97-1) according to OECD Guideline 404 and GLP. Six New Zealand White rabbits were exposed for 4 hours to 0.5 mL test substance under semiocclusive conditions and observed for subsequent 21 days. Mean erythema and oedema scores over all animals within three days were 0.8 and 0.4, respectively. Even though the effects persisted within the observation period, they are not increasing, but rather point to a slower recovery. Additionally, the gross pathology does not present thickening, ulcer, superficial blistering, hyperkeratosis or flaking during healing. Hence, the effects seen are closer to a mild irritant than one with a clear R38. Due to the fact that all other tested members of this category do not show a skin irritating potential under the correct test conditions, these effects do not justify the classification R38 / Skin Irrit. Cat.2.

The second GLP-study with C6-12AE (CAS 68439-45-2) was performed in six New Zealand White rabbits which were exposed for 4 hours to the test substance under semiocclusive conditions, according to OECD Guideline 404. Mean erythema and oedema scores over all animals within three days were 0.6 and 0.3, respectively and were fully reversible within the observation period of 14 days.

The last skin irritation study was conducted with C10AE (CAS 26183-52-8) according to OECD Guideline 404 and GLP. Like in the before mentioned studies the erythema and oedema scores over all animals within three days were very low (0.2 and 0.0, respectively) and furthermore fully reversible within 48 h. No signs of toxicity were noted.

Based on a weight of evidence approach C9-11AE does not meet the criteria for eye irritation according to Directive 67/548/EEC (DSD). According to Regulation (EC) No 1272/2008 (CLP) C9-11AE needs to be classified for Eye Irritation Category 2, H319. This classification is the result of a trend analysis performed for eye irritating properties of the members of the AE Category to evaluate the impact of carbon chain length distribution on the eye irritating properties. All available studies, performed according to OECD Guideline 405 under GLP conditions, applying AE of a high purity (>95%) and an ethoxylation degree ≤ 2.5 and allowing the evaluation of recovery (until day 21), were evaluated. According to this evaluation AE of the AE Category having a carbon chain length ≥ C12 do not need to be classified for eye irritation/severe eye irritation while AE having a carbon chain length < C12 need to be classified for Eye Irritation Category 2.

Based on this analysis C9-11AE (CAS 68439-46-3) is not classified for eye irritation according to DSD but for Eye Irritation Category 2 according to CLP. For further information please refer to the category justification.

 

To investigate the eye irritating potential of the lower carbon chain length of C9-11AE, a study with C6-10 AE (CAS 68439-45-2) conducted according to OECD Guideline 405 (Kuhn, 1994) was chosen for read-across. Six rabbits were treated with 0.1 mL of undiluted test substance without rinsing. Based on the mean 24, 48 and 72 h scores no classification according to DSD is required. However, according to CLP the test substance does need to be classified for Eye Irritation Category 2. The test substance revealed moderate effects on the cornea which were reversible within 7 days. No effects on the iris were observed whereas the conjunctival reactions observed were moderate and persisted for a maximum of 10 days.

 

A further OECD Guideline 405 study was conducted with C8-10 AE (CAS 68439-45-2). Six rabbits were treated with 0.1 mL of undiluted test substance without rinsing (Kuhn, 1992). Based on the mean 24, 48 and 72 h scores no classification according to DSD is required. However, according to CLP the test substance does need to be classified for Eye Irritation Category 2. The test substance revealed slight effects on the cornea which were reversible within 10 days in 5/6 animals but persisted in 1/6 animals until day 21. Slight iridal effects were fully reversible by latest day 17. Chemosis was moderate and fully reversible within 21 days. Moderate conjunctival redness was observed but reversed within 14 days in 4/6 animals. Conjunctival redness grade 1 was still observed in 2/6 animals by day 21. However, redness scores ≤ grade 1 was not considered a positive finding in this study protocol. Using CLP criteria, serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision which is not fully reversible within 21 days of application. As hyperemia of some conjunctival blood vessels (i.e. redness grade 1) will not lead to a decay of vision and does also not represent tissue damage, the study protocol might be followed and redness (grade 1) observed in 2/6 animals on day 21 does not need to be considered for a classification for severe eye damage. However, due to the irreversibility of corneal opacity in 1/6 animals the study represents a borderline result between Eye Irritation Category 2 and Eye Damage Category 1.

 

A study assessing the irritating potential to the eyes with C12-13AE (CAS 66455-14-9) similar to OECD Guideline 405 was chosen to represent the higher carbon chain range of C9-11AE. Three rabbits were treated with 0.2 mL test substance and observed for 7 days. The test substance revealed no effects on cornea, iris or conjunctivae. Thus, no classification is required for this test material.

 

In conclusion the weight of evidence shows that AE of a lower carbon chain length have a higher irritating potential to eyes compared to AE with a higher carbon chain length. For the lower carbon chain length (C6 - C10) the mean 24, 48 and 72 h scores of both studies indicated that a classification for Eye Irritation Category 2 is required. In total only 1/12 rabbits showed corneal opacity after 21 days. This single individual finding is considered to be not sufficient to conclude that the lower carbon chain lengths need to be classified for Eye Damage Category 1.

In absence of data C9-11AE needs to be classified for Eye Irritation Category 2.

 

Justification for selection of skin irritation / corrosion endpoint:
No study chosen due to woe approach.

Justification for selection of eye irritation endpoint:
No study chosen due to woe approach.

Effects on eye irritation: irritating

Justification for classification or non-classification

According to the classification criteria of Directive 67/548/EEC the test substance needs not to be classified for skin or eye irritation. However, according to Regulation (EC) No 1272/2008 the test substance needs to be classified with Eye Irritation Category 2, H319. No classification for skin irritation is required according to CLP.