Registration Dossier

Administrative data

Description of key information

The overall data suggests that the read-across substance C12-16 ADBAC is corrosive to skin and eyes. Based on the read-across approach, C12-14 ADBAC is also expected to be corrosive.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods.
Qualifier:
according to
Guideline:
other: Transport of dangerous goods, special recommendations relating to Class 8, United Nations handbook, 1977.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Vehicle:
water
Amount / concentration applied:
Concentration: 50 % active substance
Duration of treatment / exposure:
4 h
Observation period:
24, 48 and 72 h
Number of animals:
1 in pre-test; 3 in confirmatory test
Remarks on result:
other: 50% active substance was corrosive to the skin

after 3’: well-defined erythema with moderate oedema at 72 h; 
30’: Severe erythema (necrotic reaction) with slight oedema;
60’: Moderate to severe erythema with moderate oedema at 72 h;
4 h: Severe erythema (necrotic reaction) with severe oedema. Primary Irritation Index: 7.0

Confirmatory study in 3 rabbits, 2 sites each with exposure for 3’, and another 3 rabbits for 60’. 
Effects at 3’: no dermal reactions at any of the six sites. Results 60’: Moderate erythema with slight oedema at 4 sites
and areas of skin necrosis at the other two sites.

Primary irritation index PII: 3 min: 0; 60 min: 4.5

Interpretation of results:
Category 1B (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
There was evidence of skin necrosis when 50% active test substance was applied under occlusion to intact rabbit skin for a period of 60 minutes. No visible evidence of necrosis was seen after a 3 minute application. Under the conditions of the study, the 50% active test substance was corrosive to the skin and requires a classification of Category 1B: Corrosive, according to the EU CLP.
Executive summary:

In a guideline study, skin irritation test, 0.5 mL of a 50% solution of C12-16 ADBAC was applied under occlusive dressing to the skin of 1 rabbit for 3, 30, 60 minutes and 4 hours. The skin was washed with water upon removal of the dressing. Observations were recorded at 24, 48 and 72 hours. A confirmatory study was performed with 3 or 60 minute applications in 3 rabbits each. In the confirmatory study, no dermal reactions were observed at any of the six sites up on 3 minute application. Moderate erythema with slight oedema at 4 sites and areas of skin necrosis at the other two sites were observed following 1 hour application (Primary irritation index PII: 3 minute: 0; 60 minute: 4.5). There was evidence of skin necrosis when 50% active test substance was applied under occlusion to intact rabbit skin for a period of 60 minutes. No visible evidence of necrosis was seen after a 3 minute application. Under the conditions of the study, the 50% active test substance was corrosive to the skin (Liggett MP and Seaber JA, 1982).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a guideline compliant skin irritation study, 0.5 mL of a 50% solution of the read-across substance C12-16 ADBAC was applied under occlusive dressing to the skin of 1 rabbit for 3, 30, 60 minutes and 4 hours. The skin was washed with water upon removal of the dressing. Observations were recorded at 24, 48 and 72 hours. A confirmatory study was performed with 3 minute or 1 hour applications in 3 rabbits each. In the confirmatory study, no dermal reactions were observed at any of the 6 sites after 3 minute application. Moderate erythema with slight oedema at 4 sites and areas of skin necrosis at the other 2 sites were observed following 1 hour application (Primary irritation index PII: 3 minute: 0; 60 minute: 4.5). Under the conditions of the study, the 50% test substance solution was considered to be corrosive to skin (Liggett MP and Seaber JA, 1982).

A further guideline study was conducted to assess the skin irritation potential of undiluted C12-16 ADBAC to rabbit skin. Six animals were treated with 0.5 mL of the test substance for 4 hours under occlusive conditions. As the test proved positive for corrosion after 4 hour exposure, the test was repeated in a different group of animals for an exposure period of 60 minutes and then for an exposure period of 3 minutes. Under the test conditions, the substance was corrosive to skin (Sugar JR, 1981).

A third guideline equivalent study was conducted to assess the skin irritation potential of C12-16 ADBAC in the rabbit. The undiluted test substance was applied on intact and abraded skin sites using occlusive patches for an exposure period of 24 hours. The skin was then observed for erythema and edema formation and the scoring was done according to the Draize, Woodland and Calvery scoring system at 24 and 72 hours from the onset of exposure. Severe erythema and edema were observed in all the test animals at both the abraded and intact sites. The mean Primary Irritation Index (PII) of the test substance was calculated to be 6.29. The mean values of erythema and edema were 3.33 (intact skin site), 3.5 (abraded skin site), 2.66 (intact skin site) and 3 (abraded skin site) (Wallace, 1975).


Justification for selection of skin irritation / corrosion endpoint:
The study showing the most severe effects was chosen as the key study. The study was well conducted and comparable to a guideline study.

Justification for selection of eye irritation endpoint:
Data waiving was applied in accordance with Annex VII column 2 of the REACH regulation: the available information regarding skin irritation indicates that the criteria for classification as corrosive for the skin is met.

Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

Skin

A reliable in vivo skin irritation study showed skin necrosis when a 50% solution of the read-across substance C12-16 ADBAC was applied under occlusion to intact rabbit skin for a period of 60 minutes. As a worst-case approach, C12-14 ADBAC is proposed to be classified as C; R34 (causes burns) according to the DSD (67/548/EEC) and Skin Corr. 1B; H314: causes severe skin burns and eye according to CLP (EC 1272/2008) criteria.

It should however be noted that corrosive properties often decrease with longer chain length (fully saturated) and therefore it is possible that C12-14 ADBAC is not corrosive (lower solubility; solid rather than liquid; less molecules per weight) but irritating. The notified CLP for this substance show a large majority of registrants classifying as irritant (R24) and only two as corrosive.

Eye

As a worst-case approach, C12-14 ADBAC is expected to be corrosive to eyes. The substance should be classified as Eye Damage 1. Labelling for this endpoint is covered by the above-mentioned H314 for skin and eye effects.