Registration Dossier

Administrative data

Description of key information

Skin: 
The test material caused slight to well-defined erythema and oedema through 24 hours after the test material was removed. On Days 2 and 3, slight to moderate erythema was observed. Slight erythema was observed in some animals on Day 7. All sites were clear of irritation on Day 14. The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1.3 and 0.5 respectively, and so does not meet criteria to be be classified as irritating to skin according to the dangerous substances directive, 67/548/EEC.
Eye:
Corneal opacity mean score for the 24, 48 and 72 hour observations was 1.22 for this test substance while iritis mean score was 0.22. Conjunctival irritation and chemosis mean scores were 2.0 and 2.11, respectively. All findings were fully reversible after 14 days. The substance is considered to be irritating according to the dangerous substances directive, 67/548/EEC and Regulation (EC) 1272/2008.

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:

The key study, Duncan, 1987, (Chevron report number: CEHC 2593) was designed to test 3 similiar substances and two substance removal methods to assess study design implications for outcome. The study design was comparable to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and was conducted according to GLP. A reliability rating of 2 was assigned according to the criteria of Klimisch, 1997. This is considered the most reliable study available and of sufficient quality to use for classification.

The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1.3 and 0.5, respectively, and so does not meet the criteria to be classified as irritating according to the dangerous substances directive, 67/548/EEC.

- The Duke et al study, 1981 (Chevron report number: SOCAL 1774), although predating the OECD 404 Guideline, this study followed the basic principles of a guideline study and was GLP. However, based on comparison of the findings in this study to other skin irritation studies that used inadequate test method removal methods, Duke was considered to be flawed by inadequate methodology. As a result, Duke, 1981 was assigned a reliability rating of 3, not reliable, according to the criteria of Klimisch, 1997.

- The Meyding et al study, 1962 (Hazleton report number: 20-0169-33) was not conducted according to a recognised guideline or GLP. There are also significant deviations affecting this study such as the test substance being left on for 24 hours rather than 4 hours as suggested in recognised guidelines, and also the test material was not removed with an appropriate solvent after exposure. The study was therefore considered to have a reliability rating of 4, not assignable, according to the criteria of Klimisch, 1997.

Eye:

Morris 1996 (Report number 96 -8085 -21)) was chosen as the key study for eye irritation as the most recent and reliable study available. This study was conducted according to the OECD Guideline 405 (Acute Eye Irritation / Corrosion) and followed GLP principles. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997. Classification has been based on the results for this study. The 24, 48 and 72 hour scores were calculated as follows: corneal opacity = 1.22, iritis = 0.22, conjunctival irritation = 2.0, and chemosis = 2.11. All findings were reversible in 14 days. Based on findings in this study, CAS # 68784 -31 -6 meets the criteria for classification of Directive 76/548/EEC as a severe eye irritant, R41 and meets the criteria of Regulation (EC) 1272/2008 as a Category 1 Eye Irritant.

The other supporting studies available are as follows:

- The Meyding et al study, 1962 (Hazleton report number: 20-0169-33) was not conducted according to a recognised guideline or GLP. Methods and results were improperly reported. The study was considered to have a reliability rating of 4, according to the criteria of Klimisch, 1997 as observations were not carried out for long enough to enable revesibility of irritation. Additionally, although methods and results were reported, the conjunctivae scores were combined in the results making it impossible to use this study to classify according to current labelling guides. Consequently, this study was considered unassignable. The test material produced a significant degree of eye irritation in rabbits which has not completely subsided within 72 hours following instillation.

The Duke et al study, 1981 (Chevron report number: SOCAL 1774) was performed similarly to an OECD 404 Guideline study but was not GLP. This study was considered adequate but was not selected as the key study because a more recent study performed according to the Guideline was available.

- The Hill et al study, 1962 (Report Number 2G6613B) was not conducted according to a recognised guideline or GLP. The report summarizes findings but does not provide sufficient detail to assess the adequacy of the design. The study was therefore considered to have a reliability rating of 4, disregarded, according to the criteria of Klimisch, 1997.


Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin:

The Draize scores for erythema and edema were lower than the criteria set out in Directive 67/548/EEC and also Regulation (EC) 1272/2008, therefore classification for skin irritation was not considered to be necessary.

Eye:

The analogue substance, CAS # 68784 -31 -6, caused severe eye irritation according to the criteria of Directive 67/548/EEC and also Regulation (EC) 1272/2008, therefore classification for eye irritation is necessary.The substance meets the criteria for classification as R41 according to the DSD and as a Category 1 Eye Irritant according to the CLP.