Registration Dossier

Administrative data

Description of key information

Skin:
Easter et al, 1986, was identified as the key study for characterization of the skin irritation potential of the test substance. Although the study did not specifically follow the OECD 404 Guideline, it is sufficiently similar to merit a Klimisch Code of 1. In this study, slight irritation was seen which resolved within 14 days of exposure. This study would classify the test material as 'not irritating' according to the criteria in Directive 67/548/EEC and Regulation (EC) no 1272/2008. 
Eye:
The method used was comparable to the OECD 405 guideline. No corneal opacity or iritis was observed.
In the unrinsed eyes, moderate conjunctival irritation was observed through 24 hours and all eyes were clear by 10 days.
In the rinsed eyes, moderate conjunctival irritation was observed at one hour and all eyes were clear by four days.

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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

Easter et al, 1986 (Chevron report number: CEHC 2509), the most reliable study available, was selected as the key study for evaluation of the skin irritation potential of this substance. The study design was comparable to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and was conducted to GLP. Although there was no guideline stated and the study predates the current OECD 404 Guideline, basic scientific principles are similar to recognised guidelines and there were no major deviations from current guidelines. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997. One-half milliliter of the test material was applied to two intact and two abraded areas on the back of each of six rabbits for four hours. The test material caused slight to well-defined skin irritation, which cleared by seven days. The primary irritation score was 0.7.

Conclusion:The average of the 24-, 48-, and 72-hour scores are 0.125 for erythema and 0 for edema, therefore according to this study the test material is considered to be 'not irritating' according to the criteria in Directive 67/548/EEC and Regulation (EC) no 1272/2008.

The following studies are also available but were considered less reliable than the key study. Some protocols also had major deviations from current guidelines or inadequate information in the report to allow adequate evaluation of the study.

- The Duncan et al, 1985 study (Chevron report number: SOCAL 2409) was disregarded due to a critical flaw in the study design. Based on available information, the method used for substance removal would have been inadequate to terminate exposure. Therefore the period of actual exposure in this study is not known.. Because of this deviation from accepted test practices, this study is assigned a reliable of 3 according to the criteria of Klimisch, 1997. The study is disregarded for the purpose of hazard evaluation.

- The Cerkanowiczet al, 1981 study (Report number: SOCAL 1765) was comparable to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) but with major deviations. There was no guideline stated and the study predates OECD 404 although basic scientific principles are similar to recognised guidelines and GLP. The major protocol deviation was a 24 hour exposure period instead of the guideline advised 4 hour period which make interpretation of this study impossible under current regulatory criteria. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997.

 

The following supporting studies are also available, however they have not been taken into account for C&L as only 24 and 72 hour readings are available. These data cannot technically be used in accordance with the criteria set out in Directive 67/548/EEC and Regulation (EC) no 1272/2008:

- The Meyding & Fogleman, 1962 study was conducted similarly to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) but with significant deviations. Exposure to the test substance occurred for a period of 24 hours instead of the guideline recommeded 4 hours. In addition, irritation scores are only available at the 24 and 72 hour time points. The study predates OECD 404 although basic scientific principles are similar to recognised guidelines. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997.

Result: The primary dermal irritation index of the test material is 4.0. The test material produced a moderate response on both the intact and abraded skin areas, characterized at the 24-hour observation period by moderate to severe edema and moderate erythema. Substantial but incomplete subsidence was observed on the intact areas at the 72-hour observation period. The abraded skin areas had only slightly improved by this time.

- The Cavalli et al, 1968 study was conducted similarly to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) but with significant deviations. There was no guideline stated. The study predates OECD 404 however basic scientific principles are similar to recognised guidelines. A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997. Result: At 24 hours, there was a moderate reaction, characterized by slight swelling and redness. By 72 hours, this had decreased slightly. The primary irritation score was 2.8.

Eye

- In the key study for eye irritation (Cerkanowiczet al, 1981, Report number: SOCAL 1763) there was no mention of what guideline was followed, however the methodology suggests that it was conducted similarly to OECD 405. Study was conducted according to GLP. A reliability rating of 1 according to the criteria of Klimisch, 1997. This was considered to be the most reliable and robust study available and therefore classification is based on this study.

There are also the following supporting studies for this endpoint:

- The Cavalliet al, 1968 study was conducted similarly to the OECD Guideline 405 but with minor deviations. Although there was no guideline stated, the study predates OECD 405 and basic scientific principles are similar to recognised guidelines. A reliability rating of 2 was assigned according to the criteria of Klimisch, 1997. Result: At 24 hours, there was very slight reddening of the conjunctivae including the nictitating membrane in three of the rabbits. There was no discharge.

- The Meyding & Fogleman, 1962 study was conducted similarly to the OECD Guideline 405, however, the results are reported incorrectly and therefore the study cannot be used for classification purposes as the conjunctivae (redness & discharge) and chemosis has not been reported separately. Instead, sclera and palpebrae was added together and only one score was reported. This is likely to be the reason why the test material appears to be irritating, if the scores were reported separately this may not be the case, therefore this study is considered to be unassignable. A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997. Result: Single 0.1 ml doses of the test material instilled in the eyes of albino rabbits produced a significant degree of conjunctival irritation which had not completely subsided within a 72-hour observation period.

Justification for classification or non-classification

Skin

Based on the most reliable study available, the substance does not meet the criteria for classification according to Directive 67/548/EEC or Regulation (EC) no 1272/2008. Therefore the skin irritation / corrosion endpoint is considered "conclusive but not sufficient" for classification and the substance is not considered to cause skin irritation.

Eye

The key parameter chosen for eye irritation was less than the criteria set out in Directive 67/548/EEC and also Regulation (EC) 1272/2008, therefore classification for eye irritation was not considered to be necessary.