Registration Dossier

Administrative data

Description of key information

Skin:
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 primary irritation score was 6.2. Erythema and edema were observed one hour after unwrapping. Severe erythema was observed at 24 hours and persisted in some cases through Day 14; edema was present through Day 7.
Other signs of severe skin irritation were also observed; there were no significant differences between intact and abraded sites. Compound-related microscopic findings included acanthosis, hyperkeratosis and subacute inflammation in all sites. Epidermal exudate was also observed.
Based on a primary irritation score of 6.2, the test material is considered to be a severe skin irritant. There were compound-related microscopic observations at all treated sites. The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 3.5 and so will be classified as irritating according to the dangerous substances directive, 67/548/EEC.
Eye:
Due to inconsistencies in results from the available data for this endpoint a weight of evidence approach using the reliable and relevant studies has been used. The data indicates that the substance may be irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin:

The Waid, 1989 (Chevron report number: CEHC 2932) was chosen as the key study for skin irritation as it was comparable to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and was conducted to GLP. Although there was no guideline stated, the study predates OECD 404 and basic scientific principles look similar to recognised guidelines.

A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997. This was considered to be the most reliable study. Classification has been based on the results for this study.

The other supporting studies available are as follows:

- The Cavalli et al study, 1968 was not considered the key study as it was conducted less recently than the above key study and was not conducted according to a recognised guideline or GLP. There is also a deviation affecting this study as the test substance being left on for 24 hours rather than 4 hours as suggested in recognised guidelines. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

The test material caused a severe skin reaction in rabbits consisting of marked edema and severe erythema. The primary irritation score was 6.

- The supporting study (Randall & Robinson, 1990) is also avaiable for this endpoint. The study is considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997 as there is limited information available as the report is a summary of the study and there is no individual animal data. There is also a deviation affecting this study as the test substance being left on for 24 hours rather than 4 hours as suggested in recognised guidelines.

Primary Irritation Score = 8.0/8.0.

No in-depth skin changes observed at 7 days.

Classification according to the dangerous substances directive, 67/548/EEC and also Regulation (EC) 1272/2008 was not possible as there is no individual scoring data available.

- The Mürmann, 1984 supporting skin irritation study was not considered the key study as the exposed skin was washed with warm water to remove the test material. Due to the low water solubility of the test material, it is unlikely that washing with water would be an effective means of removing the test material a specified in the current testing guideline for skin irritation, OECD Test Guideline 404, therefore this study is considered invalid and a reliability rating of 3 was assigned according to the criteria of Klimisch, 1997.

The primary irritation score = 6.09/8.0.

Necrosis present at study termination (Day 6).

- The Mürmann, 1988 supporting skin irritation study was not considered the key study as exposure was only for 3 minutes and also the exposed skin was washed with warm water to remove the test material. Due to the low water solubility of the test material, it is unlikely that washing with water would be an effective means of removing the test material a specified in the current testing guideline for skin irritation, OECD Test Guideline 404, therefore this study is considered invalid and a reliability rating of 3 was assigned according to the criteria of Klimisch, 1997.

The primary irritation score = 6.75/8.0.

Necrosis present at study termination (Day 5).

- The Mürmann, 1991 supporting skin irritation study was not considered the key study as exposure was only for 3 minutes and also the exposed skin was washed with warm water to remove the test material. Due to the low water solubility of the test material, it is unlikely that washing with water would be an effective means of removing the test material a specified in the current testing guideline for skin irritation, OECD Test Guideline 404, therefore this study is considered invalid and a reliability rating of 3 was assigned according to the criteria of Klimisch, 1997.

The primary irritation score = 6.5/8.0.

At study termination (Day 17), all skin injuries had healed with scar formation.

Eye:

Due to inconsistencies in results from the available data for this endpoint a weight of evidence approach using the reliable and relevant studies has been used. The data indicates that the substance may be irritating to the eyes.

Data used for WoE:

- The Waid, 1990 (Chevron report number: CEHC 3191) was conducted using a method comparable to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and was conducted to GLP. Although there was no guideline stated, the study predates OECD 404 and basic scientific principles look similar to recognised guidelines.

A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

No corneal opacity or iritis was observed. Conjunctival redness, chemosis and discharge were observed at 1 through 24 hours. The mean 24-hour Draize score for treated-unrinsed eyes was 5.0/110. Conjunctival redness continued to Day 7. All eyes were clear by Day 10. The severity and persistence of irritation was comparable between rinsed and unrinsed eyes. The test substance is not classified as irritating under EU classifications.

The mean value of the scores for cornea opacity, iris lesions, redness & oedema of the conjuctivae, for 24, 48 and 72 hours was calculated and was considered to be non-irritating according to the dangerous substances directive, 67/548/EEC and also Regulation (EC) 1272/2008.

- The Cavalli et al study, 1968 was conducted less recently than the above study and was not conducted according to a recognised guideline or GLP although basic priciples looks similar to OECD guidelines. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997 as there was limited information on materials and methods and no information was recorded for reversibility of the test material in the eyes

The test material produced severe conjunctivitis in all six test rabbits, and iritis and corneal opacity in three of them.

The mean value of the scores for cornea opacity, iris lesions, redness & oedema of the conjuctivae, for 24, 48 and 72 hours was calculated and was considered to be classified as irritating according to the dangerous substances directive, 67/548/EEC and also Regulation (EC) 1272/2008.

- The Randall & Robinson, 1990 study is also available for this endpoint. The study is considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997 as there is limited information available as the report is a summary of the study and there is no individual animal data.

The test material was moderately irritating to the rabbit eye, 33.3/110.0 according to the Federal Hazardous Substances Act, 21 CFR, § 191.12 (1964). Classification according to the dangerous substances directive, 67/548/EEC and also Regulation (EC) 1272/2008 was not possible as there is no individual scoring data available.

- In the Mürmann, 1984 eye irritation study no guideline was specified and the information was obtained from the peer reviewed, 2006 OECD SIDS dossier due to the original report being unavailable which also meant no individual animal data was available and so classification according to EU regulations was not possible, therefore this study is considered to have a reliability rating of 2 according to the criteria of Klimisch, 1997.

Application of 0.1 ml of the test material (97% purity) to the eyes of six rabbits caused slight to severe conjunctival irritation in all animals that cleared by 72 hours. Five of six animals had corneal opacity and iritis, and all but one of these animals was clear of irritation by 8 days. One animal had irritation that persisted for 21 days.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin:

The key parameter chosen for skin irritation gave a result of 3.5 for the mean values of erythema and edema formation at 24, 48 and 72 hours, this falls within the range set out in the criteria in Directive 67/548/EEC to be classified an an irritant to the skin and will therefore be classified as R38, irritating to skin. In Regulation (EC) no 1272/2008, the test substance falls within the criteria to be classified as a Category 2 irritant and so will have the hazard statement H315: causes skin irritation and the 'warning' symbol.

Eye:

Due to inconsistencies in results from the available data for this endpoint a weight of evidence approach using the reliable and relevant studies has been used. The data indicates that the substance may be considered irritating to the eyes however the effects seen are reversible, and so it will therefore be classified as R36, irritating to eyes according to the criteria set out in Directive 67/548/EEC.

In Regulation (EC) no 1272/2008, the test substance falls within the criteria to be classified as a Category 2 irritant and so will have the hazard statement H319: causes serious eye irritation and the 'warning' symbol.