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 primary irritation score was 1.6.
The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1 and so will not be classified as irritating according to the dangerous substances directive, 67/548/EEC.
Eye:
Conjunctival irritation, including positive irritation (grade 2) for four rabbits, was noted for all animals. There were no iridal or corneal findings in the treated eyes. All conjunctival irritation completely subsided by day 7.
The Maximum Average Score for the test material was 5.3 at one-hour post-instillation.
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.

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)

Additional information

Skin:

The key study Brorby, 1986 (Chevron report number: SOCAL 2503) 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 are 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 and is also the most recent study available. Classification has been based on the results from this study.

- The Hirose et al study, 1986 (Chevron report number: SOCAL 2433A) was identical in methodology to the above key study. Although there was no guideline stated, the study predates OECD 404 and basic scientific principles are similar to recognised guidelines. The study was considered to have a reliability rating of 1, according to the criteria of Klimisch, 1997.

The primary irritation score was 1.3. The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 0.2 and so will not be classified as irritating according to the dangerous substances directive, 67/548/EEC.

- The Meyding et al study, 1962a (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 3, according to the criteria of Klimisch, 1997.

The test material produced a moderate degree of irritation characterized by erythema and edema involving both intact and abraded skin areas. Little improvement was observed at the 72-hour observation for although the edema had significantly subsided, erythema increased and substantial drying of the skin occurred. The primary dermal irritation index of the test material was 3.8.

The test material could not be classified according to the dangerous substances directive, 67/548/EEC as only 24 and 72 hour readings were available.

- The Meyding et al study, 1962b (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 3, according to the criteria of Klimisch, 1997.

The primary dermal irritation index of the test material is 6.2.

The test compound produced a severe reaction on both the intact and abraded surfaces. Maximum scores for edema and erythema were frequently observed; the irritation had not subsided appreciably by the 72-hour observation period.

The test material could not be classified according to the dangerous substances directive, 67/548/EEC as only 24 and 72 hour readings were available.

- The Brett, 1975 study was conducted according to the Federal Hazardous Substance Act (16 CFR 1500). A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to the following deviations: The study employed a 24 hour exposure instead of the standard 4 hour exposure. No details of test material removal from the skin. The information was obtained from the peer reviewed, 2006 OECD SIDS dossier due to the original report being unavailable. The test material could not be classified according to the dangerous substances directive, 67/548/EEC as only 24 and 72 hour readings were available, however it was considered not irritating according to the FSHA.

Irritation Index = 3.7

- The Exxon Biomedical Sciences study, 1992 was comparable to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and was conducted to GLP.

The test substance was removed using water and due to the low solubility of the test material it is unlikely that this method will have fully removed the test material from the test sites, therefore a reliability rating of 3, according to the criteria of Klimisch, 1997 was assigned.

primary irritation index = 2.42.

The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1.1 and so will not be classified as irritating according to the dangerous substances directive, 67/548/EEC.

- The Exxon Biomedical Sciences study, 1986 was comparable to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and was conducted to GLP.

The test substance was removed using water and due to the low solubility of the test material it is unlikely that this method will have fully removed the test material from the test sites, therefore a reliability rating of 3, according to the criteria of Klimisch, 1997 was assigned.

primary irritation index = 5.33.

The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 2.6 and so will be classified as irritating according to the dangerous substances directive, 67/548/EEC, however this study was not considered reliable and so will not be taken into account when classifying the substance.

Eye:

The Kern, 2000 study (Report number: WIL-168178) was chosen as the key study for skin irritation as it was conducted to the OECD Guideline 405 (Acute Eye Irritation / Corrosion) and GLP. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997. This was considered to be the most reliable study and is also the most recent study available. Classification has been based on the results for this study.

The other supporting studies available are as follows:

- The Brorby et al study, 1986 (Chevron report number: SOCAL 2325) was not considered the key study as it was conducted less recently than the above key study. There was no guideline stated, however the study predates OECD 405 and basic scientific principles look comparable to recognised guidelines. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

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.

- The Meyding et al study, 1962b (Hazleton report number: 20-0169-33) 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. Methods and results were 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 and although methods and results were reported the conjunctivae scores were combined in the results and therefore it was not possible to classify according to current labelling guides and so 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 test material could not be classified according to the dangerous substances directive, 67/548/EEC as information was limited.

- The Meyding et al study, 1962a (Hazleton report number: 20-0169-33) 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. Methods and results were 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 and although methods and results were reported the conjunctivae scores were combined in the results and therefore it was not possible to classify according to current labelling guides and so 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 test material could not be classified according to the dangerous substances directive, 67/548/EEC as information was limited.

- The Brett, 1975 study was conducted according to the Federal Hazardous Substance Act (16 CFR 1500.42). A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997 due to the following deviations: The information was obtained from the peer reviewed, 2006 OECD SIDS dossier due to the original report being unavailable. The test material could not be classified according to the dangerous substances directive, 67/548/EEC as no individual animal data was available, however it was considered not irritating according to the FSHA.

Mean draize score = 9.0

- The Exxon Biomedical Sciences study, 1984 was comparable to the OECD Guideline 405 (Acute Eye Irritation / Corrosion).

A reliability rating of 1, according to the criteria of Klimisch, 1997 was assigned. Ocular instillation of the test material elicited only conjunctival responses, including redness, chemosis and discharge. All animals were clear of irritation by the Day 7 observation. 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.

Justification for classification or non-classification

Skin:

The key parameter chosen for skin irritation was less 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 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.