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Description of key information

Skin: The primary dermal irritation potential of the test material was evaluated in rabbits under 4-hour semioccluded conditions. The test material produced very slight to well-defined erythema and slight to moderate edema reactions. No other dermal irritation was observed. All irritation cleared by the Day 7 observation. The average of the individual index scores (the total of the erythema and edema scores at 4, 24, 48, and 72 hours divided by 4) is 2.8. The average of the 24-, 48-, and 72-hour scores are 1.2 for erythema and 1.3 for edema.
The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1.2 and so will not be classified as irritating according to the dangerous substances directive, 67/548/EEC.
Eye:
The primary eye irritation potential of the test material was evaluated when 0.1 mL was instilled into one eye of each of nine rabbits (six with treated eyes unwashed and three with treated eyes washed for 1 minute starting 30 seconds after instillation). The test material produced a corneal opacity in one animal and conjunctival irritation in all unwashed eyes which cleared in all animals by 96 hours after treatment. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation. In treated eyes receiving a washout, the test material produced only conjunctival irritation which cleared in all animals by 72 hours after treatment. Positive irritation reactions were observed in two of the three animals with washed eyes which cleared in all animals by the 48-hour observation. Rinsing the eyes after treatment did not have a substantial effect on the severity and persistence of ocular irritation.
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 Glaza, 1997 study (Report number: CHW 60803942) was chosen as the key study for skin irritation as it was conducted to the OECD Guideline 404 (Acute Dermal 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 as it is conducted to an OECD guideline 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 Rittenhouse et al, 1975 (report number: 672/XVIII:111) supporting skin irritation study was not considered the key study as it was conducted less recently than the above key study and exposure time was 24 hours rather than the standard 4 hours. There was no guideline stated, however the study predates OECD 405 but with deviations. No method of removal of test material from the test site was specified. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to significant deviations from recent and relevant guidelines which may have an effect on the outcome of the study.

Most of the rabbits had very slight to well-defined erythema and edema in intact and abraded areas for 72 hours. Some erythema and edema were still present in three rabbits 7 days after treatment. The other three rabbits appeared normal. The primary irritation score was 2.9. The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1.4 and so will not be classified as irritating according to the dangerous substances directive, 67/548/EEC, this correlates with the key study.

- The Kruke et al, 1972 (report number: 359/XII:52) supporting skin irritation study was not considered the key study as it was conducted less recently than the above key study and exposure time was 24 hours rather than the standard 4 hours. The study was conducted to 21 CFR 191.10 guideline. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to significant deviations from recent and relevant guidelines which may have an effect on the outcome of the study.

Mild to severe erythema and barely perceptible to moderate edema was observed throughout the observation period. The primary irritation score was 4.7.

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 Costello, 1983 (Biosearch report number: 83-3824A) supporting skin irritation study was not considered the key study as it was conducted less recently than the above key study. The study was conducted according to the FHSA 1500.41. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to significant deviations from recent and relevant guidelines which may have an effect on the outcome of the study.

The study was conducted in accordance with a recognised guideline with good scientific principles, however the test employed a 24 hour exposure instead of a 4 hour exposure and the test sites were only wiped and not washed.

Based on the results, the test material would not be classified as a primary skin irritant to albino rabbits within the definition of the Act-Reference: Section 1500.3 (c)(4). Irritation Index = 2.92.

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.

- In the Kiplinger, 1993 (WIL report number: WIL-168077) supporting skin irritation study was not considered the key study as it was conducted less recently than the above key study and no guideline was stated but it was conducted according to GLP. Only summary presented. No information on individual animal data. A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997.

In Group 1, the Primary Irritation Index was calculated to be 4.4 for sites treated with the undiluted test material. Based on this value, the undiluted test material was not a primary skin irritant.

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 Schults, 1993 (Ricera report number: 93-0054) supporting skin irritation study was not considered the key study as it was conducted less recently than the above key study. The Guideline was not stated however it appears to be similar to OECD 404. The study was conduced according to GLP. A reliability rating of 2 was assigned according to the criteria of Klimisch, 1997 as 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 mean Draize scores for edema were 0.7 at 24 hours and 0.3 at 72 hours. An additional dermal finding, desquamation, was noted in 1 rabbit on days 5 and 6. The primary irritation index was 2.3.

- The Bonnette, 1993 (SLS report number: 3263.35) supporting skin irritation study was not considered the key study as it was conducted less recently than the above key study. Also the Guideline was not stated. The study was conduced according to GLP

A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997 as only a summary was provided and there was no information on individual animal data.

Exposure to the test article produced very slight to well-defined erythema on 6/6 test sites and very slight edema on 4/6 test sites at the 24 hour scoring Interval. The dermal irritation remained on 5/6 test sites at the 72 hour scoring interval.

Based on the EEC dermal evaluation criteria, the test material is not considered a primary irritant to the dermal tissue of the rabbit. The 24 and 72 hour average erythema scores were 1.50 and 1.33, respectively. The 24 and 72 hour average edema scores were 0.67 and 0.83, respectively. The calculated Primary Irritation Index for the test article was 2.17, this correlates with the key study.

- In the Costello, 1986 (Biosearch report number: 86-5233A) supporting skin irritation study, the study was conducted according to 40 CFR, Section 163.81-5, Federal Register, August 22, 1978. A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997 as the study provided no details of irritation effects on individual animals, but merely qualitatively stated the material produced slight irritation and so classification could not be determined.

The Test Article, when dosed as supplied, appears to produce slight skin irritation in albino rabbits. Irritation Index = 0.54.

- In the Costello, 1986 (Biosearch report number: 86-4975A) supporting skin irritation study, the study was conducted according to 40 CFR, Section 163.81-5, Federal Register, August 22, 1978. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to significant deviations from recent and relevant guidelines which may have an effect on the outcome of the study.

The Test Article, when dosed as supplied, appears to produce moderately severe skin irritation in albino rabbits.

Irritation Index = 5.96

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.

- In the Costello, 1986 (Biosearch report number: 86-4948A) supporting skin irritation study, the study was conducted according to 40 CFR, Section 163.81-5, Federal Register, August 22, 1978. A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997 as the study provided no details of irritation effects on individual animals, but merely qualitatively stated the material produced slight irritation and so classification could not be determined.

The Test Article, when dosed as supplied, appears to produce moderate skin irritation in albino rabbits. Irritation index = 2.75

- In the Costello, 1984 (Biosearch report number: 84-4286A) supporting skin irritation study, the study was conducted according to 40 CFR, Section 163.81-5, Federal Register, August 22, 1978. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to significant deviations from recent and relevant guidelines which may have an effect on the outcome of the study.

The Test Article, when dosed as supplied, appears to produce moderate skin irritation in albino rabbits. Irritation index = 2.59.

The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1.5 and so will not be classified as irritating according to the dangerous substances directive, 67/548/EEC, this correlates with the key study.

- In the Costello, 1983 (Biosearch report number: 83-3809A) supporting skin irritation study, the study was conducted according to 40 CFR, Section 163.81-5, Federal Register, August 22, 1978. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to significant deviations from recent and relevant guidelines which may have an effect on the outcome of the study.

Only 24 and 72 hour readings were available therefore no classification could be determined.

The test material appears to produce moderate skin irritation in the albino rabbit. Irritation Index = 2.59.

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.

- In the Regel, 1972 (WARF report number: 2060447) supporting skin irritation study, exposure time was 24 hours rather than the standard 4 hours. There was no guideline stated and only limited information presented. A reliability rating of 3 was assigned according to the criteria of Klimisch, 1997 due to significant deviations from recent and relevant guidelines which may have an effect on the outcome of the study.

Under the conditions specified the product had a primary skin irritation index of 5.00.

Limited information on individual animal data or results and so classification could not be determined.

- In the Harris, 1991 (Hill Top Biolabs report number: 90-4323-21 (A)) supporting skin irritation study, the study was conducted according to Federal Hazardous Substances Act (16 CFR 1500) and include EEC Categorization Criteria. A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997 as only a summary was provided, there was no individual animal data presented and testing was done on dilutions of the test material.

No evidence of corrosion (necrosis) was found for any material. A 50% w/w solution of the test material was found to be irritatiing according to EEC criteria. This does not correlate with the key study, however this study is considered less reliable and so the key study will be used for classification purposes.

Eye:

The Glaza, 1997 study (Report number: CHW 60803941) 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 as it is conducted to an OECD guideline 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:

- In the Rittenhouse et al, 1975 (report number: 672/XVIII:111) supporting eye irritation study, it was not conducted to a recognised guideline, however the study predates OECD 405 and GLP and basic scientific principles look comparable to recognised guidelines.

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

Most of the rabbits had conjunctival redness one hour after instillation which was present in only one rabbit after 72 hours. All the rabbits had normal eyes at the 7-day reading. Not irritating according to the dangerous substances directive, 67/548/EEC.

- In the Kruke et al, 1972 (report number: 359/XII:52) supporting eye irritation study, the study was conducted in accordance with a recognised guideline with good scientific principles however it pre-dates GLP and OECD guidelines. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

The test material did not cause corneal opacity or iritis in the eyes of the six rabbits tested. Slight to moderate conjunctival irritation was observed from one hour to three days after instillation. By seven days, all eyes appeared normal.

Not irritating according to the dangerous substances directive, 67/548/EEC.

- In the Costello, 1983 (Biosearch report number: 83-3824A) supporting eye irritation study, the study was conducted according to the FHSA 1500.42. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997 as the study was conducted in accordance with a recognised guideline with good scientific principles.

Based on the results, the test material is not a primary ocular irritant within the definition of the Act-Reference: Section 1500.42 (b)(1)(2) and the DSD 67/548/EEC.

- In the Costello, 1983 (Biosearch report number: 83-3809A) supporting eye irritation study, the study was conducted in accordance with a recognised guideline with good scientific principles however it pre-dates GLP and OECD guidelines. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

Based on the irritation results the test material is not a primary ocular irritant within the definition of the Act: Reference: Section 1500.42 and the DSD 67/548/EEC.

- In the Harris, 1991 (Hill Top Biolabs report number: 90-4323-21 (B)) supporting eye irritation study, the study was conducted according to Federal Hazardous Substances Act (16 CFR 1500.42). A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997 as only a summary was provided, there was no individual animal data presented and testing was done on dilutions of the test material.

The test material, undiluted, is classified as an irritant by ocular application.

The test material, as a 50% w/w formulation in OS #75788A, is classified as a non-irritant by ocular application.

- In the Regel, 1972 (WARF report number: 2060447) supporting skin irritation study, no guideline was stated and only limited information was reported. A reliability rating of 4 was assigned according to the criteria of Klimisch, 1997.

The test material did not cause corneal opacity or iritis in the eyes of the six rabbits tested. Slight conjunctival irritation was observed from 24 hours to 72 hours. After 72 hours the effects were not fully reversed.

- Supporting information, obtained from the 2000 European Chemicals Bureau IUCLID Data Set for the substance is presented, however this is secondary source information and is considered to have a reliability rating of 4, according to the criteria of Klimisch, 1997.

Justification for classification or non-classification

Skin:

The key parameter chosen for skin irritation was greater than the criteria set out in Directive 67/548/EEC and also Regulation (EC) no 1272/2008, therefore classification for skin irritation was not considered to be necessary.

Eye:

The key parameter chosen for eye irritation was greater than the criteria set out in Directive 67/548/EEC and also Regulation (EC) no 1272/2008, therefore classification for eye irritation was not considered to be necessary.