Registration Dossier

SKIN: The test item produced individual mean scores of 1.0 for erythema (both animals) and 0.0 and 1.0 respectively for edema. However,the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for both animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for erythema and edema. No corrosive effects were noted.
EYE : The test item produced a maximum group mean score of 13.5 and was considered to be a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra system. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 August 2015 - 01 September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

ANIMALS AND ANIMAL HUSBANDRY
- Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Envigo RMS Ltd, Leicestershire UK.
- At the start of the study the animals weighed 2.56 to 2.76 kg and were 12 to 20 weeks old.
- After an acclimatisation period of at least 5 days, each animal was given a unique number within the study by writing with black indelible marker-pen on the inner surface of the ear and on the cage label.
- Animals were individually housed in suspended cages.
- Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Envigo RMS Ltd, Oxon, UK) was allowed throughout the study.
- The diet and drinking water were considered not contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Temperature and elative humidity were set to achieve limits of 17 °C to 23 °C and 30 % to 70 % respectively.
- The rate of air exchange was at least 15 changes per hour.
- Lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
- The animals were provided with environmental enrichment items, which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5g of test item

Duration of treatment / exposure:

Four hours

Observation period:

Seven days

Number of animals:

Two

Details on study design:

TEST ITEM FORMULATION
- The test item was used as supplied
- The absorption of the test item was not determined.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- Individual scores and mean scores for erythema/eschar and edema are given in Table 1 (attached).
- Very slight erythema and very slight edema were noted at both treated skin sites immediately after patch removal.
- Very slight erythema with or without very slight edema were noted at both treated skin sites at the 1 hour after patch removal and at 24, 48 and 72-hour observations.
- Treated skin sites appeared normal at the 7-day observation.

Other effects:

- Individual body weights and body weight changes are given in Table 2 (attached).
- Both animals showed expected gain in body weight during the study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced individual mean scores of 1.0 for erythema (both animals) and 0.0 and 1.0 respectively for edema. However,the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for both animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for erythema and edema. No corrosive effects were noted.

Executive summary:

INTRODUCTION

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the OECD Guidelines for the Testing of Chemicals No 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002) and Commission Directive 92/69/EEC Method B.4 Acute Toxicity (Skin Irritation).

RESULTS

A single 4 -hour, semi-occluded application of the test item to the intact skin of two rabbits produced very slight erythema and very slight edema. Both treated skin sites appeared normal at the 7 -day observation.

CONCLUSION

The test item produced individual mean scores of 1.0 for erythema (both animals) and 0.0 and 1.0 respectively for edema. However,the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for both animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for erythema and edema. No corrosive effects were noted.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 September - 17 September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

ANIMALS AND ANIMAL HUSBANDRY
- Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Envigo RMS (UK) Ltd, Leicestershire, UK.
- At the start of the study the animals weighed 3.33 or 3.36 kg and were 12 to 20 weeks old.
- After an acclimatisation period of at least 5 days each animal was given a number, unique within the study, which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
- The animals were individually housed in suspended cages.
- Free access to mains drinking water and food (2930C Teklad Global Rabitt diet supplied by Envigo RMS (UK), Oxon, UK) was allowed throughout the study.
- The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70 % respectively.
- Rate of air exchange was at least 15 changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
- The animals were provided with environmental enrichment items, which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1mL of test item

Duration of treatment / exposure:

Single application

Observation period (in vivo):

72-hours

Number of animals or in vitro replicates:

Two

Details on study design:

TEST ITEM FORMULATION AND EXPERIMENTAL PREPARATION
- The test item was used as supplied.
- Absorption of the test material was not determined.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean scores

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

- Individual and group mean scores for occular irritation are given in Table 1 and Table 2 (attached).
- No corneal effects were noted during the study.
- Iridial inflammation was noted in one treated eyes 1 hour after application of the test item.
- Moderate conjunctival irritation was noted in both treated eyes at 1 hour after application of the test item with minimal conjunctival irritation noted at the 24 & 48 hour observation.
- Both treated eyes appeared normal at the 72-hour observation.

Other effects:

BODY WEIGHT
- Individual body weights are given in Table 3 (attached).
- one animal showed body weight loss and the other animal showed expected gain in body weight during the study

MEASUREMENT OF pH

- Test item undiluted as supplied.

- Aqueous preparation of test item (10 % w/w): pH 5.8 immediately; pH 6.07 after 10 minutes.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced a maximum group mean score of 13.5 and was considered to be a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra system. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008.

Executive summary:

GUIDELINE

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit using a procedure designed to be compatible with OECD Guideline for the Testing of Chemicals No 405 "Acute Eye Irritation/Corrosion" (adopted 02 October 2012) and EU Method B.5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No 440/2008.

RESULTS

A single application of the test item to the non-irrigated eye of two rabbits produced iridial inflammation and moderate conjunctival irritation. Both eyes appeared normal at the 72 hour observation.

CONCLUSION

The test item produced a maximum group mean score of 13.5 and was considered to be a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra system. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for two animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for corneal opacity, iritis, conjunctival redness and chemosis.

Endpoint conclusion:

no adverse effect observed (not irritating)

SKIN

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the OECD Guidelines for the Testing of Chemicals No 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002) and Commission Directive 92/69/EEC Method B.4 Acute Toxicity (Skin Irritation).

RESULTS

A single 4 -hour, semi-occluded application of the test item to the intact skin of two rabbits produced very slight erythema and very slight edema. Both treated skin sites appeared normal at the 7 -day observation.

CONCLUSION

The test item produced individual mean scores of 1.0 for erythema (both animals) and 0.0 and 1.0 respectively for edema. However,the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for both animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for erythema and edema. No corrosive effects were noted.

EYE

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit using a procedure designed to be compatible with OECD Guideline for the Testing of Chemicals No 405 "Acute Eye Irritation/Corrosion" (adopted 02 October 2012) and EU Method B.5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No 440/2008.

RESULTS

A single application of the test item to the non-irrigated eye of two rabbits produced iridial inflammation and moderate conjunctival irritation. Both eyes appeared normal at the 72 hour observation.

CONCLUSION

The test item produced a maximum group mean score of 13.5 and was considered to be a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra system. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for two animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for corneal opacity, iritis, conjunctival redness and chemosis.

Skin: In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for dermal irritation as the primary effects, erythema and edema, were reversed by the end of the observation period. In addition, the scores for erythema and edema did not fall within the range requiring classification.

Eye: In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for eye irritation because no corneal opacity was observed and iridial inflammation, conjunctival redness and chemosis were reversed by the end of the 72 hour observation period. Furthermore, the mean scores for each of the parameters do not fall within the range requiring classification.