Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin: The test item produced a primary irritation index of 0.7 and was considered to be a mild irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 (OECD 404 and EU Method B.4).


Eye: The test item produced a maximum group mean score of 16.0 and was considered to be a moderate irritant (Class 5 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 (OECD 405 and EU Method B.5).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 January 2015 to 23 April 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 Harlan Laboratories UK Ltd, Leicestershire UK.
- At the start of the study the animals weighed 2.51 to 2.92 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 Harlan Laboratories 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 (06:00 to 18:00) 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:
0.5 mL of the test item
Duration of treatment / exposure:
Four hours
Observation period:
Seven days
Number of animals:
Three
Details on study design:
TEST ITEM FORMULATION
- The absorption of the test item was not determined.

MEASUREMENT OF pH
- The pH of the test item was determined prior to commencement of the study.

PROCEDURE
- On the day before the test, two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers.
- Only animals with a healthy intact epidermis by gross observation were selected for the study.
- On the day of the test, a suitable test site was selected on the back of each rabbit.
- A quantity (0.5 mL) of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton guaze patch.
- The patch was secured in position with a strip of surgical adhesive tape.
- To prevent the animals interferring with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
- Four hours after application, the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Immediately following removal of the patches, and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to defined criteria (see attached scale for evaluation of skin reactions).
- If present, any other skin reactions and clinical signs of toxicity were also recorded.
- Based on the results for the initial two animals, and at the request of the sponsor, a third animal was treated as described previously.
- An additional observation was made on the initial two treated animals on Day 7 to assess the reversibility of skin reactions.
- Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74911 Male
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 74912 Male
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74993 Male
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74911 Male
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Remarks:
7 d
Remarks on result:
other: 74912 Male
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74993 Male
Irritant / corrosive response data:
- Individual scores for erythema/eschar and edema are given in Table 1 (attached).
- Very slight erythema was noted at two treated skin sites immediately and 1 hour after patch removal and at two treated sites at the 24 hour observation.
- Well defined erythema and very slight edema were noted at one treated skin site at the 48 hour and 72 hour observations.
- One treated skin site appeared normal at the 24 hour observation and the other treated skin skite appeared normal at the 7 day observation.
- No evidence of skin irritation was noted at one treated skin site during the study.
Other effects:
BODY WEIGHT
- Individual body weights and body weight change are given in Table 2 (attached).
- All animals showed expected gain in body weight during the study.

MEASUREMENT OF pH

- Test item undiluted as supplied: pH 5

- Aqueous preparation of test item (90 % v/v): pH 5 immediately; pH 10 after 10 minutes; pH 10 after 20 minutes.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a primary irritation index of 0.7 and was considered to be a mild irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted. The test material is not classified under the terms of Regulation (EC) No 1272/2008.
Executive summary:

GUIDELINE

The irritancy potential of the test item to the skin of the New Zealand White rabbits was investigated using a procedure designed to be compatible with OECD Guideline for the Testing of Chemicals No 404 "Acute Dermal Irritation/Corrosion (adopted 24 April 2002) and Method B.4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No 440/2008.

RESULTS

A single 4 hour, semi-occluded, application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight edema at two treated skin sites. One treated skin site appeared normal at all observations, one other treated skin site appeared normal at the 24 hour observation and the remaining skin site appeared normal at the 7 day observation.

CONCLUSION

The test item produced a primary irritation index of 0.7 and was considered to be a mild irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for three animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for erythema and edema.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 January 2015 to 23 April 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
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 Harlan Laboratories UK Ltd, Leicestershire, UK.
- At the start of the study the animals weighed 2.37 or 2.62 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 Harlan Laboratories Ltd, 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 (06:00 to 18:00) 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:
0.1 mL of test item
Duration of treatment / exposure:
Single application
Observation period (in vivo):
7 days
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
Remarks:
opacity
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74924 male
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
Remarks on result:
other: 74924 male
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 74924 male
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 74924 male
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74945 male
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: 74945 male
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 74945 male
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 74945 male
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 both treated eyes 1 hour after application of the test material.
- Moderate conjunctival irritation was noted in both treated eyes at 1 and 24 hours after application of the test item.
- Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 48 hour observation.
- Minimal conjunctival irritation waas noted in both treated eyes at the 72 hour observation.
- Both treated eyes appeared normal at the 7 day observation.
Other effects:
BODY WEIGHT
- Individual body weights are given in Table 3 (attached).
- Both animals showed expected gain in body weight during the study.

MEASUREMENT OF pH

- Test item undiluted as supplied: pH 5

- Aqueous preparation of test item (90 % v/v): pH 5 immediately; pH 10 after 10 minutes; pH 10 after 20 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 16.0 and was considered to be a moderate irritant (Class 5 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 7 day observation.

CONCLUSION

The test item produced a maximum group mean score of 16.0 and was considered to be a moderate irritant (Class 5 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
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN

METHOD

The irritancy potential of the test item to the skin of the New Zealand White rabbits was investigated in a key study using a procedure designed to be compatible with OECD Guideline for the Testing of Chemicals No 404 "Acute Dermal Irritation/Corrosion (adopted 24 April 2002) and Method B.4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No 440/2008.

 

RESULTS

A single 4 hour, semi-occluded, application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight edema at two treated skin sites. One treated skin site appeared normal at all observations, one other treated skin site appeared normal at the 24 hour observation and the remaining skin site appeared normal at the 7 day observation.

 

CONCLUSION

The test item produced a primary irritation index of 0.7 and was considered to be a mild irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for three animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for erythema and edema.

EYE

METHOD

A key 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 7 day observation.

 

CONCLUSION

The test item produced a maximum group mean score of 16.0 and was considered to be a moderate irritant (Class 5 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.

Justification for classification or non-classification

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 7 day observation period. Furthermore, the mean scores for each of the parameters do not fall within the range requiring classification.