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Administrative data

Description of key information

Skin irritation: not irritating (OECD 404, GLP compliant)
Eye irritation: not irritating (OECD 405, GLP compliant)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-03-18 to 2008-04-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study reliable without restrictions Deviation from guideline without an effect on the results - according to the guideline, systemic effects should be recorded. This was missing in the study report. - according to the guideline, the individual bodyweight of the rabbits at the conclusion of the study should be stated. This was missing in the study report.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
, adopted 2002-04-24
Deviations:
yes
Remarks:
, see "Rationale for reliability incl. deficiencies" above
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2007-10-15
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan France SARL, 03800 Gannat, France
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: animals were individually housed in suspended cages.
- Diet (ad libitum): Certified Rabbit Diet
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 23 °C
- Relative humidity: 30 to 70 %
- Air exchanges: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of the test material
Duration of treatment / exposure:
4 hours
Observation period:
approximately one hour following the removal of the patches, and 24, 48 and 72 hours later and on Days 7 and 14.
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area
- Type of wrap if used: 2.5 cm x 2.5 cm cotton gauze patch, which was secured in position with a strip of surgical adhesive tape. The trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing: any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: four hours after application

SCORING SYSTEM: according to the Draize scale

Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Also observed: loss of skin elasticity (at 48 and 72 h), light brown discolouration of the epidermis (at 72 h), loss of skin flexibility (at 72 h) and moderate desquamation (at Day 7).
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Also observed: light brown discolouration of the epidermis (at 72 h) and moderate desquamation (at Day 7).
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Also observed: light brown discolouration of the epidermis (at 72 h), loss of skin elasticity (at 72 h) and crust formation (at Day7).
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Very slight erythema was noted at all treated skin sites one hour after patch removal. Well-defined erythema and very slight to slight oedema were noted at all treated skin sites at the 24, 48 and 72 hour observations. Very slight erythema was noted at one treated skin site at the 7-day observation.


Loss of skin elasticity was noted at one treated skin site at the 48-hour observation and at two treated skin sites at the 72-hour observation. Loss of skin flexibility was noted at one treated skin site at the 72-hour observation. Light brown discolouration of the epidermis was noted at all treated skin sites at the 72-hour observation. Moderate desquamation was noted at two treated skin sites with crust formation noted at the remaining treated skin site at the 7-day observation.

All treated skin sites appeared normal at the 14-day observation.

No corrosive effect were noted.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test substance is not a skin irritant
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-09-30 to 2008-10-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
, adopted 2002-04-24
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2007-10-15
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.78 to 2.92 kg
- Housing: animals were individually housed in suspended cages.
- Diet (ad libitum): 2030 Teklad Global Rabbit diet supplied y Harlan Teklad, Blackthorn, Bicester, Oxon, UK
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 23 °C
- Relative humidity: 30 to 70 %
- Air exchanges: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test material
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
approximately 1 hour and 24, 48 and 72 hour following treatment
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
SCORING SYSTEM: according to the Draize scale

TOOL USED TO ASSESS SCORE:
Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation.
Minimal discharge was observed in all rabbits at the 1 hour-observation.
All treated eyes appeared normal at the 48-hour observation.
Other effects:
All animals showed expected gain in bodyweight during the study.
Pain reaction: all rabbits showed a slight initial pain reaction when the test material was instilled.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is non-irritating to the eye.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as an eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

One reliable animal study described in Bradshaw (2008) (OECD 404, GLP compliant) is considered to be reliable without restrictions. The substance was determined not to be a skin irritant.

Eye irritation

One reliable animal study described in Bradshaw (2008) (OECD 405, GLP compliant) is considered to be reliable without restrictions. The substance was determined not to be an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
GLP guideline study conducted with the test item

Justification for selection of eye irritation endpoint:
GLP guideline study conducted with the test item

Justification for classification or non-classification

Skin irritation

Reference Bradshaw (2008) is considered as the key study for in vivo skin irritation and will be used for classification. The skin irritation was scored according to the Draize scale. The mean score (24, 48, 72h) for erythema was 2, observed in each of the three animals. Odema score was noted in one of the animals 2 and in two animals 1. All effects were fully reversible within 14 days.

Thus, according toregulation (EC) 1272/2008 and subsequent amendments the substance will not be classified as irritating to the skin.

Eye irritation

Reference Bradshaw (2008) is considered as the key study for in vivo eye irritation and will be used for classification. The eye irritation was scored according to the Draize scale. The mean scores (24, 48, 72h) for conjunctivae and chemosis were 0.33 in all of the three animals. No other effects were observed. The effects were fully reversible within 48 hours.

Thus, according to Regulation (EC) 1272/2008 and subsequent amendments the substance will not be classified as irritating to the eyes.

Respiratory irritation

The classification as respiratory irritant is normally covered under the endpoint specific target organ toxicity- single exposure and repeated exposure. However, due to lack of data on acute toxicity, inhalation and repeated dose toxicity, inhalation (only REACH annex VII data available at this point in time); a short statement on respiratory irritation based on the current data base is given in the following:

 

Since (i) the substance caused only very mild, transient eye irritation (max mean score: 0.33) and therefore is not considered to cause relevant irritation on other mucosal membranes and (ii) the substance has a very low vapour pressure (0.22 Pa at 22.5°C) which means that human exposure is not likely, it can safely be assumed at this point in time that classification as respiratory irritant is not required for this substance.

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