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Administrative data

Description of key information

Acute dermal irritation/corrosion in rabbit (OECD 404): Negative (not irritatting)
Acute eye irritation/Corrosion (OECD 405): Negative (not irritating)

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:
Start of experiment: June 19, 1990 ; End of experiment: June 22, 1990
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
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
The albino rabbit is the recommended species for skin irritation/corrosion studies.
- Animal strain: New Zaeland white rabbits (Chbb:NZW)
- Acclimatisation period: At least 5 days.

Group size and husbandry:
The test was performed on 3 male rabbits, chcked for normal skin conditions, weighing between 2240 to 2490 g (approx. 9-13 weeks old). The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20 +/- 3°C, at a relative humidity of 30-70% and on 12 hours light cycle day.

The rabbits receibed ad libitum standard rabbit pellet-Nafag N°. 814, Gossau, Switzerland and fresh water. All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer.

The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972)
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: Patches were moistened before application with 0.5% (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80.
Controls:
other: Control gauze patch was applied to the contralateral flank of each rabbits.
Amount / concentration applied:
0.5 g. of the test item was applied.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 male rabbits
Details on study design:
An area of at least 36 cm2 was shaved on both flanks of the animals approximately 24 hours before treatment.
A gauze patch (Aprrox. 12-16 cm2) bearing 0.5 g of the test article was applied to the right flank of each animal. A control gauze patch was applied to the contralateral flank. Both patches were moistened before application with 0.5% (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80.
The patches were loosely covered with an aluminium foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).

SCORING SYSTEM:

Erythema and eschar formation.

- No erythema: 0
- Very slight erythema (barely perceptible): 1
- Well defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4
Total possible erythema score: 4


Edema formation
- No edema: 0
- Very slight edema (barely perceptible): 1
- Slight edema (edges of area well defined by definite raising): 2
- Moderate edema (raised approximately 1 mm): 3
- Severe edema (raised more than 1 mm and extending beyond area of exposure ): 4
Total possible edema score: 4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 male rabbits
Time point:
other: Mean 24-72 hours
Score:
0
Remarks on result:
other: 2 male rabbits showed a score of 1 for erythema one hour after removing the bandages, after 24 hours they are fully recovered.
Irritation parameter:
edema score
Basis:
mean
Remarks:
mean 3 male rabbits
Time point:
other: Mean 24-72 hours
Score:
0
Irritant / corrosive response data:
Because no reactions were obsreved at 24 hours to 72 hours after removing the bandages, the test was ended after the 72 hours evaluation.
Other effects:
No data

Individual skin reaction scores:

 Animal n°        ERYTHEMA        EDEMA
  085/M 205/M 107/M  085/M  205/M 107/M 
  CF/TF CF/TF CF/TF  CF/TF CF/TF CF/TF
 after 1 hr.  0/1   0/0   0/1   0/0  0/0   0/0 
 after 24 hrs.  0/0   0/0   0/0    0/0  0/0   0/0 
 after 48 hrs.  0/0   0/0   0/0    0/0  0/0  0/0 
 after 72 hrs.  0/0   0/0   0/0    0/0  0/0  0/0 
 mean 4 -72 hrs.  0/0  0/0  0/0   0/0 0/0   0/0

CF= control flank

TF= Test flank

M= Male

F= Female

Body weight (g)

 animal n°  085/M 205/M  107/M 
 at start if test  2490 2260  2240 
 after 3 days (end)  2570 2330  2300 
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item is classified as non-irritant to the skin rabbit.
Executive summary:

The acute skin irritation/corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of the test substance on the albino rabbit skin.

This test was besed on the OECD Guideline N°.404, adopted May 12, 1981.

Under the experimental conditions employed, the test item, induced slight erythema reactions when applied to the albino rabbits skin.

The reactions were observed only one hour after removing the bandages. Because the mean values of the recordings 24 to 72 hours after application are scored zero, the test item can be classified as non-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:
Start of experiment: June 26, 1990 ; End of experiment: July 3, 1990
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
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The albino rabbit is the recommended species for Acute Eye Irritation/Corrosion studies.
- Animal strain: New Zealand white rabbits (Chbb:NZW)
- Breeder: Dr. K. Thomae, GMBH Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Acclimatisation period: at least 5 days

The test was performed on 3 female rabbits, checked for normaleye conditions, weighing between 2320 to 2600 g (approx. 9-13 weeks old) .
The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20+/- 3 °C, at a relative humidity of 30-70 % and on a 12 hours light cycle day.

The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland - and fresh water. All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer. Analytical results are available at the animal supply office.
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye of each animal remained untreated and served as a control.
Amount / concentration applied:
0.1 ml (47 mg)
Duration of treatment / exposure:
one single application in the conjunctival sac of the left eye of each animal.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
0.1 ml (47 mg) of TK 1333 2 was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article.
The right eye remained untreated and served as a control.
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of TK 13332 according to the OECD scoring system.
A slit-lamp was used to facilitate the evaluation.

SCORING SYSTEM:

CORNEA
- Opacity: degree of density (area most dense taken for reading).
- No ulceration or opacity: 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible: 1
- Easily discernible translucent area, details of iris slightly obscured: 2
- Nacrous area, no details of iris visible, size of pupil barely discernible: 3
- Opaque cornea, iris not discernible through the opacity: 4

IRIS
- Normal: 0
- Markedly deepended rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive): 1
- No reaction to light, haemorrhage, gross destruction ( any or all of these ): 2

CONJUNCTIVAE
Redness : (refers to palpebral and bulbar conjunctivae, cornea and iris)
- Blood vessels normal: 0
- Some blood vessels definitely hyperaemic (injected): 1
- Diffuse, crimson colour, individual vessels not easily discernible: 2
- Diffusy beefy red: 3

Chemosis: lids and/or nictating membranes
- No swelling: 0
- Any swelling above normal (includes nictating membranes ): 1
- Obvious swelling with partial eversion of lids: 2
- Swelling with lids about half closed: 3
- Swelling with lids more than, half closed: 4
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Max score observed is 1 and this until 24 hours after application.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Max score observed is 1 and this until 24 hours after application.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Max score observed is 1 and this until 1 hour after application.
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Max score observed is 1 and this during the first hour after application.
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Max score observed is 1 and this during the first hour after application.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Max score observed is 2 and this until 24 hours after application and then 1 until 48 hours after application.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Max score observed is 2 and this until 24 hours after application and then 1 until 48 hours after application.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
1.67
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Max score observed is 2 and this until 48 hours after application and then 1 until 72 hours after application.
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0.67
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Max score observed is 2 and this 1 hour after application and then 1 until 48 hours after application.
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0.67
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Max score observed is 2 and this 1 hour after application and then 1 until 48 hours after application.
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean
Time point:
other: mean 24-72 hours
Score:
0.67
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Max score observed is 2 and this 24 hours after application and then 1 until 48 hours after application.
Irritant / corrosive response data:
Because reactions were observed within 72 hours after instillation of the test article, the observation period was extended to 7 days to determine the reversibility of the eye reactions.

Individual eye scores.

   CORNEA  IRIS     CONJUNCTIVA
 Animal N° 834/F  ce/te   ce/te   ce/te  ce/te 
  After 1 hr  0/1  0/1  0/2  0/2
  After 24 hrs  0/1  0/0  0/2  0/1
  After 48 hrs  0/0  0/0  0/1  0/1
  After 72 hrs  0/0 0/0   0/0  0/0
  Mean (24 - 72 hrs)  0/0.33  0/0  0/1  0/0.67
  After 7 days  0/0  0/0  0/0  0/0

 CORNEA  IRIS     CONJUNCTIVA
 Animal N° 888/F  ce/te   ce/te   ce/te  ce/te 
  After 1 hr  0/1  0/0  0/2  0/2
  After 24 hrs  0/1  0/0  0/2  0/1
  After 48 hrs  0/0  0/0  0/1  0/1
  After 72 hrs  0/0 0/0   0/0  0/0
  Mean (24 - 72 hrs)  0/0.33  0/0  0/1  0/0.67
  After 7 days  0/0  0/0  0/0  0/0

 CORNEA  IRIS     CONJUNCTIVA
 Animal N° 116/F  ce/te   ce/te   ce/te  ce/te 
  After 1 hr  0/1  0/1  0/2  0/2
  After 24 hrs  0/0  0/0  0/2  0/2
  After 48 hrs  0/0  0/0  0/2  0/1
  After 72 hrs  0/0 0/0   0/1  0/0
  Mean (24 - 72 hrs)  0/0  0/0  0/1.67  0/1
  After 7 days  0/0  0/0  0/0  0/0

ce = control eye

te = test eye

M = Male

F = Female

Body weight (g)

 Animal N°  834/F 888/F  116/F 
 At start of test 2430  2600  2320 
 After 3 days  2460 2680  2330 
 After 7 days (end)  2560 2800  2460 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Regarding the results obtained 24 to 72 hours after instillation, the test item can be classified as non-irritant to albino rabbit's eye.
The eye reactions observed were reversible until the end of the observation period on day 7.
Executive summary:

The acute eye irritation/corrosion in albino rabbits was performed to determine the irritant or corrosive potency of the test item in the albino rabbit eye and the associated mucous membranes.

This test was based on the OECD Guideline N° 405, adopted in May 12, 1981.

Under the experimental conditions employed, the test item, induced irritation of the cornea, iris , and conjunctiva when instilled into the

conjunctival sac of female albino rabbits.

Because the mean values of the readings 24 t o 72 hours after instillation are below the threshold of significance, the test item can be classified as non-irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Two in vivo experiment were performed using the test item to determine the irritant potential in eyes and skin.

The acute dermal irritation in rabbits, (OECD 404), test is negative therefore the test item is not irritating in rabbit skin.

In the vivo experiment, (OECD 405), performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.The test item produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandraclassification system.

The test item does not meet the criteria for classification according to theGlobally Harmonized Systemof Classification and Labelling of Chemicals.

In conclusion, the test item is not irritant to eyes and skin.


Justification for selection of skin irritation / corrosion endpoint:
Only this study is available and the study is Klimisch 1.

Justification for selection of eye irritation endpoint:
Only this study is available and the study is Klimisch 1.

Justification for classification or non-classification

Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).