Registration Dossier

Administrative data

Description of key information

Epyrron was not irritating to the skin of rabbits but was irritating to the eyes of rabbits at a dosage of 0.5 grams.

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
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, the Netherlands
- Age at study initiation: 6 weeks old
- Weight at study initiation: Less than 3.5 kg
- Housing: Individual cages with perforated floors
- Diet: 100 grams/day of standard laboratory rabbit diet (LKK-20 pellet Hope Farms, Woerden, The Netherlands)
- Water (e.g. ad libitum): Free access to tap-water diluted with decalcified water.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams

VEHICLE
- Amount(s) applied (volume or weight with unit): water
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Dorsal - Flank area
- Coverage: 150 cm squared
- Type of wrap if used: Scotchpak-non-woven of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Moistened tissue with tap-water
- Time after start of exposure: 4 Hours

SCORING SYSTEM:
See free text section below.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 Hour
Score:
>= 0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 Hours
Score:
>= 0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 Hours
Score:
>= 0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 Hours
Score:
>= 0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 Hour
Score:
>= 0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 Hours
Score:
>= 0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 Hours
Score:
>= 0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 Hours
Score:
>= 0
Max. score:
4
Irritant / corrosive response data:
No skin irritation or corrosion was reported on rabbits after the exposure to test substance for 4 hours through the duration of the test.
Other effects:
No staining of the treated skin area was observed during the test period.

No toxicological symptoms were observed in any of the rabbits exposed to test substance.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results and according to EU criteria the test substance when administered to rabbits at a dosage of 0.5 grams shall not be considered an irritant or corrosive to skin.
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:
3 - 17 November 1997
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 6 weeks
- Weight at study initiation: 3.5 kg
- Housing: Individual cages with perforated floors
- Diet: 100 grams per day of standard laboratory rabbit diet (LKK-20, pellet, Hope Farms, Woerden, The Netherlands)
- Water: Free access to tap-water diluted with decalcified water.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 48.6 g (approximately 0.1 mL)

Duration of treatment / exposure:
Single samples were instilled. Remnants of the test substance were present in the eyes of all rabbits up to 48-72 hours after installation.
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 50 mL of tap-water
- Time after start of exposure: 48 hours

SCORING SYSTEM:
See free text section below

TOOL USED TO ASSESS SCORE: 2% fluorescein in water for 24 hour observation of corneal epithelial damage.
All other examinations were completed using standard lighting or with the assistance of an ophthalmic examination lamp.
Irritant / corrosive response data:
Effects of irritation were observed within cornea, iris and conjunctivae.
Corneal injury consisted of opacity and epithelial damage (25-35% of corneal area).
Iridic irritation was observed in all rabbits exposed to test substance.
Irritation of conjunctivae consisted of redness, chemosis and discharge in all animals exposed to test substance.

There was no evidence of corrosion.
Other effects:
Remnants of the test substance were present in the eyes of all animals up to 48-72 hours after exposure.
No symptoms of toxicity were observed during test period, no mortality occurred.
 Individual Eye Irritation Scores                    
  Animal No. 1453 1479 1485
Time after dosing Tissue Findings Score  Comments Score  Comments Score  Comments
1 hour Corneal opacity 0 D 0 D 0 D
area 0   0   0  
Iris 1   1   1  
Conj.: redness 2(A)   2(A)   2(A)  
Chemosis 3(A)   3(A)   3(A)  
Discharge 2   2   2  
24 Hours Corneal opacity 0 25 D 0 35 D 0 25 D
area 1   2   1  
Iris 0   1   1  
Conj.: redness 3(A)   3(A)   3(A)  
Chemosis 2(A)   2(ABC)   2(ABC)  
Discharge 1   2   2  
48 Hours Corneal opacity 1 D 1 D 1 D
area 1   2   1  
Iris 0   1   0  
Conj.: redness 3(AC)   3(AC)   3(AC)  
Chemosis 1(ABC)   2(A)   2(A)  
Discharge 1   1   1  
72 Hours Corneal opacity 0 5 0 25 D 0 5 D
area 1   2   1  
Iris 0   0   0  
Conj.: redness 2(AC)   2(AC)   3(C)  
Chemosis 1(AC)   1(AC)   1(ABC)  
Discharge 0   1   1  
7 Days Corneal opacity 0 0 0 0 0 0
area 0   0   0  
Iris 0   0   0  
Conj.: redness 0   1(AC)   1(C)  
Chemosis 0   0   0  
Discharge 0   0   0  
14 Days Corneal opacity 0   0   0  
area 0   0   0  
Iris 0   0   0  
Conj.: redness 0   0   0  
Chemosis 0   0   0  
Discharge 0   0   0  
() Score given for: A=Eyelids
B=Nictitating membrane
C=Sclera
Comments
D - Remnants of the test substance in the eye
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance was administered to 3 male rabbits and appears to be irritating to the eye at a dosage of 0.5 grams.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Epyrron was not irritating to the skin of rabbits but was irritating to the eyes of rabbits at a dosage of 0.5 grams.

.


Justification for selection of eye irritation endpoint:
Epyrron was irritating to the eyes of rabbits at a dosage of 0.5 grams.

Effects on eye irritation: irritating

Justification for classification or non-classification

Epyrron is not classifiable as a skin irritant according to Directive 67/548 EEC or Regulation (EC) 1272/2008 (CLP). However, epyrron is

classified as irritating to the eyes.