Registration Dossier

Administrative data

Description of key information

Eye corrosion occurred in ocular tissues of rabbits based on OECD Guideline study 405 and EU Method B.5 after 72 hours of exposure. No skin irritation was observed after 4 hour exposure period to rabbits. 

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:
28 October 1997 - 31 October 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guideline 404 and EU Method B.4 (Acute Dermal irritation/Corrosion) without deviations and GLP practices.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Neitherlands
- Age at study initiation: At least 6 weeks old
- Weight at study initiation: Less than 3.5 kg
- Housing: Individually housed in cages with perforated floors
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pelleted diameter 4mm, Hope Farms, Woerden, The Neitherlands), approximately 100 grams per day. Additionally, hay was provided once per week.
- Water (e.g. ad libitum): Free access to tap-water with decalcified water
- Acclimation period: At least 5 days before the start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 deg C
- Humidity (%): 50%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Not documented in the study report To: Not documented in the study report
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
other: Adjacent areas of the untreated skin of each animal served as controls.
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:
Up to 72 hours after application (Observations were made 1, 24, 48 and 72 hours after exposure)
Number of animals:
Three animals of either sex
Details on study design:
TEST SITE
- Area of exposure: Skin of one flank/animal
- % coverage: % not specified in the study report, although an area of 150 square centimeters (10X15 cm2) was used for the exposure site
- Type of wrap if used: Scotchpak-non-woven patch of 2X3 cm mounted on Micropore tapeand secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the remaining test substance was removed using a tissue moistened with tap-water and subsequently a dry tissue.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize Scoring System
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritant / corrosive response data:
No irritation was caused by 4 hours of exposure to the test substance. There was no evidence of a corrosive effect on the skin.
Other effects:
No staining of the treated skin was observed. No symptoms of systemic toxicity in the animals during the test period and no mortality occurred.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No skin irritation was caused by 4 hours exposure to 0.5 grams of Epyrrol.
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 November 1997 - 6 November 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guideline 405 and EU Method B.5 (Acute Eye Irritation/Corrosion) and GLP practices.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
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:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Neitherlands
- Age at study initiation: At least six weeks old
- Weight at study initiation: Less then 3.5 kg
- Housing: Individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm., Hope Farms, Woerden, The Neitherlands), approximately 100 grams/day. Additionally, hay was provided once a week.
- Water (e.g. ad libitum): Free access to tap-water diluted with decalcified water
- Acclimation period: At least 5 days before the start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 deg C
- Humidity (%): 50%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Not provided in study report To: Not provided in study report
Vehicle:
not specified
Controls:
other: Treatment was only applied to one eye, the other eye served as the control for each animal.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 29.9 +/- 0.3 mL (0.1 mL volume)
Duration of treatment / exposure:
Single application
Observation period (in vivo):
Up to 72 hours
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): A solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled in both eyes of each animal.
- Time after start of exposure: 24 hours after treatment

SCORING SYSTEM: Evaluation of eye reactions were based on a numerical scoring system used to score eye lesions, evaluating the corneal irritation (scale of 0-4), iris (scale of 0-2), conjunctival irritation (scale of 0-3), chemosis (scale of 0-4), and discharge (scale of 0-3), with 0 being the low end of the scoring system and/or no effects.

TOOL USED TO ASSESS SCORE: Fluorescein, although in case standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
Irritant / corrosive response data:
Installation of approximately 30 mg of Epyrrol (a volume of ~ 0.1 mL) into one eye of each of three rabbits resulted in effects on the cornea, iris, and conjunctivae.

The Corneal injury consisted of opacity (maximum grades 2-3) and epithelial damage (maximum 75% of the corneal area).

Iridic irritation grade 1 was observed in all animals.

In all animals, approximately 25% of the cornea and iris could not be scored, due to oedema of the eyelids, 24 and/or 48 hours after instillation.

In one animal, approximately 35% of the iris could not be scored after 48 and 72 hours, due to the corneal injury.

The irritation of the conjunctivae consisted of readness, chemosis and discharge. Necrosis of the ocular tissue was observed in all animals from 24 hours after instillation onwards.

No signs of an early recovery of the ocular injury was observed. It was therefore decided to terminate the study and to sacrifice the animals for ethical reasons immediately after the 72 hour observation.
Other effects:
Remnants of the test substance coloration were present in the eyes of all animals on Day 1.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Animal # 1467 1468 1483
Time after Dosing Tissue/ Finding Score Fluor. Area (%) Comments Score Fluor. Area (%) Comments Score Fluor. Area (%) Comments
1 hour Corneal Opacity 2 D 2 D 2 D
Corneal Opacity area 2   1   1  
Iris 1   1   1  
Conj. Redness 3 (A)   3 (B)   2 (ABC)  
Conj chemosis 4 (ABC)   3 (ABC)   3 (ABC)  
Discharge 1   2   2  
24 hours Corneal Opacity 2 75 E 2 75 E 2 75 E
Corneal Opacity area 3   3   3  
Iris 1   1   1  
Conj. Redness 3 (AB)   3 (B)   3 (B)  
Conj chemosis 4 (ABC)   4 (ABC)   4 (ABC)  
Conj. Discoloration * B   B   B  
Discharge 1   2   3  
48 hours Corneal Opacity 2 E 3  - 3 F
Corneal Opacity area 3   1   1  
Iris 1   1   1  
Conj. Redness 3 (AB)   3 (ABC)   3 (ABC)  
Conj chemosis 4 (ABC)   3 (ABC)   4 (B)  
Conj. Discoloration * AB   b   B  
Discharge 2   3   3  
72 hours Corneal Opacity 2 75 - 3 75 - 3 75 F
Corneal Opacity area 3   1   2  
Iris 1   1   1  
Conj. Redness 3 (ABC)   3 (ABC)   3 (ABC)  
Conj chemosis 4 (A)   3 (ABC)   4 (A)  
Conj. Discoloration * AB   B   AB  
Discharge 2   2   2  
A = Eyelids
B = Nictitating membrane
C = Sclera
D = Remnants of the test substance in the eye
E = Approx. 25% of the cornea and iris could not be scored, due to oedema of the eyelids
F= Approx. 35% of the iris could not be scored due to corneal damage
* Discoloration = Gray/white discoloration of the indicated ocular tissues
Interpretation of results:
other: Risk of serious damage to the eyes (R41)
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the necrosis of the ocular tissues and on the degree and persistence of the corneal injury, it was concluded that ocular corrosion had occurred by instillation of Epyrrol into the rabbit eye in all three animals.
Executive summary:

Based on the necrosis of the ocular tissues and on the degree and persistence of the corneal injury, it was concluded that ocular corrosion had occurred by instillation of Epyrrol into the rabbit eye in all three animals. Epyrrol has serious risk of irreversible damage to eyes. Eppyrol therefore meets the criteria for classification under CLP as H314, and under DSD as R41.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
No skin irritation was caused by 4 hours exposure to 0.5 grams of Epyrrol.

Justification for selection of eye irritation endpoint:
Based on the necrosis of the ocular tissues and on the degree and persistence of the corneal injury, it was concluded that ocular corrosion had occurred by instillation of Epyrrol into the rabbit eye in all three animals.

Effects on eye irritation: corrosive

Justification for classification or non-classification