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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 02 to 30 Aug 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-amino-5-bromopyridin-3-ol
EC Number:
689-734-6
Cas Number:
39903-01-0
Molecular formula:
C5H5BrN2O
IUPAC Name:
2-amino-5-bromopyridin-3-ol
Details on test material:
- Purity: 96.2% w/w
- Batch No.: CCS-952/STG-02/00109

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L'Arbresle Cedex, France and Harlan, Belton, Leics, England
- Age at study initiation: Between 10-20 weeks old
- Weight at study initiation: 2-4 kg
- Housing: Labeled cages with perforated floors and shelters
- Diet (e.g. ad libitum): Pelleted diet approximately 100 grams per day, hay was provided at least three times a week
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0±3.0℃ (actual range: 19.0-20.0℃)
- Humidity (%): 40-70% (actual range: 50-87%)
- Air changes (per hr): Approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN-LIFE DATES: From: 2010-08-02 To: 2010-08-30

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 66.9 mg (range 66.5-67.3 mg)
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males
Details on study design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of eye irritation observed in the first animal.

Treatment:
Animals were treated by instillation of, on average, 66.9 mg (range 66.5 - 67.3 mg) of the test substance (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20%.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Fully reversible within 48 hours in one animal and within 7 days in the other two animals.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
ca. 0.3
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Fully reversible within 48 hours in all of 3 animals.
Irritant / corrosive response data:
No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.
There was no evidence of ocular corrosion.
Other effects:
No staining of (peri) ocular tissues by the test substance was observed. Remnants of the test substance were present in the eyes of two animals on Day 1.
No symptoms of systemic toxicity were observed in the animals during test period and no mortality occurred.

Any other information on results incl. tables

Individual eye irritation scores

Animal

Time after dosing

 

 

Cornea

(0-4)

Iris

(0-2)

Conjunctivae

Redness

(0-3)

Chemosis

(0-4)

Discharge

(0-3)

452

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

1

1

0

0

1

1

0

0

1

1

0

0

482

1 hour

24 hours

48 hours

72 hours

7 days

0

0

0

0

0

0

0

0

0

0

2

2

1

1

0

2

1

0

0

0

1

1

0

0

0

483

1 hour

24 hours

48 hours

72 hours

7 days

0

0

0

0

0

0

0

0

0

0

2

2

1

1

0

1

1

0

0

0

1

1

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No eye irritation was caused by exposure to the test substance.

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