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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 April 2003 to 25 April 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Details on test material:
Identification: HSY-2701
Description: Red powder
Batch: 03A-20
Purity: > 99.9 %
Test substance storage: At room temperature protected from light
Stability under storage conditions: Stable
Expiry date: 07 August 2003 (6 months from the date of receipt).

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: At least six weeks of age
- Weight at study initiation: At least 1 kg
- Housing: Individually labelled cages with perforated floors (Scanbur, Denmark, Dimension 56 x 44 x 37.5 cm).
- Diet (e.g. ad libitum):Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany), approximately 100 g per day.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 24.9 mg (23.8-26.6 mg) of the test substance at a volume of approximately 0.1 mL.
Duration of treatment / exposure:
Indefinite, no washing was performed
Observation period (in vivo):
Reported up to 72 hours as all animals had recovered by 48 hours.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
No washing reported

SCORING SYSTEM:
Immediately after 24 hours observation, a solution of 2 % fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quatitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage was estimated as a percentage of the total corneal area.

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
Mean redness score
Basis:
animal: 221
Time point:
other: 24-72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
Mean redness score
Basis:
animal: 258
Time point:
other: 24-72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
Mean redness score
Basis:
animal: 269
Time point:
other: 24-72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
The results were evaluated according to the EC criteria for classification and labelling of dangerous substance and preparations (Council directive 67/548/EEC and all adaptations to technical progress and ammendments of this Directive published in the Official Journal of the European Communities).
Instillation of approximately 25 mg of the test substance (approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which was seen as redness, chemosis and discharge. The irritation had completely resolved within 48 hours in all animals. OVer the three observation times used to calculate mean scores for EC classification purposes (24, 48, 72 hours) only grade 1 redness at 24 hours was observed.
No irridial irritation or corneal opacity was observed, and treatment of the eyes with 2 % fluorescein, 24 hours after test susbtance instillation revealed no corneal epithelial damage in any of the animals.
There was no evidence of of ocular corrosion.
Other effects:
Remnants of the test substance were present in the eyes of all animals on day 1. Yellow/orange staining of the fur on the head and paws, caused by the test substance, was noted during the observation period.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual eye irritation scores

Time after dosing

Cornea

Iris

Conjunctivae

Comments

Opacity

Area

Fluor area (%)

Redness

Chemosis

Discharge

Animal No. 221

1 hour

0

0

0

0

2

0

1

e,b

24 hours

0

0

0

1

0

0

e

48 hours

0

0

0

0

0

0

e

72 hours

0

0

0

0

0

0

e

Animal No. 258

1 hour

0

0

0

0

1

1

1

e,b

24 hours

0

0

0

1

0

0

e

48 hours

0

0

0

0

0

0

e

72 hours

0

0

0

0

0

0

e

Animal No. 269

1 hour

0

0

0

0

2

0

1

e,b

24 hours

0

0

0

1

0

0

e

48 hours

0

0

0

0

0

0

e

72 hours

0

0

0

0

0

0

e

Fluor area (%): green staining (percentage of total corneal area) after fluorescein treatment

b: Remnants of the test substance in the eye

e: Yellow/orange staining of the head and paws by the test substance.

Table 2: Mean value irritation scores

Animal # Mean 24-72 hours
Corneal opacity Iris Conjuntivae
Redness Chemosis
221 0 0 0.3 0
258 0 0 0.3 0
269 0 0 0.3 0

Table 3: Animal specifications

Animal No. Sex Age at start (weeks) Body weights (g)
Prior to application At termination
221 Male 7-9 2313 2441
258 Male 8-10 1991 2055
269 Male 8-10 1901 2059

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results, HSY-2701 is not considered an irritant to the rabbit eye.
Executive summary:

In a GLP study conducted in accordance with the OECD guideline 405, HSY-2701 was administered into the eye of three New Zealand white rabbits and observed for signs of irritation. Mild irritation of the conjunctivae occured shortly after instillation, however this had fully recovered by 48 hours. HSY-2701 was considered not irritating.

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