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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 13-JUN-2002 to 01-JUL-2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The test was performed according to OECD guideline and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations from the maximum level of temperature (with a maximum of 1°C) and from the maximum level for relative humidity (up to 23%) occurred . These protocol deviations were considered not to have affected the study integrity.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Remarks:
Tests based on dissolved material in the concentrate
Details on test material:
- Name of test material (as cited in study report): Aldolase (IUB 4.1.2.4)
- Substance type: enzyme
- Physical state: liquid
- Stability under test conditions: data not available
- Storage condition of test material: In freezer in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: 1309g, 1499g and 2367g
- Housing: individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5cm )
- Diet: Standard laboratory rabbit diet (Teklad Global Rabbit Diet, code 2030, Harlan, Blackthorn, England) approx. 100 g. per day
- Water: Free access to tap-water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 3°C
- Humidity: 30-70%
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day


IN-LIFE DATES: data not available

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye remained untreated and served as the reference control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: undiluted
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 male animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to OECD and EU guidelines


TOOL USED TO ASSESS SCORE: 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.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 - 72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks:
no effect observed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 - 72h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks:
no effect observed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 - 72h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 - 72h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks:
no effect observed
Irritant / corrosive response data:
Irritation:
Instillation of 0.1 ml of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae in 2 animals, which was seen as redness. The irritation had completely resolved within 24 hours in both animals.
No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

Corrosion:
There was no evidence of ocular corrosion.
Other effects:
Colouration:
No staining of (peri) ocular tissues by the test substance was observed.

Toxicity / Mortality:
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: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0 / 0 / 0

0 / 0 / 0

1 / 1 / 0

0 / 0 / 0

24 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

48 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

72 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Average 24h, 48h, 72h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Maximum average score (including area affected, max 110)

0

Reversibility

 yes

Average time (h) for reversion

 24h

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
ALDOLASE (I.U.B. 4.1.2.4) does not have to be classified and has no obligatory labelling requirement for eye irritation according to EU criteria.
Executive summary:

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, 8.5, "Acute Toxicity - Eye irritation" and OECD No.405, "Acute Eye Irritation/Corrosion".

Single samples of 0.1 ml of ALDOLASE (I.U.B. 4.1.2.4) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

Instillation of the test substance resulted in irritation of the conjunctivae in 2 animals, which was seen as redness. The irritation had completely resolved within 24 hours in both animals. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), ALDOLASE (I.U.B. 4.1.2.4) does not have to be classified and has no obligatory labelling requirement for eye irritation.