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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:
1992-11-16 to 1992-12-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trimethylorthoformiat (TMOF)
- Substance type: pure active substance
- Physical state: liquid, colorless
- pH: 5.02
- Water solubility: 10 g/liter
- Analytical purity: 99.8 area-% (method not stated)
- Impurities (identity and concentrations): no data
- Lot/batch No.: 20217, 222.1-263 / manufactured 1992-02-17
- Expiration date of the lot/batch: 1993 February
- Stability under test conditions: Sensitive to hydrolysis
- Storage condition of test material: Closed container, in hood


Test animals / tissue source

Species:
rabbit
Strain:
other: Kleine Weisse Russen, strain Chbb:HM, SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Kleine Weisse Russen, strain Chbb:HM, SPF
- Age at study initiation: adult
- Weight at study initiation: 2 - 3 kg
- Housing: conventional, individual animals in stainless steel cages
- Diet: ad libitum, Ssniff K 4 Alleindiaet fuer Kaninchen
- Water: communal drinking water ad libitum
- Acclimation period: > 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 1992-11-16 To: 1992-12-07

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 cm3 liquid test substance placed into the conjunctival sac of one eye
- Untreated eye serves as control

VEHICLE
- none
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48, 72 hours, 6, 8, 10, 13, 17, 20 days after application

Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: with warm physiological saline
- Time after start of exposure: 24 hours after application (after fluorescein test)

FLUORESCEIN TEST
- 24, 48, 72 hours and 6 days after application

SCORING SYSTEM: OECD Guideline 405: Table 1: Grading of ocular lesions

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 20 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 17 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 20 d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 17 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 17 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 17 d
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.45
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks:
no changes at any time point
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.78
Max. score:
4
Reversibility:
fully reversible within: 6 d
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 6 d

Any other information on results incl. tables

Time post application

 

1 h

 

 

24 h

 

 

48 h

 

 

72 h

 

 

6 d

 

8,

10,

13 d

 

17 d

 

 

20 d

 

Animal

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

Conjunctivae: erythema

2

2

2

2

3

3

2

3

3

2

3

3

2

2

2

1

1

1

0

0

1

0

Conjunctivae: chemosis

1

2

2

1

2

2

1

2

2

1

2

2

1

1

1

1

0

1

0

0

0

0

Iris

0

0

0

0

1

1

0

1

1

0

0

0

0

0

0

0

0

0

0

0

0

 

 

0

Cornea

1

1

1

0

1

1

0

1

2

0

1

1

0

0

0

0

0

0

0

0

0

 

 

0

Examination w. fluorescein

 

 

0

3

4

0

3

1

0

1

1

0

0

0

 

 

 

Exudation

x

x

x

 

x

x

 

x

x

 

 

 

 

 

 

Exudation (white, slimy)

x

 

 

 

x

x

 

x

x

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Conjunctivae incl. nictitating membrane: bleeding

 

 

 

slight

severe

severe

x

x

x

x

x

x

 

 

 

 

 

 

 

 

 

 

 

 

Iris: reddened

 

 

 

 

x

x

 

x

x

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

From the numerical scores of the individual animals at 24, 48, and 72 hours, the following averages were calculated:

 

Animal 1

Animal 2

Animal 3

Average

Conjunctivae: erythema

2.00

3.00

3.00

2.67

Conjunctivae: chemosis

1.00

2.00

2.00

1.67

Iris

0

0.67

0.67

0.45

Cornea

0

1.00

1.33

0.78

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria