Oxaceprol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984-02-13 to 1984-03-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

no

Remarks:

Study performed before introduction of OECD principles of GLP

Test material

Test material information

Constituent 1

Reference substance name:

Oxaceprol

EC Number:

251-780-6

EC Name:

Oxaceprol

Cas Number:

33996-33-7

Molecular formula:

C7H11NO4

IUPAC Name:

1-acetyl-4-hydroxy-L-proline

Test material form:

solid: crystalline

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Degussa AG / 22.2393.12.01

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: stable according to information by Degussa AG
- Solubility and stability of the test substance in the solvent/vehicle: soluble

OTHER SPECIFICS: pH-value 0 1.7 (10.0 % solution)

Test animals / tissue source

Species:

rabbit

Strain:

other: White Russian (Albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Asta Werke AG
- Age at study initiation: 5 months
- Weight at study initiation: 2.10 - 2.35 kg
- Housing: stainless steel cages, type ASTA
- Diet (e.g. ad libitum):standardised test animal food for rabbits
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 2°C
- Humidity (%): 55 % +/- 15 %
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From:1984-02-12 To: 1984-03-05

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

(21 d)

Observation period (in vivo):

21 d

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1 h, 24 h, 48 h, 72 h

Score:

56.3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

probability of severe irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

Mean value "5" derived from 4 instead of 12 individual values as assessment was not possible for 2 animals due to severe cornea opacity.

Time point:

other: 1h, 24 h, 48 h, 72 h

Score:

ca. 5

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1h, 24 h, 48 h, 72 h

Score:

15.7

Reversibility:

not fully reversible within: 21 days

Remarks on result:

probability of severe irritation

Any other information on results incl. tables

Cornea:

After application almots the entire cornea showed opacity. Details of the iris were not observable value 39 or invisible (value 4). The opacity was not fully reversible with all animals after the 3 weeks observation period. Insertion of vascular vessels into the cornea was observed with 1 animal.

Iris:

The iris of all animals showed moderate circcum corneal hyper anemia until the end of the 3 weeks observation period (value 1). This diagnostic finding could not be assessesd before day 7 or day 8, resp., with 2 animals due to severe opacity of the cornea.

Conjunctivae:

The conjunctivae responded with diffuse respectively flesh-coloured redness (value 2 respectively 3). Additionally, suppurative focuses appeared with 2 animals over a short period of time. Swelling which resulted in semi or fully closed lids (value 3 repsectively 4) was observed with all animals. These reactions resolved almost complete until the end of the 3 weeks observation period.

Hypersecretion was observed with all animals. The hypersecretion moistened significant areas araound the eye and lasted until the end of the 3 weeks observation period. In addition, hair loss around the eye occured with 2 animals.

Systemic toxic effects:

Not observed.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The irritation index could not be derived due to methodological reasons as the iris could not be assessed with 2 animals due to severe cornea opacity.

The results from cornea and conjunctivae as well as the strong acidic pH value of 1.7 lead to the conclusion that oxaceprol has eye damaging properties under the conditions of the test.

Executive summary:

Oxaceprol was tested for eye damaging properties in a guideline study according to OECD 405. The irritation index could not be derived due to methodological reasons as the iris could not be assessed with 2 animals due to severe cornea opacity. The results from cornea and conjunctivae as well as the strong acidic pH value of 1.7 lead to the conclusion that oxaceprol has eye damaging properties under the conditions of the test.