Oxaceprol

Endpoint summary

Description of key information

Oxaceprol has to be classified as Eye Dam. 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-03-09 to 2001-11-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992-07-17

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Kyowa Hakko Kogyo Co., Ltd. / lot 000703

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: highly soluble

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: grounded to fine powder

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 70 %
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2001-05-18 or earlier To: 2001-05-28

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Purity: distilled water

Duration of treatment / exposure:

1 h, 24 h, 48 h, 72 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Type of wrap if used: adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure:

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 3 min, 1 h, 24 h, 48 h, 72 h

SCORING SYSTEM:
- Method of calculation: according to Draize

Irritation parameter:

other: Erythema / eschar formation

Basis:

other: All 3 animals

Time point:

other: 1 h

Score:

2

Reversibility:

fully reversible

Irritation parameter:

other: Erythema / eschar formation

Basis:

other: All 3 animals

Time point:

24 h

Score:

1

Reversibility:

not fully reversible within:

Irritation parameter:

other: Erythema / eschar formation

Basis:

other: All 3 animals

Time point:

48 h

Score:

0

Irritation parameter:

other: Erythema / eschar formation

Basis:

other: All 3 animals

Time point:

72 h

Score:

0

Irritation parameter:

edema score

Basis:

other: All 3 animals

Time point:

other: 1 h

Score:

1

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

other: All 3 animals

Time point:

24/48/72 h

Score:

0

Interpretation of results:

GHS criteria not met

Conclusions:

The substance Oxaceprol is not irritant or corrosive to the skin

Executive summary:

The study according to OECD 404 was performed to assess the irritancy potential of Oxaceprol to the skin of the New Zealand White rabbit.

The test material procuded a primary irrittaion index of 0.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme.

Oxaceprol did not meet the criteria for classification as irritnat or corrosive to the skin according to CLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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

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)

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

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

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Additional information

The pH-value of oxaceprol was measured not only in the key study for the endpoint "eye irritation" but in other contexts as well. pH-values were between 1.4 and 2.0

Justification for classification or non-classification

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.