5-[(4-carboxybutanoyl)peroxy]-5-oxopentanoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

5-[(4-carboxybutanoyl)peroxy]-5-oxopentanoic acid

EC Number:

600-254-8

Cas Number:

10195-54-7

Molecular formula:

C10H14O8

IUPAC Name:

5-[(4-carboxybutanoyl)peroxy]-5-oxopentanoic acid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne
- Age at study initiation: 15 weeks
- Weight at study initiation: 2738 - 3158 g
- Housing: Standard Laboratory Conditions (Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, wood and haysticks for gnawing)
- Diet: Pelleted standard Kliba 3410 ("Kliba", Kliba Muhlen AG, .4303 Kaiseraugst, Switzerland) rabbit maintenance diet ad libitum (batch no. 61/98).
- Water: Community tap water from Itingen, ad libitum, in water bowls.
- Acclimation period: Five days under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3°C
- Humidity (%): 40-70% (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): The room was illuminated by fluorescent light on a 12 hour light/dark cycle. Recorded music was played for approximately 8 hours during the light period.

IN-LIFE DATES:
Delivery of the animals: 16 June 1998
Acclimatization: 17-21 June 1998
Treatment: 22 June 1998
Observation: 22 June-13 July 1998
Euthanasia of the animals: 13 July 1998

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1g per animal undiluted

Duration of treatment / exposure:

The treated eyes were not rinsed after application.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3 animals: 2 females, 1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM :The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks:

after 7 days: score 3

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 4.33.
No corrosion of the comea was observed at any of the reading times. No staining of the cornea, sclera or conjunctivae by the test article was observed.

Other effects:

The body weight of all rabbits were considered to be within the normal range of variability.
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

Under the conditions of the test according to OECD 405, the test substance is considered to be severely damaging the rabbit eye.

Executive summary:

In this study, the potential irritant and/or corrosive effects of the test substance were evaluated on the eyes of New Zealand White rabbits according ot OECD 405. Each of three rabbits received a 0.1g dose of the test article in the conjunctival sac of the left eye. The treated eyes were not rinsed after application. The contralateral eye of each animal remained untreated and served as a control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. No staining of the comea or sclera of the treated eyes by the test article was observed. The mean score (24/48/72h) for cornea opacity was between 0 and 1, not fully reversible in one animal; for conjunctivae the mean score was between 1.66 and 2, fully reversible within 14 days;chemosis score between 0.66 and 2.66, fully reversible within a maximum of 14 days. No corrosion was observed at any of the measuring intervals. Based upon the degree of chemosis and the persistent corneal opacity noted in one animal after 21 days the test item is considered to be severely eye damaging to the rabbit eye.