1,3-Isobenzofurandione, hexahydro-, reaction products with epichlorohydrin

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented pre-guideline study without GLP. Observations can be re-assessed according to present day criteria based on available data

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

A different method has been used to evaluate the study. The Draize score reading is available and therefore data can be translated in the OECD 405-type of evaluation.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Version / remarks:

FR 43, No., 163, Aug. 22, 1978

Principles of method if other than guideline:

The primary eye irritation index was determined by summing the mean reaction scores for cornea, iris and conjunctivae after 1, 2, 3 and 7 days and divided by 5.
After instillation of the substance into the conjunctival sac, the treated eye was flushed with physiological saline in three out of six animals.

GLP compliance:

no

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

Batch: 502834

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ivanovas, 7964 Kissleg/Allgau, germany and Madorin AG, 4114 Fullinsdorf, Switzerland)
- Age at study initiation: adult
- Weight at study initiation: 2-3 kg
- Housing: individual housing in metal cages
- Diet (e.g. ad libitum): Rabbit standard food, NAFAG No. 814 (Nafag, Gossau, Switzerland)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): n/a
- Photoperiod (hrs dark / hrs light): 14/10.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye of each animal was not treated and served as an untreated control.

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

In three out of six animals approximately 30 seconds after tretament the treated eye was flushed with 10 mL physiological saline.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

The test material in an amount of 0.1 mL was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. In 3 out of six animals approximately 30 seconds after tretament the treated eye was flushed with 10 mL physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal: 246, 247 and 248 (rinsed eye)

Time point:

other: 24 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal: 248

Time point:

other: 48 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Redening of the conjunctivae with vessels definitely above normal was noted in all three animals with rinsed eyes at the 24-hour reading and persisted in one animal at the 48-hour reading. No irritant effects were noted in the unrinsed treated eyes.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the condition of the study the test material was found to cause minimal irritation when applied to rabbit eye and does not have to be classified with respect to eye irritation.

Executive summary:

The primary eye irritation potential of the test material was investigated according to US EPA, FR Vol. 43, No. 163, August 22, 1978. The test item was applied by instillation of 0.1 mL into the left eye of each of six adult New Zealand White rabbits. Approximately 30 seconds afer treatment the treated eye was flushed with physiological saline in three out of six animals. Scoring of irritation effects was performed approximately 24, 48 and 72 hours as well as 4 and 7 days after test item instillation.

The instillation of the test material into the eye resulted in mild, early-onset and transient ocular changes, such as conjunctival reddening. These effects were reversible and were no longer evident 48 hours or 72 hours after treatment. No abnormal findings were observed

in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye and does not have to be classified with respect to the eye irritation.