2,4-dihydroxybenzoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Study meets the requirements of OECD Guideline 405 and EU Method B.5, though the observation period was limited to 3 days.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Observation only for 3 days in spite of persisting findings

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

directive 83/467/EEC

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dihydroxybenzoic acid

EC Number:

201-946-9

EC Name:

2,4-dihydroxybenzoic acid

Cas Number:

89-86-1

Molecular formula:

C7H6O4

IUPAC Name:

2,4-dihydroxybenzoic acid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, Kastengrund
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 3.2 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Albtromin 2123) ad libitum, appr. 15 g hay daily
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

One administration 24 hours

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

1

Details on study design:

Application of the substance to the conjunctival sac of the left eye of the animal, the right eye served as control.

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place
- Time after start of exposure: see above

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: score after 1 hour: 2.0

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: score after 1 hour: 1.0

Results 3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: score after 1 hour: 3.0

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: score after 1 hour: 3.0

Irritant / corrosive response data:

One hour after administration slight opacity of cornea, iris redness, swollen, blanched and crimson red coloured conjunctiva were recorded. The eyelids of the animal were about half closed.
After 1 to 3 days all signs of irritation increased. In addition, the nictating membrane was blanched, conjunctiva hemorrhages and definitely injected blood vessels, cornea exfoliation were observed. The eyelids were more than half closed.

Other effects:

Colourless to mucous-yellowish eye discharge was observed at all observation time-points.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The test substance caused grade 4 cornea lesions and therefore has to be classified as "serious eye damage, category 1".

Executive summary:

A study with the test item according to OECD Guideline 405 and EU Method B.5 was performed to investigate the irritation potential to the eye with one New Zealand White rabbit.

One hour after administration slight opacity of cornea, iris redness, swollen, blanched and crimson red coloured conjunctiva were recorded. The eyelids of the animal were about half closed.

After 1 to 3 days all signs of irritation increased. In addition, the nictitating membrane was blanched, conjunctiva hemorrhages and definitely injected blood vessels, cornea exfoliation were observed.

Due to the severe effects observed - cornea opacity score 4.0 (mean after 24, 48 and 72 hours) - the test substance has to be classified as category 1 (irreversible effects on the eye), H318.