5-(4-hydroxyphenyl)imidazolidine-2,4-dione

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

end on 19-APR-2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: study performed according to OECD guideline, not GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-(phenylmethyl)imidazolidine-2,4-dione

EC Number:

222-563-3

EC Name:

5-(phenylmethyl)imidazolidine-2,4-dione

Cas Number:

3530-82-3

IUPAC Name:

5-benzylimidazolidine-2,4-dione

Details on test material:

- Name of test material (as cited in study report): BHT
- Molecular formula (if other than submission substance): C10H10N2O2
- Molecular weight (if other than submission substance): 190.20
- Smiles notation (if other than submission substance): N1C(N[C@@H](C1=O)Cc1ccccc1)=O
- InChl (if other than submission substance): InChI=1/C10H10N2O2/c13-9-8(11-10(14)12-9)6-7-4-2-1-3-5-7/h1-5,8H,6H2,(H2,11,12,13,14)
- Structural formula attached as image file (if other than submission substance): see Fig. attached
- Substance type: monoconstituent substance
- Physical state: powder
- Stability under test conditions: data not available
- Storage condition of test material: at room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Margate, Kent, England
- Age at study initiation: 7 to 9 weeks old
- Weight at study initiation: 1276g, 1524g and 1568g
- Housing: Individually housed in labelled cages with perforated floors
- Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100 g. per day. In addition, hay (BMI, Helmond, the Netherlands) was provided once a week.
- Water: free access to tap-water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 30-70%
- Air changes: 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day

IN-LIFE DATES: data not available

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye remained untreated and served as the reference control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: aach animal was treated by instillation of 53.8 +/- 0.9 mg of the test substance (a volume of approximately 0.1 ml)
- Concentration (if solution): undiluted

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to OECD guideline

TOOL USED TO ASSESS SCORE: Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: mean (24,48,72h)

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: mean (24, 48, 72h)

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24h

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: mean (24, 48, 72h)

Score:

ca. 0.3

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: mean (24, 48, 72h)

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Irritant / corrosive response data:

Instillation of approximately 54 mg of the test substance (a volume of approximately 0.1 ml) into one eye of each of three rabbits resulted in effects on the iris and conjunctivae. lridial irritation (grade 1) was observed in all animals on day 1 and had resolved within 24 hours. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 24 hours in one animal, within 48 hours in another animal and within 72 hours in the last animal. No corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

Other effects:

- Corrosion: there was no evidence of ocular corrosion.
- Colouration: remnants of the test substance were present in the eyes of all animals on day 1.
- Toxicity / Mortality: no symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0	1/1/1	2/1/1	0/2/1
24 h	0/0/0	0/0/0	1/0/1	0/0/0
48 h	0/0/0	0/0/0	1/0/0	0/0/0
72 h	0/0/0	0/0/0	0/0/0	0/0/0
Average 24h, 48h, 72h	0/0/0	0/0/0	0.7/0/0.3	0/0/0
Reversibility	-	yes	yes	yes
Average time for reversion	-	After 24h	After 72h	After 24h

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

BHT is not irritating to the eyes in rabbits

Executive summary:

In a primary eye irritation study (OECD guideline 405, not GLP), 54 mg of undiluted BHT (a volume of approximately 0.1 ml) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation. Irritation was scored by the method of OECD guideline.

 

Iridial irritation (grade 1) was observed in all animals on day 1 and had resolved within 24 hours. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 24 hours in one animal, within 48 hours in another animal and within 72 hours in the last animal. No corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

Remnants of the test substance were present in the eyes of all animals on day 1.

 

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (DSD and CLP), BHT does not have to be classified and has no obligatory labelling requirement for eye irritation.