Pyrimido[5,4-g]pteridine-2,4,6,8-tetramine, 4-methylbenzenesulfonate, base-hydrolyzed

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

440-560-7

EC Name:

-

Cas Number:

346709-25-9

Molecular formula:

Unspecified

IUPAC Name:

2,6,8-triamino-4H,10H-pyrimido[5,4-g]pteridin-4-one; pyrimido[5,4-g]pteridine-2,4,6,8-tetramine

Details on test material:

- Description: Yellow solid
- Batch: MAF 382/053
- Purity: 94.8 %
- Test substance storage: At room temperature in the dark
- Stability under storage conditions: Stable
- Expiry date: 06 November 2005

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: between 1.0 and 3.5 kg
- Housing: Individually
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany)
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours

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 (volume or weight with unit): 45.4 ± 0.4 mg of the test substance (a volume of approximately 0.1 ml)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 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.
- Time after start of exposure: after the 24 hour observation

SCORING SYSTEM: Draize Scoring System

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

2

Reversibility:

other: Slight iritis was observed in all three animals after one hour.

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0.89

Max. score:

3

Reversibility:

fully reversible within: 72 hours.

Remarks on result:

other: Redness was observed after one hour in all animals. Two animals showed redness still after 24 hours, while one showed slight redness after 24 hours. Slight redness was still observed in all animals after 48 hours.

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: After 24 hours some swelling above norma was observed in all three animals

Any other information on results incl. tables

Table 1: Individual eye irritation scores

Exposition:	24 h
Animal	Reading	Opacity	Cornea area	Iritis	Redness	Chemosis	Discharge	Symptoms
1	1 h	0	0	1	2	2	1	Remnants of the test substance in the eye. Yellow staining of the head and paws by the test substance.
2	1 h	0	0	1	2	2	1	Remnants of the test substance in the eye. Yellow staining of the head and paws by the test substance.
3	1 h	0	0	1	2	2	1	Remnants of the test substance in the eye. Yellow staining of the head and paws by the test substance.
1	24 h	0	0	0	2	1	0	Yellow staining of the head and paws by the test substance.
2	24 h	0	0	0	1	1	0	Yellow staining of the head and paws by the test substance.
3	24 h	0	0	0	2	1	0	Yellow staining of the head and paws by the test substance.
1	48 h	0	0	0	1	0	0	Yellow staining of the head and paws by the test substance.
2	48 h	0	0	0	1	0	0	Yellow staining of the head and paws by the test substance.
3	48 h	0	0	0	1	0	0	Yellow staining of the head and paws by the test substance.
1	72 h	0	0	0	0	0	0	Yellow staining of the head and paws by the test substance.
2	72 h	0	0	0	0	0	0	Yellow staining of the head and paws by the test substance.
3	72 h	0	0	0	0	0	0	Yellow staining of the head and paws by the test substance.
1	24 - 72 h	0.00		0.00	1.00	0.33
2	24 - 72 h	0.00		0.00	0.67	0.33
3	24 - 72 h	0.00		0.00	1.00	0.33
mean	24 - 72 h	0.00		0.00	0.89	0.33

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met