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

Endpoint summary

Description of key information

skin irritation 
in vivo, rabbit: not irritant (GLP, OECD 404, Notox B.V. 2001) 
 
eye irritation 
in vivo, rabbit: not irritant (GLP, OECD 405, Notox B.V., 2001) 
 
respiratory irritation 
no data available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams of the test substance
- Concentration (if solution): the test substance was moistened with 0.6 ml of the vehicle and applied to the skin of one flank

Duration of treatment / exposure:

4 hours

Observation period:

72 hours after the removal of the dressings and test substance

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm
- Type of wrap if used: metalline patch which was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: dressing was removed and the skin cleaned of residual test substance using water
- Time after start of exposure: 4 hours

SCORING SYSTEM: OECD Draize Scoring System

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Table 1: Individual skin irritation scores

Exposition:	4 h
Animal	Reading	Erythema	Edema	Symptoms
1	1 h	1	1	Yellow staining of the skin by the test substance
2	1 h	1	0	Yellow staining of the skin by the test substance
3	1 h	1	1	Yellow staining of the skin by the test substance
1	24 h	1	0	Yellow staining of the skin by the test substance
2	24 h	0	0	Yellow staining of the skin by the test substance
3	24 h	1	1	Yellow staining of the skin by the test substance
1	48 h	0	0
2	48 h	0	0
3	48 h	1	0	Yellow staining of the skin by the test substance
1	72 h	0	0
2	72 h	0	0
3	72 h	0	0
1	24 - 72 h	0,33	0,00
2	24 - 72 h	0,00	0,00
3	24 - 72 h	0,67	0,33
mean	24 - 72 h	0,33	0,11

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

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

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

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

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.

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.

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

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

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are reliable studies available to assess the potential of the substance for skin and eye irritation.

 

A GLP conform in vivo study was performed to assess the acute dermal irritation or corrosion potential of the test substance in White New Zealand rabbits according to the OECD guideline 404 (Notox B.V. 2001). Three rabbits were exposed to 0.5 grams of the test substance (purity: 94.8 weight-%) applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.

Exposure to the test substance resulted in very slight erythema and no or very slight oedema in the treated skin-areas of the rabbits, which had resolved within 24, 48 or 72 hours. Mean scores of the 24 -72 h readings were 0.33 and 0.11 for erythema and edema, respectively.

Yellow staining of the treated skin by the test substance was observed between days 1 and 3 on all animals which did not hamper the scoring of the skin reactions.

 

 

To assess the acute eye irritation or corrosion potential of the test substance in vivo a GLP conform eye irritation test in White New Zealand rabbits was performed according to the method described in OECD guideline 405 (Notox B.V., 2001). Single samples of approximately 45 mg of the test substance (a volume of approximately 0.1 ml) (purity: 94.8 weight-%) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

Instillation of the test substance resulted in effects on the iris and conjunctivae. Iridial irritation (grade 1) was observed among all animals on the day of application and had resolved within 24 hours. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 72 hours in all animals. 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. Mean scores of the 24 - 72 h readings were 0.0 for both corneal opacity and iritis, 0.89 and 0.33 for conjunctivae redness and chemosis, respectively.

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

Yellow staining of the fur on the head and paws, caused by the test substance, was noted during the observation period.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin and eye irritiation under Regulation (EC) No. 1272/2008.