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

Endpoint summary

Description of key information

oral  
rat: LD50 > 2000 mg/kg bw; signs of toxicity: Hunched posture, uncoordinated movements and/or lethargy, piloerection (GLP, OECD 423; NOTOX B.V., 2001)  
 
dermal  
rat: LD50 > 2000 mg/kg bw; signs of toxicity: ptosis, hunched posture and/or piloerection (GLP, OECD 402; CIBA-Geigy, 1989)  
 
inhalation  
No data available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and OECD testing guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charies River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: males (mean) = 302; females (mean) = 203 g
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: groups of 3
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, 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): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:mortality = twice daily; body weights on days 1, 8 and 15
- Necropsy of survivors performed: yes, at the end of the observation period
- Other examinations performed: clinical signs: daily

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 0/6 animals died; clinical signs were reversible within at least 2 days ; green faeces in 2 animals between d3 and d7

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture, uncoordinated movements and/or lethargy were shown by the females on days 1 and/or 2, while piloerection was shown by one male on day 1. Additionally, one male and one female showed green faeces between days 3 and 7. No explanation could

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks old
- Weight at study initiation: males (mean): 312 g ; females (mean): 220 g
- Housing: Individually housed
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, 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): 12/12

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: i.e. approx. 25 cm2 for males and 18 cm2 for females.
- % coverage: approx. 10 % of the total body surface
- Type of wrap if used: surgical gauze patch (Surgy 1D), successively covered with aluminium foil and Coban flexible bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with water
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality = twice daily; weighing: days 1, 8 and 15
- Necropsy of survivors performed: yes, at the end of the observation period
- Other examinations performed: clinical signs = once daily

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 0/10 animals died; clinical signs were reversible within 7 to 15 days

Mortality:

No mortality occurred.

Clinical signs:

other: Two males showed ptosis, hunched posture and/or piloerection on days 1 and/or 2. Most animals also showed chromodacryorrhoea. Yellow staining of the treated skin and/or head, noted among all animals, was considered to be related to staining properties of

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

A GLP conform study was performed to assess the acute oral toxicity in the rat according to OECD guideline 423 (Acute Toxic Class Method) (NOTOX B.V., 2001).

The test substance was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture, uncoordinated movements and/or lethargy were shown by the females on days 1 and/or 2, while piloerection was shown by one male on day 1. Additionally, one male and one female showed green faeces between days 3 and 7. No explanation could be given for this finding. It may be related to staining properties of the test substance, as was yellow staining observed among one female.

The mean body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.

 

A GLP conform study was performed to assess the acute dermal toxicity in the rat according to OECD guideline 402 (NOTOX B.V., 2001).

The test substance was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Two males showed ptosis, hunched posture and/or piloerection on days 1 and/or 2.

Yellow staining of the treated skin and/or head, noted among all animals, were considered to be related to staining properties of the test substance. Other clinical signs noted during treatment among all animals consisted of chromodacryorrhoea, scales and/or scabs. The animals had recovered from the symptoms between days 7 and 15.

The body weight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.

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 acute toxicity under Regulation (EC) No. 1272/2008.