3,3-Tetramethyleneglutarimide sodium salt

Endpoint summary

Description of key information

The acute oral toxicity of the test item Natrium-3,3-Tetramethyleneglutarimide (3,3-Tetramethyleneglutarimide sodium salt) was evaluated in female Sprague Dawley rats according to OECD 423, EU Method B.1 tris and EPA (OPPTS) 870.1000 and 870.1100 guidelines and in compliance with GLP. The test substance induced mortality in the rat following oral administration of a single dose at levels of 2000, 300 and 50 mg/kg. Main clinical sings after 2000, 300 and 50 mg/kg doses were convulsions and piloerection. Gross pathology examination showed abnormal colour of the jejunum and/or duodenum, liver, lungs, brain, pituitary and mesenteric lymph nodes and abnormal contents in the stomach, jejunum and/or ileum and/or duodenum and abnormal areas in the stomach and thymus for animals died during the study. No mortality occurred at dose 5 mg/kg. Main clinical sings after 5 mg/kg dose were ataxia and piloerection. The results suggest the LD50 to be > 5 - < 50 mg/kg bw and indicate the classification of Acute Oral Toxicity Category 2.

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

Study period:

20.2.2012 - 25.6.2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Adopted 17.12.2001

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

Also Methods 870.1000 (Acute Toxicity Testing -Background)

GLP compliance:

yes

Test type:

acute toxic class method

Specific details on test material used for the study:

Name: BUS IV, (Natrium-3,3-Tetramethyleneglutarimide)
Description: White powder
Storage conditions: Room temperature

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Source: Harlan Italy S.r.l., San Pietro al Natisone (UD), Italy
- Age range: 6-7 weeks
- Weight range: 150 to 174g
- Housing: 3 during the study; up to 5 during acclimatisation
- Water: Ad libitum
- Diet: Ad libitum except for dosing procedure
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-70
- Air changes (per hr): 15-20
- Room lighting: Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours
-cage: Polycarbonate cages measuring 59x38.5x20 cm, with stainless steel mesh lid and floor

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

By gavage, using a plastic feeding tube attached to a graded syringe.

Doses:

2000 mg/kg, 300 mg/kg, 50 mg/kg, 5 mg/kg

No. of animals per sex per dose:

2000 mg/kg: 3 animals
300 mg/kg: 3 animals
50 mg/kg: 3 animals
5 mg/kg: 3 animals
5 mg/kg: 3 animals

Control animals:

no

Details on study design:

The animals were fasted overnight before dosing up to 4 hours after dosing. The animals were observed approximately 0,5; 2 and 4 hours after administration of the test item and daily thereafter. The observation period was 14 days. The animals were weighed individually on day -1 and on days 1, 2, 8 and 15. Mortality was observed twice daily.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 - < 50 mg/kg bw

Based on:

test mat.

Mortality:

All animals dosed at 2000 and 300 mg/kg died within 30 minutes after dosing. All animals dosed at 50 mg/kg died within 1,5 hours after dosing. No mortality occurred at dose 5 mg/kg.

Clinical signs:

2000 and 300 mg/kg: Convulsions were observed prior to death.
50 mg/kg: Convulsions and piloerection were observed prior to death.
5 mg/kg: Ataxia and/or piloerection, were seen on the day of dosing.

Body weight:

Changes in body weight observed during the study were within the expected range for this strain and age of animals.

Gross pathology:

Abnormal colour (dark or dark/red) of the jejunum and/or duodenum, liver, lungs, brain, pituitary (which showed also an abnormal shape in 1 animal dosed at 300 mg/kg) and mesenteric lymph nodes (1 animal dosed at 300 mg/kg), were seen in the early decedent animals dosed at 2000, 300 and 50 mg/kg. Abnormal contents were also found in the stomach (white fluid), jejunum and/or ileum and/or duodenum (brown or yellow in colour, fluid or mucoid material) and abnormal areas in the stomach and thymus. The lungs were incompletely collapsed in a number of animals. Brown or red staining of the muzzle was also observed in all the early decedent animals.
No abnormalities were observed in the surviving animals dosed at 5 mg/kg.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Oral LD50 >5 - <50 mg/kg bw
2008/1272/EC would indicate the following:
Classification: Category 2
Signal word: Danger
Hazard statement: H300 Fatal if swallowed.

Executive summary:

The acute oral toxicity of the test item Natrium-3,3-Tetramethyleneglutarimide (3,3-Tetramethyleneglutarimide sodium salt) was evaluated in female Sprague Dawley rats according to OECD 423, EU Method B.1 tris and EPA (OPPTS) 870.1000 and 870.1100 guidelines and in compliance with GLP. The test substance induced mortality in the rat following oral administration of a single dose at levels of 2000, 300 and 50 mg/kg. Main clinical sings after 2000, 300 and 50 mg/kg doses were convulsions and piloerection. Gross pathology examination showed abnormal colour of the jejunum and/or duodenum, liver, lungs, brain, pituitary and mesenteric lymph nodes and abnormal contents in the stomach, jejunum and/or ileum and/or duodenum and abnormal areas in the stomach and thymus for animals died during the study. No mortality occurred at dose 5 mg/kg. Main clinical sings after 5 mg/kg dose were ataxia and piloerection. The results suggest the LD50 to be > 5 - < 50 mg/kg bw and indicate the classification of Acute Oral Toxicity Category 2.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

27.5 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Roughly estimated LD50 27.5 mg/kg

Justification for classification or non-classification

Study result Oral LD50 >5 - <50 mg/kg bw

Classification for acute oral toxicity required under Regulation EC 1272/2008:

Classification: Category 2

Signal word: Danger

Hazard statement: H300 Fatal if swallowed.