Bulnesia sarmienti, ext., acetate

Endpoint summary

Description of key information

Acute oral toxicity: similar to OECD TG 401: LD50 is 10000 mg/kg bw.

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:

Start date 1979-11-07, report date 1980-02-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Pre-OECD and pre-GLP range-finding test in which limited numbers of male and female mice per group are used. However, the results are acceptable for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Pre-OECD and pre-GLP study. For study details see materials and methods section.

GLP compliance:

no

Remarks:

pre-GLP study

Limit test:

no

Species:

mouse

Strain:

not specified

Remarks:

White mice

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4-5 week old
- Fasting period before study: 4 hours
- Housing: Individual cages
- Diet, water: After treatment animals are fed a commercial pelleted diet and water ad lib.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The most relevant dose-level for the class of substance is selected, and three male and three female animals are dosed at this level. Two groups of one male and one female are dosed above and below this level.
The animals are intubated with the approprate volumes of the test material. Each animal on one dosage-level receives the same amount per kg body weight.

DOSE VOLUME APPLIED:
10 mL/kg bw
5.0 mL/kg bw
2.0 mL/kg bw

Doses:

10, 5.0 and 2.0 mL/kg bw

No. of animals per sex per dose:

10 mL/kg bw: 1 male and 1 female
5.0 mL/kg bw: 3 males and 3 females
2.0 mL/kg bw: 1 male and 1 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes, post-mortem examination was performed at the end of the one week observation period.
- Body weights: Animals are individually weighed before treatment. Survivors are weighed before killing for post-mortem examination at the end of the one week observation period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Mice are used; Dose levels used are in mL/kg bw. In view of the relative density being close to 1 (0.9790), 10 mL/kg bw is considered to be equal to 10000 mg/kg bw.

Mortality:

The male mouse dosed at 10.0 mL/kg bw died within 18 hours. No further mortality was observed.

Clinical signs:

other: The male mouse dosed at 10.0 mL/kg bw was showing signs of stress within 30 mins after treatment and died within 18 hours. The female mouse dosed at 10.0 mL/kg bw and the mice dosed at 2.0 and 5.0 mL/kg bw appeared unaffected by the treatment.

Gross pathology:

Autopsy of the animal that died revealed irritation of the duodenum and dehydration. This animal's kidneys were pale and the fur was stained with brown urine.
The surviving mouse dosed at 10.0 mL/kg bw and one mouse dosed at 5.0 mL/kg bw failed to gain weight during the 7 day observation period. Otherwise the mice gained weight and presented a normal appearance at autopsy, apart from one female mouse dosed at 5.0 mL/kg bw having hyperplasia of the colon.

Interpretation of results:

other: not classified: criteria not met

Remarks:

according to EU CLP (EC 1272/2008 and its amendments

Conclusions:

The acute oral range-finding toxicity test showed an LD50 of about 10.0 mL/kg bw.

Executive summary:

An acute oral range-finding toxicity study was performed, pre-OECD, pre-GLP, performed similar to OECD TG 401, using 5 male and 5 female mice for 3 doses. Undiluted test substance was administered by intubation and animals were observed for up to 7 days. Three male and three female mice were dosed with 5.0 mL/kg bw test substance. Two groups of one male and one female are dosed above and below this level at 10.0 mL/kg bw and 2.0 mL/kg bw. The male mouse dosed at 10.0 mL/kg bw was showing signs of stress within 30 mins after treatment and died within 18 hours. The female mouse dosed at 10.0 mL/kg bw and the mice dosed at 2.0 and 5.0 mL/kg bw appeared unaffected by the treatment. Autopsy of the animal that died revealed irritation of the duodenum, and dehydration. This animal’s kidneys were pale and the fur was stained with brown urine. The surviving mouse dosed at 10.0 mL/kg bw and one mouse dosed at 5.0 mL/kg bw failed to gain weight during the 7 day observation period. Otherwise the mice gained weight and presented a normal appearance at autopsy, apart from one female mouse dosed at 5.0 mL/kg bw having hyperplasia of the colon. Based on these results the LD50 derived was about 10.0 mL/kg bw (one animal survived and one animal died). In view of the relative density of the substance being close to 1 (0.9790), 10 mL/kg bw is considered to be equal to 10000 mg/kg bw. Therefore the approximate LD50 derived is about 10000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

An acute oral range-finding toxicity study was performed, pre-OECD, pre-GLP, performed similar to OECD TG 401, using 5 male and 5 female mice for 3 doses. Undiluted test substance was administered by intubation and animals were observed for up to 7 days. Three male and three female mice were dosed with 5.0 mL/kg bw test substance. Two groups of one male and one female are dosed above and below this level at 10.0 mL/kg bw and 2.0 mL/kg bw. The male mouse dosed at 10.0 mL/kg bw was showing signs of stress within 30 mins after treatment and died within 18 hours. The female mouse dosed at 10.0 mL/kg bw and the mice dosed at 2.0 and 5.0 mL/kg bw appeared unaffected by the treatment. Autopsy of the animal that died revealed irritation of the duodenum, and dehydration. This animal’s kidneys were pale and the fur was stained with brown urine. The surviving mouse dosed at 10.0 mL/kg bw and one mouse dosed at 5.0 mL/kg bw failed to gain weight during the 7 day observation period. Otherwise the mice gained weight and presented a normal appearance at autopsy, apart from one female mouse dosed at 5.0 mL/kg bw having hyperplasia of the colon. Based on these results the LD50 derived was about 10.0 mL/kg bw (one animal survived and one animal died). In view of the relative density of the substance being close to 1 (0.9790), 10 mL/kg bw is considered to be equal to 10000 mg/kg bw. Therefore the approximate LD50 derived is about 10000 mg/kg bw.

Justification for classification or non-classification

Based on the acute oral range-finding toxicity test, the substance does not have to be classified as acute toxic by the oral route in accordance with EU CLP regulation (EC 1272/2008) and its amendments.