P-1057

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Physical state: Yellow solid
- Lot/batch No.: PQR0501558 (dried)
- Purity: 96%
- Storage condition of test material: At room temperature (range of 20 ± 5 ºC), light protected.

Test animals

Species:

rat

Strain:

other: Test system Rat, HanRcc:WIST (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: 11 weeks
- Fasting period before study: The animals received a single dose of the test item by oral gavage after being fasted
for approximately 18 to 19 hours
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse mainte-nance diet, batch no. 67/06 (Provimi
Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of
illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
The dosing volume was 10 mL/kg body weight.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Number of animals per group 3 females
Total number of animals 6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3
and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5
hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: All animals were killed at the end of the observation period by Carbon dioxide
asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the end of the study period.

Clinical signs:

A slightly ruffled fur was noted in all animals on the day of treatment starting 1 or 2 hours after dosing. This
persisted up to the 3- and 5-hour reading in two animals, respectively, and up to test day 2 in four animals. Five
animals expressed a hunched posture starting at the 1-hour reading in three animals and the 2-hour reading in two
animals. This was present until the 3-hour reading in one animal and the 5-hour reading in four animals,
respectively.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified based on CLP criteria.

Conclusions:

The oral LD50 (female rat) is greater than 2000 mg/kg body weight.

Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with the test substance by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (purified water) at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. A slightly ruffled fur was noted in all animals on the day of treatment starting 1 or 2 hours after dosing. This persisted up to the 3- and 5-hour reading in two animals, respectively, and up to test day 2 in four animals. Five animals expressed a hunched posture starting at the 1-hour reading in three animals and the 2-hour reading in two animals. This was present until the 3-hour reading in one animal and the 5-hour reading in four animals, respectively. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The oral LD50 (female rat) is greater than 2000 mg/kg body weight.