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Description of key information

Acute oral toxicity: 300 mg/kg bw < LD50 < 2000 mg/kg bw (OECD 423; GLP; female rats)

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:
2006-03-29 to 2006-04-27
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001-12-17
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed November 2005
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5°C), light protected, in a desiccator and under N2.
- Stability of test item: Stable under storage conditions
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS - (Rats were SPF)
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf/Switzerland
- Age at study initiation: 12 weeks
- Weight at study initiation: 166.1 g - 193.5 g
- Fasting period before study: Animals were fasted for apporximately 17 to 18 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
- 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 (ad libitum except for fasting period, see above): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 001/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland)
- Water (ad libitum): Community tap water from Füllinsdorf
- Acclimation period: 7 days
Music during the daytime light period.

ENVIRONMENTAL CONDITIONS - air-conditioned
- Temperature: 22 ± 3°C
- Relative humidity: 30 - 70%
- Air changes: 10 - 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
Purified water was found to be a suitable vehicle.
Purified water prepared at RCC Ltd (deionised water which was processed and treated by the PURELAB Option-R unit. This latter links four purification technologies: reverse osmosis, adsorption, ion-exchange and photo oxidation).

APPLICATION VOLUME: 10 mg/kg body weight

DOSAGE PREPARATION (if unusual): The dose formulations were made shortly before each dosing occasion using a magnetic stirrer as homogenizer.
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The glass beaker was wrapped with aluminium foil to protect the test item solution against light.
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
Doses:
2000 mg/kg body weight
300 mg/kg body weight
No. of animals per sex per dose:
2000 mg/kg bw: 3 females
300 mg/kg bw: 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.
- Necropsy of survivors performed: Yes
Macroscopic examination was performed on animals found dead or killed. Animals sacrificed for ethical reasons were killed by an intraperitoneal injection of Vetanarcol at a dose of at least 2.0 mL/kg body weight (equivalent to at lesat 324 mg sodium pentobarbitone/kg body weight).
All surviving animals were killed at the end of the observation period by Carbon dioxide asphyxiation.
Statistics:
No statistical analysis was used.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One 2000 m/kg treated animal died spontaneously approximately 1 hour after treatment and the two remaining animals treated at the same dose were killed in extremis for ethical reasons approximately 2 hours after treatment. All animals treated at 300 mg/kg survived until the end of the study period.
Clinical signs:
Slightly ruffled fur with slight to moderate sedation was noted in all 2000 mg/kg treated animals at the 30-minute reading and persisted until death occurred just after the 1-hour or 2-hour reading. Moderate poor coordination was noted in all animals killed in extremis for ethical reasons. Tachypnea was noted in one animal at the 1-hour reading. Slightly ruffled fur, marked sedation, marked tremors and ventral recimbency was noted in the same animals just before they were killed for ethical reasons.
Slight to moderate ruffled fur was noted in all 300 mg/kg treated animals from the 30-minute to the 5-hour reading and slightly ruffled fur persisted in three out of six aniamls on test day 2. Slight to moderate sedation was nosted in the same animals from the 30-minute or 1-hour reading to the 3-hour reading. Slight poor coordination was noted in one animal from the 1- to the 3-hour reading and in three other animals at the 3-hour reading only Hunched posture and exophtalmos was noted in three animals at the 2- and 3-hour reading. Slight tremors were observed in one animal at the 1- and 2- hour reading and in a second animal at the 2-hour reading only.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
Liquid contents in the stomach were noted in all 2000 mg/kg treated animals at the unscheduled necropsy. No macroscopic findings were recorded at necropsy of all 300 mg/kg treated animals.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
300 mg/kg body weight < LD50 (female rat) < 2000 mg/kg body weight (LD50 cut off value: 500)
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is acutely toxic via the oral route (Category 4).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Additional information

Justification for classification or non-classification

Acute oral toxicity

The substance is acutely toxic via the oral route based on an acute oral toxicity test (OECD 423) and does require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations (Category 4; H302).

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