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Description of key information

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 300 - 2000 mg/kg bodyweight.

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:
from 2008-01-10 to 2008-01-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
2004
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Sex: females, nulliparous and non-pregnant
- Age at study initiation: eight to twelve weeks
- Weight variation at study initiation: ± 20 % of the initial/mean bodyweight of any previously dosed animal(s)
- Fasting period before and during study: overnight immediately before dosing and for approximately three to four hours after dosing
- Housing: in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 (06:00 to 18:00) / 12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL for 300 mg/kg bw dose level
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: For the purpose of the 300 mg/kg bw dose level the test material was freshly prepared, as required, as a solution in distilled water. For the purpose of the 2000 mg/kg bw dose level the test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
Doses:
300 mg/ kg bw (initial study)
300 mg/ kg bw and 2000 mg/ kg bw (main study)
No. of animals per sex per dose:
5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were recorded 30 min and 1, 2, and 4 hours after dosing and then daily for up to fourteen days. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
Preliminary study:
Dose level: 300 mg/kg bw (Initial animal)
- Mortality: There was no death.
- Clinical Observations: No signs of systemic toxicity were noted during the observation period.
- Bodyweight: The animal showed expected gains in bodyweight over the observation period.
- Necropsy: No abnormalities were noted at necropsy.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two animals were found dead three days after dosing and another animal was found dead four days after dosing in the high dose group.
Clinical signs:
other: In the high dose group signs of systemic toxicity noted during the observation period were hunched posture, ataxia, pilo-erection, prostration, decreased respiratory rate, laboured respiration and occasional body tremors.
Gross pathology:
Abnormalities noted at necropsy of the animals that died during the observation period were abnormally red lungs, dark liver, dark kidneys and slight haemorrhage of the gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the observation period.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 300 - 2000 mg/kg bodyweight.
Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (2001) and Method B1 bis "Acute Toxicity (Oral)" of Commission Directive 2004/73/EC.

Following a sighting test at dose levels of 300 mg/kg bw and 2000 mg/kg bw, a further two groups of four fasted females were given a single oral dose of undiluted test material or the test material as a solution in distilled water, at dose levels of 300 mg/kg or 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Three animals treated at a dose level of 2000 mg/kg bw were found dead three or four days after dosing. There were no signs of systemic toxicity noted in animals treated at a dose level of 300 mg/kg bw. Hunched posture, ataxia, prostration, decreased respiratory rate, laboured respiration, pilo-erection and occasional body tremors were noted in animals treated at a dose level of 2000 mg/kg bw. Surviving animals showed expected gains in bodyweight. Abnormally red lungs, dark liver, dark kidneys and slight haemorrhage of the gastric mucosa were noted at necropsy of animals that died during the observation period. No abnormalities were noted at necropsy of animals that were killed at the end of the observation period. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 300 - 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
GLP and guideline study.

Additional information

Acute Toxicity: oral route

The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of theOECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (2001) andMethod B1 bis "Acute Toxicity (Oral)" of Commission Directive 2004/73/EC.

Following a sighting test at dose levels of 300 mg/kg bw and 2000 mg/kg bw, a further two groups of four fasted females were given a single oral dose of undiluted test material or the test material as a solution in distilled water, at dose levels of 300 mg/kg or 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Three animals treated at a dose level of 2000 mg/kg bw were found dead three or four days after dosing. There were no signs of systemic toxicity noted in animals treated at a dose level of 300 mg/kg bw. Hunched posture, ataxia, prostration, decreased respiratory rate, laboured respiration, pilo-erection and occasional body tremors were noted in animals treated at a dose level of 2000 mg/kg bw. Surviving animals showed expected gains in bodyweight. Abnormally red lungs, dark liver, dark kidneys and slight haemorrhage of the gastric mucosa were noted at necropsy of animals that died during the observation period. No abnormalities were noted at necropsy of animals that were killed at the end of the observation period.The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 300 - 2000 mg/kg bw.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study in rats, the test item is classified as harmful, if swallowed in Categorie 4 (H302) according to Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.