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Description of key information

LD50(oral, rat) > 2000 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
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)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: Young adult animals (female animals approx. 9-11 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing, Makrolon cage, type III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Acclimatization period of at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The homogeneity of the test item during administration was ensured by stirring with a magnetic stirrer.
Administration volume (mL/kg bw): 1.84
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
EXPERIMENTAL PROCEDURE
Route of administration: Single oral administration by gavage.
Fasting period: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration: In the morning
Observation period: 14 days
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay.
Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
Histology: No histological examinations were performed.
Statistics:
Not applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the first test group. In the second test group, one animal was found dead at hour 5 after administration.
Clinical signs:
other: In the first 2000 mg/kg bw. test group, impaired general state was noticed in all animals at hour 1 and persisted in one of these animals until study day one. In two animals poor general state was seen at hour 2, followed by impaired general state from ho
Gross pathology:
The following macroscopic pathologic findings were observed in two surviving animals of the first 2000 mg/kg bw test group on the last day of observation (day 14): conglomerates in the stomach.
The following macroscopic pathologic findings were noted in the single animal that died in the second 2000 mg/kg bw. test group: Dark red, spotted discoloration of all lung lobes, red, spotted discoloration of the liver, dark red discoloration of the glandular stomach and small intestine, congestion in the kidneys
There were no macroscopic pathological findings in the other three animals sacrificed at the end of the observation period (first 2000mg/kg test group: 1 female; second 2000 mg/kg bw. test group: 2 females).
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of Emuldur 3643 after oral administration was assessed to be greater than 2000 mg/kg bw in rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
GLP guideline study

Additional information

In an acute oral toxicity study performed according to the Acute Toxic Class Method (OECD 423 guideline and GLP), a dose of 2000 mg/kg bw of the undiluted test item Emuldur 3643 was administered by gavage to two test groups of three fasted Wistar rats each (6 females).

The following test substance-related clinical observations were recorded, clinical signs occurred within three days after administration:

2000 mg/kg (first test group):

- No mortality occurred

- Impaired general state in all animals

- Poor general state in two animals

- Dyspnoea in all animals

- Piloerection in all animals

- Cowering position in two animals

- Reduced defecation in one animal

Macroscopic pathological findings in two animals:

- Conglomerates in the stomach

2000 mg/kg (second test group):

- Mortality in one animal

- Impaired general state in two animals

- Poor general state in two animals

- Dyspnoea in three animals

- Flat respiration in one animal

- Piloerection in all animals

- Cowering position in two animals

- Reduced defecation in one animal

- Lacrimation in one animal

- Apathy in two animals

- Abdominal position in two animals

- Lateral position in one animal

Macroscopic pathological findings in the single animal that died:

- Dark red, spotted discoloration of all lung lobes

- Dark red, spotted discoloration of all liver lobes

- Red discoloration of the glandular stomach

- Red discoloration of the small intestine

- Congestion in the kidneys

There were no macroscopic pathological findings in the other animals sacrificed at the end of the observation period (3 females). The body weights of the surviving animals increased within the normal range throughout the study period with one exception in the first test group. In one animal, the body weight decreased during the first observation week and stagnated during the second week. In this animal a conglomerate in the stomach was found after macroscopy.

The acute oral LD50 was assessed to be LD50, oral, rat > 2000 mg/kg bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The acute oral LD50 was determined to be greater than 2000 mg/kg bw. As a result the substance is not classified and labelled under Regulation (EC) No 1272/2008.