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Description of key information

Acute oral toxicity:

LD50: 300-2000 mg/kg body weight (actual value 2000 mg/kg bw) (OECD Guideline 423)

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 2019-01-07 to 2019-02-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed to current OECD guidelines with no significant deviations and run in OECD GLP certified lab.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Purity: 99.7%
Batch No.: 80031745A
Species:
rat
Strain:
other: Crl: WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8-10 weeks old
- Weight at study initiation: 161 to 208 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item
- Housing: On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilized sawdust as bedding material equipped with water bottles.
- Diet (e.g. ad libitum): Pelleted rodent diet was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24 °C (target), 20 to 21°C (actual)
- Humidity (%): 40 to 70% (target), 36 to 52% (actual)
- Air changes (per hr): Ten or greater
- Photoperiod (hrs dark / hrs light): A 12 hour light/12 hour dark cycle
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Specific gravity: 1.036
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.
Doses:
300, 2000 mg/kg body weight
No. of animals per sex per dose:
3 each for four groups
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing. Terminal body weights were collected from animals found dead or euthanized moribund after Day 1.
- Necropsy of survivors performed: yes, at the end of observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg, for the first dose group, one animal was found dead on Day 2. At 2000 mg/kg, for the second dose group, two animals were found dead on Day 2.
At 300 mg/kg, no mortality occurred.
Clinical signs:
At 2000 mg/kg, for the animals that were found dead during the study, flat and/or hunched posture, decreased locomotor activity, uncoordinated movements, slow breathing, piloerection and/or ptosis were noted on Days 1 and/or 2.
At 2000 mg/kg, for the surviving animals, hunched posture, uncoordinated movements and/or piloerection were noted for the animals between Days 1 and 6.
At 300 mg/kg, hunched posture, uncoordinated movements, piloerection and/or salivation were noted for the animals between Days 1 and 3.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
Abnormalities of the stomach (many gray-white/dark red foci glandular mucosa) and thymus (many dark red foci) were noted for animals that were found dead during the study. Beginning or advanced autolysis were noted for the animals found dead. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of the test item in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.
Executive summary:

The objective of this study was to assess the toxicity of the test item according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

The test item was administered by oral gavage to three female Wistar Han rats at 2000 mg/kg body weight. In a stepwise procedure three additional groups of three females were dosed at 2000, 300 and 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

 

At 2000 mg/kg, for the first dose group, one animal was found dead on Day 2. At 2000 mg/kg, for the second dose group, two animals were found dead on Day 2. At 300 mg/kg, no mortality occurred in both groups.

At 2000 mg/kg, for the animals that were found dead during the study, flat and/or hunched posture, decreased locomotor activity, uncoordinated movements, slow breathing, piloerection and/or ptosis were noted on Days 1 and/or 2. At 2000 mg/kg, for the surviving animals, hunched posture, uncoordinated movements and/or piloerection were noted for the animals between Days 1 and 6. At 300 mg/kg, hunched posture, uncoordinated movements, piloerection and/or salivation were noted for the animals between Days 1 and 3.

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Abnormalities of the stomach (many gray-white/dark red foci glandular mucosa) and thymus (many dark red foci) were noted for animals that were found dead during the study. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

 

The oral LD50 value of the test item in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study performed to current OECD guidelines with no significant deviations and run in OECD GLP certified lab.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

The objective of this study was to assess the toxicity of the test item according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

The test item was administered by oral gavage to three female Wistar Han rats at 2000 mg/kg body weight. In a stepwise procedure three additional groups of three females were dosed at 2000, 300 and 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

 

At 2000 mg/kg, for the first dose group, one animal was found dead on Day 2. At 2000 mg/kg, for the second dose group, two animals were found dead on Day 2. At 300 mg/kg, no mortality occurred in both groups.

At 2000 mg/kg, for the animals that were found dead during the study, flat and/or hunched posture, decreased locomotor activity, uncoordinated movements, slow breathing, piloerection and/or ptosis were noted on Days 1 and/or 2. At 2000 mg/kg, for the surviving animals, hunched posture, uncoordinated movements and/or piloerection were noted for the animals between Days 1 and 6. At 300 mg/kg, hunched posture, uncoordinated movements, piloerection and/or salivation were noted for the animals between Days 1 and 3.

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Abnormalities of the stomach (many gray-white/dark red foci glandular mucosa) and thymus (many dark red foci) were noted for animals that were found dead during the study. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

 

The oral LD50 value of the test item in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.

Justification for classification or non-classification

Acute oral: 300 LD50 2000 mg/kg body weight (actual value 2000 mg/kg bw)

Therefore in accordance with Regulation (EC) No. 1272/2008 (amendment 286/2011) Table 3.1.1, this substance should be classified as Category 4 for this endpoint.

 

Specific target organ toxicity-single exposure:

No significant non-lethal toxic effects observed in acute oral toxicity study.

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1, this substance should not be classified for this endpoint.