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Description of key information

The acute oral LD50, to female Wistar Han rats, was determined to be in excess of 2000 mg/kg bw, the highest dose level tested.

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:
05 March 2018 to 27 March 2018
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Appendix to Director General Notification, No. 12-Nousan-8147
Version / remarks:
Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000, including the most recent revisions.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Wistar Han
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ca 8 - 9 weeks old
- Weight at study initiation: 142 - 172 g
- Fasting period before study: yes, animals were fasted overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test material
- Housing: animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilised sawdust as bedding material
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21 °C
- Humidity (%): 28 - 51 %
- Air changes: 10 or more air changes per hour
- Photoperiod: 12 hour light/12 hour dark
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
DOSE SOLUTIONS
Test material dosing formulations (w/w) were homogenised to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing.
Adjustment was made for specific gravity of the vehicle. No correction was made for the purity/composition of the test material.
The dosing formulations were stirred continuously during dose administration.

DOSE VOLUME
The dose volume for each animal was based on the body weight measurement prior to dosing. A dose volume of 10 mL/kg body weight was used for each dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
The first group of three female rats was treated at a dose level of 2000 mg/kg. Based on the results, one additional group of three female rats was dosed at 2000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Post-dose 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 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes. All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the study.
Clinical signs:
Hunched posture, uncoordinated movements and/or piloerection were noted for the animals on Days 1 and/or 2.
Body weight:
The body weight gain shown by the 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:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
other: Not classified according to EU criteria
Conclusions:
Under the conditions of the study the acute oral LD50, to female Wistar Han rats, was determined to be in excess of 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and Japanese (JMAFF) No. 12 -Nousan-8147, under GLP conditions, following the Acute Toxic Class Method.

During the study, the toxicity of the test material was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.

Under the conditions of the study none of the animals died. Hunched posture, uncoordinated movements and/or piloerection were noted for the animals on Days 1 and/or 2. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

The acute oral LD50, to female Wistar Han rats, was therefore determined to be in excess of 2000 mg/kg bw, the highest dose level tested.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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 acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and Japanese (JMAFF) No. 12 -Nousan-8147, under GLP conditions, following the Acute Toxic Class Method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, the toxicity of the test material was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.

Under the conditions of the study none of the animals died. Hunched posture, uncoordinated movements and/or piloerection were noted for the animals on Days 1 and/or 2. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

The acute oral LD50, to female Wistar Han rats, was therefore determined to be in excess of 2000 mg/kg bw, the highest dose level tested.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to acute oral toxicity.