Registration Dossier

Diss Factsheets

Administrative data

Description of key information

A single dose of 2000 mg/kg/bw of the test item was administered to 6 female Sprague-Dawley rats. Acute toxicological symptoms such as abnormal gait, decreased locomotor activity/irregular respiration, decreased faecal volume and lying on one side/ soiled perineal region were all observed throughout the test. Body weight changes were observed in one rat. No grossly visible findings were observed in any animal during the test.

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:
30 January 2018 to 06 February 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)
Version / remarks:
(2001)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley rats bred by commercial supplier
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 7 weeks
- Weight at study initiation: 179.9 – 202.5 g
- Fasting period before study: Overnight before the day of administration.
- Housing: Housed individually in stainless wire mesh cages (Width: 260 mm, Diameter: 350 mm, Height: 210 mm)
- Diet (e.g. ad libitum): Pelleted rodent chow was placed in feeders and provided ad libitum
- Water (e.g. ad libitum): Filtered/irradiated public tap water was provided ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5−24.6°C
- Humidity (%): 41.7−59.3%
- Air changes (per hr): 10−15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not specified
- Amount of vehicle (if gavage): Not specified
- Justification for choice of vehicle: Not specified
- Lot/batch no. (if required): MKCC0462
- Purity: Not specified

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg body weight

DOSAGE PREPARATION (if unusual): Not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the low expected toxicity of the test substance, 2000 mg/kg was used as the starting dose.

Doses:
Doses
- 2000 mg/kg of the test substance was intended to be orally administered as a single dose to each of the two groups of female rats indicated.

Number of animals per group per dose
- G1: 2101-2103: (2000 mg/kg) 3 females
- G2: 2201-2203: (2000 mg/kg) 3 females

Since there were no mortalities after the dosing of the first two groups, the study was stopped at that point.



No. of animals per sex per dose:
Group 1 2101-2103: 3 females
Group 2: 2201- 2203: 3 females


Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Two observations were made on day 0; followed by daily observations
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight and gross pathology at necropsy

Statistics:
Not performed
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut off based on GHS classification is >=5000
Mortality:
There were no deaths of animals observed at the dose of 2000 mg/kg throughout the study.
Clinical signs:
other: Acute toxicological effects such as abnormal gait, decreased locomotor activity, irregular respiration, decreased faecal volume and lying on side or soiled perineal region were observed.
Gross pathology:
None changes in the tissues were observed

Table 1- Mortality results

Group

Dose (mg/kg)

Dose volume (mL/kg)

Animal (ID No.)

Deaths

1

2000

5

3 (2101-2103)

None

2

2000

5

3 (2201-2203)

None

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
In conclusion, the oral LD50 value is greater than 2000 mg/kg bw. According to the LD50 cut off value of ≥ 5,000 mg/kg b.w., the test substance is classified as Category 5 according to the GHS classification and unclassified according to the EU CLP criteria (EC 1272/2008).
Executive summary:

The acute oral toxicity study (2018) is a GLP-compliant study following OECD guideline 423 and is therefore reliable without restrictions (Klimisch 1).

 

A single dose of 2000 mg/kg/bw of the test item was administered to a total of 6 female Sprague-Dawley rats. Acute toxicological symptoms such as abnormal gait, decreased locomotor activity/irregular respiration, decreased faecal volume and lying on one side/ soiled perineal region were all observed throughout the test. Body weight changes were observed in one rat. No grossly visible findings were observed in any animal during the test.

 

There were no deaths observed throughout the study from the dose of 2000 mg/kg. Therefore, the LD50 was considered to be > 2000 mg/kg. Based on the LD50 cut off value of ≥ 5,000 mg/kg b.w the test substance is classified as Category 5 according to the GHS classification and unclassified according to the EU CLP criteria (EC 1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The acute oral toxicity study (2018) is a GLP-compliant study following OECD guideline 423 and is therefore reliable without restrictions (Klimisch 1).

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

Justification for classification or non-classification

An assessment of acute toxicity is required to fulfil REACH Annex VII information requirements. The acute oral toxicity study was conducted according to OECD TG 423. The GLP compliant study is considered reliable without restriction (Klimisch 1). 

 

There were no deaths observed throughout the study from the dose of 2000 mg/kg. Therefore, the LD50 was considered to be > 2000 mg/kg. Based on the LD50 cut value of ≥ 5,000 mg/kg b.w the test substance is classified as Category 5 according to the GHS classification and unclassified according to the CLP regulation.