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Administrative data

Description of key information

Oral (OECD 423), rat: LD50 > 5000 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
Study period:
14 June - 14 July 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
in compliance with GLP
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 Dec 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Remarks:
(Crl:CD(SD)), SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 183.9 - 232.3 g
- Fasting period before study: animals were fasted overnight prior to administration
- Housing: individual in wire mesh cages. Cages were washed every two weeks in a cage washer and sterilized by an autoclave.
- Diet: pellet diet Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C (Envigo RMS. Ltd., U.S.A., lot No. 2918C-020816MA), ad libitum
- Water: tap water, ad libitum (analysis was performed)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.6 - 24.1
- Humidity (%): 43.8 - 70.0
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/ 12

IN-LIFE DATES: From: 14 June TO: 28 June 2016
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 60 and 400 mg/mL
- Amount of vehicle (if gavage): 5.0 mL per kg bw
- Lot/batch no. (if required): MKBV2080V

MAXIMUM DOSE VOLUME APPLIED: 5.0 mL per kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose level for this study was selected at 300 mg/kg bw because there was no available toxicity information on the test substance.
Doses:
300 mg/kg bw and 2000 mg/kg bw
No. of animals per sex per dose:
6 females per dose
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On Day 0, all animals were observed once within 30 minutes and once each at 1, 2, 4 and 6 hours after dosing. From the next day of dosing (from Day 1 to Day 14), the animals were observed once daily. All animals were weighed on Days 0 (before dosing), 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights, complete gross postmortem examinations
Statistics:
Mean values and standard deviations were calculated for body weights.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 is a cut-off value obtained from flow-chart of OECD 423 (Annex 2c)
Mortality:
No mortality occurred during the study period.
Clinical signs:
Group 1: 300 mg/kg bw: No clinical abnormalities were observed in any animal.
Group 2: 300 mg/kg bw: No clinical abnormalities were observed in any animal.
Group 3: 2000 mg/kg bw step 1: On Day 0, salivation was observed in all 3 animals after 30 minutes lasting up to 2 hours. After 6 hours abnormal gait was observed in all 3 animals. On day 1, a decrease in fecal volume was observed in 1 of 3 animals.
Group 4: 2000 mg/kg bw step 2: On Day 0, salivation was observed in 1 of 3 animals after 30 minutes lasting up to 1 hour. After 6 hours abnormal gait was observed in 1 of 3 animals. On day 1, a decrease in fecal volume was observed in 2 of 3 animals. Furthermore 1 of 3 animals showed a soiled perineal region on day 1. From Day 2 to Day 14, no clinical signs were observed in any of the animals.
Body weight:
Normal body weight gains was observed in all animals at 300 mg/kg.
A tendency for suppression of body weight gain was observed in three animals at 2000 mg/kg on Day 1. Then, normal body weight gain was observed in these animals from Day 3. Therefore, this change was considered to be a test substance-related effect.
Gross pathology:
No abnormal morphological findings were observed in any animal at 300 and 2000 mg/kg.
Interpretation of results:
other: not classified
Conclusions:
CLP: not classified
Executive summary:

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423 and in compliance with GLP (2016). Based on lacking toxicity information on the test substance, the starting dose was selected to be 300 mg/kg bw via gavage, tested in 3 female rats. As no mortality or clinical signs occurred the test was performed again at a dose of 2000 mg/kg bw. No mortality occurred at this dose too.

Thus, a LD50 value > 5000 mg/kg bw was found in this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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

Oral

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423 and in compliance with GLP (2016). Based on lacking toxicity information on the test substance, the starting dose was selected to be 300 mg/kg bw via gavage, tested in 3 female rats. As no mortality or clinical signs occurred the test was performed again at a dose of 2000 mg/kg bw. No mortality occurred at this dose neither.

Thus, a LD50 value > 5000 mg/kg bw was found in this study.

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.