Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 September 2018 (Study Initialtion) to 30 October 2019 (Experiment Completion)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source of test material: Supplied by Nitika Pharmaceutical Specialities Pvt. Ltd.
- Lot/batch No.of test material: MNST9H122A
- Expiration date of the lot/batch: May 2023
- Purity test (release) date: 12 June 2018 (CoA)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature (Ambient). Container kept tightly closed in in a cool and well ventilated place
- Stability under test conditions: Assumed stable for the duration of the study
- Solubility and stability of the test substance in the solvent/vehicle: Formed a homogenous suspension in corn oil. Assumed stable for the duration of the study
- Reactivity of the test substance with the solvent/vehicle: None

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Prepared as a homogenous suspension in corn oil prior to dosing
- Preliminary purification step (if any): None

FORM AS APPLIED IN THE TEST (if different from that of starting material) : Test item administered as a homogenous suspension in corn oil

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Han Tac:WH
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Vivo BioTech Ltd. Pregnapur, Telangana, India
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 158.2g to 174.1 (groups 1 & 2, 300 mg/kg bw), 175.9 to 185.0g (groups 3 & 4, 2000 mg/kg bw)
- Fasting period before study: Rats were fasted overnight prior to dosing and for three hours post-dose
- Housing: Polypropylene rat cages covered with a stainless steel grid top. Autoclaved clean rice husk as bedding material. Wooden chew blocks as enrichment material. Three rats per cage
- Diet (e.g. ad libitum): yes (with the exception of overnight fasting and fasting threee hours post dose)
- Water (e.g. ad libitum): yes
- Acclimation period: 6 to 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 58 to 66%
- Air changes (per hr): Minimum of 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light and 12 hours darkness, light hours being 06:00 h – 18:00 h (maintained through an automatic timer)

IN-LIFE DATES: From: To: 26 September 2018 (Experimental start) to 30 October 2018 (Experimental completion)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL (i.e. 300 and 2000 mg/kg bw at a dose volume of 10 mL/kg bw)
- Amount of vehicle (if gavage): 1.58 to 1.74 mL (300 mg/kg bw groups) and 1.76 to 1.85 mL (2000 mg/kg bw groups)
- Justification for choice of vehicle: In accordence with OECD 423, as the test item was insoluble in water, corn oil was selected as an acceptable vehicle as it formed a homogenous dosable suspension

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no toxicological information was available on the test item, in accordance with OECD 423 a starting dose of 300 mg/kg bw was selected as the initial test dose
Doses:
300 mg/kg bw (i.e. 30 mg/mL at 10 mL/kg bw)
2000 mg/kg bw (i.e. 200 mg/mL at 10 mL/kg bw)
No. of animals per sex per dose:
6 female rats per dose (3 females/set)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 5 h post-administration on the day of dosing. Rats were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing. Clinical signs were recorded once a day. Individual body weight was recorded prior to dosing on day 0 and on days 7 and 14.

- Necropsy of survivors performed: yes, at the end of the 14 day observation period, all rats were euthanised by carbon dioxide asphyxiation and were subject to gross pathological examination, consisting of external examination and opening of the abdominal and thoracic cavities.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in rats treated with 300 or 2000 mg Fatty acids, C16-18 (even numbered), manganese(II) salts/kg bw
Clinical signs:
No clinical signs were observed in rats treated with 300 or 2000 mg Fatty acids, C16-18 (even numbered), manganese(II) salts/kg bw
Body weight:
Normal gain in body weight was observed in all rats treated with 300 or 2000 mg Fatty acids, C16-18 (even numbered), manganese(II) salts/kg bw
Gross pathology:
Necropsy (Macroscopic Findings)

External examination of terminally sacrificed rats did not reveal any abnormality.
Internal (vIsceral) examination of terminally sacrificed rats did not reveal any abnormality.

In the absence of any pathological lesion in terminally sacrificed rats, it is concluded that the test item did not produce any treatment related effect at the dose levels used.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
or unclassified
Conclusions:
The acute oral median lethal dose (LD50 cut- off value) of Fatty acids, C16-18 (even numbered), manganese(II) salts in Wistar rats was found to be 5000 mg/kg bw.

Based on results of this study, the classification for Fatty acids, C16-18 (even numbered), manganese(II) salts is as follows:
Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2017) : Category 5 or Unclassified