Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 October 2018 - 31 October 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted: 17th December 2001
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Octadecanoic acid, reaction products with diethylenetriamine, di-Me sulfate-quaternized
EC Number:
291-707-5
EC Name:
Octadecanoic acid, reaction products with diethylenetriamine, di-Me sulfate-quaternized
Cas Number:
90459-62-4
Molecular formula:
C24H55N3O6S
IUPAC Name:
bis(2-aminoethyl)amine octadecanoic acid dimethyl sulfate
Test material form:
solid
Remarks:
paste

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: In-house bred animals; Animal Facility, Bioneeds India Private Limited, Devarahosahally, Sompura Hobli, Nelamangala Taluk, Bangalore Rural District, PIN - 562 111, Karnataka, India
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 163.87 g to 177.26 g
- Fasting period before study: fasted overnight (16 to 18 hours) prior to dosing and 3 to 4 hours after dosing
- Housing: three animals per group in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill
- Diet (e.g. ad libitum): Altromin Maintenance diet for rats and mice 1324, ad libitum
- Water (e.g. ad libitum): deep bore-well water passed through Reverse osmosis unit, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1°C to 22.7°C
- Humidity (%): 49% to 66%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% w/v Carboxy Methyl Cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
A starting dose of 300 mg/kg body weight has been selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight as there is no available information on the LD50 of the test item.VEHICLE
Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
3 females for each Step-I, Step-I confirmation and Step-II, Step-II confirmation
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Individual animal body weight will be recorded at receipt, on day 1 before test item administration and on day 8 and 15 during the observation period. If the animal is found dead, then the body weight of dead animal will be recorded.
All the animals will be observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 min), 2 hrs (±10 min), 3 hrs (±10 min) and 4 hrs (±10 min) post dosing on Day 1 and at least once daily thereafter for clinical signs of toxicity throughout the experimental period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality was observed at 300 or 2000 mg/kg bw.
Clinical signs:
In Step-I, Step-I confirmation and Step-II, Step-II confirmation, the animals were dosed at 300 mg/kg body weight and in Step-II, Step-II confirmation at 2000 mg/kg body weight. No clinical signs of toxicity were observed.
Body weight:
No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg and 2000 mg/kg body weight.
Gross pathology:
No gross pathological changes were observed in any of the animals at 300 mg/kg and 2000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the experiment, it is concluded that the LD50 cut off value for the test item Leomin KP was 5000 mg/kg body weight when administered as a single dose by oral gavage to female Sprague Dawley rat as per OECD Guidelines for Testing of Chemicals (No. 423, Section 4: Health Effects) on conduct of “Acute Oral Toxicity - Acute Toxic Class Method”.
Executive summary:

The test item Leomin KP was evaluated for acute oral toxicity in Sprague Dawley rats as per OECD Guideline No. 423: Acute Oral Toxicity - Acute Toxic Class Method adopted on 17 December 2001.

A starting dose of 300 mg/kg body weight was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight as there is no available information on the LD50 of the test item.

A total of 12 females (3 females for each Step-I, Step-I confirmation and Step-II, Step-II confirmation) were used for the experiment. All the animals of Step-I, Step-I confirmation were administered with 300 mg/kg body weight of the test item and  Step-II, Step-II confirmation were administered with 2000 mg/kg body weight of the test item by oral route.

All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 mins), 2 hrs (±10 mins), 3 hrs (±10 mins) and 4 hrs (±10 mins) post dosing on Day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Body weight was recorded on Day 1 before test item administration and on day 8 and 15 during the observation period. At the end of observation period, all the surviving animals were sacrificed under carbon dioxide anaesthesia, subjected to necropsy and gross pathological examination.

No clinical signs of toxicity and mortality were observed in any of the animals dosed at 300 mg/kg and 2000 mg/kg body weight.

No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg and 2000 mg/kg body weight. All the animals revealed physiologically normal increase in the body weight.

No gross pathological changes were observed in any of the animals dosed at 300 mg/kg and 2000 mg/kg body weight.

 

Conclusion

Based on the results of the experiment, it is concluded that the LD50 cut off value for the test item Leomin KP was 5000 mg/kg body weight when administered as a single dose by oral gavage to female Sprague Dawley rat as per OECD Guidelines for Testing of Chemicals (No. 423, Section 4: Health Effects) on conduct of “Acute Oral Toxicity - Acute Toxic Class Method”.

The substance is not classified according to EU GHS criteria.