Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24/05/2016 - 18/07/2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
The test material corresponded to the approximately 45% of the registration substance. The given dose refers to the amount of the registration substance.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sainath Agencies, Bapujinagar, Musheerabad, Hyderabad 500 020

- Age at study initiation: 8 - 9 Weeks

- Weight at study initiation: 189.4 to 209.2 g

- Housing:Animals were housed individually in standard polysulfone cages (Size: approximately L 425 x B 266 x H 185 mm), with stainless steel top grill having facilities for pelleted food and drinking water in polycarbonate bottle. Additionally, polycarbonate rat huts were placed inside the cage as an enrichment object and were changed along with the cage at least once a week. Bedding: steam sterilized corn cob was used and changed once a week along with the cage.

- Diet (ad libitum):Hypro Rat & Mice Pellet Feed, manufactured by Pranav Agro Industries Ltd., Pune 411 030, Maharashtra, India, was provided to animals.

- Water (ad libitum):Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd, Mumbai 400 001, India was provided to animals in polycarbonate bottles with stainless steel sipper tubes.

- Acclimation period: After physical examination, the animals were acclimatized for five to seven days before treatment. Animals were observed once daily during acclimatization period. Females were nulliparous and non-pregnant.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 23°C
- Humidity (%):65 to 67%
- Air changes (per hr):12.9 to 13.1 air changes/hour
- Photoperiod (hrs dark / hrs light):12 hours light and 12 hours dark cycle

IN-LIFE DATES: From: 27 May 2016 To: 17 June 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
The dose level of 2000 mg/kg refers to the active ingredient, the registration substance
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:2000 mg/kg

DOSAGE PREPARATION : The undiluted test item as supplied by the sponsor was administered based on the density of the test item i.e., 1.05 g/cm3 at 20 ºC (as per TIDS provided by the sponsor) and the dose volume was 4.52 mL/kg body weight, i.e., [1.90 (dose volume as per density) x 2.38 (correction factor)] to attain the dose of 2000 mg/kg body weight (G1-FTS) as oral gavage to overnight fasted (16 to 18 hours) 3 female rats.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As per the Material Safety Data Sheet provided by the Sponsor, the acute oral LD50 rat is > 2000 mg/kg body weight. Hence the test was started as per Annex 2d of the OECD 423 test guideline. The starting dose was 2000 mg/kg body weight (G1-FTS). No test item-related mortality was observed; hence test was continued with same dose with three additional female rats second step (G1-STS). The subsequent dosing was done at approximately 48 hours after the first dosing
Doses:
Doses: 2000 mg/kg body weight (first treatment step and second treatment step)
No. of animals per sex per dose:
3 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration. The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology.

Results and discussion

Preliminary study:
Body weights, body weight changes and pre-terminal deaths are presented in Table 1.
Individual clinical signs and necropsy findings are presented in Table 2.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality
Clinical signs:
no clinical signs
Body weight:
Rats increased throughout the observation period
Gross pathology:
No abnormality detected at necropsy

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity of the registration substance was investigated according to the OECD Gudieline 423. Six female rats were treated once with the registration substance at dose of 2000 mg/kg bw. No effect was observed. The LD50 of the registration substance was determined to be higher than 2000 mg/kg bw. No classification is warranted.
Executive summary:

The acute oral toxicity of the registration substance was investigated according to the OECD Gudieline 423. Six female rats were treated once with the registration substance at dose of 2000 mg/kg bw. No effect was observed. The LD50 of the registration substance was determined to be higher than 2000 mg/kg bw. No classification is warranted.