[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11th August 2021 to 31st August 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

(2S)-1-amino-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-aminium chloride

Cas Number:

2628280-48-6

Molecular formula:

C7H13N3O2 • HCl

IUPAC Name:

(2S)-1-amino-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-aminium chloride

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF(Beijing) Biotechnology Co., Ltd.
- Females nulliparous and non-pregnant
- Age at study initiation: 49 - 56 days on arrival, in the range of 56 - 69 days at the commencement of each animal’s dosing
- Weight at study initiation: The body weight ranges were 159-191 g at arrival and 171-207 g at the end of adaption period, respectively
- Housing: Animals were housed in Room D130 of the facility’s barrier system. Animals were raised in suspended, stainless steel cages (L 32.0cm × W 28.0cm × H 20.0cm) on cage racks (L 167.0cm × W 70.0cm × H 171.0cm). Animals were housed individually during the exposure period and gregarious during the adaption period.
- Diet: SPF rodent maintenance feed supplied by Shenyang Maohua Biotechnology Co., Ltd. (Batch No.: 88001214, 88001224), ad libitum
- Water: Drinking water was purified by HT-RO1000 purity system, ad libitum
- Acclimation period: 6 days prior to the test

ENVIRONMENTAL CONDITIONS
- Temperature: 21.1 - 23.6°C
- Humidity: 44% - 69%
- Photoperiod: 12 hours light, 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/ml
- Amount of vehicle: 10ml/kgb.w

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kgb.w

Doses:

300 and 2000 mg/kgb.w

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: Inspections were made twice daily.
- Frequency of observations and weighing: Clinical observations were performed once during the first 30 minutes and at 1, 2 and 4 hours after application approximately, and then once each day for up to 14 days.
- Necropsy of survivors performed: yes
- Clinical signs including body weight - Careful observations and records of animal fur changes, eyes and mucosa, digestive, respiratory, circulatory, autonomic and central nervous system, particularly limb activity and behavior changes were made. Attention was directed to observations of tremor, convulsions, salivation, diarrhea, lethargy, sleep and coma.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

All of the surviving animals gained body weight during the test.

Gross pathology:

No abnormalities were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, the acute oral LD50 in rats for PF-07328614-01 was estimated to be more than 2000 mg/kg b.w., and the cut off value of LD50 was estimated to be 5000 or ∞ mg/kg b.w.. According to the GHS’s classification criteria for acute oral toxicity, the test item was classified as “Category 5” or “Unclassified”.

Executive summary:

The study was performed to assess the acute oral toxicity of PF-07328614-01 in Sprague Dawley rats. The method was designed to meet the OECD Guideline for Testing of Chemicals: Acute Oral Toxicity-Acute Toxic Class Method (TG 423, adopted 2001).

Method: The test item was tested using a stepwise procedure and three female animals were used for each group. The first step dosing was 300 mg/kg b.w.. The second and third step dosing was 2000 mg/kg b.w.. Clinical observations and body weights were monitored during the study. All animals under test were subjected to a gross necropsy at the end of the study.

Results:

Mortality

Dose Level-The first dosing (300 mg/kg b.w.): There were no deaths or moribund status during the test.

Dose Level-The second dosing (2000 mg/kg b.w.): There were no deaths or moribund status during the test.

Dose Level-The third dosing (2000 mg/kg b.w.): There were no deaths or moribund status during the test.

Clinical Observations

Dose Level-The first dosing (300 mg/kg b.w.): There were no abnormal symptons during the test.

Dose Level-The second dosing (2000 mg/kg b.w.): There were no abnormal symptons during the test.

Dose Level-The third dosing (2000 mg/kg b.w.): There were no abnormal symptons during the test..

Body Weights

All of the surviving animals gained body weight during the test.

Necropsy

All animals include the death one under test showed no abnormalities at necropsy.

Conclusion:

Based on the results, the acute oral LD₅₀ in rats for PF-07328614-01 was estimated to be more than 2000 mg/kg b.w., and the cut off LD₅₀ was estimated to be 5000 or ∞ mg/kg b.w.. According to the GHS’s classification criteria for acute oral toxicity, the test item was classified as “Category 5” or “Unclassified”.