Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12th June 2020 to August 2020
Reliability:
1 (reliable without restriction)

Data source

Reference
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
no
Remarks:
This is an intermediate registration and this was the study available
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
N-[(4-{5-AMINO-4-CYANO-1-[(2S)-1,1,1-TRIFLUOROPROPAN-2-YL]-1H-PYRAZOL-3-YL}PHENYL)METHYL]-5-FLUORO-2-METHOXYBENZAMIDE
EC Number:
953-182-7
Cas Number:
2101703-40-4
Molecular formula:
C22H19F4N5O2
IUPAC Name:
N-[(4-{5-AMINO-4-CYANO-1-[(2S)-1,1,1-TRIFLUOROPROPAN-2-YL]-1H-PYRAZOL-3-YL}PHENYL)METHYL]-5-FLUORO-2-METHOXYBENZAMIDE

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Sprague Dawley rats were obtained. The animals were 8 weeks old and weighed between 208g to 247 g for males and 180 to 224 g for females at the initiation of dosing. Each animal was identified using a subcutaneously implanted electronic identification chip. The animals were acclimated to their designated housing for at least 8 days before the first day of dosing.
Following randomization, animals were group housed (up to 3 animals of the same sex and same dosing group together). Prior to randomization, animals were individually housed. Polycarbonate cages containing appropriate bedding equipped with an automatic watering valve.
Environmental Conditions:
Temperature: 68°F to 79°F (20°C to 26°C)
Humidity: 30% to 70%
Light Cycle: 12 hours light and 12 hours dark (except during designated procedures)
Ventilation: 10 or more air changes per hour
Diet: Lab Diet Certified CR Rodent Diet 5CR4
Type: Pellets
Frequency/Ration: Ad libitum,
Water: Ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
On Day 0, the test article was administered orally at a dose volume of 10 mL/kg. The test article was administered using a syringe attached to a gavage cannula. Individual doses were calculated
based on the animal's fasted (Day 0) body weight. Animals were returned to ad libitum feeding after dosing. The first day of dosing for each group was designated as Day 0. The animals were staggered with Group 1 dosing first followed by Group 2.
Doses:
Testing was conducted at dose levels of 300, and 2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Observations
Mortality: At least twice daily (morning and afternoon) beginning upon arrival through termination/release.
Clinical: Two times on Day 0 (post-dose) with the first observations within approximately
30 minutes after dosing and daily thereafter (Days 1 to 14).
Duration of observation period following administration: 14 days
Weighing: Day -1 (prior to fasting), Day 0 (prior to dosing), and Days 7 and 14.
Necropsy of survivors performed: no

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study. All animals survived until scheduled euthanasia.
Clinical signs:
Group 1 – 300 mg/kg
In 2/3 males, test article-related clinical observations were limited to erected fur on Day 2.
Group 2 – 2000 mg/kg
Test article-related clinical observations included erected fur in all males on Days 0 to 3. Erected
fur was noted in all females on Day 0.
Body weight:
There were no test article-related effects on body weights or body weight gains noted during the
study.
Gross pathology:
There were no test article-related macroscopic pathology findings.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Administration of LSN3532789 by oral gavage once on Day 0 was well tolerated in rats at levels of 300 and 2000 mg/kg/day. Under the conditions of this test, the median lethal dose of LSN3532789 is estimated to be greater than 2000 mg/kg.
Executive summary:

The objective of this study was to assess the short-term toxicity of LSN3459540 when given as a single oral administration to rats. This study was intended to provide information on the potential health hazards of the test article with respect to oral exposure. Data from this study may serve as a basis for classification and/or labeling of the test article.
The study design was as follows:











































Group NoNo. of animalsDose MaterialDose (mg/kg)
MaleFemale
133LSN3459540300
233LSN34595402000
     
     



There were no test article-related effects noted during the study.
In conclusion, administration of LSN3532789 by oral gavage once on Day 0 was well tolerated in rats at levels of 300, and 2000 mg/kg/day. Under the conditions of this test, the median lethal dose of LSN3532789 is estimated to be greater than 2000 mg/kg.

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