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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12th June 2020 to 9th July 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
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:
The study was not within the scope of regulations governing the conduct of noncliniical laboratory studies and is not intended to comply with the regulations

Test material

Constituent 1
Reference substance name:
N-{[4-(2,2-DICYANO-1-HYDROXYETHENYL)PHENYL]METHYL}-5-FLUORO-2-METHOXYBENZAMIDE
IUPAC Name:
N-{[4-(2,2-DICYANO-1-HYDROXYETHENYL)PHENYL]METHYL}-5-FLUORO-2-METHOXYBENZAMIDE

Test animals

Species:
rat
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks old
- Weight at study initiation: 213 to 235 g for the males and 188 to 224 g for the females
- Fasting period before study: 1 day
- Housing: Polycarbonate cages containing appropriate bedding equipped with an automatic watering valve. Animals were individually housed.
- Diet: Lab Diet Certified CR Rodent Diet 5CR4. Ad libitum, except during designated procedures
- Water: Municipal tap water, treated by reverse osmosis and ultraviolet irradiation. Freely available to each animal via an automatic watering system (except during designated procedures).
- Acclimation period: The animals were acclimated to their designated housing for at least 7 days before the first day of dosing.
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to groups by a stratified randomization scheme designed to achieve similar group mean body weights. Males and females were randomized separately.

ENVIRONMENTAL CONDITIONS
- Temperature: 68°F to 79°F (20°C to 26°C)
- Humidity: 30% to 70%
- Air changes: 10 or more per hour
- Photoperiod: 12hrs dark / 12hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
Reverse Osmosis Deionized (RODI) Water
- Amount of vehicle (if gavage): 10 mL/kg.

- Rationale for the selection of the starting dose: As no information about oral toxicity was known, testing was conducted at dose levels of 300 and 2000 mg/kg in 3 males and 3 females per group to provide general hazard communication information.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: At least twice daily (morning and afternoon) beginning upon arrival through termination
Clinical Observations: Two times on Day 0 (postdose) with the first observations within approximately 30 minutes after dosing and daily thereafter (Days 1 to 14).
Body Weights: Day -1 (prior to fasting), Day 0 (prior to dosing), and Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
All results presented in the tables of the report were calculated using non-rounded values as per the raw data rounding procedure and may not be exactly reproduced from the individual data presented.
When appropriate, body weight means and standard deviations were calculated separately for males and females for each limit level administered.
When a limit test (or LD50 test reaching an upper bound) was performed, the LD50 was estimated as indicated below:
< 50% mortality: LD50 was estimated as greater than the administered dose.
= 50% mortality: LD50 was estimated as equal to administered dose.
> 50% mortality: LD50 was estimated as less than the administered dose.

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:
None
Clinical signs:
Clinical observations included erect fur in 1 male administered 300 mg/kg on Days 3 and 4 and
in all 3 males administered 2000 mg/kg on Day 1. Salivation was also noted in 1 female
administered 2000 mg/kg within 30 minutes following dosing. These observations were not
considered adverse. Other observations were considered incidental and/or normal for animals of
this age and strain.
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 gross pathology findings noted during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Administration of LSN3532785 by oral gavage once on Day 0 was well tolerated in rats at levels
of 300 and 2000 mg/kg. Under the conditions of this test, the median lethal dose of LSN3532785
is estimated to be greater than 2000 mg/kg.
Executive summary:

The objective of this study was to assess the acute toxicity of LSN3532785 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 No.Test MaterialDose Level
(mg/kg)
Adjusted Dose Level
(mg/kg)*
Number of Animals
MalesFemales
1LSN353278530030333
2LSN35327852000202033

*The dose level was adjusted by a correction factor of 1.01.


The following parameters and end points were evaluated in this study: clinical signs, body  weights, body weight gains, and gross pathology.
There were minor clinical observations noted including erect fur and salivation that did not persist and were not considered adverse. There were no effects noted in body weights, body weight changes, or gross pathology findings.
In conclusion, administration of LSN3532785 by oral gavage once on Day 0 was well tolerated in rats at levels of 300 and 2000 mg/kg. Under the conditions of this test, the median lethal dose of LSN3532785 is estimated to be greater than 2000 mg/kg.