Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 Oct 2018 - 28 Nov 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in compliance with Method B1 bis of Council Regulation (EC) No 440/2008 and OECD Guidelines for Testing of Chemicals, Method 420 (adopted 17 December 2001).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Method B1 bis of Council Regulation (EC) No 440/2008
Deviations:
not specified
GLP compliance:
yes
Remarks:
including Compliance Statement and signatur page
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: bulk

Test animals

Species:
rat
Strain:
other: Crl:WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Female (nulliparous, non-pregnant) Crl:WI(Han) strain rats were obtained from Charles
River (UK) Ltd., Margate
- The rats were in a body weight range of 157 to 196 g on Day 1.
- Rats were approximately 8 to 10 weeks old on Day 1.

CONDIDITIONS
- Mains water was provided ad libitum via water bottles
- Animals had access to 5LF2 EU Rodent Diet 14%, which was freely
available to the animals at all times, except for a period of fasting from the evening of the day
prior to dosing (Day-1) until approximately 3 hours after dosing.
- The animal rooms were designed to permit 15 to 20 air changes per hour. The target
temperature and humidity ranges were 20 to 24°C and 45 to 65% respectively.
- Fluorescent lighting was controlled automatically to give a cycle of 12 hours light and
12 hours dark.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
1% w/v at a dose volume of 10mL/kg
Details on oral exposure:
Doses were administered orally, by gavage, using plastic syringes and rubber catheters. Each
rat was dosed once on Day 1, by passing the tip of a catheter along the oesophagus and
instilling the test article into the gastric lumen.
Doses:
300 mg/kg bw (sighting study only)

2000 mg/kg bw
No. of animals per sex per dose:
1 female per 300mg/kg bw (sighting study)
1 female per 2000mg/kg bw (sighting study)
4 females per 2000mg/kg bw (main study)
Control animals:
no
Details on study design:
All animals were observed at the beginning and the end of the working day for signs of ill
health or overt toxicity.

Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs
were recorded immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly
between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily
from the fifth to last day of the observation period. Individual records of clinical signs were
maintained for each treated rat.

Rats were weighed on Day-1 (day before dosing) and on Days 1, 4, 8 and 15.

Results and discussion

Preliminary study:
In the preliminary study female fasted rats were given the test article as a single dose on
Day 1 by oral gavage at dose levels of 300 and 2000 mg/kg.

Since there were no deaths in the preliminary study at a dose level of 2000 mg/kg, a further
four fasted females were given a single oral dose of test article at a dose level of 2000 mg/kg
body weight.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Clinical signs were confined to hunched posture and/or piloerection, which were seen 2 to 3
hours after dosing in animals treated at 2000 mg/kg.
Body weight:
All rats achieved body weight gains during the first and second weeks of the study.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: not classified acc. CLP
Conclusions:
The test article, BI 730357 Amin MY, was considered to have no significant acute toxic risk in respect
of its acute oral toxicity and did not meet the criteria for classification according to the
Globally Harmonized System of Classification and Labelling of Chemicals (GHS).