(6-amino-2-pyridyl)-(1-methyl-4-piperidyl)methanone;dihydrate;dihydrochloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10th October 2017 to 30th Oct 2017

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2018

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

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 Sprague Dawley rat was chosen as the animal model for this study as it is an accepted rodent species for preclinical toxicity testing by regulatory agencies. The oral route was selected since this is a possible means of exposure in humans. Dose levels were selected to explore the limits of tolerability in this initial assessment of toxicity for LSN584368.

GLP compliance:

not specified

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 type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

6-(1-methylpiperidine-4-carbonyl)pyridin-2-amine dihydrate dihydrochloride

EC Number:

842-055-0

Cas Number:

2356133-42-9

Molecular formula:

C12H17N3O.2HCl.2H2O

IUPAC Name:

6-(1-methylpiperidine-4-carbonyl)pyridin-2-amine dihydrate dihydrochloride

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The Sprague Dawley rat was chosen as the animal model for this study as it is an accepted rodent species for preclinical toxicity testing by regulatory agencies. A total of 7 male and 7 female Sprague Dawley rats (Rattus norvegicus) were used.

Environmental Conditions
The targeted conditions for animal room environment will be as follows:

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

On the day prior to dosing (Day -1) the animals chosen for use on the study were weighed and fasted. On Day 0, the test article was administered orally as a single dose at a dose volume of 10 mL/kg 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.

Doses:

300mg/kg and 2000mg/kg

No. of animals per sex per dose:

7 males, 7 females

Control animals:

yes

Details on study design:

See below

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Following dose administration to the 2000 mg/kg group on Day 0, 1/3 males and 3/3 females were found dead and 2/3 males were euthanized moribund.

Clinical signs:

other: Adverse test article-related clinical signs in the 2000 mg/kg group consisted of partially closed eyes, shallow breathing, increased respiratory rate, and decreased activity. Salivation was also noted following dosing in the 2000 mg/kg group. This findi

Gross pathology:

A gross necropsy examination was performed for all animals in the 2000 mg/kg group.
Macroscopic observations were limited to abnormal stomach content for all animals, wet material accumulation on the skin for 2/6 animals, dark thymus foci for 2/6 animals, and dark stomach foci for 1/6 animals.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Mortality occurred in the 2000 mg/kg group. Following dose administration on Day 0,
1/3 males and 3/3 females were found dead and 2/3 males were euthanized moribund.
No mortality, clinical signs, or effects on body weight were observed at 300 mg/kg.
Under the conditions of this test, the median lethal dose of LSN584368 is estimated to be
greater than 300 mg/kg and less than 2000 mg/kg.