2-Pyridinamine, 5-[(4-ethyl-1-piperazinyl)methyl]-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 October 2013 to 31 October 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-amine

EC Number:

806-688-6

Cas Number:

1180132-17-5

Molecular formula:

C12H20N4

IUPAC Name:

5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-amine

Specific details on test material used for the study:

- Source and lot/batch No.of test material: RZ2-H70762-062- Storage condition of test material: Kept at room temperature under nitrogen

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Outside vendor- Age at study initiation: 8 weeks- Weight at study initiation: 222-262g (males) 160-192g (females)- Fasting period before study: Overnight prior to dosing- Housing: Polycarbonate cages containing appropriate bedding with an automatic watering valve- Diet (e.g. ad libitum): Standard certified commerical laboratory diet- Water (e.g. ad libitum): Municipal tap water- Acclimation period: 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 21-23- Humidity (%): 50-59- Air changes (per hr): minimum of 10- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

An appropriate quantity of test material was added to the requisite amount of de-ionised water and mixed manually until visibly homogeneous. Test material was administered orally as a single dose (dose volume ≤20 mL/kg). Administered dose was calculated based on weight of the animal on the day of dosing.

Doses:

300 mg/kg body weight2000 mg/kg body weight

No. of animals per sex per dose:

300 mg/kg: 3 males and 3 females2000 mg/kg: 3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Frequency of observations and weighing: detailed clinicalobservations twice daily. Weighing prior to fasting (Day -1) prior to dosing (day 0), and on Days 7 and 14- Necropsy of survivors performed: No- Other examinations performed: clinical signs, body weight

Statistics:

Body weight means and standard deviations were calculated separately for males and females

Results and discussion

Preliminary study:

Not relevant, this is not a fixed dose study

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000mg/kg mortality occurred in 2 males and 1 female. No mortality occurred at 300mg/kg

Clinical signs:

other: No abnormal clinical signs were present at 300mg/kg and in surviving animals at 2000mg/kg

Gross pathology:

A necropsy examinations were conducted on the animals that died during study. Gross necropsy observations included haircoat matting around the face, abnormal content in the trachea, stomach, and duodenum, dark areas on the glandular portion of the stomach, discoloration of the lungs, and carcass autolysis. Necropsy examinations were not conducted on the animals that survived the study.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this test, the Median Lethal Dose of LSN2812839 is estimated to be equal to 2000 mg/kg

Executive summary:

The single-dose oral toxicity of LSN2833975 was evaluated in Sprague Dawley rats. Two groups of rats (3 males and 3 females per group) were given a single oral dose of the test article at 300 mg/kg or 2000 mg/kg body weight. Following dosing, the rats were observed daily and weighed weekly. There were no test article-related clinical signs or effects on body weight observed at 300 mg/kg and in surviving animals at 2000 mg/kg. At 2000mg/kg mortality occurred in 2 males and 1 female. Gross necropsy observations included haircoat matting around the face, abnormal content in the trachea, stomach, and duodenum, dark areas on the glandular portion of the stomach, discoloration of the lungs, and carcass autolysis. Under the conditions of this test, the Median Lethal Dose of LSN2812839 is estimated to be equal to 2000 mg/kg.