[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 20 Dec 2016 to 11 Jan 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

potassium (trans-4-(methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino)-cyclohexyl)-methanesulfonate

Cas Number:

2124221-14-1

Molecular formula:

C14H19KN4O3S

IUPAC Name:

potassium (trans-4-(methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino)-cyclohexyl)-methanesulfonate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: Charles River, St. Constant Quebec Canada on 01 Dec 2016.
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable)
- Age at study initiation: The animals were born on 04 Oct 2016.
- Weight at study initiation: The pretest body weight range was 229 - 252 grams.
- Fasting period before study: 16 to 20 hours prior to dosing.
- Housing: The animals were identified by cage notation and indelible body marks, and individually
housed in suspended wire-bottom cages. Absorbent paper bedding was placed beneath the cages
and changed at least three times per week.
- Historical data:
- Diet (e.g. ad libitum): Fresh PMI Rat Chow (Diet No. 5012) was freely available except for 16 to
20 hours prior to dosing.
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: at least five days
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test article was mixed with distilled water to make dosing by gavage possible. The dose was base
d on the dry weight of the test article. Initially, a single female Sprague Dawley rat was dosed orally by
syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal survived, four additional
females were dosed at 2000 mg/kg.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

In Vivo - Animals were observed at 15 minutes, 1, 2 and 4 hours post-dosing and once daily thereafte
r for 14 days for toxicity and pharmacological effects. Observations included, but were not limited to,
evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, auto
nomic effects such as salivation, central nervous system effects including tremors and convulsions,
changes in the level of activity, gait and posture, reactivity to handling or sensory stimuli, altered
strength, and stereotypies or bizarre behavior (e.g., self-mutilation, walking backwards). All animals
were observed twice daily for mortality on Day 1 to Day 14. Body weights were recorded pre-test,
weekly, and at termination.
Post Mortem – All animals were humanely euthanized using CO2 following study termination and
examined for gross pathology.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All five female rats survived following a single 2000 mg/kg oral dose.

Clinical signs:

other: No abnormal physical signs were observed among two out of five animals. Piloerection was observed in three out of five animals only on Day 0.

Body weight:

other body weight observations

Remarks:

AII five animals gained body weight by study termination.

Gross pathology:

The gross necropsy revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test item is greater than 2000 mg/kg of body weight in female rats.

Executive summary:

The acute oral study is performed using rats, according to OECD Guideline 425 under GLP. The oral
LD50 of the test item is greater than 2000 mg/kg of body weight in female rats.