6-METHOXYPYRIDINE-3-CARBALDEHYDE

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 September - 23 September, 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

6-methoxypyridine-3-carbaldehyde

Cas Number:

65873-72-5

Molecular formula:

C7H7NO2

IUPAC Name:

6-methoxypyridine-3-carbaldehyde

Test material form:

solid: particulate/powder

Details on test material:

Batch (Lot) Number: 2019-03-29
Physical Description: Cream powder
Storage Conditions: Kept in a controlled room temperature area, protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Justification for Test System and number of animals:
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 13 male and 13 female Sprague Dawley rats were received on 03 Sept. 2019.

Six days were allowed between receipt of the animals and the start of treatment to accustom the animals to the laboratory environment. Each animal was uniquely identified using a subcutaneously implanted electronic identification chip.

Housing:
On arrival, animals were individually housed until randomization. Following, randomization, animals were socially housed in polycarbonate cages containing appropriate bedding equipped with an automatic watering valve.

Selection, Assignment, Replacement, and Disposition of Animals:
Prior to randomization procedures, the animals were weighed. Animals determined to be suitable as test subjects were assigned to groups by a stratified randomization scheme designed to achieve similar group mean body weights. Males and females were randomized separately.

Initial age: 8 weeks

Weight at the Initiation of Dosing: Males: 215 to 239 g.
Females: 152 to 181g.

Environmental Conditions:
The animal room environment and photoperiod were controlled (targeted conditions: temperature 20° C to 26°C, humidity 30% to 70%, 12 hours light and 12 hours dark, except during designated periods). The overall average temperature and relative humidity ranges during the study were 21°C to 22°C and 53% to 59%, respectively.

Food:
All animals had free access to a standard certified commercial laboratory diet.

Water:
Municipal tap water, purified by reverse osmosis and exposed to ultraviolet irradiation, was freely available, except during designated procedures.

Veterinary Care:
Veterinary care was available throughout the study; however, no veterinary examinations or medicinal treatments were administered during the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Reverse Osmosis Dionized (RODI) water

Details on oral exposure:

Administration of Test item:
On the day prior to dosing 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 (5, 50, 300, and 2000 mg/kg, 10 mL/kg) to rats (3/sex/group) 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:

5 mg/kg (group 1), 50 mg/kg (group 2), 300 mg/kg (group 3), 2,000 mg/kg (group 4)

No. of animals per sex per dose:

3/sex/group

Control animals:

no

Details on study design:

In-life Procedures, Observations, and Measurements
Mortality/Moribundity Checks:
The animals were observed for general health/mortality and moribundity at least twice daily, at least once in the morning and at least once in the afternoon, throughout the study.

Clinical observations:
Each animal was removed from the cage and observed in detail a minimum of 2 times on Day 0 (postdose), with the first observation within approximately 30 minutes after dosing, and daily thereafter (Days 1 to 14).

Body Weights:
Individual body weights were recorded for all animals prior to fasting, prior to dosing (Day 0), and on Days 7 and 14.

Terminal Procedures:
No animals died as a result of this study. Animals surviving until scheduled euthanasia were weighed, euthanized by carbon dioxide inhalation, and discarded without examination.

Statistics:

Body weight means and standard deviations were calculated separately for males and females for each limit level administered.
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:

No mortality occurred during the study. All animals survived to scheduled euthanasia on Day 14.

Clinical signs:

other: Test article-related clinical observations included hunched posture in animals administered 2000 mg/kg and erected fur in animals administered ≥300 mg/kg. All clinical signs resolved by Day 7. Group 3 – 300 mg/kg Test article-related clinical observatio

Gross pathology:

Not specified

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this test, the median lethal dose (oral LD50 value) of COM-1074 (Intermediate 2607535) in Sprague-Dawley rats was estimated to be greater than 2000 mg/kg/bw. Therefore, the GHS criteria was not met.