2-Amino-3-bromopyridine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 2016 - June 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

3-bromopyridin-2-amine

EC Number:

629-620-5

Cas Number:

13534-99-1

Molecular formula:

C5 H5 Br N2

IUPAC Name:

3-bromopyridin-2-amine

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Rat, Wistar strain Crl:WI (Han) (outbred, SPF-Quality).
Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative
humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle.
Any variations to these conditions were maintained in the raw data and had no effect on the
outcome of the study.
Accommodation
Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.)
containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier &
Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri,
Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatization period was at least 5 days before start of treatment under laboratory
conditions.
Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest,
Germany).
Water
Free access to tap water.
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was
performed according to facility standard procedures. There were no findings that could
interfere with the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

Oral gavage, using plastic feeding tubes. The test item preparations were stirred on a magnetic stirrer during dosing.

Doses:

Dose level (volume)
2000 mg/kg (10 mL/kg) body weight.
300 mg/kg (10 mL/kg) body weight.

No. of animals per sex per dose:

9 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The
first group was treated at a dose level of 2000 mg/kg.

Control animals:

no

Details on study design:

The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The
first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of
animals dosed at one step determined the next step, based on the test procedure defined in the
guidelines. The onset, duration and severity of the signs of toxicity were taken into account
for determination of the time interval between the dose groups.

Statistics:

The oral LD50 value of the test item was ranked within the following ranges: 0-5, 5-50, 50-
300 or 300-2000 mg/kg b.w. or as exceeding 2000 mg/kg b.w. The LD50 cut-off value was
established based on OECD guideline 423. No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, all animals were found dead on Day 1.
At 300 mg/kg, no mortality occurred.

Clinical signs:

other: Lethargy, flat posture, quick breathing, shallow respiration, uncoordinated movements, hunched posture, piloerection, watery discharge from the eyes, ptosis, ventro-lateral recumbency and/or slow breathing were noted for all animals on Days 1 and/or 2.

Other findings:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of QAW039-C1 in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered the LD50 cut-off value was considered to be 500 mg/kg body weight.
Based on these results, according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), QAW039-C1 should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.