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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start : 12 March 2013 Completion : 28 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterize

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Principles of method if other than guideline:
Assessment of acute oral toxicity with Amiloride Compound 5 in the rat (Acute Toxic Class Method).
JMAFF guidelines (2011) including the most recent partial revisions.
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
3-aminopyrazine-2-carboxylic acid
EC Number:
226-558-7
EC Name:
3-aminopyrazine-2-carboxylic acid
Cas Number:
5424-01-1
Molecular formula:
C5H5N3O2
IUPAC Name:
3-aminopyrazine-2-carboxylic acid
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Molecular formula C5H5N3O2
Molecular weight 139.11
CAS Number 5424-01-1
Description Tan powder

Purity/Composition 100 area%
Test substance storage In refrigerator (2-8°C) protected from light, desiccated
Stability under storage conditions Stable
Expiry date 13 March 2014 (Retest date)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean
- Housing: 3 per same group in stainless steel cage
- Diet (e.g. ad libitum): SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C,
- Humidity (%):40to 70%
- Air changes (per hr): 15 room air changes/hour
- Photoperiod (hrs dark / hrs light):12/24

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.6 % methyl cellulose aqueous solution
Details on oral exposure:
Amiloride Compound 5 was administered by oral gavage to two subsequent groups of three female
Wistar rats at 2000 mg/kg body weight
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
two subsequent groups of three female
Control animals:
not specified
Details on study design:
The toxicity of the test substance 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.

Results and discussion

Preliminary study:
No Data
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
Lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis were noted in the
animals on Day 1. Hunched posture persisted in three females up Day 2.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that
expected of normal untreated animals of the same age and strain
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of Amiloride Compound 5 in Wistar rats was established to exceed 2000 mg/kg
body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000
mg/kg body weight.
Based on these results, Amiloride Compound 5 does not have to be classified and has no obligatory
labelling requirement for acute oral toxicity according to the Globally Harmonized System of
Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No
1272/2008 on classification, labelling and packaging of substances and mixtures, including all
amendments.