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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Aminoguanidinium hydrogen carbonate
EC Number:
219-956-7
EC Name:
Aminoguanidinium hydrogen carbonate
Cas Number:
2582-30-1
Molecular formula:
CH6N4.CH2O3
IUPAC Name:
N-aminoguanidine; carbonic acid
Test material form:
other: solid
Details on test material:
content: 99.4 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5-6 weeks
- Weight at study initiation: males: 129 g, females 102 g
- Housing: konventional
- Diet ad libitum
- Water ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % aqueous cremophor solution
Details on oral exposure:
once daily application by gavage
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
no details given
Duration of treatment / exposure:
34 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
according to guideline
Positive control:
no

Examinations

Observations and examinations performed and frequency:
clinical signs and mortality, body weight development and feed intake, water consumption; hematology and clinical chemistry
Sacrifice and pathology:
sacrifice of all surviving animals, determination of organ weights (liver, spleen, kidneys, adrenals, testes, ovary) and macroscopic and microscopic evaluation (kidneys, lungs, liver, testes)
Statistics:
U-test nach Mann and Whitney, exact tests nach Fischer,

Results and discussion

Results of examinations

Details on results:
Administration of aminoguanidinium hydrogen carbonate did not lead to increased mortality at any dose.
In rats treated with 1000 mg/kg bw/day
--there was isolated cased of salivation.
--body weight gain was decreased in males compared to controls (175 g versus 191 g) which was in line with a decrease in feed intake (17.9 g/dosed rat versus 19.1 g/control rat) .
--The rats in this group also drank more water.
--Apart from an increase in the activity of alkaline phosphatase in the top dose: (male: 520 U/l versus 367 U/l of controls; female: 351 U/l versus 226 U/l of controls ) no treatment-related effects were evident in clinical chemistry and hematology tests and histopathological examination of the rats treated with aminoguanidinium hydrogen carbonate.

The 300 mg/kg bw/day dose was thus tolerated without adverse effects under the conditions described (BG Chemie).

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
300 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: 1000 mg/kg bw/day: reduced body weight development in line with reduced food intake; increase in alkaline phosphatase without histopathological correlate
Dose descriptor:
NOAEL
Effect level:
ca. 1 000 mg/kg bw/day (nominal)
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

In a study which was carried out in accordance with OECD TG 407, groups of 10 male and 10 female Wistar rats were given aminoguanidinium hydrogen carbonate by gavage in doses of 100, 300, and 1000 mg/kg bw/day. The controls were treated with a corresponding amount of the vehicle (aqueous Cremphor suspension).

 

Administration of aminoguanidinium hydrogen carbonate did not lead to increased mortality at any dose. In rats treated with 1000 mg/kg bw/day there was isolated cased of salivation. Body weight gain was decreased in males compared to controls which was in line with a decrease in feed intake. The rats in this group also drank more water. Apart from an increase in the activity of alkaline phosphatase in the top dose, no treatment related effects were evident in clinical chemistry and hematology tests and histopathological examination of the rats treated with aminoguanidinium hydrogen carbonate.

 

The 300 mg/kg bw/day dose was thus tolerated without effects(NOEL) under the conditions described (BG Chemie). The NOAEL is 1000 mg/kg bw/day.