Aminoguanidinium hydrogen carbonate

Repeated dose toxicity: oral

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

Test material information

Constituent 1

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:

carbamimidoyldiazanium hydrogen carbonate

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

1

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

2

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.