Aminoguanidinium hydrogen carbonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An extensive assessment of the toxicological behaviour of aminoguanidinium hydrogen bicarbonate was performed, taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Materials and methods

Test guideline

Qualifier:

no guideline required

Test material

Test material information

Constituent 1

Reference substance name:

Aminoguandinium hydrogen carbonate

IUPAC Name:

Aminoguandinium hydrogen carbonate

Constituent 2

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

Details on test material:

not applicable

Radiolabelling:

other: not applicable in this expert statement

Test animals

Species:

other: not applicable

Strain:

other: not applicable

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Route of administration:

other: all routes of administration are discussed in the expert statement

Vehicle:

other: not applicable

Details on exposure:

all routes of administration are discussed in the expert statement

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Based on physico-chemical properties which are not suggestive of significant absorption, absorption of the substance into the body is expected to be low via all exposure routes. No alerts were found for protein binding for the associated chemical or dissociated components.

Details on distribution in tissues:

For the target substance, the distribution is also expected to be limited as the absorption should be low. The compound can distribute to the tissues based on slight effects seen in the the liver, kidney, and thymus in a sub-acute study.

Details on excretion:

For the target substance no data is available concerning its elimination. It is believed that the test substance and any metabolites should be eliminated mainly via the urine or feces.

Metabolite characterisation studies

Details on metabolites:

If absorbed, the substance is expected to be metabolised by Phase I drugs metabolising enzymes with followed conjugation by Phase II reactions. It is expected that the substance may dissociate in vivo.

Any other information on results incl. tables

Background

There is data available on the physico-chemical properties of aminoguandinium hydrogen carbonate. The substance is as a solid that decomposes at approximately 172°C. Due to this decomposition, no boiling point or vapor pressure values could be determined. The LogKow was determined as -6.61 by calculation. The substance was shown not to be acutely toxic, the oral LD50 being above 5000 mg/kg bw and the dermal LD50 being greater than 5000 mg/kg bw. It has been shown to be neither a skin nor an eye irritant. Aminoguanidinium hydrogen carbonate was shown to bear a potential to cause allergic reactions. Repeated oral exposures during a reproductive study (OECD 421 study) revealed a NOAEL of 300 mg/kg bw/day for systemic effects and a LOAEL of 88 mg/kg bw/day for developmental toxicity. The NOAEL for reproductive toxicity was 1000 mg/kg bw/day.

Absorption, Metabolism, and Elimination

Absorption is expected to be limited based on low toxicity for systemic effects after acute and sub-acute exposures. Dermal adsorption is expected to be particularly low as the substance is neither corrosive nor irritating. In addition, inhalation absorption will also be low based on it being a solid.

Metabolism

The substance is likely to dissociate in the digestive tract. No protein binding alerts were found in OECD Toolbox for the chemical substance or the likely dissociated metabolites.

Elimination

Elimination is likely to be via the urine or feces.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
An extensive assessment of the toxicological behaviour of aminoguanidium hydrogen carbonate (expert statement), taking into account the chemical structure, the available physico-chemical-data and the available (eco-)toxicological data.

Executive summary:

Background

There is data available on the physico-chemical properties of aminoguandinium hydrogen carbonate. The substance is as a solid that decomposes at approximately 172°C. Due to this decomposition, no boiling point or vapor pressure values could be determined. The LogKow was determined as -6.61 by calculation. The substanc was shown not to be acutely toxic, the oral LD50 being above 5000 mg/kg bw and the dermal LD50 being greater than 2000 mg/kg bw. It has been shown to be neither a skin nor an eye irritant. Aminoguanidinium hydrogen carbonate was shown to bear a potential to cause allergic reactions. Repeated oral exposures as part of a reproductive study (OECD 421 study) revealed a NOAEL of 300 mg/kg bw/day for systemic effects and a LOAEL of 88 mg/kg bw/day for developmental toxicity. The NOAEL for reproductive toxicity was 1000 mg/kg bw/day.

Absorption, Metabolism, and Elimination

Absorption is expected to be limited based on low toxicity for systemic effects after acute and sub-acute exposures. Dermal adsorption is expected to be particularly low as the substance is neither corrosive nor irritating. In addition, inhalation absorption will also be low based on it being a solid.

Metabolism

The substance is likely to dissociate in the digestive tract. No protein binding alerts were found in OECD Toolbox for the chemical substance or the likely dissociated metabolites.

Elimination

Elimination is likely to be via the urine or feces.