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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

In accordance with point 8.8.1 of column 1 (Standard Information Required), Annex VIII of REACH (Regulation EC No. 1907/2006), assessment of the toxicokinetic behaviour of the substance is performed to the extent that can be derived from the relevant available information. A toxicokinetic assessment was performed based on the available physical-chemical data and toxicological information available. Further testing for the assessment of toxicokinetic behaviour is omitted on this basis.

Introduction

Aminouanidium hydrogen carbonate (CAS 2582 -30 -1) is an organic yellow odourless crystalline powder.

No experimental studies of the absorption, metabolism, distribution, or elimination of aminoguanidium hydrogen carbonate (“the substance”) in mammals are available.  Information is utilized from existing toxicology studies on the substance, or for other very similar materials, and this data is used to infer, as far as possible, the potential toxicokinetics of the substance.

Physicochemical properties

Systemic availability of the substance depends on its ability to be absorbed across body surfaces. Factors that affect this process include water solubility, lipophilicity (measured by the partition coefficient, Kow), degree of ionization (the dissociation constant, pKa), and molecular size. Aminoguanidium hydrogen carbonate has a molecular weight of 135 and a water solubility of 5 g/L.

Absorption

Oral absorption

The acute oral LD50was greater than 5000 mg/kg bw in an oral gavage study. All rats dosed with 3100 mg/kg of the test substance tolerated the treatment without clinical signs or mortality. All rats dosed with 5000 mg/kg showed sedation and poor general condition within 2 to 6 days after application of the test substance and 4/10 rats died.

In an OECD 421 reproductive toxicity screening study, treatment with the substance at dose levels up to 1000 mg/kg was associated with decreased food consumption, body weights/body weight change and decreased relative and absolute thymus weights. At 1000 mg/kg bw/day, there was also signs of chronic nephropathy and hypertrophy of the kidney tubules as well as hepatocellular hypertrophy in females (NOAEL 300 mg/kg/day in males and 88 mg/kg bw/day in females) suggesting that some absorption took place.

Lower MW components of the substance are likely more readily absorbed than the higher MW components.

The physical chemical properties do not preclude absorption. In the absence of quantitative information, 50% bioavailability following oral administration is assumed for the purposes of human risk assessment.

 

 

Dermal absorption                                                                                               

The acute dermal LD50for aminoguanidium hydrogen carbonate was greater than 50000 mg/kg bw in acute dermal toxicity studies, with no clinical signs, effects on body weight or gross abnormalities at necropsy. An in vivo skin irritation study with the substance also showed no toxicity to the test system; however the substance was a skin sensitizer in the LLNA. As the substance did not appear to show systemic effects in the dermal study, it is not likely that dermal absorption was extensive.

Lower MW components of the substance are likely be more readily absorbed than the higher MW components.

For the purposes of risk assessment however, estimation of mammalian dermal absorption is made in accordance with principles adopted by the EFSA guidance on estimating dermal absorption of pesticide active substances (EFSA, 2012). On this basis, dermal absorption is estimated at 50% for undiluted substance, which is considered conservative.

Inhalation absorption

Aminoguanidinium hydrogen carbonate is a solid therefore, absorption through inhalation is unlikely. However, using the REACH principles, inhalation absorption was considered 100% for the calculation of DNELs while oral and dermal absorption were considered 50% each.

Distribution, Metabolism and Elimination

QSAR predictions show that the parent compound is hydrolysed to an intermediate which is further hydrolized and acetylated to form three metabolites which are ultimately eliminated by phase two metabolism.

Conclusion

For the purposes of human risk assessment oral absorption of the substance is estimated at 50% and dermal absorption is estimated at 50%. Inhalation absorption is considered 100%. All DNELs are calculated using an oral OECD 421 study. Therefore, the DNELs for inhalation and dermal exposure will be very conservative.

 

 

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