N,N'''-1,6-hexanediylbis[N'-cyanoguanidine]

Endpoint summary

Additional information

TOXICOKINETIC BEHAVIOUR

 

Physico-chemical properties:

HMBDA is a white crystalline solid with a green/blue tint and the molecular weight is 250.3 g/mol. The mean measured Log P (octanol-water) of HMBDA is 0.465 and the mean water solubility of HMBDA was low at 7.05 mg/l at 25 degC.

 

The very low vapour pressure value (<0.0004 Pa at 95 degC) shows that the substance is non-volatile therefore inhalation by vapours is not a significant route of exposure. A determination of aerodynamic particle size confirmed that only 0.267% of the substance has an aerodynamic particle size of less than 10.0 μm (thoracic fraction) and only 0.196% of the substance has an aerodynamic particle size of less than 5.5μm (respirable fraction). Therefore, the substance in solid form is not respirable and human lung exposure to the substance is not considered significant.

 

Absorption:

There are no specific ADME data on the extent to which HMBDA absorbs across the gut, lungs or skin. The level of absorption will depend upon the solubility of HMBDA in the solvent/vehicle carrying it into the body. It is a low molecular weight chemical and therefore, if solubilised could undergo some absorption. The two potential routes of exposure are via ingestion or dermal contact.

 

No toxicological effects are seen in the oral 28-day study performed, nor in the acute oral study. In terms of performing oral dosing toxicological studies with HMBDA, the choice of a 0.5% (w/v) hydroxypropylmethylcellulose in 0.1% (w/v) aqueous polysorbate 80 vehicle in the 28-day study was chosen to aid homogeneity and produce as maximal systemic delivery as possible of this sparingly soluble test substance in aqueous vehicles. It is unknown as to whether the material did not absorb or whether it did absorb systemically to a certain degree but exerted no effects.

 

There are no specific skin absorption data. Given the low logKow, this material is not expected to penetrate the skin well. The substance is not irritant/corrosive and therefore no damage to the skin barrier is expected upon contact.

 

Distribution:

There are no data and no indications in any of the studies as to whether the HMBDA reached particular organs or whether distribution was extensive to major organs and in blood.

 

Metabolism:

The results of in vitro genotoxicity assays in the presence of the S9 metabolising system have shown that metabolism does not influence the results for genotoxicity. HMBDA is not genotoxic in the absence or presence of S9. There is no information regarding metabolism from the available toxicology studies.

 

Excretion:

There is no evidence to indicate the route of excretion. Any test item that is not absorbed across the gut will be excreted predominantly in the faeces.