Bicyclo[2.2.1]heptanebis(methylamine)

Endpoint summary

Description of key information

Physicochemical properties

The substance bicyclo[2.2.1]heptanebis(methylamine) (NBDA) is a clear liquid.  The molecular weight (MW) is 154 g/mol and its water solubility is >1000 g/L (water-soluble) with a measured log Pow value of 1.0 at 25 °C.  The vapour pressure was determined to be 16 Pa at 20 °C and 21 Pa at 25 °C.

Absorption

Oral absorption

The low molecular weight in combination with the high water-solubility and low octanol/water partition coefficient indicate that NBDA can be highly absorbed from the gut.

Repeated dose (subacute) oral, acute oral and reproduction/developmental toxicity (OECD 421) studies available for NBDA reported no reproductive/developmental effects.  There were, however, toxicity effects starting from the dose of 15 mg/kg bw/day.  Target organs were the liver and adrenal gland.  These data in combination with the high water solubility of NBDA, indicate that the substance is absorbed by the GI tract.  

Therefore, in the absence of any quantitative data, the default value of 100% is assumed for oral absorption in accordance with the ECHA guidance.

Dermal absorption

A substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis, and since the water solubility of NBDA is high enough, it is expected that dermal penetration will also be extensive.  This is further supported by the estimated Log Pow values, which also suggest that NBDA is dermally absorbed.

In conclusion, the above data in combination with the fact that NBDA is considered to be a skin corrosive, the default value of 100% is assumed for dermal absorption.

Inhalation absorption

With respect to inhalation absorption, in the absence of any quantitative data and as a worst-case assumption for human health risk assessment purposes absorption by inhalation of NBDA is assumed to be 100%.

Distribution

The repeat-dose oral toxicity study reported several toxicity effects and the identified target organs were the liver and the adrenal gland.  Moreover, the low molecular weight and low Log Pow value suggest water solubility.  No evidence of bioaccumulation was reported from the available repeat-dose toxicity studies, despite the substance was found to not be readily biodegradable.  On this basis, potential for bioaccumulation is considered low.

Metabolism and Elimination

Nothing could be inferred from the results of the Ames test or in vitro genotoxicity studies (chromosome aberration and gene mutations in mammalian cells), because NBDA was not genotoxic, mutagenic or clastogenic in either the presence or absence of S9 metabolising system.  The absence of toxicity effects in pups from the OECD 421, indicates that NBDA is not excreted in milk.  The nature of the substance (hydrophilicity and water solubility) suggest that both the parent compound and any metabolite will probably be excreted in urine.

Conclusion

Based on in vitro and in vivo data from studies performed with NBDA, oral, dermal and inhalation absorption are assumed to be 100%.  Furthermore, the potential for bioaccumulation is low, and the substance is expected to be completely excreted in urine.

 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

The substance has been studied in in vivo toxicity and physico-chemical studies. These results in combination with the results from in vitro and in vivo studies were used to determine a toxicokinetic profile of the substance. 

Based on in vitro and in vivo data on the substance oral, dermal and inhalation absorption are assumed to be 100%. Furthermore, the potential for bioaccumulation is low, and the substance is expected to be completely excreted in urine.