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Description of key information

A theoretical assessment of the toxicokinetic properites of the substance is made, based on exisiting toxicity data and physicochemical properties.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Theoretical assessment of the toxicokinetic properties of DBU

1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is a non-volatile liquid with a moderate LogP value of ~2.7 and which is hydrolytically stable and miscible with water.

 

Absorption

Absorption following oral exposure

 

The molecular weight, LogP value and high water solubility favour the oral absorption of DBU.  Oral bioavailability is predicted for DBU according to Lipinski’s rules.  Theoretical assessment indicates that the substance is hydrolytically stable; therefore is likely to be absorbed intact. DBU is demonstrated to be corrosive to skin; therefore toxicity testing in vivo is limited. Mortality in the acute toxicity study is associated with severe local effects on the stomach. A 14-day range-finding study and a longer-term screening study (OECD 422) performed in the rat report some toxicity, however the effects seen in these studies are almost entirely associated with local effects on the gastric mucosa.  A suggestion of increased kidney weight in the OECD 422 study may indicate the urinary excretion of DBU. Studies do not conclusively demonstrate systemic exposure; a default assumption of 50% oral absorption is therefore made for the purposes of risk assessment.

 

Absorption following dermal exposure

 

No studies of toxicity following dermal administration are available. The molecular weight, LogP value and high water solubility favour the dermal absorption of DBU.  The substance is shown to be corrosive to skin; local irritation or damage caused by dermal exposure may act to facilitate dermal absorption. A default assumption of 50% dermal absorption is made for the purposes of risk assessment.

 

Absorption following inhalation exposure

 

Inhalation absorption is only relevant for substances which are gases, volatile liquids or which are used in a manner which generates small droplets or particles (e.g. by spraying).  The physicochemical properties of DBU indicate that significant inhalation exposure is unlikely.  The extent of absorption following the inhalation of DBU is likely to be extensive. An assumption of 100% inhalation absorption is therefore made for the purposes of risk assessment.

 

Distribution

 

The available toxicity data do not provide any indication of the systemic distribution of DBU with the possible exception of the kidney; however the water solubility and low molecular weight of the substance indicates that any systemically absorbed substance would be rapidly distributed in the systemic circulation.

 

Metabolism

 

OECD QSAR Toolbox (3.0) does not predict any hepatic or dermal metabolites for DBU. 

 

Excretion

 

Data indicate that DBU will be rapidly excreted in the urine. Biliary excretion is unlikely based on the low molecular weight of the substance.

 

Bioaccumulation

 

The physicochemical properties and predicted toxicokinetic properties of DBU do not indicate any potential for bioaccumulation.