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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

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 (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

Theoretical assessment of the toxicokinetic properties of TMHDA

N,N,N',N'-tetramethylhexamethylenediamine (TMHDA) is a non-volatile liquid with a moderate predicted LogP value of 1.7 and which is hydrolytically stable and miscible with water.


Absorption following oral exposure

The molecular weight, LogP value and high water solubility favour the oral absorption of TMHDA. Oral bioavailability is predicted for TMHDA according to Lipinski’s rules. Theoretical assessment indicates that the substance is hydrolytically stable; therefore is likely to be absorbed intact. TMHDA 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 subchronic repeated dose toxicity study (OECD 408) performed in the rat reports systemic toxicity at the highest dose level of 75 mg/kg bw/d, Therefore, the standard assumption of 50% oral absorption is made for the purposes of risk assessment.

Absorption following dermal exposure

Toxicity in an acute dermal toxicity study is associated with marked local effects and is not a reliable indication of systemic exposure. The molecular weight, LogP value and high water solubility favour the dermal absorption of TMHDA. The substance is shown to be corrosive to skin; local irritation or damage caused by dermal exposure may act to facilitate dermal absorption. An 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 TMHDA indicate that significant inhalation exposure is unlikely. The extent of absorption following the inhalation of TMHDA is likely to be extensive. An assumption of 100% inhalation absorption is made for the purposes of risk assessment.


The available toxicity data do not provide any indication of the systemic distribution of TMHDA; 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.


OECD QSAR Toolbox (2.2.1) predicts a number of hepatic metabolites for TMHDA resulting from initial N-demethylation and N-oxidation. Sequential N-demethylation is predicted to result in the formation of secondary and primary amine derivatives. The primary amine groups may be further metabolised by deamination to form the corresponding aldehyde and subsequent oxidation to the carboxylic acid. N-demethylation of TMHDA will also result in the liberation of formaldehyde which would be rapidly oxides to formic acid. A total of 17 hepatic metabolites are predicted.


Data indicate that TMHDA and/or its metabolites will be rapidly excreted in the urine. Biliary excretion is unlikely based on the low molecular weight of the substance and its metabolites.


The physicochemical properties and predicted toxicokinetic properties of TMHDA do not idciate any potential for bioaccumulation.