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Ethylenediamine, propoxylated, 1-5.5 moles propoxylated is an essentially non-volatile liquid at room temperature, fully miscible with water and with a log P of < 0.3 – 1.6. There are no studies on the toxicokinetics of the propoxylated ethylenediamine. The approach employed in this toxicokinetics assessment is to examine data for the repeating unit and the initiating agent, ethylenediamine, and oligomers made using ethylenediamine as initiating agent and 1-methyl-2-oxirane as the chain-lengthening agent (in ascending order of multiples of the oligomer). These are ethylene diamine (and, for comparison, its dimer) and propane-1,2-diol and its oligomers. Conclusions for the longer oligomers are based on that data and on structure activity information. The commercially available NLP polyols are mixtures containing several individual oligomers of different molecular weight or number of repeating units. Generally the lowest commercially available NLP polyol have at least three propoxy moieties attached to the ethylenediamine. Thus it is likely that both the amine groups will be capped, with the link as a secondary or tertiary amine rather than as an ether. This is reflected in the acute toxicity data, whereby the acute toxicity of ethylenediamine and dimer is sufficient to require classification as harmful and as a skin and eye irritant and a skin sensitiser, whereas the lowest molecular weight propoxylated material (~3-4 PO) is essentially non-toxic. With the amine groups capped, the oligomer is likely to exhibit toxicokinetics based on the propane-1,2-diol oligomers. The lack of resemblance of ethylenediamine to glycerol or propane-1,2-diol means that NLP polyols are unlikely to interfere in fat absorption mechanisms and the absorption mechanism is likely to be passive diffusion.


Given the vapor pressure and water solubility of the commercial preparation, it is likely that absorption of some of the lower molecular weight components may occur via the lung.

Based on data for toluene-2,4-diamine and toluene-2,6-diamine, toluene-2,3- diamine and 4-methyl-o-phenylene diamine should be readily absorbed orally. Propane-1,2-diol, oxydipropanol and [(methylethylene)bis(oxy)]dipropanol are also absorbed, probably by passive diffusion, when administered orally. Thus it is probable that low number oligomers will be absorbed. The calculated logP suggests that the component representing the mean toxicity of the commercial preparation is likely to be absorbed orally.

Lipinski et al (1997) proposed the so-called ‘rule-of-five’ for identifying chemicals that would have poor absorption. This rule states that poor absorption is likely when any two of the following conditions are satisfied: a) molecular weight >500; b) log P > 5.0; c) number of hydrogen bond donors >5; and d) number of hydrogen bond acceptors >10.

Higher molecular weight NLP polyol oligomers and polymers (Mn > 500) with five or more hydrogen bond donating groups are unlikely to be absorbed in significant amounts.


Given the logP values, it is likely that any absorbed oligomers of propoxylated diaminotoluene will be widely distributed in the body. As metabolism is likely, it is unlikely that they will accumulate in tissues.


Based on information from the propane-1,2-diol trimer [(methylethylene)bis(oxy)]dipropanol, if absorbed, the propane-1,2-diol moiety of the propoxylated diaminotoluene could be further conjugated (with glucuronic acid or sulphate) or stepwise hydrolysed. Propane-1,2-diol is also further metabolised, entering intermediary metabolism via lactic acid/pyruvic acid, and eventually being eliminated as carbon dioxide. Based on read across, the metabolic pathways identified for the toluene diamine portion of the oligomer are hydroxylation on one of the three available carbon atoms of the phenol ring, followed by glucuronidation. If free toluene diamine is formed, it may also be metabolised by mono-or di-acetylation of the amine groups. Although the benzylic carbon of tolune is oxidised to toluyl alcohol and methylbenzoic acid, which is then conjugated to form methyl hippuric acid, this metabolic route appears to be absent when toluene diamine metabolism is examined.


In the event that higher molecular weight material is absorbed, it is likely to be excreted in bile. Lower molecular weight unmetabolised oligomer is likely to be excreted in urine. In rat the molecular weight threshold for biliary excretion is around 350, in human it is about 500 (Illing, 1989). The material most likely to be absorbed is likely to be hydrolysed and the products appear in urine. Some carbon dioxide might be formed from hydrolysis of the propane-1,2-diol groups and exhaled.


The toxicokinetics assessments are consistent with the structure-activity calculations. If absorbed, generally the NLP polyols are likely to be metabolised to yield core substances and propane-1,2-diol (or ethane-1,2-diol for the one NLP polyol containing both propoxy and ethoxy moieties). The NLP polyols formed via an amine link (ethylenediamine, diaminotoluene) are likely to release amine core substances that will probably be metabolised using pathways associated with xenobiotic metabolism, principally N-acetylation, and excreted principally in urine. The repeating units, once hydrolysed, are likely to enter endogenous metabolism.

Discussion on bioaccumulation potential result:

Given the logP values it is likely that oligomers formed by propoxylated ethylenediamine will be widely distributed in body water and it is unlikely that they will accumulate in tissues.


Reference (available in Chapter 13): Illing and Barratt(2007, revised 2009). Grouping of NLP ‘Polyols’ and their Toxicokinetics Assessments. Testing laboratory: not applicable. Owner company: ISOPA, 1160 Brussels, Belgium.