D-Glucitol, propoxylated

Endpoint summary

Additional information

D-Glucitol, propoxylated, 1-12.5 mol propoxylated is a relatively non-volatile liquid at room temperature (vapour pressure 8.02·10^-6 hPa at 25oC). The commercial material is very soluble in water (600-1000 g/L) and has log P values of –0.7-2.

There are no experimental studies on the toxicokinetics of propoxylated D-glucitol. The toxicokinetics of propoxylated D-glucitol are inferred from the toxicokinetics of the core substance and propane-1,2-diol, oxydipropanol and [(methylethylene)bis(oxy)]dipropanol.

Discussion on bioaccumulation potential result:

There are no experimental studies on the toxicokinetics of propoxylated Dglucitol. The toxicokinetics of propoxylated glucitol are inferred from the core substance and propane-1,2-diol, oxydipropanol and [(methylethylene)bis(oxy)]dipropanol. Glucitol has six free hydroxy groups, thus NLP polyols are likely to consist predominantly of chains of between one and two monomers, with some chains containing three monomers.

For the calculations of bioavailability LogP values of the commercial NLP polyol were calculated using the incremental fragment method of Suzuki and Kudo (1990). The propoxyl- groups, have an important effect on the toxicity by modulating any toxicity arising from the core substance. The substitution of a hydroxyl group on a core compound by a propoxyl- group increases its logP value by 0.24 units and its molecular weight by 58 Daltons. The combined effect of these changes is to reduce the bioavailability by a factor of 1.53 (calculated using the Potts and Guy equation). Thus the molecular weight changes are more significant than the logP changes in determining the bioavailability.

The trimer of propane-1,2-diol is 84% absorbed. As D-glucitol has a lower logP it is less likely to be well absorbed. The absorption of D-glucitol + 3 PO (3 moles propoxylation, MW 356) is less than 40% of that of the propane-1,2- diol trimer whilst that of Glucitol + 6PO, the type molecule used for toxicity purposes even lower (< 8%).

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 polyols with seven or more propoxyl units (MW 588 or higher) are containing more than five hydrogen bond donating hydroxyl groups are unlikely to be absorbed in significant amounts.

See Illing and Barrat (2007 and 2009) attached in Section 13 for further information.