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Description of key information

A theoretical assessment of the toxicokinetics of di-pentaerythritol is made, based on the molecular structure and information from toxicity studies. The theoretical assessment is supported by the results of an in vitro study of absorption; a further study of metabolism in vitro is planned (February 2014).  

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

A theoretical assessment of the toxicokinetics of di-pentaerythritol is made, based on the molecular structure and information from toxicity studies. The theoretical assessment is supported by the results of an in vitro study of absorption.

Theoretical assessment indicates rapid and extensive absorption and distribution; rapid metabolism and excretion are likely to limit systemic exposure and toxicity. No bioaccumulation is predicted.

 

Absorption

Oral absorption of di-Penta is predicted based on the substance molecular size, solubility, chemical structure and on the basis of experience with other polyol substances. The molecule satisfies Lipinski's rule of 5 (OECD QSAR Toolbox). Studies of oral toxicity do not provide any direct indication of gastrointestinal absorption; however non-specific signs of toxicity were observed in the acute oral toxicity study at the limit dose. A 14-day range-finding study in the rat reports pale faeces at dose levels of 1000 and 1500 mg/kg bw/d; findings may be consistent with incomplete oral absorption at these high gavage dose levels. An OECD 422 screening study similarly reports observations of pale faeces at the highest dose level of 1000 mg/kg bw/d. The results of an in vitro study performed using everted rat intestinal sacs reports that di-Penta is absorbed; however the extent of absorption is less than seen for other polyol compounds. 

In the absence of data, absorption following inhalation exposure is assumed to be extensive.

The dermal absorption of di-Penta is likely; the extent of dermal absorption is likely to be less than oral absorption.  In the absence of any data, the extent of oral and dermal absorption is assumed to be comparable.

Distribution

No data are available; findings from repeated dose toxicity studies do not indicate any specific targets of toxicity. Rapid and extensive distribution of absorbed di-Penta and its metabolites can be predicted based on knowledge for related substances. Di-Penta is likely to be rapidly absorbed and subject to extensive hepatic metabolism resulting in the renal excretion of water-soluble metabolites.  The systemic distribution of di-Penta is therefore likely to be limited by its metabolism and excretion.

Metabolism

Sequential oxidative metabolism of the six hydroxy groups present in the di-Penta molecule is predicted, based on known metabolic reactions and the elucidated pathways for other alcohol compounds; hydrolysis of the central ether linkage to yield pentaerythritol can also be predicted. There are no additional chemical groups known to be susceptible to mammalian metabolism. Rapid hepatic metabolism is indicated, which will facilitate excretion and therefore act to limit systemic exposure and toxicity. OECD QSAR Toolbox hepatic metabolism simulator identifies a total of seven potential metabolites arising from ether hydrolysis and/or oxidation.

 

Excretion

Rapid and extensive renal excretion of di-pentaerythritol and/or its metabolites is likely, with no potential for bioaccumulation based on chemical properties. Findings are consistent with the low toxicity seen in the repeated-dose toxicity studies.