Pentaerythritol

Endpoint summary

Description of key information

A theoretical assessment of the toxicokinetics of 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.

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 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

Extensive oral absorption of 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. Signs of toxicity in the acute oral toxicity studies are limited to diarrhoea at the highest dose level; similar effects (soft faeces/diarrhoea and an associated increase in water consumption) were noted in an OECD 422 screening study at the highest dose level of 1000 mg/kg bw/d. No effects were observed at the highest dose level of 1000 mg/kg bw/d in a 28-day study. Findings may be consistent with incomplete oral absorption at these high gavage dose levels.  The results of an in vitro study performed using everted rat intestinal sacs reports that Penta is well absorbed.

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

The dermal absorption of 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 Penta and its metabolites can be predicted based on knowledge for related substances. 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 Penta is therefore likely to be limited by its metabolism and excretion.

Metabolism

Sequential oxidative metabolism of the four hydroxy groups present in the molecule is predicted, based on known metabolic reactions and the elucidated pathways for other alcohol compounds. There are no additional chemical groups known to be susceptible to mammalian metabolism. Theoretical assessment (OECD QSAR toolbox) predicts two hepatic metabolites produced by oxidation of an alcohol group to form the corresponding aldehyde and carboxylic acid. Rapid hepatic metabolism is indicated, which will facilitate excretion and limit systemic exposure and toxicity.

Excretion

Rapid and extensive renal excretion of 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.