2-Propylheptyl octanoate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

0.12

Additional information

A specific study on the toxicokinetic properties, i.e. absorption, distribution, metabolism, elimination, of Propylheptylcaprylate (PHC) is not available. The expected toxicokinetic behaviour is derived from the physicochemical properties, the results from the available toxicological studies and the available literature following the information given in guidance document R.7c.

Absorption:

In general, the poor water solubility in conjunction with the high log Kow of 9 indicates a low potential for absorption.

Oral/GI absorption:

PHC is a liquid with ionisable groups. Its molecular weight of 285 favours absorption. However, the poor water solubility in conjunction with the high log Kow of 9 indicates a low potential for absorption in the gastro-intestinal tract. While the standard absorption mechanisms are unlikely, uptake via micellular solubilisation may be possible. As PHC was stable in a hydrolysis test it is assumed that the major circulating substance is the parent compound. However, the structure of the substance suggests a slow hydrolysis into propylheptanol and caprylic acid, which might have different toxicokinetics.PHC did not show any signs of systemic oral toxicity. In a subchronic oral toxicity study indications of systemic bioavailability, i.e. increased liver weight anddecreased pH of the urine,were observed for high doses. However, no conclusion on the extent of bioavailability can be drawn.

Respiratory absorption/Inhalation:

PHC has a low vapour pressure, so that its availability for inhalation is very limited. The poor water solubility in conjunction with the high log Kow of 9 indicates a low potential for absorption. While the standard absorption mechanisms are unlikely, uptake via micellular solubilisation may be possible. Being poorly water soluble, PHC may, however, enter the lower respiratory tract.

Dermal absorption:

The molecular weight of PHC does not favour dermal uptake, but does also not to allow to exclude it. PHC features no structural groups that may bind to skin components. The poor water solubility in conjunction with the high log Kow of 9 indicates a low potential for absorption. In particular, due to the high log Kow the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. These considerations based on physico-chemical properties were confirmed in an in vitro dermal penetration study, in which the mean dermal penetration was determined to be 0.12%. This is in line with a dermal acute toxicity study which showed no signs of systemic toxicity. In a skin irritation study, however, moderate erythema was induced indicating some absorption into the upper skin layers.

Distribution:

The poor water solubility in conjunction with the a molecular weight that does not favour distribution indicate a low potential for distribution. Being very lipophilic, PHC man be transferred into cells. The available toxicity data do not suggest any specific target organ.

Accumulative potential:

Based on the physico-chemical information the main site of accumulation is assumed to be the adipose tissue as well as skin (stratum corneum). No accumulation in bone or in lung is predicted.

Metabolism:

Due to the chemical nature of the substance it is supposed to be easily cleaved into the respective acid and alcohol, i.e.caprylic acid and propylheptanol. Decrease in the pH of urine may indicate metabolism into acidic molecules, such as caprylic acid.

Reactivity:

Available studies on genotoxicity are negative, i.e. there is no indication of a reactivity of PHC or its metabolites under the test conditions.

Excretion:

Although the poor water solubility does not suggest excretion via the urine, based on the molecular weightand the dose dependent decrease of the pH of the urine in the repeated dose study the major route of excretion can be expected to be via kidney/urine. Due to the lipophilicity of PHC excretion maybe also be possible via breast milk, salvia, sweat and via exfoliation. In contrast, no excretion via exhalation is expected.