tert-pentyl 2-ethylperoxyhexanoate

Endpoint summary

Description of key information

Based on physico-chemical characteristics, particularly water solubility, octanol-water partition coefficient and vapour pressure, limited to moderate absorption by the dermal and inhalation routes are expected. Absorption following oral exposure is anticipated moderate to high. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Absorption and Distribution :

Tert-amylperoxy-2-ethylhexanoate (TAPEH) is a colourless refrigerated liquid with a molecular weight of 230.3 g/mol. The substance is only slightly soluble in water (17.6 mg/L at 20°C). The logKow of TAPEH was measured to be 4.56 at 25°C. Based on this log Kow a BCF of 3.2 L/kg was calculated. TAPEH has a low vapour pressure of 0.019 Pa at 20 °C (DSC method) and is degraded hydrolytically. The hydrolysis by-products have not been identified but are expected to be tert-amyl alcohol and 2-ethylhexanoic acid or 2-ethylhexanol. At 37 °C, the half-life time seems to decrease with the pH: t1/2 is 15.3 h at pH 9, and 29 h at pH 7. There is currently no data at pH 4 and 7 at 37 °C, but the preliminary test performed at these pH, 50°C for 5 days, has shown a strong hydrolysis. Regarding the available hydrolysis data, hydrolysis at pH 4 and 1.2 are expected, but should remain negligible during the first hours. 

Oral absorption is favoured for molecular weights below 500 g/mol. Based on the high logKow of 4.56, TAPEH can be regarded as a lipophilic substance. Such a lipophilic compound may be taken up by micellular solubilisation. This mechanism may be of particular importance for TAPEH, as the substance is only slightly soluble and would otherwise be poorly absorbed. As TAPEH showed slight effects at 1000 mg/kg bw/day in a 28-day study by oral, it can be assumed that absorption across the gastrointestinal tract epithelium occurs, even if the observed effects were non-adverse.

Based on the low vapour pressure of 0.019 Pa at 25 °C, inhalation exposure is not likely. Nevertheless, if the substance reaches the lung, TAPEH may be absorbed by micellular solubilisation (see above). The low water solubility may enhance penetration to the lower respiratory tract. Together, this indicates low systemic availability after inhalation and if bioavailable, toxic effects via this route of administration will occur only at very high concentrations.

Similarly, based on physical-chemical properties of TAPEH, the substance is not likely to penetrate skin to a large extent as the high logKow and the low water solubility do not favour dermal penetration. Between water solubility of 1-100 mg/l absorption is anticipated to be low to moderate. For substances with a log Kow between 4 and 6, the rate of penetration is limited by the rate of transfer between the stratum corneum and the epidermis. Only the uptake into the stratum corneum should be high. Furthermore, TAPEH is not irritating to rabbit skin. Applied to the skin of guinea pigs, sensitising effects were observed, indicating that at least small amounts of the substance will become available in the body. However, the effects noted might also be linked to reaction by-products between TAPEH and molecules present in the skin.

When reaching the body, TAPEH may be distributed into cells due to its lipophilic properties and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. Based on its relatively high BCF value TAPEH may also be considered to bioaccumulate in the human body. However, it is suspected that TAPEH does not reach the blood without hydrolysing (enzymatically or hydrolytically) to its degradation products which will have lower BCF (tert-amyl acohol and 2-ethylhexanoic acid or 2-ethylhexanol).

Metabolism:

Based on the structure of the molecule and its nature, metabolism to more toxic metabolites can not completely be excluded in the human body. This is in compliance with the results obtained in the one Ames test showing only positive effects with S9 activating metabolising system.

Excretion:

As discussed above TAPEH is expected to be hydrolysed enzymatically in products having lowest molecular weight, allowing them to be excreted via the urine.