Hexadecyl acetate

Endpoint summary

Description of key information

Minimal absorption via oral, dermal or inhalation routes of exposure has been predicted based on the experimental data, physico-chemical properties of the substance and expected use patterns. Any absorbed test item is expected to be widely distributed through the body and will undergo metabolism and clearance similar to other natural saturated fatty acids. The substance will not bioaccumulate.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Physico-chemical properties

 

The test item is a monoconstituent substance with a molecular weight of 284.48 g/moL. The material is a white waxy solid (melting point 20.6 to 30.3 °C) with a determined water solubility of 0.0114 mg/L. Investigation of octanol/water partition coefficient gave a Log Kow value of 8.66 (which is > 4, the bioaccumulation limit), and the vapour pressure is low (0.0048 Pa at 25 °C). The substance is not known to have surface active properties.

 

Absorption

Oral route

 

Passive diffusion (transcellular) and passage through the aqueous pores (paracellular) are the primary absorption mechanisms of molecules from the gastro-intestinal (GI) tract. Key physico-chemical properties that determine the mechanism of absorptionare molecular weight (MW), Log Kow and aqueous solubility. Log Kow values in the range of 0 - 3 and a MW less than 500 g/moL favors paracellular transport. Molecules that pass through transcellular route aresmall (molecular weight up to around 200 g/moL) water-soluble molecules. 

 

Based on these considerations, the test item is expected to be poorly absorbed from the GI tract because of the low aqueous solubility, and a high Log Kow value (8.66). It can be concluded that oral bioavailability of the substance is expected to be low. However, chemical structure suggests that the substance is an acetate ester of a saturated fatty alcohol (cetyl alcohol) and ester linkage can undergo hydrolytic cleavage in the intestinal fluids or GI epithelium. This may result in the formation of acetic acid and the respective fatty alcohol, which could then be absorbed in to the systemic circulation.  

 

Inhalation route

 

Volatility, aqueous solubility and Log Kow values determine the inhalation uptake. The test item is a waxy solid at room temperature. However since it has a low melting point (< 30.3^oC), the potential for exposure through inhalation route exists under extreme conditions. The substance is poorly water soluble, will not readily dissolve into the mucus lining of the respiratory tract, and the high log Kow value indicates it will not be absorbed directly across the respiratory tract epithelium. However, since the substance is an ester, it has the potential to undergo hydrolytic cleavage to acetic acid and the respective fatty alcohol (cetyl alcohol) by enzymes in the lung mucosa, which may then cross the alveolar membrane barriers.

Dermal route

The skin absorption rate of molecules with a Log Kow value in the range of < -1 or > 4 and the molecular weight of > 500 g/moL is considered low. The substance is expected to be poorly absorbed through the skin considering its poor water solubility and the relatively high Log Kow.

 

Distribution

 

The extent of distribution of molecules is affected by molecular weight, lipid solubility, pKa, and plasma protein binding (PPB). Molecules that are lipophilic at pH 7.4 and high plasma protein binding are likely to have high volume of distribution (Vd). Physicochemical properties that influence PPB include lipophilicity and pKa. In general, chemicals with high lipophilicity and/or ones with acidic character will have a greater degree of PPB, than more hydrophilic or basic compounds.

 

Once absorbed, the test item is expected to have a high volume of distribution due to its high Log Kow value. Thiscan cause initial partitioning into highly vascularized lipid rich areas preferentially with subsequent slow redistribution into body fat, where they may remain for long periods of time.However, since the substance is an ester, it has the potential to undergo hydrolytic cleavage to acetic acid and cetyl alcohol by hydrolytic enzymes in the plasma which could limit the potential for high distribution in to the tissues.

 

Metabolism and excretion

 

The substance is an ester of long chain fatty alcohol,cetylalcohol and acetic acid. The ester bonds can undergohydrolysis by esterasesin vivo, resulting the formation of cetyl alcohol and acetic acid. Long-chain aliphatic alcohols such as cetyl alcohols can be further oxidized to their corresponding fatty acids in mammalian tissues followed by metabolism and clearance similar to other natural saturated fatty acids. (Ref:Final Report on the Safety Assessment of cetearyl Alcohol, Cetyl Alcohol, lsostearyl Alcohol, Myristyl Alcohol, and Behenyl Alcohol, J. American College of toxicology, Vol7, 1988).

 

Conclusion

A qualitative judgement on the toxicokineticbehaviour of the test item was made based on the physico-chemical characteristics. The substance is an ester of long chain fatty alcohol, cetyl alcohol and acetic acid. It is expected to be poorly absorbed via the oral, dermal and inhalation routes. The test item is also expected to be widely distributed through the body and can undergo ester hydrolysis in the biological fluids/tissues to form acetic acid and cetyl alcohol. Cetyl alcohol can be further oxidized in the mammalian tissues to the respective fatty acids, which canundergo metabolism and clearance similar to other natural saturated fatty acids.