2-Propenoic acid, heptadecyl ester, branched

Endpoint summary

Description of key information

Gastro-intestinaI-, respiratory- and dermal absorption of 2-propenoic acid, heptadecyl ester branched to a major extent is not expected due to its physico-chemical properties (log Pow: > 9.2; water solubility: < 0.30 µg/L, molecular weight: 310.5 g/mol). In addition, bioaccumulation is unlikely due to metabolism and a very limited absorption of the substance.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Physical chemical properties

2-Propenoic acid, heptadecyl ester, branched is a liquid with a molecular weight of 310.5 g/mol. The extrapolated log Pow value is 9.2 at 25 °C and the solubility in water is < 30 µg/L at 20 °C. No data on hydrolysis and surface tension are available since the substance is poorly soluble. The vapour pressure of the substance is 0.0000266 hPa at 20 °C. These physico-chemical properties of the substance will enable qualitative judgements of the toxicokinetic behaviour (Guidance on information requirements and chemical safety assessment Chapter R.7.c, R.7.12 Guidance on Toxicokinetics).

Absorption:

GI absorption

Based on the molecular weight, the high log Pow and a low water solubility the substance is not very likely to be absorbed in the GI tract. The log Pow of > 6 indicates that it will not diffuse well across plasma membranes. In addition, gastro-intestinal absorption will not be triggered by passage via passive diffusion through aqueous pores or carriage with the bulk passage of water, which is favoured for small (molecular weight < 200 g/mol), water soluble substances. The substance may be taken up by micellular solubilisation since this mechanism may be of particular importance for highly lipophilic compounds (log Pow > 4), particularly those that are poorly soluble in water. Overall, limited gastrointestinal absorption is expected based on its physicochemical properties. In addition, no acute toxic effects were observed in rats orally dosed up to 2000 mg/kg/bw. Moreover repeated dose studies (OECD 422) are available for structural analogues Behenylacrylate (Acrylate 22 45%) (CAS 85085-17-2) and Laurylacrylate 1214 (CAS 84238-60-8). No systemic effects were seen in these repeated dose toxicity studies after oral administration demonstrating and supporting that 2-propenoic acid, heptadecyl ester, branchedis not likely to be well absorbed in the gastrointestinal tract.

Dermal absorption

As the substance is a liquid with very low water solubility (< 30 µg/L), a molecular weight of 310.5 g/mol and a log Pow of > 6, dermal absorption is expected to be low. In addition, no effects were observed when tested for acute dermal toxicity. On the other hand, skin irritating properties may lead to a dermal absorption to a small extent. No skin irritation was observed in an in vitro assay however the substance is harmonized classified as a skin irritant cat. 2. Experiments with Lauryl methacrylate (Dodecyl methacrylate )(CAS 142-90-5) with rat skin have demonstrated that the long-chain methacrylate esters in principle are dermally absorbed at very low amounts (0.26 % over 24 h). (Jones, 2002) As a tendency confirmed with experiments on esters up to a chain length of C8, absorption decreased with increasing ester chain length. Due to the slow diffusion and the metabolic competency of the skin, the ester underwent complete hydrolysis to methacrylic acid and the long-chain alkyl alcohol (Jones, 2002) .

Respiratory absorption

No experimental data are available for respiratory absorption. The substance exhibits a low volatility (vapour pressure of 0.0000266 hPa). Therefore, only a very minimal amount of the substance is available for inhalation. However, exposure is possible when inhaling aerosols. As the log Pow of the substance is high and the water solubility is very low, absorption via inhalation would be limited.

Metabolism

Esters are supposed to be rapidly hydrolysed in local tissues as well as in blood by carboxyl esterases (high activity within many tissues and organs like liver, GI tract, nasal epithelium and skin) forming acrylic acid and the respective alcohol. However, the kinetics strongly depends on water solubility. In addition, it cannot be excluded that the long C-chain might hinder the enzyme to access to the ester bound. There is a trend towards increasing half-life of the esters in blood with increasing alcohol chain length (Jones 2002).

Nevertheless for all acrylate esters a relatively fast hydrolysis can be assumed as systemically absorbed parent esters will be effectively removed during first pass through the liver resulting in their relatively rapid elimination from the body. The primary metabolite acrylic acid is subsequently cleared rapidly from blood and this metabolism occurs by standard physiological pathways with the majority being exhaled as CO2. The respective alcohol is also predominantly cleared via the liver. In the organism, the acid is further metabolised via the valine pathway of the citric acid cycle. The alcohol will be further metabolised by the two standard metabolic pathways for fatty alcohols (1: oxidation: fatty alcohol -> aldehyde -> acid, and subsequently CoA-mediated fatty acid metabolism or 2: glucuronidation of the alcohol and excretion).

Distribution

As the expected bioavailability is very low that means neither GI- and respiratory absorption nor dermal absorption to a more than minimal extent are expected and complete metabolism is predicted, only a very low amount of the substance comes into consideration for distribution in blood or plasma and accumulation in organs and tissues. In theory the lipophilic molecule is likely to distribute into cells and then the intracellular concentration may be higher than extracellular concentration particular in fatty tissues, but this is of secondary importance as the bioavailability of the substance is very low.

Accumulation

In principle, accumulation in adipose tissue could be expected as the calculated log Pow is > 6, but before that it is expected to be completely metabolized due to rapid cleavage by esterases as described above.

Excretion

As absorption is very low respectively not expected and complete metabolism is very fast, excretion of the parent compound is not to be expected.