Propylidynetrimethanol, ethoxylated, propoxylated, esters with acrylic acid (<6.5 mol EO and <6.5 mol PO)

Endpoint summary

Description of key information

Based on physico-chemical properties, absorption via inhalation, oral or dermal exposure is limited.

Bioaccumulation of the substance is not expected after continuous exposure. There are no indications for a metabolic activation of the substance resulting in metabolites more reactive than the parent compound. The test substance and/or its metabolites are expected to be predominantly excreted via feces and to a lower extent via urine or by exhalation.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no studies available for the determination of toxicokinetics or dermal absorption.

The substances is a liquid with a weight average molecular weight of 490 g/mol and a vapour pressure of 0.001 Pa at 25 °C. In agreement with its log Pow of 4.2, only 200 mg of this rather lipophilic substance can be dissolved in one liter of water.

 

Absorption

Oral absorption of the lower molecular weight fraction of the compound (molecular weight below 500) is expected. The log Pow just above 4 and a water solubility above 1 mg/L might not favor, but also do not impair oral uptake. Absorption of the higher molecular weight fraction (< 1000, > 500) might be limited due to its increasing molecular weight and log Pow. No systemic toxicity was observed after acute and repeated oral exposure. It is assumed, that this is because of the non-toxicity of the compound, rather than because of limited uptake in the GI tract.

 

Based on the very low vapour pressure of <1E-5 hPa, inhalation exposure is considered to be negligible. Furthermore, if respiratory uptake occured, it might be partially limited by the lipophilic properties of the test substance.

 

Considering the physical chemical properties and results from toxicological studies, dermal absorption of the test substance seems possible, but might not occur to a high degree. A molecular weight close to 500 g/mol is still sufficiently small for dermal uptake. But the log Pow slightly above 4 combined with a rather low water solubility might also lead to at least partial retention of the substance in the stratum corneum, from where it is sloughed off with skin cells instead of being systemically available. This is consistent with the fact, that no sensitization, irritation or acute toxicity was observed after dermal exposure.

Distribution

In general, molecules with a high molecular weight exhibiting a low water solubility are not very likely to distribute through-out the body. Though a log Pow of 4.2 might be an indicator for bioaccumulation, no systemic toxicity was observed after exposure for 90 days. In addition, calculation performed using CATALOGIC v.5.11.2, BCF base-line model v2.05., T.E.S.T. (provided by the US EPA), and BCFBAF v.3.01 of EPISuite v4.10 indicate no significant bioaccumulation of the test compound and its major components. A passage over the placental barrier cannot be excluded. However, no effect on prenatal developmental toxicity is expected based on the low general toxicity of the substance and no effects on developmental toxicity were observed in a screening study (OECD 422).

 

Metabolism

The substance is considered to be stable in water and hydrolysis is not considered to play an important role in the fate of the substance. However, hydrolysis or enzyme-catalyzed cleavage of the acrylic acid ester bond might occur to some extent resulting in acrylic acid which in turn is mainly oxidized to carbon dioxide.

No metabolic activation of the substance is expected but rather the opposite based on the results of the micronucleus assay in vitro where a positive result was only obtained in the absence of the S9-mix. This assumption is further supported by the negative results in the available micronucleus assays in vivo from read-across substances. In addition, in the mammalian cell based genotoxicity assays cytotoxicity of the test substance was apparent at lower concentrations in the absence of the S9-mix.

 

Excretion

In general, excretion via feces is favored by high molecular weight (above 300 g/mol in the rat) and low water solubility. Therefore, the high-molecular weight fraction of the substance is expected to be excreted mostly via feces whereas the lower ones are predominantly excreted via urine due to their smaller molecular weight and increasing polarity. Carbon dioxide as a product of acrylic acid metabolism is exhaled.