Fatty acids, tall-oil, ethoxylated

Endpoint summary

Description of key information

Due to the UVCB nature of the test substance, the good water solubility and the experimental test data, bioaccumulation is not expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic analysis of the UVCB substance fatty acids, tall-oil, ethoxylated (EC 500-150-1)

There are no specific studies available that investigate the toxicokinetic behaviour of the test item. Based on the molecular structure, available data on physicochemical properties as well as on the toxicological profile, a toxicokinetic assessment can be performed.

Physico chemical properties

The test item is an organic substance with unknown or variable composition (UVCB) appearing as highly viscous, yellowish liquid at ambient conditions (20 °C). Since the substance is an UVCB molecular weight is not determinable. Considering a chain length of mainly 18 carbon atoms, a molecular weight of above 250 g/mol can be anticipated. Melting and boiling point of the substance could not be determined. Consequently, determination of vapour pressure was technically not feasible. However, vapour pressure can be anticipated to be below 10E-6 Pa. The test item shows a water solubility with a ratio of 3:7 (3 parts of test substance and 7 parts of water). The n-octanol/water partition coefficient was calculated as 5.97 at 25 °C indicating a lipophilic character of the test substance.

 

Toxicokinetics

Absorption

In principle, uptake of the target substance is expected to be possible. The water solubility and the anticipated molecular weight of the substance favor oral absorption as can be derived from ECHA guidance R7c Table R.7.12-1 (ECHA, 2017). According to the aforementioned guidance document, the logPow of 5.97 is within the favourable range for uptake via micellular solubilisation. However this might only be a possible way in case of eventual unbound fatty acids that might be available in the substance. The structure of the target substance as such might hurdle the enzymatic metabolisation in the gastro intestinal (GI) fluid and hence the adsorption. The structure does not provide any targets for enzymes in the GI fluid to attack. Uptake of the unbound fatty acids might, however, be increased due to the surface active properties of the test substance that might cause irritation in the intestinal tract. However, available oral toxicity data indicated that the ingested fraction is likely to pass the intestine unchanged and to be excreted directly via faeces. It is known that unbound fatty acids that might be absorbed do not lead to any adverse effects. This is supported by the available animal test data. No effects of systemic toxicity were observed in an acute oral toxicity study (BASF, 1971) in rats (LD50 > 10000 mg/kg bw). In the dose range finder as well as in main study of the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD 422 (BASF, 2018), no systemic effects were observed up to the limit dose of 1000 mg/kg bw/d. This indicates that the test item is not likely to become bioavailable. Furthermore, there is no experimental indication that the test item passes the placental barrier and reaches the developing fetus.

The logPow is within the optimal domain for dermal absorption. However, uptake via skin of neat substance is unlikely due to its physical state and molecular weight. This is supported by the fact that no irritation was observed in the in vitro skin and eye irritation studies (BASF, 2017). Furthermore, based on the LLNA study, in which solubilized substance was dermally administered, no irritations or other skin effects were observed as an additional indication for a lack of dermal penetration (BASF 2009).

Exposure via the inhalation route is expected to be neglible since the substance is a highly viscous, wax like liquid at room temperature with an anticipated low vapour pressure. Exposure to an inhalable aerosol may also be unlikely, because the viscous nature of the test substance limits its availability as an inhalable aerosol. In two inhalation risk hazard tests performed at 20 °C in rats, no mortality was observed during 8 hours of constant exposure (BASF, 1971).

Distribution

Based on the physico chemical properties and the results achieved from the comprehensive toxicity testing, only neglible, if any, amounts of the substance are anticipated to become systemically available. Only fractions in the form of unbound fatty acids may be available. Once adsorbed, they will most likely be transported within the body via the blood stream, gain access to the body tissues and are likely to follow the fate of fatty acids distribution and metabolism. Due to the lipophilic properties, the substance might be enriched in body fats if no metabolism and formation of more polar metabolites takes place.

Metabolism

In case neglible amounts of the substance per se may be absorbed they may be transformed within the body by Phase I enzymes while undergoing functionalisation reactions aiming to further increase the hydrophilicity. Furthermore, Phase II conjugation reactions may covalently link an endogenous substrate to the absorbed chemical, the respective Phase I metabolites or to the OH groups of the parent molecule in order to ultimately facilitate excretion. The substance is most likely not enzymatically activated (toxified) during metabolism. This assumption is supported by the cytotoxicity results of the available mutagenicity studies. The cytotoxicity of the test substance was not higher as compared to the metabolically activated test substance.

Excretion

Based on the chemicals characteristics, excretion via urine can be regarded as negligible for the test compound. Biliary excretion is assumed to be the major way of excretion.

Conclusion on toxicokinetics

Based on the available data it can be concluded that the likelihood of the substance of becoming bioavailable via the oral and dermal route can be regarded as neglible, if any. The structure of the substance does not provide any targets for enzymes in the GI fluid to attack. When fractions may be taken up by the oral route, unbound fatty acids of the UVCB substance are likely to be absorbed through the walls of the gastrointestinal tract by micellular solubilisation to a limited extent. The physicochemical properties do not favour dermal absorption. Considering the low vapour pressure and the physico chemical nature of the UVCB substance, it is regarded as non-inhalable under normal use conditions. Metabolic conversion is expected by Phase I and Phase II enzymes. Based on the chemical characteristics biliary excretion is assumed to be the major route. Bioaccumulation is not expected.

 

References

ECHA (2017), Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

Marquardt H., Schäfer S. (2004) Toxicology. Academic Press, San Diego, USA, 2nd Edition.

BASF (1971), Ergebnis der Gewerbetoxikologischen Vorprüfung

BASF (2009), Murine Local Lymph Node Assay (LLNA)

BASF (2017), In vitro Skin Irritation and Corrosion Turnkey Testing Strategy

BASF (2018), Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Wistar Rats Oral Administration (Gavage)