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Description of key information

Based on the physicochemical properties and the results obtained in the toxicity tests, the substance will most likely be absorbed via the GI tract and become systemically available.
Uptake into the systemic circulation following dermal exposure is very limited due to high water solubility of the substance at room temperature. Also, based on the high water solubility and the results obtained in the respective toxicological investigation, it is unlikely that relevant amounts of the substance will become systemically bioavailable via inhalation.
After becoming bioavailable, it is assumed that the substance will circulate within the blood stream and will finally be transported to the liver where Phase I and Phase II metabolism may occur. Ultimately the metabolism products will be excreted via the kidney in the urine.
Based on its PC values the substance is not considered to be bioaccumulative.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No study is available in which the toxicokinetic properties (distribution, metabolism, elimination) of Octadecanoic acid, sulfo-, potassium salt were investigated.

The expected toxicokinetic behaviour is derived from the physicochemical properties, the results from the available toxicological studies and the available literature following the information given in guidance document 7c.

 

Physico-Chemical Data

 

The organic reaction product composed of Octadecanoic acid, sulfo-, potassium salt appears as a powder in water clear brownish liquid at standard ambient temperature and pressure.

The molecular weight of the reaction product is 440 g/mol. The log pow of -1.3 is used for kinetic assumption.

The test item is miscible with water at room temperature in a concentration of <= 80.33 g/L

 

Toxicokinetic analysis

 

Absorption

 

Oral route:

Following oral intake, and once in contact with the digestive fluids of the stomach, it is assumed that the substance will not degrade.

Due to the high water solubility and the low logPow of the product, systemic uptake via passive diffusion is possible within the gastro intestinal (GI) tract. Furthermore, water soluble chemicals will readily dissolve into the GI fluids which in turn enhance the contact with the intestinal mucosa. 

 

More detailed information relating to the bioavailability of the reaction product into systemic circulation following oral intake can be derived from a subacute combined repeated dose toxicity study with the reproduction and developmental toxicity screening test (OECD 422) with the product. Here, results indicate that the substance reaches the systemic circulation following oral administration.

Overall, based on the physicochemical properties and the results obtained from the oral toxicity testing it can be assumed that the substance or its metabolites becomes systemically available following oral intake.

 

 

Dermal route:

Based on the good water solubility of the reaction product, dermal uptake is negligible. Its is commonly known that substances with a water solubility above 10 g/L are too hydrophilic to cross the lipid rich environment of the stratum corneum. These assumptions, based on the physicochemical properties, are further supported by results achieved from an acute dermal toxicity study with the substance performed on rats. During these studies, no systemic effects were observed and the LD50 was determined to be > 2000 mg/kg bw (limit dose). Also, no skin irritation potential is seen and also no immunological response were observed in a Murine Local Lymph Node Assay (LLNA) (OECD 429) with a close homolog.

Overall, the results from the dermal toxicity and sensitization testing do not suggest that toxicological relevant amounts of the reaction product are absorbed and become systemically available and consequently support the assumptions based on the substance’s physicochemical properties.

 

Inhalation route:

The substance is a powder with a low vapour pressure and the resulting low volatility. Therefore, an inhalation at room temperature is considered to be negligible.

Distribution

 

Once absorbed it is expected that the reaction products and its metabolites are distributed within the blood stream. Here the transport efficiency to the body tissues is limited by the rate at which the highly water soluble substances cross cell membranes. More specifically, access to the central nervous system or the testes is likely to be restricted by the blood-brain and blood-testes barriers (Rozman and Klaassen, 1996). The results observed in a subacute toxicity study provide evidence that a transport to the liver and kidney occurs. Due to the high watersolubility and the low log pow a accumulation is unlikely. 

 

Metabolism


Based on the chemical structure, the substance may be metabolized by Phase I enzymes. More specifically, based on the chemical structure a hydroxyl group is likely to be introduced by cytochrome P450 mediated oxidative de-alkylation. Furthermore, Phase II conjugation reactions may occur which covalently link an endogenous substrate to the reaction product itself or to its Phase I metabolites in order to ultimately facilitate excretion.

 

Excretion

 

Based on the expected biotransformation reactions, molecular size and water solubility, it is most likely that the final metabolites are excreted via the urine. Fractions of the chemical which are not absorbed within the GI tract will be readily excreted via the faeces.

 

Summary

 

Based on the physicochemical properties and the results obtained in the toxicity tests, the substance will most likely be absorbed via the GI tract and become systemically available.

Uptake into the systemic circulation following dermal exposure is very limited due to high water solubility of the substance at room temperature. Also, based on the high water solubility and the results obtained in the respective toxicological investigation, it is unlikely that relevant amounts of the reaction mass will become systemically bioavailable via inhalation.

After becoming bioavailable, it is assumed that the substance will circulate within the blood stream and will finally be transported to the liver where Phase I and Phase II metabolism may occur. Ultimately the metabolism products will be excreted via the kidney in the urine.

Based on its PC values the constituents of the reaction mass are not considered to be bioaccumulative.



References

 

ECHA (2008), Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

 

Marquardt H., Schäfer S. (2004). Toxicology.Academic Press,,, 2nd Edition 688-689.

 

Mutschler E., Schäfer-Korting M. (2001) Arzneimittelwirkungen. Lehrbuch der Pharmakologie und Toxikologie. Wissenschaftliche Verlagsgesellschaft, Stuttgart.

 

Rozman K.K., Klaassen C.D. (1996) Absorption, Distribution, and Excretion of Toxicants.In Klaassen C.D. (ed.) Cassarett and Doull's Toxicology: The Basic Science of Poisons.McGraw-Hill, New York.

 

Bonse G., Metzler M. (1978) Biotransformation organischer Fremdsubstanzen. Thieme Verlag, Stuttgart.