9-Octadecen-1-ol, (Z)-, phosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2013-05-06

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Expert statement according to ECHA Guidance 2008, chapter R.7c

Test material

Test material information

Constituent 1

Reference substance name:

9-Octadecen-1-ol, (Z)-, phosphate

EC Number:

253-455-4

EC Name:

9-Octadecen-1-ol, (Z)-, phosphate

Cas Number:

37310-83-1

Molecular formula:

C18H37O4P

IUPAC Name:

[(9Z)-octadec-9-en-1-yloxy]phosphonic acid

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

ORAL ABSORPTION

The reaction product of oleyl alcohol is poorly water soluble independent of the pH and will not readily dissolve into the gastrointestinal fluids. Suitably in addition the log Pow of the main compound oleyl phosphate is above 4. Therefore, even if the molecular weight of the main compound is below 500 g/mol and the phosphate group is ionisable the oral absorption is not favoured.

With regard to toxicological data, a study in rats revealed an LD50 value above 2000 mg/kg bw (limit dose). In a 14 day dose range finder study and the related subacute 28 day study no signs of systemic toxicity were observed up to the highest test concentration of 1000 mg/kg bw/day.

Taken together, due to its physico-chemical properties, primarily the low water solubility, and the absence of systemic toxicity in acute and subacute studies the oral absorption is expected to be negligible.

DERMAL ABSORPTION

The physico-chemical properties of the reaction product of oleyl alcohol with polyphosphoric acid do not favour dermal absorption. The low water solubility of the test item below 1 mg/L makes dermal uptake unlikely since the substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. The surface tension as a parameter for dermal absorption was not determined because of the low water solubility. Molecular weights less than 100 g/mol favour the dermal uptake; the molecular weight of the main compound oleyl phosphate is 348.47 g/mol. In addition, the log Pow of the main compound is above 4. Therefore, transfer between the stratum corneum and the epidermis is limited.

Consequently, an acute systemic dermal toxicity test with the reaction product of oleyl alcohol with polyphosphoric acid in rats did not reveal that toxicological relevant amounts were absorbed into the systemic circulation. Here, no systemic effects were observed and the LD50 was determined to be greater than 2000 mg/kg bw (limit dose).

Taken together, based on its physico-chemical properties and absence of toxicity in an acute dermal toxicity study very limited absorption into the systemic circulation is expected after dermal application.

RESPIRATORY ABSORPTION

Considering the very low vapour pressure, the resulting low volatility of the high viscous liquid it is unlike that the substance will be inhaled either in vapour form or as dust particles under use conditions.

Details on distribution in tissues:

Since the absorption is expected to be very low the assessment of the distribution of the poorly water soluble reaction product of oleyl alcohol with polyphosphoric acid is not considered to be relevant. According to this no signs of systemic toxicity and no target organs were observed in acute and subacute toxicity studies in rats.

Details on excretion:

The absorption is expected to be very low, thus, the reaction product of oleyl alcohol with polyphosphoric acid will be likely be excreted on the faecal route after oral exposure.

Metabolite characterisation studies

Details on metabolites:

Due to the very low absorption the assessment of the metabolism and the accumulation potential of the poorly water soluble reaction product of oleyl alcohol with polyphosphoric acid is not considered to be relevant. According to this no signs of systemic toxicity and no target organs were observed in acute and subacute toxicity studies in rats. If low amounts will be systemically available metabolism pathways which mediates the chain degradation of the fatty acid by esterases and β-oxidation are likely.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
In accordance with the Guidance on Information Requirements and Chemical Saftey Assessment, chapter R.7c (ECHA, 2008) the profile on basic toxicokinetics of the reaction product of oleyl alcohol with polyphosphoric acid was derived from its physico-chemical data and toxicological data.

Due to its physico-chemical properties, primarily the low water solubility, and the absence of systemic toxicity in acute and subacute studies the oral absorption is expected to be negligible.

Based on its physico-chemical properties and absence of toxicity in an acute dermal toxicity study very limited absorption into the systemic circulation is expected after dermal application.

Considering the very low vapour pressure, the resulting low volatility of the high viscous liquid it is unlike that the substance will be inhaled either in vapour form or as dust particles under use conditions.

Since the absorption is expected to be very low the assessment of distribution, metabolism, accumulating potential and excretion of the poorly water soluble reaction product of oleyl alcohol with polyphosphoric acid is not considered to be relevant. According to this no signs of systemic toxicity and no target organs were observed in acute and subacute toxicity studies in rats.