Octadecan-1-ol, ethoxylated, phosphates

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: Assessment based upon available information.

Adequacy of study:

key study

Study period:

May 2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information selected for the toxicokinetic assessment is primarily study data. Studies were conducted inaccordance with recognised testing guidelines.

The substance, Octadecan-1-ol, ethoxylated, phosphates, is a complex combination of mono- and di-phosphate esters of ethoxylated octadecanol, phosphate esters of non-ethoxylated octadecanol, non-esterified ethoxylated octadecanol, and unreacted octadecanol. No more than 10% of other fatty alcohols are present. The physical state of the substanceis white solid pastilles with melting point approximately 33 to 58 deg.C and is not expected to be respirable.

 

The substance is practically insoluble with a measured water solubility of ≤14.5 mg/L. This substance is an Unknown or Variable composition, Complex reaction products or Biological materials (UVCB) with multiple constituents comprised of fairly soluble components, insoluble components, and extremely insoluble components. The partition coefficients (Log Pow) are in the range 2.7 to >6.5, at pH 5.0 using HPLC as described by guideline OECD 117. Using area normalization, 96% of the substance showed a Log Pow of >6.5 at pH 5.0.

These data indicate that the substance is practically insoluble in water and is highly lipophilic, and thus the substance is not bioavailable via the oral route based on Lipinski Rule Oasis of the structure-activity relationship (SAR) analysis. Additionally, the substance did not result in any systemic effects up to the limit doses tested in the oral toxicology studies in rats, including up to 2000 mg/kg in the acute oral toxicity study and up to1000 mg/kg/day in the10-day repeated dose oral range-finding toxicity study and the combined repeated dose oral toxicity study with the reproductive/developmental toxicity screening test. SAR analysis also shows that the substance may be hydrolyzed releasing fatty alcohol ethoxylates and phosphoric acid under basic or neutral condition. The hydrolytic metabolites of the substance, fatty alcohol ethoxylates, might be absorbed through gastrointestinal (GI) tract, however. Alcohol ethoxylates are non-ionic surfactants that are widely used in cosmetics and household laundry and cleaning detergents. A toxicokinetic study of ¹⁴C-labeled C₁₂AE₃, C₁₂AE₆ and C₁₂AE₁₀ in rats was reported.* In the study, the three alcohol ethoxylates were absorbed from the GI tract and the¹⁴C activity was recovered primarily in the urine, but also in the feces and expired air. No parent compounds were detected in the urine. The main materialism of alcohol ethoxylates was a function of chain Length and appeared to be the degradation of the ether linkage and oxidation of the alkyl chain to form ethoxylates of varying length and ultimately CO₂ and water.

 

The extremely low water solubility and very high lipophilicity of the substance also indicate that the substance is not expected to be absorbed via the dermal route, either. The hydrolytic metabolites of the substance, fatty alcohol ethoxylates, may be absorbed through skin, however. In dermal metabolism studies with hairless mice treated with 0.25% laureths in ethanol, the percutaneous absorption decreased with increasing number of ethylene oxide units. Absorbed laureths were rapidly metabolized to CO₂and excreted with expired air. With increasing number of ethylene oxide units, the percentage in expired air was decreased, and the amount excreted in feces and urine increased.+

 

The ready biodegradability test of the substance showed that it was not considered readily biodegradable. The measured test concentrations of the substance in aquatic medium were very low (≤0.67 mg/L) in the acute toxicity test in algae. The substance is therefore expected to have low potential for bioaccumulation in aquatic organisms although the substance is persistent and its Log Pow exceeds 5.

 

In conclusion, based upon the available data, bioavailability of the substance,Octadecan-1-ol, ethoxylated, phosphates,is expected to be limited and the substance has low systemic toxicity.

* HERA, alcohol ethoxylates, 2009, available at https://www.heraproject.com/files/34-F-09%20HERA%20AE%20Report%20Version%202%20-%203%20Sept%2009.pdf

+ CIR, Safety Assemment of Alkyl PEG Ether as Used in Cosmetics. IJT 31(Suppl. 2):169-244, 2012

Conclusions:

In conclusion, based upon the available data, bioavailability of the substance,Octadecan-1-ol, ethoxylated, phosphates,is expected to be limited and the substance has low systemic toxicity.

Description of key information

The toxicokinetic assessment is based upon the available data on the test item contained within this dossier. Data is taken from reliable sources, all rated as a 2 or higher for reliability and relevance according to the Klimisch scale as identified in Klimisch et al,  1997 scale. The toxicokinetic assessment is therefore considered reliable, based upon the information available.

Additional information

Based upon the available data, bioavailability of the substance,Octadecan-1-ol, ethoxylated, phosphates,is expected to be limited and the substance has low systemic toxicity.