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Description of key information

Octyl phosphate potassium salt is expected to dissociate to potassium and octyl phosphate esters in an aqueous environment and the octyl phosphate esters are further expected undergo hydrolysis to octanol and phosphate via phosphoesterases. The absorption of the biotransformation products of octanol, phosphate and potassium is assumed to be 100% by oral, dermal and inhalation routes of exposure.  These biotransformation products are expected to be widely distributed throughout the body. The aliphatic alcohol octanol would undergo oxidation, glucuronidation or sulfonation metabolism. The phosphate and potassium would be incorporated into the body’s normal physiological processes and ultimately excreted via the urine and feces. The octanol would be exhaled if oxidized completely to carbon dioxide or excreted in the urine following glucuronidation or sulfonation.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

To date, no relevant analytical toxicokinetic testing data has been generated for octyl phosphate potassium salt. However, toxicological information is available from in vitro testing and in vivo oral exposure of octyl phosphate potassium salt and information on the physicochemical properties can be used as a basis for the assessment to toxicokinetics.

Absorption

The diffusion of a substance across biological membranes in a test species is governed by the physicochemical properties of the substance, particularly its molecular weight, log P and water solubility (ECHA, 2017). For the UVCB octyl phosphate potassium salt, the molecular weight ranges from ≥ 214 to 322 g/mol, the log P is < 0.30, and the water solubility is > 400000 mg/L.

Biotransformation is a major consideration which can greatly affect the absorption of a substance. Octyl phosphate potassium salt is expected to dissociate topotassium and octyl phosphate estersin an aqueous environment and the octyl phosphate esters are further expected undergo hydrolysis to octanol and phosphate via phosphoesterases. The ultimate biotransformation products would be octanol, phosphate and potassium. Phosphate and potassium are endogenous compounds within the body; therefore, the exogenous phosphate and potassium originating from the dissociation and hydrolysis of the octyl phosphate potassium salt will be absorbed and incorporated within the body in a similar manner as the endogenous forms. The absorption of the octanol need only be further considered when this biotransformation step occurs.

Oral

The registered substance is expected to dissociate prior to ingestion as it is marketed as a solution. Solid forms of the registered substance are expected to undergo spontaneous dissociation and hydrolysis by phosphatases in the aqueous environment of the gastrointestinal tract. The oral absorption rate of the octanol biotransformation product is significantly increased by its smaller molecular weight. To further assess the absorption potential of the octyl phosphate potassium salt via the oral route, several toxicology studies are taken into consideration. Neither the acute nor the repeated dose (subacute) toxicity studies showed any significant systemic toxicity (Charles River, 2018; Charles River, 2019). The toxicity testing results are consistent with the low hazard of the expected biotransformation products i.e., octanol, phosphate and potassium. In the absence of specific absorption data and consideration of the physicochemical properties of the biotransformation products, a default value for oral absorption of the registered substance is set as 100%.

Inhalation

The following physicochemical properties need to be considered to predict respiratory absorption: vapour pressure; particle size; log P; water solubility; and hydrolysis information (ECHA, 2017). Octyl phosphate potassium salt has a low volatility with an estimated vapour pressure of ≤ 0.0000858 Pa at 20 °C based on the Modified Watson Correlation and the decomposition prior to melting temperature of 325 °C. The low volatility would indicate that octyl phosphate potassium salt is not available as a vapour for inhalation. While pure octyl phosphate potassium salt is a solid, it is marketed as a solution; therefore, there would be no inhalable or respirable particles to consider.

In general, water soluble aerosols would readily diffuse/dissolve into the mucus lining the respiratory tract. Lipophilic substances (Log P > 0) would have the potential to be absorbed directly across the respiratory tract epithelium. However, complete dissociation and subsequent phosphodiesterase-mediated hydrolysis is expected to occur if aerosol droplets of the registered substance are inhaled and contact the airway mucus. The octanol biotransformation product has more potential to be absorbed via the respiratory tract due to a much lower molecular weight compared to the parent substance. Subsequently absorption via inhalation is comparable to the oral route and a default value for inhalation absorption is set as 100%. 

Dermal

The water solubility of > 400000 mg/L and the Log P value of < 0.3 suggests octyl phosphate potassium salt may be too hydrophilic to cross the lipid rich environment of the stratum corneum. However, in vitro testing, supported by experience during manufacturing, indicate that octyl phosphate potassium salt is a skin irritant (XCellR8 Ltd., 2018) and the surface tension of a 1000 mg/L solution of 38.6 mN/m (Goulston Technologies, 2018) indicates the substance is a surfactant. Skin irritants and surfactants enhance skin penetration, therefore dermal absorption cannot be precluded based solely on the water solubility and Log P values. As there are no in vivo dermal toxicity studies to consider, the default value of 100% dermal absorption will we considered for risk assessment purposes.

Distribution

The octyl phosphate potassium salt biotransformation products of octanol, phosphate and potassium are expected to be widely distributed throughout the body.

Metabolism

Octyl phosphate potassium salt is expected to dissociate to potassium and octyl phosphate esters in an aqueous environment and the octyl phosphate esters are further expected undergo hydrolysis to octanol and phosphate via phosphoesterases. The biotransformation products would be octanol, phosphate and potassium. This prediction is consistent with the low hazard of these expected biotransformation products which is further supported by the lack of any significant systemic toxicity reported in either the acute or the repeated dose (subacute) toxicity studies (Charles River, 2018; Charles River, 2019).

The phosphate and potassium would be utilised within the body by normal physiological processes. The aliphatic alcohol octanol would undergo oxidation with cytochrome P450, alcohol dehydrogenase, or catalase; undergo glucuronidation with UDP-glucuronosyltransferase; or undergo sulfonation with sulfotransferase (Klaassen, 2013).

Excretion

The biotransformation products phosphate and potassium would be incorporated into the body’s normal physiological processes and ultimately excreted via the urine and feces. The biotransformation product octanol would be exhaled if oxidized completely to carbon dioxide or excreted in the urine following glucuronidation or sulfonation. This excretion pattern supports a conclusion of no bioaccumulation potential.

References

Charles River (2018). An Acute Study of 1-Octanol, reaction products with phosphorus oxide (P2O5), potassium salts by Oral Gavage in Rat (Acute Toxic Class Method. Study No. 20153212. See this IUCLID dossier 7.2.1.

Charles River (2019). Combined 28-Day Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test of 1-Octanol, reaction products with phosphorus oxide (P2O5), potassium salts by Oral Gavage in Rats. Study No. 20153214. See this IUCLID dossier 7.5.1.

ECHA (2017). Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. Volume 3.0, July 2017. Available at:https://echa.europa.eu/documents/10162/13632/information_requirements_r7c_en.pdf/e2e23a98-adb2-4573-b450-cc0dfa7988e5

Goulston Technologies (2018). Technical Report: Chemical and Physical Properties of 1-Octyl Phosphate Potassium Salt. See this IUCLID dossier 4.10.

Klaassen, C.D. ed. (2013). Casarett and Doull's toxicology: the basic science of poisons (Eighth Edition). New York: McGraw-Hill.

XCellR8 Ltd. (2018). In Vitro Assessment of the Skin Irritation Potential of Agent 447C according to OECD Test Guideline 439 (Reconstructed Human Epidermis Test Method). Study No. 18GOU01. See this IUCLID dossier 7.3.1.

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