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Description of key information

The available experimental data in animals show evidence of oral absorption and systemic distribution of the submitted substance since adverse effects were reported the acute oral toxicity study. No indications on the submitted substance metabolism and excretion were obtained.

Key value for chemical safety assessment

Additional information

No specific toxicokinetic studies are available on Phosphoric acid, mixture of pentyl esters. A toxicokinetic assessment was made, based on the physico-chemical properties of the submitted substance and the results of the acute toxicity study.

Physico-chemical properties of Phosphoric acid, mixture of pentyl esters:

Water solubility: 42.5 g/L (at 20°C)

Boiling point: As the test item decomposed, it was not possible to experimentally determine the boiling temperature

Partition coefficient in octanol/water: -1.94 for the monoester content and 0.08 for the the diester content

Vapour pressure: 3 x 10-5Pa (at 25°C)

Density: 1.09 (at 20°C)

 

Absorption:

Inhalation:

No data were available for this route of exposure. However, the submitted substance is a liquid with a low volatility, as evidenced by the very low vapour pressure. Therefore it can be considered that the absorption by the inhalation route is limited.

 

Oral:

Mortality was observed after the single oral administration of Phosphoric acid, mixture of pentyl esters to rats at the dose of 2000 mg/kg bw. Additional signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg bw were decreased respiratory rate, gasping, noisy or laboured respiration, pilo-erection, tiptoe gait, pallor of the extremities, lethargy, diuresis, increased salivation and red/brown staining around the eyes, mouth and snout.

All these effects suggest that the submitted substance is absorbed by the gastrointestinal tract.

 

Another acute oral toxicity study performed on the reaction mass of diisobutyl hydrogen phosphate and isobutyl dihydrogen phosphate showed clinical signs in rats exposed to this analog of the submitted substance, such as dyspnea, piloerection, hunched posture. Therefore it can be assumed that this structural analog substance is also absorbed by the oral route of exposure.

 

Dermal route:

Since the submitted substance is classified as corrosive, no in vivo study was performed by the dermal route. However, it can be assumed that the corrosive properties of the submitted substance would enhance the dermal penetration of the substance (see Guidance on information requirements and chemical safety assessment: Chapter R.7c: Endpoint specific guidance). The absorption by the dermal route is therefore possible.

 

Distribution:

In the acute oral toxicity study available on the submitted substance Phosphoric acid, mixture of pentyl esters, abnormalities were noted at necropsy of the animal that was humanely killed during the study. Haemorrhagic lungs, dark kidneys and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach were observed. If the two last adverse effects are the sign of local irritation due to the corrosive properties of the substance, the effects observed in the lung and in the kidneys support a systemic distribution of the submitted substance.

 

Metabolism:

No genotoxicity studies were performed on the submitted substance Phosphoric acid, mixture of pentyl esters. However, in vitro data were available on structural analogs (the reaction mass of diisobutyl hydrogen phosphate and isobutyl dihydrogen phosphate): all gave negative results with indication of cytotoxicity either with or without metabolic activation. As such, these studies showed no genotoxic potential by extrapolation to the submitted substance but did not provide any information on possible metabolism.

 

Elimination:

There is no information to indicate a route of excretion for Phosphoric acid, mixture of pentyl esters but its high water and relatively fat solubility indicate that excretion of unchanged parent substance and/or metabolites could occur by renal or biliary routes and that bioaccumulation is unlikely. The parent substance could not be eliminated via the lungs in expired air due to its low volatility.