Phosphoric acid, 2-ethylhexyl ester

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics, other

Type of information:

other: In accordance with REACH Annex VIII (8.8.1) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII (8.8.1).

Objective of study:

toxicokinetics

Qualifier:

no guideline required

Principles of method if other than guideline:

In accordance with REACH Annex VIII (8.8.1) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information. The assessment is based on the Guidance on information requirements and chemical safety assessment R.7c: Endpoint specific guidance (ECHA, May 2008)

GLP compliance:

no

Remarks:

Not relevant for assessment

TOXICOKINETIC BEHAVIOUR

The substance is composed, as listed in the Section 1.2 of IUCLID. It is an amber coloured liquid and the molecular weight is 210.21 – 322.42 g/mol. The low vapour pressure value (8.5 x 10^-2 Pa at 25°C) and predicted negative explosive and oxidising properties shows that the substance is non volatile therefore inhalation is not a significant route of exposure. The substance is considered as flammable.

The substance has a low log octanol/water partition coefficient value (Log10 Pow <0.3- 2.18) and low water solubility (5.95 x 10^-3 – 13.2 g/l at 20°C).

The available acute dermal irritation/corrosion (OECD 404) and repeated dose reproductive screening studies showed evidence of absorption however the repeated dose reproductive screening study did not show evidence of metabolism or excretion.

The test item was non-mutagenic in bacteria , non-clastogenic in mammalian cells in vitro and non-mutagenic in mammalian (CHO) cells in vitro in either the absence or presence of an auxiliary metabolising system.

Absorption

Although the test item is lipophobic in nature the small molecular size of the substance should allow absorption through passive diffusion. This would suggest that the gastrointestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood.

Limited absorption may also take place via the skin due to small molecular size. The substance is corrosive therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The low vapour pressure value (8.5 x 10^-2 Pa at 25°C) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

Distribution

Once absorbed, the substance may be distributed in plasma due to the water solubility and may therefore be distributed systemically. The lipophobic nature of the test item suggests that bioaccumulation in body fat is unlikely.

Metabolism

The results of the repeated dose/reproductive screening study did not show evidence to indicate any test item influenced hepatic metabolism. The results of the genotoxicity assays have shown that genotoxicity is neither enhanced or diminished in the presence

of the S9 metabolising system.

Excretion

There is no evidence to indicate the route of excretion but water-soluble products are not favourable for biliary excretion and therefore urinary excretion may well be a significant route for this material. Any test item that is not absorbed will be excreted in the faeces.

Conclusions:

Interpretation of results (migrated information): other: See summary in conclusions sectionThe available information suggests that absorption of the test substance from the gastrointestinal tract can take place. Some absorption may also take place via the skin. Once absorbed, the substance would be distributed in the serum and urine is the significant route of excretion. There is no evidence to suggest that the test substance may be metabolised, however no studies have been conducted to identify metabolites.

Executive summary:

The available information suggests that the substance is readily available via the oral route; however absorption via the skin is also possible. This is supported by the physicochemical properties of the substance. Once absorbed, the substance would result in distribution in the serum.There is no evidence to indicate the route of excretion.

Reference 2

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Nov - Dec 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well performed non guideline study with sufficient reporting and scientitifc sound test design.

Objective of study:

excretion

metabolism

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

one dose group

GLP compliance:

not specified

Radiolabelling:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Age at study initiation: 12 weeks- Weight at study initiation: 250-300 g- Fasting period before study: no data- Individual metabolism cages: yes (transparent Macrolan)- Diet (e.g. ad libitum): Altromin, ad libitum- Water (e.g. ad libitum): tap water, ad libitum- Acclimation period: 5 daysIN-LIFE DATES: From: 24.11. To: 01.12.2000

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Phosphoric acid, 2-ethylhexyl ester was administered to rats by stomach tube at a dose of 200 mg/kg bw . Total volume: 1 mL

Duration and frequency of treatment / exposure:

Single dose

Remarks:

Doses / Concentrations:200 mg/ kg bw

No. of animals per sex per dose / concentration:

5

Control animals:

no

Positive control reference chemical:

none

Details on study design:

After application urine and feces was collected every 12 h for a total of 72 h.

Details on dosing and sampling:

Samples were analysed via P31-NMR spectroscopy.Sodium hydroxide was added to 700 µL urine sample to reach a pH of 9. Thereafter, the samples were mixed with 200 µL D2O and measured.

Statistics:

none

Preliminary studies:

No data

Type:

metabolism

Results:

complete hydrolysis of the phosphoric acid, 2-ethylhexyl ester

Type:

excretion

Results:

via urine within 24 h

Metabolites identified:

yes

Details on metabolites:

Only Phosphate peak was found in the urine samples. Therefore, it was concluded, that Phosphoric acid, 2-ethylhexyl ester is quantitatively hydrolysed to Phosphate and the alcoholic compound, 2-Ethylhexanol.

Bioaccessibility (or Bioavailability) testing results:

Since a quantitative hydrolsis takes place good bioaccessibility can be assumed.

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study resultsFrom this study it appears that Phosphoric acid, 2-ethylhexyl ester is efficiently absorbed, metabolised and excreted quantitatively by the body. Hydrolysis of the ester linkage provides an adequate degradation mechanism. There was no sign of accumulation.

Executive summary:

5 male and 5 female rats received 200 mg/kg bw Phosphoric acid, 2 -ethylhexyl ester via gavage. Urine and feces were collected in 12 h intervals for 72 h. The samples were analysed by NMR spectroscopy.

Besides the Phosphate peak no other peaks were detected indicating a complete hydrolysis of the Phosphoric acid ester into Phosphate and 2 -Ethylhexanol.

Description of key information

Dunster, J.S. (2012) Assessment of toxicokinetic behaviour
Dekant, W. (2001) Tokicokinetics of Mono-di-2-ethylhexylposphosphoric acid ester MADH in the rat

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

The available information suggests that absorption of the test substance from the gastrointestinal tract takes place. Some absorption may also take place via the skin. Once absorbed, the substance would be distributed in the plasma and urine is the significant route of excretion.

A metabolism study conducted, where a group of 5 rats were given a single dose of the substance at 200 mg/kg by oral gavage, indicated that the substance is efficiently metabolised and excreted via the urine, and faeces, within 24 hours. Hydrolysis of the ester linkages for each constituent is the proposed route of transformation, and the metabolites excreted are believed to be phosphate and 2-ethylhexanol.