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Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2000 to 2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
excretion
metabolism
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
yes one dose group
Radiolabelling:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals 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 days
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
Dose / conc.:
200 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5
Control animals:
no
Positive control:
no
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 s
ample to reach a pH of 9. Thereafter, the samples were mixed with 200 μL D2O and measured.
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 testing results:
Since a quantitative hydrolsis takes place good bioaccessibility can be assumed.

.

Conclusions:
Interpretation of results suggests no bioaccumulation potential based on the study results.

From the data 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:

Phosphoric acid, 2 -ethylhexyl ester is member of the Phosphoric acid, alcyl ester family. The characteristic and functional active center of such substances is the ester binding between the alcoholic compound and Phosphate. With reference to the occurrence of endogenous esterases which take part in the mammalian phase 1 metabolism it can be assumed that Phosphoric acid esters are hydrolysed independently from the constitution of the alcoholic part. Since the ester binding is the specific target of endogenous esterases it is justified to perform a read across between analogue ester type substances to estimate their potential metabolism.

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
Study period:
2012
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 requ irements 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: Endpo
int specific guidance (ECHA, May 2008)
GLP compliance:
no
Conclusions:
The 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..

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reason / purpose:
read-across source
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.
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
Reason / purpose:
read-across source
Conclusions:
The 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 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..

Description of key information

 Phosphoric acid, 2 -ethylhexyl ester is member of the Phosphoric acid, alcyl ester family. The characteristic and functional active center of such substances is the ester binding between the alcoholic compound and Phosphate. With reference to the occurrence of endogenous esterases which take part in the mammalian phase 1 metabolism it can be assumed that Phosphoric acid esters are hydrolysed independently from the constitution of the alcoholic part. Since the ester binding is the specific target of endogenous esterases it is justified to perform a read across between analogue ester type substances to estimate their potential metabolism

Interpretation of results suggests no bioaccumulation potential based on the study results.

From the data 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.

 

.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
90

Additional information

Based on the results from the toxicokinetic studies, the orally dosed toxicity studies, the small molecular size of the test substance and it's physico-chemical characteristics, it can be assumed that the test substance would be readily absorbed through the gastrointestinal tract. It is likely that the majority of the test substance would be absorbed via the oral route and therefore it may be assumed that in the region of 90% oral absorption would likely occur.