Phosphoric acid, butyl ester

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Objective of study:

excretion

metabolism

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

one dose group

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Phosphoric acid, 2-ethylhexyl ester

EC Number:

235-741-0

EC Name:

Phosphoric acid, 2-ethylhexyl ester

Cas Number:

12645-31-7

Molecular formula:

Mono-Ester: C8H19O4P Di-Ester: C16H35O4P Esters of 2-ethylhexan-1-ol with diphosphoric acid: P2O7(H)4-n(C8H17)n where n = 1-4

IUPAC Name:

Reaction mass of bis(2-ethylhexyl) hydrogen phosphate and 2-ethylhexyl dihydrogen phosphate and esters of 2-ethylhexan-1-ol with diphosphoric acid

Test material form:

other: liquid

Radiolabelling:

no

Test animals

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 days


IN-LIFE DATES: From: 24.11. To: 01.12.2000

Administration / exposure

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

Doses / concentrations

Remarks:

Doses / Concentrations:
200 mg/kg bw

No. of animals per sex per dose / concentration:

5

Control animals:

no

Positive control reference chemical:

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 sample to reach a pH of 9. Thereafter, the samples were mixed with 200 µL D2O and measured.

Statistics:

no

Results and discussion

Preliminary studies:

No data

Main ADME results

Main ADME results 1

Type:

metabolism

Results:

complete hydrolysis of the phosphoric acid, 2-ethylhexyl ester

Main ADME results 2

Type:

excretion

Results:

via urine within 24 h

Metabolite characterisation studies

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)

Bioaccessibility (or Bioavailability) testing results:

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

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
From 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:

Phosphoric acid, 2 -ethylhexyl ester (the test item used in this metabolism/excretion study) and the Phosphoric acid, butyl ester (the substance to be registered) are member of the Phosphoric acid, alcyl ester family.The characteristic and functional active center of both 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 I metabolism it can be assumed that both Phosphoric acid esters are hydrolysed independent 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 the both ester type substances Phosphoric acid, 2 -ethylhexyl ester and Phosphoric acid, butyl ester in order to estimate its potential metabolism.

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.