Dibutyl phosphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

The quantitative evaluation of the substance and its degradation products in biological systems was performed in order to define and evaluate whether a substance gives rise to degradation products, particularly to 1-butanol.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyl phosphonate

EC Number:

217-316-1

EC Name:

Dibutyl phosphonate

Cas Number:

1809-19-4

Molecular formula:

C8H19O3P

IUPAC Name:

dibutyl phosphonate

Test material form:

liquid

Results and discussion

Main ADME results

Type:

metabolism

Results:

the formation and presence of butanol following incubation of DBHP with biological matrices and S9 Rat liver fraction was supported using gas mass spectrometry with headspace extraction technique

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

1-butanol was identified following incubation with S9 rat liver metabolic fraction and biological matrices. The test item was no longer detected at the end of the study period.

Any other information on results incl. tables

A graph showing the calibration line for 1-butanol in the concentration range of 10-200 ppb was formed; the line of best fit was y = 271.12x + 6712 (R² = 0.9971).

Furthermore, the ion chromatogram relative to the test item in a concentration of 1 ppb (LOD value of the method) by means of head space analysis confirmed the presence or absence of DBHP in the investigated samples and 1-butanol chromatogram detected in the sample under investigation.

The pure DBHP compound was also analysed, and its ionic chromatogram demonstrated the formation and presence in the pure butanol compound.

The table below shows the quantitative values detected in the samples under investigation.

Table 1: Quantitative determination of butanol and DBHP in samples under investigation.

Name	Description	Butanol (ppb)	DBHP (ppb)
N7 Blank (NADPH + S9 + Dulbecco Buffer + 0.1% DMSO)	blank	n.d.	n.d.
N1 (DBP + S9 + Dulbecco Buffer + 0.1% DMSO)	T0 control	50.74	n.d.
N2 (DBP + S9 + Dulbecco Buffer + 0.1% DMSO)	T60 control	52.43	n.d.
N3	T0 incubation n.1	44.43	n.d.
N4	T60 incubation n.1	50.55	n.d.
N5	T0 incubation n.2	50.65	n.d.
N6	T60 incubation n.2	52.78	n.d.

As seen in the table concerning quantitative results, a very similar level of butanol was found among the different types investigated in all the samples. However, the presence of DBHP was not found in any sample subjected to analysis. In the N7 sample (considered a blank reference and consisting of NADPH + S9 + Dulbecco Buffer + 0.1 % DMSO), no DBHP or butanol was detected.

It should be noted, in all the samples, the acetonitrile compound used for the preparation of the same is strongly interfered with.

Applicant's summary and conclusion

Conclusions:

DBHP is metabolised to 1-butanol in the presence of biological matrices and S9 rat liver fraction.

Executive summary:

The potential metabolism of the test item to 1-butanol was evaluated in an in vitro experimental study. Samples were evaluated using gas mass spectrometry with headspace extraction technique, and 1-butanol and DBHP were quantified in the samples at 0 minutes and 60 minutes.

DBHP is metabolised to 1-butanol in the presence of biological matrices and S9 rat liver fraction.