Dibutyl methylenedithiodi(acetate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

key study

Study period:

2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert judgement is combined with the prediction of metabolism provided by the OECD QSAR Application Toolbox.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

No guideline exists for this type of appraisal.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyl methylenedithiodi(acetate)

EC Number:

238-289-2

EC Name:

Dibutyl methylenedithiodi(acetate)

Cas Number:

14338-82-0

Molecular formula:

C13H24O4S2

IUPAC Name:

butyl 2-({[(2-butoxy-2-oxoethyl)sulfanyl]methyl}sulfanyl)acetate

Constituent 2

Reference substance name:

MBTester

IUPAC Name:

MBTester

Details on test material:

not applicable

Test animals

Species:

other: not applicable

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Route of administration:

other: oral and dermal route are considered

Details on exposure:

not applicable

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral absorption of MBTester is predicted to be high. The Danish EPA QSAR database predicts an oral absorption of 100 % following a dose of 1 mg.
The EPI Suite DermWin program predicts a very low dermal absorption of 0.00025 mg/cm²/event.

Details on distribution in tissues:

The substance will be hydrolysed; the hydrolysis products are water soluble and are predicted to have no accumulation potential. They are expected to enter the urine shortly after systemic absorption.

Details on excretion:

The hydrolysis products of MBTester as well as the oxidised metabolites are soluble in water (MBTAA: ca. 200 g/L and 1-Bu: ca. 70 g/L; calculated with EPI Suite, WSKOW v1.42) and will be excreted rapidly via urine, either as such or as conjugates with glucuronic acid or sulphate. Significant faecal excretion is not expected.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

MBTester will undergo enzymatic and non-enzymatic ester hydrolysis. This is a stepwise process and mixed hydrolysis and oxidation products are likely to occur at least as intermediate metabolites.
The resulting molecules, 2,2'-(methylenebis(thio))bisacetic acid (MBTAA; CAS: 2068-24-8) and 1-butananol (1-Bu; CAS: 71-36-3), are soluble in water. Both substances can be further oxidised [R2S to R2S(=O)2; -CH2OH to -COOH]. Carboxylic acids can be subject to sulphation and glucuronidation (mediated by sulfotransferases and UGT-isozymes) prior to urinary excretion.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
MBTester is predicted to be bioavailable via the oral route but is very poorly absorbed via skin.
MBTester is expected to undergo stepwise hydrolysis of the two ester bonds yielding 2,2'-(methylenebis(thio))bisacetic acid (MBTAA; CAS: 2068-24-8) and 1-butananol (1-Bu; CAS: 71-36-3). Both substances are very polar and thus subject to renal elimination. Concomitant oxidation of the hydrolysis products is likely.
Both substances are water soluble and thus subject to renal elimination. Tissue accumulation can be excluded.

Executive summary:

The toxicokinetic behaviour of MBTester [CAS: 14338-82-0; Acetic acid, 2,2'- methylenebis(thio) bis-, dibutyl ester] was assessed. The OECD QSAR Application Toolbox was used to make a qualitative prediction of metabolites formed in liver, skin and gastrointestinal tract (data not shown).

The Danish EPA QSAR Database and the EPI Suite DermWin program were used to predict dermal and oral bioavailability of MBTester.

The fate of these metabolites is predicted on the basis of their chemical structure based on expert judgement and computer tools like EPI Suite.

MBTester is predicted to be highly bioavailable via the oral route but is very poorly absorbed via skin.

MBTester is expected to undergo stepwise hydrolysis of the two ester bonds yielding 2,2'-(methylenebis(thio))bisacetic acid (MBTAA; CAS: 2068-24-8) and 1-butananol (1-Bu; CAS: 71-36-3). Both substances are water soluble and thus subject to renal elimination. Tissue accumulation can be excluded.