Registration Dossier

Diss Factsheets

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Neither under GLP nor REACH approved guidelines but reliable enough for the purpose of this evaluation.

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to guideline
other: Guidance for Food Contact Materials, Annex 1.
Principles of method if other than guideline:
The test substance (monomer or additive) is dissolved in an appropriate solvent. An aliquot of the solution is transferred to the digestive fluid simulant, which is concentrations of both parent constituent and hydrolysis products are determined in the simulant by using an appropriate analytical method (in this case NMR spectroscopy) and calculate percentage hydrolysis from the results.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Dibutyl maleate
EC Number:
EC Name:
Dibutyl maleate
Cas Number:
Molecular formula:
dibutyl but-2-enedioate
Details on test material:
Name (as cited in report): Maleic acid, dibutyl ester (DBM)
Batch No.: 001030324
Purity: 96.49% DBM and 2.43% dibutylfumarate

Test animals

other: not applicable
other: not applicable
Details on test animals or test system and environmental conditions:
Not applicable

Administration / exposure

Route of administration:
other: not applicable
other: not applicable
Details on exposure:
Digestive fluid simulants including saliva, gastric-juice and intestinal juice, were prepared to conduct this study. A maximum of 2 mg of dibutyl maleate (DBM) was added to 1 ml of digestive fluids simulants and a pure H2O-D2O mixture (9:1, v/v) in order to determine the chemical shift of the respective substances using Nuclear magnetic Resonance (NMR). For the hydrolysis tests, 10 ml of saliva, gastric and intestinal-fluid simulants was stirred and transferred to a high precision NMR. The experiment was repeated with a second solution under the same conditions.
Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
Doses / Concentrations:
not applicable
No. of animals per sex per dose / concentration:
not applicable
Control animals:
other: not applicable
Positive control reference chemical:
not applicable
no data

Results and discussion

Applicant's summary and conclusion

Interpretation of results (migrated information): no bioaccumulation potential based on study results
There was not formation of maleic acid in any of the hydrolysis tests.
Executive summary:

A quantitative real-time NMR measurement of DBM in saliva, gastric and intestinal fluids simulants were tested to identify the hydrolysis products of DBM under simulated bodily conditions. The pH of the simulants were 9 (saliva), 1.2 (gastric fluid ) and 7.5 (intestinal fluid), respectively. Only in the alkaline saliva simulant (pH = 9) was DBM hydrolyzed to the monoester. No hydrolysis was seen at the almost neutral pH of 7.5 or the strongly acidic pH 1.2. Formation of maleic acid does not occur during any of the experiments, i.e. in any of the physiological simulants.

The halt of the hydrolysis at the stage of the monoester was expected, since at pH 9, the monocarboxylic acid immediately reacts to the carboxylate form which effectively screens a second OH- from attacking the remaining monoester.