Dimethyl maleate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: compilation and interpretation of available data

Adequacy of study:

supporting study

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Compilation and interpretation of available data.

Data source

Reference

Reference Type:

other: compilation and interpretation of available data

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Objective of study:

other: Compilation and interpretation of available data.

Test guideline

Qualifier:

no guideline required

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl maleate

EC Number:

210-848-5

EC Name:

Dimethyl maleate

Cas Number:

624-48-6

Molecular formula:

C6H8O4

IUPAC Name:

dimethyl (Z)-but-2-enedioate

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Absorption, distribution: Systemic effects were detected in the acute and the repeated dose oral toxicity studies at high doses, indicating an absorption of the test substance in the gastrointestinal tract. Indications for a dermal absorption were obtained from the subacute dermal toxicity study. The vapour pressure is medium, the saturation concentration only produced death in rats after ca. 8 h exposure.
The water solubility is rather high (78 g/L), the n-octanol/water partition coefficient is low (logPow = 0.52), the molecular mass is low (144), therefore it is anticipated also from the physico-chemical parameters that the notified substance is able to penetrate biological membranes to some extent.
Metabolism: No genotoxicity was detected in the bacterial reverse mutation assay with and without metabolizing enzymes and no indication of the importance of the metabolism of the notified substance was obtained from this study.
Excretion: No relevant data are available, which could provide evidence on the route and extent of excretion.
Bioaccumulation: No statement on the bioaccumulation can be derived from the comparison of the effective doses in the acute and the repeated dose dermal toxicity study, when also considering the different extent of the investigations in both studies. From the low logPow no relevant bioaccumulation potential is anticipated.

Executive summary:

The toxicokinetic behaviour of dimethyl maleate was estimated from available data for the purpose of registration of the substance.

Absorption, distribution: Systemic effects were detected in the acute and subacute oral toxicity study at high doses, indicating an absorption of the test substance in the gastrointestinal tract.

No indication for a dermal absorption was obtained from the acute dermal toxicity study. The difference between oral and dermal acute toxicity indicate a low or a slow dermal absorption. Systemic effects were observed in a subacute dermal toxicity study with rats at high doses, indicating a dermal absorption to some degree. A slight dermal absorption is also derived from the positive skin sensitisation study (GPMT). The rather high water solubility and the low n-octanol/water partition coefficient would impede a dermal absorption, whereas the low molecular mass would favour it.

The vapour pressure is medium, the saturation concentration only produced death in rats after ca. 8 h exposure.

The water solubility is rather high (78 g/L), the n-octanol/water partition coefficient is low (logPow = 0.52), the molecular mass is low (144), therefore it is anticipated also from the physico-chemical parameters that the notified substance is able to penetrate biological membranes to some extent.

Metabolism: No genotoxicity was detected in the bacterial reverse mutation assay with and without metabolizing enzymes and no indication of the importance of the metabolism of the notified substance was obtained from this study.

Excretion: No relevant data are available, which could provide evidence on the route and extent of excretion.

Bioaccumulation: No statement on the bioaccumulation can be derived from the comparison of the effective doses in the acute and the repeated dose oral and dermal toxicity studies, when also considering the different extent of the investigations in both studies. From the low logPow no relevant bioaccumulation potential is anticipated.