Butyl hydrogen maleate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Evaluation based on all available information.

Adequacy of study:

key study

Study period:

The assessment was conducted in March 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

according to guideline

Guideline:

other: Summaries of studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH.

Deviations:

not applicable

GLP compliance:

no

Remarks:

Not applicable.

Test material

Test material information

Constituent 1

Reference substance name:

Butyl hydrogen maleate

EC Number:

213-116-3

EC Name:

Butyl hydrogen maleate

Cas Number:

925-21-3

Molecular formula:

C8H12O4

IUPAC Name:

(2Z)-4-butoxy-4-oxobut-2-enoic acid

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Butyl Hydrogen Maleate
- Physical state: Pale yellow liquid

Radiolabelling:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Results of the repeated dose reproductive screening study showed evidence to support the gastric absorption of the test item. The test item is lipophobic in
nature and because of the high water solubility (37.0 g/L at 20°C + 0.5°C) and small molecular size of the substance absorption through passive diffusion is possible. This would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood.
Limited absorption may also take place via the skin due to small molecular size and water solubility. The substance is corrosive therefore damage to the skin
surface may allow for increased penetration of the substance through the skin. The low vapour pressure value (0.2 Pa at 25°C) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

Details on distribution in tissues:

Systemic distribution is evident from the repeated dose reproductive screening study because of the organ changes observed.
Once absorbed, the substance may be distributed in serum due to the water solubility and may therefore be distributed systemically. The low log octanol/water partition coefficient (log10 Pow 1.39) and high water solubility (37.0 g/L) would also suggest that the test item is not lipophilic and would not accumulate in body fat.

Details on excretion:

The results of the repeated dose reproductive screening study would suggest that the most likely route of excretion is the kidney due to the likely systemic
distribution and water solubility of the test item. In addition to the high water solubility, a molecular weight of below 300 g/mol in the rat is also a characteristic favourable for urinary excretion. Any test item that is not absorbed from the gastro intestinal tract will be excreted in the faeces.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

The results of the repeated dose reproductive screening study showed evidence of an adaptive response in the liver and thyroids in rats; which is normally
associated with enhanced metabolism. The results of the genotoxicity assays showed that genotoxicity is neither enhanced nor diminished in the presence of the S9 metabolising system.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The available information suggests that absorption of the test substance from the gastrointestinal tract can take place. Some absorption may also take place via the skin.
Once absorbed, the substance would be distributed in the serum and urine is the significant route of excretion. There is evidence to suggest that the test substance may be metabolised, however no studies have been conducted to identify metabolites.

Executive summary:

The available information suggests that the substance is readily available via the oral route; however absorption via the skin is also possible. This is supported by the physicochemical properties of the substance. Once absorbed, the substance would result in distribution in the serum. Urinary excretion is considered to be the significant route for the substance.