Registration Dossier
Registration Dossier
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EC number: 478-130-6 | CAS number: 50940-49-3
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- other: An assessment of the toxicokinetic behaviour based on evaluation using the data from various studies included in this dossier.
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- An assessment of the toxicokinetic behaviour has been provided and attached in this dossier (section 13) as required by the REACH Regulation section 8.8.1.
Data source
Reference
- Reference Type:
- other: Evaluation attached in this dossier (section 13)
- Title:
- Assessment of toxicokinetic behaviour
- Author:
- Ashland Services
- Year:
- 2 015
- Bibliographic source:
- Ashland Services B.V., Marten Meesweg 8-10, 3068 AV Rotterdam, Netherlands
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- An assessment of the toxicokinetic behaviour as required by the REACH Regulation section 8.8.1.
- GLP compliance:
- yes
- Remarks:
- This evaluation is based on data from studies performed according to international guidelines under GLP.
Test material
- Reference substance name:
- -
- EC Number:
- 478-130-6
- EC Name:
- -
- Cas Number:
- 50940-49-3
- Molecular formula:
- C9H12O6
- IUPAC Name:
- 2-(acryloyloxy)ethyl hydrogen succinate
Constituent 1
- Specific details on test material used for the study:
- See respective studies.
- Radiolabelling:
- no
Test animals
- Species:
- other: divers
- Details on species / strain selection:
- See respective studies.
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: oral route is exclusively applied in referred animal studies.
- Details on exposure:
- See respective studies.
- Duration and frequency of treatment / exposure:
- See respective studies.
Doses / concentrations
- Remarks:
- See respective studies.
- No. of animals per sex per dose / concentration:
- See respective studies.
- Control animals:
- other: See respective studies.
- Positive control reference chemical:
- See respective studies.
- Details on study design:
- See respective studies.
- Details on dosing and sampling:
- See respective studies.
- Statistics:
- See respective studies.
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Absortion after oral uptake, whereas exposure through skin and inhalation is not likely.
- Type:
- distribution
- Results:
- The substance is likely to be retained in body water and be metabolized in the liver.
- Type:
- metabolism
- Results:
- 2-acryloyloxyethanol, acrylic acid, 2hydroxyethyl hydrogen succinate, succinic acid and ethane-1 ,2-diol (ethylene glycol), carbondioxide.
- Type:
- excretion
- Results:
- If absorbed, the substance and its metabolites are likely to appear in urine
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- The substance is both water soluble and fat soluble. Thus, absorption following oral administration might be expected. However, it is likely that hydrolysis will take place during absorption, thus it would not be possible to identify whether the parent moiety or the hydrolysis products are absorbed. Because of the corrosivity characteristics of the substance, absorption through the skin in the absence of hydrolysis is unlikely. Given the lack of vapour pressure, little material is likely to be inhaled.
- Details on distribution in tissues:
- If absorbed and not metabolised, the substance is likely to be retained in body water. Accumulation in fat is unlikely.
- Details on excretion:
- Following oral administration, main part of the substance is exctreted in the feaces, while the absorbed part is most likely to appear unchanged in urine. The end products of metabolism are likely to include urinary metabolites and exhaled carbon dioxide.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Most probably, hydrolysis will occur as the substance is absorbed. In most cases, the products are a mixture of 2-acryloyloxyethanol, acrylic acid, 2hydroxyethyl hydrogen succinate, succinic acid and ethane-1 ,2-diol (ethylene glycol). These are likely to enter intermediary metabolism to reach ultimate degradation to carbon dioxide. Intermediary products may include the acid produced by oxidising ethane-1 ,2-diol.
Any other information on results incl. tables
MAES is 2-(acryloyloxy)ethyl hydrogen succinate, molecular 216. It is an involatile liquid at room temperature, freezing at -17°C and decomposing at 139°C. The substance is soluble in water (solubility 162 g/L). It has a log Pow of 0.254. It is very slowly hydrolysed in acid (half life 295 d at pH 4 and 25°C), but relatively readily hydrolysed in alkali (half life 46.5 h at pH 9 and 25°C).
The toxicity information indicates that the substance is harmful if swallowed. Although there was no evidence of corrosivity in the TER test, the substance was corrosive in a conventional skin sensitisation assay. In the 28 day repeated dose study effects were seen in the stomach (acanthosis/hyperkeratosis) at 150 and 300 mg/kg bw/d and, in males at all dose levels (15, 150 and 1000 mg/kg bw/d) , duodenum (mucosal hypertrophy). Systemic effects were only seen at 300 mg/kg bw/d, suggesting they were secondary to the effects at the site of administration (the stomach) due to the corrosive nature of the administered substance and/or hydrolysis products, and in the duodenum of males, possibly due to the corrosivity being enhanced as hydrolysis is speeded as the pH of the gastro-intestinal tract content is raised. The substance was negative in a bacterial reverse mutation assay and a mouse micronucleus assay for genotoxicity, but positive in a chromosomal aberration study in vitro.
One possible hydrolysis product may be acrylic acid. Acrylic acid is also known to be harmful if swallowed and corrosive and is listed on Annex 1 to Directive 67/548/EEC as harmful - R20/21/22 (harmful if swallowed, in contract with skin and by inhalation) and corrosive - R35 (causes severe burns).
Applicant's summary and conclusion
- Conclusions:
- MAES, 2-(acryloyloxy)ethyl hydrogen succinate, is readily hydrolized and metabolites are excreted in urine or as carbondioxice by respiration.
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