Butanedioic acid, 1-[2-[(1-oxo-2-propen-1-yl)oxy]ethyl] ester

Endpoint summary

Description of key information

The key information is based on a Repeat Dose Toxicity study with MAES. The oral administration of MAES to rats for a period of up to twenty-eight consecutive days at dose levels of 15, 150, and 300 mg/kg/day resulted in minor but occasionally significant treatment-related effects in animals of either sex treated with 300 or 150 mg/kg/day. These effects can be considered not to represent "serious damage" to health as defined by the criteria given in the EC labelling guide of Commission Directive 200l/59/EC. In both sexes, the dose of 300 mg/kg/day can be regarded as a "No Observed Adverse Effect Level" (NOAEL) for systemic effects, whereas 15 mg/kg/day can be regarded as a NOAEL for local effects.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Guideline study performed under GLP including a 14-d rangefinder and a 28-d definitive study.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeat dose toxicity (Oral):

In the 28-day oral study, effects on bodyweight gain and food efficiency were observed for animals of either sex treated with 300 mg/kg/day together with a slight but not always significant anaemic response, and incidents of increased salivation with a raised limiting ridge (margo plicatus) and microscopic changes identified as acanthosis/hyperkeratosis of the forestomac in the 150 mg/kg/day dose group during the final two weeks of treatment. However, these effects were marginal and only occasionally statistically significant and can be considered as due to repeated local irritation caused by the corrosiveness of MAES.

Repeat dose toxicity (dermal): In accordance with column 2, adaptation of Annex VIII (section 8.6.1) of the REACH Regulation 1272/2008 testing by dermal route is appropriate if skin contact in production and /or use is likely. Skin contact is not the most relevant route of exposure for the substance. Therefore since dermal exposure for humans is considered unlikely the study is deemed inaproppriate.

Repeat dose toxicity (Inhalation): In accordance with column 2, adaptation of Annex VIII (section 8.6.1) of the REACH Regulation (EC) No. 1272/2008 testing by inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possiblity of exposure to aerosols, particulate or droplets of inhalation size. The vapour pressure of the submission substance is considered relatively low such that exposure by the inhalation route is deemed unlikely. Therefore, the study is considered unnecessary. In addition, DNELs have been calculated based on the results for analogue and metabolite of MAES: HEA (hydroxyethyl acrylate). The justification of this read across is appended to the Chemical Safety Report (CSR).

Justification for classification or non-classification

Originally the DSD classification included R37 and R48/22 classifications probably based on an earlier EU Notification campaign resulting in submission to the UK Competent Authority. These can be translated to STOT SE 3 and STOT RE 2, respectively. However, there is no harmonized classification for MAES. Evidence according to the Guidance on CLP Classification that may account for a possible STOT RE 2 classification of a corrosive substance like MAES is the criterion of significant organ damage noted at necropsy and/or subsequently seen or confirmed at microscopic examination. In the 28-day oral study, microscopic changes were identified as marginal acanthosis/hyperkeratosis of the forestomach and limiting ridge, mucosal basophilia and mucosal hypertrophy of the stomach and duodenum (males only). It is questionable as these can be thought of as inducing consistent damage to the functioning of the respective organs. Further, there were no treatment related changes in any organ weights measured. Another point against a STOT RE classification is that MAES is not considered as bioaccumulative. In conclusion, the effects seen at 300 mg/kg bw/day do not justify classification of MAES as STOT RE cat. 1 or 2, and more severe effects are expected only at dosages > 300 mg/kg bw /day in a 28-day repeated exposure study.