Malonic acid diesters. Dimethylmalonate, 108-59-8, and diethylmalonate, 105-53-3.
HERO ID
1141389
Reference Type
Technical Report
Year
2005
Language
English
| HERO ID | 1141389 |
|---|---|
| Year | 2005 |
| Title | Malonic acid diesters. Dimethylmalonate, 108-59-8, and diethylmalonate, 105-53-3. |
| Authoring Organization | Organisation for Economic Co-operation and Development |
| Publisher Text | UNEP |
| City | Degussa AG, Germany |
| Volume | Screening Information Data Set for High Production Volume Chemicals |
| Abstract | The production and use pattern of Diethylmalonate (DEM) and Dimethylmalonate (DMM) are comparable. The two chemicals have very similar physico-chemical properties and both esters are hydrolyzed via a two step reaction to malonic acid and the corresponding alcohol, methanol or ethanol. It is likely that unspecific esterases in the body catalyze the hydrolysis. The alcohols and malonic acid are physiological substances that are metabolized via physiological pathways. Ethanol (CAS No. 64-17-5) and methanol (CAS No. 67-56-1) were assessed at SIAM 19. For ethanol it was concluded that the chemical is currently of low priority for further work, because the hazardous properties of ethanol are manifest only at doses associated with consumption of alcoholic beverages. As it is impossible to reach these exposure levels as a consequence of the manufacture and use of malonates, it can be expected that malonic acid will be the metabolite that determines the toxicity of DEM. For methanol, SIAM 19 decided that this chemical is a candidate for further work. Methanol exhibits potential hazardous properties for human health (neurological effects, CNS depression, ocular effects, reproductive and developmental effects, and other organ toxicity). The effects of methanol on the CNS and retina in humans only occur at doses at which formate accumulates due to a rate-limiting conversion to carbon dioxide. In primates, formate accumulation was observed at methanol doses greater than 500 mg/kg bw (which would require a DMM dose of more than 1000 mg/kg bw). As there were no indications of a methanol associated toxicity from a well performed repeated dose toxicity study with DMM in rodents (which are, however, known to be less sensitive to methanol toxicity than humans), and because methanol toxicity would not be expected up to doses as high as 1000 mg DMM/kg bw/day, it was concluded that methanol does not make a relevant contribution to the toxicity profile of DMM. A possible mode of action for systemic toxicity of DMM and DEM can only be deduced from the repeated dose study with DMM, indicating a reversible liver hypertrophy at the cellular level at high doses of 1000 mg/kg bw/day. This effect can be an indication of an induction of metabolism in the liver rather than a clear systemic toxicity. |
| Report Number | RISKLINE/2007020012 |
| Url | https://hpvchemicals.oecd.org/UI/handler.axd?id=3a1e8ac2-7862-4b86-8376-ca6c61817b0e |
| Is Certified Translation | No |
| Dupe Override | No |
| Number Of Pages | 182 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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