Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

Authors of the USEPA (2008) reported that metabolism of the diesters in animals would be expected to occur initially via enzymatic hydrolysis leading to the corresponding diacids acids (e.g., maleic acid) and branched alcohols (e.g., 2 -ethylhexanol) can be further metabolized or conjugated (e.g., glucuronides, sulfates, etc.) to polar products that are excreted in the urine.

In addition, in a hydrolysis test in digestive simulants (saliva, gastric and intestinal), dibutyl maleate hydrolyzed to monoester only in the alkaline saliva simulant (pH = 9). No hydrolysis was seen at the almost neutral pH of 7.5 (intestine simulant) or the strongly acidic (stomach simulant) pH 1.2. Experiments with all physiological stimulants did not form maleic acid. The halt of the hydrolysis at the stage of the monoester was expected since at pH 9 the monocarboxylic acid immediately reacts to the carboxylate form which effectively screens a second OH-from attacking the remaining monoester.

Literature review of the physicochemical and structural molecule indicate that in the absence of significant data on dioctyl maleate (DOM) itself, a weight of evidence approach to assess toxicokinetics and metabolism of DOM is valid. N-butyl maleic acid, DOM and dibutyl maleate (DBM) are close analogues and all three can be associated to maleic acid biotransformation. Available data presented in detail in this dossier for n-butyl maleate (Rosonald et al., 2010), dibutyl maleate (Abutin, 2010), metabolism of diesters (USEPA, 2008) in combination with data on dioctyl maleate are used to support this read across assessment.

NOTE: References listed under the endpoint with the exeption of CIRP (2007). Final Report on the Safety Assessment of Maleic Acid. International Journal of Toxicology, 26(Suppl. 2):125–130, 2007.

Categories Display