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Description of key information

Short description of key information on bioaccumulation potential result: 
In accordance with Regulation (EC) No 1907/2006 Annex VIII section 8.8.1, a toxicokinetics study is not required as assessment of the toxicokinetic behaviour of the substance has been derived from the relevant available information. This assessment is located within the endpoint summary for toxicokinetics, metabolism and distribution.

Key value for chemical safety assessment

Additional information

Considering the physicochemical properties of MEK, [i.e.,low molecular weight (72.11 g/mol), small log Pow value (0.3), and vapor pressure of 12.6 kPa], absorption of MEK from various routes of exposure, such as oral, dermal or inhalation is expected. However, absorption of MEK is expected to mainly occur via oral and inhalation routes, with limited potential for dermal absorption. 

Animal data show that s-butanol (sBA) is absorbed, distributed and excreted rapidly in urine, mainly as MEK, following oral administration. A small percentage of sBA is also excreted via urine and exhalation. Orally administered sBA is metabolized via alcohol hydrogenase to MEK. The maximum concentration of MEK in blood was seen six hours after dosing. Further oxidation of MEK appeared to proceed by hydroxylation of the omega-1 carbon to form 3-hydroxy-2-butanone, which is further reduced to 2,3-butanediol. 2,3-Butanediol was also detected in human urine following inhalation exposure to MEK. The main portion of the inhaled MEK is converted to acetate or acetoactate via 3-hydroxy-2-butanone intermediate metabolite. Following absorption, MEK is anticipated to be distributed evenly throughout the body.

The pharmacokinetic data available for the structurally-related surrogate, sBA demonstrate that sBA may be used as a surrogate for MEK considering that sBA is rapidly metabolized to MEK, and that the two share common metabolites (3-hydroxy-2-butanone and 2,3-butanediol). Metabolic fate of MEK has been reported to include both oxidative and reductive pathways, with the latter leading to the production of sBA. The oxidative pathway involves MEK oxidation catalyzed by liver microsomal mixed-function oxidases to form 3-hydroxy-2-butanone, which is subsequently reduced to 2,3-butanediol. The hydroxylation product of MEK, 3-hydroxy-2-butanone is expected either to undergo conjugation with sulfate or glucuronic acid and elimination of the conjugated metabolites in the urine, or to enter intermediary metabolism to form carbon dioxide. Taking into consideration the low molecular weight and log P, and its considerable water solubility, MEK is not expected to bioaccumulate.

Please refer to the document attached to Section 13 for further discussion of toxicokinetics.