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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

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.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

A rat pharmacokinetic model was developed to assess the biotransformation of 2 -butanol (sBA) and its metabolites including 2 -butanone (methyl ethyl ketone; MEK) (Dietz et al, 1981). In this study, male Sprague Dawley rats were given orally a single dose of 2.2 ml sBA/kg body weight. Plasma samples were collected at regular intervals up to 30 h post-administration. Concentrations of sBA reached a mean maximum plasma concentration of 0.59 g/L within 2 hours, and declined thereafter to less than 0.05 g/L at 16 h post-administration. As the blood concentration of sBA fell, the plasma concentrations of its metabolites including MEK, 3-hydroxy-2-butanone, and 2,3-butanediol rose to maximum levels of 0.78, 0.04, and 0.21 g/L at 8, 12, and 18 hours post-administration, respectively. It was concluded that approximately 97% of the administered sBA dose was converted to MEK by alcohol dehydrogenase within 16 hours. Transformations of sBA to MEK and of 3 -hydroxy-2 -butanone (3H2B) to 2,3-butanediol were rapid; however, metabolism of MEK to 3-hydroxy-2-butanone occurred at much slower rate.

Aside from the studies in sBA, the metabolism of MEK was also evaluated in the same rat strain. The data showed that the metabolic profiles of sBA and MEK are similar. Similar to sBA, 3 -hydroxy-2 -butanone and 2,3 -butanediol were the predominant metabolites observed with exposure to MEK alone. The data also showed that exposure to MEK may also lead to exposure to sBA, since sBA is formed by the reduction of MEK. A peak concentration of 0.033 mg/ml sBA was reported in rats exposed to MEK alone, with total AUC values of 414 +/-38 mg hr/liter. Below is a comparison of peak blood concetrations of the different metabolites following exposure to sBA or MEK.

Peak blood concentrations of downstream metabolites following sBA and MEK oral administration in rats

Peak Blood Concentration

Downstream Metabolites

Sec-Butanol (1776 mg/kg)

MEK (1690 mg/kg)


0.78 mg/ml (8 hours)

0.95 mg/ml (4 hours)


0.04 mg/ml (12 hours)

0.027 mg/ml (8 hours)


0.21 mg/ml (18 hours)

0.26 mg/ml (18 hours)


As shown in the table, identical peak blood concentrations of each metabolite were observed, with the exception that peak blood concentrations of MEK and 3 -hydroxy-2 -butanone are reached 4 hours slower with sBA exposure compared to exposure with MEK. This difference is accounted for by the time required to convert sBA to MEK via alcohol dehydrogenase.

The toxicokinetics of MEK was also evaluated in guinea pigs following intraperitoneal administration. Similar to the data shown in rats, there was no difference in the metabolic profile of MEK in guinea pigs. MEK was rapidly cleared following exposure, with a half life of 270 mins (4.5 hours) and clearance time of 12 hours. As shown in the rat studies, 2,3 -butanediol, 3 -hydroxy-2 -butanone and sBA were identified as the main metabolites. The metabolism of MEK was also studied in a different specie (humans) and route of exposure (inhalation). In the human volunteers, pulmonary uptake of MEK was rapid (53% through a 4 hour exposure period to 200 ppm). Elimination was also rapid, with a biphasic elimination phase comprising of an alpha phase (half life of 30 minutes) and a beta phase (half life of 81 minutes). Most of the absorbed dose was completely metabolized, as shown by the low level of absorbed dose excreted unchanged (3%). As reported in the rat study (Dietz et al, 1981), the metabolic rate of MEK was slow, with an observed clearance rate of about 0.33 - 0.44 liter/minute/kg. 2,3 -butanediol and and 3 -hydroxy-2 -butanone were reported to be the primary metabolites of MEK in the urine, although these were only found in small amounts.

Since MEK is a direct metabolite of sBA (>97% sBA rapidly converted to MEK following exposure), such that the metabolic profiles of MEK and sBA are identical across different species and routes of exposure, it is considered that MEK can function as a metabolic analogue to sBA for read-across purposes. Hence, it is possible to predict the metabolism and/or kinetics of sBA using data obtained from MEK. As isopropanol (IPA) is structurally similar to sBA (both secondary alcohols differing by one methyl group), IPA was also considered as a potential read-across analogue for sBA. The pharmacokinetics of IPA was evaluated in rats across different routes of exposure (oral and inhalation) (Slauter et al, 1994). Similar to sBA, IPA is oxidatively metabolized, via alchohol dehydrogenase, to the same carbon-numbered ketone (acetone). The highest blood levels of IPA and acetone were observed with oral exposures compared to inhalation exposures, most likely as a result of more rapid elimination of IPA and acetone in exhaled breath with inhalation exposure.

In conclusion, sBA is absorbed, distributed and excreted rapidly in urine, mainly as MEK, 3 -hdyroxy-2 -butanone and 2,3 -butanediol, following oral administration. A small percentage of sBA is also excreted via urine and exhalation. The pharmacokinetic data available for sBA indicate that sBA is rapidly metabolized to MEK, which is further hydroxylated to form 3-hydroxy-2-butanone. 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, sBA is not expected to bioaccumulate. The conclusion on bioaccumulation is supported by data in the IPA rat study that showed identical AUC, half life and Cmax values with rats administered a single 300 mg/kg dose of IPA or multiple 300 mg/kg/day doses of IPA for 8 days. Regardless of whether exposures were single or repeated, all blood IPA and acetone were efficiently eliminated within 96 hours, even at doses that exceeded metabolic saturation.