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EC number: 203-551-7 | CAS number: 108-11-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Short description of key information on bioaccumulation potential result:
The absorption and metabolism of methyl iso-butyl carbinol (MIBC) was investigated in rats in a GLP-compliant study. MIBC was rapidly absorbed in rats following a single oral exposure and was rapidly metabolized to MIBK with subsequent metabolism to diacetone alcohol (DAA).
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
As mentioned, metabolic data indicate that MIBC is rapidly metabolized to MIBK, which is subsequently metabolized to DAA, the major metabolite formed. MIBC has been reported to be metabolized to MIBK by alcohol dehydrogenase. Additionally, MIBK was reported to be metabolized to DAA via oxidation by the mixed function oxidase system. MIBK may be converted back to MIBC via reduction by ketone reductase; however such conversion has been reported to be negligible (<0.1% of the total dose). Hydroxylation products of MIBK, such as MIBC and DAA, are expected either to be conjugated with sulfate or glucuronic acid and excreted in urine or to enter intermediary metabolism to be converted to carbon dioxide. Based on the available metabolic data and taking into consideration its low molecular weight and log Pow value, MIBC is not expected to bioaccumulate. This conclusion is also supported by a recent publication (Saghir and Rick, 2008) showing no accumulation of MIBK (the primary metabolite of MIBC) in workers repeatedly exposed through inhalation.
Taken together, the data demonstrate that toxicological information on MIBK and /or DAA may be used as an appropriate surrogate for MIBC considering that MIBC is rapidly metabolized to MIBK and that the two substances share a common major metabolite, DAA.
Discussion on bioaccumulation potential result:
The mammalian metabolism of secondary alcohols proceeds primarily through their respective ketones. It has been demonstrated (Granvil et al., 1994) that MIBC is metabolized to methyl isobutyl ketone (MIBK: CAS No. 108-10-1) and subsequently to the primary metabolite of MIBK, 4-hydroxy-4-methyl-2-pentanone (HMP; CAS No. 123-42-2)[i.e. diacetone alcohol, DAA] in rats. In this study, no MIBC was detected in blood of rats following oral dosing although low concentrations of MIBC were found following inhalation exposure. Based on these preliminary findings, a study (Guillaumat, 2002; Gingell et al., 2003) was performed to confirm metabolism of MIBC to MIBK and to allow the use of the extensive toxicity database for MIBK to support the hazard assessment of MIBC.
Male Sprague-Dawley rats were orally dosed with MIBC or MIBK at a dose of 5 mmol/kg in corn oil (approximately 500 mg/kg). Following oral dosing of MIBC to rats, absorption is rapid with Cmax occurring at approximately 0.25 to 0.5 hours post-dosing. The half-life for MIBC in blood is approximately 2.3 hours. MIBC is rapidly metabolized to methyl isobutyl ketone (MIBK) and subsequently to the primary metabolite of MIBK, 4-hydroxy-4-methyl-2-pentanone (HMP). Plasma samples were collected at 0.125, 0.25, 0.5, 0.75, 1, 1.5, 3, 4.5, 6, 9 and 12 hours post-dosing. Plasma concentrations of MIBC, MIBK and HMP were measured at each time point. Selected pharmacokinetic parameters (non-compartmental) are listed in the following table:
Test Substance |
Analyte |
Cmax [mmole/L] |
Time of Cmax[hr] |
Half Life [hr] |
AUC0-12hr [mmole*hr/L] |
% Total AUC |
MIBK Total AUC |
MIBC |
0.014 |
NA |
4.657 |
0.089 |
0.05 |
MIBK |
0.644 |
0.25 |
2.529 |
3.558 |
20 |
|
HMP |
2.030 |
9 |
4.831 |
13.756 |
79 |
|
17.436 |
||||||
MIBC Total AUC |
MIBC |
0.588 |
0.5 |
2.256 |
0.819 |
6 |
MIBK |
0.450 |
1.5 |
1.571 |
2.268 |
17 |
|
HMP |
1.64 |
9 |
3.377 |
10.408 |
77 |
|
13.495 |
NA = Not applicable; no peak concentration could be determined due to the low concentrations at each measurement.
Following oral dosing of either MIBC or MIBK, absorption is rapid with Cmax for both compounds occurring at approximately 0.25 to 0.5 hours post-dosing. The half-life for both compounds in blood was short (approximately 2.3 and 2.5 hours, respectively). MIBC was not detectable by 9 hours following MIBC dosing. Total exposure (based on AUC0-12) to MIBK following dosing with either MIBC or MIBK was similar (2.3 and 3.6 mmol*h/l, respectively) as was exposure to HMP (10.4 and 13.8 mmol*h/l, respectively). Compared to MIBK and HMP, internal exposure to MIBC was minimal following dosing with MIBC (0.8 mmol*h/l), representing approximately 6% of the exposure to the three compounds over 12 hours. Therefore, the internal exposure to MIBC is minimal following MIBC dosing, and oral dosing of MIBC or MIBK results in similar internal exposure to MIBK and HMP.
The extent of metabolism of MIBC to MIBK can be determined by comparing the combined AUC for MIBK plus HMP, after administration of MIBC, to the combined AUC for these same materials after administration of MIBK. This analysis indicates the proportion of MIBC metabolized through MIBK to HMP is 12.676/17.314, or 73% of the administered dose of 5 mmole/kg. This value should be considered to be a lower estimate. It is likely that some MIBC is not absorbed or is rapidly excreted as a glucuronide or sulfate conjugate in the urine after oral bolus administration. This would decrease the amount available for metabolism to MIBK and HMP in the blood, as compared to that available after MIBK.Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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