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EC number: 203-620-1 | CAS number: 108-83-8
- 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
Key value for chemical safety assessment
Effects on fertility
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 11 635 mg/m³
Additional information
In an OECD 421 screening study, with oral gavage administration of Diisobutyl Ketone (DIBK) at 100, 300 and 1000 mg/kg bw/kg bw/day, two females in the high dose group were adversely affected during lactation. There was an overall suppression of group mean bodyweight gains in males receiving 1000 mg/kg bw/day. No treatment related adverse effects on fertility were observed in this study. The NOAEL for general toxicity was 300 mg/kg bw/day in adults and 1000 mg/kg bw/day in offspring.
No further fertility studies are available for DIBK as such. However, a 2-generation reproduction toxicity study in rats is available for the structurally related methyl isobutyl ketone (MIBK). MIBK and DIBK are closely related in molecular structure and physicochemical properties and thus, the potential for toxicological effects. They are liquids with comparable physical chemical properties. Increasing boiling point and vapor pressure are consistent with increasing molecular weight. Both ketones are neutral lipophilic compounds of small molecular weight with relatively low Kow and no appreciable ionization at biological pH (neutral compound). Absorption of DIBK is expected to be similar to MIBK. Due to its lipophilicity DIBK will have high oral bioavailability, but will be rapidly eliminated from the system either in urine after conjugation with sulphate or glucuronic acid or converted to carbon dioxide, similar to MIBK, with little remaining in the tissues shortly after the secession of exposure. This conclusion is also supported by the very high LD50 of DIBK following oral, dermal and inhalation exposures. Based on the structural similarity between DIBK and MIBK, it is expected that DIBK will be metabolised in the same ways as MIBK. MIBK is metabolized to 4-methyl-2-pentanol (4-MPOL), which is formed by the reduction of ketone group of MIBK with ketone reductase, and 4-hydroxy-4-methyl-2-pentanone (HMP) formed by cytochrome P450 oxidation of the C-H bond at 4 position of the aliphatic chain in MIBK. In a similar metabolic pattern, DIBK will be expected to be metabolised to 2,6-dimethylheptan-4-ol (ketone reduction) and 2-hydroxy-2,6-dimethylheptan-4-one (C-H bond oxidation). No major differences in the toxicological profile have been observed between MIBK and DIBK for other endpoints. Both substances have a low acute toxicity via the dermal and oral route, and may cause respiratory irritation. No effects have been observed with either ketone in sensitisation and mutagenicity studies. The target organs for repeated dose toxicity of both MIBK and DIBK are liver and kidney, with DIBK being the less toxic compound with higher no effect levels in the repeated dose studies compared to MIBK.
The reproductive toxicity of MIBK was evaluated in a GLP-compliant multi-generation toxicity study in rats. The study design was equivalent to OECD test guideline 416. Rats were administered MIBK at target concentrations of 0, 500, 1000 and 2000 ppm (mean measured concentrations were 0, 491, 999, and 1996 ppm) by whole body inhalation. Parental (F0) findings included transient decreased body weight during the first 2 weeks of exposure at the 2000 ppm dose concentration and increases in absolute and relative liver weights at 2000 ppm. Significant increases in parental F0 and F1 mean absolute and relative kidney weights were observed for males in all MIBK-treated groups relative to the control group; however, mean kidney weights of female rats were unaffected. These increases in mean kidney weight were attributed to an alpha2µ-mediated mechanism and are not considered relevant to human risk identification (see IUCLID Section 7.9.3). Offspring findings included a single mortality and signs of CNS depression in the F1 group following MIBK exposure on postnatal day (PND) 22 to 25. As a result, MIBK exposure of the F1 group was suspended until PND 27. CNS depressive effects were observed until PND 31, but not after. F1 animals in the 1000 and 2000 ppm groups showed reduced reactivity to novel stimulus during exposure, which was attributed to a sedative effect. There were no effects on reproductive parameters reported. Based on these findings the NOAEL for parental systemic toxicity and neonatal toxicity was considered to be 1000 ppm. The NOAEL for reproductive toxicity was considered to be 2000 ppm, the highest dose tested.
Short description of key information:
A GLP-study according to OECD guideline 421 (oral gavage) is
available for diisobutyl ketone and a GLP-study according to OECD
guideline 416 (inhalation) is available for the structural analogue
methyl isobutyl ketone.
Effects on developmental toxicity
Description of key information
A GLP-study according to OECD guideline 421 (oral gavage) is available for diisobutyl ketone and two GLP-studies equivalent to OECD guideline 414 (inhalation) in rats and in mice are available for the structural analogue methyl isobutyl ketone.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
- Dose descriptor:
- NOAEC
- 5 808 mg/m³
Additional information
In an OECD 421 screening study with oral gavage administration of diisobutyl ketone (DIBK) up to 1000 mg/kg bw/day, there was no effect on the number of implantations or proportion of pups born live in any dose group and there were no clinical observations in pups which were considered to be related to DIBK administration.
No further developmental toxicity studies are available for DIBK as such. However, two inhalation teratology studies in rats and mice are available for the structural analogue methylisobutyl ketone (MIBK).
Developmental and maternal toxicity were evaluated in groups of 35 pregnant Fischer 344 rats and 30 pregnant CD-1 mice exposed by inhalation to 0, 300, 1000, or 3000 ppm MIBK for 6 hrs/day on gestation days 6 through 15. Animals were sacrificed on gestation day 21 (rats) or 18 (mice). Dams were evaluated for exposure-related changes in clinical signs, body weight, food consumption, organ weights (kidney, liver, and gravid uterus), and reproductive parameters; fetuses were evaluated for exposure-related changes in body weight and viability, and for external, skeletal, and thoracic and peritoneal visceral alterations. Maternal mean body weight, weight gain, and food consumption were significantly decreased in rats exposed to 3000 ppm (but not to 1000 ppm or lower) during the exposure period, but they had recovered to control levels by the day of sacrifice; maternal body weight was not affected in mice. Maternal clinical signs observed in rats or mice included coordination loss, hindlimb weakness, paresis, irregular gait, hypoactivity, ataxia, unkempt fur, negative tail or toe pinch, piloerection, lacrimation, or red perioral encrustation. These clinical signs were observed only during the exposure period and only at 3000 ppm. Three maternal deaths (12% of the animals in the group) occurred in mice exposed to 3000 ppm after the first exposure on gestation day 6; no further deaths occurred in that group, and no exposure-related deaths occurred in the other mouse or rat exposure groups. Neonates from those dams were not considered in the final evaluation. Statistical analyses by the authors were per dam or per litter. No exposure-related effects were observed in rats or mice with respect to numbers of corpora lutea, total implants, percent implantation loss, live fetuses per litter, nonviable implants per litter, percent live fetuses, and sex ratio. In mice, there was an increased mean number of dead fetuses per litter at 3000 ppm (0.6 per litter compared to 0.1 in controls). Fetal body weights (litter weight, male weight per litter, and female weight per litter) were significantly reduced in rats exposed to 300 ppm (the mean by 3%) and 3000 ppm (the mean by 6%) but not to 1000 ppm; and in mice, fetal body weights were statistically significantly reduced at 3000 ppm (the mean by 13%) but not at 1000 ppm or below. The authors indicated that the reduction in rat fetal body weight was confounded by a skewed distribution of litter size, whereby higher doses had very small litters and smaller litters had varied mean weights across dose, while lower-dosed dams appeared to have larger litters and larger litters showed a dose-dependence in mean weight. There was no statistically significant increase in the number of rat or mouse fetuses per litter. The authors decided the reductions in rat fetal body weight was not treatment-related. No exposure-related change in the incidence of malformations of any type were observed in rat and mouse fetuses. The number of litters with observations indicating retarded skeletal ossification was significantly increased to various degrees in both rats and mice at 3000 ppm relative to controls for a variety of skeletal endpoints, with scattered increases in litters with retarded ossification at lower exposure levels that were not considered to be exposure-exposure-related.
Justification for classification or non-classification
No developmental effects or effects on fertility were observed with diisobutyl ketone. Hence, no classification is required according to DSD and CLP.
Additional information
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