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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 35
CCOHS Chemical Name: Diisobutyl ketone

Synonyms:
DIBK
2,6-Dimethyl-4-heptanone
Isobutyl ketone
Isovalerone
Dibutyl ketone (non-specific name)
sec-Diisopropyl acetone
sym-Diisopropylacetone
2,6-Dimethylheptan-4-one

Chemical Name French: Diisobutylcétone
Chemical Name Spanish: Diisobutilcetona
CAS Registry Number: 108-83-8
UN/NA Number(s): 1157
RTECS Number(s): MJ5775000
EU EINECS/ELINCS Number: 203-620-1
Chemical Family: Saturated aliphatic ketone / alkanone / nonanone
Molecular Formula: C9-H18-O
Structural Formula: CH3-CH(CH3)-CH2-C(=O)-CH2-CH(CH3)-CH3

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless liquid with a peppermint odour.(22)

Odour Threshold:
Greater than 0.11 ppm (absolute perception limit); 0.31 ppm (50-100% recognition) (23)

Warning Properties:
GOOD - TLV is more than 10 times the odour threshold.

Composition/Purity:
Diisobutyl ketone is commercially available in grades with purity of 75-100%. The technical material consists of a mixture of diisobutyl ketone (75-85%) and the closely related chemical (isomer), 4,6-dimethyl-2-heptanone (15-25%).(24) 2,6-Dimethyl-4-heptanol may also be present as a minor impurity (less than 2%).

Uses and Occurrences:
Diisobutyl ketone is used as a solvent for paints, stains, dyes, adhesives, roll-coating inks, nitrocellulose, lacquers, rubber, many natural and synthetic resins (e.g. vinyl resins), waxes and vinyl chloride copolymers; as a dispersant for polyvinyl chloride organosols; as an extraction agent; and as a solvent and feedstock for organic synthesis.(24,25,26)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless liquid with a peppermint odour. COMBUSTIBLE LIQUID AND VAPOUR. Can form explosive peroxides after prolonged storage (12 months) and exposure to air. Peroxides may explode violently when heated. Liquid can float on water and may travel to distant locations and/or spread fire. Vapour may be irritating to the eyes, nose, throat and upper respiratory tract. Central nervous system depressant. Vapour may cause headache, fatigue, nausea, dizziness, drowsiness, confusion and incoordination. Aspiration hazard. Swallowing or vomiting of the liquid may result in aspiration (breathing) into the lungs.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Diisobutyl ketone forms a vapour at room temperature. Exposure is expected to cause irritation of the nose, throat and upper respiratory tract and signs of central nervous system (CNS) depression such as fatigue, headache, nausea, dizziness and loss of coordination. Diisobutyl ketone is detectable by odour at relatively low concentrations (0.11 ppm) and provides a good warning of exposure. Slight nose and throat irritation is expected to occur at 50-100 ppm and intolerable irritation is expected at 287 ppm. Slight CNS effects (headache and dizziness) have been reported at 100 ppm.

Two men exposed to 50 ppm for 3 hours reported temporary slight irritation of the nose at the beginning of the exposure. There was no change in pulse rate or blood pressure during the exposure and no changes in the urine chemistry at 1 and 24 hours after exposure. Three men exposed to 100 ppm for 3 hours reported slight irritation of the nose, which decreased somewhat during exposure. Slight throat irritation, slight headache were also noted. After exposure, two men reported slight dizziness. All volunteers had normal pulse rates, normal blood pressure and normal urine chemistry.(6) Twelve men and women exposed to diisobutyl ketone for 15 minutes reported an unpleasant odour when exposed to concentrations above 25 ppm. The highest concentration to which the majority estimated they could be comfortably exposed to for 8 hours was 25 ppm.(7)

Skin Contact:
Diisobutyl ketone is a mild irritant, based on animal information. Repeated or prolonged exposure may cause dry, red, scaling skin (dermatitis) due to defatting.(21) There is no human information available.
Diisobutyl ketone is not expected to produce harmful effects if absorbed through the skin, based on animal toxicity information.

Eye Contact:
Liquid diisobutyl ketone is not irritating or a mild irritant, based on animal information. The vapour is expected to be slightly irritating above 25 ppm. Exposure to 287 ppm is expected to produce intolerable irritation, based on animal toxicity testing.
Twelve men and women reported eye irritation when exposed to concentrations above 25 ppm for 15 minutes.(7) Two men exposed to 50 ppm for 3 hours reported temporary slight irritation of the eyes at the beginning of the exposure. Three men exposed to 100 ppm for 3 hours reported slight irritation of the eyes and tearing, which decreased somewhat during exposure.(6)

Ingestion:
Diisobutyl ketone is not expected to be toxic if ingested, based on animal information. There is no human information available. Although there are no case reports, diisobutyl ketone can probably be aspirated into the lungs during ingestion or vomiting, based on animal information and its physical properties. Aspiration of even a small amount of liquid could result in severe lung irritation, significant damage to the lung tissues (edema), and, in some cases, death. Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

Nervous System:
It is not possible to draw conclusions about diisobutyl ketone from an unusual and extreme exposure situation described in a case report. A 60-year-old male was exposed to unreported, but predictably very high, concentrations of diisobutyl ketone vapour, while experimenting with using diisobutyl ketone heated to 700 deg C and placed under 2300 pounds of pressure to strip iron ore. After exposure for approximately one month he developed severe headaches and a 20-minute loss of vision. Magnetic resonance imaging (MRI) indicated brain injury.(20) In addition to the extreme exposure conditions, there might have been concurrent exposure to the iron ore or other contaminants.

Skin:
Diisobutyl ketone is expected to cause dry, red, scaly skin (contact dermatitis) following repeated or prolonged contact, based on animal information and comparison to other ketones.

Skin Sensitization:
Diisobutyl ketone is not expected to be a skin sensitizer. No human information was located. No sensitization was observed in an unpublished Guinea Pig Maximization Test.

Carcinogenicity:

There is no human or animal information available.

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has not assigned a carcinogenicity designation to this chemical.

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
There is no human information available. Information from an unpublished reproductive toxicity screening test using rats suggests that diisobutyl ketone does not cause developmental toxicity.

Reproductive Toxicity:
There is no human information available. Information from an unpublished reproductive toxicity screening test using rats suggests that diisobutyl ketone does not cause reproductive toxicity.

Mutagenicity:
There is no human or animal information available. The information available from short-term tests does not indicate that diisobutyl ketone is mutagenic.

Toxicologically Synergistic Materials:
There is no information available.

Potential for Accumulation:
Probably does not accumulate. Other ketones are quickly metabolized and excreted by guinea pigs and rats.(21) There is no human information available.


SECTION 4. FIRST AID MEASURES

Inhalation:
If symptoms are experienced, remove source of contamination or move victim to fresh air. Obtain medical advice.

Skin Contact:
Remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Gently blot or brush away excess chemical. Wash gently and thoroughly with lukewarm, gently flowing water and non-abrasive soap for 5 minutes. If irritation persists, repeat flushing and obtain medical advice. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Gently blot or brush chemical off the face. Flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes, while holding the eyelid(s) open. If irritation persists, repeat flushing and obtain medical advice.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness or is unconscious or convulsing. Rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. If vomiting occurs naturally, have the victim lean forward to reduce the risk of aspiration. Have victim rinse mouth with water again. Immediately obtain medical attention.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
49 deg C (120 deg F) (closed cup) (12,22)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not available at room temperature; 0.8% at 93 deg C (200 deg F) (12)

Upper Flammable (Explosive) Limit (UFL/UEL):
Not available at room temperature; 7.1% at 93 deg C (200 deg F) (12)

Autoignition (Ignition) Temperature:
396 deg C (745 deg F) (12)

Sensitivity to Mechanical Impact:
Probably not sensitive. Stable material.

Sensitivity to Static Charge:
Diisobutyl ketone will probably not accumulate static charge since it has a medium dielectric constant.(27,28) Diisobutyl ketone vapour will not be ignited by a static discharge at room temperature due to its moderately high flash point.

Electrical Conductivity:
Not available

Minimum Ignition Energy:
Not available

Combustion and Thermal Decomposition Products:
Carbon monoxide, carbon dioxide and other toxic and irritating gases and fumes.

Fire Hazard Summary:
COMBUSTIBLE LIQUID. Can release vapours that form explosive mixtures with air at, or above, 49 deg C. Liquid can float on water and may travel to distant locations and/or spread fire. During a fire, irritating/toxic gases and fumes may be generated. Can form explosive peroxides during prolonged exposure to air. Peroxides may explode violently when heated. Closed containers may rupture violently and suddenly release large amounts of product when exposed to fire or excessive heat for a sufficient period of time.

Extinguishing Media:
Carbon dioxide, dry chemical powder, appropriate foam, water spray or fog. Fire fighting foams, such as multipurpose, alcohol-resistant foams, are recommended for most flammable/combustible liquid fires.(12) Foam manufacturers should be consulted for recommendations regarding types of foams and application rates.

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products. Wear full protective suit if exposure is possible. See Protection of Firefighters.
Closed containers may rupture violently when exposed to the heat of fire and suddenly release large amounts of products. Stay away from ends of tanks, but be aware that flying material (shrapnel) from ruptured tanks may travel in any direction.
If possible, isolate materials not yet involved in the fire and move containers from fire area if this can be done without risk. Protect personnel. Otherwise, cool fire-exposed containers, tanks or equipment by applying hose streams. Cooling should begin as soon as possible (within several minutes) and should concentrate on any unwetted portions of the container. Apply water from the side and a safe distance. Cooling should continue until well after the fire is out. If this is not possible, use unmanned monitor nozzles and immediately evacuate the area.
If a leak or spill has not ignited, use water spray in large quantities to disperse the vapours, to flush spills away from ignition sources and to protect personnel attempting to stop the leak. Dike fire control water for appropriate disposal. Solid streams of water may be ineffective and spread material.
For an advanced or massive fire in a large area, use unmanned hose holders or monitor nozzles; if this is not possible withdraw from fire area and allow the fire to burn. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank. Tanks or drums should not be approached directly after they have been involved in a fire, until they have been completely cooled down.
After the fire has been extinguished, toxic atmospheres may remain. Before entering such an area, especially confined areas, check the atmosphere with an appropriate monitoring device while wearing full protective gear.

Protection of Fire Fighters:
Diisobutyl ketone is an inhalation hazard. Firefighters may enter the area if positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) and full Bunker Gear is worn.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 1 - Exposure would cause significant irritation, but only minor residual injury.
NFPA - Flammability: 2 - Must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur.
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 142.24

Conversion Factor:
1 ppm = 5.81 mg/m3; 1 mg/m3 = 0.17 ppm at 25 deg C (calculated)

Physical State: Liquid
Melting Point: -41.5 deg C (-42.7 deg F).(27,28) Also reported as -46.04 deg C (-50.9 deg F) (29)
Boiling Point: 168.24 deg C (334.8 deg F) (29,30); 169.4 deg C (336.9 deg F) (22,27)
Relative Density (Specific Gravity): 0.806 at 20 deg C (29); 0.802 at 25 deg C (31) (water = 1)
Solubility in Water: Practically insoluble (50 mg/100 mL at 20 deg C).(22,23) Also reported as slightly soluble (264 mg/100 mL at 24 deg C).(32)
Solubility in Other Liquids: Miscible with ethanol, diethyl ether, benzene, chloroform and most common organic solvents; soluble in carbon tetrachloride.(24,27,28)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 2.56 (estimated) (33)
pH Value: Not applicable
Acidity: Ketones are weak acids.(36)
Dissociation Constant: pKa = 21 (37)
Viscosity-Dynamic: 1.02 mPa.s (1.02 centipoises) at 20 deg C (22); 0.95 mPa.s (0.95 centipoises) at 25 deg C (34); also reported as 0.903 mPa.s (0.903 centipoises) at 20 deg C (29)
Viscosity-Kinematic: 1.27 mm2/s (1.27 centistokes) at 20 deg C; 1.18 mm2/s (1.18 centistokes) at 25 deg C (calculated); also 1.12 mm2/s (1.12 centistokes) at 20 deg C (calculated)
Saybolt Universal Viscosity: 29.5-30 Saybolt Universal Seconds at 37.8 deg C (100 deg F) (calculated)
Surface Tension: 24.54 mN/m (24.54 dynes/cm) at 20 deg C (35)
Vapour Density: 4.9 (air = 1) (calculated)
Vapour Pressure: 0.22 kPa (1.65 mm Hg) at 25 deg C (30)
Saturation Vapour Concentration: 2200 ppm (0.22%) at 25 deg C (calculated)
Evaporation Rate: 0.19 (n-butyl acetate = 1) (31,34)
Henry's Law Constant: 11.9 Pa.m3/mol (cited as 1.17 x 10(-4) atm.m3/mol) at 25 deg C (32); log H = -2.32 (dimensionless constant; calculated)

Other Physical Properties:
DIELECTRIC CONSTANT: 9.91 at 20 deg C (27,28)

Physical Properties Comments:
Note: The physical properties reported here are for pure diisobutyl ketone. However, commercial diisobutyl ketone is available as a mixture of isomers and the mixture physical properties may be different.


SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable. Prolonged (12 months) exposure to air can produce peroxides.(42) Concentrated solutions of ketone peroxides (greater than 30%) may explode.(22)

Hazardous Polymerization:
Does not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


STRONG OXIDIZING AGENTS (e.g. bromine, chromium trioxide, nitric acid, nitric acid-sulfuric acid mixture) - may react violently or explosively, with increased risk of fire.(10,12,38)
PERCHLORIC ACID - ketones may undergo violent decomposition in contact with 68-72% acid.(12,38)
HYDROGEN PEROXIDE or MIXTURES of HYDROGEN PEROXIDE and NITRIC ACID - may overheat and explode violently due to the formation of shock- and heat-sensitive peroxides.(12,38)
MIXTURES of HALOFORMS (e.g. chloroform or bromoform) and STRONG BASES (e.g. potassium hydroxide) - may react vigorously or explosively, with evolution of heat.(38)

Hazardous Decomposition Products:
Unstable peroxides (following prolonged storage, and in the presence of air).

Conditions to Avoid:
Open flames, heat, hot surfaces and other ignition sources and prolonged exposure to air.

Corrosivity to Metals:
There is no specific information available for diisobutyl ketone. In general, ketones are not corrosive (corrosion rate less than 0.05 mm/year) at 20 deg C to common metals, such as stainless steel (e.g. types 302, 304, 316, 400 series and Carpenter 20Cb-3), aluminum (types 3003 and Cast B-356), carbon steel (types 1010, 1020,1075 and 1095), cast iron (e.g. gray, ductile high nickel and high silicon), nickel, nickel-base alloys (e.g. Hastelloy C, Inconel, Incoloy and Monel), copper, copper-nickel, aluminum and silicon bronze, naval brass, tantalum, titanium and zirconium.(39)

Corrosivity to Non-Metals:
Diisobutyl ketone attacks plastics, such as polyvinylidene chloride (PVDC (Saran)), chlorinated polyvinyl chloride (CPVC), polyvinyl chloride (PVC), polyurethane and polystyrene (40); and elastomers, such as nitrile Buna-N (NBR), Viton, chloroprene, polyurethane, isoprene, fluorosilicone and silicone.(41) Diisobutyl ketone does not attack plastics, such as Teflon and other fluorocarbons, and polypropylene (40); and elastomers, such as ethylene-propylene, butyl rubber, styrene-butadiene (SBR), Chemraz and Kalrez.(41).

Stability and Reactivity Comments:
Saturated C9 ketones, e.g. diisobutyl ketone, are thermally stable up to pyrolysis temperatures (500-700 deg C).(22)


SECTION 11. TOXICOLOGICAL INFORMATION

LD50 (oral, mouse): 2820 mg/kg (cited as 3.5 mL/kg) (10-40% "temporary emulsion" in 1% Tergitol) (3)
LD50 (oral, rat): 5750 mg/kg (cited as 5.75 gm/kg) (1)
LD50 (oral, mouse): 1416 mg/kg (2,4-unconfirmed)

LD50 (dermal, rabbit): 16120 mg/kg (cited as 20 mL/kg) (1)
LD50 (dermal, rat): greater than 2000 mg/kg (43, unconfirmed)

Eye Irritation:

Diisobutyl ketone is a non- to mild eye irritant.

In an OECD-compliant test, application of 0.1 mL of undiluted diisobutyl ketone caused no irritation in rabbits (corneal opacity: 0/4; iris injury: 0/2; redness: 0.11/4; chemosis: 0/4).(14) Application of 0.1 mL undiluted diisobutyl ketone resulted in mild irritation (scored 4/110 at 24 hours and 0/110 at 72 hours).(3) Application of 0.5 mL of undiluted diisobutyl ketone caused no or mild injury (scored 0-1 where 5 is severe injury; graded 1/10).(1)

Skin Irritation:

Most studies indicate that diisobutyl ketone is a mild irritant. An unconfirmed study reports moderate irritation in guinea pigs.

Application of 0.01 mL undiluted diisobutyl ketone produced mild irritation in rabbits (graded 3/10).(1) Application of an unspecified amount of undiluted diisobutyl ketone for 8.5 hours caused slight redness in 2/2 rabbits.(3) Application of an unspecified amount of undiluted diisobutyl ketone to covered and uncovered skin of guinea pigs caused moderate irritation. In another study, application of 10 mg/kg under an airtight wrap for 24 hours caused mild irritation in rabbits.(4, unconfirmed) In an OECD-compliant test, application of 0.5 mL undiluted diisobutyl ketone for 1 or 4 hours was found to be irritating to rabbits when applied under an airtight patch, but non-irritating under an air-permeable patch. The degree of irritation is not reported, but the criteria used for determining irritancy are those given in the EEC directive.(15)

Effects of Short-Term (Acute) Exposure:

The main effects noted from inhalation exposure are irritation of the respiratory system and depression of the central nervous system (CNS). Exposure to high concentrations (905 ppm) for 9 days caused reversible kidney injury (hyaline droplet nephrosis) in male rats. However, male rats are particularly sensitive to this effect and the significance of this observation to human exposures to questionable. Repeated skin contact caused some redness in rabbits. Ingestion of large oral doses (1000 mg/kg/day for 3 weeks) caused minor kidney changes.

Inhalation:
Mice exposed by inhalation to 184, 205, 235, 290, or 351 ppm for 15 minutes exhibited a concentration-related decrease in respiratory rate. The RD50 (the dose resulting in a decrease in the respiratory rate by 50%) was calculated to be 287 ppm. The RD50 is an indicator of sensory irritation (irritation to the eyes and nose).(17) People exposed to the RD50 would experience intolerable burning of the eyes, nose and throat. Neurobehavioural changes were evaluated by measuring the period of immobility during a "behavioural despair" swimming test. Mice exposed to 243, 275, 300 or 379 ppm for 4 hours showed a concentration-related decrease in the total duration of the immobility phase and the ID50 (dose resulting in a decrease in the immobility period by 50%) was calculated to be 310 ppm. This test shows early signs of CNS depression.(16) No deaths were observed in rats or guinea pigs exposed once to a saturated vapour (approximately 2200 ppm) for 7.5-16 hours. Mice exposed to a saturated vapour for 9.5-11.5 hours became unconscious after 3 hours and died in 7 hours. No deaths occurred in mice given twelve 3-hour exposures to the saturated vapour.(3) The susceptibility of rats to diisobutyl ketone appears to depend on the strain and the sex tested. For Sherman rats, 7/12 females and 0/6 males died when exposed to 2000 ppm for 8 hours. For Carworth Farm Wistar rats, both sexes survived exposure to 2000 ppm for 8 hours.(6) Exposure to 2000 ppm for 8 hours caused death 5/6 female rats. Exposure to the concentrated vapour (approaching 2300 ppm) for 4 hours produced no deaths in 6 female rats.(1,6) Rats were exposed daily to 0, 98, 300 or 905 ppm for 9 days (6 hrs/d). At 905 ppm, there was decreased body weight gain, mild eye irritation, a 20% increase in platelet count, some minor changes in blood chemistry, and an increase in liver and kidney weights in both sexes. In males, the increase in kidney weight was larger and was accompanied by an increase in water intake and urine volume, changes in urine chemistry and some signs of degeneration in the kidney. At 300 ppm, an increase in platelet count, minor changes in blood chemistry, and an increase in urine volume were observed in males. Increased liver weights were noted in males and females. The only effect reported at 98 ppm was an increase in urine volume for males. All effects decreased or disappeared when rats were allowed to recover for 2 weeks.(5) No changes in weight gain, liver or kidney weights, serum or blood chemistry, or tissue structure were observed in male rats following twelve 6-hour exposures to 400 ppm.(4, unconfirmed)

Skin Contact:
Twelve 5-hour applications of an unspecified amount of undiluted diisobutyl ketone over 21 days caused some redness in 2/2 rabbits.(3)

Ingestion:
Male rats were orally administered 0, 1000, 2000, or 4000 mg/kg/day for 3 weeks (5 d/wk). At 4000 mg/kg/day, all rats died during the first week of exposure from severe CNS depression, liver toxicity and dehydration. At 2000 mg/kg/day, 2/3 rats showed severe CNS depression after the first doses, but both quickly developed tolerance to diisobutyl ketone. There were no effects on body weight or food consumption, but there were minor changes in the kidneys and slight enlargement of liver cells. At 1000 mg/kg/day, only minor changes in the kidneys were observed.(18) In studies designed to assess aspiration potential of chemicals, diisobutyl ketone was aspirated into the lungs of rats resulting in death by respiratory arrest and/or cardiac failure.(19)

Effects of Long-Term (Chronic) Exposure:

Inhalation:
Rats (Sherman stock) were exposed to 0, 125, 250, 530, 920, or 1650 ppm and guinea pigs to 0, 125 or 250 ppm for 6 weeks (7 hrs/d). Female rats were more affected than male rats. At 1650 ppm, 15/15 female rats and 2/15 male rats died. Males that survived exposure to 1650 ppm had lower body weights, and higher kidney and liver weights than controls. At the lower concentrations, no rats died. Increased kidney and liver weights were noted in both rat sexes at 920 and 530 ppm, in females at 250 ppm, and were not seen in either sex at 125 ppm. In guinea pigs, the only response noted was a decrease in liver weight for males exposed to 250 ppm.(6)

Ingestion:
No deaths or gross pathological changes were noted in male rats ingesting 2000 mg/kg/day for 90 days. Body weights were significantly reduced at the end of the study, primarily because of decreased food consumption during the first week of exposure. The treated rats had significantly decreased glucose levels and increased liver, kidney (relative weight), and adrenal gland weights. Brain and heart weights (absolute) were significantly lower. Examination of tissues showed an increase in size of liver cells, minor changes in the kidneys, and chronic irritation of the digestive tract. No evidence of neurotoxicity was found.(18)

Skin Sensitization:
Diisobutyl ketone did not produce sensitization in an unpublished Guinea Pig Maximization Test conducted in compliance with OECD Guidelines.(43, unconfirmed)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
No developmental effects were observed in an unpublished reproductive toxicity screening test (see "Reproductive Toxicity" below).

Reproductive Toxicity:
An unpublished screening test suggests that diisobutyl ketone is not harmful to reproduction.
In an unpublished reproductive toxicity screening test, rats (10/sex/group) were orally given 0, 100, 300, or 1000 mg/kg/day diisobutyl ketone in corn oil from two weeks prior to mating throughout pregnancy until weaning day 5 after birth. Two dams exposed to 1000 mg/kg/day died and male body weight gains were suppressed at this dose level. There was no evidence of an effect on any of the reproductive parameters investigated or on any of the surviving litters. There was no effect on the number of pregnancies, litters born, number of implantations or proportion of pups born live in any dose group.(43, unconfirmed)

Mutagenicity:
The available information does not indicate that diisobutyl ketone is mutagenic.
A negative result (chromosome aberrations) was obtained in cultured mammalian cells.(9) Negative results (gene mutation) were also obtained in 5 strains of bacteria, in the presence and absence of metabolic activation (8,9), and in yeast (9).


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Smyth, Jr., H.F. , et al. Range-finding toxicity data: list III. Journal of Industrial Hygiene and Toxicology. Vol. 31 (1949). p. 60-62
(2) National Institute for Occupational Safety and Health (NIOSH). Diisobutyl ketone. Last updated: 2002-10. In: Registry of Toxic Effects of Chemical Substances (RTECS(R)). [CD-ROM]. Canadian Centre for Occupational Health and Safety (CCOHS). Issue: 2003-1. Also available from World Wide Web: <http://ccinfoweb.ccohs.ca/rtecs/search.html>
(3) McOmie, W.A., et al. Comparative toxicological effects of some isobutyl carbinols and ketones. University of California, Berkeley, Publications in Pharmacology. Vol. 2 (1949). p. 217-230
(4) Topping, D.C., et al. Ketones of six to thirteen carbons. In: Patty's toxicology. 5th ed. Edited by E. Bingham, et al. Vol. 6. John Wiley and Sons, 2001. p. 317-321
(5) Dodd, D.E., et al. Hyalin droplet nephrosis in male Fischer-344 rats following inhalation of diisobutyl ketone. Toxicology and Industrial Health. Vol. 3, no. 4 (Dec. 1987). p. 443-457
(6) Carpenter, C.P., et al. Toxicity and hazard of diisobutyl ketone vapors. AMA Archives of Industrial Hygiene and Occupational Medicine. Vol. 8 (1953). p. 377-381
(7) Silverman, L., et al. Further studies on sensory response to certain industrial solvent vapors. Journal of Industrial Hygiene and Toxicology. Vol. 28, no. 6 (1946). p. 262-266
(8) Mortelmans, K., et al. Salmonella mutagenicity tests. 2. Results from the testing of 270 chemicals. Environmental Mutagenesis. Vol. 8, suppl. 7 (1986). p. 1-119
(9) Brooks, T. M., et al. The genetic toxicology of some hydrocarbon and oxygenated solvents. Mutagenesis. Vol. 3, no. 3 (1988). p. 227-232
(10) Diisobutyl ketone. In: NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety and Health, June 1997. p. 108-109
(11) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(12) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 325, 491 (ketones)
(13) European Economic Community. Commission Directive 93/72/EEC. Sept. 1, 1993
(14) Eye irritation: reference chemicals data bank. 2nd ed. Technical Report No. 48. June 1998
(15) Potokar, M., et al. Studies on the design of animal tests for the corrosiveness of industrial chemicals. Food Chemistry and Toxicology. Vol. 23, no. 6 (1985). p. 615-617
(16) De Ceaurriz, J., et al. Concentration-dependent behavioral changes in mice following short-term inhalation exposure to various industrial solvents. Toxicology and Applied Pharmacology. Vol. 67, no. 3 (1983). p. 383-389
(17) De Ceaurriz, J., et al. Quantitative evaluation of sensory irritating and neurobehavioural properties of aliphatic ketones in mice. Food and Chemical Toxicology. Vol. 22, no. 7 (1984). p. 545-549
(18) Initial submission: letter from Eastman Kodak Co. to USEPA regarding toxicity studies of 5-methyl-2-hexanone and other chemicals with attachments and cover letter dated 09/28/92. Eastman Kodak Co. Date produced: Sept. 28, 1992. EPA/OTS 88-920009460. NTIS/OTS0571116.
(19) Gerarde, D.F., et al. The aspiration hazard and toxicity of a series of ketones. Fairleigh Dickinson University. Date produced: Apr. 12-13, 1968. EPA/OTS 878210934. NTIS/OTS0206264.
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2006-12-15



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