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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 17
CCOHS Chemical Name: 1-Butanol

Synonyms:
n-Butanol
Butyric alcohol
Butyl alcohol (non-specific name)
1-Hydroxybutane
Propylcarbinol
n-Butyl alcohol

Chemical Name French: Alcool butylique normal
Chemical Name Spanish: Alcohol n-butílico
CAS Registry Number: 71-36-3
UN/NA Number(s): 1120
RTECS Number(s): EO1400000
EU EINECS/ELINCS Number: 200-751-6
Chemical Family: Saturated primary aliphatic alcohol / primary alkanol / primary alkyl alcohol / butanol / butyl alcohol
Molecular Formula: C4-H10-O
Structural Formula: CH3-CH2-CH2-CH2-OH

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless liquid with a sweet rancid odour.(8,11)

Odour Threshold:
Reported values vary widely; 0.12-11 ppm (geometric mean: 1.2 ppm) (detection); 1-20 ppm (geometric mean: 5.8 ppm) (recognition) (37)

Warning Properties:
GOOD - TLV is about 8.5 times the geometric mean recognition odour threshold.

Composition/Purity:
Available commercially at greater than 99% purity. 1-Butanol is one of the chemical forms (isomers) of butyl alcohol or butanol. This CHEMINFO review contains the available information specific for 1-butanol, supplemented with general information on alcohols which is applicable to 1-butanol.

Uses and Occurrences:
1-Butanol is used to make other chemicals, e.g. n-butyl acrylate, n-butyl methacrylate, glycol ethers, such as 2-butoxyethanol, n-butyl acetate, dibutyl phthalate, dibutyl sebacate, butylated melamine-formaldehyde resins and mono-, di- and tributylamines and herbicides. It is also used as a direct solvent for fats, paints, other surface coatings, gums, dyes, alkaloids, camphor, and in the formulation of pharmaceuticals, waxes, and natural and synthetic resins; in a mixture with other solvents as a solvent in the production of nitrocellulose lacquers, and as a thinner; as an extractant in the manufacture of antibiotics, hormones, vitamins, hop and vegetable oils; as a swelling agent in textiles; as a component of brake fluids, cleaning formulations, degreasers, and repellents; as a flotation agent; and as a protective agent for glass objects.(8,38)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless liquid with a sweet rancid odour. FLAMMABLE LIQUID AND VAPOUR. Vapour is heavier than air and may spread long distances. Distant ignition and flashback are possible. Mild central nervous system depressant. Very high vapour may cause headache, nausea, dizziness and drowsiness. EYE AND SKIN IRRITANT. Causes severe eye irritation and moderate eye irritation. Aspiration hazard. Swallowing or vomiting of the liquid may result in aspiration into the lungs.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
1-Butanol readily forms a vapour at normal temperatures. Inhalation can cause irritation of the nose and throat. High concentration of the vapour or mists can cause headaches, dizziness, and drowsiness. These are symptoms of central nervous system (CNS) depression.
Human volunteers were exposed to varying concentrations of 1-butanol vapour. Mild nose and throat irritation was experienced at 25 ppm. Mild headaches and pronounced irritation were reported at 50 ppm.(1) Men inhaling 200 ppm for 30 minutes while doing heavy physical exercise did not show any effects.(2) Brief exposure (5-6 minutes) to 1270-3010 ppm is expected to produce intolerable nose and throat irritation in humans, based on animal information.

Skin Contact:
1-Butanol is a slight to moderate skin irritant, based on animal information. No human information was located.
1-Butanol is absorbed through skin.(8,61) However, significant toxicity by this route of exposure is not expected.

Eye Contact:
The liquid is a severe eye irritant, based on animal information. No human information was located.
Vapour concentrations exceeding 50 ppm can irritate the eyes.(3) Inflammation of the eyes, blurred vision, tearing and sensitivity to light were observed in employees exposed to higher concentrations (100-200 ppm).(4) It is not clear if these effects are due to short- or long-term exposure. In a study using 8 volunteers, exposures of up to 1000 ppm for up to 1 hour produced only very slight eye irritation.(5) Brief exposure (5-6 minutes) to 1270-3010 ppm is expected to produce intolerable eye irritation in humans, based on animal information.

Ingestion:
1-Butanol is not considered toxic if ingested, based on animal toxicity values. In general, ingestion of large amounts of butyl alcohols can cause effects resembling "alcohol" intoxication such as headache, dizziness, confusion, nausea and vomiting. In severe cases, breathing difficulty, unconsciousness, coma and death can occur. Liver injury has been reported in individuals who ingested butyl alcohol non-occupationally.(6) If ingested or vomited, 1-butanol can be aspirated into the lungs where it can cause severe lung damage, with accumulation of fluid (pulmonary edema), and possibly death. Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

Nervous System:
No firm conclusions can be drawn about possible long- term effects on the nervous system based on the limited information available.
There is one case report of an employee developing severe dizziness (vertigo) following a 1 year exposure to 1-butanol, 2-3 hours/day. While performing his work, he experienced digestive discomfort, nausea and dizziness.(12) It is not possible to draw firm conclusions from this report. The individual involved was exposed to other potentially harmful chemicals and exposure information is not available.

Skin:
1-Butanol can remove essential oils from the skin and prolonged or repeated skin contact may result in dry, red, cracked skin (dermatitis).(3)

Skin Sensitization:
There is insufficient information to conclude that 1-butanol is a skin sensitizer.
A positive patch test was reported in an individual who also tested positive to isopropanol, 2-butanol and formaldehyde. This individual had a history of slight, itching lesions on the skin of her fingers and hands.(13) It is not clear that she did not have a previous history of allergies or that she was occupationally exposed to 1-butanol.

Eyes/Vision:
Historical reports suggest that prolonged exposure to concentrations of approximately 100 ppm or above may cause harmful effects to the eyes. There are no recent reports of this effect.
Inflammation of the eyes, blurred vision, tearing and sensitivity to light were observed in employees exposed to high concentrations (100-200 ppm).(4) It is not clear if these effects are due to short- or long-term exposure.
Another report describes corneal lesions with symptoms such as burning of the eyes and a feeling that there was something in the eyes developing in 28/75 employees exposed to 15-100 ppm 1-butanol for 2 months. The authors were unable to reproduce these effects in animals.(7) There was exposure to other potential harmful chemicals at the same time as the 1-butanol exposure occurred.
The physical condition of a small number employees (15-111) exposed to 1-butanol was followed for ten years. Other than eye irritation, no significant harmful effects were observed.(4)

Hearing:
Limited evidence suggests that occupational exposure to 1-butanol, in conjunction with noise exposure, may cause hearing impairment.
Exposure to 80 ppm 1-butanol, in combination with unprotected noise exposure, caused dizziness and hearing impairment in a small number of employees. Nine out of 11 workers exposed from 3-11 years, without personal protective equipment from noise, experienced greater hearing loss compared to controls with slightly higher noise exposure, but no exposure to 1-butanol. The age of the affected workers was 20-39 years.(8,9,10,11) The original study is unavailable in English.

Carcinogenicity:

No human or animal information was located.

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:
No human information was located. Animal evidence suggests that fetotoxicity and teratogenicity may be observed at doses that also cause harmful effects in the mothers.

Reproductive Toxicity:
No human information was located. The limited animal evidence available has not shown reproductive effects.

Mutagenicity:
It is not possible to conclude that 1-butanol is mutagenic. No human or animal information was located. Mostly negative results have been obtained in short-term tests using bacteria and cultured mammalian cells.

Toxicologically Synergistic Materials:
Alcohols may interact synergistically with chlorinated solvents (e.g. carbon tetrachloride), aromatic hydrocarbons (e.g. xylene) or dithiocarbamates (e.g. disulfiram).

Potential for Accumulation:
1-Butanol is readily absorbed following inhalation, skin contact and ingestion. There is no evidence that it accumulates in the body. It is rapidly oxidized to n-butyraldehyde, n-butyric acid, and then to carbon dioxide and water. It is also reported to be conjugated and excreted in the urine as glucuronide and sulfate conjugates.(8,61)


SECTION 4. FIRST AID MEASURES

Inhalation:
This chemical is flammable. Take proper precautions (e.g. remove any sources of ignition). If symptoms are experienced, remove source of contamination or move victim to fresh air. If symptoms persist, immediately obtain medical attention.

Skin Contact:
As quickly as possible, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Immediately flush with lukewarm, gently flowing water for 15-20 minutes. Immediately obtain medical attention. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 15-20 minutes, while holding the eyelid(s) open. If a contact lens is present, DO NOT delay irrigation or attempt to remove the lens until flushing is done. Take care not to rinse contaminated water into the unaffected eye or onto the face. Immediately obtain medical attention.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. If vomiting occurs naturally, have victim lean forward to reduce 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:
37 deg C (98 deg F) closed cup (39)

Lower Flammable (Explosive) Limit (LFL/LEL):
1.4% (39)

Upper Flammable (Explosive) Limit (UFL/UEL):
11.2% (39)

Autoignition (Ignition) Temperature:
343 deg C (650 deg F) (39)

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

Sensitivity to Static Charge:
1-Butanol will not accumulate static charge since it has a high electrical conductivity. Mixtures of 1-butanol vapour and air at concentrations in the flammable range may be ignited by a static discharge of sufficient energy.

Electrical Conductivity:
(9.1 X 10(5) pS/m) (40,41)

Combustion and Thermal Decomposition Products:
Irritant gases, which may include unburned alcohol and toxic constituents.

Fire Hazard Summary:
Flammable liquid. Can release vapours that form explosive mixtures with air at, or above, 37 deg C. Vapour is heavier than air and may travel a considerable distance to a source of ignition and flash back to a leak or open container. During a fire, irritating/toxic smoke and fumes may be generated. Vapour can accumulate in confined spaces resulting in a flammability hazard. 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, alcohol foam (39,42,43) or water spray. Alcohol resistant fire-fighting foam is recommended for use on all water-soluble liquids or polar solvent-type liquids. Alcohols are water-soluble and will break down the common foams. Water may be ineffective, since it may not cool 1-butanol below its flash point.(39)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or protected location. Approach fire from upwind to avoid toxic decomposition products.
Stop leak before attempting to stop the fire. If the leak cannot be stopped, and if there is no risk to the surrounding area, let the fire burn itself out. If the flames are extinguished without stopping the leak, vapours could form explosive mixtures with air and reignite.
Water can extinguish the fire if used under favourable conditions and when hose streams are applied by experienced firefighters trained in fighting all types of flammable liquid fires. If possible, isolate materials not yet involved in the fire, and move containers from fire area if this can be one without risk, and protect personnel. Otherwise, fire-exposed containers or tanks should be cooled by application of hose streams and this should begin as soon as possible and should concentrate on any unwetted portions of the container. 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 and to protect personnel attempting to stop a leak. Water spray can be used to dilute spills to non-flammable mixtures and flush spills away from ignition sources. Solid streams of water may be ineffective and spread material. For a massive fire in a large area, use unmanned hose holder or monitor nozzles; if this is not possible withdraw from fire area and allow fire to burn. Stay away from ends of tanks, but be aware that flying material from ruptured tanks may travel in any direction. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire.

Protection of Fire Fighters:
1-Butanol is only slightly hazardous to health. Firefighters may enter the area if positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) and full Bunker Gear is worn.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 2 - Intense or continued (but not chronic) exposure could cause temporary incapacitation or possible residual injury.
NFPA - Flammability: 3 - Liquids and solids that can be ignited under almost all ambient temperature conditions.
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 74.12

Conversion Factor:
1 ppm = 3.03 mg/m3; 1 mg/m3 = 0.33 ppm at 25 deg C (calculated)

Physical State: Liquid
Melting Point: -89.3 deg C (-128.7 deg F) (38,43,44)
Boiling Point: 117.7 deg C (243.9 deg F) (38,43,44)
Relative Density (Specific Gravity): 0.810 at 20 deg C (water = 1) (43,45)
Solubility in Water: Moderately soluble (7.7 g/100 g at 20 deg C (11,43,44)); 7.4 g/100 g at 25 deg C (46)
Solubility in Other Liquids: Very soluble in acetone; soluble in all proportions in ethanol, diethyl ether, and many other organic solvents.(11,47)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 0.88 (75)
pH Value: Not available. Alcohols are both weak acids and weak bases.
Acidity: pKa = 16.1 (50)
Viscosity-Dynamic: 3.0 mPa.s (3.0 centipoises) at 20 deg C (40,44); 2.6 mPa.s (2.6 centipoises) at 25 deg C (48)
Viscosity-Kinematic: 3.7 mm2/s (3.7 centistokes) at 20 deg C (calculated)
Saybolt Universal Viscosity: 33.88 Saybolt seconds at 37.8 deg C (100 deg F) (26)
Surface Tension: 24.6 mN/m (24.6 dynes/cm) at 20 deg C (16,48); 25.4 mN/m (25.4 dynes/cm) at 20 deg C (51)
Vapour Density: 2.56 (air = 1) (calculated)
Vapour Pressure: 0.586-0.667 kPa (4.4-5.0 mm Hg) at 20 deg C (76); 0.89-0.93 kPa (6.7-7.0 mm Hg) at 25 deg C (49,50)
Saturation Vapour Concentration: 5790-6580 ppm (0.58-0.66%) at 20 deg C; 8815-9210 ppm (0.88-0.92%) at 25 deg C (calculated)
Evaporation Rate: 0.47 (n-butyl acetate = 1); 33 (diethyl ether = 1) (40)

Other Physical Properties:
DIELECTRIC CONSTANT: 17.5 at 25 deg C (38)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable

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.


OXIDIZING AGENTS (e.g. calcium hypochlorite, chlorine oxides, chromium trioxide, hydrogen peroxide, nitric acid and nitrates) - may react violently or explosively. Increased risk of fire and explosion.(52)
ALUMINUM - reacts at elevated temperatures, forming hydrogen gas.(52)
ALKALI METALS (e.g. sodium or potassium) - reaction may be violent resulting in explosions. Hydrogen gas is given off.(41,52,53)
HALOGENS (e.g. bromine or chlorine) - reaction may be vigorous or violent, resulting in explosions.(52)
PERCHLORIC ACID or METAL PERCHLORATES (e.g. barium perchlorate) - may form shock-sensitive or explosive compounds.(39,52)
ACIDS, ACID ANHYDRIDES, or ACID CHLORIDES - reaction may be vigorous or violent, with the evolution of heat.(42)
LITHIUM ALUMINUM HYDRIDE - reaction may be vigorous.(39)
ISOCYANATES (e.g. toluene diisocyanate, hexamethylene diisocyanate or methyl isocyanate) - may react vigorously, violently or explosively with the generation of heat.(39,53)
In addition, mixtures or reactions of alcohols with the following materials may cause explosions: acetaldehyde, dialkylmagnesiums, N-haloimides (e.g. N- bromosuccinimide or N-chlorosuccinimide), ethylene oxide, hydrogen peroxide and sulfuric acid, hypochlorous acid, nitrogen tetraoxide, nitryl hypochlorite, permonosulfuric acid and tri-isobutyl aluminum.(39,52)

Hazardous Decomposition Products:
None reported

Conditions to Avoid:
Sparks, open flames, heat, and other ignition sources

Corrosivity to Metals:
1-Butanol is not corrosive to the common metals. Stainless steels, steel, cast iron, high silicon iron, copper, brass, bronze, naval bronze, nickel and its alloys, tantalum, titanium and zirconium have good resistance (less than 20 mils (505 um)/year).(54,55) Published data indicate that primary butyl alcohols are not corrosive to aluminum up to at least 75 deg C (54,55), although it is reported to react with aluminum at high temperatures.(52)

Corrosivity to Non-Metals:
1-Butanol is not corrosive to most plastics and elastomers.(54) However, it can attack some plastics (e.g. ABS, PVC, and CPVC and Epoxy at high temperatures), elastomers (e.g. polyether-urethane), and coatings.(43,54)


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (rat): greater than 8000 ppm (4-hour exposure) (14)

LD50 (oral, rat): 2510 mg/kg (15)
LD50 (oral, male rat): 790 mg/kg (16)*
LD50 (oral, female rat): 2020 mg/kg (16)*
*NOTE: the rats used in this study appear to have been very young (60-100 grams). In addition, the liver and kidney toxicity observed may have been caused by impurities.(61)
LD50 (oral, hamster): 1200 mg/kg (11, original unavailable in English)

LD50 (dermal, rabbit): 4200 mg/kg (8,11, original unavailable in English)

Eye Irritation:

1-Butanol is a severe eye irritant.

Application of 0.1 mL of undiluted 1-butanol produced severe irritation in rabbits (Modified Maximum Average Score: 60.8/110). Average scores at 24, 48 and 72 hours for each of 4 rabbits were: corneal opacity: 2.67/4, 2.33/4, 1.67/4, 1.33/4; iris injury: 1/2, 0.67/2, 0.67/2, 0.67/2; redness: 3/3, 2.33/3, 2.33/3, 2/3; chemosis: 2.33/4, 2/4, 2/4, 2/4. All scores were 0/110 by day 21.(18) Application of 0.1 mL produced severe irritation in rabbits (average scores at 24, 48 and 72 hours: redness: 2.39/3; chemosis: 0.55/4; iris injury: 0.33/2; corneal opacity: 1.22/4). Reversibility was not assessed.(19) Application of 0.005 mL of in excess of a 40% solution of 1-butanol caused severe injury in rabbits (graded 7/10; scored over 5 where 5 is severe injury).(17) Application of 0.1 mL of undiluted butanol (isomer not specified) produced severe irritation (scored 61/110) in rabbits. Application of 25 or 30% solutions produced moderate irritation (scored 34 or 45/110, respectively), and 10 and 15% solutions produced minimal irritation in rabbits (scored 3 or 5/110, respectively).(20) In an interlaboratory comparison study, 20/24 laboratories would rate 1-butanol as a severe eye irritant.(22)

Skin Irritation:

1-Butanol is a slight to moderate irritant.

1-Butanol was applied to the skin of rabbits as 0.5 mL of 5, 10, 25, 50 or 100% in polyethylene glycol 400 for 4 hours, under a patch. Undiluted 1-butanol caused a redness score of greater than or equal to 2/4. The other concentrations tested caused redness scores of less than 2/4.(29) In an interlaboratory comparison study, 0.5 mL of 1-butanol was applied to rabbit skin for 24 hours. Seven laboratories rated 1-butanol as a very mild irritant (scored less than or equal to 2/8). Six laboratories rated 1-butanol as a mild to moderate irritant (scored 2.1-4.9/8). Three laboratories rated 1-butanol as a severe irritant (scored greater than or equal to 5/8).(22)

Effects of Short-Term (Acute) Exposure:

1-Butanol is a central nervous system (CNS) depressant causing incoordination, unconsciousness and deaths following high inhalation or ingestion exposures. It is irritating to the nose and throat following brief exposure to concentrations above 1000 ppm. It can be absorbed through the skin. It is an aspiration hazard.

Inhalation:
Exposure of male mice to 1268 ppm butyl alcohol (isomer not specified) for 5 minutes caused a 50% decrease in the respiratory rate (RD50), due to irritation of the upper respiratory tract.(24) In another study, the RD50 in male mice was 3010 ppm for a 6 minute exposure.(23) Exposure to the RD50 concentration is expected to produce intolerable eye, nose and throat irritation (sensory irritation) in humans. Inhalation exposure of mice to 650 or 3300 ppm for 7 hours caused no toxicity. Exposure to 6600 ppm produced signs of marked central nervous system (CNS) depression, including inability to stand (prostration) after 2 hours, unconsciousness after 3 hours and some deaths.(8, unconfirmed) In another study, nervous system effects, as measured by a rotarod performance test, were observed in rats exposed to 6530 ppm for 4 hours.(23) Male rats were exposed continuously to 500 ppm for 5 days or 2000 ppm for 3 days. There were increases in metabolic enzymes in the kidneys, liver and lungs for both groups. However, the only significant increase was for liver enzymes in animals exposed to 2000 ppm.(63)

Skin Contact:
Significant skin absorption was observed in female guinea pigs exposed to 1-butanol for 1 minute every 30 minutes for 8 times.(25)

Ingestion:
Symptoms of central nervous system depression were observed in rats orally administered 2500 mg/kg in an LD50 study.(15) 1-Butanol was shown to be an aspiration hazard in a study designed to assess this affect. Instant death was observed in 9/10 rats after aspiration of 0.2 mL 1-butanol. Death was attributed to respiratory and cardiac arrest. The lungs showed bleeding and accumulation of fluid (edema).(26)

Effects of Long-Term (Chronic) Exposure:

Limited studies have shown minor effects including changes in some blood parameters and symptoms of central nervous system depression (muscle incoordination and reduced activity) following inhalation or ingestion.

Inhalation:
Male rats were exposed to 50 or 100 ppm 1-butanol for 3 months (6 hr/d, 5 d/wk). There were no deaths, signs of toxicity or effects on body or organ weights. There was a slight, but significant, decrease in hemoglobin levels at 50 ppm and higher and in red blood cell count at 100 ppm. There was no detailed examination of the tissues reported. Nervous system effects were measured by a rotarod performance test and a hot plate avoidance test. At 50 and 100 ppm, there was a decrease in rotarod performance as the study progressed but not in hot plate avoidance.(64) Reversibility of the observed effects was not evaluated. In a limited study, exposure of guinea pigs to 100 ppm butanol (isomer not specified) for 4-10.5 weeks (4 hr/d, 6-7 d/wk) caused a decrease in red blood cells and an increase in lymphocytes (white blood cells).(27) No significant effects on hearing were observed in male rats exposed to 4000 ppm 1-butanol for 5 days.(28) This study is limited by the small number of animals per group and the fact that only one exposure level was used. In a study, which is reported by abstract, rats exposed to 0, 0.15, 0.44, 1.3, or 4.8 ppm for 30 days (cited as 0, 0.45, 1.36, 3.98 or 14.6 mg/m3; hrs/d not reported). Neurotoxicity, liver toxicity, a decrease in adrenal weight, and an increase in metabolic enzymes were reported.(65) There are insufficient details available to evaluate this study.

Skin Contact:
Rats were orally exposed to 0, 30, 125 or 500 mg/kg/day for 13 weeks. Most findings were negative. Slight, but significant, changes in some blood parameters were observed in the mid- and high-dose females, but this effect was considered temporary. Muscle incoordination and reduced activity was consistently observed at the high dose during the last 6 weeks of the study.(66) In a study, which is reported by abstract, rats were given 0, 0.04, 0.2, 1 or 5 mg/kg/day for 30 days. Effects reported were an increase in metabolic enzymes, liver toxicity and a decrease in weight of the adrenal glands.(65) There are insufficient details available to evaluate study.

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
The available information indicates that 1-butanol is not a developmental toxin. In an inhalation and an oral study using rats, fetotoxicity (reduced weight) and teratogenicity (skeletal malformations) were observed only at doses that also cause maternal toxicity.
Rats were given 0, 0.2, 1, or 5% in the drinking water on days 0-20 of pregnancy. (Reported estimated doses were 316, 1454 or 5654 mg/kg/day). In the mothers, there was a significant decrease in body weight gain at 5654 mg/kg/day and in food consumption at 1454 mg/kg/day and higher. At 5654 mg/kg/day, there was a significant decrease in fetal body weight and a significant increase in the total number of fetuses with skeletal abnormalities.(67) Rats were exposed by inhalation to 0, 3500, 6000 or 8000 ppm on days 1-19 of pregnancy. At 8000 ppm, 2/18 mothers died and narcosis was observed in half of the animals exposed in a range-finding phase of the study. Fetotoxicity (reduced weight) and teratogenicity (skeletal malformations) were observed at this concentration. At 6000 ppm, maternal food consumption was decreased and fetotoxicity (reduced weight) was observed. No effects were observed at 3500 ppm.(30) Female rats were exposed by inhalation to 0, 3000 or 6000 ppm throughout pregnancy. Male rats were similarly exposed for 6 weeks prior to mating unexposed females. The offspring were subjected to 78 different behavioural tests. Few behavioural effects (4/78 at the high dose) were observed and the data obtained from all tests were within the range of historical controls.(31) Rats were exposed to 1-butanol in drinking water at doses of 0.24, 0.8 or 4% (estimated reported doses were 300, 1000 or 5000 mg/kg/day). Animals were exposed continuously for 8 weeks prior to mating, and throughout mating and pregnancy. No significant maternal toxicity was observed. Fetal size (crown-rump length) was reduced at the high dose. Dose-related developmental effects including central nervous system and kidney effects were also observed. Skeletal effects were observed at 5000 mg/kg/day.(32) This study is limited because of the small number of animals per group (11-17). In addition, the highest dose exceeds the oral LD50. No conclusions can be drawn from another study which has only been reported in abstract form.(33)

Reproductive Toxicity:
The studies located have not shown reproductive effects.
Exposure of male rats to 0, 3000 or 6000 ppm 1-butanol for 6 weeks (7 hr/day) before mating to unexposed females had no effect on the rate of pregnancy.(31) No effects on testicular tissue were observed in rats orally dosed with approximately 500 mg/kg 1-butanol for 4 days.(34) No effects on fertility were observed in female rats exposed continuously to 300, 1000 or 5000 mg/kg/day in drinking water for 8 weeks prior to mating, during mating and pregnancy.(32)

Mutagenicity:
The available evidence does not suggest that 1-butanol is mutagenic. A negative result was obtained in an unpublished study using live mice. Mostly negative results were obtained in cultured mammalian cells and in bacteria.
In an unpublished study, negative results (micronuclei induction) were obtained in live mice given oral doses of 0, 500, 1000 or 2000 mg/kg 1-butanol in olive oil.(61, unconfirmed)
A negative result (micronuclei induction) was obtained in cultured mammalian cells, without metabolic activation.(68) A negative result (sister chromatid exchange) was obtained in cultured mammalian cells, without metabolic activation for butanol (isomer not specified).(69) A positive result (aneuploidy) was obtained in cultured mammalian cells, without metabolic activation.(70) Negative results (gene mutation, DNA damage) were obtained in tests using bacteria, with and without metabolic activation.(61-unconfirmed, 71,72,73) A positive result (inhibition of DNA synthesis) was obtained for butyl alcohol (isomer not specified) in bacteria, without metabolic activation.(74)

Toxicological Synergisms:
1-Butanol and m-xylene and 1-butanol and n-butyl acetate have been shown to have an additive effect on the nervous system of rats exposed by inhalation, as measured by rotarod performance.(23,35)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Nelson, K.W., et al. Sensory response to certain industrial solvent vapors. Journal of Industrial Hygiene and Toxicology. Vol. 25, no. 7 (1943). p. 282-285
(2) Astrand, I., et al. Exposure to butyl alcohol: uptake and distribution in man. Scandinavian Journal of Work, Environment and Health. Vol. 2, no. 3 (1976) p. 165-175
(3) Tabershaw, I.R., et al. Industrial exposure to butanol. Journal of Industrial Hygiene and Toxicology. Vol. 26, no. 10 (Dec. 1944). p. 328-330
(4) Sterner, J.H., et al. A ten-year study of butyl alcohol exposure. American Industrial Hygiene Association Quarterly. Vol. 10, no. 3 (Sept. 1949). p. 53-59
(5) Hempel-Jorgensen, A., et al. Time course of sensory eye irritation in humans exposed to n-butanol and 1-octene. Archives of Environmental and Occupational Medicine. Vol. 54, no. 2 (Mar./Apr. 1999). p. 86-94
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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: 2006-02-15

Revision Indicators:
Bibliography 2006-04-05



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