Furan

Other Classes -> Ethers, Other

Carcinogens

log Kow = 1.34

1.34

1.34

0.9371 at 66.92 °F (EPA, 1998) - Less dense than water; will float

0.9731 at 19.4 °C/4 °C

Density = 0.9514 g/cu cm at 20 °C

Relative density (water = 1): 0.94

0.9514 @ 20°C

0.38 cP at 20 °C

0.38 mPa*s

less than 1 mg/mL at 72 °F (NTP, 1992)

Soluble in alcohol and ether

Slightly soluble in chloroform; very soluble in ethanol, ether; soluble in acetone, benzene

In water, 1X10+4 mg/L at 25 °C

10 mg/mL at 25 °C

Solubility in water, g/l at 25 °C: 10

Less than 32F (EPA, 1998)

-32 °F (-35 °C) (Closed cup)

-35 °C

90 °F at 758 mmHg (EPA, 1998)

31.5 °C

32.00 °C. @ 758.00 mm Hg

31.3 °C

31.5 °C @760 [mm Hg]

When heated to decomposition it emits acrid smoke and irritating fumes.

Furan is a heat-stable compound although, @ 670 °C in the absence of catalyst, or @ 360 °C in the presence of nickel, it decomposes to form a mixture consisting mainly of carbon monoxide, hydrogen, and hydrocarbons.

Danger

H224: Extremely flammable liquid and vapor [Danger Flammable liquids]

P203, P210, P233, P240, P241, P242, P243, P260, P261, P264, P270, P271, P273, P280, P301+P317, P302+P352, P303+P361+P353, P304+P340, P317, P318, P319, P321, P330, P332+P317, P362+P364, P370+P378, P403+P235, P405, and P501 (click each P-code to see the statement)

Danger

H224 (100%): Extremely flammable liquid and vapor [Danger Flammable liquids]

P203, P210, P233, P240, P241, P242, P243, P260, P261, P264, P270, P271, P273, P280, P301+P317, P302+P352, P303+P361+P353, P304+P340, P317, P318, P319, P321, P330, P332+P317, P362+P364, P370+P378, P403+P235, P405, and P501 (click each P-code to see the statement)

Chemical: Furan

Regulation (EC) No 1333/2008 (amended)

Furan is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Furan are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 27-02-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/10633

Substance: Furan

Furan: HSNO Approval: HSR001255 Approved with controls

Very dangerous, upon exposure to heat or flame. It may form unstable peroxides on exposure to air. Contact with acids can initiate a violent, heat producing reaction. Avoid acids, oxidizing agents. Upon standing in air, it may form unstable peroxides. (EPA, 1998)

· HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames.

Extremely flammable. Vapour/air mixtures are explosive.

The vapors are narcotic. Acute exposure to furan by inhalation may involve both reversible and irreversible changes. Acute exposure by ingestion or skin absorption, as well as chronic exposure, are associated with high toxicity. (EPA, 1998)

CAUTION: Petroleum crude oil (UN1267) may contain TOXIC hydrogen sulphide gas.

Inhalation can cause anesthesia; Absorbed through skin; [Merck Index] May cause liver damage; Corrosive to the mouth and GI tract in toxicology studies; [HSDB] Causes narcosis; Contact can irritate or burn skin and eyes; [CHRIS] Furan is a skin irritant. [Quick CPC] A respiratory tract irritant; Inhalation of vapor can cause pulmonary edema; [ICSC] Doses as low as 2 mg/kg can cause severe injury to the liver and kidneys. Causes liver tumors in high-dose animal studies; No data on human use; Worker exposure by all routes should be minimized to the fullest extent possible. [AIHA]

Boyd MR; Adv Exp Med Biol 136B (Biol React Intermed - 2, Chem Mech Biol Eff, Pt B): 865-79 (1982). A review with 41 ref covering acute tissue lesions caused by furan derivatives, toxification and detoxification pathways, ultimate metabolites, effects of species, age, sex, and inducer treatment on liver and other target organ metabolism and toxicity, and the significance of cell-specific activation in target tissues.

DHHS/NTP; Toxicology & Carcinogenesis Studies of Furan in F344/N Rats and B6C3F1 Mice (Gavage Studies) Technical Report Series No. 402 (1993) NIH Publication No. 93-2857

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Furan (110-00-9) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s090fura.pdf]

Move container from fire area if this can be accomplished without risk. Spray cooling water on containers that are exposed to flames until well after fire is out. For massive fires in cargo area, use unmanned hose holder or monitor nozzles; if this is impossible withdraw from area and let fire burn. Withdraw immediately in case of rising sound from venting safety device or any discoloration of tank due to fire. Isolate for 1/2 mile in all directions if a tank car or truck is involved. Water may be ineffective. Small fires: dry chemical, carbon dioxide, water spray, or alcohol foam. Large fires: water spray, fog, or alcohol foam. (EPA, 1998)

Use water spray, powder, alcohol-resistant foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Fresh air, rest. Half-upright position. Administration of oxygen may be needed. Refer immediately for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer immediately for medical attention.

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

Signs and Symptoms of Furan Exposure: Acute exposure to furan may produce dizziness, nausea, vomiting, diarrhea, and anorexia. Irritation and burning of the eyes and skin may occur. Furan vapor is a central nervous system depressant.

General First Aid:

· Wear positive pressure self-contained breathing apparatus (SCBA).

0.02 [ppm]

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may spread fire. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use foam, dry chemical, or carbon dioxide.

Water may be ineffective. Small fires: use dry chemical, carbon dioxide, water spray, or alcohol foam. Large fires: water spray, fog, or alcohol foam. Move container from fire area if this can be accomplished without risk. Spray cooling water on containers that are exposed to flames until well after fire is out. For massive fires in cargo area, use unmanned hose holder or monitor nozzles; if this is impossible, withdraw from area and let fire burn. Withdraw immediately in case of rising sound from venting safety device or any discoloration of tank due to fire. Isolate for 1/2 mile in all directions if a tank car or truck is involved. Vapors are heavier than air and will collect in low areas. Vapors may travel long distances to ignition sources and flashback. Vapors in confined areas may explode when exposed to fire. Containers may explode in fire. Storage containers and parts of containers may rocket great distances, in many directions. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position ... The only respirators recommended for fire fighting are self-contained breathing apparatuses that have full facepieces and are operated in a pressure-demand or other positive-pressure mode.

Before entering confined space where this chemical may be present, check to make sure that an explosive concentration does not exist. Store in an explosion-proof refrigerator. Keep in a tightly closed container under an inert atmosphere and protect from light for long-term storage. A regulated, marked area should be established where this chemical is handled, used, or stored ...

Fireproof. Separated from strong oxidants, acids. Cool. Well closed. Store only if stabilized ... Closed system, ventilation, explosion-proof electrical equipment and lighting. Do NOT use compressed air for filling, discharging, or handling. Use non-sparking handtools.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Containers for furan should be able to withstand the vapor pressure exerted during storage under variable climatic conditions. Furan should be stored in a cool place where the drums will not be heated.

Evacuate and restrict persons not wearing protective equipment from area of spill or leak until cleanup is complete. Avoid breathing vapors. Keep upwind. Do not handle broken packages without protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. Shut off ignition sources; no flares, smoking, or flames in hazard area. Stop leak if you can do so without risk. Use water spray to reduce vapors. Small spills: absorb with sand or other noncombustible absorbent material and place into containers for later disposal. Large spills: dike far ahead of spill for later disposal. The exposure concentration limit of 10 ppm together with the low boiling point of furan requires that adequate ventilation be provided in areas handling this chemical. Establish forced ventilation to keep levels below explosive limit. Contact with liquid must be avoided since this chemical can be absorbed through the skin. Keep furan out of a confined space, such as a sewer, because of the possibility of an explosion, unless the sewer is designed to prevent the build-up of explosive concentrations. Thorough washing with soap and water followed by prolonged rinsing should be done immediately after accidental contact. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your Department of Environmental Protection or your regional office of the federal EPA for specific recommendations.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U124, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A good candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds. Also, good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. Also, a good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. /From table/

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for Furan (7 total), please visit the HSDB record page.

Remove all ignition sources. Evacuate danger area! Consult an expert! Personal protection: self-contained breathing apparatus. Do NOT wash away into sewer. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

Furan was detected in the expired air of 2 of 3 male smokers and 4 of 5 male nonsmokers at the Brooks Air Force Base, TX with the rate of expiration ranging from 0.25-98 ug/hour for smokers and from 0.33-28 ug/hour for nonsmokers(1). This compound was also identified in 15 of 387 samples of expired air taken from 54 male and female nonsmokers from Chicago, IL mean concentration 0.547 ng/L(2). Furan was qualitatively identified in 1 of 12 samples of mother's milk obtained from women in 4 different urban areas(3). Body burden levels of furan in the serum of 96 subjects was measured at 2.7 to 25.6 toxic equivalents; 34 subjects from Lake Michigan had concentration ranges of 2.7 to 19.4, 26 subjects from Lake Heron had concentration ranges of 3.8 to 25.2 toxic equivalents, and 36 had concentration ranges of 3.4 to 25.6 toxic equivalents(4).

Groups of 10 Swiss albino mice (GP strain) given furan (purity not given) at a single dose of 300 mg/kg body weight in 0.9% sodium chloride intraperitoneally had centrilobular hepatic necrosis and coagulative necrosis of the proximal convoluted tubules of the outer renal cortex. Treatment of mice with the cytochrome p450 inhibitor piperonyl butoxide reduced the extent of liver necrosis and totally inhibited the renal necrosis.

Diethyldithiocarbamate and carbon disulfide prevented mice from renal injury induced by furan as evidenced by suppression of elevations in plasma urea nitrogen concn and kidney calcium content and by morphological alterations. In carbon tetrachloride-poisoned mice, furan nephrotoxicity was augmented. The augmented furan nephrotoxicity was also prevented by diethyldithiocarbamate or carbon disulfide. Thus, furan may exert nephrotoxicity through active metabolites formed in the kidney. Diethyldithiocarbamate and carbon disulfide also protected against hepatotoxicity induced by furan. As an extension of these studies, similar experiments were undertaken with furan, bromobenzene and cephaloridine, and other nephrotoxic agents that are also thought to require metabolic activation. Diethyldithiocarbamate or carbon disulfide prevented mice from suffering renal injury induced by furan and bromobenzene, as evidenced by suppression of elevations in plasma urea nitrogen concentration and kidney calcium content and of morphologic alterations. Cephaloridine nephrotoxicity, however, was not prevented. In carbon tetrachloride-poisoned mice, furan nephrotoxicity was augmented, whereas bromobenzene and cephaloridine nephrotoxicity was suppressed. The augumented furan nephrotoxicity was also prevented by diethyldithiocarbamate or carbon disulfide. These observations suggest that furan, like chloroform and 1,1-dichloroethylene, may exert nephrotoxicity through active metabolites formed in the kidney. For bromobenzene and cephaloridine nephrotoxicity, a renal bioactivation mechanism is suspected. Diethyldithiocarbamate and carbon disulfide also protected against hepatotoxicity induced by furan and thiophene.

EC50; Species: Pimephales promelas (Fathead minnow, age 29-31 days, length 18 mm, weight 0.100 g); Conditions: freshwater, flow through, 23.2 (22.0-24.6) °C, pH 8.00, hardness 44.5 mg/L CaCO3, alkalinity 41.5 mg/L CaCO3, dissolved oxygen 80.0% (65.5-87.4%); Concentration: 99000 ug/L for 24 hr; Effect: behavior change, equilibrium /> or = 99% pure/

EC50; Species: Pimephales promelas (Fathead minnow, age 29-31 days, length 18 mm, weight 0.100 g); Conditions: freshwater, flow through, 23.2 (22.0-24.6) °C, pH 8.00, hardness 44.5 mg/L CaCO3, alkalinity 41.5 mg/L CaCO3, dissolved oxygen 80.0% (65.5-87.4%); Concentration: 71000 ug/L for 48 hr; Effect: behavior change, equilibrium /> or = 99% pure/

LC50; Species: Pimephales promelas (Fathead minnow, age 29-31 days, length 18 mm, weight 0.100 g); Conditions: freshwater, flow through, 23.2 (22.0-24.6) °C, pH 8.00, hardness 44.5 mg/L CaCO3, alkalinity 41.5 mg/L CaCO3, dissolved oxygen 80.0% (65.5-87.4%); Concentration: 99000 ug/L for 24 hr /> or = 99% pure/

LC50; Species: Pimephales promelas (Fathead minnow, age 29-31 days, length 18 mm, weight 0.100 g); Conditions: freshwater, flow through, 23.2 (22.0-24.6) °C, pH 8.00, hardness 44.5 mg/L CaCO3, alkalinity 41.5 mg/L CaCO3, dissolved oxygen 80.0% (65.5-87.4%); Concentration: 71000 ug/L for 48 hr /> or = 99% pure/

LC50; Species: Pimephales promelas (Fathead minnow, 29-31 days); Conditions: flow-through bioassay, 23.2 °C, pH 8.00, water hardness 44.5 mg/L CaCO3; Concentration: 61 mg/L for 96 hr

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that furan is expected to have high mobility in soil(SRC). Volatilization of furan from moist soil surfaces is expected to be an important fate process(SRC) given a Henry's Law constant of 5.4X10-3 atm-cu m/mole(SRC), based upon its vapor pressure, 600 mm Hg(3), and water solubility, 10,000 mg/L(4). Furan is expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). A 4% of theoretical BOD using activated sludge in the Japanese MITI test(5) suggests that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that furan is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon a Henry's Law constant of 5.4X10-3 atm-cu m/mole(SRC), derived from its vapor pressure, 600 mm Hg(4), and water solubility, 10,000 mg/L(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 2.5 hours and 3.3 days, respectively(SRC). According to a classification scheme(6), BCFs of 0.9-1.5 and <3.2-13 measured in carp (Cyprinus carpio) at furan concentrations of 1 and 0.1 mg/L(7), respectively, suggest that bioconcentration in aquatic organisms is low(SRC). A 4% of theoretical BOD using activated sludge in the Japanese MITI test(7) suggests that biodegradation is not an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), furan, which has a vapor pressure of 600 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase furan is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 9 to 10 hours, calculated from its rate constants of 3.83X10-11 to 4.23X10-11 cu cm/molecule-sec(3-5). Furan will also react with nitrate radicals and ozone radicals in the atmosphere with half-lives of 50 minutes and 4.5 to 4.6 days, calculated from rate constants of 1.4X10-12 cu cm/molecule sec(4) and 2.4X10-18(4) to 2.5X10-18(6), respectively.

Furan has been identified as a volatile component of roasted filberts(1). Furan has been identified in the volatile component of mutton, chicken, and beef(2). Furan was detected in infant formula with iron at 8.5-8.6 ng/g (brand 1) and 16.8-18.8 ng/g (brand 2), ready to eat infant formula at not detected to 2.5 ng/g, sweet potato baby food at 91.0-93.1 ng/g (brand 1), 75.7-81.1 ng/g (brand 2), and 73.8-82.9 ng/g (brand 3), spaghetti sauce at 5.9-6.1 ng/g (brand 1), 3.1-3.5 ng/g (brand 2), baked beans at 117-122 ng/g, canned luncheon meat loaf at 1.8-1.9 ng/g, pork and beans at 78.7-85.6 ng/g, chicken broth at 8.2-9.1 ng/g (brand 1) and 15.2-18.2 ng/g (brand 2), peanut butter at 6.1-7.1 ng/g, cut green beans at 5.9-8.2 ng/g, chicken dinner baby food at 29.4-39.7 ng/g, chicken and stars baby food at 15.9-23.6 ng/g, apple juice at 1.2-2.2 ng/g(3).

Furan is a potent hepatotoxin and hepatocarcinogen in rodents, causing hepatocellular adenomas and carcinomas in rats and mice, and high incidences of cholangiocarcinomas in rats at doses ≥ 2 mg/kg bw. A genotoxic mode of action cannot be excluded for furan-induced tumor formation. Furan is metabolized by cytochrome P450 (CYP) enzymes, predominantly CYP2E1, to its major metabolite cis-2-butene-1,4-dial (BDA, maleic dialdehyde), a highly reactive electrophile identified as the key mediator of furan toxicity and carcinogenicity. Furan-mediated effects on glutathione (GSH) levels and cell viability can be suppressed by the CYP inhibitor 1-phenylimidazole and increased by pretreatment of rats with acetone (a CYP2E1-inducing agent), indicating that furan cytotoxicity depends on its metabolic activation. BDA has been shown to react with cellular nucleophiles such as GSH and amino acids and to cause cross-links between thiols and amino groups, giving rise to lactam and pyrrole derivatives. Furan reduced the percentage of DNA in the comet tail in turkey liver fetal hepatocytes. Furan was also shown to induce chromosomal aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. A statistically significant increase of micronucleated cells was recently reported in the spleen of furan-treated mice. A reduction of percentage of DNA in comet tail in liver cells was observed following treatment of turkey fetuses in ovo. Exposure to furan at doses associated with increased tumor incidences initially causes hepatocellular necrosis, accompanied by inflammation and sustained regenerative proliferation of hepatocytes, which may present key events in furan-induced hepatocellular carcinogenicity. Subcapsular and centrilobular necrosis accompanied by markedly increased liver enzymes is the primary response to furan treatment. The involvement of inflammatory processes in furan toxicity is also reflected by increased expression of cytokines and other inflammation-associated genes, such as IFN-γ, IL-1β, IL-6, IL-10, and components of the complement system, which may, however, also derive from lesions involving the biliary tract. Indeed, increased production of reactive oxygen species in response to furan is suggested by immunohistochemical detection of 8-oxo-dG within nuclei of hepatocytes of centrilobular areas following high-dose exposure and changes in the expression of genes responsive to oxidative stress in rats and/or mice. (A15446)

Sore throat. Cough. Chest tightness. Shortness of breath. Laboured breathing.

Redness.

Redness. Pain.

U124; As stipulated in 40 CFR 261.33, when furan, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Furan is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 lbs.

Furan

1

10000

Flammable chemical that can be released at a facility.

Furan administered by gavage for 2 yr has been reported to induce hepatocellular carcinomas in male and female B6C3F1 mice and in male but not female F344 rats. Chronic exposure studies ... using bioassay conditions showed extensive hepatocellular toxicity and sustained increases in regenerative cell proliferation after 1, 3, and 6 wk of treatment in male and female rats and male mice. Altered expression of growth-control genes associated with this hyperproliferative state may enhance the susceptibility of these genes to mutation or may provide a selective growth advantage to preneoplastic cells. Quantitative northern blot analysis of mRNA was used to examine the expression of the oncogenes myc, fos, and Ha-ras in the livers of animals treated with furan. In male rats, a single administration of 30 mg/kg furan produced necrosis and a subsequent wave of cell proliferation 48 hr after treatment and induced transient peaks in the expression of myc, fos, and Ha-ras 6-24 hr after treatment. In male rat liver from our cell proliferation studies, only a slight increase in myc expression was seen at the end of week 1 of treatment. However, beginning at week 3 and increasing at week 6, up to a 15-fold increase over control values was observed in the expression of myc in the treated animals. The only other notable increase in expression observed in any animals from the cell proliferation study was a threefold increase in myc at week 6 in treated female rats. The absence of an increase in Ha-ras expression in the male mouse liver suggests that the unique pattern of Ha-ras mutations previously reported in furan-induced mouse liver tumors is not due to increased mutational susceptibility related to overexpression of this gene. The lack of sustained expression of myc, fos, and Ha-ras in rapidly proliferating liver suggests that continuous expression of these genes is not necessary to maintain increased rates of cell replication. The large increase in myc expression in male but not female rats suggests an adaptive change that may be related to the sex-specific incidence of furan-induced hepatocellular carcinomas in rats.

A current hypothesis for the mechanism of furan-induced carcinogenesis is metabolic activation of furan by cytochrome P450 to a reactive and cytotoxic intermediate that stimulates cell replication, increasing the likelihood of tumor induction. The postulated reactive metabolite is cis-2- butene-1,4-dial, which was recently characterized as a furan metabolite. This reactive metabolite probably explains furan's binding reactivity with proteins both in vitro (uninduced and induced F344 male rat liver microsomes) and in vivo (F344 male rat liver protein) in biological systems. Furan metabolites may react with DNA, but no ... radiotracer /was detected/ in DNA from livers of rats treated with 14(C)furan.

... Hepatic and renal injury produced by furan is the result of metabolic activation of the compound by cytochrome p450 oxygenases into chemically reactive metabolites.

... Previous studies indicate that furan is oxidized to a reactive alpha,beta-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), in a reaction catalyzed by cytochrome P450. Five previously characterized metabolites are derived from the reaction of BDA with cellular nucleophiles such as glutathione and protein. They include the monoglutathione reaction product, N-[4-carboxy-4-(3-mercapto-1H-pyrrol-1-yl)-1-oxobutyl]-l-cysteinylglycine cyclic sulfide, and its downstream metabolite, S-[1-(1,3-dicarboxypropyl)-1H-pyrrol-3-yl]methylthiol, as well as (R)-2-acetylamino-6-(2,5-dihydro-2-oxo-1H-pyrrol-1-yl)-1-hexanoic acid and N-acetyl-S-[1-(5-acetylamino-5-carboxypentyl)-1H-pyrrol-3-yl]-l-cysteine and its sulfoxide. The last two compounds are downstream metabolites of a BDA-derived cysteine-lysine cross-link, S-[1-(5-amino-5-carboxypentyl)-1H-pyrrol-3-yl]-l-cysteine. In this report, ... the characterization of seven additional urinary furan metabolites, all of which are derived from this cross-link /is described/. The cysteinyl residue is subject to several biotransformation reactions, including N-acetylation and S-oxidation. Alternatively, it can undergo beta-elimination followed by S-methylation to a methylthiol intermediate that is further oxidized to a sulfoxide. The lysine portion of the cross-link either is N-acetylated or undergoes a transamination reaction to generate an alpha-ketoacid metabolite that undergoes oxidative decarboxylation. Some of these metabolites are among the most abundant furan metabolites present in urine as judged by LC-MS/MS analysis, indicating that the oxidation of furan to BDA and BDA's subsequent reaction with cellular cysteine and lysine residues may represent a significant in vivo pathway of furan biotransformation. Because they are derived from cellular BDA reaction products, these metabolites are markers of furan exposure and bioactivation and could be explored as potential biomarkers in human studies.

Furan has known human metabolites that include (E)-2-Butenedial.

Absorbed ... by way of dermal route.

RESP UPTAKE IN DOGS WAS 90-95%, VARYING INVERSELY WITH VENTILATORY RATE. RETENTION WAS NOT AFFECTED BY TIDAL VOL CHANGES BUT WAS DIRECTLY RELATED TO CONCN INHALED FROM CIGARETTE SMOKE. FURAN IS READILY ABSORBED BY INHALATION ROUTE.

... The kinetics of furan biotransformation of male F344 rats were studied in vivo and in vitro in order to understand target tissue dosimetry. A physiologically based pharmacokinetic (PBPK) model for furan in rats was developed from gas uptake studies using the initial furan concn of 100, 500, 1050, and 3850 ppm. Tissue partition coefficients for furan were determined in vitro using vial equilibration techniques. Furan gas uptake kinetics in vivo were described by a single saturable process with a V(max) of 27.0 umol/hr/250 g rat and a K(m) of 2.0 uM. Furan metabolism in vivo was inhibited by pyrazole. The furan PBPK model adequately simulated blood and liver furan concn following 4 hr inhalation exposures to 52, 107, and 208 ppm furan. The biotransformation of furan was studied in freshly isolated rat hepatocytes exhibited a K(m) of 0.4 uM and a V(max) of 0.018 umol/hr/1x10(6) cells. Inhibition and induction studies indicated that cytochrome p450 was the catalyst of furan oxidation. ... /This data/ suggests that freshly isolated hepatocytes are a valuable in vitro system for predicting chemical pharmacokinetics in vivo.

Used as a chemical intermediate; [HSDB]

CHEMICAL INTERMEDIATE FOR TETRAHYDROFURAN

Organic synthesis, especially for pyrrole, tetrahydrofuran, thiophene

Used mainly in the preparation of specialty chemicals such as alpha-acetylfuran, 2,5-dimethoxy-2,5-dihydrofuran, 2,2-difurylpropane, 2,2-di(tetrahydrofurfuryl)propane, and pyrrole derivatives

Furan is ... used in the formation of lacquers, as a solvent for resins, and in the production of agricultural chemicals (insecticides), stabilizers, and pharmaceuticals

2023: 1,000,000 - <5,000,000 lb

Furan is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#258]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Furan. Aggregated National Production Volume: 1 to < 10 million lbs.

PROBABLY 100% CONSUMED CAPTIVELY AS AN INT FOR TETRAHYDROFURAN (FURAN ITSELF IS NOT IMPORTANT COMMERCIALLY) (1975)

(1974) 3.63X10+10 G (EST-CAPTIVELY CONSUMED)

Prepared by decarboxylation of 2-furancarboxylic acid. Has been prepared directly from furfural over hot soda-lime or by dropping furfural on fused mixture of sodium and potassium hydroxides.

Dry distillation of furoic acid from furfural.

By heating furfural in the liquid phase in the presence of a palladium catalyst.

High yields of furan have been obtained when butanediol is oxidized by dichromate in acidic soln, followed by dehydration.

Furan is produced commercially by the decarbonylation of furfural over a noble metal catalyst, preferably palladium on charcoal.

All Other Basic Organic Chemical Manufacturing

Furan: ACTIVE