ヘキサクロロベンゼン

Hazardous Air Pollutants (HAPs)

Urban Hazardous Air Pollutants (HAPs) - EPA specified greatest potential health threat in urban areas

Carcinogens

Semi-Volatile Organic Compound (SVOC)

Pesticide -> EPA IRIS

Agrochemicals -> Pesticide active substances

Active substance -> EU Pesticides database: Not approved

Pesticides -> Organochlorine Pesticides

Organochlorine pesticide

Pesticide (Hexachlorobenzene (HCB)) -> USDA PDB

log Kow = 5.73

5.73

5.5/6.2

2.044 at 75.2 °F (USCG, 1999) - Denser than water; will sink

2.044 g/cu-cm at 23 °C

2.0 g/cm³

2.044 at 75.2 °F

2.044 @ 23°C

White needles

Colorless and sublimable prismatic crystals

Colorless crystals

less than 1 mg/mL at 68 °F (NTP, 1992)

In water, 4.7X10-3 mg/L at 25 °C

Sparingly soluble in cold alcohol; soluble in benzene, chloroform, and ether

Soluble in carbon disulfide; sparingly soluble in carbon tetrachloride

6.2e-06 mg/mL at 25 °C

Solubility in water, g/l:

468 °F (NTP, 1992)

242 °C (closed cup)

242 °C c.c.

468 °F

612 °F at 760 mmHg (sublimes) (NTP, 1992)

325 °C

323-326 °C

612 °F

325 °C @760 [mm Hg]

441 to 444 °F (NTP, 1992)

228.83 °C

MP: 200 °C /Technical product/

226 °C

231 °C

441-444 °F

Danger

H350: May cause cancer [Danger Carcinogenicity]

P203, P260, P264, P270, P273, P280, P318, P319, P391, P405, and P501 (click each P-code to see the statement)

Danger

H350 (100%): May cause cancer [Danger Carcinogenicity]

P203, P260, P264, P270, P273, P280, P318, P319, P391, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Bioaccumulation; Carcinogenicity; Developmental Toxicity; Environmental Persistence; Environmental tox; Hepatotoxicity and Digestive System Toxicity; Immunotoxicity; Nephrotoxicity and Other Toxicity to the Urinary System; Neurotoxicity; Reproductive Toxicity

Commission Regulation No 844/2012

Benzene, 1,2,3,4,5,6-hexachloro- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzene, 1,2,3,4,5,6-hexachloro- 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)

Substance: Hexachlorobenzene

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Special Hazards of Combustion Products: They contain highly toxic chloride fumes.

· Combustible material: may burn but does not ignite readily.

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

Harmful by dust inhalation or if swallowed. Irritating to eyes, skin and mucous membranes. Prolonged periods of ingestion may cause cutaneous porphyria. (USCG, 1999)

· Highly toxic, may be fatal if inhaled, ingested or absorbed through skin.

Hexachlorobenzene was widely used as a pesticide to protect the seeds of onions and sorghum, wheat, and other grains against fungus until 1965. It was also used to make fireworks, ammunition, and synthetic rubber. Currently, there are no commercial uses of hexachlorobenzene in the United States. Hexachlorobenzene is a white crystalline solid that is not very soluble in water. It does not occur naturally in the environment. It is formed as a by-product while making other chemicals, in the waste streams of chloralkali and wood-preserving plants, and when burning municipal waste.

Hexachlorobenzene is formed as a byproduct during the manufacture of other chemicals. It was widely used as a pesticide until 1965. Chronic (long-term) oral exposure to hexachlorobenzene in humans results in a liver disease with associated skin lesions. Epidemiologic studies of persons orally exposed to hexachlorobenzene have not shown an increased cancer incidence. However, based on animal studies that have reported cancer of the liver, thyroid, and kidney from oral exposure to hexachlorobenzene, EPA has classified hexachlorobenzene as a probable human carcinogen (Group B2). Very little inhalation data are available.

In Turkey between 1955-1958, about 4000 people developed a cutaneous porphyria syndrome six months after eating bread contaminated with hexachlorobenzene. [Ladou, p. 265] No evidence of hepatic injury in humans as the result of environmental contamination. [Zimmerman, p. 414] May affect liver and nervous system causing impaired organ function and skin lesions; May be toxic to human reproduction, based on animal studies; [ICSC] The liver is the primary target organ of toxicity; Interferes with porphyrin metabolism which may lead to acquired porphyria cutanea tarda; Crosses the placenta and is excreted in breast milk; May cause skin, eye, nose, throat and lung irritation; No evidence of inhalation causing porphyria cutanea tarda or other adverse effects; Skin absorption not considered major route of exposure, although dermal absorption has been shown in studies of rats; [INCHEM PIM]

The major hazards encountered in the use and handling of hexachlorobenzene stem from its toxicologic properties. Toxic by all routes (ie, inhalation, ingestion, and dermal contact), exposure to this white crystalline substance may occur from its use as a fungicide, and as an intermediate or additive in the production of rubber, polyvinyl chloride, pyrotechnic compositions, dyes, and pentachlorophenol. Effects from exposure may include dermal irritation, CNS excitation, seizures, pneumonitis, and respiratory depression. Also, it should be noted that the EPA Carcinogen Assessment Group has placed hexachlorobenzene on a list of substances that it considers possibly carcinogenic to humans. Likewise, the International Agency for Research on Cancer (IARC) considers the substance to be possibly carcinogenic to humans. In activities or situations where over exposure may occur, wear a self-contained breathing apparatus and protective clothing. If contact should occur, immediately flush affected skin or eyes with running water for at least 15 minutes, and remove contaminated clothing and shoes at the site. While hexachlorobenzene does not ignite easily, it can burn with the production of irritating and poisonous gases. Fires involving hexachlorobenzene may be extinguished with dry chemical, CO2, Halon, water spray, fog, or standard foam. Hexachlorobenzene may be shipped via air, rail, road, and water in containers bearing the label, "Keep away from food". Small spills of hexachlorobenzene may be taken up with sand or other noncombustible material, and placed into containers for later disposal. Large spills should first be diked far ahead of the spill. Hexachlorobenzene is a potential candidate for rotary kiln incineration. Before implementing land disposal of waste hexachlorobenzene, consult with environmental regulatory agencies for guidance.

Courtney KD; hexachlorobenzene (HCB): A Review, Environ Res 20 (2): 225-366 (1979). A review with 162 references on occurrence in humans, as well as experimental studies with lower mammals and birds.

Renner G; Biotransformation of the Fungicides Hexachlorobenzene and Pentachloronitrobenzene, Xenobiotica 11 (7): 435-46 (1981).

USEPA; Ambient Water Quality Criteria Doc: Chlorinated Benzenes (1980) 440/5-80-028

USEPA/ECAO; Hazard Profile: Hexachlorobenzene (1980)

For more Special Reports (Complete) data for HEXACHLOROBENZENE (10 total), please visit the HSDB record page.

U127; As stipulated in 40 CFR 261.33, when hexachlorobenzene, 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).

D032; A solid waste containing hexachlorobenzene may or may not become characterized as a hazardous waste when subjected to the Toxicity Characteristic Leaching Procedure listed in 40 CFR 261.24, and if so characterized, must be managed as a hazardous waste.

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:

Use water spray, foam, powder, carbon dioxide.

Fresh air, rest.

Rinse and then wash skin with water and soap.

Rinse with plenty of water (remove contact lenses if easily possible). Refer for medical attention if irritation persists.

Rinse mouth. Seek medical attention if you feel unwell.

· 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.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

General First Aid:

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

TIH (Toxic Inhalation Hazard) - Term used to describe gases and volatile liquids that are toxic when inhaled. Some are TIH materials themselves, e.g., chlorine, and some release TIH gases when spilled in water, e.g., chlorosilanes. [ERG 2016].

Use water spray, foam, powder, carbon dioxide.

Dry chemical.

If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire. (Material itself does not burn or burns with difficulty.) use water in flooding quantities as fog. use foam, dry chemical, or carbon dioxide. Keep run-off water out of sewers and water sources.

Separated from food and feedstuffs. Well closed.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable 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/

Keep container tightly closed in a dry and well-ventilated place. Keep in a dry place.

Absorb the spills with paper towels or like materials. Place in hood to evaporate followed by burning the towel. Dissolve in a combustible solvent. Scatter the spray of the solution into the furnace with after burners and alkali scrubber.

Hexachlorobenzene was successfully removed in four of five plants using biologic waste-water treatment process (accumulation of the compound in activated sludge in aeration and decantation tanks). Hexachlorobenzene was removed from the effluent at the rate of 96%.

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/

Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U127 and D032, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

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": Total destruction ... by 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/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for HEXACHLOROBENZENE (10 total), please visit the HSDB record page.

Personal protection: chemical protection suit and particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into sealable containers. Carefully collect remainder. Then store and dispose of according to local regulations.

BLOOD - chlorinated solvents factory workers, 14-233 ppb, vegetable spraymen, 0-310 ppb(1). ADIPOSE TISSUE-US, 6115 samples. 0.05 ppm (average) (US National Human Adipose Tissue Survey)(11). Canada, 99 samples, 10-667 ppb(2). Japan, 0.06-0.21 ppm(3,4). Rome, Italy, 28 samples, 0.49 ppm, avg(5). United Kingdom, 0.02-3.2 ppm(6). HUMAN MILK - Canada, 0-5.13 ppm(7). Norway, 133 women, 2.1 ppb (fat basis)(8). Finland, 50 samples, 0.7-6 ppb(9). SERUM - positive detections in 3.3% of 2269 USA persons (aged 12-74 yr) (at levels of 1-17 ppb) monitored between 1976 and 1980(10).

Hexachlorobenzene was detected in Ankra, Turkey citizens human adipose tissue at a mean concentration of 0.164 mg/kg(1) and citizens of Tebriz, Iran at a mean concentration of 0.055 mg/kg(2). Hexachlorobenzene was detected at a mean concentration of 5.38 ug/g in human blood lipids of Slovak Republic citizens(3). Hexachlorobenzene was detected at concentrations of 0-7 ug/L in the blood of humans residing in Zagreb, Croatia(4) and at concentrations of 0.13-0.17 ng/g in US citizens(5). Hexachlorobenzene was detected at concentrations of 50-1,400 ng/g in blood samples of aluminum foundry workers using hexachloroethane for degassing(6).

Hexachlorobenzene (HCB) is widely distributed and persists in the environment. In the 1970s, restrictions on HCB use as a fungicide for cereal grains were initiated, but there are other uses and releases from chemical manufacturing industries and waste disposal operations. Representative values for HCB in environmental media and in man have been used in an exposure commitment assessment. The human body burden of HCB, estimated at 0.7 mg, is derived mainly from dietary intake of fatty foods, diet contributing approximately 0.2 ug/day. Inhalation is estimated to contribute about two orders of magnitude less. The assessment indicates a low exposure to HCB from the general environment, but populations exposed to direct contamination have had increased intake via one or both pathways.

Hexachlorobenzene (HCB) 0.02% diet + diethylstilbestrol dipropionate 6 mg/kg ip or chlorotrianisene 5 mg gave more male rat liver porphyrin than HCB only. Diethylstilbestrol dipropionate or chlorotrianisene only: no effect. HCB + diethylstilbestrol dipropionate or chlorotrianisene: less liver HCB than with HCB only. Estrogen-induced porphyria due to stimulated HCB metabolism.

The effects of extended oral administration of small amounts of aromatic organohalide cmpd on the toxicity of carbon tetrachloride were studied in rats. Male Sprague-Dawley rats were maintained on diets containing hexachlorobenzene (HCB) at 30 mg/kg by gavage every 72 hr. After 20 days of treatment, rats were given an ip dose of carbon tetrachloride at up to 2.0 ml/kg. Growth, renal function, and hepatocellular damage were compared to those rats receiving carbon tetrachloride without pretreatment. Survival after various ip doses of carbon tetrachloride was determined in rats with pretreatments with HCB. HCB increased the susceptibility of the rats to the toxic effects of carbon tetrachloride. Growth retardation induced by carbon tetrachloride was more severe in pretreated rats. Renal tubular function was more impaired in pretreated rats although only minor histological changes due to carbon tetrachloride were apparent in the kidneys. Morphological liver injury and hepatocellular necrosis were more severe in the animals pretreated with HCB. Survival after acute doses of carbon tetrachloride was reduced in animals pretreated with HCB. It was concluded that the toxicity of carbon tetrachloride is potentiated by prior exposure to HCB.

Dietary administration of n-hexadecane (5%) increased fecal excretion of (14)C from (14)C-hexachlorobenzene (HCB) by 4 to 13-fold in rats and rhesus monkeys. Mineral oil (5%) in the diet of rhesus monkeys elicited a 6 to 9-fold increase in fecal excretion of (14)C, but cholestyramine had no effect.

The present work deals with the effect of desferrioxamine on hexachlorobenzene (HCB) induced porphyria in female rats with the purpose of further investigation of the role of iron in the development of this porphyria. The results obtained show that the repeated injection of desferrioxamine (three times a week: 100 mg/kg each im) delayed and diminished remarkably the urinary excretion of precursors and porphyrins as well as the accumulation of the latter in liver promoted by HCB (1 g/kg daily given by stomach tube). This was probably due to attenuation by desferrioxamine of the alterations produced by the fungicide in the two key enzymes: porphyrinogen carboxylase and delta-aminolevulinate synthase. In fact, deferrioxamine by reducing liver iron levels produced a smaller decrease of the target enzyme and a concomitant smaller induction of delta-aminolevulinate synthase. Desferrioxamine alone did not modify any of these variables or the liver to body weight ratio. Desferrioxamine added at 10(-2) and 10(-3) M to the incubation media of delta-aminolaevulinate synthase and porphyrinogen carboxylyase did not alter either of the enzymatic activities, whether in normal or HCB-porphyric preparations.

For more Interactions (Complete) data for HEXACHLOROBENZENE (9 total), please visit the HSDB record page.

Cancer, Developmental (effects during periods when organs are developing) , Hepatic (Liver), Neurological (Nervous System), Reproductive (Producing Children)

Hepatic

Chronic exposure to hexachlorobenzene can damage the liver, thyroid, nervous system, bones, kidneys, blood, and immune and endocrine systems. It also causes a syndrome, called black sore, that is characterized by dermal blistering and epidermolysis, pigmentation and scarring, alopecia, photosensitivity, hepatomegaly, porphyria, suppurative arthritis, osteomyelitis, and osteoporosis of the bones of the hands. It may also cause a liver disease called porphyria cutanea tarda. This disease can cause red-colored urine, skin sores, change in skin color, arthritis, and problems of the liver, nervous system, and stomach. Hexachlorobenzene also affects development and results in lower survival rates of children of exposed mothers. It is also believed to be a human carcinogen. (T10, L225)

LC50; Species: Oncorhynchus kisutch (coho salmon) weight 0.5 g; Conditions: static bioassay, 7 °C; Concentration: >50 mg/L for 96 hr (95% confidence limit) /technical 80-96%/

LC50; Species: Pimephales promelas (fathead minnow) weight 0.7 g; Conditions: static bioassay, 20 °C; Concentration: 22 mg/L for 96 hr @ 20 °C (95% confidence limit) /technical 80-96%/

LC50; Species: Ictalurus punctatus (channel catfish) weight 0.8 g; Conditions: static bioassay, 20 °C; Concentration: 14 mg/L for 96 hr (95% confidence limit, 11-16 mg/L) /technical 80-96%/

LC50; Species: Lepomis macrochirus (bluegill) weight 1.0 g; Conditions: static bioassay, 20 °C, hard water; Concentration: 12 mg/L for 96 hr /technical 80-96%/

For more Ecotoxicity Values (Complete) data for HEXACHLOROBENZENE (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a recommended classification scheme(1), measured log Koc values in the range of 3.6-5.5(2-4) indicate that hexachlorobenzene is expected to be immobile in soil(SRC). Volatilization of hexachlorobenzene from moist soil surfaces is expected to be an important fate process(SRC) given a Henry's Law constant of 5.8X10-4 atm-cu m/mole at 25 °C(5). However, adsorption to soil is expected to attenuate volatilization(SRC). Hexachlorobenzene is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.72X10-5 mm Hg at 25 °C(6). Hexachlorobenzene is persistent to either abiotic or biodegradation processes in soil(7). One study measured a half-life (first-order kinetics) of 3-6 years for hexachlorobenzene in soils(7,8). The half-life for residence of hexachlorobenzene in soil has been estimated to be 970-2100 days with the major loss process from soil at the surface being volatilization(9).

AQUATIC FATE: Based on a classification scheme(1), measured log Koc values of 4.9-5.5) measured in sediment(2,3) indicate that hexachlorobenzene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon a Henry's Law constant of 5.8X10-4 atm-cu m/mole(5), but adsorption is expected to attenuate this process(SRC). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 7.5 hours and 7.5 days, respectively, if adsorption is ignored(SRC). The volatilization half-life from a model pond (2 m deep) is approximately 5 years if adsorption is considered(6). According to a classification scheme(7), BCF values in the range of 1,600 to 30,000 in fish(8) suggest that bioconcentration in aquatic organisms is very high. Hexachlorobenzene is resistant to aerobic biodegradation(8). Anaerobic biodegradation in water-sediment varies widely with half-lives ranging from weeks to years(8) with an intermediate value of roughly 1.7 years(8). Hydrolysis is not an important fate process for hexachlorobenzene(8). Photolysis half-lives in shallow water exposed to sunlight may be on the order of 70 days(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), hexachlorobenzene, which has a vapor pressure of 1.71X10-5 mm Hg at 25 °C(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Monitoring studies have demonstrated that the vapor phase generally predominates(3). Vapor-phase hexachlorobenzene 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 1.6 years(SRC) from its rate constant of 2.7X10-14 cu cm/molec-sec(SRC). Results of vapor phase photolysis studies indicate direct photolysis is not expected to be an important fate process in the atmosphere(3). Particulate-phase hexachlorobenzene may be physically removed from the air by wet and dry deposition(SRC). Hexachlorobenzene has been detected in many precipitation monitoring studies (both rain water and snow)(4); therefore, removal from air occurs via wet deposition(SRC).

Hexachlorobenzene was detected in 33 of 300 adult food composites in the US at concentrations of 0.001-0.002 ppb(1), in 13 of 117 infant composites at 0.001-0.006 ppm(2) and in 27 of 132 toddler food composites at 0.001-0.006 ppm(2) in 1976-1977. Hexachlorobenzene was detected in 17 of 98 infant foods at 0.003-0.008 ppm and 29 of 110 toddler foods at 0.001-0.010 ppm in 1977-1978(3). Hexachlorobenzene was detected in 46 of 327 food composites collected in 27 US cities at trace levels to 0.005 ppm in 1981-1982(4). In a compilation of hexachlorobenzene levels in food items from the Food and Drug Administration's Total Diet Study Market Baskets 1991-1993 through 2003-2004 collected between September 1991 and October 2003, positive mean hexachlorobenzene concentrations ranged from 0.00001 to 0.00030 ppm(5); highest concentrations were in various meats and fish(5). In a compilation of hexachlorobenzene levels in food items from the Food and Drug Administration's Total Diet Study Market Baskets 2004 through 2005 collected Between October 2003 and August 2005, positive mean hexachlorobenzene concentrations ranged from 0.00001 to 0.00023 ppm(5); highest concentrations were in ground beef, butter and salmon(5).

Mean values of 11-15 ug/kg of hexachlorobenzene were reported in pork(1). Hexachlorobenzene was identified, not quantified, in 251 of 6,138 meat and poultry samples in the US(2). Hexachlorobenzene was detected at concentrations of 0.47 mg/kg (fresh butter), 0.30 mg/kg (table butter) and 0.60 mg/kg (low fat butter)(3). Hexachlorobenzene was detected at an average concentration of 0.05 ug/g in cheese from Mexico(4) and at concentrations of 0-48.4 ng/g in cheese from Spain(5). The concentration of hexachlorobenzene in beef muscle, beef liver and pork from South Korea was 0.45 ng/g, 0.64 ng/g and 0.13 ng/g respectively(6). Hexachlorobenzene was detected at an average concentration of 0.0006 ug/g in 81 of 230 food items sampled in the US(7). Hexachlorobenzene was detected at a maximum concentration of 0.02 ppm in rice imported to the US(8). The average concentration of hexachlorobenzene in food products from northern Spain were, 0.2 ng/g (legumes), 0.2 ng/g (cereal), 1.6 ng/g (eggs) and 0.1 ng/g (fish)(9).

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

Oral (L225); inhalation (L225) ; dermal (L225)

U127; As stipulated in 40 CFR 261.33, when hexachlorobenzene, 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).

D032; A solid waste containing hexachlorobenzene may or may not become characterized as a hazardous waste when subjected to the Toxicity Characteristic Leaching Procedure listed in 40 CFR 261.24, and if so characterized, must be managed as a hazardous waste.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Hexachlorobenzene is produced, as an intermediate or a final product, by process units covered under this subpart.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Hexachlorobenzene is included on this list.

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 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

The following maximum contaminant level for synthetic organic contaminants apply to community water systems and non-transient, non-community water systems: Hexachlorobenzene, MCL 0.001 mg/L.

Toxic pollutant designated pursuant to section 307(a)(1) of the Federal Water Pollution Control Act and is subject to effluent limitations. /Chlorinated benzenes/

(AZ) ARIZONA 0.02 ug/L

(ME) MAINE 0.2 ug/L

(MN) MINNESOTA 0.2 ug/L

Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5uM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30mg/kg bw) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). /The/ results show that HCB (5uM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3mg/kg bw) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30mg/kg bw) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, /the authors/ observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status ... /suggesting/ that HCB may be a risk factor for human breast cancer progression.

During feeding of hexachlorobenzene (HCB; 0.2%) to rats (female, Wistar) to induce experimental porphyria, partial uncoupling of oxidative phosphorylation of liver mitochondria was observed after 20 days. This uncoupling is due to the action of pentachlorophenol endogenously formed by metabolism of HCB. A comparison between the pattern of pentachlorophenol concn and of urinary and hepatic porphyrin levels during the time course of intoxication that pentachlorophenol is not involved in the development of HCB-induced porphyria.

Immunoreactive and catalytic uroporphyrinogen decarboxylase was measured in the livers of rodents made porphyric by hexachlorobenzene (HCB). Catalytic activity decreased progressively as porphyria developed but was not accompanied by a fall in the concentration of immunoreactive enzyme protein. These findings suggest that HCB specifically inactivates uroporphyrinogen decarboxylase without affecting those regions of the molecule that determine its antigenic activity and without increasing its rate of catabolism. In vitro, uroporphyrin-catalysed photoinactivation of uroporphyrinogen decarboxylase was similarly unaccompanied by loss of immunoreactivity, whereas reaction of sulfhydryl groups with N-ethylmaleimide led to loss of both catalytic activity and immunoreactivity. HCB may induce chronic porphyria by modifying sulfhydryl groups in the enzyme; the effect is restricted to catalytic or substrate-binding sites.

Control mouse liver uroporphyrinogen decarboxylase was markedly inhibited in vitro by addition of cytosol fractions from livers of porphyric mice chronically treated with 2,3,7,8-tetrachlorodibenzo-para-dioxin (25 ug/kg per week, ip). Inhibition was proportional to the amount of fraction added and was not observed if the inhibitor fraction was dialysed before incubation. Increasing the substrate concentration did not reverse enzyme inhibition; the Vmax value calculated for the control enzyme in the presence of the inhibitor fraction was decreased, but Km did not vary.

For more Mechanism of Action (Complete) data for HEXACHLOROBENZENE (10 total), please visit the HSDB record page.

Half-life in rats and monkeys was measured at 3-4 months and 2 1/2 to 3 years, respectively. [EXTOXNET]

The half-life for hexachlorobenzene in sheep, chickens, and pigs was 10-18 weeks, 8-14 weeks and 10-12 weeks, respectively.

/In rats/ ... the biologic half-life was 4 to 5 months.

After iv injection of hexachlorobenzene (1.5 mg/kg), the estimated half-life of HCB was 24 days in rats (male, Sprague-Dawley) and 32 days in rabbits (male). Dietary hexadecane (5%, weight/weight) increased fecal excretion and decreased half-life to 8 days in rats and 12 days in rabbits. Although half-lives are usually derived from plasma concn, these estimates represent underestimations in terms of the mass of persistent, lipophilic chemical remaining in the body.

The distribution of HCB was studied in male beagles after a single 1 mg/kg iv dose of either (14)C HCB or unlabeled HCB. Distribution was also determined in animals after 7 daily oral administrations of 10 or 100 mg/kg HCB. ... Biological half-life values were projected to range from 6 wk to 3 yr.

After ip and oral admin of (14)C hexachlorobenzene in rats was dose-dependent ... major urinary metabolites were ... pentachlorophenol, tetrachlorohydroquinone, and pentachlorothiophenol. Other urinary metabolites were tetrachlorobenzene, pentachlorobenzene, 2,4,5- & 2,4,6-trichlorophenols ... 2,3,4,6- and 2,3,5,6-tetrachlorophenols; 2,3,4-trichlorophenol and other tetrachlorophenols were present in traces. These metabolites were excreted as conjugates or in free form in urine. Unchanged hexachlorobenzene was found in the feces and in fat.

When 110 ug/day (14)C-hexachlorobenzene was given orally to macaca mulatta monkeys for 11-15 months, 50% of radioactivity found in urine was pentachlorophenol and 25% pentachlorobenzene, the remainder was unidentified metabolites and unchanged hexachlorobenzene. In feces, 99% of radioactivity was unchanged HCB.

Hexachlorobenzene (HCB) was metabolized by phenobarbital induced liver microsomes from male rats to pentachlorobenzene, pentachlorophenol, tetrachloro-1,2-benzenediol, and tetrachloro-1,4-benzenediol (1:88:2:9). Metabolites were identified and quantified by electron capture gas-liquid chromatography. Structures were confirmed by selective ion monitoring gas-liquid chromatography/mass spectrometry. The formation of pentachlorophenol was dependent on the presence of NADPH and oxygen and inhibited by carbon monoxide SKF 525A, and metyrapone. Conversion of HCB to pentachlorophenol was stimulated by pretreatment of rats with phenobarbital but not by 3-methylcholanthrene, or 2,3,7,8-tetrachlorodibenzo-p-dioxin. In contrast, the conversion of pentachlorophenol to tetrachloro-1,4-benzenediol was markedly induced by 3-methylcholanthrene but poorly by phenobarbital. HCB, Aroclor 1254, and isosafrole stimulated both hydroxylations. The cytochrome p450 inhibitor 9-hydroxyellipticine inhibited conversion of pentachlorophenol to tetrachlorobenzenediols by HCB and beta-naphthoflavone induced micrsomes. In addition to hydroxylation reactions, evidence was obtained for the conjugaton of HBC with glutathione catalyzed by a microsomal glutathione transferase. Radioactivity from (14)carbon HCB was bound to microsomal protein during aerobic incubations. Binding was inhibited by GSH and N-acetyl-cysteine.

The induction by organochloride pesticides of rat hepatic microsomal monooxygenases which hydroxylate benzo(a)pyrene and testosterone was compared with that of phenobarbital, in order to investigate their activity as inducers of different cytochrome p450 isozymes. Long Evans rats were administered intraperitoneal injections of 400 umol/kg phenobarbital for 4 consecutive days and were sacrificed the following day, or were administered single doses of heptachlor, chlordane, hexachlorobenzene, toxaphene, dieldrin, lindane, or p,p'-DDT and were sacrificed 4 days later. Microsomal liver fractions were analyzed for benzo(a)pyrene and testosterone metabolism. All the compounds tested except lindane induced both benzo(a)pyrene and testosterone hydroxylases. Hexachlorobenzene induced formation of benzo(a)pyrene 9,10-dihydrodiol and 7,8-dihydrodiol metabolites. A different combination of testosterone hydroxylases was induced by each of the chemicals. Phenobarbital induced the activities of the 15-beta, 16-alpha, and 16-beta testosterone hydroxylases. With the exception of lindane, all of the pesticides tested induced the 16-alpha and 16-beta testosterone hydroxylases.

For more Metabolism/Metabolites (Complete) data for HEXACHLOROBENZENE (7 total), please visit the HSDB record page.

HEXACHLOROBENZENE has known human metabolites that include Pentachlorophenol.

... In rats over a 53 week period ... /hexachlorobenzene/ was given orally every other day ... 9 weeks after start of treatment an equilibrium was reached between intake and elimination of the compound and its metabolites.

... Male wistar rats, fed by stomach tube 8 mg /hexachlorobenzene/ ... per kg (in sunflower oil) for 19 days. Tissue concentration at termination of treatment period were for body fat, 82 ppm; muscle, 17 ppm; total liver, 125 ug; total kidney, 21 ug; total spleen, 9 ug; total heart, 1.5 ug; and adrenal, 0.5 ug each.

... With labeled hexachlorobenzene ... four weeks after administration, 7% of radioactivity was excreted in rats via kidneys and 27% with feces. Nearly the total in urine was contained in metabolites of hexachlorobenzene, and 69% ... in feces was ... unchanged drug.

... Cd-1 mice ... treated with hexachlorobenzene by gastric intubation at ... 10, 50, or 100 mg/kg/day. Concentration in fetuses ranged from 0.76 ppm to ... 19.09 ppm and appeared ... related to level of dose received by mother. Fetal ... levels were higher in mice treated before implantation than in those treated on days 6-11 of gestation. ...

For more Absorption, Distribution and Excretion (Complete) data for HEXACHLOROBENZENE (20 total), please visit the HSDB record page.

There are currently no commercial uses of hexachlorobenzene in the United States. Hexachlorobenzene is currently formed as a byproduct during the manufacture of other chemicals (mainly solvents) and pesticides.

Was used as a pesticide until 1965; it may be produced as a waste product from chloralkali and wood-preserving plants or as an emission from municipal incinerators; it can bioaccumulate in lichens, fish, marine animals, birds, and caribou; [ATSDR ToxFAQs] Used as a seed fungicide to prevent common and dwarf bunt on wheat; [EXTOXNET] Hexachlorobenzene differs chemically and toxicologically from hexachlorocyclohexane, the gamma isomer of which (lindane) is still a widely-used insecticide. [EPA Pesticides] Used in organic synthesis; [Merck Index] Used to make rubber, electrodes, dyes, pentachlorophenol, and aromatic fluorocarbons; Also used as plasticizer for polyvinyl chloride, wood preservative, in military pyrotechnics, and to impregnate paper; [HSDB] Uses likely discontinued: as a wood preservative and in manufacture of munitions, aluminum (fluxing agent), graphite anodes, and rubber; Used as fungicidal seed treatment in some countries until 1985; Still produced in appreciable quantities as by-product in manufacture of chlorinated solvents and pesticides; [INCHEM HSG]

Banned from use as a pesticide in the U.S. [EXTOXNET]

Aluminum Producing [Category: Industry]

For hexachlorobenzene (USEPA/OPP Pesticide Code: 061001) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

In organic syntheses. Formerly as agricultural fungicide.

(1977) 2.44X10+6 G

(1982) 1.73X10+7 G

2023: <50,000 lb

(1977) AT LEAST 4.54X10+8 G

(1982) NO EVIDENCE OF COMMERCIAL PRODUCTION IN USA

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#3501]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Benzene, 1,2,3,4,5,6-hexachloro-. Aggregated National Production Volume: < 500,000 pounds.

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Benzene, 1,2,3,4,5,6-hexachloro-. National Production Volume: Withheld.

Chlorination of benzene; isolation from by-product residues of tetrachloroethylene production; reaction of hexachlorocyclohexane with chlorine or sulfuryl chloride

Hexachlorobenzene can be produced by exhaustive chlorination of benzene, using chlorine in the presence of such catalysts as ferric chloride. The reaction is conducted at a temperature above 230 °C in the liquid or vapor phase. Because much of the chlorine remains unreacted and because hexachlorobenzene sublimes, the off-gas from the process is passed through fresh starting material, in the course of which the chlorine is reacted and the sublimate washed out. The difficulties caused by sublimed hexachlorobenzene can be eliminated by batch chlorination with liquid chlorine in an autoclave.

... Produced by ... hexachlorocyclohexane in the presence of chlorine.

Preparation: Becke, Sperber, United States of America patent 2792434 (1957 to BASF)

Dust: 15%, 20%; Powder 15%, 20%

The technical grade used in agriculture contains 98% hexachlorobenzene, 1.8% pentachlorobenzene, and 0.2% 1,2,4,5-tetrachlorobenzene.

... In technical pentachlorophenol up to 13%, in herbicide DCPA /propanil/ up to 10-14%, in pesticide PCNB /pentachloronitrobenzene/ between 1 and 6%.

Agsco DB-Green-A: dust, 18.75% Lindane (Gamma-isomer of benzene hexachloride), 40% Maneb, 10% Hexachlorobenzene.

Chemical Classes -> Pesticides (chemicals used for killing pests, such as rodents, insects, or plants)

FUNGICIDES

All Other Basic Organic Chemical Manufacturing

Benzene, 1,2,3,4,5,6-hexachloro-: ACTIVE

The WHO Recommended Classification of Pesticides by Hazard identifies hexachlorobenzene (technical grade) as Class IA: extremely hazardous; Main Use: fungicide, for seed treatment. The international trade of ... hexachlorobenzene ... is regulated by the Rotterdam convention on Prior Informed Consent ... which entered into force on 24 February 2004. ... The use and production hexachlorobenzene is severely restricted by the Stockholm convention on persistent organic pollutants, which entered into force on 17 May 2004.

Mixed formulations: (hexachlorobenzene+)fuberidazole and mercury fungicides.

Previously sold in combination with other seed protectants.