1,2-Dichlorobenzene

Pesticide -> EPA IRIS

Volatile Organic Compound (VOC) (Pesticide/Volatile Organic Compound (VOC)/Semi-Volatile Organic Compound (SVOC))

log Kow = 3.43

3.38

3.34

Pleasant odor

... Pleasant, aromatic odor

1.306 at 68 °F (USCG, 1999) - Denser than water; will sink

1.3059 g/mL at 20 °C/4 °C

Saturated liquid density 81.45 lb/cu ft @ 70 °F

Saturated vapor density= 0.00065 lb/cu ft @ 70 °F

Relative density (water = 1): 1.3

1.306

Colorless liquid

Colorless to pale-yellow liquid ...

less than 1 mg/mL at 76.1 °F (NTP, 1992)

Miscible with alcohol, ether, benzene.

In water, 156 mg/L at 25 °C

Solubility in water: very poor

0.01%

151 °F (NTP, 1992)

151 °F

155 °F (Open Cup); 151 °F (Closed Cup)

68 °C, closed cup; 74 °C, open cup

66 °C c.c.

151 °F

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.2% (1 of 546) of reports.

Warning

H302+H332 (24.7%): Harmful if swallowed or if inhaled [Warning Acute toxicity, oral; acute toxicity, inhalation]

Chemical: Benzene, 1,2-dichloro-

Hazard Traits - Dermatotoxicity; Endocrine Toxicity; Hematotoxicity; Hepatotoxicity and Digestive System Toxicity; Nephrotoxicity and Other Toxicity to the Urinary System; Neurotoxicity; Ocular Toxicity; Other Toxicological Hazard Traits; Respiratory Toxicity

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

T - indicates a substance that is the subject of a final TSCA section 4 test rule.

Status: Active Update: 13-03-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/13734

1,2-Dichlorobenzene: Does not have an individual approval but may be used under an appropriate group standard

Special Hazards of Combustion Products: Poisonous vapors including hydrogen chloride gas, chlorocarbons, chlorine (USCG, 1999)

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

Combustible. Above 66 °C explosive vapour/air mixtures may be formed.

Chronic inhalation of mist or vapors may result in damage to lungs, liver, and kidneys. Acute vapor exposure can cause symptoms ranging from coughing to central nervous system depression and transient anesthesia. Irritating to skin, eyes, and mucous membranes. May cause dermatitis. (USCG, 1999)

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

Liver and kidney injury occur in animal inhalation studies. Inhalation of saturated vapor by mice results in narcosis and death. A case of skin sensitization reported, but sufficient data were not available to recommend a SEN notation. [ACGIH] Inhalation of high concentrations may cause CNS effects; A skin, eye, and respiratory tract irritant; [ICSC]

1591 152

1591 152

USEPA; Ambient Water Quality Criteria Doc: Dichlorobenzenes (1980) EPA 440/5-80-039

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

USEPA; Health Assessment Document: Chlorinated Benzenes (1985) EPA-600/8-84-015F

USEPA/OWRS: Quality Criteria for Water 1986 1,2-Dichlorobenzene (1986) EPA 440/5-86-001

For more Special Reports (Complete) data for 1,2-DICHLOROBENZENE (14 total), please visit the HSDB record page.

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

Use water spray, powder, foam, carbon dioxide.

Fresh air, rest. Refer 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. Give one or two glasses of water to drink. Do NOT induce vomiting. Refer 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.

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:

(General first aid procedures)

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

182.0 [ppm]

10.0 [ppm]

Approach fire from upwind to avoid hazardous vapors and toxic decomposition products. Use water spray, dry chemical, foam, or carbon dioxide. Use water spray to keep fire-exposed containers cool. Extinguish fire using agent suitable for surrounding fire.

Wear full protective clothing and positive pressure self-contained breathing apparatus.

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.

Land spill: Dig a pit, pond, lagoon, or holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or concrete. Absorb bulk liquid with fly ash, or cement power. Apply "universal" gelling agent to immobilize spill.

Water spill: Use natural deep water pockets, excavated lagoons, or sand bag barriers to trap material at bottom. If dissolved in region of 10 ppm or greater concn apply activated carbon at 10 times the spilled amount. Remove trapped material with suction hoses. Use mechanical drifts or lifts to remove immobilized masses of pollutants and precipitates.

1. Remove all ignition sources. 2. Ventilate area of spill or leak. 3. For small quantities, absorb on paper towels. Evaporate in a safe place (such as a fume hood). Allow sufficient time for evaporating vapors to completely clear the hood ductwork. Burn the paper in a suitable location away from combustible materials. Large quantities can be reclaimed or collected and atomized in a suitable combustion chamber equipped with an appropriate effluent gas cleaning device.

Approach release from upwind. Stop or control the leak, if this can be done without undue risk. Control runoff and isolate discharged material for proper disposal.

For more Cleanup Methods (Complete) data for 1,2-DICHLOROBENZENE (6 total), please visit the HSDB record page.

Generators of waste (equal to or greater than 100 kg/month) containing this contaminant, EPA hazardous waste number U070 & F002, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

... Halogenated compounds may be disposed of by incineration provided they are blended with other compatible wastes or fuels so that the composite contains less than 30% halogens and the heating value is from 7000 to 9000 BTU/1b. Liquid injection, rotary kiln, and fluidized bed incinerators are typically used to destroy liquid halogenated wastes. ... Temperatures of at least 2000 - 2200 °F and residence times /of more than 2 sec/ ... are required for the destruction of halogenated aromatic hydrocarbons.

Potential candidate for rotary kiln incineration, with a temperature range of 820 to 1,600 °C, and a residence time of seconds. Also a potential candidate for liquid injection incineration, with a temperature range of 650 to 1,600 °C, and a residence time of 0.1 to 2 seconds.

Chemical Treatability of 1,2-Dichlorobenzene; Concentration Process: Stripping; Chemical Classification: Aromatic; Scale of Study: Full Scale, Continuous Flow; Type of Wastewater Used: Domestic Wastewater; Results of Study: 70% reduction by air stripping.

Dichlorobenzene was detected in whole blood (3.12 ng/g) and adipose tissue (2.28 ng/g) from the general population of Canada(1). 1,2-Dichlorobenzene was detected in the personal air of Los Angeles, CA residents at concns of 0.3-0.4 ug/cu m and residents of Contra Costa, CA at concns of 0.6 ug/cu m(2). 1,2-Dichlorobenzene was detected in the breath of Los Angeles, CA residents at concns of 0.04-0.1 ug/cu m and residents of Contra Costa, CA at concns of 0.08 ug/cu m(2).

Following oral exposure, administer charcoal as a slurry; administer oxygen to all cyanotic or symptomatic patients. In case of methemoglobinemia, administer 1 to 2 mg/kg of 1% methylene blue slowly IV in symptomatic patients; also consider adjunctive therapy. In case of inhalation exposure, move patient to fresh air; monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. Following eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. Following dermal exposure, skin should be thoroughly washed with soap and water; contaminated clothing and shoes should be discarded. Administer 100 percent humidified supplemental oxygen with assisted ventilation as required. Treat for methemoglobinemia and sequelae. Signs and symptoms of methemoglobinemia may be delayed. (T36)

Effect of 1,2-DCB on sulfur metabolism as measured in the urine was studied in 5 dogs given 50 mg/kg bw or 250 mg/kg bw 1,2-DCB. ...Urinary output of sulfur was increased in 1,2-DCB dosed animals compared to controls.

The hepatic toxicity of ortho-dichlorobenzene was studied in Fischer 344 rats given methyl palmitate in order to inhibit Kupffer-cell function or superoxide dismutase (conjugated to polyethylene glycol) to scavenge superoxide anions. Administration of either compound dramatically reduced the severity of ortho-dichlorobenzene-induced liver injury, and both agents reduced the increase in plasma alanine aminotransferase activity by 80%; light microscopic examination confirmed that the reductions in enzyme activity reflected protection from hepatocellular injury. Interestingly, methyl palmitate did not protect against ortho-dichlorobenzene-induced hepatotoxicity in phenobarbital-pretreated rats, and the degree of inhibition of hepatotoxicity by polyethylene glycol-superoxide dismutase was not significantly different from that in normal rats. The lack of significant inhibition of phenobarbital-potentiated hepatotoxicity by both polyethylene glycol-superoxide dismutase and methyl palmitate suggests that reactive oxygen species released from a non-parenchymal source are not as crucial to the hepatotoxicity of ortho-dichlorobenzene in phenobarbital-pretreated as in the normal rats. The results suggest that reactive oxygen species released from Kupffer cells play a major role in the progression of orthodichlorobenzene hepatotoxicity.

Inhaling the vapor or dusts of 1,2-DCB at very high concentrations could be very irritating to eyes and nose and cause burning and tearing of the eyes, coughing, difficult breathing, and an upset stomach. Ingestion of 1,2-DCB can cause effects in the kidneys and blood, and that 1,3-DCB caused thyroid and pituitary effects. (L395)

EC50; Species: Cyclotella meneghiniana (Diatom, exponential growth phase); Conditions: static, 15 °C; Concentration: 23330 ug/L for 48 hr; Effect: percent DNA reduction

EC50; Species: Pseudokirchneriella subcapitata (Green algae, initial concentration 500,000 cells/L); Conditions: static, 20 °C; Concentration: 2200 ug/L for 96 hr; Effect: general growth

EC50; Species: Scenedesmus subspicatus (Green algae, log growth phase); Conditions: static, 24 °C, pH 8.0-9.3; Concentration: 14000 ug/L for 48 hr; Effect: decreased population biomass

EC50; Species: Scenedesmus subspicatus (Green algae, log growth phase); Conditions: static, 24 °C, pH 8.0-9.3; Concentration: 13500 ug/L for 48 hr; Effect: general population changes

For more Ecotoxicity Values (Complete) data for 1,2-DICHLOROBENZENE (36 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a recommended classification scheme(1), Koc values of 280(2) and 320(3) measured in soil, indicates that 1,2-dichlorobenzene is expected to have moderate mobility in soil(SRC). Volatilization of 1,2-dichlorobenzene is expected from moist soil surfaces given its Henry's Law constant of 1.5X10-3 atm-cu m/mole at 20 °C(4). Volatilization of 1,2-dichlorobenzene from dry soil surfaces is expected based on a vapor pressure of 1.4 mm Hg at 25 °C(5). The volatilization half-life of 1,2-dichlorobenzene from Captina and McLaurin sandy loam soils was measured as about 4 days(6). 1,2-Dichlorobenzene at 100 mg/L achieved 0% of its theoretical BOD using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(7), suggesting that biodegradation is expected to be slow in soil(SRC). 1,2-Dichlorobenzene is resistant to biodegradation in soils, with half-lives expected to be greater than 9 months(8).

AQUATIC FATE: Based on a recommended classification scheme(1), log Koc values of 3.7(2) and 4.3(3) measured in sediment indicate that 1,2-dichlorobenzene is expected to adsorb to suspended solids and sediment in water(SRC). 1,2-Dichlorobenzene is expected to volatilize from water surfaces(4) given its Henry's Law constant of 1.5X10-3 atm-cu m/mole at 20 °C(5). Using this Henry's Law constant and an estimation method(4), estimated volatilization half-lives for a model river and model lake are 4 and 120 hours, respectively(SRC). According to a classification scheme(6), BCF values in the range of 90 to 560, measured in carp(7) and trout(8), suggest that bioconcentration in aquatic organisms is moderate to high. 1,2-Dichlorobenzene at 100 mg/L achieved 0% of its theoretical BOD using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(7), suggesting that biodegradation is expected to be slow in water under aerobic conditions(SRC). The biodegradation half-life of 1,2-dichlorobenzene in an acclimated anaerobic sediment slurry obtained from the Tsurumi River, Japan was 37 days(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,2-dichlorobenzene, which has a vapor pressure of 1.4 mm Hg at 25 °C(2), is expected to exist in the vapor phase in the ambient atmosphere. Vapor-phase 1,2-dichlorobenzene 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 about 38 days(SRC), calculated from its rate constant of 4.2X10-13 cu cm/molecule-sec (3). 1,2-Dichlorobenzene does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to undergo direct photolysis by sunlight(4).

1,2-Dichlorobenzene was detected at a concn of 1.0 ng/g in market meat samples in Yugoslavia(1) and in 45 of 234 table ready foods in the US at an avg concn of 9.47 ppb(2). 1,2-Dichlorobenzene was detected in high-fat foods at concns of 49-113 ng/g and in low-fat foods at 11-78 ng/g(3). 1,2-Dichlorobenzene was detected in potato core at a concn of 0.328 ug/kg and pea seeds at a concn of 0.112 ug/kg(4).

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

inhalation, skin absorption, ingestion, skin and/or eye contact

Inhalation (L554) ; oral (L554) ; dermal (L554)

Mean 1,2-dichlorobenzene of 13 ug/kg (fat basis) detected in Yugoslavian human adipose tissue and 9 ug/kg (as is basis) or 230 ug/kg (fat basis) in human milk.

A survey of human milk from the general population of Canada found 1,2-dichlorobenzene residues in 17 percent of the samples at an avg concn of 2 ppb(1). 1,2-Dichlorobenzene was detected in human milk at 9 ug/kg(2). 1,2-Dichlorobenzene was detected at average concns of 0.04, 0.05 and 0.04 ng/mL in whole milk, 2% milk, and 1% milk, respectively(3).

Gas chromatographic and mass spectral identification of 1,2-DCB was confirmed in cow milk fat; its origin may be from pesticides.

... 1,2-Dichlorobenzene has been shown to cause eye and respiratory irritation in humans at exposure levels above 100 ppm. Skin irritation has been observed following dermal application in humans and animals. 1,2-Dichlorobenzene is absorbed via the oral route. Absorption via the dermal or inhalation routes is poorly characterized. Inhalation is expected to be the major route for human exposure. The available toxicological data indicate that metabolic profiles and effects from 1,2-dichlorobenzene exposure are similar in rats, mice and humans. Animal studies with rats and mice have shown 1,2-dichlorobenzene to induce acute hepatotoxic effects. The LD50 for a single oral exposure to 1,2-dichlorobenzene for the rat ranges from 1516 to 2138 mg/kg bw. The LC100 for the rat is </= 977 ppm (5.9 mg/L) for a 10 hour exposure. During a 4 hour exposure, 1 of 20 rats died at 941 ppm (5.6 mg/L). In humans, the acute effects of 1,2-dichlorobenzene by ingestion or inhalation are reported to be headache, nausea, vomiting, vertigo, malaise and unconsciousness. Several oral studies of rats and mice ranging from 10 days to 2 years duration indicate that the adverse effects include increases in liver and kidney weights and hepatotoxicity. From these repeat dose studies, the NOAEL for non-neoplastic effects was 60 mg/kg bw, while the LOAEL was 120 mg/kg bw due to increased renal tubular regeneration in male mice. In several microbial organisms and mammalian systems, 1,2-dichlorobenzene tested negative in vitro. However, it did induce sister chromatid exchanges in Chinese Hamster ovary cells and increased mutation frequency in mouse lymphoma cells, both in the presence of metabolic activation. 1,2-dichlorobenzene was negative in several in vivo mammalian tests, except one of two micronuclei assays in mouse bone marrow was positive. In a two-year oral study in rats and mice, 1,2-dichlorobenzene was considered not to be carcinogenic (maximum dose of 120 mg/kg bw). In an inhalation 2-generation reproduction study in rats, no fertility effects were observed and reduced pup weight during lactation occurred at doses toxic to adults. The NOAEL and LOAEL (kidney and liver effects) for adult rats were 50 (0.3 mg/L) and 150 ppm (0.6 mg/L) respectively. In developmental studies in rats and rabbits, developmental effects were only seen in rats at maternally toxic doses (400 ppm, 2.4 mg/L). No human epidemiological studies have been conducted. ... 1,2-Dichlorobenzene has been tested on a wide range of aquatic organisms under acute exposure, although chronic data are scarce. Results for fish ranged from 96 hr LC50=1.58 mg/L for rainbow trout to 57 mg/L for fathead minnow. Both acute and chronic toxicity to aquatic invertebrates were obtained with two results showing high acute toxicity, namely EC50's of 0.78 mg/L and 0.66 mg/L to Daphnia and Ceriodaphnia respectively. Results from exposure to algae showed EC50 values in the 1-100 mg/L range for 1,2-dichlorobenzene. Toxicity to microorganisms can be considered slight. Although the major compartment expected to be exposed to 1,2-dichlorobenzene is the atmosphere, there are no ecotoxicity results available for organisms exposed through the gas phase. The chlorine substituents on the chemical suggest a potential for effects on stratospheric ozone. However, the chemical is unlikely to persist long enough to escape the troposphere, although it may persist long enough to undergo long range atmospheric transport. While there are a large number of acute data covering all trophic levels, chronic data are scarce. Therefore, an assessment factor of 100 has been chosen. The result used for determining the PNEC was the lowest chronic value obtained, i.e. 21 d NOEC = 0.63 mg/L for Daphnia magna. The PNECaquatic was therefore determined to be 6.3 ug/L.

1,2-DCB was found to covalently bind to DNA, RNA, and proteins of liver, kidney, lung, and stomach. (L395)

F002; When 1,2-dichlorobenzene is a spent solvent, it is classified as a hazardous waste from a nonspecific source (F002), as stated in 40 CFR 261.31, and must be managed according to state and/or federal hazardous waste regulations.

U070; As stipulated in 40 CFR 261.33, when 1,2-dichlorobenzene, 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).

Pursuant to section 8(d) of TSCA, EPA promulagated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,2-Dichlorobenzene is included on this list. Effective date 10/4/82; Sunset date 10/4/92.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date 8/4/95; Reporting date 10/3/95.

All persons who manufacture (including import or manufacture as a byproduct) or process or intend to manufacture or process one or more of the substances in paragraph c of this section, other than as an impurity, after July 29, 1988, to the end of the reimbursement period shall submit letters of intent to conduct testing, submit study plans, conduct tests, and submit data, or submit exemption applications for those substances they manufacture or process, or intend to manufacture or process, as specified in this section, subpart A of this part, and parts 790 and 792 of this chapter for single-phase rulemaking. 1,2-Dichlorobenzene is included on this list. Required testing: hydrolysis.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA, as amended in 1988, were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. 1,2-Dichlorobenzene is found on List C. Case No: 3057; Pesticide type: Antimicrobial; Case Status: No products containing the pesticide are actively registered ... The case /is characterized/ as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.; Active ingredient (AI): 1,2-Dichlorobenzene; AI Status: The active ingredient is no longer contained in any registered pesticide products ... "cancelled."

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. o-Dichlorobenzene is produced, as an intermediate or a final product, by process units covered under this subpart.

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).

o-Dichlorobenzene is designated as a hazardous substance under section 311(b)(2)(A) of the Federal Water Pollution Control Act and further regulated by the Clean Water Act Amendments of 1977 and 1978. These regulations apply to discharges of this substance. This designation includes any isomers and hydrates, as well as any solutions and mixtures containing this substance.

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

(AZ) ARIZONA 620 ug/L

(ME) MAINE 63 ug/L

(MN) MINNESOTA 600 ug/L

1,2-dichlorobenzene (1,2-DCB), an industrial solvent, is a known hepatotoxicant. Two oxidative events in the liver contribute to 1,2-DCB-induced liver injury: an initial hepatocellular oxidative stress, followed by oxidant stress associated with an inflammatory response. We hypothesize that the initial hepatocellular oxidative event triggers molecular and cellular processes within hepatocytes that lead to the production of factors that contribute to Kupffer cell (KC) activation and upregulation of the inflammatory cascade. To investigate the molecular effects of 1,2-DCB, primary cultures of Fischer-344 (F-344) and Sprague-Dawley (SD) rat hepatocytes were incubated with 1,2-DCB (3.6-12.4 umol) and examined for enhanced DNA-binding activity of the oxidant-sensitive transcription factors activator protein-1 (AP-1), nuclear factor-kappa B (NF-kappaB), and electrophile responsive element (EpRE), and production and release of the chemokine cytokine-induced neutrophil chemoattractant (CINC). In F-344 rat hepatocytes, the activities of AP-1 and NF-kappaB were increased by as much as 3-fold by 6 h of 1,2-DCB treatment, when compared to control. Nuclear translocation of EpRE was also enhanced by 3-fold and occurred 2 h following 1,2-DCB treatment. These events were greater in F-344 than in SD rat hepatocytes incubated with 1,2-DCB. Moreover, F-344 rat hepatocytes produced and released CINC following incubation with 1,2-DCB, but SD rat hepatocytes did not. Lastly, conditioned media from 1,2-DCB-treated F-344 rat hepatocytes stimulated KC activity as determined by enhanced NF-kappaB-binding activity and increased nitric oxide production. Collectively, these data suggest that the mechanisms of 1,2-DCB-induced hepatotoxicity involve intercellular communication whereby compromised hepatocytes may signal KC activation via the production and release of oxidant-sensitive chemokines and cytokines.

... Although, hepatotoxic injury of o-DCB is greater in Fischer 344 (F344) when compared with Sprague Dawley (S-D) rats, this interstrain difference does not transcend into any difference in lethal effects of o-DCB. Interstrain difference in compensatory tissue repair has been suggested as the underlying mechanism for the lack of strain differences in lethality ... The objectives of the present study were (1) to investigate if the differences in compensatory tissue repair are reflected in differential protooncogene expression in S-D versus F344 rat livers and (2) to investigate if changes in protooncogene expression could explain the decrease and delay in tissue repair response beyond a threshold of 0.6 mL o-DCB/kg. Male S-D and F344 rats (8/9 weeks old) were administered either 0.6 or 1.2 mL o-DCB/kg and changes in expression of protooncogenes c-myc (immediate early) and Ha-ras (delayed early) were examined over a time course. Findings of this study indicate that the timing and extent of c-myc and Ha-ras expression varies in the two strains following administration of o-DCB. ...

The more pronounced toxicity to the liver of the ortho-isomer has been associated with a more pronounced binding of the compound or its intermediate metabolites to liver proteins...

para-Dichlorobenzene, but not ortho-dichlorobenzene, induces renal tumors specifically in male rats. There is substantial evidence that para-dichlorobenzene induces these tumors through an alpha2u-globulin-associated response. Although para-dichlorobenzene does not bind to DNA in the male rat kidney, there is weak evidence that it binds to DNA in several tissues in treated mice. Both ortho- and para-dichlorobenzene have been reported to bind to proteins and DNA in the same mouse tissues. No attempt was made to isolate any DNA adducts. The data available on the genotoxicity of para-dichlorobenzene and ortho-dichlorobenzene also do not allow any distinction to be made between these two compounds, which differ significantly in their tumorigenicity: ortho-dichlorobenzene does not cause tumors, whereas para-dichlorobenzene causes liver tumors in mice and kidney tumors in male rats. Overall, the data on genotoxicity do not support a mechanism for renal-cell tumor induction in rats involving direct interaction of para-dichlorobenzene with DNA. Therefore, the overall data, including those on genotoxicity, indicate that para-dichlorobenzene causes renal tumors in male rats through an alpha2u-globulin associated response.

2,3- and 3,4-Dichlorophenyl methyl sulfoxides and 2,3- and 3,4-dichlorophenyl methyl sulfones (2,3- and 3,4-DCPSO2Mes) were detected in the urine of rats administered o-dichlorobenzene (o-DCB). After administration of o-DCB to rats, swift decreases were observed in the concentrations of o-DCB in blood, liver, and kidneys, whereas 3,4-DCPSO2Me appeared in blood, liver, kidneys, and adipose tissue. The concentrations of 3,4-DCPSO2Me in the blood and three tissues reached maxima at 24 hr. Both aminopyrine N-demethylase and aniline hydroxylase activities and cytochrome P450 content of hepatic microsomes decreased 24 hr after administration of o-DCB. In contrast, 3,4-DCPSO2Me increased the activities of these enzymes and cytochrome P450 and b5 contents in rat liver microsomes. In both antibiotic-pretreated and bile duct-cannulated rats dosed with o-DCB, the concentrations of 2,3- and 3,4-DCPSO2Mes in blood, liver, kidneys, and adipose tissue were dramatically reduced. These findings suggest that the process of formation of methylsulfonyl metabolites of o-DCB involves biliary secretion of DCPSO2Mes and/or their precursors which will be subjected to metabolism by intestinal microflora. In antibiotic-pretreated rats, the inhibitory effects of o-DCB administration on the activities of aminopyrine- and aniline-metabolizing enzymes and the contents of cytochromes P450 and b5 in hepatic microsomes were greater than those observed in the intact rats. In bile duct-cannulated rats, the decrease in aminopyrine N-demethylase activity after administration of o-DCB was greater than that observed in the intact rats. These findings suggest that the apparent inhibition of drug-metabolizing enzymes by o-DCB is the result of simultaneous contrary effects, namely, the inductive effect of 3,4-DCPSO2Me and the stronger inhibitory effect of an unknown factor(s) on drug-metabolizing enzymes.

After ingestion of o-dichlorobenzene, urine of rabbits was found to contain 2,3- and 3,4-dichlorophenol free and o-glucuronic and sulfuric acid conjugates, 3,4- and 4,5-dichlorocatechol free and as the o-glucuronide and sulfate, and 3,4-dichlorophenylmercapturic acid.

The effect of inducers and inhibitors of microsomal mixed-function oxidases on the fate of metabolism and the extent of binding of ortho- and para-dichlorobenzene to cellular constituents suggests that arene oxides (epoxide) may be precursors of the excreted metabolites...

o-Dichlorobenzene yielded N-acetyl-S-(3,4-dichlorophenoxy)-L-cysteine in rabbits. /from table/

For more Metabolism/Metabolites (Complete) data for 1,2-DICHLOROBENZENE (15 total), please visit the HSDB record page.

1,2-dichlorobenzene has known human metabolites that include 2,3-dichlorophenol and 3,4-dichlorophenol.

Urine samples collected from 8 volunteers for 36 hr after exposure to 1,2-DCB in the range of 0.03-0.3 mg/L and, in one case up to 0.54 mg/L for two 4 hr periods with a 45 min interval were analysed for the presence of isomeric dichlorophenylmercapturic acids; ethyl esters of 2,3-dichlorophenylmercapturic acid and 3,4-dichlorophenylmercapturic acid were detected in the urine, with a linear correlation found between urinary dichlorophenylmercapturic acid concentration and the level of 1,2-DCB exposure; a first-order excretion kinetic was determined for the two dichlorophenylmercapturic acids; the half lives of 3,4-dichlorophenylmercapturic acid and 2,3-dichlorophenylmercapturic acid were determined to be 5.9 +/- 1.7 hr and 5.3 +/- 3.0 hr respectively.

The dichlorobenzenes may be absorbed through the lung, gastrointestinal tract, and intact skin. Relatively low water solubility and high lipid solubility favor their penetration of most membranes by diffusion, including pulmonary and GI epithelia, the brain, hepatic parenchyma, renal tubules, and the placenta. /Dichlorobenzenes/

The relationship between the metabolism and the toxicity of ortho-dichlorobenzene was investigated by evaluating its biotransformation, tissue distribution, blood kinetics and excretion after oral administration of 5, 50 or 250 mg/kg bw to male Wistar rats. The dose of 250 mg/kg bw had been demonstrated to be toxic in previous studies. The major route of elimination of ortho-dichlorobenzene (75-85%) was via the kidneys; excretion in the feces represented 19% of the low dose and 7% of the high dose. Excretion was nearly complete within 24 hr after the low and intermediate doses and within 48 hr after the high dose. Pretreatment with phenobarbital accelerated excretion of the high dose and resulted in an overall higher proportion of urinary excretion. Biliary excretion constituted 50-60% of the dose, indicating significant enterohepatic recirculation. The highest concentrations of radiolabel after a low dose were found in fat, liver and kidney 6 hr after administration; these then declined rapidly. The maximal concentration in blood was reached 6-8 hr after administration of the low and intermediate doses and 24 hr after the high dose. ortho-Dichlorobenzene was detected in blood only during the first 2 hr after administration of 5 mg/kg bw. The major route of biotransformation was via the glutathione pathway, 60% of the urinary metabolites being mercapturic acids; the major metabolites in bile were also conjugates of glutathione. Other major metabolites in urine were the sulfate conjugates of 2,3- and 3,4- dichlorophenol. No significant differences in metabolic profiles were observed with dose. Induction with phenobarbital increased excretion of sulfate conjugates (30% in induced rats, 20% in control rats), the main one being the conjugate of 3,4-dichlorophenol. The mercapturic acids in urine and the glutathione conjugates in bile were epoxide-derived metabolites, and no quinone- or hydroquinone-derived metabolites were observed. A high dose of ortho-dichlorobenzene results in depletion of glutathione, followed by oxidative stress and possibly binding to macromolecules.

1,2-Dichlorobenzene is well absorbed via the oral route. In rats, absorption of 1,2-dichlorobenzene from the gastrointestinal tract was considered complete at doses of 5 and 50 mg/kg bw but incomplete (83% absorption) at 250 mg/kg bw. There are no quantitative data for the dermal and inhalation absorption of 1,2-dichlorobenzene in animals or absorption of the chemical via any route in humans. Studies with rats have shown that 1,2-dichlorobenzene is distributed primarily to the adipose tissue with lesser amounts detected in the kidneys, liver and plasma. 1,2-Dichlorobenzene equivalents were bound to the kidneys, liver and plasma with covalent binding accounting for a substantial proportion of bound material. In particular, ...non-specific covalent binding to the alpha2u-globulin fraction of the rat kidney /was observed/. Several studies have found that the administration of a single dose of 1,2-dichlorobenzene by either the oral, intraperitoneal or intravenous route results in high initial tissue levels of 1,2-dichlorobenzene equivalents. Peak tissue levels occur within 1 and 6 hours, depending on the method of administration, followed by rapid decline thereafter

For more Absorption, Distribution and Excretion (Complete) data for 1,2-DICHLOROBENZENE (9 total), please visit the HSDB record page.

Used as a chemical intermediate, solvent, heat transfer liquid, deodorant, and insecticide; [ACGIH] Used as a degreasing agent, a paint solvent, paint remover, a cylinder lubricant, and a solvent for waxes, gums, resins, tars, rubber, oils, and asphalts; [HSDB]

Cancelled: no registered pesticide products in the USA; [HSDB]

Metal Degreasing [Category: Clean]

For 1,2 Dichlorobenzene (USEPA/OPP Pesticide Code: 059401) 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./

The active ingredient is no longer contained in any registered pesticide products ... "cancelled."

Solvent for waxes, gums, resins, tars, rubbers, oils, asphalts, insecticide for termites and locust borers

1,4-dichlorobenzene /at/ 0.5-l% w/w.

High purity grade: less than 0.2% 1,2,4-trichlorobenzene and less than 0.005% monochlorobenzene. Technical grade: less than 19.0% other dichlorobenzenes isomers, less than 1.0% trichlorobenzenes & less than 0.05% monochlorobenzene.

(1972) Estimated to be negligible

CHEMICAL PROFILE: o-Dichlorobenzene. Exports: 2002: 19 million pounds; 2003: 18 million pounds

(1972) 6.30X10+06 GRAMS

(1975) 1.23X10+9 GRAMS (PRINCPL CUSTMS DISTS)

CHEMICAL PROFILE: o-Dichlorobenzene. Imports: 2002: 700,000 pounds; 2003: 900,000 pounds

2023: 50,000 - <250,000 lb

(1972) 2.83X10+10 GRAMS

(1975) 2.48X10+10 GRAMS

6.4 to 40.9X10+9 g

2.2X10+9 g

For more U.S. Production (Complete) data for 1,2-DICHLOROBENZENE (8 total), please visit the HSDB record page.

53% for organic synthesis (chiefly for pesticides); 20% for solvent in toluene di-isocyanate process; 15% for misc solvent uses; 8% for dyestuffs mfr, 4% for misc uses (1973)

Organic synthesis (mainly for production of 3,4-dichloroaniline), 70%; solvents for toluene diisocyanate production, 15%; miscellaneous solvent usage, 8%; dye manufacture 4%; and other application, 3% (1978)

CHEMICAL PROFILE: o-Dichlorobenzene. Demand: 1995: 35 million lb; 1996: 35 million lb; 2000 /projected/: 36 million lb.

CHEMICAL PROFILE: o-Dichlorobenzene. Demand: 2002: 4 million pounds; 2003: 3 million pounds; 2007: 3 million pounds, projected

CHLORINATION OF BENZENE OR MONOCHLOROBENZENE IN THE PRESENCE OF A CATALYST

... by Sandmeyer procedure from appropriate chloroaniline, and along with o- and p-dichlorobenzenes, by chlorination of chlorobenzene.

Chlorobenzenes are prepared industrially by reaction of liquid benzene with gaseous chlorine in the presence of a catalyst at moderate temperature and atmospheric pressure. Hydrogen chloride is formed as a byproduct. Generally, mixtures of isomers and compounds with varying degrees of chlorination are obtained ... . /Chlorobenzenes/

... Avail in USA as technical grade typically containing 98.7% by wt of ortho-isomer & 1.3% of meta- & para-isomers combined. It has ... moisture content of 80 ppm. ... also avail in USA in grade which ... contains 83% of ortho-isomer, 17% of meta- & para-isomers ... an emulsifiable form of ... latter product can ... /be obtained/.

High purity grade: 98.0% minimum active ingredient; technical grade: 80-90% active ingredient

Technical-grade ortho-dichlorobenzene typically consists of 70-85% ortho-dichlorobenzene, <0.05% chlorobenzene and <0.5% trichlorobenzene, with the remainder as meta- and para-dichlorobenzene. Pure-grade ortho-dichlorobenzene consists of >99.8% ortho-dichlorobenzene, <0.05% chlorobenzene, <0.1% trichlorobenzene and <0.1% para-dichlorobenzene. ...Trade names for ortho-dichlorobenzene include Cloroben, Dilatin DB and Dowtherm E.

Composition of technical grade product: 65-85% 1,2-dichlorobenzene, <0.05 % chlorobenzene, <0.5 % trichlorobenzene, remainder 1,4- and 1,3-dichlorobenzene. Pure grade: >99.8% 1,2-dichlorobenzene, <0.05% chlorobenzene, <0.1% trichlorobenzene, <0.1% 1,4-dichlorobenzene.

Synthetic Rubber Manufacturing

Benzene, 1,2-dichloro-: ACTIVE

Separation of mixt containing m-, o-, and p-dichlorobenzenes by distillation and crystallization: Mueller, Wolz, French patent 1,374,863 (1964 to Bayer), CA 62, 493e (1965), corresponding to British patent 999,845.

Product discontinued by The Dow Chemical Company