Absorption, Distribution and Excretion
The material is apparently well absorbed by the gastrointestinal tract and from lung but not appreciably through skin.
Moth repellent para-dichlorobenzene was detected in human adipose tissue and blood as pollutant together with polychlorinated biphenyls.
Absorption of 1,4-dichlorobenzene through the gastrointestinal tract is rapid. Oral doses of 200 or 800 mg/kg to male Wistar rats appeared in the blood and adipose, kidney, liver, lung, heart, and brain tissue within 30 minutes.
The dichlorobenzenes may be absorbed through the lungs, gastrointestinal tract, and the 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/
For more Absorption, Distribution and Excretion (Complete) data for 1,4-Dichlorobenzene (14 total), please visit the HSDB record page.

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Metabolism / Metabolites
A novel in vitro system was used to evaluate tissue specific toxicity. This system utilizes precision cut organ slices in dynamic organ culture and is viable for up to 24 hrs. The three isomers of dichlorobenzene were added to liver slices prepared from Sprague Dawley rats or human donors. The precursor dichlorobenzenes were radiolabelled and metabolites were separated by classes (i.e. glucuronides, sulfates and glutathione and cysteine conjugates). Covalent Binding of the dichlorobenzenes was also determined after extensive extraction of the tissue. The total amount of metabolism of the dichlorobenzenes varied depending on the isomer and the type of tissue. For example, the Sprague-Dawley rat liver slices metabolized 1,2-DCB and 1,3-DCB at approximately the same rate while 1,4-DCB was metabolized at a slower rate. This metabolism profile was also seen in the majority of the adult human liver slices. However, the fetal human slices showed that 1,4-DCB was metabolized to a greater extent than 1,3-DCB or 1,2-DCB while 1,3-DCB was metabolized at a faster rate than 1,2-DCB. Our results show that liver slices in organ culture are a suitable system for species comparisons and of structure/activity relationships in xenobiotic metabolism with an emphasis on the fate of reactive intermediates. In addition, this system is suitable for evaluation of hepatotoxic potency.
After ingestion of p-dichlorobenzene, 2,5-dichlorophenol (30%) free and as the glucuronide and sulfate and 2,5-dichloroquinol (6%) were excreted. In humans, 2,5-dichlorophenol was also found in the urine.
After oral administration of para-dichlorobenzene to rats, 2 metabolites detected in blood. Metabolites M-1 and M-2 are 2,5-dichlorophenyl methyl sulfoxide and 2,5-dichlorophenyl methyl sulfone. Concentration of M-1 in blood was higher than M-2 for 12 hr after dosing, but blood level of M-2 was higher thereafter. After oral administration of p-DCB to rats 2,5-dichlorophenol was major metabolite.
Rabbits were fed an oral dose of 0.5 g/kg of p-dichlorobenzene /which was then/ oxidized to 2,5-dichlorophenol (35%); conjugated to form glucuronide (36%) and ethereal sulfate (27%); or excreted as 2,5-dichloroquinol (6%).
For more Metabolism/Metabolites (Complete) data for 1,4-Dichlorobenzene (9 total), please visit the HSDB record page.
1,4-dichlorobenzene has known human metabolites that include 2,5-dichlorophenol.
Absorption of 1,4-DCB is rapid and essentially complete following inhalation or oral exposure. It is distributed throughout the body, preferentially to the fat tissue and organ-specific sites within the body, following the order: adipose > kidney > liver > blood. 1,4-DCB is initially metabolized by cytochrome P-450 enzymes, specifically P4502E1, to an active epoxide followed by hydrolysis to 2,5-dichlorophenol, which may be further oxidized to dichlorocatechols, or possibly a dichlorohydroquinone. More often, it might be conjugated to sulfate, or to form the glucuronide, or mercapturic acid; conjugation occurs extensively, with virtually no unconjugated metabolites reported in the available studies. Metabolism is believed to occur mainly in the liver, but may occur at lower levels in other tissues, such as the kidney or lung. 1,4-DCB is eliminated almost exclusively in the urine, primarily as conjugates of 2,5-dichlorophenol. (L395)

Toxicity Summary
IDENTIFICATION AND USE: 1,4-Dichlorobenzene (p-DCB) is a solid. It is used as moth repellent, general insecticide, germicide, space odorant, in manufacture of 2,5-dichloroaniline, dyes, intermediates, pharmacy, agriculture (fumigating soil). HUMAN STUDIES: Fumes from the surface of hot p-DCB may irritate skin slightly when contact is repeated or prolonged. Leukoencephalopathy has been described following ingestion of p-DCB mothballs. Hemolytic anemia and methemoglobinemia is more rarely reported in such cases. p-DCB increased the frequency of sister chromatid exchange in human peripheral blood lymphocytes in the absence of metabolic activation. ANIMAL STUDIES: p-DCB induces renal tumors specifically in male rats through an alpha2u-globulin-associated response. p-DCB failed to exhibit genotoxic effects in vivo, exhibiting negative responses in unscheduled DNA synthesis, in the chromosome aberration assay, in the dominant lethal assay, and in the in vivo micronucleus assay. It was reported as positive in one DNA strand breakage assay and in one in vivo micronucleus assay. p-DCB bound to DNA in the liver, lung, and kidney of mice but not in that of male rats. It also induced DNA damage in the liver and spleen but not in the kidney, lung, or bone marrow of mice. p-DCB was not mutagenic in Salmonella typhimurium strains TA 98, TA 100, TA 1535, or TA 1537 with or without metabolic activation. Acute and subchronic neurotoxicity studies have been performed with p-DCB. In rats, acute exposure to p-DCB at the rate of 50, 200 or 600 ppm caused decreased forelimb and hindlimb grip strengths and motor activity in males but not females at the high-dose. p-DCB was not teratogenic in rabbits. ECOTOXICITY STUDIES: Acute and chronic toxicity to freshwater aquatic life occur at concentrations as low as 1,120 and 763 ug/L. Acute toxicity to saltwater aquatic life occurs at concentrations as low as 1,970 ug/L. p-DCB was toxic to cell cultures of the tomato, soybean, and carrot. Concentrations of 0.5 mM caused 50% growth inhibition in carrot and soybean cultures. The tomato cultures were more sensitive, with 0.05 mM causing 50% growth inhibition.
The hepatotoxicity and nephrotoxicity observed in laboratory animals are likely due to the formation of toxic intermediates formed while converting 1,4-DCB to 2,5-dichlorophenol by cytochrome P-450, or by depletion of GSH at higher doses of 1,4-DCB, or both. (L395)

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Toxicity Data
LD50: >6000 mg/kg/day (Dermal, Rat) (L395)
LD50: 500 mg/kg/day (Oral, Rat) (L395)

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Interactions
In a model of liver carcinogenesis, groups of 12 (vehicle control) or 18 male Fischer 344 rats, 10 weeks of age, received a single intraperitoneal injection of either 200 mg/kg bw N-nitrosodiethylamine (NDEA) dissolved in 0.9% saline or saline alone. Two weeks after the NDEA or saline injection, para-dichlorobenzene (purity unspecified) was administered by gavage at doses of 0.1 or 0.4 mmol/kg bw/day in corn oil for 6 weeks; control groups received only corn oil or NDEA in corn oil. One week after the start of para-dichlorobenzene treatment (i.e. week 3), all animals underwent a partial hepatectomy. The study was terminated at the end of week 8. Hepatic foci were identified by immunohistochemical staining for the placental form of glutathione S-transferase. The incidence of hepatic foci was not increased, and the authors concluded that para-dichlorobenzene is not a liver tumor promoter.
The role of endogenous glutathione in protecting against 1,4-dichlorobenzene induced hepatotoxicity was demonstrated in ddY male mice. Unique oral administration of 1,4-dichlorobenzene (100 to 400 mg/kg) in ddY male mice pre-treated by ip injection with a depletor of glutathione synthesis (buthionine sulfoximine BSO) resulted in a dose-dependent hepatotoxicity (serum ALT activity up to X 100, liver necrosis) but 1,4-dichlorobenzene alone (up to 1,200 mg/kg) resulted in no hepatotoxicity. Administration of GSH monoethylester protected mice from the hepatotoxicity of 1,4- dichlorobenzene in combination with BSO; treatment with cytochrome P450-dependent monooxygenase inhibitors prevented hepatotoxicity of 1,4-dichlorobenzene in combination with BSO: this suggests that a metabolite formed by a cytochrome P450-dependent reaction is responsible for the 1,4-dichlorobenzene hepatotoxicity and that this metabolite is likely detoxified by glutathione in mice since 1,4-dichlorobenzene showed no sign of hepatotoxicity in the absence of BSO. On the other hand, inducers of cytochrome P450-dependent monooxygenase did not increase hepatotoxicity of 1,4-dichlorobenzene in combination with BSO probably because they stimulate not only activating but also detoxicating pathways of 1,4-dichlorobenzene metabolism.
In a research program with Syrian Hamster Embryo (SHE) cells examining the relationship between polyamine metabolism and cell transformation, ...the effect of 1,4-dichlorobenzene in comparison and in combination with 12-O-tetradecanoyl phorbol-13- acetate (TPA) on ornithine decarboxylase (ODC) and soluble 72 kDa proteolytic enzymes /was compared/. In addition, DNA fragmentation, considered to be the result of apoptosis, was measured. Activity of ODC was measured by a radioisotope method, the proteolytic enzyme activity was measured following electrophoresis on polyacrylamide gels in which either casein or gelatine had been incorporated and apoptosis was measured by ELISA as 180-200 bp fragments of DNA labelled with BrdU released into the cytoplasm. TPA 0.1 ug/mL induced ODC within the first 1 hr, the enzyme activity reaching a maximum of about 2.0-fold the untreated level in 5-6 hours before returning towards control levels after 8-10 hours. Treatment with 1,4-dichlorobenzene, 10 ug/mL, for 5 hours had no effect on ODC activity, while simultaneous treatment with TPA and 1,4- dichlorobenzene for 5 hours, or TPA for 5 hours followed by 1,4-dichlorobenzene for 2 hours had little effect (slightly inhibitory) on that observed with TPA alone. In contrast, treatment with 1,4-dichlorobenzene for 1 hour followed by TPA for 5 hours increased the ODC activity by about 2.6-fold. Similar treatment protocols led to a TPA-induced reduction in proteolytic enzyme activity to about 92% after 5 hours of treatment, a slight increase by 1,4-dichlorobenzene alone (105%) or after simultaneous exposure to TPA and 1,4-dichlorobenzene for 5 hours (109%) and a slightly greater increase after sequential treatment was with 1,4-dichlorobenzene for 1 hour followed by TPA for 5 hours (121%). Apoptosis was inhibited 30% by TPA, 1.0 ug/mL, and inhibited 25% by 1,4-dichlorobenzene, 5.0 ug/mL.

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Non-Human Toxicity Values
LD50 Rat (male, adult) oral 3863 mg/kg (95% confidence interal 3561-4153 mg/kg) /From table/
LD50 Rat (female, adult) oral 3790 mg/kg (95% confidence interval 3425-4277 mg/kg) /From table/
LD50 Rat (male, adult) dermal > 6000 mg/kg /From table/
LD50 Rat (female, adult) dermal > 6000 mg/kg /From table/
For more Non-Human Toxicity Values (Complete) data for 1,4-Dichlorobenzene (10 total), please visit the HSDB record page.

[1]. M. Tschickardt. Dichlorobenzene isomers (1,2-dichlorobenzene, 1,3-dichlorobenzene and 1,4 dichlorobenzene).

p-Dichlorobenzene can cause cancer according to an independent committee of scientific and health experts.
P-dichlorobenzene appears as a white colored liquid with the odor of moth balls. Denser than water and insoluble in water. Flash point below 200 °F. Used as a moth repellent, to make other chemicals, as a fumigant, and for many other uses.
1,4-dichlorobenzene is a dichlorobenzene carrying chloro groups at positions 1 and 4. It has a role as an insecticide.
The primary exposure to 1,4-dichlorobenzene is from breathing contaminated indoor air. Acute (short- term) exposure to 1,4-dichlorobenzene, via inhalation in humans, results in irritation of the skin, throat, and eyes. Chronic (long-term) 1,4-dichlorobenzene inhalation exposure in humans results in effects on the liver, skin, and central nervous system (CNS). No information is available on the reproductive, developmental, or carcinogenic effects of 1,4-dichlorobenzene in humans. A National Toxicology Program (NTP) study reported that 1,4-dichlorobenzene caused kidney tumors in male rats and liver tumors in both sexes of mice by gavage (experimentally placing the chemical in their stomachs). EPA has classified 1,4- dichlorobenzene as a Group C, possible human carcinogen.
Paradichlorobenzene is a synthetic, white crystalline solid that is practically insoluble in water and soluble in ether, chloroform, carbon disulfide, benzene, alcohol and acetone. It is used primarily as a space deodorant in products such as room deodorizers, urinal and toilet bowl blocks, and as an insecticide fumigant for moth control. When 1,4-dichlorobenzene is heated to decomposition, toxic gases and vapors (such as hydrochloric acid and carbon monoxide) are released. The primary route of potential human exposure to this compound is inhalation. Acute inhalation exposure to 1,4-dichlorobenzene can result in coughing and breathing difficulties. Breathing high levels of this chemical can cause headaches, dizziness and liver damage. Contact with 1,4-dichlorobenzene can irritate the eyes, leading to burning and tearing. It is reasonably anticipated to be a human carcinogen. (NCI05)
1,4-Dichlorobenzene (p-DCB, para-dichlorobenzene) is an organic compound with the formula C6H4Cl2. This colorless solid has a strong odor. In terms of its structure, the molecule consists of two chlorine atoms substituted for hydrogen at opposing sites on a benzene ring. p-DCB is used a pesticide and a deodorant, most familiarly in mothballs in which it is a replacement for the more traditional naphthalene. p-DCB is also used as a precursor in the production of the polymer poly(p-phenylene sulfide). Under California's Proposition 65, p-DCB is listed as known to the State to cause cancer.[8] A probable mechanism for the carcinogenic effects of mothballs and some types of air fresheners containing p-DCB has been identified.
See also: ... View More ...

C6H4CL2

147.00

145.969

106-46-7

1,4-Dichlorobenzene-d4;3855-82-1

4685

White crystals
Volatile crystals
White crystals or leaflets
Colorless or white crystalline solid

1.3±0.1 g/cm3

174.1±0.0 °C at 760 mmHg

52-54 °C(lit.)

65.6±0.0 °C

1.6±0.3 mmHg at 25°C

1.549

3.34

0

0

0

8

54.9

0

ClC1C([H])=C([H])C(=C([H])C=1[H])Cl

OCJBOOLMMGQPQU-UHFFFAOYSA-N

InChI=1S/C6H4Cl2/c7-5-1-2-6(8)4-3-5/h1-4H

1,4-dichlorobenzene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 100 mg/mL (680.27 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (17.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (17.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (17.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)