Absorption, Distribution and Excretion
This substance is clearly well absorbed by the gastrointestinal tract and lungs, but almost not by the skin. 1,4-Dichlorobenzene has been detected in human adipose tissue and blood, present as a contaminant along with polychlorinated biphenyls (PCBs). 1,4-Dichlorobenzene is rapidly absorbed from the gastrointestinal tract. In male Wistar rats, after oral administration of 200 or 800 mg/kg, the substance was detected within 30 minutes in blood, adipose tissue, kidneys, liver, lungs, heart, and brain tissue. Dichlorobenzene compounds can be absorbed through the lungs, gastrointestinal tract, and intact skin. Their relatively low water solubility and high lipid solubility facilitate their penetration of most membranes via diffusion, including the lung and gastrointestinal epithelium, brain, liver parenchyma, renal tubules, and placenta. /Dichlorobenzene/ For more complete data on the absorption, distribution, and excretion of 1,4-dichlorobenzene (14 in total), please visit the HSDB records page.

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Metabolism/Metabolites
We employed a novel in vitro system to assess tissue-specific toxicity. This system utilizes precisely cut organ sections in dynamic organ culture, maintaining activity for up to 24 hours. Three isomers of dichlorobenzene were added to liver sections prepared from Sprague-Dawley rats or human donors. The precursor dichlorobenzene was radiolabeled, and metabolites were isolated by category (i.e., glucuronide, sulfate, and glutathione and cysteine conjugates). The covalent binding of dichlorobenzene was also determined after adequate tissue extraction. The total metabolic rate of dichlorobenzene varied depending on the isomer and tissue type. For example, Sprague-Dawley rat liver sections metabolized 1,2-dichlorobenzene (1,2-DCB) and 1,3-dichlorobenzene (1,3-DCB) at roughly the same rate, while 1,4-dichlorobenzene (1,4-DCB) was metabolized more slowly. This metabolic pattern was also observed in most adult liver sections. However, fetal liver sections showed that 1,4-DCB was metabolized more extensively than 1,3-DCB or 1,2-DCB, while the metabolic rate of 1,3-DCB was higher than that of 1,2-DCB. Our results indicate that organ-cultured liver sections are a suitable system for species comparison and for studying structure/activity relationships in xenobiotic metabolism, with particular attention to metabolic pathways of bioactive intermediates. Furthermore, this system is suitable for hepatotoxicity assessment. Following ingestion of p-dichlorobenzene, 2,5-dichlorophenol (30%) was excreted in its free, glucuronide, and sulfate forms, and 2,5-dichloroquinoline (6%) was also excreted. In humans, 2,5-dichlorophenol was also detected in urine. Following oral administration of p-dichlorobenzene to rats, two metabolites were detected in the blood. Metabolites M-1 and M-2 were 2,5-dichlorophenylmethyl sulfoxide and 2,5-dichlorophenylmethyl sulfone, respectively. Within 12 hours after administration, the blood concentration of M-1 was higher than that of M-2, but thereafter the blood concentration of M-2 was higher. In rats, 2,5-dichlorophenol was the major metabolite after oral administration of p-dichlorobenzene (p-DCB). In rabbits, after oral administration of 0.5 g/kg p-dichlorobenzene, its metabolites included: oxidation to 2,5-dichlorophenol (35%); conjugation to glucuronide (36%) and ether sulfate (27%); or excretion as 2,5-dichloroquinoline (6%). For more complete data on the metabolism/metabolites of 1,4-dichlorobenzene (a total of 9 metabolites), please visit the HSDB record page. Known human metabolites of 1,4-dichlorobenzene include 2,5-dichlorophenol. 1,4-dichlorobenzene is rapidly and substantially completely absorbed after inhalation or oral administration. 1,4-Dichlorophenol (1,4-DCB) is distributed throughout the body, preferentially in adipose tissue and specific organs, in the following order: adipose tissue > kidneys > liver > blood. 1,4-DCB is first metabolized by cytochrome P-450 enzymes (especially P450 2E1) to reactive epoxides, which are then hydrolyzed to 2,5-dichlorophenol, which can be further oxidized to dichlorocatechol or dichlorohydroquinone. More commonly, it conjugates with sulfates, forming glucuronides or thiouric acid; conjugation reactions occur extensively, and there are almost no reports of unconjugated metabolites in existing studies. Metabolism mainly occurs in the liver, but may also occur in small amounts in other tissues such as the kidneys or lungs. 1,4-DCB is almost entirely excreted in the urine, primarily as 2,5-dichlorophenol conjugates. (L395)

Toxicity Summary
Identification and Uses: 1,4-Dichlorobenzene (p-DCB) is a solid. It can be used as a moth repellent, general insecticide, fungicide, and air freshener. It is also used in the production of 2,5-dichloroaniline, dyes, intermediates, and in pharmaceuticals and agriculture (soil fumigation). Human Studies: Repeated or prolonged exposure to the fumes produced by hot p-DCB surfaces may cause mild skin irritation. Leukoencephalopathy has been reported after ingestion of p-DCB mothballs. Reports of hemolytic anemia and methemoglobinemia are rare. p-DCB can increase the frequency of sister chromatid exchange in human peripheral blood lymphocytes without metabolic activation. Animal Studies: p-DCB can specifically induce kidney tumors in male rats via α2u globulin-related responses. p-DCB has not shown genotoxicity in vivo; no positive results were observed in unplanned DNA synthesis assays, chromosomal aberration assays, dominant lethality assays, and in vivo micronucleus assays. It has been reported to be positive in a single-strand DNA breakage assay and an in vivo micronucleus assay. p-DCB binds to DNA in the liver, lungs, and kidneys of mice, but not to DNA in male rats. It also induces DNA damage in the liver and spleen of mice, but not in the kidneys, lungs, or bone marrow. Regardless of metabolic activation, p-DCB is not mutagenic to Salmonella typhimurium strains TA 98, TA 100, TA 1535, or TA 1537. Acute and subchronic neurotoxicity studies of p-DCB have been conducted. In rats, acute exposure to concentrations of 50, 200, or 600 ppm of p-DCB resulted in decreased grip strength and motor function in the forelimbs and hindlimbs of male rats, but this was not observed in female rats at high doses. p-DCB is not teratogenic in rabbits. Ecotoxicity studies: p-DCB exhibits acute and chronic toxicity to freshwater organisms at concentrations as low as 1120 and 763 μg/L. It also exhibits acute toxicity to marine organisms at concentrations as low as 1970 μg/L. p-DCB is toxic to cell cultures of tomato, soybean, and carrot. A concentration of 0.5 mM can cause 50% growth inhibition in carrot and soybean cell cultures. Tomato cultures are more sensitive, with 0.05 mM causing 50% growth inhibition. The hepatotoxicity and nephrotoxicity observed in laboratory animals may be due to toxic intermediates formed during the conversion of 1,4-dichlorophenol to 2,5-dichlorophenol by cytochrome P-450, or due to the consumption of glutathione by higher doses of 1,4-dichlorophenol, or both. (L395)

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Toxicity Data
LD50: >6000 mg/kg/day (skin, rat) (L395)
LD50: 500 mg/kg/day (oral, rat) (L395)

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Interactions
In a liver cancer model, 12 (vector control group) or 18 10-week-old male Fischer 344 rats received a single intraperitoneal injection of 200 mg/kg body weight of N-nitrosodiethylamine (NDEA) (dissolved in 0.9% saline) or saline. Two weeks after NDEA or saline injection, p-dichlorobenzene (purity unspecified), dissolved in corn oil, was administered by gavage at a dose of 0.1 or 0.4 mmol/kg body weight/day for 6 weeks; the control group received only corn oil or corn oil containing NDEA. One week after the start of p-dichlorobenzene treatment (i.e., week 3), all animals underwent partial hepatectomy. The study was terminated at the end of week 8. Hepatic lesions were identified by immunohistochemical staining for placental glutathione S-transferase. The incidence of hepatic lesions was not increased, leading the authors to conclude that dichlorobenzene is not a promoter of liver tumors. The role of endogenous glutathione in resisting 1,4-dichlorobenzene-induced hepatotoxicity was demonstrated in male ddY mice. In male ddY mice pre-injected with a glutathione synthesis depleting agent (butyrosine sulfoxide imine BSO), oral administration of 1,4-dichlorobenzene alone (100 to 400 mg/kg) resulted in dose-dependent hepatotoxicity (a 100-fold increase in serum ALT activity and liver necrosis), but administration of 1,4-dichlorobenzene alone (up to 1200 mg/kg) did not produce hepatotoxicity. Administration of GSH monoethyl ester protected mice from hepatotoxicity induced by the combined use of 1,4-dichlorobenzene and BSO; treatment with a cytochrome P450-dependent monooxygenase inhibitor prevented hepatotoxicity induced by the combined use of 1,4-dichlorobenzene and BSO. This suggests that the metabolite formed by the cytochrome P450-dependent response is the cause of 1,4-dichlorobenzene hepatotoxicity, and that this metabolite is likely detoxified by glutathione in mice, as 1,4-dichlorobenzene did not show signs of hepatotoxicity in the absence of BSO. On the other hand, the combined use of cytochrome P450-dependent monooxygenase inducers with BSO did not increase the hepatotoxicity of 1,4-dichlorobenzene, possibly because they stimulated not only the activation pathway of 1,4-dichlorobenzene metabolism but also its detoxification pathway. In an experiment using Syrian hamster embryonic (SHE) cells to study the relationship between polyamine metabolism and cell transformation, researchers compared the effects of 1,4-dichlorobenzene alone and in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA) on ornithine decarboxylase (ODC) and soluble 72 kDa proteolytic enzymes. Furthermore, they examined DNA fragmentation, considered a result of apoptosis. ODC activity was determined using a radioisotope assay; proteolytic enzyme activity was determined using polyacrylamide gel electrophoresis, with casein or gelatin incorporated into the electrophoresis mixture; apoptosis was detected using ELISA, detecting the release of BrdU-labeled 180-200 bp DNA fragments into the cytoplasm. Treatment with 0.1 μg/mL TPA for 1 hour induced ODC activity, with enzyme activity peaking at 5-6 hours (approximately twice the untreated level), and returning to control levels after 8-10 hours. Treatment with 10 μg/mL 1,4-dichlorobenzene for 5 hours had no effect on ODC activity. Simultaneous treatment with TPA and 1,4-dichlorobenzene for 5 hours, or treatment with TPA for 5 hours followed by 1,4-dichlorobenzene for 2 hours, had minimal effect on ODC activity (slight inhibitory effect), showing no significant difference compared to TPA treatment alone. In contrast, treatment with 1,4-dichlorobenzene for 1 hour followed by TPA for 5 hours increased ODC activity by approximately 2.6-fold. Similar treatment regimens resulted in a decrease in TPA-induced proteolytic enzyme activity to approximately 92% after 5 hours of treatment. Treatment with 1,4-dichlorobenzene alone (105%) or simultaneous exposure to TPA and 1,4-dichlorobenzene for 5 hours (109%) slightly increased activity, while treatment with 1,4-dichlorobenzene for 1 hour followed by TPA for 5 hours slightly increased activity (121%). TPA (1.0 μg/mL) inhibited apoptosis by 30%, and 1,4-dichlorobenzene (5.0 μg/mL) inhibited apoptosis by 25%.

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Non-human toxicity values
Oral LD50 in adult male rats: 3863 mg/kg (95% confidence interval: 3561-4153 mg/kg) / Data from table /
Oral LD50 in adult female rats: 3790 mg/kg (95% confidence interval: 3425-4277 mg/kg) / Data from table /
Dermal LD50 in adult male rats: > 6000 mg/kg / Data from table /
Dermal LD50 in adult female rats: > 6000 mg/kg / Data from table /
For more complete data on the non-human toxicity values of 1,4-dichlorobenzene, please refer to the HSDB record page (out of 10).

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

According to an independent committee of scientific and health experts, p-dichlorobenzene may be carcinogenic. p-Dichlorobenzene is a white liquid with a camphor-like odor. It is denser than water and insoluble in water. Its flash point is below 200°F (approximately 93°C). It is used as a moth repellent, a raw material for manufacturing other chemicals, a fumigant, and for many other purposes. 1,4-Dichlorobenzene is dichlorobenzene with chlorine atoms at the 1 and 4 positions. It is an insecticide. The main route of exposure to 1,4-dichlorobenzene is through inhalation of contaminated indoor air. Acute (short-term) inhalation of 1,4-dichlorobenzene in humans can cause skin, throat, and eye irritation. Chronic (long-term) inhalation of 1,4-dichlorobenzene in humans can cause damage to the liver, skin, and central nervous system (CNS). Currently, there is no information regarding the reproductive, developmental, or carcinogenic effects of 1,4-dichlorobenzene in humans. A study by the U.S. National Toxicology Program (NTP) reported that administering 1,4-dichlorobenzene via gavage (experimentally placing the chemical in the stomach of mice) caused kidney tumors in male rats, and administering it to both male and female mice caused liver tumors. The U.S. Environmental Protection Agency (EPA) has classified 1,4-dichlorobenzene as a Group C carcinogen, meaning it is a possible human carcinogen. Dichlorobenzene is a synthetic white crystalline solid, practically insoluble in water, but soluble in ether, chloroform, carbon disulfide, benzene, alcohols, and acetone. It is primarily used as a deodorant, such as in deodorizers, urinal and toilet deodorizers, and as an insecticidal fumigant to control moths. When heated, 1,4-dichlorobenzene decomposes, releasing toxic gases and vapors (such as hydrochloric acid and carbon monoxide). The main route of human exposure to this compound is inhalation. Acute inhalation of 1,4-dichlorobenzene can cause coughing and difficulty breathing. Inhalation of high concentrations of this chemical can cause headaches, dizziness, and liver damage. Exposure to 1,4-dichlorobenzene can irritate the eyes, causing burning and tearing. It is reasonably expected to be a human carcinogen. (NCI05)
1,4-Dichlorobenzene (p-DCB) is an organic compound with the molecular formula C6H4Cl2. This colorless solid has a strong odor. Structurally, the molecule consists of two chlorine atoms replacing hydrogen atoms in opposite positions on a benzene ring. p-DCB is used as an insecticide and deodorant, most commonly as a substitute for mothballs, replacing traditional naphthalene. p-DCB is also used as a precursor in the production of the polymer poly(p-phenylene sulfide). Under California Proposition 65, p-dichlorobenzene (p-DCB) is listed as a known carcinogen in the state. [8] The possible mechanisms of carcinogenicity of mothballs and certain air fresheners containing p-dichlorobenzene have been identified.
See also: … See 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.)