94 Hexachlorobenzene Hexachlorobenzene is an agricultural fungicide, belonging to the family of Chlorobenzenes. These are compounds containing a chlorine atom attached to a benzene moiety. 118-74-1 8370 C6Cl6 281.813120 White powder. 226°C 323-326°C 6.2e-06 mg/mL at 25°C Oral (L225); inhalation (L225) ; dermal (L225) CYP1A1 (P04798), CYP2B6 (P20813), Delta-aminolevulinic acid dehydratase (P13716), Porphobilinogen deaminase (P08397), Uroporphyrinogen decarboxylase (P06132), 5-aminolevulinate synthase (P22557)(P13196), Estrogen sulfotransferase (P49888), Caspase-1 (P29466) Hexachlorobenzene causes porphyria by modifying sulfhydryl groups in the catalytic or substrate-binding sites of uroporphyrinogen decarboxylase. This inhibits uroporphyrinogen decarboxylase, resulting in a deficiency of the decarboxylation of uroporphyrinogen III and accumulation of uroporphyrins in the liver. In addition, metabolism of hexachlorobenzene by the cytochrome P-450 enzymes is believed to produce reactive electrophilic metabolites that covalently bind to cellular proteins and DNA, causing irreversible damage. Exposure to hexochlorobenzene also causes macrophages to be attracted to organs such as the spleen, lungs, and skin, where they become activated by the hexochlorobenzene. This leads to a cascade of reactions involving innate immune cells. The gene expression profiles provide evidence for the importance of macrophages and granulocytes and mediators released by these cells in the adverse inflammatory response against hexochlorobenzene. In this way, co-stimulatory or danger signals are generated that could polyclonally activate T cells. Hexachlorobenzene is a weak agonist for aryl hydrocarbon receptor and may exhibit some of its toxic effects by activating the gene-regulatory properties of this protein, possibly inducing cytochome P-450 enzymes. It may also act at certain endocrine receptors. (A14, L225, A156, A157, A60) Hexachlorobenzene is mainly absorbed via ingestion, but also through inhalation and oral routes. It preferentially distributes to adipose tissue and other organs with high fat content. In animals, hexachlorobenzene is slowly metabolized to pentachlorophenol by the hepatic cytochrome P-450 system, conjugated with glutathione to yield pentachlorothiophenol, or reductively dechlorinated to form pentachlorobenzene. Other metabolites include less chlorinated benzenes, chlorophenols, S-conjugated phenols, and benzenes. Hexachlorobenzene is slowly metabolized in mammals, and the majority of hexachlorobenzene is excreted unchanged in the feces, while metabolites are excreted in the urine. (L225) LD50: 3500 mg/kg (Oral, Rat) (T10) 2B, possibly carcinogenic to humans. (L135) Hexachlorobenzene was previously used as a pesticide to protect the seeds of onions and sorghum, wheat, and other grains against fungus. It was also used to make fireworks, ammunition, and synthetic rubber. As it can persist in the environment for long periods of time, today exposure occurs mainly from contact with contaminated water, food, soil, or air. (L225) Acute Oral: 0.008 mg/kg/day (L134) Intermediate Oral: 0.0001 mg/kg/day (L134) Chronic Oral: 0.00005 mg/kg/day (L134) 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) Hexachlorobenzene 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. (L225) Treatment is mainly symptomatic and may include gastric lavage, administering activated charcoal, and controlling convulsions. (L226) 2009-03-06T18:58:04Z 2014-12-24T20:21:05Z Cytochrome P450 3A4 (P08684) (L225) C11042 5692 CPD-1125 D006581 Hexachlorobenzene 691 true Cytochrome P450 3A4 (P08684) (L225) ClC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl C6Cl6 InChI=1S/C6Cl6/c7-1-2(8)4(10)6(12)5(11)3(1)9 InChIKey=CKAPSXZOOQJIBF-UHFFFAOYSA-N 284.782 281.813116242 Exogenous Solid 5.73 HMDB32566 CHEMBL228514 8067