DINITROPYRENE

0

292.04840674

DTXSID30229080

MP(1) 274-276 °C; MP(2): 297-298 °C; light brown needles, recrystallized from benzene and methanol, orange crystalline solid; moderately soluble in toluene. /1,3-Dinitropyrene/|MP(1) >300 °C; MP(2) 310 °C; light brown needles, recrystallized from benzene and methanol, yellow crystalline solid; moderately soluble in toluene. /1,6-Dinitropyrene/|MW 292.3; MP(1) >300 °C; MP(2) 300 °C; light brown needles, recrystallized from benzene and methanol, yellow, fluffy, crystalline solid. /1,8-Dinitropyrene/|Molecular weight: 292.3 /from table; 1,6-Dinitropyrene/|Fluffy yellow crystals /from table/ /1,8-Dinitropyrene/

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. 1,6-Dinitropyrene (42397-64-8) and 1,8-Dinitropyrene (42397-65-9) are listed as reasonably anticipated to be human carcinogens. /Nitroarenes (Selected)/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s121nitr.pdf]

Diesel emissions are known to induce tumors in experimental animals and are suspected of being carcinogenic in humans. Of the compounds associated with diesel exhaust, 1,6-dinitropyrene is a particularly potent mutagen and carcinogen. In ... the lungs of male F344 rats one major DNA adduct, N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, was detected by HPLC and/or 32P-postlabeling analyses. The levels of this adduct reached a maximum 1-7 days following treatment and decreased to 13-50% of the peak values by 28 days after dosing. In the lung, a 2-fold increase in dose resulted in a 2-fold increase in DNA binding up to the 30-micrograms dose; in the liver the same relationship was observed up to 10 micrograms 1,6-dinitropyrene. At higher doses, the extent of adduct formation still increased, but the rate was much lower ... . mutation induction at the hypoxanthine-guanine phosphoribosyltranferase locus in spleen T lymphocytes... increased until 21 weeks, remained constant until week 40, and then began to decrease. Mutant induction was dose related, with the increase in mutant frequency being significant at doses > or = 1 microgram 1,6-dinitropyrene. These data indicate that 1,6-dinitropyrene ... is metabolically activated by nitroreduction to give DNA adducts in target and surrogate tissues. They further suggest that T-lymphocyte mutations may be a more sensitive and longer-lived biomarker than DNA adducts for assessing previous exposures to nitropolycyclic aromatic hydrocarbons. /1,6-Dinitropyrene/|Nitroarenes are environmental contaminants produced during incomplete combustion processes. It has been reported that nitroreduction, the most important pathway of nitroarene toxification, occurs mainly in the liver and intestine. ... red cells also possess the metabolic competence to reduce nitroarenes. In particular, 1,8-dinitropyrene ... . /1,8-dinitropyrene/|/In rats/ concentrations of 1,6-dinitropyrene that produce a dose-dependent induction of lung tumors also result in a dose-dependent formation of DNA adducts and induction of lymphocyte mutations but that the dose-response curves for DNA binding and mutations are different. /1,6-dinitropyrene/|1,6-Dinitropyrene ... is much more mutagenic and carcinogenic /than 1-nitropyrene/. ... After a single ip injection of 1-nitropyrene, covalent DNA binding could not be detected in vivo; however, 1,6-dinitropyrene formed N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene as the major DNA adduct in rat liver, kidney, urinary bladder, and mammary gland, with the highest levels being found in the bladder. ...DNA binding of both 1-nitropyrene and 1,6-dinitropyrene in vitro was twofold higher when cytosol from rats pretreated with 1-nitropyrene was used. However, pretreatment of rats with 1-nitropyrene only slightly increased the amount of in vivo DNA binding by 1,6-dinitropyrene except in the kidney, where there was a 60 percent increase. ...when 1,8-dinitropyrene was administered in vivo and the extent of binding was assayed in liver, bladder, and intestinal DNA, there was more binding in/slow-acetylator phenotype hamster/ strain Bio. 1.5 than in /fast-acetylator phenotype/ strain Bio. 87.20. /Dinitropyrenes/|For more Mechanism of Action (Complete) data for DINITROPYRENE (9 total), please visit the HSDB record page.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SPECIAL STUDIES/ ... Correlation analysis and inhibition studies with 7,8-benzoflavone and antibodies indicate that human cytochrome P-450 enzymes in the IA family are most effective in detoxicating /1,3-dinitropyrene/...; the contribution of cytochrome P-450PA (P-450 IA2, the phenacetin O-deethylase) is deemed more important, but a role for the small amount of cytochrome P1-450 (P-450 IA1) in the liver cannot be ruled out. In contrast to the case of 1,3-dinitropyrene, the inactivation of 1,6-dinitropyrene is well correlated with levels of cytochrome P-450NF (P-450 IIIA4, nifedipine oxidase) and its catalytic activities. The inactivation of 1,8-dinitropyrene was not correlated with any of the above parameters and only correlated with the conversion of benzo(a)pyrene to its 3-hydroxy and 4,5-dihydrodiol products, for which the principal enzymes involved in human liver are unknown. Thus, distinct human cytochrome P-450 enzymes are involved in the detoxication of different dinitropyrene congeners, and the situation appears to contrast with that in rat liver. /1,3-, 1,6-, and 1,8-dinitropyrene/|/SPECIAL STUDIES/ The ability of 1,6-dinitropyrene to induce chromosome damage in peripheral human lymphocyte cultures has been demonstrated. ... The fact that a positive result was obtained using human lymphocytes shows that, in the presence of the appropriate activation system, dinitropyrene is genotoxic in human cells. /1,6-dinitropyrene/

1,6-Dinitropyrene is available for research purposes at > or = 98% purity. It is also available in 14C- or 3H-labeled form at > or = 98% radiochemical purity. /1,6-Dinitropyrene/|1,8-Dinitropyrene is available for research purposes at > or = 98% purity. It is also available in 14C- or 3H-labeled form at > or = 98% radiochemical purity. /1,8-Dinitropyrene/