1- and 3-nitrobenzo[a]pyrene (1- and 3-nitro-BaP) are environmental pollutants and are S9-mediated mutagens in the Chinese hamster ovary (CHO) cell/hypoxanthine-guanine phosphoribosyl transferase assay. In this study, the pathways leading to the mutagenic activation of these compounds in CHO cells were examined. The microsomal metabolites of 1- and 3-nitro-BaP, the 1- and 3-nitro-BaP trans-7,8-dihydroxy-7,8-dihydrodiols (trans-7,8-dihydrodiols) and the 1- and 3-nitro-BaP trans-9,10-dihydrodiols, were isolated and tested for mutagenicity. At the concentrations assayed, both trans-9,10-dihydrodiols were non-mutagenic with and without S9 activation. In contrast, the trans-7,8-dihydrodiols of 1- and 3-nitro-BaP were direct-acting mutagens and these responses were similar in magnitude to the S9-mediated mutagenicities of the parent nitro-BaPs. S9 increased the mutagenic responses of the trans-7,8-dihydrodiols approximately 20-fold. Inhibition of epoxide hydrolase decreased the S9-mediated mutagenicity of 1-nitro-BaP by half, but doubled the S9-mediated mutagenicity of 3-nitro-BaP. These results suggest that in CHO cells: (i) the major route of mutagenic activation of 1- and 3-nitro-BaP involves S9-generated derivatives of the trans-7,8-dihydrodiols, e.g. bay-region diol epoxides; (ii) reactive nitroarene oxides may contribute to mutation induction by 3-nitro-BaP; and (iii) metabolic routes involving trans-9,10-dihydrodiol formation result in detoxification.
The environmental pollutants 1- and 3-nitrobenzo[a]pyrene (1- and 3-NBaP) are metabolized by mammalian microsomes through ring oxidation to 1-NBaP trans-7,8-dihydrodiol and 3-NBaP trans-7,8-dihydrodiol, and by nitroreduction to 1- and 3-aminobenzo[a]pyrene. To determine if these compounds are tumorigenic, 1- and 3-NBaP, along with several of their metabolites and the parent benzo[a]pyrene (BaP) and its trans-7,8-dihydrodiol metabolite, were tested in the neonatal CD-1 mouse bioassay. Male mice were administered i.p. injections at a total dose of 100 or 400 nmol per mouse on 1, 8 and 15 days after birth. While the liver tumor incidences for BaP, BaP trans-7,8-dihydrodiol, and the positive control 6-nitrochrysene (6-NC) were significantly higher than in the solvent control animals, all the other tested compounds exhibited no tumorigenicity. The frequency of Ha- and Ki-ras mutations in liver tumors of mice treated with BaP, BaP trans-7,8-dihydrodiol, and 6-NC were higher than in the few liver tumors isolated from control mice or mice treated with the NBaPs or their metabolites. Since 1- and 3-NBaP and their metabolites are potent mutagens in the Salmonella assay and moderate mutagens in the Chinese hamster ovary (CHO) mammalian mutagenicity assay, our results indicate that the in vitro mutagenicity of these compounds does not correlate with their tumorigenicity.
The compounds 1-, 3-, and 6-nitrobenzo[a]pyrene (nitro-BaP) are environmental pollutants and have been shown to be potent bacterial mutagens. The anaerobic metabolism of these isomeric nitro-BaPs was investigated by the incubation of rat intestinal microflora with each isomer for 48 hr. Aliquots were removed at several time intervals, extracted, fractionated by high-pressure liquid chromatography (HPLC), and the radioactivity determined. Metabolites were identified by comparison of their chromatographic, ultraviolet-visible absorption, and mass spectral properties with those of authentic standards. The order of the extent of nitroreduction for these isomers was 3-nitro-BaP greater than 6-nitro-BaP greater than 1-nitro-BaP. After 48 hr of exposure, 84% of the added 3-nitro-BaP was present as 3-amino-BaP, 51% of the 6-nitro-BaP was metabolized to 6-amino-BaP, and 1-nitro-BaP was reduced to 1-amino-BaP (13%) and 1-nitroso-BaP (4%). The order of the extent of microbial nitroreduction for these nitro-BaP isomers is different from the predictions based on electronic and steric hindrance effects. These results suggest that intestinal microflora nitroreductases exhibit a markedly high degree of substrate specificity toward nitro-BaPs that affects the extent of nitroreduction.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). 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 0.9% saline (NS) 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 ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
/LABORATORY ANIMALS: Acute Exposure/ A series of environmentally occurring nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) including those containing nitro-groups oriented coplanarly to the aromatic rings, such as 1- and 3-nitrobenzo[a]pyrene (1- and 3-NBAP), 6-nitrochrysene, and 1- and 4-nitropyrene, and those with a molecular orientation of the nitro-groups perpendicular to the aromatic moieties, such as 7-nitrobenz[a]anthracene and 6-nitrobenzo[a]pyrene (6-NBAP), were used to study the induction of certain rat hepatic phase II conjugating enzymes. Effects of these two different classes of nitro-PAHs on microsomal UDP-glucuronyltransferase (UDPGT), cytosolic glutathione S-transferases (GSTs) and sulfotransferases (STs) were investigated. After three consecutive daily i.p. injections, 1- and 3-NBAP and 6-nitrochrysene significantly increased the activities of UDPGT and GST, whereas their parent PAHs did not induce UDPGT (and GST activity was also unaltered by benzo[a]pyrene). UDPGT and GST activities were also significantly increased by 1-nitropyrene. In contrast, the sulfotransferases directed to 2-naphthol were not significantly induced by any PAH or nitro-PAH when assayed at either pH 5.5 or 7.5; however, the activities of aryl STs III and IV (pH 5.5) were significantly decreased following treatment with pyrene and two nitro-compounds, 6-NBAP and 7-nitrobenz[a]anthracene, in which the nitro-group is oriented perpendicular to the aromatic moiety. These results indicate that a coplanar orientation of the nitro-group of certain nitrated PAHs facilitates the induction of hepatic phase II enzymes by these compounds in rats, and the comparable induction patterns for P450IA1, UDPGT, and GST provide further evidence supporting the coordinate regulation (through the Ah receptor) of these phase I and phase II activities.
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The nitropolycyclic aromatic hydrocarbons (nitro-PAHs) 1-, 2-, and 3-nitrobenzo(a)pyrene, 1- and 3-nitrobenzo(e)pyrene, 2- and 3-nitrofluoranthene, 9-nitrodibenz(a,c)anthracene, and two of the parent PAHs fluoranthene and dibenz(a,c)anthracene were tested for tumorigenicity in the neonatal male B6C3F1 mouse. 6-Nitrochrysene was used as a positive control. Mice were administered three intraperitoneal injections of test agent (400 nmol total) on 1, 8, and 15 days after birth and evaluated for liver and lung tumors at 12 months of age. 2-Nitrobenzo(a)pyrene and 6-nitrochrysene induced a high incidence of liver tumors (91-100%), while the remaining test compounds did not induce tumors at a rate significantly higher than the solvent control. 6-Nitrochrysene was the only test agent to produce a significant increase in the frequency of lung tumors. K- and H-ras mutations were analyzed in liver tumors of treated mice and mainly occurred at the first base of K-ras codon 13, resulting in GGC - CGC transversion. Since most of the tested nitro-PAHs are mutagens in vitro, the results of this study indicate that the in vitro mutagenicity of these compounds does not correlate with their tumorigenicity in the neonatal B6C3F1 mouse bioassay. Also, the results indicate that liver tumors from mice treated with nitro-PAHs possess ras mutations typical of PAHs and their derivatives.
Synthesis, chemical properties and mutagenicity of 1,6- and 3,6-dinitrobenzo(a)pyrenes.
作者：Kiyoshi FUKUHARA、Naoki MIYATA、Michiko MATSUI、Keiko MATSUI、Motoi Jr. ISHIDATE、Shozo Kamiya
DOI：10.1248/cpb.38.3158
日期：——
Nitration of benzo[a]pyrene (BaP) with HNO3 (d = 1.38) produced a mixture of dinitroBaPs (1,6- and 3,6-isomers) and mononitroBaPs (1-, 3- and 6-isomers). Pure 1,6-dinitroBaP and 3,6-dinitroBaP were obtained by the reduction of the dinitroBaPs mixture with NaSH to yield the separable products 1-amino-6-nitroBaP and 3-amino-6-nitroBaP, followed by conversion to dinitroBaPs via the the diazonium salts
The present invention relates to compounds of the general formula (I), to the use thereof in electronic devices, preferably as host material for fluorescent dopants or as fluorescent dopant, to a process for the preparation of the compounds of the formula (I), and to electronic devices comprising compounds of the formula (I).
Synthesis, spectral analysis, and mutagenicity of 1-, 3-, and 6-nitrobenzo[a]pyrene
作者：M. W. Chou、R. H. Heflich、D. A. Casciano、D. W. Miller、J. P. Freeman、F. E. Evans、P. P. Fu
DOI：10.1021/jm00375a012
日期：1984.9
1-, 3-, and 6-nitrobenzo[a]pyrene in high yield. Comparison of the spectral data of these compounds with those obtained from direct nitration of benzo[a]pyrene confirmed that 1- and 3-nitrobenzo[a]pyrenes are indeed the minor products of the latter reaction. This confirmation also verifies that 1- and 3-nitrobenzo[a]pyrene were the minor nitrated products of benzo[a]pyrene formed in model air atmospheres
Atmospheric Heterogeneous Reactions of Benzo(a)pyrene
作者：M. Cazaunau、K. Le Ménach、H. Budzinski、E. Villenave
DOI：10.1524/zpch.2010.6145
日期：2010.8.1
Abstract
This experimental study deals with heterogeneous reactions of benzo(a)pyrene (BaP) with ozone, nitrogen dioxide and hydroxyl radicals. BaP was adsorbed on silica particles chosen here as a model of mineral atmospheric particles. Compound extractions were assisted by focused microwave and analyses were performed by gas chromatography coupled with mass spectroscopy in single ion monitoring mode. Pseudo-first order rate constants were obtained from the fit of experimental decays of particulate-BaP concentration versus reaction time. Second order rate constants were determined considering the different oxidant gaseous concentrations except for the case of hydroxyl radicals where only a pseudo-first order rate constant was proposed. Values obtained at room temperature are (2.1±0.5)×10−15 cm3 molecule−1 s−1 for (BaP + ozone), (5.8±1.4)×10−16 cm3 molecule−1 s−1 for (BaP + nitrogen dioxide) and (3.4±0.8)×10−2 s−1 for (BaP + OH) reactions. Products have only been investigated for the NO2 and the OH (in the presence of NOx) reactions. 1-, 3- and 6-nitrobenzo(a)pyrenes were detected as degradation products and quantified. Reaction rate constants for product formation are (3.7±0.9)×10−16 cm3 molecule−1 s−1 for 6-NBaP, (2.2±0.6)×10−17 cm3 molecule−1 s−1 for 1-NBaP and (5.3±1.3)×10−17 cm3 molecule−1 s−1 for 3-NBaP. 1-, 3- and 6-nitroBaP account respectively for approximately 5%, 12% and 83% of total nitrated species. If in the presence of only nitrogen dioxide, BaP was totally degraded within few minutes, only 20 to 25 % of the initial BaP led to nitrated compounds when reacting with OH (in the presence of NOx).
Mutagenic nitrated benzo[a]pyrene derivatives in the reaction product of benzo[a]pyrene in NO2–air in the presence of O3 or under photoirradiation
作者：Satoko Ishii、Yoshiharu Hisamatsu、Koji Inazu、Takaaki Kobayashi、Ken-ichi Aika
DOI：10.1016/s0045-6535(00)00029-1
日期：2000.12
should be considered. Benzo[a]pyrene lactones were identified in a highly mutagenic fraction of the products of the dark reaction in the presence of O3 and photoreaction and a nitrobenzo[a]pyrene lactone was also identified in a highly mutagenic fraction of the dark reaction products in the presence of O3. Nitrated oxygenated benzo[a]pyrenederivatives such as nitrobenzo[a]pyrene lactone were considered
