4-Nitropyrene

247.25 g/mol

247.25

XOT1408EDI

DTXSID5074844

C44325

Orange needles from methyl carbonate/methanol|Slender orange needles

45.8 Ų

log Kow = 4.75 (est)

196-197.5 °C

In water, 6.8X10-2 mg/L at 25 °C (est)

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

5.52X10-8 mm Hg at 25 °C (est)

Henry's Law constant = 2.45X10-8 atm-cu m/mol at 25 °C (est)

When heated to decomposition ... emits toxic fumes of NOx

PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/|For more Disposal Methods (Complete) data for 4-Nitropyrene (6 total), please visit the HSDB record page.

WHO; Environmental Health Criteria 229: Selected Nitro- and Nitro-Oxy-Polycyclic Aromatic Hydrocarbons (2003). EHC are designed for scientists and administrators responsible for the establishment of safety standards and regulations and provide basic scientific risk evaluations of a wide range of chemicals and groups of chemicals.[Available from, as of November 18, 2009: http://www.inchem.org/pages/ehc.html]|IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; Diesel and Gasoline Engine Exhausts and Some Nitroarenes (vol 46) pp.367-373 (1989). IARC Monographs provide critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations.[Summary available from; as of November 18, 2009: http://monographs.iarc.fr/ENG/Monographs/vol46/volume46.pdf]|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. 4-Nitropyrene (57835-92-4) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of September 23, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s121nitr.pdf]

|Warning|H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms & sides & fitted with a filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for 4-Nitropyrene (9 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

URBAN/SUBURBAN: 4-Nitropyrene was detected in an unknown number of ambient air samples of Baltimore, Maryland in January 2001 at concentrations ranging from 1.2-4.2 pg/cu m and in July 2001 at concentrations ranging from 0.2-1.2 pg/cu m(1). 4-Nitropyrene was also detected in an unknown number of ambient air samples in of Fort Meade, Maryland in January 2001 at concentrations ranging from 1.0-2.6 pg/cu m and in July 2001 at concentrations ranging from 0.050-0.30 pg/cu m(1). 4-Nitropyrene was detected in 6 out of 6 airborne samples in air and diesel particulates collected from Baltimore, Maryland at concentrations ranging from 5.5-173 ng/g(2).

4-Nitropyrene's limited production and use as a laboratory chemical(1) may result in its release to the environment through various waste streams. Its presence in the atmosphere due to reactions of parent polyaromatic hydrocarbons released in various manufacturing processes(2) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 86,000(SRC), determined from a structure estimation method(2), indicates that 4-nitropyrene is expected to be immobile in soil(SRC). Volatilization of 4-nitropyrene from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.5X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 4-Nitropyrene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.5X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2009).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 86,000(SRC), determined from a structure estimation method(2), indicates that 4-nitropyrene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.5X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 630(SRC), from an estimated log Kow of 4.8(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Biodegradation data were not available(SRC, 2009).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-nitropyrene, which has an estimated vapor pressure of 5.5X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase 4-nitropyrene may be removed from the air by wet or dry deposition(SRC). 4-Nitropyrene contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

4-Nitropyrene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). 4-Nitropyrene contains chromophores that absorb at wavelengths >290 nm(1) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 630 was calculated in fish for 4-nitropyrene(SRC), using an estimated log Kow of 4.8(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-nitropyrene can be estimated to be 86,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-nitropyrene is expected to be immobile in soil.

The Henry's Law constant for 4-nitropyrene is estimated as 2.5X10-08 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 4-nitropyrene is expected to be essentially nonvolatile from water surfaces(2). 4-Nitropyrene's Henry's Law constant indicates that volatilization from moist soil surfaces will not occur(SRC). 4-Nitropyrene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.5X10-8 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to 4-nitropyrene may occur through inhalation and dermal contact with this compound at workplaces where 4-nitropyrene is produced as a contaminant in manufacturing processes. Monitoring data indicate that the general population may be exposed to 4-nitropyrene via inhalation of ambient air and dermal contact with this compound. (SRC)

4-Nitropyrene seems to differ from 1- and 2-nitropyrene concerning elimination and excretion patterns, metabolites and DNA adducts ... This may account for 4-nitropyrene being the most carcinogenic of the nitropyrenes in rat mammary gland.

The in vitro and in vivo metabolism of ... 4-nitropyrene, was studied ... Initially, 4-nitropyrene was metabolized by rat liver microsomes, or rat liver 9000g supernatant, to yield primarily two metabolites; one of these was identified as 4-nitropyrene-9,10-dione. The major metabolite of 4-nitropyrene in the presence of 3,3,3-trichloropropylene-1,2-oxide was 9,10-epoxy-9,10-dihydro-4-nitropyrene. In parallel studies, oral administration of 58 mg (0.3 mCi/mmol)/kg body weight of [3H]4-nitropyrene to female Sprague-Dawley rats, which are susceptible to mammary carcinogenesis by this agent, yielded 32% and 30.6% of the dose after 48 hr as urinary and fecal excretion products, respectively. Excretion of the radioactivity remained slightly higher in the urine than in feces throughout 168 hr after administration. Some of the fecal metabolites (isolated amounts expressed as % of dose) were identified as 4-aminopyrene (5.4), 9(10)-hydroxy-4-(acetylamino)pyrene (3.3), and unmetabolized 4-nitropyrene (2.4). Sulfates (3.3) and glucuronides (2.4) of 9(10)-hydroxy-4-(acetylamino)pyrene were identified in the urine. This study indicates that nitroreduction and ring oxidation are metabolic pathways of 4-nitropyrene in vivo; similar findings were obtained previously with its structural isomers 1- and 2-nitropyrene. However, the pattern of excretion of 4-nitropyrene is different ...|... The ability of 15 human hepatic and 8 pulmonary microsomal samples to metabolize / 1-, 2-, and 4-nitropyrene were compared/. Human hepatic microsomes were competent in metabolizing all three isomers. Qualitatively similar metabolic patterns were observed, although at much lower levels, upon incubating mono-NP with pulmonary microsomes. Ring-oxidized metabolites (phenols and trans-dihydrodiols) were produced from all three isomers. However, the nitroreductive metabolism leading to the formation of aminopyrene was evident only with 4-NP. The role of specific P450 enzymes in the human hepatic microsomal metabolism of mono-NP was investigated by correlating the P450-dependent catalytic activities in each microsomal sample with the levels of individual metabolites formed by the same microsomes and by examining the effects of agents that can either inhibit or stimulate specific P450 enzymes in mono-NP metabolism ... Most of the hepatic microsomal metabolism of 1- and 4-NP /was attributed/ to P450 3A4, although a minor role for P450 1A2 cannot be ruled out. Specifically, P450 3A4 was responsible for the formation of 3-hydroxy-1nitropyrene from 1-NP and the formation of trans-9,10-dihydro-9,10dihydroxy-4-nitropyrene, 9(10)-hydroxy-4-nitropyrene, and 4-aminopyrene from 4-NP. None of the P450 enzymes examined (P450s 3A4, 1A2, 2E1, 2A6, 2D6, and 2C9) appeared to be involved in catalyzing the formation of trans-4,5-dihydro-4,5-dihydroxy-2-nitropyrene and 6-hydroxy-2-nitropyrene from 2-NP in human hepatic microsomes ...|4-nitropyrene has known human metabolites that include (4R,5R)-9-nitro-4,5-dihydropyrene-4,5-diol and 4-aminopyrene.

Carcinogens

/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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Nitrates, nitrites, and related compounds/|/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 necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat as 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. Administer activated charcoal ... . /Nitrates, nitrites, and related compounds/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Monitor cardiac rhythm and treat arrhythmias if necessary. Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. If unresponsive to these measures, vasopressors may be helpful. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. DIRECT PHYSICIAN ORDER ONLY ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Nitrates, nitrites, and related compounds/

/GENOTOXICITY/ The mutagenicity (trifluorothymidine resistance at the thymidine kinase locus) of 1-, 2-, and 4-nitropyrene (1-, 2-, and 4-NP), 1,3-, 1,6-, and 1,8-dinitropyrene (1,3-, 1,6-, and 1,8-DNP), and pyrene was assessed in a quantitative forward mutation assay using a metabolically competent line (MCL-5) of human B-lymphoblastoid cells. These cells contain endogenous cytochrome P450 activity (CYP1A1) and two plasmids that express cDNAs for four additional P450s (CYP1A2, CYP2A6, CYP2E1, CYP3A4) and microsomal epoxide hydrolase found in human liver. The major finding is that 2-NP and 1,3-DNP, both potent bacterial mutagens, were nonmutagenic in this assay. The following mutagenic potency series, expressed as the minimum detectable mutagen concentration (MDMC) in nmol/mL, was obtained: 1,6-DNP (0.8), 1,8-DNP (1.5), 4-NP (3.1), 1-NP (9.1), 2-NP (> 81), 1,3-DNP (> 86), pyrene (> 494). There was over an 11-fold difference between the most potent (1.6-DNP) and the least potent (1-NP) mutagen. 1,6-DNP was approximately twice as mutagenic as 1,8-DNP, which was almost twice as mutagenic as 4-NP, which, in turn was nearly three times as potent as 1-NP...|/GENOTOXICITY/ ... To examine whether the PAH- and nitro-PAH-DNA derived adducts can be further differentiated, hepatocyte cultures were preincubated with 2,3,7,8-tetrachloro-p-dioxin (TCDD) to induce the activity of cytochrome P450 1A1. TCDD pretreatment strongly increased the levels of PAH-DNA adducts, whereas, the levels of nitro-PAH adducts were markedly decreased. NCI-H322 cells, a human lung tumor cell line derived from Clara cells, exhibited PAH-DNA adduct levels between 10 and 100, and nitro-PAH-DNA adducts at levels between 0.2 to about 30 adducts per 108 nucleotides, respectively. In contrast to hepatocytes, incubations with extractable organic matter (EOM) and the neutral aromatic EOM fraction displayed several distinct spots in the chromatograms of NCI-H322 cells. The major spot was assigned by cochromatography to be identical with the major DNA adduct formed by incubation with B[a]P alone ...

4-nitropyrene

Health Hazards -> Carcinogens