1,8-Dinitropyrene

292.24600

292.25

51U7E9MW6I

DTXSID2073514

C44300

Light brown needles recrystalized from benzene and methanol|Yellow, fluffy, crystalline solid

2904209090

91.64000

5.44680

1.574g/cm3

>300 °C

515.2ºC at 760 mmHg

261.6ºC

1.887

In water, 5.4X10-2 mg/L at 25 °C (est)

Keep container tightly closed in a dry and well-ventilated place.|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/

9.1X10-10 mm Hg at 25 °C (est)

Henry's Law constant = 1.29X10-10 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 5.4X10-11cu cm/molec-sec at 25 °C (est)

3

R40

UR2456000

Xn

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.|Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.|PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /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 1,8-Dinitropyrene (7 total), please visit the HSDB record page.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, vol. 46, p. 231 (1999). IARC Monographs provide critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations.[Available at: http://monographs.iarc.fr/index.php]|WHO; Environmental Health Criteria Document No. 229: Nitro- and nitro- oxypolycyclic aromatic hydrocarbons, selected. 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 October 1, 2010: http://www.inchem.org/pages/ehc.html ]|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. 1,8-Dinitropyrene (42397-65-9) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of November 26, 2010: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s012iq.pdf]

|Warning|H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory.|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|impervious clothing, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special protective equipment for fire-fighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES Personal precautions Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.|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/

Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.|If inhaled ... , move person into fresh air. If not breathing, give artificial respiration. Consult a physician. In case of skin contact, wWash off with soap and plenty of water. Consult a physician. In case of eye contact, fFlush eyes with water as a precaution. If swallowed, never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.|For more Preventive Measures (Complete) data for 1,8-Dinitropyrene (15 total), please visit the HSDB record page.

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/|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/

1,8-Dinitropyrene concentration in emissions from a diesel power plant on the Harvard campus in Massachusetts was less than 8 ppm in the soluble organic fraction. Concentration ranged from not detected to 4 ppm in the soluble organic fraction of diesel-powered mobile emission sources; sampling was conducted in 1983. The emission rate of 1,8-dinitropyrene from the power plant was <6X10-8 lb/BTU (quantification limit), with an annual contribution to Boston ambient air of <0.14 tons from both the plant and mobile diesel sources(1). The concentration of 1,8-nitropyrene in emission particulates from diesel (1986 model) and gasoline (1989 model) engine vehicles was reported as 0.44 and 0.45 pmol/mg particulate, respectively(2). Exhaust particle concentrations of 3.4 and 0.013-0.7 mg/kg have been reported for heavy-duty and light-duty diesel engines, respectively(3). 1,8-Dinitropyrene daily emission at a typical US airport has been estimated at 20 g/day(4). Emissions of 1.88 and 0.88 mg/kg extract have been reported for gas and liquified petroleum gas burner, respectively, used for home heating and cooking(5).

URBAN/SUBURBAN: 1,8-Dinitropyrene was detected in Baltimore, MD and Fort Meade, MD, during January 24-27 and July 15-23, 2001. Mean concentrations in Baltimore and Fort Meade were <0.7 pg/cu m in both January and July, respectively(1). The mean concentrations in air samples from downtown Kanazawa, Japan collected from spring 1989 to winter 1992 were 2.90 (spring, 2.35 (summer), 4.04 (autumn), and 5.28 (winter), with an annual mean of 3.63 mol/cu m(2). A maximum of 29.8 to a minimum of 1.1 mol/cu m during the time frame of 9-11AM and in ambient air samples collected from urban (Detroit Science Center, summer 1981; downtown Detroit), suburban (Warren, MI in December 1982 and June 1984) areas were 0.0025 and <0.004 ug/g particulates, respectively(3).|RURAL/REMOTE: For 1,8-dinitropyrene, mean concentrations of 0.0024 and 0.0035 ug/g particulates were reported in ambient air samples collected in rural Cape Henlopen State Park, DE, 0.8 km from the Atlantic Ocean and in remote southwest Bermuda 9 km from Hamilton, respectively(1).|SOURCE DOMINATED: The concentration ranges for 1,8-dinitropyrene were 58.3-293.0 pg/cu m (indoors) and 3.2-22.5 pg/cu m (outdoors) in air samples from a Taiwanese temple in Taichung County, central Taiwan; the source was attributed to burning of incense. Atmospheric concentrations ranged from 2.8-12.0 pg/cu m and the overall indoor emission average was 180.5 pg/cu m(1). The mean concentration of 1,8-dinitropyrene in ambient air samples collected from two industrial areas (River Rouge, MI 2-4 km from industries including steel mills, coke ovens, power plants, a refinery, and chemical works, 1982-1983 and from Dearborn, MI - steel mills and coke ovens, 1980-1983) was reported to be 0.0131 and 0.0200 ug/g particulates, respectively(2).

Chronic Exposure or Carcinogenicity/ The carcinogenic effects of a mixture of 1-nitropyrene and three dinitropyrenes (1,3-, 1,6- and 1,8-dinitropyrene) were investigated in rats. Female F344/Jcl rats were given one of three doses (5, 10 and 20 mg/kg bw) of the mixture by repeated intragastric instillations twice a week for 55 weeks, and then autopsied 49 weeks later. Mammary adenocarcinomas were induced in rats of all the three experimental groups dose-dependently, while no adenocarcinoma was induced in the control rats which were given only vehicle. Clitoral gland tumors, most of which were diagnosed as squamous cell carcinomas, were also commonly observed in the NP-treated rats in a dose-dependent way. In addition, high incidences of mononuclear cell leukemias were noted in the NP-treated rats. Other tumors were frequently induced in the uterus and endocrine organs, such as the pituitary, adrenal, and thyroid glands. However, the incidences of these tumors were almost equal in both the control and NP-treated groups...|/GENOTOXICITY/ ... The lambda/lacZ transgenic mouse (Muta Mouse) /was used/ to examine induction of mutations in multiple organs. A commercially available mixture of DNPs (1,3-, 1,6-, 1,8-, and unidentified isomer (s) with a content of 20.2, 30.4, 35.2, and 14.2%, respectively) was injected intragastrically at 200 and 400 mg/kg once each week for 4 weeks. Seven days after the final treatment, liver, lung, colon, stomach, and bone marrow were collected for mutation analysis. The target transgene was recovered by the lambda packaging method and mutation of lacZ gene was analyzed by a positive selection with galE(-) E. coli. In order to determine the sequence alterations by DNPs, the mutagenicity of the lambda cII gene was also examined by the positive selection with hfl(-) E. coli. Since cII gene (294bp) is much smaller than the lacZ (3024bp), it facilitated the sequence analysis. Strongest increases in mutant frequencies (MFs) were observed in colon for both lacZ (7.5x10-5 to 43.3x10-5) and cII (2.7x10-5 to 22.5x10-5) gene. Three-four-fold increases were observed in stomach for both genes. A statistically significant increase in MFs was also evident in liver and lung for the lacZ gene, and in lung and bone marrow for the cII gene. The sequence alterations of the cII gene recovered from 37 mutants in the colon were compared with 50 mutants from untreated mice. Base substitution mutations predominated for both untreated (91%) and DNP-treated (84%) groups. The DNPs treatment increased the incidence of G:C to T:A transversion (2-43%) and decreased G:C to A:T transitions (70-22%). The G:C to T:A transversions, characteristic to DNPs treatment, is probably caused by the guanine-C8 adduct, which is known as a major DNA-adduct induced by DNPs, through an incorporation of adenine opposite the adduct ("A"-rule). /This/ study showed a relevant use of the cII gene as an additional target for mutagenesis in the Muta Mouse and revealed a mutagenic specificity of DNPs in vivo.

1,8-Dinitropyrene is a nitrated polycyclic aromatic hydrocarbon which is formed as a result of combustion of petrochemical fuel, preparation of food with grilling, cigarette smoking, activities associated with occupational settings such as the coke-oven industry, or photochemical reactions of polycyclic aromatic hydrocarbons with ambient or atmospheric hydroxyl radicals and NO2 which form nitrated polycyclic aromatic hydrocarbons(1). These processes may result in the release of 1,8-dinitropyrene to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.4X10+5(SRC), determined from a structure estimation method(2), indicates that 1,8-dinitropyrene is expected to be immobile in soil(SRC). Volatilization of 1,8-dinitropyrene from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.3X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 1,8-Dinitropyrene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.1X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2010).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.4X10+5(SRC), determined from a structure estimation method(2), indicates that 1,8-dinitropyrene 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 1.3X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 480(SRC), from an estimated log Kow of 4.57(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 in water were not available(SRC, 2010).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,8-dinitropyrene, which has an estimated vapor pressure of 9.1X10-10 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 1,8-dinitropyrene may be removed from the air by wet or dry deposition(SRC). 1,8-Dinitropyrene absorbs at wavelengths >310 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC).

1,8-Dinitropyrene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Half-lives of 0.7 and 5.7 days were reported when the compound was exposed to light at >310 nm in DMSO and following coating on to silica, respectively(2).

An estimated BCF of 480 was calculated in fish for 1,8-dinitropyrene(SRC), using an estimated log Kow of 4.57(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 1,8-dinitropyrene can be estimated to be 1.4X10+5(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,8-dinitropyrene is expected to be immobile in soil.

The Henry's Law constant for 1,8-dinitropyrene is estimated as 1.3X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 1,8-dinitropyrene is expected to be essentially nonvolatile from water surfaces(2). 1,8-Dinitropyrene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.1X10-10 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to 1,8-dinitropyrene may occur through inhalation and dermal contact with this compound at workplaces where 1,8-dinitropyrene is formed. The most likely pathway by which the general public is exposed to 1,8-dinitropyrene is by inhalation due to the release of this substance from combustion of diesel fuels and in smoke. (SRC)

Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. (See all compounds classified as Mutagens.)|Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. (See all compounds classified as Carcinogens.)

The disposition of ... 1,8-dinitropyrene (DNP) in female BALB/c mice was investigated. In the first 48 hr after oral administration of 1,8-dinitro[4,5,9,10-14C)pyrene ((14C)DNP), 42% of the dose was eliminated in the feces and 12% in the urine. Feces was the major pathway of excretion with 45% of the dose being eliminated by this route in 9 days. Distribution of DNP in various tissues (blood, liver, spleen, lungs, kidneys, stomach, small and large intestine) was studied over 9 days. There was a linear increase in the concentration of radioactive material in the blood, liver and kidneys up to 6 hr after (14)CDNP administration, representing 0.27, 2.9 and 0.21% of the radioactive dose, respectively. The corresponding figures after 24 hr decreased to 0.1, 1.6 and 0.12%, respectively. In comparison, radioactivity present in the spleen and lungs was low and did not significantly change with time. In studies with ligated sections of the gastrointestinal tract, DNP absorption was from the small and large intestine and there was none from the stomach. The rate of absorption of DNP from the small intestine was greater than that from the large intestine, although overall uptake of the compound was poor (more than 80% of the original dose was recovered from the ligated small intestine after 120 min). The data from these studies suggest that although absorption of orally administered DNP is slow, the compound or its metabolites persist in the body for long periods and the liver should be considered as the major target organ.

... 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, the nitroarene chosen as model compound, was reduced to the corresponding mono- and diamino-derivatives, 1-amino-8-nitropyrene and 1,8-diaminopyrene, by human lysate supplemented with cofactors.|Dinitropyrenes are contaminants in diesel emissions that are mutagenic in bacteria and mammalian cells, and tumorigenic in laboratory animals. In this project, ... the factors that contributed to the extreme genotoxicity of dinitropyrenes in bacteria /were investigated/ and ... if these factors were important in mammalian cells /was determined/. Xanthine oxidase, a mammalian nitroreductase, catalyzed the conversion of the dinitropyrenes to DNA-bound products, but the level of binding did not exceed that observed with 1-nitropyrene. This suggested that factors in addition to nitroreduction were important in the metabolic activation of dinitropyrenes. 1-Nitro-6-nitrosopyrene and 1-nitro-8-nitrosopyrene were synthesized and reacted with DNA under reducing conditions. The same C8-substituted deoxyguanosine adducts were formed that were found in the xanthine oxidase-catalyzed reactions, which confirmed that incubation with this nitroreductase generated reactive N-hydroxy arylamine intermediates. In incubations with rat and human liver microsomes and cytosol, 1-nitropyrene and 1,3-dinitropyrene were reduced to a lesser extent than 1,6- and 1,8-dinitropyrene, which was in accord with their relative mutagenicities. Each of the cytosolic incubations were similar in that oxygen decreased aminopyrene, but not nitrosopyrene, formation. The data indicated that reduced derivatives of the nitrosopyrenes were redox cycling with oxygen, which decreased cytosolic aminopyrene formation. In cytosolic incubations, oxygen inhibited the reduction of 1-nitropyrene and 1,3-dinitropyrene to a greater extent than 1,6- and 1,8-dinitropyrene. By comparison, in microsomal investigations, the nitroreduction of each nitrated pyrene was equally oxygen-sensitive. This apparently was caused by the initial nitroanion radicals reacting with oxygen to decrease nitrosopyrene formation. Although more extensive nitroreduction of each compound was detected in anaerobic incubations, aerobic reduction of these compounds did occur and may be important during in vivo exposure to nitrated pyrenes. When rat liver cytosol was incubated with the nitrated pyrenes, very low levels of DNA binding were detected. Addition of acetyl coenzyme A (AcCoA) to these incubations increased the binding of the dinitropyrenes 20- to 40-fold, while the binding of 1-nitropyrene was not affected. The extent of AcCoA-dependent binding of the dinitropyrenes reflected the amount of nitroreduction; however, the increase in binding did not occur with dog liver cytosol, which was known to be deficient in N-acetylases. These results indicated that cytosolic nitroreductases catalyzed the formation of N-hydroxy arylamine intermediates, which in the case of dinitropyrenes were converted to reactive N-acetoxy arylamines by cytosolic AcCoA-dependent acetylases.|... The ability of rabbit lung to metabolize 1,8-dinitro(4,5,9,10-3H)pyrene by both oxygen-dependent and oxygen-independent pathways has been investigated. Using lung 9000 g supernatant, the biotransformation of 1,8-dinitropyrene to stable metabolites was more extensive in the absence of oxygen. A major proportion of the metabolites was ether-extractable. Five metabolite peaks (A-E) were detected by HPLC in the absence of oxygen. Formation of metabolites A, C, D and E was decreased under aerobic conditions. Metabolites B and C co-chromatographed with the reference standards 1,8-diaminopyrene and 1-acetyl-amino-8-nitropyrene, respectively. The formation of metabolites A and C was dependent on the presence of acetyl coenzyme A. Binding of radiolabel to calf thymus DNA occurred under both anaerobic and aerobic conditions, although there was significantly higher binding in the presence of oxygen. Omission of acetyl coenzyme A significantly increased DNA binding. In experiments where calf thymus DNA was omitted from the incubation medium, covalent binding of radiolabel to acid-precipitable lung S9 macromolecules was detected only under aerobic conditions (11.1 +/- 4.3 pmol/mg protein). The results indicate that rabbit lung can metabolize 1,8-dinitropyrene by both reductive and oxidative pathways. Reductive metabolism is the major pathway for formation of stable metabolites while alkylation of cellular macromolecules occurs primarily via oxidation. There was no correlation between acetyl coenzyme A-dependent acetylation and activation of 1,8-dinitropyrene to reactive species which bind to DNA.|The metabolic activation of dinitropyrenes occurs by reduction of one nitro group to yield N-hydroxy-1-amino-x-nitropyrene, where x is 3, 6 or 8, depending on the original compound. These N-hydroxyarylamine intermediates can undergo acid-catalyzed DNA binding or, in contrast to 1-nitropyrene, which is only N-acetylated, can be converted into highly reactive O-acetyl metabolites by bacterial and mammalian transacetylases. This activation pathway has been shown to be responsible for their extreme mutagenicity in Salmonella. In rat liver cytosolic incubations, 1-nitropyrene and 1,3-dinitropyrene were reduced to a much lesser extent than 1,6- or 1,8-dinitropyrene, which suggests that there may be fundamental differences in the reduction pathways between these nitroPAHs. /Dinitropyrenes/|For more Metabolism/Metabolites (Complete) data for 1,8-Dinitropyrene (10 total), please visit the HSDB record page.|1,8-dinitropyrene has known human metabolites that include 1-amino-8-nitropyrene.

Carcinogens, Mutagens

/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/|/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/

/GENOTOXICITY/ ...The mutagenic ... effects of benzene (B), nitrobenzene (NB), phenol (P), 2-nitrophenol (2-NP), 2,4-dinitrophenol (2,4-DNP), pyrene (Py), 1-nitropyrene (1-NPy), 1,3-dinitropyrene (1,3-DNPy), 1,6-dinitropyrene (1,6-DNPy), and 1,8-dinitropyrene (1,8-DNPy) ... were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then ... both cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes on human lymphocytes /were used/ in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1-NPy and 1,8-DNPy can be considered as human potential carcinogens...|/GENOTOXICITY/ The mutagenicity, metabolism, DNA adduction and induction of unscheduled DNA synthesis (UDS) of 1-nitropyrene and 1,8-dinitropyrene were investigated in the human hepatoma cell line HepG2. Previous results had demonstrated that 1-nitropyrene was both mutagenic at the hgprt locus and induced UDS in these cells. In /this/ study ... the dinitropyrenes, although highly mutagenic in Salmonella typhimurium, /were/ not mutagenic and /did/ not induce UDS in the HepG2...|/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/ N-Acetylcysteine (NAC) ... inhibits the mutagenicity of 1,8-dinitropyrene (1,8-DNP) and 1-nitropyrene (1-NP) known to be present in diesel exhaust and to be activated by cellular O- transacetylases and nitropyrene reductases. NAC inhibits also the induction of SCE in human lymphocytes by diesel extract.|/GENOTOXICITY/ The genotoxicities of 8 nitroarenes, i.e., 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, 1,8-dinitropyrene, 2,7-dinitrofluorene, 3-nitrofluoranthene, 1-nitro-3-hydroxypyrene and 1-nitro-3-acetoxypyrene, were examined in DNA repair tests using human isolated hepatocytes. Out of the tested nitroarenes, 5 compounds, i.e., 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, 1,8-dinitropyrene and 1-nitro-3-acetoxypyrene, clearly elicited positive responses of DNA repair. Among the chemicals which elicited positive responses, the levels of unscheduled DNA synthesis induced by the three dinitropyrene isomers were much higher than those of the other nitroarenes. Three chemicals, i.e., 2,7-dinitrofluorene, 3-nitrofluoranthene and 1-nitro-3-hydroxypyrene, elicited negative responses. The negative responses of 2,7-dinitrofluorene and 3-nitrofluoranthene, which had been positive in DNA repair tests with rodent hepatocytes, suggest some species differences between humans and rats in the metabolic activity of hepatocytes toward these agents.

1,8-dinitropyrene

Health Hazards -> Carcinogens, Mutagens