1,6-Dinitropyrene

292.24 g/mol

292.25

66Q2ZUF83N

DTXSID90872819

C44299

Light-brown needles, recrystallized from benzene and methanol

91.6 Ų

log Kow = 4.57 (est)

309 °C

Moderately soluble in toluene|In water, 5.4X10-3 mg/L at 25 °C (est)

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: -20 °C|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 = 5.4X10-11 cu cm/molec-sec at 25 °C (est)

Observe all federal, state, and local environmental regulations. 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.|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.|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 1,6-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, 1972-PRESENT. (vol 46, 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.[Available at: http://monographs.iarc.fr/index.php]|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) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of No ember 26, 2010: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s012iq.pdf]

|Danger|H350 (100%): May cause cancer [Danger 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.|Warning|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 N99 (US) or type P2 (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).|Hand protection: Handle with gloves. Eye protection: Safety glasses. Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substance at the work place.

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 dust. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods for cleaning up: Pick up and arrange disposal without creating dust. 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/

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|Avoid exposure - obtain special instructions before use. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.|For more Preventive Measures (Complete) data for 1,6-Dinitropyrene (14 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/

1,6-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 1,6-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 1,6-nitropyrene in emission particulates from diesel (1986 model) and gasoline engine (1989 model) vehicles was reported as 0.39 and 0.43 pmol/mg particulate, respectively(2). Exhaust particle concentrations of 0.81-1.2 and 0.033-0.6 mg/kg have been reported for heavy-duty and light-duty diesel engines, respectively(3). Dinitropyrenes are emitted by kerosene heaters at a rate of 0.2 ng/hr; a mixture of 1,6- and 1,8-dinitropyrene was reported at 3.25 mg/kg particulate extract. 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(4).

URBAN/SUBURBAN: 1,6-Dinitropyrene was detected in air samples from Baltimore, MD and Fort Meade, MD, during January 24-27 and July 15-23, 2001. Mean concentrations in Baltimore and Fort Meade were <1.0 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 3.16 (spring, 2.78 (summer), 4.29 (autumn), and 5.87 (winter), with an annual mean of 4.03 mol/cu m. A maximum of 28.8 to a minimum of 1.3 mol/cu m during the time frame of 9-11AM and 1-3PM, respectively, was reported(2). The mean concentration of 1,6-dinitropyrene 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 0.0036 and <0.006 ug/g particulates, respectively(3).|RURAL/REMOTE: For 1,6-dinitropyrene, mean concentrations of 0.0049 and 0.0081 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 1,6-dinitropyrene were 14.98-96.0 pg/cu m (indoors) and 0.06-9.9 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 0.3-5.2 pg/cu m and the overall indoor emission average was 52.1 pg/cu m(1). The mean concentration of 1,6-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) were reported as 0.046 and 0.0410 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.

1,6-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 1,6-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 1,6-dinitropyrene is expected to be immobile in soil(SRC). Volatilization of 1,6-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). 1,6-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 1,6-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 were not available(SRC, 2010).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,6-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 1,6-dinitropyrene may be removed from the air by wet or dry deposition(SRC). 1,6-Dinitropyrene did absorb light at wavelengths at 312 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC).

1,6-Dinitropyrene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). 1,6-Dinitropyrene did absorb light at wavelengths at 312 nm(2), and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 480 was calculated in fish for 1,6-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 1,6-dinitropyrene can be estimated to be 1.4X10+5(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,6-dinitropyrene is expected to be immobile mobility in soil.

The Henry's Law constant for 1,6-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 1,6-dinitropyrene is expected to be essentially nonvolatile from water surfaces(2). 1,6-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 1,6-dinitropyrene may occur through inhalation and dermal contact with this compound at workplaces where 1,6-dinitropyrene is formed. The most likely pathway by which the general public is exposed to 1,6-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.)

Under argon atmosphere, rat and dog liver cytosol catalyzed the reduction of 1,6-dinitropyrene to 1-amino-6-nitropyrene and 1,6-diaminopyrene ... 1-acetylamino-6-nitropyrene was also detected as a metabolite ...|This study was aimed at monitoring N-acetyltransferase activities of continuous cell lines, which differ in their sensitivity to the toxic effects of nitroaromatic compounds. Transferase activities were measured toward the acetyl acceptors sulfamethazine and p-aminobenzoic acid in partially purified preparation of cytosols. Cell lines such as hamster V79, BHK, rat hepatoma H4IIEC3G- or fibroblast 208F, which are sensitive to 1,6-dinitropyrene (1,6-DNP), possess high transferase activities ranging from 120-270 nmol/min x mg protein. In contrast, human lung cells NCI-H322, mouse and rat hepatoma cells BW1J and H5, respectively, which are resistant to 1,6-DNP contain no or low transferase activity of less than 15 nmol/min x mg. There was no apparent correlation between 1,6-DNP sensitivity and acetyltransferase levels in a few cell lines, e.g. rat hepatoma HTC, 2sFou and 5L, which express intermediate transferase activities ranging from 25-50 nmol/min x mg protein. The results suggest that acetylation is an essential step in activating 1,6-DNP to toxic products in mammalian cells.|Dinitropyrenes are mutagenic environmental pollutants. Of these compounds, 1,6-dinitropyrene is a potent tumorigen while 1,3-dinitropyrene appears to be weakly or non-tumorigenic. Two-electron reduction of dinitropyrenes yields nitro-nitrosopyrenes, which have been shown previously to be the major aerobic metabolites of these compounds in vitro. Further reduction of nitrosopyrenes is required for their activation to a DNA-reactive N-hydroxylamines. In this work, 1-nitro-3-nitrosopyrene was synthesized and the electrochemical and enzyme-catalyzed reduction of 1-nitro-3-nitrosopyrene has been compared with that of 1-nitro-6-nitrosopyrene. As determined by cyclic voltammetry, the reduction potentials of 1-nitro-3-nitrosopyrene, 1-nitro-6-nitrosopyrene and their parent dinitropyrenes were similar, although 1-nitro-3-nitrosopyrene did have a slightly more negative cathodic peak potential than the other three compounds. The NADPH-mediated reduction of 1-nitro-6-nitrosopyrene to intermediates which reduce succinoylated cytochrome c was faster than that of 1-nitro-3-nitrosopyrene. In the presence of rat liver microsomes or cytosol, the reduction of 1-nitro-6-nitrosopyrene was faster than that of 1-nitro-3-nitrosopyrene. These differences in the rates of nitro-nitrosopyrene reduction may be one factor contributing to the lower tumorigenic potential of 1,3-dinitropyrene relative to 1,6-dinitropyrene.|1-Nitro-6-nitrosopyrene, 1-amino-6-nitropyrene and 1,6-diaminopyrene were detected as metabolites in rat mammary gland cytosol incubated with 1,6-dinitropyrene under anaerobic conditions.|For more Metabolism/Metabolites (Complete) data for 1,6-Dinitropyrene (8 total), please visit the HSDB record page.

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 (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/ The effects of 1,6-dinitropyrene (1,6-DNP) on the fidelity of cell division were studied in the transformed human fibroblast cell line MRC5VA. Over a dose range of 0.1-10 ug/mL of 1.6-DNP, ... significant increases /were observed/ in the levels of abnormal division stages, associated with damage to the spindle apparatus of the cell. Qualitative changes in spindle morphology and a quantitative decrease in pole-to-pole spindle length were also observed with increasing doses of 1.6-DNP. Such changes in the size and morphology of the spindle corresponded with an accumulation of cells blocked at metaphase. The presence of catalase did not modify the response, suggesting that the effects on the spindle apparatus and cell division were not caused by the generation of radicals but by the direct action of 1,6-DNP.|/GENOTOXICITY/ The ability of 1,6-dinitropyrene to induce chromosome damage in peripheral human lymphocyte cultures has been demonstrated. Low levels of clastogenic activity were detected following 3-hr treatments with 1,6-dinitropyrene in the presence of a rat-liver cytosol fraction. The clastogenic activity reached a peak at a concentration of 1.25 ug/mL of 1,6-dinitropyrene after which the frequency of aberrations decreased. This unusual genotoxic dose response is similar to that found previously in yeast and rat-liver cells. 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.|For more Human Toxicity Excerpts (Complete) data for 1,6-Dinitropyrene (8 total), please visit the HSDB record page.

1,6-dinitropyrene

Health Hazards -> Carcinogens, Mutagens