1-Methylpyrene

216.28

216.28

219-178-8

AB8420OXQA

90776

DTXSID0025654

Plates (in ethanol) or brown-green powder

2902909090

0

5.48 (est)

Plates (in ethanol) or brown-green powder. (NTP, 1992)

1.213 g/cu cm

70-71 °C

372 °C

178.9±12.8 °C

1.816

DMSO: soluble

Keep container tightly closed in a dry and well-ventilated place. Light sensitive. Storage class (TRGS 510): Non Combustible Solids.

1.6X10-6 mm Hg at 25 deg C (est)

Henry's Law constant = 3.2X10-6 atm-cu m/mole at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.3X10-10 cu cm/molecule-sec at 25 °C (est)

Insoluble in water.

Hydrocarbons, Aromatic

Vigorous reactions, sometimes amounting to explosions, can result from the contact between aromatic hydrocarbons, such as 1-METHYL PYRENE, and strong oxidizing agents. They can react exothermically with bases and with diazo compounds. Substitution at the benzene nucleus occurs by halogenation (acid catalyst), nitration, sulfonation, and the Friedel-Crafts reaction. This chemical may be sensitive to prolonged exposure to light.

92.3 kJ/mol

NONH for all modes of transport

3

36/37/38

26-36

UR2460000

Xi

Stable under recommended storage conditions.

P280-P304 + P340 + P312-P305 + P351 + P338-P337 + P313

H315-H319-H335

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

Strong oxidizers.

Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 42 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315: Causes skin irritation [Warning Skin corrosion/irritation]

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material under ambient temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)|Eye/face protection: 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).|Skin protection: Handle with gloves.|Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|For more Personal Protective Equipment (PPE) (Complete) data for 1-Methylpyrene (6 total), please visit the HSDB record page.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: 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: 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.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: 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: Do not let product enter drains.|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|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.|For more Preventive Measures (Complete) data for 1-Methylpyrene (8 total), please visit the HSDB record page.

Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 0.2 mg/cu m. /Coal tar pitch volatiles (benzene soluble fraction), anthracene, BaP, phenanthrene, acridine, chrysene, pyrene/

Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 0.1 mg/cu m (cyclohexane-extractable fraction). /Coal tar pitch volatiles/|NIOSH considers coal tar pitch volatiles to be potential occupational carcinogens. NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible concentration. /Coal tar pitch volatiles/

The concentration of 1-methylpyrene in diluted heavy-duty diesel exhausts was determined to average 0.75 ug/km in particulate matter(1). The average concentration of 1-methylpyrene from the stack of a coal preparation plant was determined to be 0.45 ug/sample(2). The average concentration of 1-methylpyrene detected as coal combustion byproducts and tire crumb combustion byproducts was determined to be 49.1 ug/g coal and 62.33 ug/g tire, respectively(3). 1-Methylpyrene has been detected in both gasoline or diesel exhaust(4). Lawn mower exhaust emissions contained 1-methylpyrene(5).

SEDIMENT: 1-Methylpyrene was qualitatively identified in sediment collected near various industrial emission sources on the Swedish Baltic Coast(1). 1-Methylpyrene was positively identified in sediment from the Black River, Ohio, concentration not reported(2). Sediments collected from Saudafjorden, West Norway in October 1976 contained 0.2 to 513.5 ppb 1-methylpyrene, depending upon depth(3). 1-Methylpyrene was identified in crude sediment (from St. John's Harbour, Canada) and purified sediment at concentrations of 1.6 and 6.2 ng/g, respectively(4). 1-Methylpyrene levels of 0.6-27 ng/g dry wt were detected in sediments from 19 depositional areas along the lower Missouri River in 2002(5).|SOIL: Coastal sandy loam soil contaminated with coal tar taken from a site in southern New Jersey at a depth of 180 cm below the surface was found to contain 36.6 ug/g 1-methylpyrene/methylfluoranthene(1). 1-Methylpyrene was qualitatively detected in soil samples collected from a former gasworks site in Stockholm, Sweden(2).

URBAN/SUBURBAN: Airborne aerosol samples taken in England, France, Scotland, and Norway from November 1975 to February 1976 contained a 1-methylpyrene range of 9 to 147 ng/1000 cu m(1). The concentration of 1-methylpyrene in urban air collected from Kokkola, Finland from 13-17 May and from 18-23 November was determined to range from <0.1 to 0.3 ng/cu m(2). 1-Methylpyrene has been identified in airborne particles collected in Southeast Germany, concentration not reported(3). Methylpyrene was identified in the air particulate matter collected from the lightly industrialized urban area of Christchurch, New Zealand, concentration not reported(4). Atmospheric air with particle samples (PM2.5) collected three northeastern US sites (Boston, MA, Rochester, NY Quabbin Resevoir, MA) contained 1-methylpyrene concentrations of 180, 31 and 15 pg/cu m respectively(5). Outdoor residential air sampled during Feb and Mar 2003 at Hagfors, Sweden had a 1-methylpyrene concentration range of <0.05 to 0.45 ng/cu m(6).|INDOOR AIR: The concentration of 1-methylpyrene in the air of three different types of saunas in Finland was determined to have an average gaseous phase concentration of 2.48 ug/cu m and an average particulate phase concentration of 3.52 ug/cu m(1). Indoor air in 13 Swedish homes using wood-burning appliances had 1-methylpyrene levels of <0.05-0.35 ng/cu m while 10 home not using wood-burning had levels of <0.05-0.16 ng/cu m(2).|SOURCE DOMINATED: Air monitoring near aircraft exhaust from taxiing and on/off loading of aircraft at the Savannah, GA Air National Guard base in 1999 detected 1-methylpyrene concentrations of 2.7-14.6 ng/cu m(1).

1-Methylpyrene was qualitatively detected in food packaging wax(1). The concentration of 1-methylpyrene in lubricating oil from three different vehicles fueled with gasoline, diesel, gas, and methanol/gasoline was determined to be 31, 0.59, 1.6, and 100 ppm, respectively(2). The concentration of 1-methylpyrene in eight diesel fuels ranged from 0.021 to 4.6 mg/L. The concentration of 1-methylpyrene in diesel fuel and diesel exhaust from different vehicles ranged from 9.0 to 5200 ug/km and 0.47 to 6.4 ug/km, respectively(3). 1-Methylpyrene was identified in crude oil and purified oil at concentrations of 63 ug/g and 48 ug/g, respectively(4). The concentration of 1-methylpyrene in mineral oil was determined to be 7.8 ug/10 g(5). The concentration of 1-methylpyrene in oil from a spill in Vassa Archipelago, Finland was determined to be 122.9 ug/kg(6). Methylpyrene was identified as a combustion product of polyethylene(7). The 1-methylpyrene concentrations in a Swedish diesel fuel and a reference diesel fuel were 0.1 and 50.3 mg/L respectively(8).|1-Methylpyrene has been identified as a constituent of tobacco smoke(1). The level of 1-methylpyrene in charcoal smoke and in charcoal + meat smoke from charcoal grilling was determined to be 0.89 ug/kg and 4.4 ug/kg, respectively(2). The concentration of 1-methylpyrene in mesquite smoke and hickory smoke was determined to be 27 ug/kg and 18 ug/kg, respectively(3).

IDENTIFICATION AND USE: 1-Methylpyrene (1-MP) is a polynuclear aromatic hydrocarbon. HUMAN EXPOSURE AND TOXICITY: A Chinese hamster V79-derived cell line expressing both human CYP2E1 and human SULT1A1 was used to investigate the ability of 1-MP to induce cytotoxicity, micronuclei and Hprt gene mutations. 1-MP induced micronuclei in V79-hCYP2E1-hSULT1A1 cells in a concentration-dependent manner; however, it was inactive in V79 cells. It caused an increase in Hprt mutant frequency in V79-hCYP2E1-hSULT1A1 cells, bur not in V79 cells. The results suggest that human CYP2E1 and SULT1A1 cooperate to activate 1-MP and cause genotoxicity in mammalian cells. 1-methylpyrene or perylene, individually or when combined, significantly upregulated IL-1alpha and IL-6 secretion from human skin keratinocytes. 1-methylpyrene also exerted a cytotoxic effect on human keratinocytes. ANIMAL STUDIES: 1-MP was inactive in Chinese hamster V79-derived cell line without metabolic activation. Modification of adenine residues by 1-MP caused termination of DNA replication by E. coli DNA polymerase I (Klenow fragment) in vitro at the position opposite the MP adduct and at the preceding base.

Methylpyrenes, including 1-methylpyrene and 2-methylpyrene, have been detected in crude oils and in sedimentary rock extracts with Early Paleozoic and Cenozoic origins(1).

1-Methylpyrene's production and use as a fluorescent probe for the determination of micellar aggregation number(1) may result in its release to the environment through various waste streams(SRC).|1-Methylpyrene is one of many polycyclic aromatic hydrocarbons (PAH) that occur as ubiquitous products of incomplete combustion of fossil fuels, wood, diesel oils and gasoline fuels(1). 1-Methylpyrene's presence in exhaust from these combustion sources will release the compound directly to the environment(SRC). 1-Methylpyrene occurs in tobacco smoke(2), charcoal smoke, and meat smoke from charcoal grilling(3). 1-Methylpyrene has been identified as a constituent of gasoline and diesel fuels(4,5).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 89,000(SRC), determined from a structure estimation method(2), indicates that 1-methylpyrene is expected to be immobile in soil(SRC). Volatilization of 1-methylpyrene from moist soil surfaces may occur given an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(2). However, adsorption to soil is expected to attenuate volatilization(SRC). 1-Methylpyrene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). PAHs with four or more rings, such as 1-methylpyrene, are generally expected to be resistant to biodegradation(3). By analogy to pyrene, biodegradation is expected to occur slowly in soils, with estimated half-lives ranging from several weeks to years(4,5). Faster biodegradation rates occur with exposure to acclimated microbes(6). Degradation of 1-methylpyrene during a bioslurry method reached 38% after 29 days of incubation using a contaminated soil from a former gasworks(7). By analogy to pyrene which absorbs strongly at wavelengths >290 nm(8), 1-methylpyrene is expected to be susceptible to direct photolysis on surfaces exposed to sunlight(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 89,000(SRC), determined from a structure estimation method(2), indicates that 1-methylpyrene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 17 and 130 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is >10 years if adsorption is considered(4). According to a classification scheme(5), an estimated BCF of 1920(SRC), from an estimated log Kow of 5.48(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). However, 1-methylpyrene may not bioconcentrate in aquatic organisms which contain microsomal oxidase, such as some fish, as this enzyme enables the rapid metabolism of certain polycyclic aromatic hydrocarbons(6). A measured fish biotransformation half-life of 2.08 days has been reported for the analogous pyrene(7). The near surface half-life for direct photolysis of analogous pyrene in water by sunlight was measured as 0.68 hours(8) and 0.85 hours(9). PAHs with four or more rings, such as 1-methylpyrene, are generally expected to be resistant to biodegradation(10). By analogy to pyrene, biodegradation is expected to occur slowly in soils, with estimated half-lives ranging from several weeks to years(11,12). Faster biodegradation rates occur with exposure to acclimated microbes(13). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(3).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1-methylpyrene, which has an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 1-methylpyrene is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2.9 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase 1-methylpyrene may be removed from the air by wet and dry deposition(SRC). By analogy to pyrene which absorbs strongly at wavelengths >290 nm(3,4), 1-methylpyrene is expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 1-methylpyrene with photochemically-produced hydroxyl radicals has been estimated as 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.9 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Methylpyrenes (including 1-methylpyrene) have practically identical UV absorption spectra as pyrene(2). Pyrene absorbs strongly at wavelengths >290 nm(3,4) and therefore, 1-methylpyrene is expected to be susceptible to direct photolysis by sunlight(SRC). Approximately 6% photolytic degradation occurred when pyrene was adsorbed to a fly ash substrate and exposed to natural sunlight for 5 hours(5). The near surface half-life for direct photolysis of pyrene in water by sunlight was measured as 0.68 hours(6) and 0.85 hours(7). The photolysis half-life of pyrene on spruce needle surfaces exposed to full sunlight in Munich, Germany in July 2001 was 37 hours(8). 1-Methylpyrene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(9).

An estimated BCF of 1920 was calculated in fish for 1-methylpyrene(SRC), using an estimated log Kow of 5.48(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC). However, 1-methylpyrene may not bioconcentrate in aquatic organisms which contain microsomal oxidase, such as fish, as this enzyme enables the rapid metabolism of certain polycyclic aromatic hydrocarbons(3). A measured fish biotransformation half-life of 2.08 days has been reported for the analogous compound pyrene(4).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1-methylpyrene can be estimated to be 89,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1-methylpyrene is expected to be immobile in soil.

The Henry's Law constant for 1-methylpyrene is estimated as 3.2X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This value indicates that 1-methylpyrene is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the estimated volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as approximately 17 days(SRC). The estimated volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as approximately 130 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is >10 years if adsorption is considered and 189 days if adsorption is ignored(3). 1-Methylpyrene's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 1-Methylpyrene is not expected to volatilize from dry soil surfaces based on an estimated vapor pressure of 1.6X10-6 mm Hg(SRC), determined from a fragment constant method(1).

SURFACE WATER: 1-Methylpyrene was detected in waters collected from the Keating Coral Reef in southern Taiwan during 2006 and 2007 sampling at levels of roughly 0.1-0.5% of total PAHs detected(1). Methylpyrene concentrations ranged from about 3 to 100 ng/L in six stations located in the Guanabara Bay Basin, Rio de Janeiro, Brazil, sampled from September 2011 to August 2012(2).

1-Methylpyrene was found in the following Finnish fats (ug/kg): butter/vegetable oil mixture (0.03), cooking margarines (0.89), table margarines (0.40), sunflower oil (0.02), cold pressed sunflower oil (3.0), cold pressed corn oil (0.32), olive oil (0.22), soybean oil (1.3), and coconut fat (3.0)(1). The concentration of 1-methylpyrene in lettuce grown at varying distances from a highway in Sweden was determined to range from 0.7 to 2.8 ug/kg fresh weight(2). The concentration of 1-methylpyrene in a grilled mesquite wood beef patty 70% lean, 80% lean, and 90% lean was determined to be 4, 1, and 1 ug/kg. The concentration of 1-methylpyrene in a grilled hardwood charcoal beef patty 70% lean was determined to be 3 ug/kg(3). 1-Methylpyrene was determined to have a concentration range of 0.05 to 0.82 ug/kg fresh wt in 23 lettuce samples cultivated in private gardens in southern Finland in 1984(4).

Occupational exposure to 1-methylpyrene may occur through inhalation and dermal contact with this compound at workplaces where 1-methylpyrene is produced as a product of incomplete combustion of fossil fuels. Monitoring data indicate that the general population may be exposed to 1-methylpyrene via inhalation of ambient air, inhalation of tobacco smoke, ingestion of char-broiled or smoked food and dermal contact with particulate matter resulting from combustion(SRC). Occupational and general population exposure to PAHs, such as 1-methylpyrene, generally occurs as a mixture(1). PAHs, such as 1-methylpyrene, can occur in foods that are char-broiled(1) or smoked(2). The concentration of 1-methylpyrene in the atmosphere of an aluminum anode plant in Soderberg, Norway ranged from 0.02 to 0.5 ug/cu m and in the atmosphere of a vertical pin plant ranged from 0.09 to 1.7 ug/cu m(3).

Alkyl-substituted polycyclic aromatic hydrocarbons may be metabolized to highly reactive benzylic sulfuric acid esters via benzylic hydroxylation and subsequent sulfonation. We have studied the benzylic hydroxylation of 1-methylpyrene (MP), a hepatocarcinogen in rodents, and 1-ethylpyrene (EP), whose benzylic hydroxylation would produce a secondary alcohol (alpha-HEP), in contrast to the primary alcohol (alpha-HMP) formed from MP. The hydrocarbons were incubated with hepatic microsomal preparations from humans and rats, as well as with V79-derived cell lines engineered for the expression of individual cytochrome P450 (CYP) forms from human (1A1, 1A2, 1B1, 2A6, 2E1, 3A4) and rat (1A1, 1A2, 2B1). All microsomal systems and CYP-expressing cell lines used, but not CYP-deficient V79 cells, showed biotransformation of both hydrocarbons. Formation of the benzylic alcohol was detected in each case. alpha-HMP and its oxidation product, 1-pyrenylcarboxylic acid (COOH-P), accounted for a major part of the total amount of the metabolites formed from MP in the presence of human liver microsomes (38-64%) and cells expressing human 3A4, 2E1 or 1B1 (80-85%). Likewise, cells expressing human 1A1 showed a higher contribution of alpha-HMP and COOH-P to the total metabolites (45%) than cells expressing the orthologous enzyme of the rat (3%). EP was metabolized at a higher rate and with modified regioselectivity compared with MP, although omega-hydroxylation of the side chain was not detected with the cell lines and only accounted for a small percent of the biotransformation by the microsomal preparations. The highest contributions of alpha-HEP to the total metabolites from EP were detected with the cells expressing human 1A1, 1B1 and 3A4 (38-51%). alpha-HEP accounted for 16% of the metabolites formed in the presence of human hepatic microsomes. Thus, benzylic hydroxylation is a major initial step in the metabolism of MP and EP. This pathway appears to be even more important in humans than in rats. Previously, we had shown that the second step of the activation, the sulfonation of alpha-HMP and alpha-HEP, is also efficiently catalysed by various forms of human sulfotransferases.|1-Methylpyrene, an alkylated polycyclic aromatic hydrocarbon and environmental carcinogen, is activated by side-chain hydroxylation to 1-hydroxymethylpyrene (1-HMP) and subsequent sulfo conjugation to the DNA-reactive 1-sulfooxymethylpyrene. In addition to the bioactivation, processes of metabolic detoxification and transport greatly influence the genotoxicity of 1-methylpyrene. For a better understanding of 1-HMP detoxification in vivo we studied urinary and fecal metabolites in rats following intraperitoneal doses of 19.3 mg 1-HMP/kg body weight (5 rats) or the same dose containing 200?Ci [(14)C]1-HMP/kg body weight (2 rats). After 48h, 48.0% (rat 1) and 29.1% (rat 2) of the radioactivity was recovered as 1-HMP in the feces. Six major metabolites were observed by UV and on-line radioactivity detection in urine samples and feces after HPLC separation. The compounds were characterized by mass spectrometry, (1)H NMR and (1)H-(1)H COSY NMR spectroscopy, which allowed assigning tentative molecular structures. Two prominent metabolites, 1-pyrene carboxylic acid (M-6) and the acyl glucuronide of 1-pyrene carboxylic acid (M-5) accounted for 17.7% (rat 1) and 25.2% (rat 2) of the overall radioactive dose. Further, we detected the acyl glucuronide of 6-hydroxy-1-pyrene carboxylic acid (M-1) and 8-sulfooxy-1-pyrene carboxylic acid (M-3) together with two regioisomers of M-3 (M-2 and M-4) differing in position of the sulfate group at the pyrene ring. In urine samples, the radioactivity of 1-pyrene carboxylic acid and its five derivatives amounted to 32.4% (rat 1) or 45.5% (rat 2) of the total [(14)C]1-HMP dose.|Transformation of nonsubstituted and alkyl-substituted polycyclic aromatic hydrocarbons (PAHs) by the benthic invertebrate Nereis diversicolor was compared in this study. Pyrene and 1-methylpyrene were used as model compounds for nonsubstituted and alkyl-substituted PAHs, respectively. Qualitative and quantitative analyses of metabolites and parent compounds in worm tissue, water, and sediment were performed. Transformation of 1-methylpyrene generated the benzylic hydroxylated phase I product, 1-pyrenecarboxylic acid that comprised 90% of the total metabolites of 1-methylpyrene, and was mainly found in water extracts. We tentatively identified 1-methylpyrene glucuronides and 1-carbonylpyrene glycine as phase II metabolites not previously reported in literature. Pyrene was biotransformed to 1-hydroxypyrene, pyrene-1-sulfate, pyrene-1-glucuronide, and pyrene glucoside sulfate, with pyrene-1-glucuronide as the most prominent metabolite. Transformation of 1-methylpyrene (21% transformed) was more than 3 times as efficient as pyrene transformation (5.6% transformed). Because crude oils contain larger amounts of C?-C?-substituted PAHs than nonsubstituted PAHs, the rapid and efficient transformation of sediment-associated 1-methylpyrene may result in a high exposure of water-living organisms to metabolites of alkyl-substituted PAHs, whose toxicities are unknown. ...|The common polycyclic aromatic hydrocarbon 1-methylpyrene is hepatocarcinogenic in the newborn mouse assay. In vitro studies showed that it is metabolically activated via benzylic hydroxylation and sulphation to a reactive ester, which forms benzylic DNA adducts, N(2)-(1-methylpyrenyl)-2'-deoxyguanosine (MPdG) and N(6)-(1-methylpyrenyl)-2'-deoxyadenosine (MPdA). Formation of these adducts was also observed in animals treated with the metabolites, 1-hydroxymethylpyrene and 1-sulphooxymethylpyrene (1-SMP), whereas corresponding data are missing for 1-methylpyrene. In the present study, we treated mice with 1-methylpyrene and subsequently analyzed blood serum for the presence of the reactive metabolite 1-SMP and tissue DNA for the presence of MPdG and MPdA adducts. We used wild-type mice and a mouse line transgenic for human sulphotransferases (SULT) 1A1 and 1A2, males and females. All analyses were conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry, for the adducts with isotope-labelled internal standards. 1-SMP was detected in all treated animals. Its serum level was higher in transgenic mice than in the wild-type (p < 0.001). Likewise, both adducts were detected in liver, kidney and lung DNA of all exposed animals. The transgene significantly enhanced the level of each adduct in each tissue of both sexes (p < 0.01-0.001). Adduct levels were highest in the liver, the target tissue of carcinogenesis, in each animal model used. MPdG and MPdA adducts were also observed in rats treated with 1-methylpyrene. Our findings corroborate the hypothesis that 1-SMP is indeed the ultimate carcinogen of 1-methylpyrene and that human SULT are able to mediate the terminal activation in vivo.|For more Metabolism/Metabolites (Complete) data for 1-Methylpyrene (6 total), please visit the HSDB record page.

1.29 Days|92.00 Days

ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits acrid smoke and fumes. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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 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. /Aromatic hydrocarbons and related compounds/|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 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 L of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/|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 if necessary ... . Start IV administration of D5W TKO /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. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aromatics hydrocarbons and related compounds/

/GENOTOXICITY-DNA ADDUCTS/ The procarcinogen 1-methylpyrene is activated by hepatic enzymes via 1-hydroxymethylpyrene to 1-sulfooxymethylpyrene (1-SMP), a highly reactive and mutagenic metabolite. Previously, high levels of 1-SMP DNA adducts were observed in rat kidneys after intraperitoneal administration of 1-hydroxymethylpyrene or 1-SMP. This study examined whether organic anion transporters (OAT) that are expressed at the basolateral membrane of proximal tubule cells are involved in uptake of SMP. Human epithelial kidney (HEK293) cells that stably express human OAT1 (hOAT1) and hOAT3 were used. Stable isomers of 1-SMP, (2-SMP and 4-SMP) competitively inhibited the uptake of characteristic substrates p-aminohippurate for hOAT1 and estrone sulfate for hOAT3. Both inhibitors exhibited high affinity for hOAT1 (K(i) = 4.4 uM for 2-SMP; K(i) = 5.1 uM for 4-SMP) as well as hOAT3 (K(i) = 1.9 uM for 2-SMP; K(i) = 2.1 uM for 4-SMP). The uptake rate of 4-SMP (at a concentration of 10 uM) by hOAT1- and hOAT3-expressing cells was 3.0 and 1.6 times higher, respectively, than in control cells. Uptake of the reactive isomer 1-SMP was investigated using as the end point the level of DNA adducts that were formed in the cells. After exposure to 1-SMP (10 uM), the DNA adduct level was 4.6 and 3.0 times higher in hOAT1- and hOAT3-expressing cells, respectively, than in control cells. The enhanced DNA adduct formation in hOAT-expressing cells was abolished in the presence of the OAT inhibitor probenecid. This study indicates that OAT can mediate the basolateral uptake of reactive sulfuric acid esters into proximal tubule cells and thereby participate in kidney cell damage by these compounds.|/ALTERNATIVE and IN VITRO TESTS/ The cytotoxic effects of two polycyclic aromatic hydrocarbons (PAH) (1-methylpyrene and perylene) were investigated on human skin keratinocytes. Normal human keratinocytes were cultured in the presence of various concentrations of 1-methylpyrene and perylene either alone or in combination. Following incubation, keratinocyte adhesion, viability, proliferation, colony-forming efficiency, and apoptosis/necrosis level were examined. The effects of PAH on wound healing were also determined in vitro using a scrape-wound healing assay on epidermis-like tissue. In addition, the inflammatory cell response to PAH insult was examined through interleukin-1 (IL-1) alpha and interleukin-6 (IL-6) secretion. Each individual PAH significantly decreased keratinocyte adhesion and viability in a concentration-dependent manner, which was associated with a reduced ability of keratinocytes to proliferate and form colonies. When PAH were combined, a greater effect on keratinocyte adhesion, viability, and proliferation was noted. Decreased cell proliferation/colony-forming efficiency was accompanied by increased cell apoptosis following incubation with either PAH. This effect was enhanced by the inhibitory influence on keratinocyte migration, as assessed by culture scratching. Each PAH also exerted a significant effect on keratinocyte immune functions by modulating the secretion of inflammatory mediators. Indeed, 1-methylpyrene or perylene, individually or when combined, significantly upregulated IL-1alpha and IL-6 secretion. This effect was greater and was concentration dependent when the PAH combination was used. Overall results indicate that 1-methylpyrene and perylene exerted a cytotoxic effect on human keratinocytes. ...

1-methylpyrene

The alkylated polycyclic aromatic hydrocarbon 1-methylpyrene is a carcinogen in rodents and has been detected in various environmental matrices and foodstuffs. It is activated metabolically by benzylic hydroxylation to 1-hydroxymethylpyrene followed by sulfoconjugation to yield electrophilic 1-sulfooxymethylpyrene (1-SMP) that is prone to form DNA adducts. An LC-MS/MS method using multiple reaction monitoring (MRM) of fragment ions has been developed for specific detection and quantification of N (2)-(1-methylpyrenyl)-2'-deoxyguanosine (MP-dGuo) and N (6)-(1-methylpyrenyl)-2'-deoxyadenosine (MP-dAdo) formed in DNA in the presence of 1-SMP. DNA samples were spiked with stable isotope internal standards, [(15)N 5, (13)C 10]MP-dGuo and [(15)N 5]MP-dAdo, followed by enzymatic digestion to 2'-deoxynucleosides and solid-phase extraction to remove unmodified 2'-deoxynucleosides prior to analysis by LC-MS/MS. The limits of detection were 10 fmol of MP-dGuo and 2 fmol of MP-dAdo or three molecules of MP-dGuo and 0.6 molecules of MP-dAdo per 10 (8) 2'-deoxynucleosides using 100 mug of herring sperm DNA as the sample matrix. The method was validated with herring sperm DNA reacted with 1-SMP in vitro. Hepatic DNA was analyzed from rats that were dosed intraperitoneally with 9.3 mg 1-SMP per kg body weight and killed after various time periods. Levels of MP-dGuo and MP-dAdo in rat liver were found to increase, reaching their maxima at approximately 3 hr, and then decrease over time. A good correlation was observed between the results obtained using LC-MS/MS and MRM and those from (32)P-postlabeling. MRM allowed the more precise quantification of specific 1-MP adducts, in addition to a time reduction of the analysis when compared with (32)P-postlabeling.