Benzo[g]chrysene

278.35

278.35

E7MQ64XU75

DTXSID40173267

Needles from acetic acid

2902909090

0

6.70 (est)

1.232 g/cu cm

114.5-115 °C

525℃

265℃

1.8120 (estimate)

In water, 1.03X10-2 mg/L at 25 deg C (est)

2.03X10-8 mm Hg at 25 deg C (est)

Flammable; burning produces irritating fumes

Henry's Law constant = 1.23X10-7 atm-cu m/mol at 25 °C (est)

Constant pressure heat capacity of gas: 286.1 kJ/mol at 298.15 K|Hydroxyl radical reaction rate constant = 5.0X10-11 cu cm/molec-sec at 25 °C (est)

Ventilated, low temperature and dry

P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501

H315

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.

Strong oxidizers.

|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|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Respirator Recommendations: At concentrations above the NIOSH REL, or where there is no REL, at any detectable concentration: /Coal tar pitch volatiles/[Table#4731]|Respirator Recommendations: Escape conditions: /Coal tar pitch volatiles/[Table#4732]

The worker should wash daily at the end of each work shift, and prior to eating, drinking, smoking, etc. /Coal tar pitch volatiles/|Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premises. /Coal tar pitch volatiles/|SRP: Contaminated protective clothing should be segregated in a manner such that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.

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/

Benzo(g)chrysene was found in mineral oil, concentration unknown(1). The compound has been identified as a constituents of tobacco smoke(2,3). Benzo(g)chrysene has been found to occur in water, air and gasoline or diesel exhaust, concentrations unknown(3).

IDENTIFICATION AND USE: Benzo(g)chrysene (B(g)C) is a polynuclear aromatic hydrocarbon (PAH). It is not produced commercially, and it is used mostly in biochemical research. PAHs are ubiquitous in combustion products of organic matter, including cigarette smoke. HUMAN EXPOSURE AND TOXICITY: Four major DNA adducts were detected in human fibroblasts. ANIMAL STUDIES: B(g)C is a moderate carcinogen. B(g)C is metabilically activated in mouse skin and forms DNA adducts. The adenine adducts accounted for 64% of the total major adducts formed in B[g]C-treated mouse skin. B(g)C metabolites formed also DNA adducts in Chinese hamster V79 cell.

Benzo(g)chrysene is one of many polycyclic aromatic hydrocarbons (PAH), a group of chemicals that are formed during the incomplete burning of coal, oil, gas, wood, garbage, or other organic substances. PAHs generally occur as complex mixtures, for example as part of combustion products such as soot, not as single compounds. PAHs occur naturally in volcanoes and forest fires. They can also be found in substances such as crude oil and coal. They are found throughout the environment in the air, water, and soil(1). /Polycyclic aromatic hydrocarbons/

Polycyclic aromatic hydrocarbons (PAHs), such as benzo(g)chrysene, occur as ubiquitous products of incomplete combustion of fossil fuels, wood, diesel oils and gasoline fuels(1). PAHs generally occur as complex mixtures, for example as part of combustion products such as soot, not as single compounds. /Polycyclic aromatic hydrocarbons/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.0X10+6(SRC), determined from a structure estimation method(2), indicates that benzo(g)chrysene is expected to be immobile in soil(SRC). Volatilization of benzo(g)chrysene from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.2X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Benzo(g)chrysene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). In general, polycyclic aromatic hydrocarbons (PAHs) with four or more benzene rings do not biodegrade readily(7).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.0X10+6(SRC), determined from a structure estimation method(2), indicates that benzo(g)chrysene 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 1.2X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 1.2X10+4(SRC), from an estimated log Kow of 6.70(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. Benzo(g)chrysene 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(6). In general, polycyclic aromatic hydrocarbons(PAHs) with four or more benzene rings do not biodegrade readily(7).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzo(g)chrysene, which has an estimated vapor pressure of 2.0X10-8 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 benzo(g)chrysene 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 0.2 days(SRC), calculated from its rate constant of 5.0X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase benzo(g)chrysene may be removed from the air by wet and dry deposition(SRC). Benzo(g)chrysene contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of benzo(g)chrysene with photochemically-produced hydroxyl radicals has been estimated as 5.0X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 0.2 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Benzo(g)chrysene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Benzo(g)chrysene contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 1.2X10+4 was calculated in fish for benzo(g)chrysene(SRC), using an estimated log Kow of 6.70(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). Benzo(g)chrysene 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).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of benzo(g)chrysene can be estimated to be 2.0X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that benzo(g)chrysene is expected to be immobile in soil(SRC).

The Henry's Law constant for benzo(g)chrysene is estimated as 1.2X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that benzo(g)chrysene is expected to be essentially nonvolatile from water and moist soil surfaces(2). Benzo(g)chrysene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-8 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to benzo(g)chrysene may occur through inhalation and dermal contact with this compound at workplaces where benzo(g)chrysene is produced as a product of incomplete combustion of fossil fuels. Limited monitoring data indicate that the general population may be exposed to benzo(g)chrysene via smoking, inhalation of air and dermal contact with particulate matter resulting from combustion. (SRC)

Metabolism of polycyclic aromatic hydrocarbons in mammalian cells results in the formation of vicinal diol epoxides considered as ultimate carcinogens if the oxirane ring is located in a bay- or fjord-region of the parent compound. In the present study, individual stereoisomers of the bay-region diol epoxides of chrysene, dibenz[a,h]anthracene, and benzo[a]pyrene as well as of the fjord-region diol epoxides of benzo[c]phenanthrene, benzo[c]chrysene, and benzo[g]-chrysene have been incubated with GSH in the presence of human glutathione transferases GSTM1-1 (a mu-class enzyme) and GSTP1-1 (a pi-class enzyme). As previously shown with GSTA1-1 (an alpha-class enzyme) both M1-1 and P1-1 demonstrate considerable activity toward a number of the diol epoxides studied, although a great variation in catalytic efficiency and enantioselectivity was observed. With GSTM1-1, the bay-region diol epoxides, in particular the syn-diastereomers were in most cases more efficiently conjugated with GSH than the fjord-region analogues. GSTM1-1 demonstrated an enantioselectivity ranging from no preference (50%) to high preference (> or = 90%) for conjugation of the enantiomers with R-configuration at the benzylic position of the oxirane ring. With GSTP1-1, the enzyme demonstrated appreciable activity toward both bay- and fjord-region diol epoxides and, in most cases, a preference for the anti-diastereomers. In contrast to GSTM1-1 and as previously shown for GSTA1-1, GSTP1-1 showed an exclusive preference for conjugation of the enantiomers with R-configuration at the benzylic oxirane carbon. With both GSTM1-1 and GSTP1-1, the chemically most reactive diol epoxide, the (+)-syn-enantiomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,-10-tetrahydrobenzo[a]pyrene (BPDE), was the best substrate. As for GSTA1-1, no obvious correlation between chemical reactivity or lipophilicity of the compounds and catalytic efficiencies was observed. Molecular modeling of diol epoxides in the active sites of GSTP1-1 and -A1-1 is in agreement with the assumption, based on functional studies, that the H-site of GSTA1-1 can accommodate stereoisomers of different sizes. Further, modeling of the enantiomers of anti- and syn-BPDE in the active site of GSTP1-1 provides an explanation for the exclusive preference for the enantiomers with R-configuration at the benzylic oxirane carbon. These isomers could be snuggly fitted in the H-site close to the GSH sulfur, whereas those with opposite stereochemistry could not.|Metabolic activation of the racemic benzo[c]chrysene-trans-9,10-, benzo[g]chrysene-trans-11,12- and dibenzo[a,l]pyrene-trans-11,12-dihydrodiols to fjord region syn- and anti-dihydrodiol epoxides by microsomes of Aroclor 1254-treated Sprague-Dawley rats has been examined. Since the fjord region dihydrodiol epoxides were hydrolytically unstable under the experimental conditions, their enzymatic formation was determined by analyzing the tetraols as their products of acidic hydrolysis upon addition of perchloric acid. The various stereoisomeric tetraols formed were separated by HPLC and identified by co-chromatography with authentic tetraols, which had been prepared by acidic hydrolysis of synthetically available syn- and anti-dihydrodiol epoxides and characterized by NMR and UV spectroscopy. Under standardized conditions the acidic hydrolysis of syn-dihydrodiol epoxides of benzo[c]chrysene, benzo[g]chrysene and dibenzo[a,l]pyrene resulted in the formation of two tetraols with cis/trans ratios of 81:19, 77:23 and 80:20, respectively, whereas the anti-dihydrodiol epoxides underwent almost exclusively trans hydrolysis. The proportion of the stereoisomeric tetraols obtained from microsomal incubations indicates that all three dihydrodiols are predominantly oxidized at the adjacent olefinic double bond to the anti-diastereomers of the corresponding fjord region dihydrodiol epoxides accounting for 4-35% of the ethyl acetate-extractable metabolites. To allow quantitative assessment of the metabolites (3)H-labeled trans-dihydrodiols were synthesized by reduction of the corresponding o-quinones with sodium borotritide. Metabolic conversion of benzo[c]chrysene-trans-9,10- and dibenzo[a,l]pyrene-trans-11,12-dihydrodiol by rat liver microsomes were in a similar low range during the first 10 min of incubation (6.2 +/- 1.2 and 3.4 +/- 1.0 nmol substrate/nmol cytochrome P450/10 min, respectively), whereas the conversion of benzo[g]chrysene-trans-11,12-dihydrodiol was much higher (20.6 +/- 2.2 nmol substrate/nmol cytochrome P450/10 min). Given the strong intrinsic mutagenic and carcinogenic activity of the fjord region dihydrodiol epoxides, our data indicate that their formation, even at a relatively low level, may contribute significantly to the biological activity of the parent hydrocarbons.|Mammalian metabolism of polycyclic aromatic hydrocarbons results in the formation of vicinal diol epoxides (existing as enantiomeric pairs of two diastereomers) considered as important ultimate carcinogens if the oxirane ring is located in a bay or fjord region of the parent hydrocarbon. In the present study, individual stereoisomers of the bay region diol epoxides of chrysene, dibenz[a,h]-anthracene and benzo[a]pyrene, as well as of the fjord region diol epoxides of benzo[c]phenanthrene, benzo[c]chrysene and benzo[g]chrysene, have been incubated with glutathione (GSH) in the presence or absence of human glutathione S-transferase isoenzyme GST A1-1, a class Alpha enzyme. The formation of GSH conjugates was determined and quantified by HPLC. The results demonstrate that the GST A1-1 isoenzyme catalyzes the formation of GSH conjugates of all diol epoxides tested, although a marked variation in catalytic efficiency (>20-fold) was observed. With both bay and fjord region anti-diol epoxides a significant preference for conjugation of the enantiomer with the R configuration at the benzylic position of the oxirane ring was noted. Among the syn diastereomers of the fjord region diol epoxides a similar substrate enantioselectivity was noted, i.e. the enantiomer with the corresponding R configuration was again preferentially conjugated. In contrast, for the bay region syn-diol epoxides this substrate selectivity was reversed, resulting in a preference for the enantiomer with the S configuration. The chemically more reactive syn diastereomers were in general better substrates for GST A1-1 than the corresponding anti diastereomers. However, a comparison between different diol epoxide diastereomers revealed no obvious correlation between chemical reactivity of the compounds and catalytic efficiencies. Furthermore, no significant correlation between diol epoxide lipophilicity and catalytic efficiency was observed. It is suggested that stereochemical factors, including the size and the geometry of the aromatic ring system and the preferred conformation of the diol epoxide, are involved as the major determinant for the rate of catalysis by GST A1-1.

/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 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. /Naphthalene and Related Compounds/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat 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. Administer activated charcoal ... . /Naphthalene and Related Compounds/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Start IV administration of 0.9% saline (NS) or lactated Ringer's (LR). Adequate hydration must be maintained to prevent renal failure secondary to myoglobinuria unless signs of cerebral or pulmonary edema are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Naphthalene and Related Compounds/

/GENOTOXICITY-DNA ADDUCTS/ Benzo(g)chrysene is a widespread environmental contaminant and potent carcinogen. We have measured the formation and nucleotide excision repair of covalent DNA adducts formed by the DNA-reactive metabolite of this compound in human fibroblasts, in which expression of the p53 tumor suppressor gene could be controlled by a tetracycline-inducible promoter. Cells were exposed for 1 hr to 0.01, 0.1, or 1.2 uM (+/-)-anti-benzo(g)chrysene diol-epoxide, and DNA adducts were assessed at various post-treatment times by subjecting isolated DNA to (32)P-postlabeling analysis. Four major DNA adducts were detected, corresponding to the reaction of either the (+)- or (-)-anti-benzo(g)chrysene diol-epoxide stereoisomer with adenine or guanine. Treatment with 1.2 uM resulted in a level of 1100 total adducts/10(8) nucleotides for both p53-proficient and -deficient cells; removal of adducts was not observed in either case. In cells treated with 0.1 uM, the maximum level of total adducts at 24 hr was 150/10(8) nucleotides in p53-proficient cells and 210 adducts/10(8) nucleotides in p53-deficient cells. A concentration of 0.01 microM resulted in a maximum of 20 adducts/10(8) nucleotides in p53-proficient cells at 4 hr, but 40 adducts/10(8) nucleotides persisted in p53-deficient cells at 24 hr. Whereas there were clear differences in the time course of adduct levels in p53-proficient compared with p53-deficient cells treated with 0.1 uM or 0.01 uM, these levels did not decrease extensively over 3 days. This is likely because of the stabilization of the diol-epoxide in cells, and consequent exposure and formation of adducts for many hours after the initial treatment. Furthermore, despite minor quantitative differences, all 4 of the adducts behaved similarly with respect to the effect of p53 expression on their removal. p53 appears to minimize the appearance of benzo(g)chrysene adducts in human cells by up-regulating global nucleotide excision repair and reducing the maximum adduct levels achieved. The fact that this p53-dependent effect is noted at levels of DNA adducts that are commonly found in human tissues (i.e., <100 adducts/10(8) nucleotides) because of environmental factors such as smoking is particularly significant with respect to human carcinogenesis related to environmental exposure. /(+/-)-Anti-benzo(g)chrysene diol-epoxide, metabolite/|/GENOTOXICITY-DNA ADDUCTS/ Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in combustion products of organic matter, including cigarette smoke. Metabolically activated diol epoxides of these compounds, including benzo[a]pyrene diol epoxide (B[a]PDE), have been suggested as causative agents in the development of lung cancer. We previously mapped the distribution of B[a]PDE adducts within the p53 tumor suppressor gene (also known as TP53), which is mutated in 60% of human lung cancers, and found that B[a]PDE adducts preferentially form at lung cancer mutational hotspots (codons 154, 157, 158, 245, 248, and 273). Other PAHs may be important in lung cancer as well. Here we have mapped the distribution of adducts induced by diol epoxides of additional PAHs: chrysene (CDE), 5-methylchrysene (5-MCDE), 6-methylchrysene (6-MCDE), benzo[c]phenanthrene (B[c]PDE), and benzo[g]chrysene (B[g]CDE) within exons 5, 7, and 8 of the p53 gene in human bronchial epithelial cells. CDE exposure produced only low levels of adducts. Exposure of cells to the other activated PAHs resulted in DNA damage patterns similar to those previously observed with B[a]PDE but with some distinct differences. 5-MCDE, 6-MCDE, B[g]CDE, and B[c]PDE efficiently induced adducts at guanines within codons 154, 156, 157, 158, and 159 of exon 5, codons 237, 245 and 248 of exon 7, and codon 273 of exon 8, but the relative levels of adducts at each site varied for each compound. B[g]CDE, B[c]PDE, and 5-MCDE induced damage at codon 158 more selectively than 6-MCDE or B[a]PDE. The sites most strongly involved in PAH adduct formation were also the sites of highest mutation frequency (codons 157, 158, 245, 248, and 273). The data suggest that PAHs contribute to the mutational spectrum in human lung cancer.|/ALTERNATIVE and IN VITRO TESTS/ Polycyclic aromatic hydrocarbons (PAHs) are carcinogens with varying potencies. These compounds are metabolized to diol epoxides that react to form DNA adducts. Nucleotide excision repair is a critical cellular defense against these bulky DNA adducts which, if not repaired, can lead to mutations and the initiation of cancer. The structural features of the PAH-adducts play a role in differential repair of these adducts by the global genomic repair subpathway of nucleotide excision repair. DNA adducts derived from the PAHs containing bay-regions are repaired more rapidly than adducts derived from PAHs containing fjord-regions. We have employed the host cell reactivation assay to examine the rate of repair of these adducts in an actively transcribing gene. The pGL3 plasmid containing a luciferase gene was damaged with diol epoxides of benzo[a]pyrene (B[a]P-DE), dibenzo[a,l]pyrene (DB[a,l]P-DE), benzo[g]chrysene (B[g]Ch-DE), and benzo[c]phenanthrene (B[c]Ph-DE). The plasmids were transfected into B-lymphocytes with normal repair capacity as well as lymphocytes derived from patients with the XP-A, XP-C and CS-B syndromes. We found that XPA cells were able to transcribe slowly past B[g]Ch-adducts but not the other PAHs. Using the amount of luciferase produced as a measure of DNA repair, we found that the relative rates of repair in the actively transcribing luciferase gene was B[a]P-DE>DB[a,l]P-DE, B[g]Ch-DE, >B[c]Ph-DE in repair proficient and XP-C cells. These results indicate that the abilities to transcribe past and to repair the PAH adducts are dependent on different structural features of the DNA adducts.

benzo(g)chrysene