Benzo[c]chrysene

278.35

278.35

0I8Z8V58Z4

DTXSID3073894

Needles from acetic acid|Solid

2902909090

0

7.11

1.232 g/cu cm

122 °C

356.16°C (rough estimate)

264.5±15.1 °C

1.8120 (estimate)

In water, 3.26X10-3 mg/L at 25 deg C (est)

2-8°C

9.03X10-10 mm Hg at 25 deg C (est)

Flammable; burning produces irritating fumes

Henry's Law constant = 4.89X10-7 atm-cu m/mol at 25 °C (est)

Ionization potential: 7.71; Absorption coefficient for thermal electrons: 1.2|Enthalpy of fusion: 22.7 kJ/mol at 298.5 K|Hydroxyl radical reaction rate constant = 5.0X10-11 cu cm/molec-sec at 25 °C (est)

Ventilated, low temperature and dry

P201, P202, P281, P308+P313, P405, P501

H351

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|H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 12 companies from 1 notifications 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#4729]|Respirator Recommendations: Escape conditions: /Coal tar pitch volatiles/[Table#4730]

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/

SEDIMENT: Benzo(c)chrysene was found in 2 of 3 urban harbor sediment samples from the New York area, at reported concentrations of 6X10-9 g/g and 5X10-9 g/g(1).

IDENTIFICATION AND USE: Benzo(c)chrysene (B(c)C) is polynuclear aromatic hydrocarbon (PAH). It is not produced commercially, and it used mostly in biochemical research. PAHs are ubiquitous in combustion products of organic matter, including cigarette smoke. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: It has moderate carcinogenic activity. B(c)C is a unique polycyclic aromatic hydrocarbon that possesses both a bay region and a fjord region in the same molecule. Both bay region and fjord region terminal rings are involved in the in vitro metabolism of BcC. Metabolites of B(c)C form DNA adducts. The extent of DNA adduct formation by B[c]C in mouse skin DNA was lower than that of other moderately carcinogenic PAHs. Benzo[c]chrysene was capable of stimulating epoxide hydrolase activity, but the effect was modest, and it is a potent inducers of rat hepatic CYP1A1 activity.

Benzo(c)chrysene is one of many polycyclic aromatic hydrocarbons (PAH), a group of chemicals that are formed during the incomplete burning of coal, wood 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(c)chrysene, occur as ubiquitous products of incomplete combustion of fossil fuels, wood, diesel oils and gasoline fuels. PAHs generally occur as complex mixtures, for example as part of combustion products such as soot, not as single compounds. They are found throughout the environment in the air, water, and soil(1). /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(c)chrysene is expected to be immobile in soil(SRC). Volatilization of benzo(c)chrysene from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.9X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Benzo(c)chrysene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.0X10-10 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(4).|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(c)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 4.9X10-7 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 its log Kow of 7.11(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism. Benzo(c)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(7). In general, polycyclic aromatic hydrocarbons (PAHs) with four or more benzene rings do not biodegrade readily(8).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzo(c)chrysene, which has an estimated vapor pressure of 9.0X10-10 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 benzo(c)chrysene may be removed from the air by wet and dry deposition(SRC). Benzo(c)chrysene contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

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

An estimated BCF of 1.2X10+4 was calculated in fish for benzo(c)chrysene(SRC), using a log Kow of 7.11(1) and a regression-derived equation(2). According to a classification scheme(3), 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(c)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(4).

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

The Henry's Law constant for benzo(c)chrysene is estimated as 4.9X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that benzo(c)chrysene is expected to be essentially nonvolatile from water or moist soil surfaces(2). Benzo(c)chrysene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.0X10-10mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to benzo(c)chrysene may occur through inhalation and dermal contact with this compound at workplaces where benzo(c)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(c)chrysene via dermal contact with or inhalation of particulate matter resulting from combustion. (SRC)

Benzo[c]chrysene (BcC), an environmental pollutant, is a unique polycyclic aromatic hydrocarbon that possesses both a bay region and a fjord region in the same molecule. We previously demonstrated that both bay region and fjord region terminal rings are involved in the in vitro metabolism of BcC. In the present investigation, we prepared [14-(3)H]BcC and tested the hypothesis that BcC can be activated to both bay region and fjord region diol epoxides in female CD rats. At 6 weeks of age, rats were gavaged with a single dose of [14-(3)H]BcC (5 mg/rat; specific activity, 6.7 Ci/mmol) in 0.5 mL of trioctanoin. During the first 48 h, 20.3% of the dose was eliminated in the feces and 2.8% was eliminated in the urine. After 1 week, cumulatively, 23.2 and 3.5%, respectively, were eliminated. 3-Hydroxybenzo[c]chrysene, 10-hydroxybenzo[c]chrysene, and trans-7,8-dihydroxy-7,8-dihydrobenzo[c]chrysene were the major fecal metabolites. In urine, trans-1,2-dihydroxy-1,2-dihydrobenzo[c]chrysene, 2-hydroxybenzo[c]chrysene, (+/-)-1,t-2,t-3,c-4-tetrahydroxy-1,2,3,4-tetrahydrobenzo[c]chrysene, and (+/-)-9,t-10,t-11,c-12-tetrahydroxy-9,10,11,12-tetrahydrobenzo[c]chrysene were detected, primarily as glucuronic acid and sulfate conjugates. The identification of the two tetraols clearly indicates that both bay region and fjord region diol epoxides are formed as intermediates in the metabolism of BcC in vivo. The second goal of this study was to test the hypothesis that the location of the epoxide moiety (fjord vs bay region) determines the carcinogenic activity. Thus, we compared the carcinogenicity of the bay region (+/-)-anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrobenzo[c]chrysene and the fjord region (+/-)-anti-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrobenzo[c]chrysene in the rat mammary gland. The results clearly showed that the fjord region diol epoxide is a potent mammary carcinogen, while the bay region diol epoxide lacks activity in this model assay. ...|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.|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.|Carcinogenic activity of many polycyclic aromatic hydrocarbons (PAHs) is mainly attributed to their respective diol epoxides, which can be classified as either bay or fjord region depending upon the location of the epoxide function. The Pi class human glutathione (GSH) transferase (hGSTP1-1), which is polymorphic in humans with respect to amino acid residues in positions 104 (isoleucine or valine) and/or 113 (alanine or valine), plays an important role in the detoxification of PAH-diol epoxides. Here, we report that the location of the epoxide function determines specificity of allelic variants of hGSTP1-1 toward racemic anti-diol epoxide isomers of benzo[c]chrysene (B[c]C). The catalytic efficiency (k(cat)/K(m)) of V104,A113 (VA) and V104,V113 (VV) variants of hGSTP1-1 was approximately 2.3- and 1.7-fold higher, respectively, than that of the I104,A113 (IA) isoform toward bay region isomer (+/-)-anti-B[c]C-1,2-diol-3,4-epoxide. On the other hand, the IA variant was approximately 1.6- and 3.5-fold more efficient than VA and VV isoforms, respectively, in catalyzing the GSH conjugation of fjord region isomer (+/-)-anti-B[c]C-9,10-diol-11,12-epoxide. The results of the present study clearly indicate that the location of the epoxide function determines specificity of the allelic variants of hGSTP1-1 in the GSH conjugation of activated diol epoxide isomers of B[c]C.|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/

/OTHER TOXICITY INFORMATION/ ... In this communication, we report that the I104,A113 allele of hGSTP1-1, which is most frequent in human populations, is also most efficient in the GSH conjugation of carcinogenic anti-diol epoxides of benzo[g]chrysene and benzo[c]phenanthrene (anti-BGCDE and anti-BCPDE, respectively). The catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BGCDE, 0.36 mM(-1) x s(-1), was approximately 1.7-fold higher (P < 0.05) compared with hGSTP1-1(V104,V113). Interestingly, the frequency of codon 104-valine alleles is significantly higher in certain cancers compared with codon 104-isoleucine alleles. Like anti-BGCDE, the catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BCPDE was higher by about 1.4- to 2.2-fold (P < 0.05) than those of other hGSTP1-1 variants. These observations are interesting because we have shown previously that the V104,V113 variant, not the I104,A113 isoform, is most efficient in the GSH conjugation of bay-region anti-diol epoxide of benzo(a)pyrene (anti-BPDE), which, unlike anti-BGCDE or anti-BCPDE, is a planar molecule. In conclusion, our results suggest that hGSTP1-1 polymorphism may be an important factor in differential susceptibility of humans to cancers where polycyclic aromatic hydrocarbons are etiological factors and that I104,A113 variant may play a major role in the detoxification of nonplanar, sterically hindered fjord-region diol epoxides (e.g., anti-BGCDE).

1,2,5,6-dibenzphenanthrene