9,10-Phenanthrenedione

208.21

208.21

608838

201-515-5

42L7BZ8H74

10446|7389

DTXSID3058901

Orange-red crystals|Orange needles, orange-red plates

29146990

34.1

2.5

Orange-brownish Powder

1.405 g/cm³ @ Temp: -6.7 °C

206-207 °C

360 °C (approx)

245 °C

1.659

Insoluble in water.

2-8°C

8.5X10-7 mm Hg at 25 deg C (est)

Abdominal cavity-rat LDL0: 165 mg/kg

Henry's Law constant = 2.7X10-9 atm-cu m/mol at 25 °C (est)

Sublimes above 360 °C|With concentrated sulfuric acid gives a dark green color|Cyclohexane/water partition coefficient: 1.39 (log)|Hydroxyl radical reaction rate constant = 6.2X10-12 cu cm/molecule-sec at 25 °C (est)

III

9

UN3077

3

36/37/38

26-36-24/25-22

SF7875000

Xi

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

Stable. Incompatible with strong oxidizing agents.

P261-P305 + P351 + P338

H315-H319-H335

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.

|Warning|H315 (97.3%): 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 185 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

SOIL: 9,10-Phenanthrenedione was detected at a concentration of 17.0 ug/g soil in contaminated soil samples collected from a former gas work site in Stockholm, Sweden(1).

URBAN/SUBURBAN: 9,10-Phenanthrenedione was detected particulate matter of air samples collected from Kenmore Station, Boston MA in the summer of 1994 at a concentration of 0.427 ng/cu m(1). Mean 9,10-phenanthrenedione concentrations of 1.1 and 0.31 ng/cu m were detected in ambient air samples collected in Fresno CA in the winter (2004-2005) and summer (2005), respectively(2).

9,10-Phenanthrenedione was qualitatively detected in the diesel exhaust particulates from a Volkswagen Rabit(1). 9,10-Phenanthrenedione was detected in the emissions from the combustion of synthetic logs at an emission rate of 0.38 mg/kg, but was not detected in the emissions from the combustion of pine or oak woods(2). 9,10-Phenanthrenedione was detected in the particle-phase material emitted from two diesel vehicles at emission rates of 6.9 and 80 ug/L, respectively(3). Diesel particle soot and gasoline soot had reported 9,10-phenanthrenedione levels of 63.1 and 3.8-31.6 ug/km, respectively(4).

highly toxic

9,10-Phenanthrenedione has been identified as a biodegradation metabolite of phenanthrene in soil(1).

9,10-Phenanthrenedione's production and use as an intermediate in the production of dyes, herbicides, plant growth regulators, fungicides and pharmaceuticals and in UV-curable coatings and adhesives(1,2) may result in its release to the environment through various waste streams(SRC). The atmospheric gas-phase reaction of phenanthrene with OH and NO3 radicals may be a major source of 9,10-phenanthrenedione found in the ambient atmosphere(3). 9,10-Phenanthrenedione has been identified as a biodegradation metabolite of phenanthrene in soil(4). 9,10-Phenanthrenedione is emitted in the particulate emissions from diesel exhaust(4).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 28(SRC), determined from a structure estimation method(2), indicates that 9,10-phenanthrenedione is expected to have very high mobility in soil(SRC). Volatilization of 9,10-phenanthrenedione from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(2). 9,10-Phenanthrenedione is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.5X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). One biodegradation study found 9,10-phenanthrenedione resistant to biodegradation(3).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 28(SRC), determined from a structure estimation method(2), indicates that 9,10-phenanthrenedione is not 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 2.7X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 21(SRC), from its log Kow of 2.52(5), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 9,10-Phenanthrenedione is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). 9,10-Phenanthrenedione absorbs UV light strongly at wavelengths >290 nm(6) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). One biodegradation study found 9,10-phenanthrenedione resistant to biodegradation(7).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 9,10-phenanthrenedione, which has an estimated vapor pressure of 8.5X10-7 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 9,10-phenanthrenedione 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 2.6 days(SRC), calculated from its rate constant of 6.2X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase 9,10-phenanthrenedione may be removed from the air by wet and dry deposition(SRC). 9,10-Phenanthrenedione absorbs UV light strongly at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 9,10-phenanthrenedione with photochemically-produced hydroxyl radicals has been estimated as 6.2X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.6 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 9,10-Phenanthrenedione absorbs UV light strongly at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). 9,10-Phenanthrenedione is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3).

An estimated BCF of 21 was calculated in fish for 9,10-phenanthrenedione(SRC), using a log Kow of 2.52(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 9,10-phenanthrenedione can be estimated to be 28(SRC). According to a classification scheme(2), this estimated Koc value suggests that 9,10-phenanthrenedione is expected to have very high mobility in soil.

The Henry's Law constant for 9,10-phenanthrenedione is estimated as 2.7X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 9,10-phenanthrenedione is expected to be essentially nonvolatile from water surfaces(2). 9,10-Phenanthrenedione's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). 9,10-Phenanthrenedione is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.5X10-7 mm Hg(SRC), determined from a fragment constant method(1).

RAIN WATER: 9,10-Phenanthrenedione concentrations of 0.3-0.4 ug/L were detected in rainwater collected in Los Angles CA between Dec 30, 1981 and Mar 26, 1982(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 3675 workers (632 of these were female) were potentially exposed to 9,10-phenanthrenedione in the US(1). Occupational exposure to 9,10-phenanthrenedione may occur through dermal contact with this compound or other products containing 9,10-phenanthrenedione and through inhalation exposure to diesel exhaust(SRC). Monitoring data indicate that the general population may be exposed to 9,10-phenanthrenedione via inhalation of ambient air(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.)

Both K-region and non-K-region o-quinones of polycyclic aromatic hydrocarbons are excellent substrates for human placental NADP linked 15-hydroxyprostaglandin dehydrogenase. These compounds are reduced with kcat/Km values ranging from 3 to 20 s/m. The glutathione thioethers of menadione and toluquinone are reduced with similar catalytic efficiencies. Furthermore, these substances and certain other glutathione thioethers are potent inhibitors of prostaglandin B1 oxidation and polycyclic aromatic hydrocarbon quinone reduction. The possibility exists that the potential toxicity of quinones of polycyclic aromatic hydrocarbons and other xenobiotic substances may be altered in the placenta by an oxidoreductase for which prostaglandins are relatively poor substrates and the presence in placental tissue of certain glutathione thioethers could influence the reduction of these quinones and other xenobiotic substances by this enzyme.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the oxidative phosphorylation of glyceraldehyde 3-phosphate to 1,3-diphosphoglycerate, one of the precursors for glycolytic ATP biosynthesis. The enzyme contains an active site cysteine thiolate, which is critical for its catalytic function. As part of a continuing study of the interactions of quinones with biological systems, /the authors/ have examined the susceptibility of GAPDH to inactivation by 9,10-phenanthrenequinone (9,10-PQ). In a previous study of quinone toxicity, this quinone, whose actions have been exclusively attributed to reactive oxygen species (ROS) generation, caused a reduction in the glycolytic activity of GAPDH under aerobic and anaerobic conditions, indicating indirect and possible direct actions on this enzyme. In this study, the effects of 9,10-PQ on GAPDH were examined in detail under aerobic and anaerobic conditions so that the role of oxygen could be distinguished from the direct effects of the quinone. The results indicate that, in the presence of the reducing agent DTT, GAPDH inhibition by 9,10-PQ under aerobic conditions was mostly indirect and comparable to the direct actions of exogenously-added H2O2 on this enzyme. GAPDH was also inhibited by 9,10-PQ anaerobically, but in a somewhat more complex manner. This quinone, which is not considered an electrophile, inhibited GAPDH in a time-dependent manner, consistent with irreversible modification and comparable to the electrophilic actions of 1,4-benzoquinone (1,4-BQ). Analysis of the anaerobic inactivation kinetics for the two quinones revealed comparable inactivation rate constants (k(inac)), but a much lower inhibitor binding constant (K(i)) for 1,4-BQ. Protection and thiol titration studies suggest that these quinones bind to the NAD+ binding site and modify the catalytic thiol from this site. Thus, 9,10-PQ inhibits GAPDH by two distinct mechanisms: through ROS generation that results in the oxidization of GAPDH thiols, and by an oxygen-independent mechanism that results in the modification of GAPDH catalytic thiols.

/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/

/ALTERNATIVE and IN VITRO TESTS/ The trophoblast cell line, JEG-3, was used to study the cytotoxicity of phenanthrene, 9,10-phenanthrenequinone (PHEQ), anthracene, and 9,10-anthracenedione alone and with copper. The endpoints were the capacity of cultures to reduce alamar Blue (AB), a measure of energy metabolism, and to convert carboxyfluorescein diacetate acetoxymethyl ester (CFDA AM) to carboxyfluorescein, an indication of membrane integrity. Only PHEQ elicited a cytotoxic response. PHEQ caused a concentration-dependent decline in AB but not in CFDA AM readings, suggesting an impairment to energy metabolism. In the presence of copper, PHEQ concentration-response curves were shifted to the left for AB and were obtained with CFDA AM. The Cu/PHEQ synergy is attributed to an increase in redox cycling and production of reactive oxygen species (ROS), which overwhelm antioxidant defenses, damaging energy metabolism first and then membrane integrity. The impermeable copper chelator, bathocuproine, reduced the PHEQ/copper interaction, but the permeable chelator, neocuproine, and copper together were cytotoxic.|/ALTERNATIVE and IN VITRO TESTS/ A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock-down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity.|/ALTERNATIVE and IN VITRO TESTS/ Persistent inhalation of diesel exhaust particles results in damaged lung cells through formation of reactive oxygen species (ROS), but the details of the toxicity mechanism against monocytes are poorly understood. In this study, we used human promyelomonocytic U937 cells as surrogates of monocytes and investigated the toxicity mechanism initiated by exposure to 9,10-phenanthrenequinone (9,10-PQ), a major quinone component in diesel exhaust particles. A 24-hr incubation with 9,10-PQ provoked apoptotic cell death, which was due to signaling through the enhanced ROS generation and concomitant caspase activation. Flow cytometric analyses of U937 cells after long-term exposure to 9,10-PQ revealed induction of differentiation that was evidenced by increasing expression of CD11b/CD18, a cell-surface marker for monocytic differentiation into macrophages. The 9,10-PQ-induced differentiation was significantly abolished by ROS inhibitors, suggesting that ROS generation contributes to cell differentiation. The 9,10-PQ treatment increased the expression of aldo-keto reductase (AKR) 1C3, which reached a peak at 1 to 2 day post-treatment and then declined. The bell-shaped curve of the AKR1C3 expression by 9,10-PQ resembled that caused by phorbol 12-myristate 13-acetate, a differentiation inducer. Additionally, the concomitant treatment with tolfenamic acid, a selective AKR1C3 inhibitor, sensitized the differentiation induced by 9,10-PQ. These results suggest that ROS formation during 9,10-PQ treatment acutely leads to apoptosis of U937 cells and the initiation of monocytic differentiation, which proceeds after the provisional overexpression of AKR1C3.|/ALTERNATIVE and IN VITRO TESTS/ 9,10-Phenanthrenequinone (9,10-PQ), a major component in diesel exhaust particles, is suggested to generate reactive oxygen species (ROS) through its redox cycling, leading to cell toxicity. l-Xylulose reductase (XR), a NADPH-dependent enzyme in the uronate pathway, strongly reduces alpha-dicarbonyl compounds and was thought to act as a detoxification enzyme against reactive carbonyl compounds. Here, we have investigated the role of intracellular ROS generation in apoptotic signaling in human acute T-lymphoblastic leukemia MOLT-4 cells treated with 9,10-PQ and the role of XR in the generation of ROS. Treatment with 9,10-PQ elicited not only apoptotic signaling, including mitochondrial membrane dysfunction and activation of caspases and poly(ADP-ribose) polymerase, but also intracellular ROS generation and consequent glutathione depletion. The apoptotic effects of 9,10-PQ were drastically mitigated by pretreatment with intracellular ROS scavengers, such as N-acetyl-l-cysteine, glutathione monoethyl ester, and polyethylene glycol-conjugated catalase, indicating that intracellular ROS generation is responsible for the 9,10-PQ-evoked apoptosis. Surprisingly, the ROS generation and cytotoxicity by 9,10-PQ were augmented in an XR-transformed cell line. XR indeed reduced 9,10-PQ and produced superoxide anion through redox cycling. In addition, the expression levels of XR and its mRNA in the T lymphoma cells were markedly enhanced after the exposure to 9,10-PQ, and the induction was completely abolished by the ROS scavengers. Moreover, the 9,10-PQ-induced apoptosis was partially inhibited by the pretreatment with XR-specific inhibitors. These results suggest that initially produced ROS induce XR, which accelerates the generation of ROS.

9,10-phenanthraquinone

9,10-Phenanthrenedione: ACTIVE

Normal phase high performance liquid chromatography used to separate solution original fractions of diesel particulates into subfractions suitable for subsequent chemical analysis and bioassay. The transition fraction contains polynuclear aromatic hydrocarbons and dihydroxy derivatives.