PRODUCTS

CUMENE HYDROPEROXIDE

Cumene Hydroperoxide is an organic hydroperoxide intermediate in the cumene process for synthesizing phenol and acetone from benzene and propene.
Cumene Hydroperoxide is typically used as an oxidizing agent.
Products of decomposition of Cumene Hydroperoxide are methylstyrene, acetophenone, and cumyl alcohol.

CAS Number: 80-15-9
EC Number: 201-254-7
IUPAC Name: 2-Phenylpropane-2-peroxol
Chemical Formula: C9H12O2

Other names: 80-15-9, Cumyl hydroperoxide, Cumenyl hydroperoxide, Hydroperoxide, 1-methyl-1-phenylethyl, 2-hydroperoxypropan-2-ylbenzene, Cumolhydroperoxid, Cumolhydroperoxide, 7-Cumyl hydroperoxide, alpha,alpha-Dimethylbenzyl hydroperoxide, Cument hydroperoxide, 1-Methyl-1-phenylethyl hydroperoxide, Hydroperoxyde de cumene, Hydroperoxyde de cumyle, Cumeenhydroperoxyde, Kumenylhydroperoxid, Isopropylbenzene hydroperoxide, Hydroperoxide de cumene, Idroperossido di cumene, Idroperossido di cumolo, Percumyl H, DTXSID3024869, PG7JD54X4I, CHEBI:78673, Hydroperoxide, alpha,alpha-dimethylbenzyl-, alpha-Cumyl hydroperoxide, alpha-Cumene hydroperoxide, LUPEROX CU 80, TRIGONOX K 90, DTXCID404869, cumylhydroperoxide, isopropyl benzene hydroperoxide, alpha, alpha-dimethylbenzyl hydroperoxide, 201-254-7, 7-Hydroperoxykumen, RCRA waste number U096, 2-Phenylpropane-2-peroxol, MFCD00002129, .alpha.,.alpha.-Dimethylbenzyl hydroperoxide, Hydroperoxide, .alpha.,.alpha.-dimethylbenzyl, Cumene Hydroperoxide (80per cent, Technical grade), Cumolhydroperoxid [German], Cumeenhydroperoxyde [Dutch], Kumenylhydroperoxid [Czech], 7-Hydroperoxykumen [Czech], CCRIS 3801, HSDB 254, Cumene Hydroperoxide (80%, Technical grade), Hydroperoxyde de cumene [French], Hydroperoxyde de cumyle [French], Idroperossido di cumene [Italian], Idroperossido di cumolo [Italian], EINECS 201-254-7, RCRA waste no. U096, alpha,alpha-Dimethylbenzylhydroperoxide, UNII-PG7JD54X4I, BRN 1908117, Hydroperoxide, 1-methyl-1-phenylethyl-, Hyperiz, cumyl-hydroperoxide, PH 80, Trigonox K 80, Trigonox K-95, Trigonox R 239A, (1-hydroperoxy-1-methyl-ethyl)benzene, Hydroperoxide, alpha,alpha-dimethylbenzyl, EC 201-254-7, .alpha.-Cumyl hydroperoxide, CHP-5, .alpha.-Cumene hydroperoxide, SCHEMBL15251, 4-06-00-03221 (Beilstein Handbook Reference), 2-hydroperoxy-2-phenylpropane, SCHEMBL9347042, SCHEMBL9694332, CHEMBL1518369, SCHEMBL11416594, SCHEMBL28838178, (2-Phenylpropan-2-yl)dioxidanyl, CHP-158, DTXSID00992375, 2-phenylpropan-2-yl hydroperoxide, CUMENE HYDROPEROXIDE [HSDB], Tox21_300283, STL453641, AKOS015841738, CCG-207896, UN 2116, CAS-80-15-9, NCGC00091748-01, NCGC00091748-02, NCGC00091748-03, NCGC00254045-01, Cumene Hydroperoxide technical grade, 80%, Cumene hydroperoxide, technical grade, 80%, C2223, NS00009523, ST50824346, Cumene hydroperoxide, technical, ~80% in cumene, Q414439

One of the key uses for the material is as a free radical initiator for acrylate and methacrylate monomers, and polyester resins.

Cumene Hydroperoxide is involved as an organic peroxide in the manufacturing of propylene oxide by the oxidation of propylene. This technology was commercialized by Sumitomo Chemical.[4] Oxidation of cumene affords Cumene Hydroperoxide

C6H5(CH3)2CH + oxidation → C6H5(CH3)2COOH
The oxidation by Cumene Hydroperoxide of propylene affords propylene oxide and the byproduct cumyl alcohol. The reaction follows this stoichiometry:

CH3CHCH2 + C6H5(CH3)2COOH → CH3CHCH2O + C6H5(CH3)2COH
Dehydrating and hydrogenating cumyl alcohol recycles the cumene.

Public safety
Cumene Hydroperoxide is believed to be one of the chemicals of concern[6] at the Arkema facility in Crosby, Texas in the aftermath of Hurricane Harvey.

Cumene Hydroperoxide is a colorless to light yellow liquid with a sharp, irritating odor. Flash point 175°F. Boils at 153°C and at 100°C at the reduced pressure of 8 mm Hg. Slightly soluble in water and denser than water. Hence sinks in water. Readily soluble in alcohol, acetone, esters, hydrocarbons, chlorinated hydrocarbons. Toxic by inhalation and skin absorption. Used in production of acetone and phenol, as a polymerization catalyst, in redox systems.

Cumene Hydroperoxide penetrates human red blood cells ... reduced by glutathione in the reaction catalyzed by glutathione peroxidase. Cumenol, water, and oxidized gluthathione were products.

Enzymatic reduction of Cumene Hydroperoxide leads to the formation of cumenol (2-phenylpropan-2-ol) in vitro.

Cumene Hydroperoxide has known human metabolites that include (2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-(2-phenylpropan-2-ylperoxysulfanyl)propan-2-yl]amino]-5-oxopentanoic acid.

The Cumene Hydroperoxide-hematin system reacts with 5,5-dimethyl-1-pyrroline-1-oxide to form the nitroxide 5,5-dimethyl-pyrrolidone-(2)-oxyl-(1) (DMPOX). DMPOX is formed via spin trapping of a cumene hydroperoxyl radical followed by an intramolecular carbanion displacement. Activation of carcinogen n-hydroxy-2-acetyl aminofluorene by Cumene Hydroperoxide-hematin system is most likely mediated by cumene hydroperoxyl radical.

Cumene Hydroperoxide oxidized cholesterol to the carcinogen 5,6-epoxide (5,6-alpha-epoxy-5-alpha-cholestan-3-beta-ol).

Chemical Properties
Cumene Hydroperoxide, an organic peroxide, is a colorless to pale yellow to green liquid. Mild odor.

USES
Production of acetone and phenol; polymerization catalyst, particularly in redox systems, used for rapid polymerization.

Uses
Cumene Hydroperoxide is used for the manufactureof acetone and phenols; for studyingthe mechanism of NADPH-dependent lipidperoxidation; and in organic syntheses.

Definition
ChEBI: A peroxol that is cumene in which the alpha-hydrogen is replaced by a hydroperoxy group.

General Description
Colorless to light yellow liquid with a sharp, irritating odor. Flash point 175°F. Boils at 153°C and at 100°C at the reduced pressure of 8 mm Hg. Slightly soluble in water and denser than water. Hence sinks in water. Readily soluble in alcohol, acetone, esters, hydrocarbons, chlorinated hydrocarbons. Toxic by inhalation and skin absorption. Used in production of acetone and phenol, as a polymerization catalyst, in redox systems.

Air & Water Reactions
Slightly soluble in water and oxidized in air at approximately 130°C.

Reactivity Profile
Cumene Hydroperoxide is a strong oxidizing agent. May react explosively upon contact with reducing reagents Violent reaction occurs upon contact with copper, copper alloys, lead alloys, and mineral acids. Contact with charcoal powder gives a strong exothermic reaction. Decomposes explosively with sodium iodide [Chem. Eng. News, 1990, 68(6), 2]. Can be exploded by shock or heat [Sax, 2 ed., 1965, p. 643]. May ignite organic materials.
Hazard Toxic by inhalation and skin absorption. Strong oxidizing agent; may ignite organic materials.

Health Hazard
Cumene Hydroperoxide is a mild to moderateskin irritant on rabbits. Subcutaneousapplication exhibited a strong delayed reactionwith symptoms of erythema and edema(Floyd and Stockinger 1958). Strong solutionscan irritate the eyes severely, affectingthe cornea and iris.
Its toxicity is comparable to that of tertbutylhydroperoxide. The toxic routes areingestion and inhalation. The acute toxicitysymptoms in rats and mice were muscleweakness, shivering, and prostration.Oral administration of 400 mg/kg resulted inexcessive urinary bleeding in rats.

LD50 value, oral (rats): 382 mg/kg
LD50 value, intraperitoneal (rats): 95 mg/kg
Although Cumene Hydroperoxide is toxic,its pretreatment may be effective against thetoxicity of hydrogen peroxide. In humans, itstoxicity is low.
Cumene Hydroperoxide is mutagenic andtumorigenic (NIOSH 1986). It may causetumors at the site of application. In mice,skin and blood tumors have been observed.Its cancer-causing effects on humans are notknown.

Health Hazard
Inhalation of vapor causes headache and burning throat. Liquid causes severe irritation of eyes; on skin, causes burning, throbbing sensation, irritation, and blisters. Ingestion causes irritation of mouth and stomach.

Fire Hazard
Flammable; highly reactive and oxidizing. Flash point 79°C (174.2°F); vapor density 5.2 (air= 1); autoignition temperature not reported; self-accelerating decomposition temperature 93°C (199.4°F).
When exposed to heat or flame, it may ignite and/or explode. A 91–95% concentration of Cumene Hydroperoxide decomposes violently at 150°C (302°F) (NFPA 1986). Duswalt and Hood (1990) reported violent decomposition when this compound mixed accidentally with a 2-propanol solution of sodium iodide.
It forms an explosive mixture with air. The explosive concentration range is not reported. Hazardous when mixed with easily oxidizable compounds. Fire-extinguishing agent: water from a sprinkler or fog nozzle from an explosion-resistant location.

Potential Exposure
Cumene Hydroperoxide is used as polymerization initiator, curing agent for unsaturated polyester resins and cross-linking agent; as an intermediate in the process for making phenol plus acetone from cumene.
storage Cumene Hydroperoxide is stored in a cool,dry and well-ventilated area isolated fromother chemicals. It should be protectedagainst physical damage. It may be shippedin wooden boxes with inside glass or earthenwarecontainers or in 55-gallon metal drums.

IDENTIFICATION: Cumene Hydroperoxide is a colorless to pale yellow liquid. It is moderately soluble in water. It is a member of a class of chemicals called organic peroxides. It can be formed in small amounts from the breakdown of the naturally occurring compound cumene. USE: Cumene Hydroperoxide is an important commercial chemical used in the production of plastics and to make other chemicals. It is an ingredient in an auto detail product and home maintenance product.

EXPOSURE: Workers that use Cumene Hydroperoxide may breathe in vapors or have direct skin contact. The general population may be exposed by vapors from limited use in two consumer products. If Cumene Hydroperoxide is released to the environment, it will be broken down in air. It is expected to be broken down by sunlight. It will not move into air from moist soil and water.

It is expected to move slowly through soil. It is not expected to build up in fish. However, organic peroxides such as Cumene Hydroperoxide are very reactive and will explode and burn if not stored properly. RISK: Chemical burns have been reported following direct skin contact to Cumene Hydroperoxide. Allergic skin rashes may occur with repeated, low-dose skin contact. Additional data on the potential for Cumene Hydroperoxide to cause toxic effects in humans are not available.

However, several toxic effects associated with exposure to organic peroxides (as a group) have been reported. Splashes directly to the eye can cause severe damage and potential blindness. Stomach pain, burning sensation and shock or collapse have been reported following accidental ingestion of organic peroxides. Sore throat, burning sensation, cough, difficulty breathing and shortness of breath have been reported following inhalation of organic peroxide vapors.

A build-up of fluid in the lungs may occur hours after the initial exposure, especially following exertion. Available data in laboratory animals indicate that human exposure to Cumene Hydroperoxide will likely cause effects consistent with general organic peroxide exposure (listed above). Additional effects reported in animals exposed to Cumene Hydroperoxide include excitement, convulsions, decreased body weight, and evidence of damage to various organs at lethal doses, particularly the kidney.

No data on the potential for Cumene Hydroperoxide to cause infertility, abortion, or birth defects are available. In laboratory animals, skin exposure to Cumene Hydroperoxide caused an increase in cancerous skin tumors caused by a known tumor agent (dimethyl-benz[a]anthracene). Exposure to Cumene Hydroperoxide alone did not induce skin tumors following direct skin exposure or injection under the skin. The potential for Cumene Hydroperoxide to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, or the U.S. National Toxicology Program 14th Report on Carcinogens.

Cumene Hydroperoxide is obtained by oxidizing cumene with air, usually in a cascade of stirred-tank reactors or bubble columns at temperatures in the range of 100-140 °C and a pressure of 6-7 bar and usually with small amounts of a buffer to prevent acids from building up. Since Cumene Hydroperoxide, as a tertiary alkyl hydroperoxide, is much more stable than ethylbenzene hydroperoxide, the oxidation can be taken to a higher conversion with still reasonable selectivity. Usually the conversion is limited to around 20%, leading to selectivities to Cumene Hydroperoxide in the range of 90-95%.

Cumene Hydroperoxide is a good candidate for incineration by liquid injection incineration with a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds. It is also a good candidate for rotary kiln incineration, with a temperature range of 820 to 1600 °C and a residence time of seconds, and fluidized bed incineration, with a temperature range of 450 to 980 °C and a residence time of seconds.

An explosion occurred in our laboratory during the purification of 100 mL of Cumene Hydroperoxide. The explosion was violent enough to completely shatter the ceramic top of a magnetic stir plate. Modifications of the published procedure ("Purification of Laboratory Chemicals," D. D. Perrin, W. L. F. Armarego, and D. R. Perrin, 2nd Ed.) were used and involved washing the sodium salt of the hydroperoxide with toluene rather than benzene and drying the hexane extracts of the Cumene Hydroperoxide over anhydrous magnesium sulfate.

The magnesium sulfate had been removed by filtration, and the hexane was evaporated under vacuum at ambient temperature when the flask exploded. Most of the hexane appeared to have been removed because the residue in the flask was quite viscous. The Cumene Hydroperoxide was probably present in very high concentration, with little hexane remaining just before the explosion. All other aspects of the procedure were identical to those published in the book cited. The exact cause of the explosion is not known. The only modification of the procedure that could possibly be connected to the explosion is the use of magnesium sulfate.

It does not seem likely that substituting toluene for benzene would have any effect. This modified procedure has been used many times by several researchers in our laboratories with no problems; however, the incident serves as a poignant reminder of the sensitive nature of hydroperoxides, even those hydroperoxides known to be thermally quite stable, such as Cumene Hydroperoxide. Cumene Hydroperoxide at 0.2 M concentration in benzene is thermally stable with a half-life of 29 hours at 145 °C. The material, as it is purchased, is often listed as 80% Cumene Hydroperoxide.

We know from analysis that the impurities are decomposition products of Cumene Hydroperoxide (alpha- methyl styrene, acetophenone, and cumyl alcohol). Many vendors warn that in the concentrated state, as purchased, Cumene Hydroperoxide should be stored at temperatures below 80 °C. The thermal data on hydroperoxides can be misleading and lull one into a false sense of security. The literature is full of examples showing that cumene, as well as other hydroperoxides, can undergo rapid decomposition at room temperature with a wide range of compounds, even when these compounds are present in trace or catalytic concentrations (acids and metal are examples). If one happens to be purifying a relatively large quantity of the hydroperoxide in a neat or concentrated state, the potential for an uncontrolled reaction and explosion is high.

During a purification procedure, there are many opportunities to inadvertently introduce small amounts of materials that may prove to be active catalysts for hydroperoxide decomposition. This can occur even when using well-established purification procedures. We recommend staying with the published procedures and not using active drying agents such as magnesium sulfate. The drying agent could contain traces of unidentified materials that may catalyze decomposition of the hydroperoxide.

We also recommend purifying small quantities of Cumene Hydroperoxide (<5 g) and using it immediately. One should also take advantage of all available protective measures. Such measures include keeping the hood clear of any other flammable or potentially dangerous materials during purification. This precaution helps to avoid the possibility of secondary accidents being initiated by the uncontrolled reaction of the hydroperoxide during purification. Safety visor, apron, and heavy gloves should also be worn and explosion-proof shields used.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Cumene Hydroperoxide is produced, as an intermediate or a final product, by process units covered under this subpart.

This modified procedure has been used many times by several researchers in our laboratories with no problems; however, the incident serves as a poignant reminder of the sensitive nature of hydroperoxides, even those hydroperoxides known to be thermally quite stable, such as Cumene Hydroperoxide. Cumene Hydroperoxide at 0.2 M concentration in benzene is thermally stable with a half-life of 29 hours at 145 °C. The material, as it is purchased, is often listed as 80% Cumene Hydroperoxide. We know from analysis that the impurities are decomposition products of Cumene Hydroperoxide (alpha methyl styrene, acetophenone, and cumyl alcohol). Many vendors warn that in the concentrated state, as purchased, Cumene Hydroperoxide should be stored at temperatures below 80 °C. The thermal data on hydroperoxides can be misleading and lull one into a false sense of security.

In recent years, considerable efforts have been made to identify new chemopreventive agents which could be useful for man. Myrica nagi, a subtropical shrub, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiological disorders. We have shown a chemopreventive effect of Myrica nagi on Cumene Hydroperoxide-induced cutaneous oxidative stress and toxicity in mice.

Cumene Hydroperoxide treatment at a dose level of 30 mg/animal/0.2 mL acetone enhances susceptibility of cutaneous microsomal membrane for iron-ascorbate-induced lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and depletion in the level of cutaneous glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes such as glutathione S-transferase and quinone reductase has been observed.

Application of Myrica nagi at doses of 2.0 mg and 4.0 mg/kg body weight in acetone prior to that of Cumene Hydroperoxide (30 mg/animal/0.2 mL acetone) treatment resulted in significant inhibition of Cumene Hydroperoxide-induced cutaneous oxidative stress and toxicity in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation induced by iron ascorbate and xanthine oxidase activities were significantly reduced (p<0.05).

In addition the depleted level of glutathione, the inhibited activities of antioxidants, and phase II metabolizing enzymes were recovered to a significant level (p<0.05). The protective effect of Myrica nagi was dose-dependent. In summary our data suggest that Myrica nagi is an effective chemopreventive agent in skin and capable of ameliorating Cumene Hydroperoxide-induced cutaneous oxidative stress and toxicity.

Organic peroxides are widely used in the chemical industry as initiators of oxidation for the production of polymers and fiber-reinforced plastics, in the manufacture of polyester resin coatings, and pharmaceuticals. Free radical production is considered to be one of the key factors contributing to skin tumor promotion by organic peroxides. In vitro experiments have demonstrated metal-catalyzed formation of alkoxyl, alkyl, and aryl radicals in keratinocytes incubated with Cumene Hydroperoxide.

The present study investigated in vivo free radical generation in lipid extracts of mouse skin exposed to Cumene Hydroperoxide. The electron spin resonance (ESR) spin-trapping technique was used to detect the formation of alpha-phenyl-N-tert-butylnitrone (PBN) radical adducts, following intradermal injection of 180 mg/kg PBN. It was found that 30 min after topical exposure, Cumene Hydroperoxide (12 mmol/kg) induced free radical generation in the skin of female Balb/c mice kept for 10 weeks on vitamin E-deficient diets.

In contrast, hardly discernible radical adducts were detected when Cumene Hydroperoxide was applied to the skin of mice fed a vitamin E-sufficient diet. Importantly, total antioxidant reserve and levels of GSH, ascorbate, and vitamin E decreased 34%, 46.5%. 27%, and 98%, respectively, after mice were kept for 10 weeks on vitamin E-deficient diet. PBN adducts detected by ESR in vitamin E-deficient mice provide direct evidence for in vivo free radical generation in the skin after exposure to Cumene Hydroperoxide.

Hemidesmus indicus has been shown to possess significant activity against immunotoxicity and other pharmacological and physiological disorders. In this communication, we have shown the modulating effect of H. indicus on Cumene Hydroperoxide-mediated cutaneous oxidative stress and tumor promotion response in murine skin.

Cumene Hydroperoxide treatment (30 mg per animal) increased cutaneous microsomal lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes and depletion in the level of glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes was observed.

Cumene Hydroperoxide treatment also induced the ornithine decarboxylase activity and enhanced the [(3)H]-thymidine uptake in DNA synthesis in murine skin. Application of ethanolic extract of H. indicus at a dose level of 1.5 and 3.0 mg/kg body weight in acetone prior to that of Cumene Hydroperoxide treatment resulted in significant inhibition of Cumene Hydroperoxide-induced cutaneous oxidative stress, epidermal ornithine decarboxylase activity and enhanced DNA synthesis in a dose-dependent manner.

Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation and xanthine oxidase activity were significantly reduced (p<0.01). In addition the depleted level of glutathione, inhibited activities of antioxidants and phase II metabolizing enzymes were recovered to significant level (p<0.05). In summary, our data suggest that H. indicus is an effective chemopreventive agent in skin and capable of ameliorating hydroperoxide-induced cutaneous oxidative stress and tumor promotion.

USE
Cumene peroxide is a colorless to pale-yellow liquid. It is used in production of acetone and phenol; as polymerization catalyst, particularly in the redox systems, used for rapid polymerization. HUMAN STUDIES: Normal human epidermal keratinocytes undergo profound lipid oxidation with preference for phosphatidylserine followed by phosphatidylserine externalization upon exposure to Cumene Hydroperoxide. ANIMAL STUDIES: Application of 1-2 drops of Cumene Hydroperoxide (73%) to rabbit skin (circular area, 2 cm diameter) produced erythema, edema, and vesiculation within 2-3 days.

1 mg applied to the eye of rabbits caused redness of palpebral conjunctiva and chemosis. Skin carcinoma formed in DMBA/cumene peroxide-exposed mice in initiation/promotion study. Mutagenic activity of Cumene Hydroperoxide was observed in the Drosophila melanogaster test. Cumene Hydroperoxide was evaluated for mutagenicity in the Salmonella microsome preincubation assay.

Cumene Hydroperoxide was tested in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of metabolic activation. Cumene Hydroperoxide was positive in the Ames test with the last positive dose tested 33 ug/plate. ECOTOXICITY STUDIES: Toxic action of water pollutants was tested by measuring the immobilization of Daphnia magna, strain ircha. The mean effective concentration (EC50) for Cumene Hydroperoxide was less than 10 mg/L.

Reactive oxygen species not only modulate important signal transduction pathways, but also induce DNA damage and cytotoxicity in keratinocytes. Hydrogen peroxide and organic peroxides are particularly important as these chemicals are widely used in dermally applied cosmetics and pharmaceuticals, and also represent endogenous metabolic intermediates. Lipid peroxidation is of fundamental interest in the cellular response to peroxides, as lipids are extremely sensitive to oxidation and lipid-based signaling systems have been implicated in a number of cellular processes, including apoptosis.

Oxidation of specific phospholipid classes was measured in normal human epidermal keratinocytes exposed to Cumene Hydroperoxide after metabolic incorporation of the fluorescent oxidation-sensitive fatty acid, cis-parinaric acid, using a fluorescence high-performance liquid chromatography assay. In addition, lipid oxidation was correlated with changes in membrane phospholipid asymmetry and other markers of apoptosis. Although Cumene Hydroperoxide produced significant oxidation of cis-parinaric acid in all phospholipid classes, one phospholipid, phosphatidylserine, appeared to be preferentially oxidized above all other species.

Using fluorescamine derivatization and annexin V binding, it was observed that specific oxidation of phosphatidylserine was accompanied by phosphatidylserine translocation from the inner to the outer plasma membrane surface where it may serve as a recognition signal for interaction with phagocytic macrophages. These effects occurred much earlier than any detectable changes in other apoptotic markers such as caspase-3 activation, DNA fragmentation, or changes in nuclear morphology.

Thus, normal human epidermal keratinocytes undergo profound lipid oxidation with preference for phosphatidylserine followed by phosphatidylserine externalization upon exposure to Cumene Hydroperoxide. It is, therefore, likely that normal human epidermal keratinocytes exposed to similar oxidative stress in vivo would undergo phosphatidylserine oxidation/translocation. This would make them targets for macrophage recognition and phagocytosis, and thus limit their potential to invoke inflammation or give rise to neoplastic transformations.

Acute Exposure/ Rats (n=2) exposed to 50 ppm of Cumene Hydroperoxide for three 4-hr periods experienced incoordination, tremor, and /CNS depression/. One died. Autopsy (histological) indicated congested lung and kidneys. Rats (n=6) exposed to 31.5 ppm of Cumene Hydroperoxide for seven 5-hr periods exhibited salivation, respiratory difficulty, tremors, and hyperemia of ears and tail. Histological examination indicated emphysema and thickening of alveolar walls. Rats (n=6) exposed to 16 ppm of Cumene Hydroperoxide for twelve 4.5-hr periods experienced salivation, and nose irritation while autopsy indicated organs to be normal.

Subchronic toxicity was evaluated in groups of 20 Fischer 344 rats (10 males and 10 females) exposed daily for 6 hours to 1, 6, 31, or 124 mg/cu m Cumene Hydroperoxide, 5 days a week for 3 months. Exposure at 124 mg/m3 was terminated after 5 days due to excessive toxicity; mortality was observed in 6/10 male, and 3/10 female rats at 12 days at which time the surviving animals were sacrificed. Clinical observations of animals in the 124 mg/cu m dose group at 12 days included eye and nose irritation, breathing difficulties, and decreased body weights.

Pathological observations attributed to the effect of the test article in animals that died or were sacrificed in the 124 mg/cu m dose group included ulceration and inflammation of the cornea, nasal turbinates and lining of the stomach; while observations of thymic atrophy, depletion of lymphoid tissue in the germinal centers of some lymph nodes and the spleen, decreased lipid content of the liver, and decreased circulating white blood cells, were attributed to stress.

Hematological observations in the 124 mg/cu m dose group included a generalized decrease in PCV, RBC and WBC count and a decrease in hemoglobin levels. Cumene Hydroperoxide did not induce biologically significant changes in clinical, pathological, hematological, and biochemical parameters, or in urinalysis values, when administered at concentrations of 1, 6, or 31 mg/cu m in the animals maintained on exposure for the full 90 days.

Cumene Hydroperoxide's production and use in the manufacture of acetone, phenol, and alpha-methylsytrene, as a polymerization catalyst, and as a polyester resin crosslinking agent, may result in its release to the environment through various waste streams. Small quantities might be formed in the atmosphere and natural waters from cumene. If released to air, a vapor pressure of 3.27X10-3 mm Hg at 25 °C indicates Cumene Hydroperoxide will exist solely as a vapor in the atmosphere.

Vapor-phase Cumene Hydroperoxide will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 45 hours. If released to soil, Cumene Hydroperoxide is expected to have low mobility based upon an estimated Koc of 2000. Volatilization from moist soil surfaces is not expected based upon an estimated Henry's Law constant of 4.7X10-8 atm-cu m/mole.

Cumene Hydroperoxide is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Utilizing the Japanese MITI test, 0% of the Theoretical BOD was reached in 4 weeks indicating that biodegradation is not an important environmental fate process. Hydroperoxides react with a variety of compounds and are degraded readily to the corresponding alcohols. If released into water, is expected to adsorb to suspended solids and sediment based upon the estimated Koc.

Volatilization from water surfaces is not expected based upon this compound's estimated Henry's Law constant. An estimated BCF of 12 suggests the potential for bioconcentration in aquatic organisms is low. Occupational exposure to Cumene Hydroperoxide may occur through inhalation and dermal contact with this compound at workplaces where Cumene Hydroperoxide is produced or used.

Cumene Hydroperoxide's production and use in the manufacture of acetone, phenol, and alpha-methylsytrene, as a polymerization catalyst(2), and as a polyester resin crosslinking agent(3), may result in its release to the environment through various waste streams.

Based on a classification scheme, an estimated Koc value of 2000, determined from a structure estimation method(2), indicates that Cumene Hydroperoxide is expected to have low mobility in soil. Volatilization of Cumene Hydroperoxide from moist soil surfaces is not expected given an estimated Henry's Law constant of 4.7X10-8 atm-cu m/mole, based upon its vapor pressure, 3.27X10-3 mm Hg, and water solubility, 13,900 mg/L. Cumene Hydroperoxide is not expected to volatilize from dry soil surfaces based upon its vapor pressure.

A 0% of Theoretical BOD using activated sludge in the Japanese MITI test suggests that biodegradation is not an important environmental fate process in soil. However, hydroperoxides react with a variety of compounds and are reduced readily to the corresponding alcohols. They are decomposed readily by multivalent metal ions, are photo- and thermally-sensitive and undergo initial oxygen-oxygen bond homolysis, and they are readily attacked by free radicals, undergoing induced and self-induced decomposition. Therefore, chemical degradation is expected to be the dominant fate process in soil.

According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere, Cumene Hydroperoxide, which has a vapor pressure of 3.27X10-3 mm Hg at 25 °C, is expected to exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase Cumene Hydroperoxide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 45 hours, calculated from its rate constant of 8.6X10-12 cu cm/molecule-sec at 25 °C determined using a structure estimation method. Cumene Hydroperoxide absorbs light in the environmental spectrum and has the potential for direct photolysis.

The rate constant for the vapor-phase reaction of Cumene Hydroperoxide with photochemically-produced hydroxyl radicals has been estimated as 8.6X10-12 cu cm/molecule-sec at 25 °C using a structure estimation method. This corresponds to an atmospheric half-life of about 45 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm. Hydroperoxides are decomposed by redox reactions with multivalent metal ions (any oxidation state) and attack by free radicals and photodissociation. No specific data could be found on the degradation rates of Cumene Hydroperoxides by these degradation mechanisms. Reactions with free radicals are rapid and would be expected to result in decomposition in natural waters and urban atmospheres.

Using a structure estimation method based on molecular connectivity indices, the Koc of Cumene Hydroperoxide can be estimated to be 2000. According to a classification scheme, this estimated Koc value suggests that Cumene Hydroperoxide is expected to have low mobility in soil. Hydroperoxides react with multivalent metal ions and other species ubiquitous in soil and are readily reduced to the corresponding alcohols. Therefore, it is expected to chemically degrade rapidly in soil and is not expected to travel long distances in soil or migrate to groundwater.

The Henry's Law constant for Cumene Hydroperoxide is estimated as 4.7X10-8 atm-cu m/mole derived from its vapor pressure, 3.27X10-3 mm Hg, and water solubility, 13,900 mg/L. This Henry's Law constant indicates that Cumene Hydroperoxide is expected to be essentially nonvolatile from water and moist soil surfaces. Cumene Hydroperoxide is not expected to volatilize from dry soil surfaces based upon its vapor pressure.

Cumene Hydroperoxide may be emitted as an air pollutant from industrial sources that produce cyclic crudes and intermediates, and industrial organic chemicals.

According to the 2016 TSCA Inventory Update Reporting data, 6 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of Cumene Hydroperoxide in the United States may be as low as 10 workers and as high as 500 workers per plant; the data may be greatly underestimated due to confidential business information (CBI) or unknown values.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 234,305 workers (69,933 of these are female) were potentially exposed to Cumene Hydroperoxide in the US. Occupational exposure to Cumene Hydroperoxide may occur through inhalation and dermal contact with this compound at workplaces where Cumene Hydroperoxide is produced or used. Cumene Hydroperoxide was detected at 0-60 ug/cu m in air samples measured at a electrical cable insulation plant in the extrusion area, it was not detected in a vulcanization area of a shoe sole factory or vulcanization and extrusion areas of a tire retreading factory.

Cumene Hydroperoxide is a relatively stable organic peroxide. This oxidizing agent is commercially available with a purity of ~80%. A 0.2 M solution in benzene has a half-life of 29 hours at 145°C. The decomposition products of Cumene Hydroperoxide are methylstyrene, acetophenone, and cumyl alcohol. Pure Cumene Hydroperoxide can be stored at room temperature, but the potential for an uncontrolled reaction and explosion is high. Cumyl as well as other hydroperoxides can undergo rapid decomposition under the influence of a wide range of trace compounds, such as acids and metals.