Dibenz[b,f][1,4]oxazepine

195.21700

195.22

607-782-8

C1Q77A87V1

293779

3448

DTXSID8059764

Pale yellow crystalline solid

2934999090

21.59000

2.97850

Dibenz(b,f)(1,4)oxazepine is a colorless liquid, odorless to fruity.

1.16g/cm3

68-69 °C

329.3ºC at 760mmHg

125ºC

1.625

In water, 124 mg/L at 25 deg C (est)

2.2X10-4 mm Hg at 25 deg C (est)

Pepper-like odor

Henry's Law constant = 4.1X10-3 atm-cu m/mole at 25 °C (est)

Hydroxyl radical reaction rate constant = 3.7X10-10 cu cm/molecule-sec at 25 °C (est)

No rapid reaction with air. No rapid reaction with water.

Amines, Phosphines, and Pyridines

As an amine, it probably behaves less as a base than other aliphatic amines as due to it's cyclic structure. However it will react as a weak base.

3448

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Excerpt from ERG Guide 159 [Substances (Irritating)]: Some of these materials may burn, but none ignite readily. Containers may explode when heated. (ERG, 2016)

Excerpt from ERG Guide 159 [Substances (Irritating)]: SMALL FIRE: Dry chemical, CO2, water spray or regular foam. LARGE FIRE: Water spray, fog or regular foam. Move containers from fire area if you can do it without risk. Dike fire-control water for later disposal; do not scatter the material. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn. (ERG, 2016)

Excerpt from ERG Guide 159 [Substances (Irritating)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

Excerpt from ERG Guide 159 [Substances (Irritating)]: Do not touch or walk through spilled material. Stop leak if you can do it without risk. Fully encapsulating, vapor-protective clothing should be worn for spills and leaks with no fire. SMALL SPILL: Pick up with sand or other non-combustible absorbent material and place into containers for later disposal. LARGE SPILL: Dike far ahead of liquid spill for later disposal. Prevent entry into waterways, sewers, basements or confined areas. (ERG, 2016)

Excerpt from ERG Guide 159 [Substances (Irritating)]: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. (ERG, 2016)

Since inhalation is likely to be the primary route of exposure, leave the area where the riot control agents were released and get to fresh air ... If the riot control agents were released outdoors, move away from the area where the agents were released. Avoid dense, low-lying clouds of riot control agent vapor. Go to the highest ground possible, because riot control agents will form a dense vapor cloud that can travel close to the ground ... /Riot control agents/|If you think you may have been exposed to riot control agent, you should remove your clothing, rapidly wash your entire body with soap and water, and get medical care as quickly as possible. Removing your clothing: Quickly take off clothing that may have riot control agent on it. Any clothing that has to be pulled over the head should be cut off the body instead of pulled over the head. If you are helping other people remove their clothing, try to avoid touching any contaminated areas, and remove the clothing as quickly as possible ... /Riot control agents/|... If your eyes are burning or your vision is blurred, rinse your eyes with plain water for 10 to 15 minutes. If you wear contacts, remove them and put them with the contaminated clothing. Do not put the contacts back in your eyes (even if they are not disposable contacts). If you wear eyeglasses, wash them with soap and water. You can put your eyeglasses back on after you wash them. If you are wearing jewelry that you can wash with soap and water, you can wash it and put it back on. If it cannot be washed, it should be put with the contaminated clothing. /Riot control agents/|SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|For more Preventive Measures (Complete) data for DIBENZ(b,f)[1,4]OXAZEPINE (6 total), please visit the HSDB record page.

Dibenzoxazepine (CR) /is a/ tear agent /with/ instantaneous rate of action /and/ irritates eyes, skin, and respiratory tract. /From table/

Dibenz(b,f)-1,4-oxazepine (CR), a potent peripheral sensory irritant material, has been shown to have a very low acute lethal and sub-lethal toxicity by intravenous, intraperitoneal, oral, percutaneous and inhalation routes to several species of laboratory mammal. There was no organ-specific pathology. Comparison of the acute toxicity of CR with that of two other peripheral sensory irritants, 1-chloroacetophenone (CN) and 2-chlorobenzyl-lidene malononitrile (CS), shows CR to be significantly less toxic than either of them. Pyrotechnically generated CR smoke was more toxic than pure (thermally generated) aerosols of CR; this was due to the presence of pyrotechnic decomposition products in the atmosphere from the burning of the smoke generating composition. However, the median lethal toxicity of pyrotechnically generated CR smoke was very significantly less than that of either pyrotechnically generated CN or CS smokes. Short-term cumulative toxicity did not occur following multiple oral dosing with CR. The acute toxicology of three ether intermediates encountered in the synthesis of CR from 1-chloro-2-nitrobenzene and sodium phenoxide (2-nitrodiphenyl ether, 2-aminodiphenyl ether and 2-formamidodiphenyl ether) was investigated; all three ethers were found to be less acutely toxic than CR itself. /Dibenz(b,f)-1,4-oxazepine/

LCt50 Human probably higher than 100,000 mg.min/cu m (estimated)

Dibenz(b,f)[1,4]oxazepine's production may result in its release to the environment through various waste streams; its use as a riot control (tear gas) agent(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1020(SRC), determined from an estimated log Kow of 3.01(2) and a regression-derived equation(3), indicates that dibenz(b,f)[1,4]oxazepine is expected to have low mobility in soil(SRC). Volatilization of dibenz(b,f)[1,4]oxazepine from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.1X10-3 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Dibenz(b,f)[1,4]oxazepine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-4 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available for dibenz(b,f)[1,4]oxazepine in soil(SRC, 2008).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1020(SRC), determined from an estimated log Kow of 3.01(2) and a regression-derived equation(3), indicates that dibenz(b,f)[1,4]oxazepine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.1X10-3 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 2 hours and 6 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 42(SRC), from an estimated log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is moderate. Biodegradation data were for dibenz(b,f)[1,4]oxazepine not available in water(SRC, 2008).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dibenz(b,f)[1,4]oxazepine, which has an estimated vapor pressure of 2.2X10-4 Hg at 25 °C(2), is expected to exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase dibenz(b,f)[1,4]oxazepine 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 1 hour(SRC), calculated from its rate constant of 3.7X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Dibenz(b,f)[1,4]oxazepine contains chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight(4).

The rate constant for the vapor-phase reaction of dibenz(b,f)[1,4]oxazepine with photochemically-produced hydroxyl radicals has been estimated as 3.7X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1 hour at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Dibenz(b,f)[1,4]oxazepine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Dibenz(b,f)[1,4]oxazepine contains chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight(2).

An estimated BCF of 42 was calculated for dibenz(b,f)[1,4]oxazepine(SRC), using an estimated log Kow of 3.01(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

The Koc of dibenz(b,f)[1,4]oxazepine is estimated as 1020(SRC), using an estimated log Kow of 3.01(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that dibenz(b,f)[1,4]oxazepine is expected to have low mobility in soil(SRC).

The Henry's Law constant for dibenz(b,f)[1,4]oxazepine is estimated as 4.1X10-3 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that dibenz(b,f)[1,4]oxazepine is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 2 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 6 days(SRC). Dibenz(b,f)[1,4]oxazepine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Dibenz(b,f)[1,4]oxazepine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-4 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure and exposure to the general population to dibenz(b,f)[1,4]oxazepine should be rare since this compound is solely used as a riot control agent. (SRC)

The fate of dibenz[b,f]-1,4-[11(14)-C]oxazepine (CR) in rats, rhesus monkey and guinea-pig and in isolated perfused rat livers has been examined. 14C-CR was administered to rats at doses from 1.56 to 3470 umol/kg and irrespective of dose or route of administration most (59-93%) was eliminated in the urine as primarily the sulfates of the 7-, 4- and 9-hydroxylated 10,11-dihydrodibenz[b,f]-1,4-oxazepine-11(10H)-one. In blood, both in vivo and in liver perfusates, CR concentrations decreased biphasically to be replaced initially with CR-lactam (dihydrodibenz[b,f]-1,4-oxazepine-11(10H)-one), followed by the sulfates of the 7-, 4- and 9-hydroxylactams. The rate of disappearance of CR in liver perfusates was slower than in vivo. Bile contained only small amounts of sulphate conjugates and significant amounts of conjugated 2-amino-2'-hydroxymethyldiphenyl ether (amino alcohol). This was not identified in the urine or blood of rats. Preliminary studies in rhesus monkey and the guinea-pig show similar excretory patterns and metabolites. However, only free hydroxylactams were isolated from monkey urine and traces of the amino alcohol were detected in guinea-pig urine. Whole-body autoradiography of mice confirm the rapid disappearance of CR from blood into heart, liver, kidneys and small intestine with evidence of biliary excretion. It is consistent with the rat studies showing the rapid absorption of a highly lipophilic compound undergoing hepatic metabolism, biliary secretion, enterohepatic recirculation and renal excretion. /Dibenz[b,f]-1,4-[11(14)-C]oxazepine (CR)/|CR (dibenz[b,f]-1,4-oxazepine) is metabolized by rat liver 105,000 g supernatant fractions by (a) ring opening and reduction to 2-amino-2'-hydroxymethyldiphenyl ether and (b) oxidation at C11 to give a cyclic lactam. Reaction (a) is NADPH-dependent, decreased by dialysis and methylene blue, whereas reaction (b) is heat-resistant, inactivated by dialysis, inhibited by CN-, p-chloromercuribenzoate, amytal and menadione, and stimulated by methylene blue, phenazine methosulphate and 2,6-dichlorophenol indophenol. Reaction (a) is similar to that of aldehyde reductases (E.C.1.1.1.2) and reaction (b) to that of molybdenum hydroxylases (E.C.1.2.3.1). Reaction (a) is also catalysed by an NADH-dependent enzyme in liver microsomes and subsequent hydroxylation of the lactam also occurs in this cell fraction. Some extrahepatic metabolism of CR occurs via the same routes in kidney, small intestine and lung, though the yield is limited. Digestive gland extract of Helix pomatia converts CR to its lactam in significant amounts. The metabolism of CR in vitro is similar to that predicted from observations in vivo. /CR (dibenz[b,f]-1,4-oxazepine)/|The fates of several intermediates of dibenz[b,f]-1,4-oxazepine (CR) metabolism in vivo and in vitro in rats have been examined to establish the metabolism and excretory sequence of CR. The ring-opened 2-amino 2'-hydroxymethyldiphenyl ether (amino alcohol) added to isolated perfused rat liver was rapidly cleared in bile as a mixture of highly polar conjugates, whereas the major route of excretion in vivo was as the 4-, 7- and 9-hydroxylactam sulfates in urine. The lactam of CR was eliminated exclusively in urine giving the same products as obtained for CR, but the distribution of metabolites of the C10-C11 dihydro derivative of CR was unlike that of the parent compound indicating that it occupies only a peripheral role in the fate of CR in vivo. A mixture of 7-, 4- and 9-hydroxylactams derived from the enzymic hydrolysis of urinary sulphates was rapidly removed from blood, sulphated and secreted as sulphates into blood both in vivo and in isolated perfused liver. Little biliary excretion occurred. When the urinary sulfates of the hydroxy lactams were administered i.v. to rats, 70% was eliminated in urine within 1 hr; however, if the kidneys were ligated biliary excretion of sulphate was higher (58% in 5 h). After intraduodenal administration of the biliary conjugates of CR metabolism, all of the dose was resorbed to be re-secreted in bile or excreted as sulphates in urine. These studies confirm that the major metabolic fate of CR in the rat is oxidation to lactam, followed by ring hydroxylation, sulfation and urinary excretion. /Dibenz[b,f]-1,4-oxazepine (CR)/

Excerpt from ERG Guide 159 [Substances (Irritating)]: Inhalation of vapors or dust is extremely irritating. May cause burning of eyes and flow of tears. May cause coughing, difficult breathing and nausea. Brief exposure effects last only a few minutes. Exposure in an enclosed area may be very harmful. Fire will produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may cause pollution. (ERG, 2016)

Excerpt from ERG Guide 159 [Substances (Irritating)]: Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves. Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim calm and warm. Effects should disappear after individual has been exposed to fresh air for approximately 10 minutes. (ERG, 2016)

Treatment consists of helping the affected person get more oxygen in his or her blood and of stopping agent-caused chemical burns from getting worse. Medications that are used to treat asthma (such as bronchodilators and steroids) may also be used to help the person breathe. Eye exposures are treated by rinsing the eyes with water until there is no evidence of riot control agents in the eyes. No antidote exists for poisoning from riot control agents. Burn injuries to the skin are treated with standard burn management techniques, including use of medicated bandages. /Riot control agents/

/HUMAN EXPOSURE STUDIES/ The chemical irritants o-chlorobenzylidene malononitrile (CS), n-nonanoylvanillylamine (VAN) and dibenzoxazepine (CR) and several of its derivatives have been assayed using the human blister base. The relative potencies found by this method, CR greater than VAN greater than CS, conflicted with those found in non-human test systems but the rank order of potency of CS and CR reflected that reported in tests on the human eye and tongue. Data derived from humans thus appear to be of importance when assessing irritant potency. Interactions between CS, CR, VAN, capsaicin and bradykinin were investigated to discover any common pathways of irritant activity. Self-desensitization developed on repeated application of all agents to the blister base and selective cross-desensitization also occurred.|/SIGNS AND SYMPTOMS/ Irritant incapacitants, also called riot control agents, lacrimators and tear gases, are aerosol-dispersed chemicals that produce eye, nose, mouth, skin and respiratory tract irritation. Tear gas is the common name for substances that, in low concentrations, cause pain in the eyes, flow of tears and difficulty in keeping the eyes open. Only three agents are likely to be deployed: (i) 1-chloroacetophenone (CN); (ii) 2-chlorobenzylidene malononitrile (CS); or (iii) dibenz[b,f]-1,4-oxazepine (CR). CN is the most toxic lacrimator and at high concentrations has caused corneal epithelial damage and chemosis. It has accounted for at least five deaths, which have resulted from pulmonary injury and/or asphyxia. CS is a 10-times more potent lacrimator than CN but is less systemically toxic. CR is the most potent lacrimator with the least systemic toxicity and is highly stable. CN, CS and CR cause almost instant pain in the eyes, excessive flow of tears and closure of the eyelids, and incapacitation of exposed individuals. Apart from the effects on the eyes, these agents also cause irritation in the nose and mouth, throat and airways and sometimes to the skin, particularly in moist and warm areas. In situations of massive exposure, tear gas, which is swallowed, may cause vomiting. Serious systemic toxicity is rare and occurs most frequently with CN; it is most likely to occur when these agents are used in very high concentrations within confined non-ventilated spaces. Based on the available toxicological and medical evidence, CS and CR have a large safety margin for life-threatening or irreversible toxic effects. There is no evidence that a healthy individual will experience long-term health effects from open-air exposures to CS or CR, although contamination with CR is less easy to remove. /Dibenz[b,f]-1,4-oxazepine (CR)/|/SIGNS AND SYMPTOMS/ ... Dibenzoxazepine (CR) ... belongs to a class of agents collectively known as riot control agents or "tear gas."... Most exposures are inhalational, ocular, or dermal and typically lead to complaints of eye, nose, and throat irritation; hacking cough; suffocation or choking sensation; and dyspnea ... high-dose exposures in an enclosed space may lead to the development of airway edema, noncardiogenic pulmonary edema, and possibly respiratory arrest. /Riot control agents/|/SIGNS AND SYMPTOMS/ Immediate signs and symptoms of exposure to a riot control agent ... : Eyes: excessive tearing, burning, blurred vision, redness; Nose: runny nose, burning, swelling; Mouth: burning, irritation, difficulty swallowing, drooling; Lungs: chest tightness, coughing, choking sensation, noisy breathing (wheezing), shortness of breath; Skin: burns, rash; Other: nausea and vomiting. Long-lasting exposure or exposure to a large dose of riot control agent, especially in a closed setting, may cause severe effects such as the following: blindness, glaucoma (a serious eye condition that can lead to blindness), immediate death due to severe chemical burns to the throat and lungs, respiratory failure possibly resulting in death ... Prolonged exposure, especially in an enclosed area, may lead to long-term effects such as eye problems including scarring, glaucoma, and cataracts, and may possibly cause breathing problems such as asthma. If symptoms go away soon after a person is removed from exposure to riot control agents, long-term health effects are unlikely to occur. /Riot control agents/|/SIGNS AND SYMPTOMS/ In humans, the effects caused by CR are qualitatively similar to those caused by CS, but there is an approximately 5-fold difference in potency. A splash of a solution in the range of 0.01% to 0.1% causes immediate eye pain, blepharospasm, and lacrimation, which persist for 15 to 30 minutes, and conjunctival injection and minimal edema of lid margins, which last for 3 to 6 hours. A solution splashed in the mouth causes burning of the tongue and palate and salivation for 5 to 10 minutes. If a splash enters the nose, it causes irritation and rhinorrhea. Skin exposure causes burning within a few minutes, which persists for 15 to 30 minutes, and an erythema lasting for 1 to 2 hours. A blood pressure increase may accompany the subjective discomfort; this is thought to be caused by the stress of the irritation, since the amount of CR that could be absorbed is much too small to cause a pharmacological effect.

CR irritant

Currently used only in solution for dissemination in liquid dispensers. The solutions in the dispensers contains 0.1% dibenzoxazepine in 80 parts propylene glycol and 20 parts water.

Dibenz[b,f][1,4]oxazepine: ACTIVE