디벤즈-(b,f)-1,4-옥사제핀

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.

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.

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/

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 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).

/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.

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 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).

/LABORATORY ANIMALS: Acute Exposure/ Three groups of 18 /rats/ were exposed respectively to the following large doses of dibenz (b.f)-1:4 oxazepine (CR) aerosols, 78,200,140,900 and 161,300 mg/min/cu m. Animals were killed at intervals from 15 min to 2 days, and the lungs examined macroscopically, by electron microscopy and conventional histology. There were no deaths during or after exposure. Macroscopically the lungs from all rats appeared normal. Microscopically there were a few areas of mild congestion, hemorrhage and emphysema, but there was little variation between the different groups. Electron micrographs revealed some morphological alteration of the epithelium and endothelium but only occasional changes in the interstitium. The alterations took the form of "ballooning" of the endothelium with isolated foci of swelling and thickening of the epithelium. Interstitial edema was observed in one animal only which was exposed to the highest concentration. The effects appeared similar in all groups, and are thought to be transient. The results of this investigation suggest that even high doses of CR aerosols cause minimal damage to the lung, and the structural alterations which do occur are believed to be due to the stress to which the animals were subjected during the exposure period.

/LABORATORY ANIMALS: Acute Exposure/ Lung damage caused by inhalation (single exposure for 60 min) of sublethal concentration of pure aerosols of dibenz(b,f)-1,4-oxazepine (CR) and 1-chloroacetophenone (CN) have been examined at different time intervals in rats. The damage was not severe with CR (2830 mg/cu m) but in the case of CN (60.26 mg/cu m) it was evident up to 30th day post exposure. Necrobiosis, attenuation of bronchiolar epithelium, edema in the air ways and also in the lumen of alveoli leading to substantial changes in the histoarchitecture of the lung were observed during CN exposure. On the other hand CR caused degenerative changes which disappeared on 30th day. /Dibenz(b,f)-1,4-oxazepine (CR)/

/LABORATORY ANIMALS: Acute Exposure/ The biochemical changes in blood samples of rats at different intervals after O-Chloroacetophenone (CN) and Dibenz (b,f)-1,4 oxazepine (CR) were studied. After a single subacute (1/10 LC50) exposure, both the compounds induced hyperglycaemia which was abolished within 24 hr. The level of plasma urea was unaltered. CR exposed animals did not show any significant changes in plasma GOT, acid and alkaline phosphatase activities at different intervals. However, in CN exposed animals, a significant elevation of the activities of GOT, GPT, acid and alkaline phosphatase was observed at different intervals. All the parameters became normal within seven days after the exposure. Inhalation of CN aerosols can thus lead to tissue damaging effects in rats. /Dibenz (b,f)-1,4 oxazepine (CR)/:

/LABORATORY ANIMALS: Acute Exposure/ Toxicological evaluation was made on the effects of two peripheral sensory irritants (tear gases): 1-chloroacetophenone (CN) and dibenz[b,f]-1,4-oxazepine (CR). Animals had a 15-min daily inhalation exposure to average vapor concentrations of 87.6 mg CN/cu m or 1008 mg CR/cu m (both equal to 0.05 LC50) for 5 or 10 days and were sacrificed 24 hr after the last exposure, when biochemical and histopathological observations were made. Both chemicals caused a significant decrease in body weight gain. Histological changes in lung, liver and kidneys were more severe after 10 than after 5 days of exposure and were more severe in CN-exposed than in CR-exposed mice. Organ weight to body weight ratios remained normal except for the spleen to body weight ratio, which decreased in CN-exposed mice after both 5 and 10 days of exposure. Biochemical indicators showed a toxic response only in CN-exposed mice, but the only consistent change was an increase in blood glucose. Hepatic alkaline phosphatase was not influenced, malondialdehyde concentration and acid phosphatase activity were increased only after 5 days of exposure and liver GSH concentration decreased after 10 days of exposure. Results indicate that CN is not only more toxic than CR in absolute terms but is also more toxic at the 5% level of their LC50. /Dibenz[b,f]-1,4-oxazepine (CR)/

For more Non-Human Toxicity Excerpts (Complete) data for DIBENZ(b,f)[1,4]OXAZEPINE (8 total), please visit the HSDB record page.

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).

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 will result in its direct release to the environment. If released to air, a vapor pressure of 2.1X10-4 mm Hg at 25 °C indicates that dibenz(b,f)[1,4]oxazepine will exist solely as a vapor in the ambient atmosphere. Vapor-phase dibenz(b,f)[1,4]oxazepine 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 1 hour. Dibenz(b,f)[1,4]oxazepine contains chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight; however, the kinetics of this potential reaction are not known. If released to soil, an estimated Koc value of 1020 indicates that dibenz(b,f)[1,4]oxazepine is expected to have low mobility in soil. Volatilization from moist soil is expected to be an important environmental fate process based on an estimated Henry's Law constant of 4.1X10-3 atm-cu m/mole. Dibenz(b,f)[1,4]oxazepine is not expected to volatilize from dry soil surfaces based on its estimated vapor pressure. If released into water, dibenz(b,f)[1,4]oxazepine is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important environmental fate process based upon the estimated Henry's Law constant of this compound. Estimated volatilization half-lives for a model river and model lake are 2 hours and 6 days, respectively. An estimated BCF of 42 suggests the potential for bioconcentration in aquatic organisms is moderate. 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. 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)/