Chlornaphazine

268.181

268.18

207-785-0

U46E473275

62209

2810

DTXSID3060087

C1047

PLATELETS FROM PETROLEUM ETHER

3.2

4.535 (est)

Chlornaphazine appears as colorless plates or brown solid. (NTP, 1992)

1.234g/cm3

54-56 °C

210 °C @ Press: 5 Torr

204.4ºC

1.63

VERY SPARINGLY SOL IN WATER, GLYCEROL; MORE SOL (IN ASCENDING DEGREE) IN PETROLEUM ETHER, ETHANOL, OLIVE OIL, ETHER, ACETONE, BENZENE

Storage site should be as close as practicable to lab in which carcinogens are to be used, so that only small quantities required for expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ) that bears appropriate label. An inventory should be kept, showing quantity of carcinogen & date it was acquired Facilities for dispensing should be contiguous to storage area.

2X10-6 mm Hg at 25 deg C (est)

LD50 intraperitoneal in mouse: 1300mg/kg

Insoluble in water.

Amines, Phosphines, and Pyridines

Explosive

CHLORNAPHAZINE reacts with nucleophiles (NTP, 1992).

2810

QM2450000

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

H350

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U026, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.|PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/|For more Disposal Methods (Complete) data for CHLORNAPHAZINE (7 total), please visit the HSDB record page.

CLEMMESEN J, HJALGRIM-JENSEN S; ARCH TOXICOL (SUPPL) (3): 19-25 (1980). IN A RECENT REVIEW OF CHEMICALS ASSOCIATED WITH CANCER PRODUCTION IN MAN FROM US NATIONAL CANCER INSTITUTE & TWO FEDERAL AGENCIES, SEVEN DRUGS WERE LISTED. THE EVIDENCE FOR THE CARCINOGENICITY OF CHLORNAPHAZINE WILL BE REVIEWED.|National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Chlornaphazine (494-03-1) is delisted as known to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/append/appb.pdf]

Flash point data are not available for this chemical, but it is probably combustible. (NTP, 1992)

|Danger|H350: May cause cancer [Danger Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501

Fires involving this compound should be controlled using a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: 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)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves. RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)|PRECAUTIONS FOR "CARCINOGENS": ... dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for CHLORNAPHAZINE (10 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

The major hazards encountered in the use and handling of chlornaphazine stem from its toxicologic properties. The primary effect from exposure to this crystalline substance is cancer. Chlornaphazine has been indicated as a human carcinogen (Group 1) by the International Agency for Research on Cancer (IARC). Exposure should be controlled by mechanical ventilation with high-effici ency particulate arrestors (HEPA) or charcoal filters to minimize the amount of the substance in exhausted air. In activities or situations where over-exposure may occur, wear full protective clothing and a carefully fitted respirator. If contact should occur, immediately irrigate affected eyes with copious amounts of tepid water for at least 15 minutes and wash affected skin extremely thoroughly with soap and water. Contaminated clothing should be removed and discarded or left at the work site for cleaning before reuse. Smoking, eating, and drinking should be prohibited in chlornaphazine work areas. Chlornaphazine should be stored and transported in securely sealed glass bottles or ampoules, which are in turn placed inside strong screw-cap or snap-top containers. This substance is a good candidate for disposal by rotary kiln or fluidized bed forms of incineration.

U026; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

As stipulated in 40 CFR 261.33, when chlornaphazine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

CHLORNAPHAZINE NONCOMPETITIVELY BLOCKED THE ACTIVATION OF RAT HEPATIC GUANYLATE CYCLASE BY N'-NITRO-N-NITROSO-N-PROPYLGUANIDINE & HYDRAZINE.

Chlornaphthazine has not been reported to occur as such in nature.

TERRESTRIAL FATE: Chlornaphazine has a measured aqueous hydrolysis half-life of 216 hrs at 25 °C and pH 7(1) which indicates that the compound will hydrolyze in moist soil(SRC). An estimated Koc value of 21000, which was derived from an estimated log Kow of 4.535, suggests that chlornaphazine will be essentially immobile in soil and not expected to leach(2,3,4,SRC). No data are available to predict the biodegradability of chlornaphazine in soil(SRC).|AQUATIC FATE: Chlornaphazine has a measured aqueous hydrolysis half-life of 216 hrs at 25 °C and pH 7(1) indicating that hydrolysis will be a major environmental fate process in water. An estimated Koc value of 21000, which was derived from an estimated log Kow of 4.535(2,3,SRC), suggests that chlornaphazine may partition from the water column to sediment and suspended material; however, concurrent hydrolysis may greatly diminish the potential importance of adsorption to sediment(SRC). Chlornaphazine is not expected to volatilize from water based upon an estimated Henry's Law Constant of 1X10-7(3,4,SRC). No data are available to predict the biodegradability of chlornaphazine in water(SRC).|ATMOSPHERIC FATE: Based upon a reported boiling point of 210 °C at 5 mm Hg(1), the vapor pressure of chlornaphazine at 25 °C can be estimated to be roughly 2X10-6 mm Hg using a Clausius-Clapeyron relationship(2,SRC). This estimated vapor pressure suggests that chlornaphazine may exist in both the vapor-phase and particulate-phase in the ambient atmosphere(3,SRC). Vapor-phase chlornaphazine is expected to degrade rapidly in the ambient atmosphere by reaction with photochemically formed hydroxyl radicals; the half-life for this reaction in typical air can be estimated to be about 1.4 hrs(4,SRC). Chlornaphazine associated with atmospheric particulate material will be subject to physical removal by wet (rainfall, etc) and dry deposition(SRC).

At 25 °C, the neutral aqueous hydrolysis rate constant for chlornaphazine has been experimentally determined to be 0.0032/hr which corresponds to a half-life of 216 hrs at pH 7(1). The rate constant for the vapor-phase reaction of chlornaphazine with photochemically produced hydroxyl radicals has been estimated to be 270.4X10-12 cu cm/molecule-sec at 25 °C which corresponds to an atmospheric half-life of about 1.4 hrs at an atmospheric concn of 5X10+5 hydroxyl radicals per cu cm(2,SRC).

Based upon an estimated Log Kow of 4.535(1), the BCF for chlornaphazine can be estimated to be about 1650 from a recommended regression-derived equation(2,SRC). This BCF value suggests that bioconcentration in aquatic organisms may be important(SRC).

Based upon an estimated log Kow of 4.535(1), the Koc for chlornaphazine can be estimated to be about 21000 from a regression-derived equation developed for aromatic and polyaromatic compounds(2,SRC). This Koc value suggests that chlornaphazine may be essentially immobile in soil(3).

The Henry's Law constant for chlornaphazine can be estimated to be about 1.7X10-7 atm cu m-mole at 25 °C using a chemical structure estimation method(1,SRC). The value of this Henry's Law constant suggests that chlornaphazine is essentially nonvolatile from water(2).

No data are available to suggest that the general population of the US is exposed to chlornaphazine(SRC).

THIS CMPD HAS BEEN USED IN A NUMBER OF COUNTRIES AS A CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF LEUKEMIA & OF HODGKIN'S DISEASE AS WELL AS FOR THE CONTROL OF POLYCYTHEMIA VERA.|ALTHOUGH IT STILL APPEARS IN SOME DRUG DIRECTORIES, N,N-BIS(2-CHLOROETHYL)-2-NAPHTHYLAMINE PROBABLY DOES NOT HAVE WIDE THERAPEUTIC USAGE.

IT HAS REPORTEDLY BEEN WITHDRAWN FROM USE IN DENMARK BECAUSE OF DETECTED INSTANCES OF CANCER OF BLADDER FOLLOWING ITS ADMIN.

RATS INJECTED WITH N,N-BIS(2-CHLOROETHYL)-2-NAPHTHYLAMINE EXCRETED 2-AMINO-1-NAPHTHYL HYDROGEN SULFATE & 2-ACETAMIDO-6-NAPHTHYL HYDROGEN SULFATE.

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONS FORMULATED FOR HYDROLYSIS OF SEVERAL ANILINE MUSTARDS & THEIR ANTITUMOR ACTIVITY AGAINST WALKER 256 TUMOR & L1210 & P388 LEUKEMIA. THE ANTITUMOR ACTIVITY PARALLELS HYDROLYSIS; TOXICITY PARALLELS ANTITUMOR EFFICACY.

SYMPTOMS: This compound may cause nausea, vomiting, headache, diarrhea, bladder tumors, and depression of bone marrow function. It may also cause severe local irritation of eyes, skin and other tissues. ACUTE/CHRONIC HAZARDS: This compound is a skin, eye and mucous membrane irritant. It is toxic by ingestion, inhalation and skin absorption. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

ELEVEN SEPARATE CASES OF BLADDER CANCER ASSOC WITH USE OF CHLORNAPHAZINE WERE REPORTED. THREE FURTHER CASES HAVE BEEN IDENTIFIED.|A COMMON FACTOR AMONG 10 PT IN WHOM BLADDER TUMORS HAVE BEEN DIAGNOSED IS THAT 9 OF THE PATIENTS WERE ALSO TREATED WITH (32)P AS SODIUM PHOSPHATE INJECTIONS. HOWEVER, ... /IT HAS BEEN REPORTED/ THAT OUT OF 46 PATIENTS TREATED WITH (32)P AS SODIUM PHOSPHATE ALONE WITHOUT CHLORNAPHAZINE, NO CASES OF BLADDER TUMORS WERE REPORTED.|CHLORNAPHAZINE, FORMERLY USED IN THE TREATMENT OF POLYCYTHEMIA, HAS BEEN PROVEN TO INDUCE BLADDER CANCER IN 30% OF THE PATIENTS TREATED.|TWO CASES OF BLADDER CARCINOMA FOLLOWING TREATMENT WITH CHLORNAPHAZINE FOR HODGKIN'S DISEASE ARE PRESENTED. BLADDER CANCER DEVELOPED 5 & 6 YR AFTER THERAPY, WHEN THE DRUG WAS STOPPED.|Among 61 patients with polycythemia vera treated with chlornaphazine in 1954-1962 and followed until 1974, eight developed invasive carcinoma of the bladder, five developed papillary carcinomas of the bladder and eight had abnormal urinary cytology. The invasive carcinomas were seen in four of five patients given 50-99 g and in one of 31 patients given less than 50 g. No noncausal explanation can be suggested.

chlornaphazin

Not produced or used commercially in the United States ... Currently, this drug does not have wide therapeutic usage.|Chlornaphazine has reportedly been withdrawn from use in Denmark because of detected instances of cancer of the bladder following its administration.

INFLUENCE OF SUBSTITUENTS & OF SOLVENTS ON UV SPECTROPHOTOMETRIC BEHAVIOR OF 12 MEDICINALS (INCL CHLORNAPHAZINE) WAS STUDIED. DISPLACEMENT OF ABSORPTION BANDS E, K, & B OF ABSORPTION MAX & MIN ARE DISCUSSED. RESULTING DATA CAN BE APPLIED TO THE QUANTITATIVE DETERMINATION OF PURE SUBSTANCES OR OF THEIR PREPARATIONS.