Chlornaphazin

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.

PRECAUTIONS FOR "CARCINOGENS": 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. /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/

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.

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.

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.

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.

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/

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).

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

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).

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.

Chlornaphazine

Group 1: Carcinogenic to humans

Volume 4: (1974) Some Aromatic Amines, Hydrazine and Related Substances, N-Nitroso Compounds and Miscellaneous Alkylating Agents

2012

2008

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).

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).

IN 4 GROUPS OF 30 A/J MICE GIVEN TOTAL DOSES OF 280, 1119, 4477 & 17,900 UMOL/KG BODY WT (EQUIVALENT TO 75, 300, 1200, & 4800 MG/KG BODY WT) IN AQUEOUS SOLUTION BY IP INJECTION 3 TIMES WEEKLY FOR 4 WK, DOSE RELATED INCR IN INCIDENCE OF PULMONARY ADENOMAS, & IN NUMBER OF LUNG TUMORS PER MOUSE, WAS OBSERVED. THE MICE WERE FIRST INJECTED WHEN 4 TO 6 WEEKS OLD AND WERE KILLED AT 39 WK AFTER THE FIRST INJECTION. THE RESPECTIVE INCIDENCES OF LUNG TUMORS PER MOUSE IN THE TREATED GROUPS WERE 0.5, 0.9, 2.0 & 3.6, & 0.48 IN THE VEHICLE CONTROL GROUP (SHIMKIN ET AL, 1966).

REPEATED SC INJECTIONS OF 40 MG N,N-BIS(2-CHLOROETHYL)-2-NAPHTHYLAMINE INDUCED LOCAL SC SARCOMAS IN 7 RATS (KOLLER, 1953).

CHLORNAPHAZIN, A CARCINOGEN, WAS POS IN SALMONELLA/MICROSOME TEST. THERE WAS HIGH CORRELATION (AMONG AGENTS TESTED) BETWEEN MUTAGENICITY & CARCINOGENICITY.

... Nitrogen mustard chlornaphazine (CN) has been confirmed to be mutagenic to Salmonella and, unexpectedly, the more so when evaluated in the presence of liver S9 mix. It also has been established as clastogenic to Chinese hamster lung cells exposed in vitro to dose levels > 2.5 ug/ml. Chlornaphazine subdued mice at doses of 5 g/kg, but only the occasional death occurred during the 4 days following oral administration of this dose in corn oil. Consequently, a median lethal dose level was not established. Nonetheless, dose levels of 500 mg/kg or greater gave a clear positive response in both the mouse and the rat bone marrow micronucleus assay. Although depression of erythropoiesis was observed in mice, a clastogenic response still was observed in the bone marrow 24 hr after dosing. The positive response in the rat was greater than that observed in the mouse. The present data provide a further instance of an established human carcinogen being readily detected by standard in vitro and in vivo mutagenicity assays.

Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) evidence in animals: limited. Overall summary evaluation of carcinogenic risk to humans is Group 1: The agent is carcinogenic to humans. /From table/

Chlornaphazine: delisted as known to be a human carcinogen.

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).

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).

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).