Azaserine

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical 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/

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U015, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A poor candidate for incineration.

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/

For more Disposal Methods (Complete) data for AZASERINE (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 AZASERINE (9 total), please visit the HSDB record page.

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:

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/

Chemoprevention by a synthetic retinoid, selenium, and these agents in combination during the postinitiation stages of carcinogenesis induced in rats by azaserine was evaluated. Male Lewis rats were given three weekly injections of 30 mg/kg azaserine while being fed a purified diet. One week after completion of carcinogen treatment, groups of rats were switched to the purified diet supplemented with either a retinoid, N-(2-hydroxethyl)retinamide, at a level of 0.5 or 1 mmol/kg diet, or with 5 ppm sodium selenite, or with a combination of retinoid and selenium. One year after the diet change, the incidence of pancreatic and other neoplasms was determined by autopsy and histologic study. The incidence of pancreatic carcinoma (including carcinoma-in-situ, CIS) among nonretinoid-treated controls was 68%. Since the dietary supplements were fed after completion of exposure to the carcinogen, the effects on both pancreatic and liver carcinogenesis were exerted during postinitiation phase of carcinogenesis. As in previous studies, the retinoid inhibited the progression of pancreatic carcinogenesis in a dose-related fashion. Selenium alone had no effect. However, the combination of retinoid plus selenium was more effective than retinoid alone, although the increase in inhibition was not large. The retinoid was also found to inhibit liver carcinogenesis induced by azaserine. Selenium, either alone or in combination with retinoid, was ineffective.

Effect of dietary intake of fish (menhaden) oil and fish (cod) protein on the development of pancreatic preneoplastic lesions was examined in male Wistar rats. Fourteen day old animals were given a single ip injection of 30 mg L-azaserine/kg body weight; diazoacetate serine (ester). At 21 days of age they were weaned and maintained on dietary treatment for 4 months. Fish protein did not appear to produce a significantly different preneoplastic response when compared to casein as a protein source. However, a 20% menhaden oil diet, rich in omega 3 fatty acids, produced a significant decrease in the development of both the size and number of preneoplastic lesions when compared to a 20% corn oil diet rich in omega 6 fatty acids. This study provides evidence that fish oils, rich in omega 3 fatty acids, may have potential as inhibitory agents in cancer development.

Diets containing raw soybean products fed ad libitum caused a reduction in food consumption and growth, pancreatic enlargement, hypersecretion of digestive enzymes, and enlargement of intestinal segments and their contents in rats, chicks and geese. These effects were found to be related to the concentration of trypsin inhibitor in the diet. ... In long-term studies the incidence of pancreatic nodules was correlated to the level of trypsin inhibitor in the diet. Feeding raw soybean products potentiated the carcinogenic effect of azaserine and meal feeding enhanced the incidence and size of the pancreatic nodules in rats fed raw soybean products.

Effects of coffee and dietary fat (alone and in combination) on the development of preneoplastic lesions in exocrine pancreas were investigated in rats and hamsters, treated with azaserine or N-nitrosobis(2-oxopropyl)amine, respectively. Animals were given the respective diets (5% or 25% corn oil) and coffee (instead of drinking water) within one week after the treatment with carcinogen. At four months postinitiation, the pancreata were quantitatively examined for the number and size of preneoplstic foci. In rats, coffee alone inhibited growth of acidophilic foci and, moreover, slightly inhibited the positive modulating effect of fat on growth of these foci, pointing to a negative rather than a positive interaction between these two life-style factors. In hamsters, coffee alone enhanced growth of cystic foci, whereas fat alone enhanced growth of ductular foci. An interaction between fat and coffee on pancreatic carcinogenesis in hamsters could not be demonstrated.

For more Interactions (Complete) data for AZASERINE (8 total), please visit the HSDB record page.

TERRESTRIAL FATE: Information pertaining to the biodegradation of azaserine in soil was not located in the available literature. Azaserine should hydrolyze rapidly in moist acidic soils. Azaserine is an amino-acid with a pKa of 8.55(1) that will dissociate in soil in varying proportions that are pH dependent. Ions are not expected to volatilize, nor do they generally adsorb to particulate matter as strongly as do their neutral counterparts(2). Both estimates of the Henry's Law constant of 2.56X10-16 atm-cu m/mole(3) and the vapor pressure of 1.53X10-10 at 25 °C indicate that the volatilization of azaserine from either moist or dry soil surfaces should not be important fate processes(3). An estimated Koc of 7(2) indicates azaserine should be highly mobile in soil(4); and it may leach to ground water if released to soil(SRC).

AQUATIC FATE: Information pertaining to the biodegradation of azaserine in water was not located in the available literature. Azaserine should hydrolyze rapidly in acidic waters. Rate constants for the acid, neutral and base hydrolysis of azaserine in aqueous solution at pHs of 3, 7 and 11 and 25 °C were KA = 328 M-1 hr-1, 2.6X10-4 hr-1 and 6.8X10-3 M-1 hr-1(5), which correspond to half-lives of 2.1 hours, 111 days and 425 days, respectively(SRC). Azaserine is an amino-acid with a pKa of 8.55(1) that will dissociate in natural waters in varying proportions that are pH dependent. Ions are not expected to volatilize, nor do they generally adsorb to sediments as strongly as do their neutral counterparts(2). An estimated Henry's Law constant of 2.56X10-16 atm-cu m/mole at 25 °C(3) indicates that the volatilization of azaserine from natural bodies of water should not be an important fate process(3). An estimated Koc of 7(2) indicates azaserine should not partition from the water column to organic matter(4) contained in sediments and suspended solids; and an estimated bioconcentration factor (log BCF) of -0.10(2) indicates that azaserine should not bioconcentrate among aquatic organisms(SRC).

ATMOSPHERIC FATE: Based upon a vapor pressure of 1.53X10-0 mm Hg at 25 °C, which has been calculated from the water solubility and Henry's Law constant, azaserine is expected to exist almost entirely in the particulate phase in ambient air(2). However, if released to the atmosphere as a gas, the vapor phase reaction of azaserine with photochemically produced hydroxyl radicals is likely to be an important fate process. The rate constant for the vapor-phase reaction of azaserine with photochemically produced hydroxyl radicals has been estimated to be 4.0X10-11 cu cm/molecule-sec at 25 °C; which corresponds to an atmospheric half-life of about 10 hours at an atmospheric concn of 5X10+5 hydroxyl radicals per cu cm(1). Also, both wet and dry deposition can occur.

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 water solubility of 1.36X10+5 mg/L at 25 °C(1), a Koc for azaserine of 7 has been calculated using regression-derived equations(2,SRC). This Koc value indicates that azaserine should be highly mobile in soil(3), and it should not partition from the water column to organic matter contained in sediments and suspended solids(SRC). In addition, azaserine is an amino-acid with a pKa of 8.55(4) that will dissociate in environmental media in varying proportions that are pH dependent. Generally ions do not adsorb to particulate matter as strongly as their neutral counterparts(2).

As of 1975, azaserine was not commercially manufactured in the US(1). Current production and import/export data were not located in the available literature. It was however, produced in small quantities for research purposes(1). Azaserine has been used in veterinary medicine as an antibiotic, antineoplastic and abortifacient(1). It may be released to the environment via effluents at sites where it is produced or used(SRC).

Azaserine

Group 2B: Possibly carcinogenic to humans

Volume 10: (1976) Some Naturally Occurring Substances

1987

1987

Based upon an estimated water solubility of 1.36X10+5 mg/L at 25 °C(1), a bioconcentration factor (log BCF) of -0.10 for azaserine has been calculated using a recommended regression-derived equation(2,SRC). This BCF value indicates that azaserine should not bioconcentrate among aquatic organisms(SRC).

Azaserine is an amino-acid with a pKa of 8.55(1) that will dissociate in environmental media in varying proportions that are pH dependent. Ions are not expected to volatilize from water. The Henry's Law constant of 2.56X10-16 atm- cu m/mole at 25 °C for azaserine has been estimated using a bond contribution method(2). Based upon this Henry's Law constant, volatilization of azaserine from natural bodies of water and moist soil should not be an important fate process(3). Based upon a vapor pressure of about 1.53X10-10 mm Hg at 25 °C, which has been calculated from the water solubility and Henry's Law constant, azaserine is not expected to evaporate from dry surfaces(SRC).

ESCHERICHIA COLI WP2 - REVERSE MUTATION STUDIES: POSITIVE.

DNA REPAIR-DEFICIENT BACTERIAL TESTS: POSITIVE.

AMONG 18 /CHARLES RIVER WISTAR/ RATS GIVEN /WEEKLY/ IP INJECTIONS /OF 5 MG/KG IN SALINE/ & KILLED 12 OR MORE MO AFTER INITIAL TREATMENT, 5 ADENOCARCINOMAS OF PANCREAS & 1 PROBABLE CARCINOMA, ... METASTASES IN LIVER OCCURRED ... NO PANCREATIC OR KIDNEY TUMORS OCCURRED IN 17 CONTROL RATS, INJECTED WITH SALINE ... .

... CHARLES RIVER WISTAR RATS ... GIVEN WEEKLY OR TWICE WEEKLY IP INJECTIONS OF 5 MG/KG BODY WT AZASERINE IN SALINE FOR 6 MO. OF 23 RATS ... 12 OR MORE MO AFTER INITIAL TREATMENT, 9 HAD ADENOCARCINOMAS OF PANCREAS & 3 HAD PROBABLE CARCINOMAS. NO PANCREATIC OR KIDNEY TUMORS OCCURRED IN 17 CONTROL RATS INJECTED WITH SALINE ... .

For more Non-Human Toxicity Excerpts (Complete) data for AZASERINE (21 total), please visit the HSDB record page.

U015; As stipulated in 40 CFR 261.33, when azaserine, 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 1 lb or 0.454 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).