1-부틸-1-니트로소우레아

Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further treated with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues.

No female rats treated with a small amount of N-nitrosobutlyurea (NBU) developed mammary tumors, multiple mammary tumors developed if adminstration of a small amount of NBU was followed by a prolonged treatment of either diethylstilbesterol or 17-beta-estradiol.

Effects of barbital (BB) on neuro-oncogenesis were examined in a rat transplacental carcinogenesis model. Pregnant F344 rats were divided into 7 groups. Dams in group I received subcutaneous injections of 10 mg/rat 1-butyl-1-nitrosourea (BNU) on the days 15, 18 and 21 of pregnancy and dams in groups II-IV, 1 mg/rat 1-butyl-1-nitrosourea on the same time schedule. In addition to the treatment with 1-butyl-1-nitrosourea, dams in group IV were given 0.125% barbital solution as their drinking water from the day 12 of pregnancy to parturition. Offspring in groups III and IV received 0.125% barbital solution as drinking water from 4 weeks of age until the termination of the study. Animals in groups V and VI were given 0.25% and 0.125% barbital solutions, respectively, in the peri- and postnatal period without 1-butyl-1-nitrosourea treatment. Dams in group VII received 250 mg/kg barbital subcutaneously on the days 15, 18 and 21 of pregnancy. Offspring in all groups were observed until 105-116 weeks of age. High yields of neurogenic tumors, such as gliomas and neurinomas, were observed in group I. In groups II, III and IV, single cases of a chordoma, a granular cell tumor, and a neurinoma and a malignant reticulosis, which are known to occur spontaneously, were noted, although no gliomas were found. No neurogenic tumors were observed in groups V-VII. With regard to lesions other than those in neurogenic organs, a significant increase in liver tumors was observed in group III compared to group II. In contrast, lung tumors were not found in group III, while they were observed in groups II and IV. These results suggest that BB has no neuro-carcinogenic activity in the rat transplacental carcinogenesis model.

The enhancing effects of o-vanillin ... on structural chromosome aberrations induced by alkylating agents were studied in cultured Chinese hamster cells. o-Vanillin was not a clastogen by itself. When cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the presence of 400 ug/mL of o-vanillin for 2 hr, the frequency of aberrant cells with chromosome aberrations was increased 2.8-fold compared with cells treated with N-methyl-N'-nitro-N-nitrosoguanidine alone. The total number of breakage-type and exchange-type aberrations was increased 18.5- and 8.3-fold, respectively. The enhancing effects were also observed for chromosome aberrations induced by N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea. On the other hand, those induced by N-butyl-N-nitrosourea were only slightly enhanced. ...

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 30(SRC), determined from a log Kow of 1.04(2) and a regression-derived equation(3), indicates that N-nitroso-N-butylurea is expected to have very high mobility in soil(SRC). Volatilization of N-nitroso-N-butylurea from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.3X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). N-Nitroso-N-butylurea is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.3X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2018).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 30(SRC), determined from a log Kow of 1.04(2) and a regression-derived equation(3), indicates that N-nitroso-N-butylurea is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.3X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). According to a classification scheme(5), an estimated BCF of 2(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2018).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N-nitroso-N-butylurea, which has an estimated vapor pressure of 5.3X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase N-nitroso-N-butylurea 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 2 days(SRC), calculated from its rate constant of 8.4X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). N-Nitroso compounds, like N-nitroso-N-butylurea, commonly absorb at wavelengths of approximately 330 nm(3) and, therefore, N-nitroso-N-butylurea may be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC).

IDENTIFICATION AND USE: N-Nitroso-N-butylurea (BNU) is not produced commercially in the USA. HUMAN STUDIES: There are no data available. ANIMAL STUDIES: The increased incidence of neoplasms in rats and mice fed butylurea and sodium nitrite in combination may result from in vivo formation of the carcinogen BNU. Considerable number of ovarian tumors were produced in adult rats treated with multiple oral or im administration of BNU. Cases of ameloblastic odontomas were found in rats treated with multiple oral administration of BNU. BNU, a strong leukemogen for rats and mice, was administered prenatally, neonatally, and to sucklings via maternal milk in the rats. Contrary to expectations, leukemia developed in only one rat of all the offspring of the mother animals that received the BNU treatment during their pregnancy. BNU was injected once at dosage levels of 150 or 75 mg/kg into 3- or 6-week-old male mice. Intestinal tumors occurred in 100% of the mice that survived more than 15 weeks after injection with a high dose of BNU at 6 weeks of age, and in 35 to 70% of the mice in other treatment groups. T-cell leukemias have been induced in adult mice by 12 or 15 weeks of exposure to BNU in the drinking water. Repeated BNU (5 mg/day, orally) administration to rats caused atrophies of thymus, lymph nodes and spleen at early stage of treatment. O6-Butylguanine was detected in the urine of rats given the butylating agent BNU. This suggests that O6-butylguanine formation in nucleic acids might be repaired in vivo, possibly by base excision, besides other mechanisms.

The Koc of N-nitroso-N-butylurea is estimated as 30(SRC), using a log Kow of 1.04(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that N-nitroso-N-butylurea is expected to have very high mobility in soil(SRC).

An estimated BCF of 2 was calculated in fish for N-nitroso-N-butylurea(SRC), using a log Kow of 1.04(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for N-nitroso-N-butylurea is estimated as 2.3X10-10 atm-cu m/mole(SRC) developed using a fragment constant estimation method(1). This Henry's Law constant indicates that N-nitroso-N-butylurea is expected to be essentially nonvolatile from water surfaces(2). N-Nitroso-N-butylurea's Henry's Law constant indicates that volatilization from moist soil surfaces is not likely to occur(SRC). N-Nitroso-N-butylurea is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.3X10-3 mm Hg(SRC), determined from a fragment constant method(1).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In projected 485-day studies, Fischer 344 rats and C57BL/6 mice were fed 0.58% butylurea and 0.50% sodium nitrite mixed in the diet separately or in combination. The number and type of neoplasms were not significantly increased in either species receiving butylurea or sodium nitrite only. Feeding the two chemicals simultaneously induced neoplasms of the lung, Zymbal's gland, forestomach, intestine and hemopoietic tissues in rats, and malignant lymphomas in mice. The increased incidence of neoplasms in rats and mice fed butylurea and sodium nitrite in combination may result from in vivo formation of the carcinogen, N-butyl-N-nitrosourea.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Considerable number (8.2 approximately 10.7%) of ovarian tumors were produced in Sprague-Dawley adult rats treated with multiple oral or intramuscular administration of heavy doses of N-butylnitrosourea. Histologically the tumor was a clear-cell adenma which reminded of embryonal testicular tissue. Electron micrograph revealed secretory function of the tumor cells. It was not possible to find histogenesis in the normal ovarian components.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Four cases of ameloblastic odontomas were found in the Long-Evans rats treated with multiple oral administration of a heavy dose of N-butylnitrosourea. The tumor was found as an expansive enlargement over the mandible and was roentgen-opaque. The tumor was histologically characterized by various elements such as odontogenic epithelium, stellated reticulum tissue, enamel, and/or dentine, and was classified as ameloblastic odontoma.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ 1-Butyl-1-nitrosourea (BNU), a strong leukemogen for rats and mice, was administered prenatally, neonatally, and to sucklings via maternal milk in the ACI/N rats. A high incidence of neurogeneous tumor was obtained in the offspring of the mother rats that received 3 subcutaneous injections of 10 mg/rat of BNU at the late stage of pregnancy and also in the animals that received one subcutaneous injection of 100 mg/kg of BNU within 24 hr after birth. Though in low incidence, the tumors also developed in the offspring of the mothers that received the BNU treatment at the middle stage of their pregnancy or in the rats that were nursed by the mother rats which received 3 subcutaneous injections of 300 mg/kg of BNU during lactation. Contrary to expectations, leukemia developed in only one rat of all the offspring of the mother animals that received the BNU treatment during their pregnancy.

For more Non-Human Toxicity Excerpts (Complete) data for N-Nitroso-N-butylurea (15 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of N-nitroso-N-butylurea with photochemically-produced hydroxyl radicals has been estimated as 8.4X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). N-Nitroso-N-butylurea may undergo hydrolysis in the environment based on structurally similar compounds; stability of N-nitroso-N-methylurea and N-nitroso-N-ethylurea in aqueous solutions at 20 °C were reported to be pH dependant with half-lives of 0.05 to 190 hours at pH values ranging from 4.0-9.0(2). N-Nitroso compounds, like N-nitroso-N-butylurea, commonly absorb at wavelengths of approximately 330 nm(3) and, therefore, N-nitroso-N-butylurea may be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC).

No evidence was found that N-nitroso-N-butylurea is produced or used commercially. If released to air, an estimated vapor pressure of 5.3X10-3 mm Hg at 25 °C indicates N-nitroso-N-butylurea will exist solely as a vapor in the atmosphere. Vapor-phase N-nitroso-N-butylurea 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 2 days. N-Nitroso compounds, like N-nitroso-N-butylurea, absorb UV light at wavelengths of approximately 330 nm and, therefore, N-nitroso-N-butylurea may be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm. If released to soil, N-nitroso-N-butylurea is expected to have very high mobility based upon an estimated Koc of 30. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 2.3X10-10 atm-cu m/mole. N-Nitroso-N-butylurea is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil and water were not available. If released into water, N-nitroso-N-butylurea is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 2 suggests the potential for bioconcentration in aquatic organisms is low. N-Nitroso-N-butylurea may undergo hydrolysis in the environment based on half-lives of 0.05 to 190 hours for structurally similar compounds. Occupational and general population exposure should be low or non-existent since no evidence was found that N-nitroso-N-butylurea is produced or used commercially. (SRC)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Nitrates, nitrites, and related compounds/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat as necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Nitrates, nitrites, and related compounds/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Monitor cardiac rhythm and treat arrhythmias if necessary. Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. If unresponsive to these measures, vasopressors may be helpful. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Nitrates, nitrites, and related compounds/