4-Nitrochinolin-N-oxid

309 °F (NTP, 1992)

154 °C

Yellowish-brown plates or needles or yellow solid. (NTP, 1992)

Yellow solid; [HSDB] Yellowish-brown or yellow solid; Hygroscopic and sensitive to light; [CAMEO] Yellow or orange crystalline powder; [Alfa Aesar MSDS]

This chemical does not meet GHS hazard criteria for 6% (3 of 50) of reports.

Danger

H350 (92%): May cause cancer [Danger Carcinogenicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 50 reports by companies from 6 notifications to the ECHA C&L Inventory.；Reported as not meeting GHS hazard criteria per 3 of 50 reports by companies.；There are 5 notifications provided by 47 of 50 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Mutagenic to human cells; Evidence for carcinogenicity in experimental animals; [HSDB] May cause irritation; [CAMEO] Increased incidence of congenital abnormalities and tumors observed in offspring of mice; [REPROTOX] Causes acute pulmonary edema, dyspnea, and decreased body temperature in subcutaneous lethal-dose studies of rats; [RTECS] May cause irritation; [Alfa Aesar MSDS]

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)

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone 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 protect this material from exposure to light and moisture, and store it under refrigerated temperatures. If possible, it would be prudent to store this compound under inert atmosphere. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:；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 the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank 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, 2024)

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)

EFFECTS WERE STUDIED OF SODIUM CHLORIDE ON PRODUCTION OF GASTRIC CARCINOMAS BY 4-NITROQUINOLINE-1-OXIDE IN MALE WISTAR RATS. NACL GIVEN ALONE HAD NO APPARENT CARCINOGENICITY BUT WHEN ADMIN WITH 4-NITROQUINOLINE-1-OXIDE IT ENHANCED CARCINOGENIC EFFECTS IN STOMACH.

ADMIN OF 4-NITROQUINOLINE 1-OXIDE TO RATS FOLLOWING PRIOR TREATMENT WITH N-METHYL-N'-NITRO-N-NITROSOGUANIDINE RESULTED IN UNDIFFERENTIATED ADENOCARCINOMAS IN 29% OF TUMORS INDUCED IN GLANDULAR STOMACH.

The modifying effect of three doses of DL-alpha-difluoromethylornithine given orally during the post-initiation phase of tongue carcinogenesis initiated by 4-nitroquinoline 1-oxide was studied in male ACI/N rats. Animals were given 4-nitroquinoline 1-oxide at 20 ppm for 8 wk in the drinking water to induce tongue neoplasms. One wk after the stop of 4-nitroquinoline 1-oxide treatment, rats were transferred to the drinking water containing DL-alpha-difluoromethylornithine at concn of 100, 1000, and 2000 ppm for 25 wk. The other groups consisted of rats given 2000 ppm DL-alpha-difluoromethylornithine alone or untreated rats. Thirty four wk after the start of the experiment, all animals were necropsied, and the incidences of neoplasms and preneoplastic lesions in the tongue, polyamine levels in the bloods and tongue tissues, and cell proliferation estimated by the number and area of silver stained nucleolar organizer regions in the tongue epithelium were compared among the groups. Feeding of DL-alpha-difluoromethylornithine at all doses significantly inhibited the incidence of tongue neoplasms compared to the group given 4-nitroquinoline 1-oxide alone. DL-alpha-difluoromethylornithine at levels of 1000 and 2000 ppm significantly reduced the incidence of preneoplastic lesions of the tongue. Results analyzed by the linear regression method suggested a dose dependent inhibition in the incidences of neoplastic and preneoplastic lesions of the tongue with increasing levels of DL-alpha-difluoromethylornithine. Increased levels in polyamines in the blood and tongue tissue were significantly suppressed by the treatment of DL-alpha-difluoromethylornithine. Also, silver stained nucleolar organizer region indices were significantly reduced by the DL-alpha-difluoromethylornithine exposure. These results indicate that increasing levels of DL-alpha-difluoromethylornithine in the drinking water inhibited 4-nitroquinoline 1-oxide induced tongue carcinogenesis in a dose dependent manner

The modifying effects of indole-3-carbinol and sinigrin on the initiation and post-initiation phases of tongue carcinogenesis induced by 4-nitroquinoline 1-oxide were investigated in male ACI/N rats. Rats were divided into eight groups: group 1 was given 4-nitroquinoline 1-oxide (10 ppm) in the drinking water for 12 wk, starting at 7 wk of age; groups 2 and 3 were given 4-nitroquinoline 1-oxide and fed the diets containing indole-3-carbinol (1,000 ppm) and sinigrin (1,200 ppm) for 14 wk, respectively, starting at 6 wk of age; groups 4 and 5 were given 4-nitroquinolin 1-oxide and then they were fed indole-3-carbinol and sinigrin containing diets for 23 wk, respectively, starting one wk after 4-nitroquinoline 1-oxide exposure; groups 6 and 7 were given indole-3-carbinol and sinigrin alone, respectively, during the experiment; group 8 served as an untreated control. At the termination of the experiment (wk 37), the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) in group 2 (1/15, 7%), group 3 (1/15, 7%), group 4 (3/15, 20%) or group 5 (2/15, 13%) was significantly smaller than that in group 1 (12/17, 71%) (p= 0.0003, p= 0.005 or p= 0.002). No tongue carcinomas developed in rats of groups 2, 3, and 5. Similarly, the incidence of preneoplastic lesions (hyperplasia and dysplasia) of the tongue in group 2 (11/15, 73%), group 3 (10/15, 67%), group 4 (11/15, 73%) or group 5 (10/15, 67%) was significantly lower than tha in group 1 (17/17, 100%) (p= 0.04 or p= 0.02). There were no tongue neoplasms in rats of groups 6, 7, and 8. Administration of indole-3-carbinol and sinigrin also caused significant decreases in the number and area of silver stained nucleolar organizer regions protein, a new cell proliferation index, of tongue squamous epithelium. Thus, indole-3-carbinol and sinigrin inhibited rat tongue carcinogenesis in both the initiation and post-initiation phases, when administered in these respective phases together with, or following treatment with

For more Interactions (Complete) data for 4-NITROQUINOLINE-N-OXIDE (6 total), please visit the HSDB record page.

Normal human fibroblasts (the OUMS-24 strain), derived from a 6 wk old human embryo, were transformed (into the OUMS-24F line) and immortalized by repeated treatments (59 times) with 4-nitroquinoline 1-oxide. Treatment began during primary culture and ended at the 51st population doubling level. At the 57th population doubling level (146 days after the last treatment), morphologically altered, epithelial type cells appeared, began to grow and became immortal (now past the 100th population doubling level). However, the control fibroblasts, which were not treated with 4-nitroquinoline 1-oxide, senesced at the 62nd population doubling level. The finding that extensive, repeated treatments with 4-nitroquinoline 1-oxide are required for the immortalization of normal human cells, indicates that multiple mutational events are involved in the immortalization of human cells in general. In other words, immortalization itself seems to be a multi-step process. Karyotypic analysis showed that many cells were hypodiploid before immortalization, but that afterwards chromosomes were distributed broadly in the diploid to tetraploid regions. The immortalized cells showed amplification and enhanced expression of c-myc. Two-dimensional electrophoretic analysis showed that the number of disappearing cellular proteins was greater than the number of the newly appearing ones after the cells became immortalized.

The present study was carried out in order to analyze how persistent the lesions in DNA are which elicit sister chromatid exchanges, induced by three different chemical agents, mitomycin C, 4-nitroquinoline-1-oxide and ethyl methanesulfonate, in proliferating human lymphocytes. Cells were exposed to the mutagens for 1 hr just before starting bromodeoxyuridine substitution and sister chromatid exchanges were examined in third cycle metaphases showing three way differential staining, by means of our previously standardized method. The results show that, in spite of the fact that these three cmpd have different modes of action, the lesions induced by all of them seem to be capable of persisting in DNA and eliciting sister chromatid exchanges for at least three successive cell cycles.

Human cytomegalovirus has been shown to increase the frequency of chromosome aberrations, primarily chromatid type, in human peripheral blood lymphocytes. Because human cytomegalovirus persists in most humans, pathologically activates cells, and may perturb the cell cycle, the possibility that human cytomegalovirus infected cells have a modified sensitivity to chromosome damage induced by genotoxic chemicals was investigated. Uninfected peripheral blood lymphocytes exposed to bleomycin (3 to 100 ug/ml) demonstrated a linear increase in the frequency of chromosome aberrations. Human cytomegalovirus infection of peripheral blood lymphocytes at an intensity that did not cause detectable damage followed by exposure to the same concentrations of bleomycin resulted in a significant enhancement (p< 0.01) in the frequency of chromosome aberrations relative to the effect of bleomycin alone. A more than additive enhancement of the frequency of chromosome aberrations was also noted in human cytomegalovirus infected peripheral blood lymphocytes exposed to 4-hydroxyaminoquinoline-1-oxide (0.1 to 0.3 ug/ml) relative to uninfected cells treated with 4-hydroxyaminoquinoline-1-oxide alone. No increase in the percentage of aberrant cells or the frequency of chromosome aberrations was observed in human cytomegalovirus infected cells treated with 4-nitroquinoline-1-oxide relative to similarly treated uninfected peripheral blood lymphocytes. These results suggest that human cytomegalovirus can potentiate the induction of chromosome aberrations in human peripheral blood lymphocytes caused by potent DNA damaging agents.

The effects of the UV mimetic chemical 4-nitroquinoline-1-oxide upon cell lines heterozygous or homozygous for the recessive mutant xeroderma pigmentosum were investigated. Human lymphoblastoid cell lines, which were established from 4 xeroderma pigmentosum homozygote patients (XPL15, XPL17, XPL19 and XPL20). 2 xeroderma pigmentosum heterozygote individuals (XPPL17 and XPML17) and 58 normal individuals, were cultured in the presence of 4-nitroquinoline-1-oxide at doses of 0, 2, 4 and 8X10-6 M. Then the total cell number was counted and the viability of the cells was measured by the dye exclusion method using trypan blue and a newly devised fluorometric method with fluorescein diacetate. Results showed that 4-nitroquinoline-1-oxide affected, in increasing order of impairment, the cell lines: normal less than xeroderma pigmentosum heterozygote less than xeroderma pigmentosum homozygote.

For more Human Toxicity Excerpts (Complete) data for 4-NITROQUINOLINE-N-OXIDE (9 total), please visit the HSDB record page.

MUTAGENICITY: MUTATION RESEARCH 76: 169 (1980). ESCHERICHIA COLI WP2,UVRA - REVERSE MUTATION STUDIES: POSITIVE.

MUTAGENICITY: MUTATION RESEARCH 87: 17 (1981). SISTER CHROMATID EXCHANGE -IN VITRO CHROMOSOMAL EFFECT STUDIES, HUMAN: POSITIVE; IN VITRO CHROMOSOMAL EFFECT STUDIES, NON-HUMAN: POSITIVE; IN VIVO CHROMOSOMAL EFFECT STUDIES, HUMAN: POSITIVE.

MUTAGENICITY: MUTATION RESEARCH 87: 211 (1981). DNA REPAIR DEFICIENT BACTERIAL TESTS: POSITIVE.

MUTAGENICITY: MUTATION RESEARCH 86: 355 (1981). MOUSE IN VIVO SOMATIC MUTATION ASSAY (SPOT TEST) - COAT COLOR MUTANTS: POSITIVE.

For more Non-Human Toxicity Excerpts (Complete) data for 4-NITROQUINOLINE-N-OXIDE (25 total), please visit the HSDB record page.

YIELDS 4-HYDROXYLAMINOQUINOLINE-N-OXIDE IN RATS; SUGIMURA, T, OKABE, K, & NAGAO, M, CANCER RES, 26. 1717 (1966); IN MICE; KAWAZOE, Y, UEHARA, N, ARAKI, M, & TAMURA, M, GANN, 60, 617 (1969). /FROM TABLE/

... IS RAPIDLY REDUCED BY RAT-LIVER SOL FRACTION. ... RATE OF REDN IN VITRO OF SERIES OF NITROQUINOLINE N-OXIDES CORRELATES WITH THEIR CARCINOGENICITY. SOL ENZYME RESPONSIBLE FOR THIS REDN IS THOUGHT TO BE DT DIAPHORASE, ENZYME (FLAVOPROTEIN) WHICH CATALYZES OXIDN OF NADPH & NADH.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.

Used as a research chemical; Not commercially produced in the US; [HSDB]

RESEARCH CHEMICAL

(1977) NOT PRODUCED COMMERCIALLY IN US

(1979) NOT PRODUCED COMMERCIALLY IN US