4-ビフェニリルアミン

Hazardous Air Pollutants (HAPs)

Carcinogens

log Kow = 2.86 at pH 7.5

2.86

2.9

2.86

Floral odor

Characteristic odor

1.16 at 68 °F (NTP, 1992) - Denser than water; will sink

1.16 at 68 °F (20 °C)

1.2 g/cm³

1.16

1.16

Colorless crystals

Leaflets from alcohol or water

Colorless to yellowish-brown crystals or light brown solid

less than 0.1 mg/mL at 66 °F (NTP, 1992)

Slightly soluble in cold water; readily soluble in hot water

Soluble in ethanol, ether, acetone, chloroform

Soluble in dichloromethane, DMSO, methanol

Soluble in lipids

Solubility in water, g/100ml at 25 °C: 0.2 (poor)

greater than 235 °F (NTP, 1992)

Flash point > 235 °F

113 °C (235 °F) - closed cup

153 °C (closed cup)

113 °C c.c.

>235 °F

576 °F at 760 mmHg (NTP, 1992)

302 °C

302 °C

576 °F

331 °C @760 [mm Hg]

576 °F

Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx).

When heated to composition it emits toxic fumes of /nitrogen oxides/.

127 °F (NTP, 1992)

51.0 °C

53.5 °C

53 °C

127 °F

53.5 °C

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Carcinogenicity; Nephrotoxicity and Other Toxicity to the Urinary System; Neurotoxicity

Restricted substance: 4-Aminobiphenyl xenylamine

Substance: Biphenyl-4-ylamine

4-Aminodiphenyl: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

This chemical is probably combustible. (NTP, 1992)

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

Slight to moderate when exposed to heat, flames, (sparks) or powerful oxidizers.

This chemical is a combustible solid.

Limited exposure to 4-aminobiphenyl occurs since it is no longer produced commercially. Acute (short- term) inhalation exposure to 4-aminobiphenyl produces headaches, lethargy, cyanosis, urinary burning, and hematuria (the presence of blood in urine) in humans. 4-Aminobiphenyl is a known human bladder carcinogen and animal studies have reported an increase in bladder and liver tumors from oral exposure. EPA has not classified 4-aminobiphenyl for potential carcinogenicity; however, the International Agency for Research on Cancer (IARC) has classified 4-aminobiphenyl as a Group 1 carcinogen, the agent is carcinogenic to humans.

A potential occupational carcinogen that can cause hemorrhagic cystitis and methemoglobinemia; [CAMEO] An eye irritant; [ICSC] Bladder cancer--regulated as a carcinogen by OSHA; see Carcinogens in 29 CFR 1910.1003;

Kadlubar FF et al; Assessment of Exposure and Susceptibility to Aromatic Amine Carcinogens; IARC Sci Pub 89: 166-74 (1988). Assessing exposure and susceptibility to carcinogenic aromatic amines was discussed. The role of acetylation polymorphism in human urinary bladder and colorectal cancers was considered.

Gorrod JW, Manson D; Xenobiotica 16 (10/11): 933-55 (1986). The metabolism of aromatic amines and their roles as carcinogens were reviewed.

DHHS/National Toxicology Program; Report on Carcinogens, Fourteenth Edition: 4-Aminobiphenyl (November 2016). 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. 4-Aminobiphenyl (92-67-1) is listed as known to be a human carcinogen.[Available from, as of November 3, 2016: http://ntp.niehs.nih.gov/pubhealth/roc/index-1.html]

This section applies to any area in which the 13 carcinogens addressed by this section are manufactured, processed, repackaged, released, handled, or stored, but shall not apply to transshipment in sealed containers, except for the labeling requirements under paragraphs (e)(2), (3) and (4) of this section. 4-Aminodiphenyl is included on this list.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. 4-Biphenylamine is included on this list.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use water spray, dry powder, foam, carbon dioxide.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer for medical attention .

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.

(General first aid procedures)

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical, or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

To fight fire use water spray, mist, dry chemical.

Use dry chemical, carbon dioxide, water spray or alcohol foam extinguishers. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. ... The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode.

Keep container tightly closed in a dry and well-ventilated place.

Store in a secure poison location. ... Store in accordance with OSHA Standard 1910.1011. Storage area should be marked, regulated, and maintained under negative pressure. Keep away from heat and sources of ignition, oxidizers.

/Store/ Separated from strong oxidants. Well closed

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Evacuate persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Cover spills with dry lime or soda ash and collect powdered material, then collect powdered material in the most convenient and safe manner and deposit in sealed containers. Absorb liquids in vermiculite, dry sand, earth, or a similar material and deposit in sealed containers. Ventilate area after cleanup is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.

Transformation of amines to water/methanol soluble salts and if necessary, conversion to corresponding Schiff base.

A new method was developed for the removal of carcinogenic aromatic amines from industrial aqueous effluents. It includes the treatment of aqueous solutions containing the carcinogens with horseradish peroxidase and hydrogen peroxide. Such treatment results in a nearly complete precipitation of carcinogenic aromatic amines from water due to enzymatic crosslinking. This method was used to remove 4-aminobiphenyl from water.

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.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (>/= 100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal. Controlled incineration whereby oxides of nitrogen are removed from the effluent gas by scrubber, catalytic or thermal devices.

Personal protection: complete protective clothing including self-contained breathing apparatus. Sweep spilled substance into sealable containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for 4-BIPHENYLAMINE (21 total), please visit the HSDB record page.

Among 41 confirmed nonsmokers, the geometric mean 4-biphenylamine concentration in urine was 1.64 pg/mg creatinine (1.30-2.07); conversely, in 89 smokers, the geometric mean 4-biphenylamine concentration was significantly greater, at 8.69 pg/mg creatinine (7.43-10.16)(1). Smokers (N = 10) excreted significantly higher amounts of 4-biphenylamine (15.3 versus 9.6 ng/24 h) than nonsmokers (N = 10)(2).

... In the present study, we analyzed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 uM 4-ABP with and without co-exposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no effect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was confirmed by Western blot analysis of CYP1A1 protein expression. A similar effect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the influence of B[a]P on Ah receptor-dependent genes.

Administration of a dietary supplement of 6 g d,l-tryptophan/day for 4 1/2 yr following the administration of a single dose of 50 mg 4-aminobiphenyl/kg produced a bladder tumor in 1 of 4 beagle dogs. No tumors were observed in 6 dogs given the same dose of 4-aminobiphenyl without supplemental tryptophan. Experiment suggest that d,l-tryptophan plays as role as a co-carcinogen or promoter in the induction of bladder cancer.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2470(SRC), determined from a structure estimation method(2), indicates that 4-biphenylamine is expected to have slight mobility in soil(SRC). Aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(3,4), suggesting that 4-biphenylamine may be immobile in some soils. Volatilization of 4-biphenylamine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(1). 4-Biphenylamine is not expected to volatilize from dry soil surfaces(SRC) based upon an extrapolated vapor pressure of 3.2X10-4 mm Hg(5). Biodegradation rates of 0-50% over 28 days and 50% after 7 days in static system procedures(6,7) suggest that biodegradation may be an important environmental fate process in soil(SRC). 4-Biphenylamine absorbs at wavelengths >290 nm(8) and, therefore, may be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC).[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.11. Nov, 2012. Available from, as of Aug 22, 2016: http://www2.epa.gov/tsca-screening-tools (3) Bollag JM et al; J Agric Food Chem 26: 1302-6 (1978) (4) Adrian P et al; Toxicol Environ Chem 20-21: 109-20 (1989) (5) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data Compilation. Design Institute for Physical Property Data, American Institute of Chemical Engineers. New York, NY: Hemisphere Pub Corp (2002) (6) Tabak HH et al; pp. 267-328 in Test protocols for environmental fate and movement of toxicants. AOAC 94th Mtg (1981) (7) Fochtman EG; Biodegradation and Carbon Adsorption of Carcinogenic and Hazardous Organic Compounds. EPA-600/S2-81-032. Cincinnati, OH (1981). Available from, as of August 22, 2016: https://nepis.epa.gov/ (8) NIST; NIST Chemistry WebBook.

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2470(SRC), determined from a structure estimation method(2), indicates that 4-biphenylamine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.5X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 36(SRC), from its log Kow of 2.86(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation rates of 0-50% over 28 days and 50% after 7 days in static system procedures(6,7) suggest that biodegradation may be an important environmental fate process in water(SRC). Analogous compounds, aniline and biphenyl, were classified as readily biodegradable by the Japanese MITI test with respective theoretical BODs of 85 and 66% over 2 weeks(8) which also suggests that biodegradation may be an important environmental fate process in water(SRC). 4-Biphenylamine is an aromatic amine and aromatic amines in surface waters exposed to sunlight react with photo-oxidants with a half-life on the order of 30 days(9). Humic acids in natural water photosensitize the photo-oxidation reaction of aromatic amines and enhances degradation rates(10). 4-Biphenylamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-biphenylamine, which has an extrapolated vapor pressure of 3.2 X10-4 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-biphenylamine 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 5 hours(SRC), calculated from its rate constant of 8.0X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 4-Biphenylamine absorbs at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data Compilation. Design Institute for Physical Property Data, American Institute of Chemical Engineers. New York, NY: Hemisphere Pub Corp (2002) (3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.11. Nov, 2012. Available from, as of Aug 22, 2016: http://www2.epa.gov/tsca-screening-tools (4) NIST; NIST Chemistry WebBook.

Occurrence of 4-biphenylamine in foods may be possible because food additives (specific food dyes) may contain trace amounts of 4-biphenylamine as an impurity(1,2).

According to toxicological studies, there are several unidentified mutagens derived from cooking oil fumes appearing in kitchens of Chinese homes where women daily prepare food. Data are limited to an analysis of aromatic amines from cooking oil fumes, which are known to be carcinogenic for bladder cancer. Fume samples from three different commercial cooking oils frequently used in Taiwan were collected and analysed for mutagenicity in the Salmonella/microsome assay. Aromatic amines were extracted from the samples and identified by HPLC and confirmed by gas chromatography/mass spectrometry (GC/MS). Extracts from three cooking oil fumes were found to be mutagenic in the presence of S-9 mix. All samples contained 2-naphthylamine (2-NA) and 4-aminobiphenyl (4-ABP). Concentrations of 2-NA and 4-ABP were 31.5 and 35.7 ug/cu m in fumes from sunflower oil, 31.9 and 26.4 mg/cu m in vegetable oil, and 48.3 and 23.3 ug/cu m in refined-lard oil, respectively. Mutagenicities of the three cooking oil condensates were significantly reduced (P<0.05) by adding the antioxidant catechin (CAT) into the oils before heating. Significant difference existed between the amounts of aromatic amines with and without adding CAT (P<0.05). These results indicate that exposure to cooking oil fumes in Taiwan might be an important but controllable risk factor in the aetiology of bladder cancer.

The substance can be absorbed into the body by inhalation of dust, through the skin and by ingestion.

inhalation, skin absorption, ingestion, skin and/or eye contact

Oral (T36) ; inhalation (T36) ; dermal (T36)

IDENTIFICATION AND USE: 4-Biphenylamine (BPA) is a solid. It is used in detection of sulfates, and as carcinogen in cancer research. HUMAN EXPOSURE AND TOXICITY: BPA is a known human carcinogen. It is an occupational bladder carcinogen and may cause cancer of the ureters and renal pelves. Eleven percent of 171 workers in a plant manufacturing BPA developed bladder tumors. Tumors appeared 5 to 19 years after initial exposure, which ranged in duration from 1.25 to 10 years. BPA forms BPA-DNA adducts in normal human urothelial mucosa and bladder tumor tissues. Levels of BPA- hemoglobin adducts in smokers of blond (flue-cured) and black (air-cured) tobacco have been found to be proportional to bladder cancer risk. Risk of bladder cancer due to exposure to occupational carcinogens is elevated in genetically determined slow acetylators. ANIMAL STUDIES: A comparison between DNA adducts and tumorigenesis indicated a linear correlation between adduct levels and the incidence of liver tumors in female mice. In the bladders of male mice, however, the relationship was markedly nonlinear. Seven rabbits were given BPA orally, and the treatment was continued until the onset of the final illness. Bladder carcinomas were observed in three rabbits, the earliest after four years of treatment. Four young adult female mongrel dogs were given BPA orally. Bladder carcinomas were observed in all four dogs after 21- 34 months. The total dose until first appearance of tumors was 87.5-144.0 g per dog (8.2-14.1 g/kg bw). In BPA- treated mice dose-related neoplasms were angiosarcomas, bladder urothelial carcinomas and hepatocellular neoplasms. The non-neoplastic dose-related lesions were left atrial thrombosis, bladder urothelial hyperplasia, splenic hemosiderosis and splenic erythropoiesis. The incidences of bladder carcinoma and atrial thrombosis were higher in the males and the incidences of hepatocellular neoplasms and angiosarcomas were higher in the females. BPA gave positive results in the mouse bone marrow micronucleus test. BPA produced both frameshift and base pair substitution mutations In Salmonella typhimurium TA-98 and TA-100. ECOTOXICITY STUDIES: The system most sensitive to BPA was D. magna immobilization, followed by development of zebrafish embryos, and inhibition of mammalian cell proliferation.

4-Aminobiphenyl requires metabolic activation in order to exert its toxicity. This is catalyzed by N-hydroxylation via cytochrome P450 1A2, then followed by O-sulfation and O-acetylation by sulfotransferase 1A1 and arylamine N-acetyltransferase 2. The metabolites of 4-aminobiphenyl may form adducts with DNA, inducing mutations. 4-Aminobiphenyl and its metabolites may also cross the placenta and have fetal effects. (A2454, A2455, A2456, A2457)

/AQUATIC SPECIES/ ... In this study, the effects of 4-aminobiphenyl (4-ABP) were investigated using a battery of ecotoxicological model systems, including immobilization of Daphnia magna, development of zebrafish embryos, and inhibition of mammalian cell proliferation. The growth inhibition effects of 4-ABP were assessed on mouse connective tissue fibroblast cells (L929 cells) and human hepatocelluar carcinoma cells (HepG2 cells) by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-trazolium bromide reduction assay. The results reveal that 4-aminobiphenyl is toxic for aquatic organisms and mammalian cells. The system most sensitive to 4-aminobiphenyl is D. magna immobilization, followed by development of zebrafish embryos, and inhibition of cell proliferation. L929 and HepG2 cell growth inhibition bioassays show low sensitivity. These findings indicate that a single model for the possible harmful effect of 4-ABP has its limitations; only a test battery, composed of bioassays on different species, can provide an accurate assessment of the action of 4-ABP in the whole environment.

No acute symptoms expected.

MAY BE ABSORBED!

Further see Inhalation.

headache, dizziness; drowsiness, dyspnea (breathing difficulty); ataxia, lassitude (weakness, exhaustion); methemoglobinemia; urinary burning; acute hemorrhagic cystitis; [potential occupational carcinogen]

Symptoms of 4-aminobiphenyl may include dyspnea, headache, dizziness, lethargy, and ataxia. (T36)

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. 4-Biphenylamine is included on this list.

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. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

No reports found; [TDR, p. 83]

... ((3)H)-4-Aminobiphenyl (ABP, 5 mg) given ip to rat had elimination half-lives of 15.6, 17 and 17 hr, respectively, for urinary, fecal and total 3H elimination. 14C-ABP administered orally to rats at 100 mg/kg gave elimination half-lives of 31, 36.7 and 34 hr, respectively, for urinary, fecal and total (14)C elimination. Semi-log plots of percentage dose remaining in the body versus time indicated that: (i) 82% of 3H activity was excreted in 36 hr with a half-life of 14.4 hr and 18% with a half-life of 46.2 hr, and (ii) 77% of (14)C activity was excreted in 48 hr with a half-life of 15 hr and 23% with a half-life of 180 hr.

To investigate the mode of action of sc injected intestinal carcinogens, the mutagenicity assay of bile collected from noninbred Sprague-Dawley rats treated sc with carcinogens was conducted in the presence and absence of beta-glucuronidase. The bile samples from rats inoculated with 4-aminobiphenyl were mutagenic for Salmonella typhimurium TA100 only in the presence of beta-glucuronidase ... .

Multistep in vitro/in vivo transformation system was used to test the transforming effect(s) of the human bladder procarcinogen 4-amino-biphenyl (ABP) and two putative proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N-OH-ABP) and N-hydroxy-4-acetylamino-biphenyl (N-OH-AABP), on a clonally derived nontumorigenic SV40-immortalized human uroepithelial cell line, SV-HUC. SV-HUC were exposed in vitro to concentrations of ABP, N-OH-ABP, or N-OH-AABP that caused a range of cytotoxicity from 5 to 76%. Tumorigenic transformation of SV-HUC, as assessed by the ability of the exposed cells to form carcinomas when inoculated s.c. into athymic nude mice, was achieved after a single exposure to ABP, N-OH-ABP, or N-OH-AABP. ... Forty independent carcinomas generated in athymic nude mice recapitulated diverse cancer phenotypes (including different growth kinetics and histopathological subtypes and grades) represented in clinical bladder cancers. These results demonstrate for the first time the transforming effects of the potent human carcinogen ABP and two of its proximate N-hydroxy metabolites on a prime human target cell type, HUC.

... Here we found that CYP2A13 can metabolically activate 4-aminobiphenyl (ABP) to show genotoxicity by Umu assay. The K(m) and V(max) values for ABP N-hydroxylation by recombinant CYP2A13 in E. coli were 38.5 +/- 0.6 uM and 7.8 +/- 0.0 pmol/min/pmol CYP, respectively. The K(m) and V(max) values by recombinant CYP1A2 were 9.9 +/- 0.9 uM and 39.6 +/- 0.9 pmol/min/pmol CYP, respectively, showing 20-fold higher intrinsic clearance than CYP2A13. In human bladder, CYP2A13 mRNA, but not CYP1A2, is expressed at a relatively high level. Human bladder microsomes showed ABP N-hydroxylase activity (K(m) = 34.9 +/- 4.7 uM and V(max) = 57.5 +/- 1.9 pmol/min/mg protein), although the intrinsic clearance was 5-fold lower than that in human liver microsomes (K(m) = 33.2 +/- 2.0 uM and V(max) = 293.9 +/- 5.8 pmol/min/mg protein). The activity in human bladder microsomes was prominently inhibited by 8-methoxypsoralen, but not by fluvoxamine, anti-CYP1A2 or anti-CYP2A6 antibodies. CYP2S1, which is expressed in human bladder and has relatively high amino acid identities with CYP2As, did not show detectable ABP N-hydroxylase activity. In conclusion, although the enzyme responsible for ABP N-hydroxylation in human bladder microsomes could not be determined, we found that CYP2A13 metabolically activates ABP.

Metabolites of the human carcinogen 4-aminobiphenyl (4-ABP) form hemoglobin (Hb) adducts, which represent a useful biomarker for exposure. However, not every individual responds to a similar degree to 4-ABP exposure, and variations in 4-ABP-Hb adduct formation might be explained by genetic polymorphisms in genes coding for enzymes involved in 4-ABP metabolism. 4-ABP-Hb adducts were measured in blood samples from 57 smoking and 10 non-smoking volunteers. An association was found between cigarette smoking and 4-ABP-Hb adduct levels in smokers (R(2) = 0.5, p<0.001). Subsequently, subjects were genotyped for 12 polymorphisms in seven genes involved in biotransformation reactions. From this selection of polymorphisms, a significant impact was found for the CYP1B1 Leu(432)Val polymorphism (p=0.021), which has been reported to lead to a decrease in enzyme activity. Indeed higher levels of 4-ABP-Hb adducts were observed in homo- and heterozygous carriers of the CYP1B1 (432)Leu as compared to the double CYP1B1 (432)Val genotype. A significant interaction between these CYP1B1 genotypes and the level of exposure was found (p=0.003). Noteworthy, a saturation effect was observed for 4-ABP-Hb adduct formation at high smoking doses limited to carriers of the CYP1B1 (432)Leu allele. No effect of polymorphisms in other genes were found. This ... study ... /suggests/ a crucial role of the CYP1B1 enzyme in 4-ABP metabolism, indicating a protective effect of the CYP1B1 Leu(432)Val polymorphism against the formation of 4-ABP-Hb adduct levels, depending on the smoking dose.

For more Metabolism/Metabolites (Complete) data for 4-BIPHENYLAMINE (25 total), please visit the HSDB record page.

4-aminobiphenyl has known human metabolites that include 4-aminobiphenyl, N-oxide.

The personal use of hair dye products is currently under discussion due to the potentially increased risk of bladder cancer among long-time users described in epidemiological literature. In order to investigate the dermal absorption of aromatic diamines as well as aromatic amines possibly present as contaminants in hair dye formulations, we conducted a biomonitoring study under real-life conditions and calculated kinetics and doses for the urinary excretion. Urine samples of two female subjects were collected for a time period of 48 hr after personal application of a hair dye cream and analyzed for aromatic diamines as well as o-toluidine and 4-aminobiphenyl using highly specific GC/MS-methods. 2,5-Toluylenediamine (2,5-TDA) as active ingredient of hair dyes is rapidly absorbed dermally. After a distribution phase of 12 hr, 2,5-TDA is excreted with a half-time of 8 hr. Excretion was 90% complete within 24 hr after application. The doses of 2,5-TDA excreted within 48 hr were 700 ug for application of a brown-reddish hair dye cream and 1.5 mg for the application of a brown-black hair dye cream. Urinary 4-aminobiphenyl as well as contaminations with other aromatic diamines were not detectable in our study. Due to the artifactual formation of o-toluidine in the presence of high concentrations of urinary 2,5-TDA, our results could not prove an increased internal exposure of humans to carcinogenic amines after personal application of hair dyes.

/MILK/ The potential for 4-aminobiphenyl (4-ABP) to be transferred from circulating blood into the milk of lactating Sprague-Dawley rats was determined. The distribution of 14C-labeled 4-ABP into milk was examined at time intervals of less than 1, 20, 60, 120, 240 and 480 min after iv dose administration. Elimination of radioactivity from blood and milk was determined to be biphasic. The levels of 4-ABP and/or metabolites were lower in milk than in blood at all time points examined. The levels of radioactivity detected in blood declined less rapidly than in milk. That is, the percent of the dose per ml of blood declined from 0.81-0.45, while the percent of the dose per ml of milk declined from 0.38-0.06 during the 8 hr time period. The radioactivity present in milk was partially extractable with ethyl acetate with 43% of the radioactivity being extractable at the earliest time point while only 16% was extractable after 8 hr. The level of radioactivity associated with the protein precipitate of the milk samples increased from 4-21% within 4 hr after treatment.

... A sensitive (32)P-postlabeling method enabled us to study the binding of the environmental carcinogens safrole (600 umol/kg p.o.), 4-aminobiphenyl (800 umol/kg), and benzo(a)pyrene (200 umol/kg) to the DNA of various maternal and fetal tissues after administration of test carcinogens to pregnant ICR mice on day 18 of gestation. The results show that these carcinogens bound to the DNA of maternal and fetal liver, lung, kidney, heart, brain, intestine, skin, maternal uterus, and placenta, with organ-specific quantitative and qualitative differences. It was possible for the first time to analyze DNA adduct patterns in minute amounts of tissue, for example those available from fetal heart. The covalent binding index (umol adducted nucleotides per mol of DNA nucleotides/umol carcinogen administered per g body weight) 24 hr after safrole treatment was estimated for the different organs and ranged from 0.1 to 247 and 0.1 to 5.8 for maternal and fetal DNA, respectively. Covalent binding index values of 0.2 to 13 and 0.1 to 0.3 for maternal and fetal DNA, respectively, were found for 4-aminobiphenyl. Benzo(a)pyrene treatment yielded covalent binding index values of 0.6 to 6.5 and 0.3 to 0.7 for maternal and fetal DNA, respectively. In both maternal and fetal tissues, safrole exhibited preferential binding to liver DNA. 4-Aminobiphenyl bound preferentially to DNA of maternal liver and kidney but showed no preference among fetal tissues. Benzo(a)pyrene exhibited weak tissue preference in both maternal and fetal organs. For all of the compounds studied, the fetal adduct levels were generally lower than the corresponding maternal adduct levels, especially when the level of maternal adduction was high. The major finding was that several carcinogens of diverse structure or their metabolites readily crossed the placenta and gave rise to DNA adducts in fetal organs. ...

Maternal-fetal exchange of a potent tobacco related human carcinogen, 4-aminobiphenyl, was studied in smoking (n= 14) and nonsmoking (n= 38) pregnant women. N-Hydroxy-4-aminobiphenyl, the active metabolite of 4-aminobiphenyl, forms chemical addition products (adducts) with hemoglobin. Levels of 4-aminobiphenyl hemoglobin adducts were measured in maternal fetal paired blood samples obtained from smoking and nonsmoking women during labor and delivery. Carcinogen hemoglobin adducts were detected in all maternal and fetal blood samples. Levels of such adducts were significantly higher (p<0.001) in maternal and fetal blood samples from smokers: the mean 4-aminobiphenyl hemoglobin adduct level was 92 +/- 54 pg/g of hemoglobin in blood samples from fetuses of smokers, and 17 +/- 13 pg/g of hemoglobin in blood samples from fetuses of nonsmokers; the mean maternal 4-aminobiphenyl hemoglobin adduct level was 183 +/- 108 pg/g of hemoglobin in smokers, and 22 +/- 8 pg/g of hemoglobin in nonsmokers. Fetal carcinogen adduct levels were consistently lower than maternal levels: the mean maternal to fetal ratio was 2.4 +/- 1.1 in smokers and 1.9 +/- 0.98 in nonsmokers. Fetal 4-aminobiphenyl hemoglobin adduct levels were strongly associated (correlation coefficient r2= 0.51, p=0.002) with maternal 4-aminobiphenyl hemoglobin adduct levels when paired samples from smoking mothers were analyzed. A measure of third trimester tobacco smoke exposure based on number of cigarettes smoked per day, amount of each cigarette smoked, and depth of inhalation was associated (r2= 0.59, p=0.029) with maternal 4-aminobiphenyl levels but not with fetal 4-aminobiphenyl levels. This study demonstrates that a potent tobacco related carcinogen, 4-aminobiphenyl, or its active metabolite, N-hydroxy-4-aminobiphenyl, crosses the human placenta and binds to fetal hemoglobin in concentrations that are significantly higher in smokers than in nonsmokers.

For more Absorption, Distribution and Excretion (Complete) data for 4-BIPHENYLAMINE (7 total), please visit the HSDB record page.

4-Aminobiphenyl is no longer manufactured commercially; it was used as a rubber antioxidant and a dye intermediate in the past.

No longer produced commercially; [ACGIH]

See 29CFR1910.1003 (Code of Federal Regulations pertaining to the manufacturing, processing, repackaging, releasing, handling, and storing of this carcinogen).

In detection of sulfates. Formerly as rubber antioxidant. As carcinogen in cancer research.

A new class of materials was prepared from aniline-containing oligomers that are covalently linked to the nucleobases of duplex DNA. Oligomers composed of repeating aniline (PANI) or 4-aminobiphenyl (PAB) units having the properties of conducting polymers conjoined to the DNA were prepared by the reaction of horseradish peroxidase and H2O2 with DNA having the appropriate monomers aligned within the major groove. These oligomers exhibit the spectral and chemical properties typical of para-linked polyanilines. This method of preparation enables utilization of the unique self-recognizing properties and sequence programmability of DNA to create tailored oligomers. This ability was demonstrated experimentally by preparation of PAB oligomers from alternating benzene and aniline monomers. Conjoined conducting polymers carrying the sequence information of DNA may have applicability as nanowires.

Chemical intermediate for dyes (former use)

(1978) NOT PRODUCED COMMERCIALLY IN USA

(1982) NOT PRODUCED COMMERCIALLY IN USA

[1,1'-Biphenyl]-4-amine: ACTIVE

It is no longer manufactured in most countries because of /carcinogenic effect/... .