4-Aminophenol

109.13

109.13

385836

204-616-2

R7P8FRP05V

1545

2512

DTXSID3024499

Orthorhombic plates from water|White plates from water|Colorless crystals|White or reddish yellow crystals turn violet on exposure to light

2922299090

46.2

0.04

White to cream Crystalline Powder

1.21g/cm3

189.6-190.2 °C

284 °C

189 °C

1.5764 (20ºC)

H2O: 1.5 g/100 mL (20 ºC);slightly soluble

Refrigerator

4.0X10-5 mm Hg at 25 deg C

Oral-rat LD50: 375 mg/kg; Abdominal cavity-mouse LDL0: 100 mg/kg

Open flame flammable; decomposed by heat; burning releases toxic nitrogen oxide fumes

Henry's Law constant = 3.6X10-10 atm-cu m/mole at 25 °C (est)

pK1 = 5.48 at 25 °C (conjugate acid)|pK2 = 10.46

Heat of formation = -190.6 kJ/mol|4-Aminophenol crystals exist in two forms. The less stable beta form (from acetone) exists as acicular crystals that turn into the alpha form on standing; they are orthorhombic bipyramidal or pyramidal /beta-4-Aminophenol/|Crystalline powder; gradually becomes darker. Decomposes about 306 °C. Very soluble in water; soluble in alcohol /p-Aminophenol hydrochloride/|Hydroxyl radical reaction rate constant = 7.4X10-11 cu cm/molecule-sec at 25 °C (est)

Insoluble in water.

Phenols and Cresols

Heat (decomposition forming HCN, nitrous vapors, CO); water (CO2); reacts violently with acids, bases, alcohols and amines causing fire and explosion hazards [Handling Chemicals Safely 1980 p. 647].

III

6.1

UN 2512 6.1/PG 3

3

20/22-50/53-68-40-R68-R50/53-R20/22

28-36/37-60-61-28A-S61-S60-S36/37-S28A

SJ5075000

Xn,N

Treasury is ventilated at low temperature and dry; stored separately from oxidants and food additives

Deteriorates under influence of air and light

P201, P202, P260, P261, P264, P270, P271, P272, P273, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P308+P313, P312, P314, P321, P330, P333+P313, P363, P391, P405, P501

H302

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. 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 soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.|Incineration. /Aminophenols/

Strong oxidants. /Aminophenols/

UN 2512

Flash point data are not available for this chemical. It is probably combustible. (NTP, 1992)

|Warning|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P273, P281, P301+P312, P304+P312, P304+P340, P308+P313, P312, P330, P391, P405, and P501|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|Aggregated GHS information provided by 279 companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|P201, P202, P260, P261, P264, P270, P271, P272, P273, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P308+P313, P312, P314, P321, P330, P333+P313, P363, P391, P405, and P501|Danger|P201, P202, P260, P261, P264, P270, P272, P273, P280, P281, P285, P301+P312, P302+P352, P304+P341, P305+P351+P338, P308+P313, P314, P321, P330, P333+P313, P337+P313, P342+P311, P363, P391, P405, and P501|P201, P202, P260, P261, P264, P270, P271, P272, P280, P281, P285, P301+P312, P302+P352, P304+P312, P304+P340, P304+P341, P305+P351+P338, P307+P311, P308+P313, P312, P314, P321, P330, P332+P313, P333+P313, P337+P313, P342+P311, P363, P405, and P501

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]: As an 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, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck 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, 2016)

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 chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)|Wear protective gloves and clothing to prevent any reasonable probability of skin contact ... Wear dust-proof chemical goggles and face shield unless full facepiece respiratory protection is worn. /Aminophenols/

Use dry chemical, carbon dioxide, or alcohol foam extinguishers. Vapors are heavier than air and will collect in low areas. Vapors may travel long distances to ignition sources and flashback. Vapors in confined areas may explode when exposed to fire. Storage containers and parts of containers may rocket great distances, in many directions. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors or shows any signs of deforming), withdraw immediately to a secure position ... The only respirators recommended for fire fighting are self-contained breathing apparatuses that have full facepieces and are operated in a pressure-demand or other positive-pressure mode. /Anisidines/|If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire. (Material itself does not burn or burns with difficulty.) Use water in flooding quantities as fog. Use foam, dry chemical, or carbon dioxide. Keep run-off water out of sewers and water sources. /Aminophenols/

Spill handling: keep dust under control. Use a vacuum or wet method to reduce dust during clean-up. Do not sweep. Evacuate persons not wearing protective equipment from area of spill or leak until clean-up is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after clean-up 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. Contact your Department of Environmental Protection of your regional office of the federal EPA for specific recommendations. /Aminophenols/

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|... Disposable natural rubber latex gloves and disposable PVC gloves should not be used repeatedly for handling the hair dye products /p-aminophenol, m-aminophenol, o-aminophenol, and p-phenylenediamine/.|If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. /Aminophenols/|Personnel protection: Avoid breathing dusts, and fumes from burning material. Keep upwind ... Avoid bodily contact with the material ... Do not handle broken packages unless wearing appropriate personal protective equipment. /Aminophenols/

/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. /Aminophenols/|/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. /Aminophenols/|/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Public Safety: CALL Emergency Response Telephone Number ... As an 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. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. /Aminophenols/|/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Aminophenols/|For more DOT Emergency Guidelines (Complete) data for 4-Aminophenol (8 total), please visit the HSDB record page.

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./|The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.|The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.

... skin and eye irritant.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. p-Aminophenol is produced, as an intermediate or a final product, by process units covered under this subpart.

| 4 - Materials that, under emergency conditions, can be lethal.| 1 - Materials that must be preheated before ignition can occur. Materials require considerable preheating, under all ambient temperature conditions, before ignition and combustion can occur.| 0 - Materials that in themselves are normally stable, even under fire conditions.

highly toxic

p-Aminophenol (pAP, 225 mg/kg) administration to rats induced renal failure and has been associated with markers of endoplasmic reticulum (ER) stress, as well as calpain and caspase-12 activation in kidneys. To determine the importance of ER stress and calpain during pAP-induced nephrotoxicity, rats were pretreated with low, nontoxic, doses of ER stress inducers or with the selective calpain inhibitor PD150606 (3 mg/kg). Prior ER stress induced by tunicamycin and oxidized dithiothreitol did not result in protection against renal failure, but PD150606 administration was protective and decreased significantly the rise in creatinine and blood urea nitrogen observed after 24-hr post-pAP administration. pAP-induced XBP1 upregulation was not modified by calpain inhibition, but a trend to lower GRP94 induction was determined, suggesting that pAP-induced ER stress was mostly calpain independent. In contrast, pAP-induced caspase-12 cleavage products were significantly decreased with PD150606 pretreatment, demonstrating that caspase-12 activation was calpain dependent ...|The effects of a glutathione depletor, buthionine sulfoximine (BSO) and biliary cannulation on the nephrotoxicity of p-aminophenol (PAP) have been investigated in the F344 rat. Pretreatment with BSO completely protected against the nephrotoxicity of a 50 mg/kg dose of PAP, assessed by clinical chemistry, renal histopathology, and (1)H-NMR urinalysis. Biliary cannulation partially protects against nephrotoxicity induced by 100 mg/kg PAP. These data suggest that the nephrotoxicity of PAP may be due in part to the formation of a proximate toxic metabolite in the liver which is excreted in the bile, subsequently reabsorbed and transported via the systemic circulation to the kidney where the toxic effects occur.|Screening tests revealed that aniline increased urine trimethoprim (TMP) excretion in rat. The study attempted to investigate the effect of aniline under conditions of repeated exposure on the course of TMP excretion with urine. ... Three groups of rats (10 rats each) were used. Group I was exposed for 12 days (6 hr a day) to aniline vapour. Group II received TMP only. Group III was exposed both to aniline & TMP. Concns of TMP & p-aminophenol (an aniline metabolite) were determined in the 24 hr urine samples after 1, 6, & 12 days. The exposure to aniline vapors was found to cause almost 3-fold incr of TMP removal. No effect of TMP on p-aminophenol excretion was observed.|An investigation was carried out of the effects of ortho-aminophenol (95556) (o-AP), meta-aminophenol (591275) (m-AP), para-aminophenol (123308) (p-AP) & acetaminophen (103902) (AAP) on the induction of preneoplastic lesions in the liver & kidney of male Fischer-344-rats by N-ethyl-N-hydroxyethylnitrosamine (13147256) (EHEN). The rats in this 52 wk investigation included those give 0.1% EHEN in their drinking water for 2 wk & then, beginning 1 wk later, given 0.8% of either o-AP, m-AP, p-AP or AAP in the basal diet for 49 wk; those given EHEN & thereafter only the basal diet; & those given one of the test cmpds without prior EHEN admin. Body, liver & kidney weights were determined for sacrificed rats, & liver sections were subjected to immunohistochemical exam of glutathione-S-transferase placental type (GSTP) positive foci. The numbers of GSTP positive foci in the liver were significantly decreased in rats given o-AP, m-AP, p-AP or AAP after EHEN as compared to values for rats given EHEN alone. However, lowered incidences of GSTP positive foci were observed only in rats given o-AP or AAP after EHEN. Only p-AP & AAP gave significantly higher incidences of microadenoma & adenoma in the kidney.

LD50 Rat oral 375 mg/kg|LD50 Rat oral 671 mg/kg|LD50 Rat oral 1270 mg/kg|LD50 Mouse oral 420 mg/kg|For more Non-Human Toxicity Values (Complete) data for 4-Aminophenol (6 total), please visit the HSDB record page.

4-Aminophenol's production and use as a photographic developer; as a dyeing agent for textiles, fur, feathers, hair; in pharmaceuticals; as an antioxidant; as an oil additive(1) and as a chemical intermediate(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 90(SRC), determined from a structure estimation method(2), indicates that 4-aminophenol is expected to have high mobility in soil(SRC). However, anilines 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 mobility may be much lower in some soils(SRC). Measured pKa values are 5.48(5) and 10.46(6), for the amine and hydroxy functional groups, respectively(7). 4-Aminophenol is amphoteric and behaves either as a weak acid or weak base; the basic character usually predominates(8). Volatilization of 4-aminophenol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.6X10-10 atm-cu m/mole(SRC), based upon its vapor pressure, 4X10-5 mm Hg(9), and water solubility, 16,000 mg/L(10). 4-Aminophenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(9). A 6% of theoretical BOD using activated sludge in the Japanese MITI test(11) suggests that biodegradation may not be important environmental fate process in soil(SRC). However, 87% chemical oxygen demand removal was reached in 5 days in a screening test using acclimated activated sludge at 100 mg/L and 4-aminophenol at 200 mg/L chemical oxygen demand(12).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 90(SRC), determined from a structure estimation method(2), indicates that 4-aminophenol 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 3.6X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 4X10-5 mm Hg(4), and water solubility, 16,000 mg/L(5). According to a classification scheme(6), BCFs of 10-39 and 15-46 in carp (Cyprinus carpio)(7) suggest bioconcentration in aquatic organisms is low to moderate(SRC). 4-Aminophenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). 4-Aminophenol, under aerobic conditions, seems to biodegrade as shown by studies where 85 and 100% of 10 mg/L 4-aminophenol was degraded in river and seawater, respectively, however at 50 mg/L no biodegradation was observed(8). Under denitrifying and methanogenic conditions in sediment, 4-aminophenol was mineralized following a long lag phase at a rate of 15.7 and 20 umol/L/day, respectively(9).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-aminophenol, which has a vapor pressure of 4X10-5 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 4-aminophenol 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 7.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 4-aminophenol may be removed from the air by wet or dry deposition(SRC). 4-Aminophenol absorbs light at wavelengths of 294 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 4-aminophenol with photochemically-produced hydroxyl radicals has been estimated as 7.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 4-Aminophenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 4-Aminophenol is expected to undergo fairly rapid oxidation in the presence of air(3) and may be susceptible to direct photolysis due to its absorption in the environmental UV spectrum (UV max = 294 nm)(3). Measured pKa values are 5.48(4) and 10.46(5), for the amine and hydroxy functional groups, respectively(6). 4-Aminophenol is amphoteric and behaves either as a weak acid or weak base; the basic character usually predominates(3).

BCFs of 10-39 and 15-46 in carp (Cyprinus carpio) were reported for a 8 week study using 1.5 and 0.15 mg/L 4-aminophenol, respectively(1). According to a classification scheme(2), these BCFs suggest the potential for bioconcentration in aquatic organisms is low to moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-aminophenol can be estimated to be 90(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-aminophenol is expected to have high mobility in soil. However, anilines 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 mobility may be much lower in some soils(SRC). Measured pKa values are 5.48(5) and 10.46(6), for the amine and hydroxy functional groups, respectively(7). 4-Aminophenol is amphoteric and behaves either as a weak acid or weak base; the basic character usually predominates(8).

The Henry's Law constant for 4-aminophenol is estimated as 3.6X10-10 atm-cu m/mole(SRC) derived from its vapor pressure, 4X10-5 mm Hg(1), and water solubility, 16,000 mg/L(2). This Henry's Law constant indicates that 4-aminophenol is expected to be essentially nonvolatile from water surfaces(3). 4-Aminophenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

According to the 2006 TSCA Inventory Update Report, the number of persons reasonably likely to be exposed in the industrial manufacturing, processing, and use of 4-aminophenol is 100 to 999; the data may be greatly underestimated(1).|NIOSH (NOES Survey 1981-1983) has statistically estimated that 49,882 workers (37,110 of these were female) were potentially exposed to 4-aminophenol in the US(1). Occupational exposure to 4-aminophenol may occur through dermal contact with this compound at workplaces where 4-aminophenol is produced or used(SRC). Use data indicate that the general population may be exposed to 4-aminophenol via dermal contact with consumer products, particularly hair dye products, containing 4-aminophenol(SRC).

4.4 = very toxic: probable oral lethal dose (human) 50-500 mg/kg, between 1 teaspoon & 1 oz for 70 kg person (150 lb). ... causes methemoglobinemia, but less toxic than aniline in animals. ... diln used in photography do not have significant percutaneous toxicity in most cases.

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. (See all compounds classified as Mutagens.)

An absorption and excretion study of permanent hair dye intermediates containing 14-C was conducted in hairless Wistar rats under conditions of oxidation hair dyeing (ie, intermediates were mixed with H202 immediately before application). The cutaneous penetration of 14C-4-aminophenol (PAP) alone and in admixture with a nonradioactive coupler (3-amino-6-methylphenol, a 3-aminophenol (MAP) derivative) and that of the resultant 14C-indamine (N-[4-hydroxyphenyl}-3-amino-6-methyl benzoquinone imine) was determined. Hair dye solutions containing uniformly labeled PAP (0.75% or 70 nM) in a simple vehicle were applied to a 10 sq cm dorsal surface of up to 5 rats. Doses of PAP of 0.14 uM/sq cm, 0.69 uM/sq cm, and 3.44/ uM/sq cm yielded respective concentrations of 15.9 +/- 4.76 nM/sq cm, 52.04 +/- 6.73 nM/sq cm, and 58.4 +/- 11.5 nM/sq cm, which penetrated the skin and were detected in the excreta, the viscera, and the skin (excluding PAP found at the site of application) of the treated rats after 4 days. At the highest 14C-PAP concentration applied, the total quantity of 14C-PAP detected per sq cm of skin was approximately the same for PAP alone as for PAP mixed with nonradioactive MAP coupler (56.8 +/- 4.0 nM/sq cm). Penetration of the 14C-indamine was approximately 17 times less (3.6 +/- 0.46 nM) than that of PAP or of the mixture of PAP with the nonradioactive coupler..

... Hepatocytes prepared from male Sprague-Dawley rats ... converted para-aminophenol (PAP) to two major metabolites (PAP-GSH conjugates and PAP-N-acetylcysteine conjugates) and several minor metabolites [PAP-O-glucuronide, acetaminophen (APAP), APAP-O-glucuronide, APAP-GSH conjugates, and 4-hydroxyformanilide]. Preincubating hepatoyctes with 1-aminobenzotriazole, an inhibitor of cytochromes P450, did not alter the pattern of PAP metabolism. In conclusion, we found that PAP was metabolized in hepatocytes predominantly to PAP-GSH conjugates and PAP-N-acetylcysteine conjugates in sufficient quantities to account for the nephrotoxicity of PAP.|... The hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells /were examined/. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S-yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3-(glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S-2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase.|4-Aminophenol in the presence of oxyhemoglobin forms numerous adducts with glutathione (GSH). Using (14)C-4-aminophenol and (3)H-glutathione, ten different thioethers were isolated, by HPLC, with isotope ratios of 1:1, 1:2, 1:3, respectively ... In erythrocytes of humans and dogs, and in dog blood, in vivo, the same pattern of 4-aminophenol conjugates with GSH was found. In vivo, 5% of administered 4-aminophenol is converted into thioethers within erythrocytes, accompanied by a 60% decrease in the cellular GSH, indicating the role of erythrocytes in the biotransformation of xenobiotics.|p-Aminophenol yields p-acetamidophenol, p-aminophenyl-beta-d-glucuronide, p-aminophenyl sulfate, 4-aminoresorcinol, and p-methylaminophenol in rabbit.|For more Metabolism/Metabolites (Complete) data for 4-Aminophenol (12 total), please visit the HSDB record page.|4-aminophenol is a known human metabolite of aniline.

... Markers of ER stress (XBP1 messenger RNA processing and protein expression; GRP78 and GRP94 upregulation) and ER-mediated cell death (caspase-12 and calpain activation) were examined in kidney tissue of rats exposed to nephrotoxic doses of cisplatin (CIS), gentamicin (GEN), and p-aminophenol (PAP), a nephrotoxic metabolite of acetaminophen. XBP1 signaling was observed with all three drugs and was associated with increased expression of GRP94 and GRP78 in GEN- and PAP-treated animals, but not after CIS exposure. m-Calpain expression was increased after 7 days of CIS treatment, whereas it was decreased in PAP-treated rats. Caspase-12 cleavage products were increased after CIS, GEN, and PAP administration. The results of this study demonstrate that three clinically relevant nephrotoxic drugs are all associated with changes in markers of ER stress and ER-mediated cell death in vivo ...|4-Aminophenol (4-AP), D-serine, and cisplatin are established rodent nephrotoxins that damage proximal tubules within the renal cortex ... High throughput 2D gel proteomics to profile protein changes in the plasma of compound-treated animals, ... /demonstrated/ several markers of kidney toxicity. Male F344 and Alpk rats were treated with increasing doses of 4-AP, D-serine, or cisplatin, and plasma samples were collected over time ... Several isoforms of the rat-specific T-kininogen protein were identified in each study. T-kininogen was elevated in the plasma of 4-AP-, D-serine-, and cisplatin-treated animals at early time points, returning to baseline levels 3 weeks after treatment. The protein was not elevated in the plasma of control animals or those treated with nontoxic compounds. /It was proposed/ that T-kininogen may be required to counteract apoptosis in proximal tubular cells in order to minimize tissue damage following a toxic insult. In addition, T-kininogen may be required to stimulate localized inflammation to aid tissue repair ... Several isoforms of the inter-alpha inhibitor H4P heavy chain /were identified/ in the 4-AP and D-serine studies. In each case, the protein expression levels in the blood samples paralleled the extent of kidney toxicity, highlighting the correlation between protein alterations and clinical chemistry endpoints. A further set of proteins correlating with kidney damage was found to be a component of the complement cascade and other blood clotting factors, indicating a contribution of the immune system to the observed toxicity. These observations underscore the value of proteomics in identifying new biomarkers and in the elucidation of mechanisms of toxicity.|One of the primary effects found from exposure to p-aminophenol is the formation of methemoglobin. This effect has been found in many species with a wide degree of susceptibility. The oxidation of hemoglobin to methemoglobin interferes with normal oxygen transport functions of hemoglobin and can result in a chemical asphyxia (usually at levels of 60% or more). It is believed that p-aminophenol forms a covalent bond with the reactive -SH groups of hemoglobin and transfers electrons to oxygen to created methemoglobin.|p-Aminophenol is a significantly toxic chemical and one mechanism associated with its cytotoxicity has been attributed to its activity as a tissue respiratory (oxidative phosphorylation) inhibitor ... .

SYMPTOMS: Symptoms of exposure to this chemical may include asthma, irritation of the skin and eyes, dermatitis and methemoglobinemia with cyanosis. ACUTE/CHRONIC HAZARDS: This compound is a skin and eye irritant and an allergen. When heated to decomposition it emits toxic fumes. (NTP, 1992)

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. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. 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. Phenols are very toxic poisons AND corrosive and irritating, so that inducing vomiting may make medical problems worse. IMMEDIATELY call a hospital or poison control center and locate activated charcoal, egg whites, or milk in case the medical advisor recommends administering one of them. If advice from a physician is not readily available and the victim is conscious and not convulsing, give the victim a glass of activated charcoal slurry in water or, if this is not available, a glass of milk, or beaten egg whites and IMMEDIATELY transport victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, assure 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. (NTP, 1992)

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. /Aniline and related compounds/|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 if 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 patent can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aniline and related compounds/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Monitor cardiac rhythm and treat arrhythmias as 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. Consider vasopressors if hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aniline and related compounds/

/HUMAN EXPOSURE STUDIES/ An examination of 31 employees from a chemical factory producing 4-aminophenol (PAP) and other aromatic compounds was conducted using single 48-hr occlusive patches with five of the suspected chemicaIs. Ten of the 31 employees reacted positively to PAP in petrolatum at one or more of the applied doses. Generally dose related, these responses ranged from 1+ at 0.1% PAP (1/31) to 2+ (3/31) and 3+ (1/31) at 1% PAP, with 6/10 employees having 1+ reactions at 0.5% PAP. PAP did not induce primary irritant contact dermatitis in any of the 5 controls, and none of the 31 sensitized subjects who were tested with PAP had cross sensitization when later challenged with dinitrochlorobenzene.|/HUMAN EXPOSURE STUDIES/ Aqueous solutions of 1.0% 3-aminopheol (MAP) and 0.5% 4-aminophenol (PAP) were tested for depigmentation and discoloration after repeated topical application to the skin on one of the forearms of 26 volunteers (20 black and 6 white). The subjects were separated into 2 groups of 13; 1 group received 0.1 5 mL applications of the PAP solution, and the other group received 0.1 5 mL of the MAP solution. Sites were washed by the subjects 1 hr after application of the solutions. The solutions were applied to the same sites for 3 consecutive days the first week and for 4 consecutive days the second and third weeks. Three days after the 11th application, the subjects' arms were evaluated for "circumscribed areas on either forearm in which the skin color appeared different from that of the surrounding area." Subjects were asked to comment on the test procedure or any adverse effects experienced during the study. There was no evidence of skin color changes, lightening or darkening, in any of the 6 white subjects. No lightening of skin color was observed in any of the black subjects. A slight darkening of the skin of 2 black subjects treated with the PAP solution was noted. Slight to moderate primary skin irritation was found in I subject after three to seven applications of the PAP solution.|/HUMAN EXPOSURE STUDIES/ In 80 patients, positive to at least one hapten of the para group (para-phenylenediamine, diaminodiphenylmethane, benzocaine, PPD mix), patch tests were carried out with freshly prepared solutions of para-phenylenediamine (PPD) and of 3 selected aromatic compounds related structurally to PPD (para-aminophenol, ortho-aminophenol, hydroquinone). The number of positive reactions correlated with the rate of decomposition of the substances as evaluated by high-pressure liquid chromatography. PPD, which was almost decomposed after 24 hr, gave the highest number of positive reactions, followed by ortho-aminophenol and by para-aminophenol, while hydroquinone, which was oxidized to the extent of 35%, did not give any reactions ... The results suggest that the rate of decomposition and therefore the amount of quinone(s) generated, might be the key to eliciting patch test responses to oxidizable aromatic haptens.|/SIGNS AND SYMPTOMS/ Short term exposure: Aminophenols can be absorbed through the skin, thereby increasing exposure. Can cause lung irritation. Poisonous if swallowed. These chemicals lower the blood's ability to carry oxygen (methemoglobinemia). This condition causes a bluish color to the skin and lips, headaches, dizziness; higher exposures can result in unconsciousness and death. Irritates eyes, skin, and respiratory tract. Skin contact can cause burning sensation and rash ... May produce dermatitis, methemoglobinemia, bronchial asthma, and restlessness. Long term exposure: prolonged or repeated contact can cause blood damage, skin disorders, liver, kidney, and brain damage. Aminophenols may cause mutations, and there is limited teratogenic evidence. Skin allergy or asthma may develop; future exposures, even in low doses, can cause symptoms to occur. /Aminophenols/|For more Human Toxicity Excerpts (Complete) data for 4-Aminophenol (16 total), please visit the HSDB record page.

4-aminophenol

Grades: Technical; photographic

All other basic organic chemical manufacturing|Phenol, 4-amino-: ACTIVE|TP - indicates a substance that is the subject of a proposed TSCA section 4 test rule.

Choice of TLC systems for routine screening for acidic drugs during toxicological analyses.|Nitrogen flame ionization detector/flame ionization detector ratio as aid for identification of forensically relevant cmpd.|Hair dyes acting by oxidation. Their identification & estimation by high-performance liq phase chromatography.|Chloramin "fahlberg"--a new detection reagent for identification & semiquantitative determination of nitro- & aminophenols in polluted water. A TLC determination.|Methods for analysis of arylamines & their N- & C-hydroxylated metabolites, including high-pressure liq chromatography & spectrophotometric methods.

Cosmetics -> Hair dyeing|Environmental transformation -> Pesticide transformation products (metabolite, successor)

4-hydroxy benzonitrile is a known environmental transformation product of Bromoxynil.