4-tert-Butylphenol

H315: Causes skin irritation [Warning Skin corrosion/irritation]

H318: Causes serious eye damage [Danger Serious eye damage/eye irritation]

H361f: Suspected of damaging fertility [Warning Reproductive toxicity]

H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P203, P264, P264+P265, P273, P280, P302+P352, P305+P354+P338, P317, P318, P321, P332+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.2% (7 of 3826) of reports.

H314 (12.2%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

H315 (87.6%): Causes skin irritation [Warning Skin corrosion/irritation]

H317 (12.7%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H318 (55.8%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H319 (50.4%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (57.1%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H361 (40.1%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H410 (11.8%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

H411 (48.2%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P203, P260, P261, P264, P264+P265, P271, P272, P273, P280, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P351+P338, P305+P354+P338, P316, P317, P318, P319, P321, P332+P317, P333+P317, P337+P317, P362+P364, P363, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3826 reports by companies from 74 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 7 of 3826 reports by companies.

There are 73 notifications provided by 3819 of 3826 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.

H335: May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H401: Toxic to aquatic life [Hazardous to the aquatic environment, acute hazard]

H411: Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P203, P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P354+P338, P317, P318, P319, P321, P332+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]

H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P260, P261, P264, P264+P265, P270, P271, P272, P280, P302+P352, P304+P340, P305+P354+P338, P317, P319, P321, P332+P317, P333+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

H360: May damage fertility or the unborn child [Danger Reproductive toxicity]

Fresh air, rest.

Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention .

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

Rinse mouth. Give one or two glasses of water to drink. Rest. 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.

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)

A fire in your laboratory involving this chemical should be extinguished with a dry chemical, carbon dioxide or halon extinguisher. (NTP, 1992)

Use alcohol-resistant foam, powder, carbon dioxide.

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.

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (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)

Personal protection: filter respirator for organic gases and particulates adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. 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. Discharge into the environment must be avoided. 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.

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.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product.

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. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. 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 p-tert-Butylphenol (6 total), please visit the HSDB record page.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong 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 store this material in a refrigerator. (NTP, 1992)

Well closed.

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

0.08 [ppm]

1 [mg/m3]

40 [mg/m3]

240 [mg/m3]

0.5 mg/m

Evaporation at 20 °C is negligible; a harmful concentration of airborne particles can, however, be reached quickly when dispersed.

The substance is severely irritating to the eyes, skin and respiratory tract. The substance may cause effects on the skin. This may result in depigmentation.

Repeated or prolonged contact with skin may cause dermatitis. Repeated or prolonged contact may cause skin sensitization. The substance may have effects on the liver, spleen, thyroid and nervous system. This may result in impaired functions.

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.

RECOMMENDED GLOVE MATERIALS: Permeation data indicate that butyl rubber gloves may provide protection to contact with this compound. Butyl rubber over latex gloves is recommended. However, if this chemical makes direct contact with your gloves, or if a tear, hole or puncture develops, remove them at once. (NTP, 1992)

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166 (EU).

Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

NO open flames.

PREVENT DISPERSION OF DUST! STRICT HYGIENE!

Use local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear safety goggles or eye protection in combination with breathing protection.

Do not eat, drink, or smoke during work.

Crystals or practically white flakes. Has a disinfectant-like odor. May float or sink in water. Insoluble in water. (NTP, 1992)

Liquid; Other Solid; Liquid; Other Solid; Dry Powder; CBI; Large Crystals

White solid with a disinfectant-like odor; [CAMEO] Hygroscopic; [ICSC] White crystalline powder; [MSDSonline]

WHITE HYGROSCOPIC FLAKES.

White needle-like crystals, phenolic odour

Crystals or white flakes with disinfectant-type odor.

Needles from water

Needles from lignin

White crystals

Crystals, needles, or practically white flakes

Distinctive odor

463.1 °F at 760 mmHg (NTP, 1992)

237.00 °C. @ 760.00 mm Hg

463.1 °F

214 °F (NTP, 1992)

235 °F (NTP, 1992)

113 °C (235 °F) - closed cup

115 °C o.c.

Insoluble (NTP, 1992)

In water, 580 mg/L at 25 °C

In water, 610 mg/L at 25 deg (OECD Guideline 105)

In water, 607.2 mg/L at 25 °C (pH 6-7) National Standard ASTM E 1148 - 02, which is similar to OECD Guideline No. 105)

Soluble in ethanol, ether, chloroform, alkalis

0.58 mg/mL at 25 °C

Solubility in water: none

insoluble in water; soluble in ethanol; soluble in ether

moderately soluble (in ethanol)

0.908 at 176 °F (NTP, 1992) - Less dense than water; will float

1.037 at 25 °C

Density: 0.908 g/cu cm at 80 °C

0.9 g/cm³

1.037 @25 °C

5.1 (NTP, 1992) - Heavier than air; will sink (Relative to Air)

5.1 (Air = 1)

1 mmHg at 158 °F (NTP, 1992)

0.03 [mmHg]

0.00919 mm Hg at 25 °C

Vapor pressure, Pa at 50 °C: 30

1 [mm Hg] @70 °C

log Kow = 3.31

Insoluble in water.

Phenols and Cresols

Phenols, such as 4-TERT-BUTYL PHENOL, do not behave as organic alcohols, as one might guess from the presence of a hydroxyl (-OH) group in their structure. Instead, they react as weak organic acids. Phenols and cresols are much weaker as acids than common carboxylic acids (phenol has pKa = 9.88). These materials are incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides. Flammable gas (H2) is often generated, and the heat of the reaction may ignite the gas. Heat is also generated by the acid-base reaction between phenols and bases. Such heating may initiate polymerization of the organic compound. Phenols are sulfonated very readily (for example, by concentrated sulfuric acid at room temperature). The reactions generate heat. Phenols are also nitrated very rapidly, even by dilute nitric acid.

Incompatible materials: Bases, acid chlorides, acid anhydrides, oxidizing agents, brass, copper.

IDENTIFICATION AND USE: p-tert-Butylphenol (4-TBP) is a solid. It is used as a plasticizer for cellulose acetate, intermediate for antioxidants, special starches, oil-soluble phenolic resins, as a pour-point depressors and emulsion breakers for petroleum oils and some plastics, as a synthetic lubricants, industrial odorants, and motor-oil additives. It is no longer used as insecticide. HUMAN STUDIES: In a routine test series of the North American Contact Dermatitis Group in 1,900 patients with contact dermatitis revealed 1.9% positive reactions and the test series with 900-2,000 contact dermatitis patients revealed 1.1% positive reactions to 2% of 4-TBP. Ten shoemakers with eczema due to occupational exposure to 4-TBP containing glues were patch-tested for sensitization. Positive reactions to the glue, its ingredients and 4-TBP were observed in all patients. After 24 hours, reaction in the 4-TBP test was erythema, edema or papules, and some patients showed a few vesicles. After 48 hours, all patients showed these symptoms. In the search for environmental compounds responsible for contact or occupational vitiligo, it was found that the most potent was 4-TBP. In vitro 4-TBP induced oxidative stress that was more readily overcome by melanocytes from normally pigmented individuals than from two individuals with vitiligo. ANIMAL STUDIES: Sluggishness, unsteady gait, prostration, unkempt appearance, and nasal discharge were observed as the principal signs of toxicity in acute studies in rats. After inhalation exposure in rats, clinical signs observed on the day of exposure and up to 7 days after it included mucosal irritation and respiratory distress. Male hamsters given a 15 g/kg in a diet developed hyperplasia in the forestomach and papillomatous lesions. Male rats given a 15 g/kg in a diet for 51 weeks developed forestomach hyperplasia, but no tumors in the other organs. there were no treatment related toxic effects on pregnant and lactating females or their offspring in developmental studies in rats. 4-TBP did not induce gene mutation in S. Typhimurium TA100, TA98, TA1535, TA1537 and E. coli WP2 uvrA with and without exogenous metabolic activation system. However, 4-TBP induced both structural and numerical chromosome aberrations in vitro.

4-Tert-butylphenol is structurally similar to the melanin precursor tyrosine, and acts as a substrate for tyrosinase. Tyrosinase oxidizes 4-tert-butylphenol to a quinone (4-tert-butylcyclohexa-3,5-diene-1,2-dione) which in turn rapidly reacts with glutathione (GSH). A depletion of the GSH defence system may allow the quinone to generate reactive oxygen species that damage melanocytes and induce apoptosis, leading to leukoderma/vitiligo. (A15209, A15210)

No indication of carcinogenicity to humans (not listed by IARC).

Leukoderma, vitiligo.

The substance can be absorbed into the body by inhalation of its aerosol and through the skin.

Cough. Sore throat.

Redness. Pain.

Nausea. Vomiting.

Loss of skin pigmentation.

Neurotoxin - Other CNS neurotoxin

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

LCLo (rat) = 911.46 ppm/4h

LD50 Rat oral 4,000 mg/kg

LD50 Rabbit dermal 2,318 mg/kg

LD50 Rat ip 225 mg/kg

LD50 Rat oral 3.25 mL/kg

For more Non-Human Toxicity Values (Complete) data for p-tert-Butylphenol (6 total), please visit the HSDB record page.

Inhalation: Fresh air, rest. Skin: Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention. Eyes: First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention. Ingestion: Rinse mouth /SRP: if patient awake alert with good airway protection reflexes./ Rest. Refer for medical attention.

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

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . 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 ... . Administer activated charcoal ... . Dilution may be contraindicated because if may increase absorption. Do not use emetics. Cover skin burns with dry, sterile dressings after decontamination ... . Maintain body temperature. /Phenols and related compounds/

/SRP:/ 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. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is 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 ... . /Phenols and related compounds/

/HUMAN EXPOSURE STUDIES/ One data reported that in a routine test series of the North American Contact Dermatitis Group in 1974/75, 1,900 patients with contact dermatitis revealed 1.9% positive reactions and the test series in 1975/76 with 900-2,000 contact dermatitis patients revealed 1.1% positive reactions to 2% of p-t-butylphenol.

/HUMAN EXPOSURE STUDIES/ Ten shoemakers with eczema due to occupational exposure to p-t-butylphenol containing glues were patch-tested for sensitization in 1957. Positive reactions to the glue, its ingredients formaldehyde-p-t-butylphenol resin (50% in ethyl acetate; three patients: 75% in ethyl acetate) and p-t-butylphenol (50% in ethyl acetate) were observed in all patients. After 24 hours, reaction in the p-t-butylphenol test was erythema, edema or papules, and some patients showed a few vesicles. After 48 hours, all patients showed these symptoms.

/HUMAN EXPOSURE STUDIES/ 100 consecutive cases of contact depigmentation due to bindi during a period of 11 months were studied. Bindi adhesive material was found to contain 80% para-tertiary-butylphenol (PTBP), by thin-layer chromatography, infrared spectrophotometry and high-pressure liquid chromatography. The possibility of hypersensitivity to PTBP was ruled out as none of the 15 patients tested with 2% PTBP and 1% para-tertiary-butylphenol-formaldehyde resin gave any positive reactions. Development of depigmentation could have been due either to individual susceptibility or to constant use for a prolonged period. The area of contact being very small, generalized vitiligo as a result of systemic absorption appeared to be a remote possibility.

/CASE REPORTS/ 10 male workers (25-53 years old) occupationally exposed to p-t-butylphenol, formaldehyde and derivatives developed vitiligo 10 months to 7 years after the beginning of their exposure (p-tbutylphenol concentration in dust: 0.12-0.96 mg/cu m air). This symptom occurred especially at the skin of exposed body sites like hands and forearms and consisted of more or less intensively spread finger-nail to palm-sized depigmented spots with irregular configuration. Visible mucous membranes, hair and nails were without any findings. No irritation occurred prior to or during the development of vitiligo. An enlarged liver and spleen was observed in 4 and 1 of these vitiligo patients, respectively. Some liver enzyme activities were increased in two cases, of which one case showed increase in the BSP clearance. In thyroid gland, one patient showed microsomal autoantibodies (titer: 1 : 25600) and thyreoglobuline-auto-antibodies (titer: 1 : 25), and another showed struma diffusa of grade 1 (WHO classification). A stringent combination of vitiligo, hepatosplenopathy and struma could not be found in any patient.

For more Human Toxicity Excerpts (Complete) data for p-tert-Butylphenol (8 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ Para-tertiary butylphenol [(PTBP) ... has applications as a raw material in the manufacture of resins and also as an industrial intermediate. Acute peroral LD50 values (95% confidence limits) of 5.4 (3.6-7.9) g/kg and 3.6 (3.0-4.4) g/kg were obtained for male and female albino rats, respectively. Occluded cutaneous applications of moistened PTBP at 16 g/kg for 24 hr produced no mortalities in male or female rabbits, but signs of local toxicity and irritation were apparent at the site of application. A 6 hr exposure to a substantially saturated vapor under static conditions produced no mortality, while a 4 hr exposure to a dynamically generated respirable dust aerosol at a concentration of 5.6 mg/L produced 20% mortality. Occluded dermal contact (4 hr) with 0.5 g moistened PTBP produced a range of effects from no reaction to necrosis. PTBP placed in the conjunctival sac of rabbits produced severe ocular injury which generally persisted for 21 days after exposure. The major hazard associated with acute exposure to PTBP appears to be the irritation produced by dermal or ocular contact.

/LABORATORY ANIMALS: Acute Exposure/ The effects of p-tert-butylphenyl trans-4-guanidinomethylcyclohexane carboxylate hydrochloride (NCO-650) and its metabolite, p-tert-butylphenol(BP), on the drug-metabolizing enzymes and fine structure in the rat liver were examined. Aminopyrine demethylase activity was inhibited by the administration of NCO-650 and BP at a dose of 2 and 10 mg/kg, p.o. The increases of microsomal cytochrome b5 and cytochrome P-450 contents were noticed at 1, 12 and 24 hr after NCO-650 and BP administration. Ascorbate-dependent lipid peroxidation of mitochondria and microsome increased by the administration of NCO-650 and BP, but NADPH-dependent lipid peroxidation decreased by these drugs. In the morphological observations of fine structure in the liver, NCO-650 and BP caused the swelling and decrease of rough endoplasmic reticulum and the increase of smooth endoplasmic reticulum. The morphological changes of liver fine structure were related to the changes of drug-metabolizing enzymes in the liver by the administration of NCO-650 and BP, which may be suggest the transitory and functional responses of these drugs in the liver. The effect of BP on the drug-metabolizing enzymes and fine structure in the liver was similar to that of NCO-650.

/LABORATORY ANIMALS: Acute Exposure/ In one study, LD50 /oral/ was 5,360 mg/kg b.w. and 3,620 mg/kg b.w. for male and female rats, respectively. Sluggishness, unsteady gait, prostration, unkempt appearance, and nasal discharge were observed as the principal signs of toxicity. Signs of toxicity subsided in survivors at 3 to 7 days after dosing. Deaths were induced from 2 hours to 5 days after dosing. In rats died during the study, there were mottling of the lungs and livers as the principal macroscopic lesions in female but no significant gross lesions in male.

/LABORATORY ANIMALS: Acute Exposure/ Rats were exposed for 4 hours to this chemical as dust aerosol of 5,600 mg/cu cm with additional vapor component of 30 mg/cu cm. Within one to two days following exposure, 1/5 rat of each sex died, which showed dark red of purple discoloration of the lungs and/or kidneys but not survivors. Clinical signs observed on the day of exposure and up to 7 days postexposure included signs of mucosal irritation (perinasal, perioral, and periocular encrustation) and signs of respiratory distress (audible respiration, gasping, and a deceased respiration rate).

For more Non-Human Toxicity Excerpts (Complete) data for p-tert-Butylphenol (14 total), please visit the HSDB record page.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of August 9, 2018: http://actor.epa.gov/dashboard/]

Vitiligo presents with depigmented cutaneous lesions following localized melanocyte death. Multiple factors contribute to cell death, including genetically determined susceptibility to trauma, and environmental factors, such as exposure to 4-tert-butylphenol (4-TBP). We demonstrate that 4-TBP induces oxidative stress that is more readily overcome by melanocytes from normally pigmented individuals than from two individuals with vitiligo. The antioxidant catalase selectively and significantly reduced death of melanocytes derived from two individuals with vitiligo, indicating a role for oxidative stress in vitiligo pathogenesis. In normal melanocytes, oxidative stress results in reduced expression of microphthalmia-associated transcription factor (MITF). Melanocyte-stimulating hormone-induced expression of MITF protein caused increased sensitivity to 4-TBP, whereas sensitivity of melanomas correlated with MITF expression. MITF stimulates melanin synthesis by up-regulating expression of melanogenic enzymes such as tyrosinase-related protein-1 (Tyrp1). Although melanin content per se did not affect sensitivity to 4-TBP, expression of Tyrp1 significantly increased sensitivity. Melanocytes and melanomas that express functional Tyrp1 were significantly more sensitive to 4-TBP than Tyrp1-null cells. Thus, normal melanocytes respond to 4-TBP by reducing expression of MITF and Tyrp1. We hypothesize that melanocytes in vitiligo demonstrate reduced ability to withstand oxidative stress due, partly, to a disruption in MITF regulation of Tyrp1.

LC50; Species: Crangon septemspinosa (Bay Shrimp, Sand Shrimp) length 6.4-8.3 cm, weight 2.4-4.5 g; Conditions: saltwater, renewal, 10 °C; Concentration: 1900 ug/L for 96 hr

EC50; Species: Daphnia magna (Water Flea) age 6-24 hr; Conditions: freshwater, static, 20 °C, pH > or =7.0; Concentration: 4200 ug/L for 24 hr (95% confidence interval: 3800-4700 ug/L); Effect: intoxication, immobilization /formulated product/

EC50; Species: Daphnia magna (Water Flea) age 6-24 hr; Conditions: freshwater, static, 20 °C, pH > or =7.0; Concentration: 3900 ug/L for 48 hr (95% confidence interval: 3400-4500 ug/L); Effect: intoxication, immobilization /formulated product/

LC50; Species: Pimephales promelas (Fathead Minnow) age 31-35 days, weight 97 mg; Conditions: freshwater, flow through, 24.6 °C, pH 6.9-7.7, hardness 44.9 mg/L CaCO3 (42.4-46.6 mg//L CaCO3), alkalinity 42.9 mg/L CaCO3 (39.6-61.4 mg/L CaCO3), dissolved oxygen 7.4 mg/L (4.6-8.8 mg/L); Concentration: 6210 ug/L for 24 hr (95% confidence interval: 5780-6680 ug/L) />99% purity/

For more Ecotoxicity Values (Complete) data for p-tert-Butylphenol (8 total), please visit the HSDB record page.

The substance is toxic to aquatic organisms. Bioaccumulation of this chemical may occur in fish.

LC50; Species: Crangon septemspinosa (Bay Shrimp, Sand Shrimp) length 6.4-8.3 cm, weight 2.4-4.5 g; Conditions: saltwater, renewal, 10 °C; Concentration: 1900 ug/L for 96 hr

EC50; Species: Daphnia magna (Water Flea) age 6-24 hr; Conditions: freshwater, static, 20 °C, pH > or =7.0; Concentration: 4200 ug/L for 24 hr (95% confidence interval: 3800-4700 ug/L); Effect: intoxication, immobilization /formulated product/

EC50; Species: Daphnia magna (Water Flea) age 6-24 hr; Conditions: freshwater, static, 20 °C, pH > or =7.0; Concentration: 3900 ug/L for 48 hr (95% confidence interval: 3400-4500 ug/L); Effect: intoxication, immobilization /formulated product/

LC50; Species: Pimephales promelas (Fathead Minnow) age 31-35 days, weight 97 mg; Conditions: freshwater, flow through, 24.6 °C, pH 6.9-7.7, hardness 44.9 mg/L CaCO3 (42.4-46.6 mg//L CaCO3), alkalinity 42.9 mg/L CaCO3 (39.6-61.4 mg/L CaCO3), dissolved oxygen 7.4 mg/L (4.6-8.8 mg/L); Concentration: 6210 ug/L for 24 hr (95% confidence interval: 5780-6680 ug/L) />99% purity/

For more Ecotoxicity Values (Complete) data for p-tert-Butylphenol (8 total), please visit the HSDB record page.

The substance is toxic to aquatic organisms. Bioaccumulation of this chemical may occur in fish.

p-tert-Butylphenol's production and use as a chemical intermediate for a variety of applications (especially polycarbonates and epoxy resins) and as a plasticizer for cellulose acetate may result in its release to the environment through various waste streams. Small percentages of unreacted p-tert-butylphenol occur in polycarbonates and epoxy resins, and p-tert-butylphenol has been detected in landfill leachates and incinerator emissions. If released to air, a vapor pressure of 0.00919 mm Hg at 25 °C indicates p-tert-butylphenol will exist solely as a vapor in the atmosphere. Vapor-phase p-tert-butylphenol will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 9.5 hours. p-tert-Butylphenol absorbs at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, p-tert-butylphenol is expected to have low mobility based upon an estimated Koc of 1290. The pKa of p-tert-butylphenol is 10.16, indicating that this compound will exist almost entirely in the neutral form in the environment. Volatilization from moist soil surfaces is not expected to be an important fate process based upon a Henry's Law constant of 1.19X10-6 atm-cu m/mole. p-tert-Butylphenol is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Results of biodegradation screen tests suggest p-tert-butylphenol can be readily biodegradable via adapted microorganisms and at concentrations below inhibitory effects. Therefore, biodegradation is expected to be an important fate process in both soil and water. If released into water, p-tert-butylphenol is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to occur based upon this compound's Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 38 and 279 days, respectively. An BCF range of 20-120 suggests bioconcentration in aquatic organisms is low to moderate. p-tert-Butylphenol is stable to hydrolysis at pH 4, pH 7 and pH 9. Occupational exposure to p-tert-butylphenol may occur through inhalation and dermal contact with this compound at workplaces where p-tert-butylphenol is produced or used. Monitoring and use data indicate that the general population may be exposed to p-tert-butylphenol via inhalation of ambient air and dermal contact with consumer products containing p-tert-butylphenol. Potential consumer exposure is via use of products with phenolic resins or epoxy resins containing residual p-tert-butylphenol. Consumers may be exposed to p-tert-butylphenol in drinking water from drinking water reservoirs coated with epoxy-based paints or from pipelines. Consumers may also be exposed to p-tert-butylphenol from polycarbonate used for food contact material. (SRC)

p-tert-Butylphenol's production and use as a chemical intermediate for a variety of applications and as a plasticizer for cellulose acetate(1,2) may result in its release to the environment through various waste streams(SRC). The major use is in chemical synthesis for the production of polycarbonate, phenolic resins, epoxy resins(2). Small amounts of unreacted p-tert-butylphenol can exist in polycarbonate and resin products(2) and p-tert-butylphenol has been detected in landfill leachates(3). p-tert-Butylphenol has been detected in combustion emissions from incinerators(4).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1290(SRC), determined from a structure estimation method(2), indicates that p-tert-butylphenol is expected to have low mobility in soil(SRC). The pKa of p-tert-butylphenol is 10.16(3), indicating that this compound will exist almost entirely in the neutral form in the environment. Volatilization of p-tert-butylphenol from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 1.19X10-6 atm-cu m/mole(4). p-tert-Butylphenol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.00919 mm Hg at 25 °C(5). Results of biodegradation screen tests suggest p-tert-butylphenol can be readily biodegradable via adapted microorganisms and at concentrations below inhibitory effects(6). Therefore, biodegradation is expected to be an important fate process(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1290(SRC), determined from a structure estimation method(2), indicates that p-tert-butylphenol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon a Henry's Law constant of 1.19X10-6 atm-cu m/mole(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 38 and 279 days, respectively(SRC). According to a classification scheme(5), a measured BCF range of 20-120(6,7), suggests the potential for bioconcentration in aquatic organisms is low to moderate(SRC). Results of biodegradation screen tests suggest p-tert-butylphenol can be readily biodegradable via adapted microorganisms and at concentrations below inhibitory effects(8). Therefore, biodegradation is expected to be an important fate process(SRC). p-tert-Butylphenol was found to be stable to hydrolysis at pH 4, pH 7 and pH 9 using OECD Guideline 111(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), p-tert-butylphenol, which has a vapor pressure of 0.00919 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase p-tert-butylphenol 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 9.5 hours(SRC), calculated from its rate constant of 4.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). p-tert-Butylphenol absorbs at wavelengths >290 nm(4,5) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

AEROBIC: p-tert-Butylphenol, present at 100 mg/L, reached 0% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1) which classified the compound as not readily biodegradable; however, it was likely that an inhibitory concentration of p-tert-butylphenol was used in the test(2). In a DOC-Die Away Test (OECD Guideline 301A) using unadapted activated sludge, p-tert-butylphenol (13 mg/L) was degraded 98% during a 28-day incubation period with a 10-day window criterion fulfilled classifying the compound as readily biodegradable(2,3); however, it can not be excluded that the inoculum might have been adapted to p-tert-butylphenol, as it was taken from a heavily industrialized area treatment plant(2). Using OECD Guideline 301B (CO2 Evolution Test) with an activated sludge inoculum, p-tert-butylphenol achieved final mean degradation of 58.5 and 63.6% (at 5 and 10 mg/L respectively), but did not pass the ready biodegradability criterion (60% degradation within a 10-days window, counting from the time the biodegradation passes the 10% level)(2). Using a Manometric Respiratory test system (OECD Guideline 301F) and an in-house unadapted activated sludge, p-tert-butylphenol achieved 28-day theoretical BODs of 60% (15 mg/L) and 42% (25 mg/L) with lag-phases of 12-16 days before initial degradation begins(2); the criterion of ready biodegradability was not met(2); the results of this study indicates that municipal sludge microorganisms require an adaptation period in order to degrade p-tert-butylphenol rapidly(2). When activated sludge from a municipal sewage treatment plant was used as the inoculum, <0.1% of initial p-tert-butylphenol (50 ug/L) was degraded to CO2 within 5 days(4). Tests using natural and sterilized conditions found that removal from the environmental waters was likely caused by biodegradation(5).

The rate constant for the vapor-phase reaction of p-tert-butylphenol with photochemically-produced hydroxyl radicals has been estimated as 4.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 9.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the estimated OH radical reaction of p-tert-butylphenol with hydroxyl radicals in aqueous solutions at pH 9 is 1.9X10+10 L/mol-sec(2); this corresponds to an aquatic half-life of 42 days at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(3). p-tert-Butylphenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). Using OECD Guideline 111, p-tert-butylphenol was found to be stable to hydrolysis at pH 4, pH 7 and pH 9(5). p-tert-Butylphenol absorbs in the UV region at wavelengths >290 nm(5,6) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). In a photodegradation test where p-tert-butylphenol was adsorbed to silica gel and irradiated with light >290nm, 46.8% was degraded(7). Direct photolysis of p-tert-butylphenol was found to yield 4-tert-butylcatechol and 4-tert-butylphenol dimer(8).

A BCF range of 20-88 for p-tert-butylphenol was measured in fish using carp (Cyprinus carpio) which were exposed over an 8-week period(1). The BCF determined in Golden Ide fish (Leuciscus idus melanotus) was 120 over a 30-day exposure(2). According to a classification scheme(3), these BCFs suggest the potential for bioconcentration in aquatic organisms is low to moderate (SRC). A 1-day exposure BCF of 30 was measured in green algae (Chlorella fusca)(2).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of p-tert-butylphenol can be estimated to be 1290(SRC). According to a classification scheme(2), this estimated Koc value suggests that p-tert-butylphenol is expected to have low mobility in soil. The pKa of p-tert-butylphenol is 10.16(3), indicating that this compound will exist almost entirely in the neutral form in the environment(SRC); a small percentage of p-tert-butylphenol may exist in anionic form and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for p-tert-butylphenol has been measured as 1.19X10-6 atm-cu m/mole(1). This Henry's Law constant indicates that p-tert-butylphenol is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 38 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 279 days(SRC). p-tert-Butylphenol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). p-tert-butylphenol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.00919 mm Hg(3).

GROUNDWATER: p-tert-Butylphenol was detected in 3 of 4 contaminated groundwater samples collected in Cape Cod, MA in 1996-1997(1).

DRINKING WATER: p-tert-Butylphenol was not detected (MDL of 0.9 ng/L) in various well and tap water samples collected in Cape Cod, MA in 1996-1997(1).

SURFACE WATER: One seawater sample collected near the industrial port of Tarragona, Spain during 2001-2002 contained a p-tert-butylphenol concentration of 0.13 ug/L(1). Analysis of water samples taken the Elbe River and tributaries in 1998 identified p-tert-butylphenol concentrations of 1.4-78 ng/L(2). Water collected from the North Sea in 1998 and 1999 had p-tert-butylphenol concentrations of 0.1-43 ng/L(2). Water collected from the Fujima and Shiratori Rivers (near Lake Biwa, Japan) during 1999-2000 had p-tert-butylphenol concentrations of 0-0.10 and 0-0.02 ng/mL respectively(3). Water from Taihu Lake, China had an average p-tert-butylphenol concentration of 1.26 ppb (range of 0.208-2.32 ppb)(4). Surface water from the Yangtze River, China had p-tert-butylphenol concentrations of 225-1121 ng/L(5).

Leachate samples collected at four landfills in the Gothenburg region, Sweden had a median p-tert-butylphenol concentration of 0.97 ug/L (range of 0.027-8.1 ug/L)(1). Leachate samples collected from a municipal landfill in Gryta, Sweden in May 1990 contained tert-butylphenol(2). p-tert-Butylphenol was qualitatively detected in trench leachate samples collected from low-level radioactive waster disposal sites at Maxey Flats, KY and West Valley, NY(3). p-tert-Butylphenol was detected in the influent to a waste treatment facility in North Carolina (possibly due to its use as a detergent constituent)(4). p-tert-Butylphenol was detected in emissions from incinerators(5). Untreated wastewater and septage samples from Cod Cod, MA (1996-1997 sampling) contained p-tert-butylphenol concentrations of 2.2-3.5 and 0.16-3.9 ug/L respectively(6).

SEDIMENT: Analysis of sediment samples taken from the Elbe River, Germany, and tributaries in 1998 identified p-tert-butylphenol concentrations of 19-82 ug/kg dry mass(1).

URBAN/SUBURBAN: p-tert-Butylphenol was detected in outdoor air from Tokyo, Japan(1).

INDOOR AIR: Indoor air samples collected from houses and offices in Tokyo, Japan contained maximum p-tert-butylphenol concentrations of 387 ng/cu m and a detection frequency of >97%(1); concentrations were higher in indoor air compared to outdoor air(1).

p-Butylphenol (isomers not specified) was qualitatively detected in cassava volatiles(1).

Fish (Tilapia and Gambusia) collected from the Tres Rios Wetlands near Phoenix, AZ in 1998 and 2000 contained p-tert-butylphenol concentrations of 16-35 ng/L(1).

The present study determined concentrations of estrogenic bisphenol A (BPA), nonylphenol, octylphenol (4-tert-octylphenol), butylphenol (4-tert-butylphenol), and progestogenic norethindrone by liquid chromatography-tandem mass spectrometry in bile extracts from field fish from the Xin'an River and market fish in Shanghai, China. Compared with the field fish, endocrine disrupting chemical (EDC) concentrations in market fish bile were at relatively high levels with high detectable rates. The average concentrations of BPA, nonylphenol, 4-tert-octylphenol, 4-tert-butylphenol, and norethindrone in field fish bile were 30.1 ug/L, 203 ug/L, 4.69 ug/L, 7.84 ug/L, and 0.514 ug/L, respectively; in market fish bile they were 240 ug/L, 528 ug/L, 76.5 ug/L, 12.8 ug/L, and 5.26 ug/L, respectively; and in the surface water of Xin'an River they were 38.8 ng/L, 7.91 ng/L, 1.98 ng/L, 2.66 ng/L, and 0.116 ng/L, respectively. The average of total estrogenic activity of river water was 3.32 ng/L estradiol equivalents. High bioconcentration factors (BCFs) were discovered for all 5 EDCs (998-fold) in field fish bile. Furthermore, the authors analyzed the BCF value of BPA in fish bile after 30-days exposure to environmentally relevant concentrations of BPA in the laboratory, and the analysis revealed that BCF in fish bile (BCFFish bile) changed in an inverse concentration-dependent manner based on the log10-transformed BPA concentration in water. Strikingly, the data from the field study were well fitted within this trend. The data together suggested that analysis of fish bile extracts could be an efficient method for assessing waterborne EDCs exposure for aquatic biota.

p-tert-Butylphenol was not detected (detection limit not reported) in snails collected from the Fujima and Shiratori Rivers (near Lake Biwa, Japan) during 1999-2000(1).

Polycarbonates have a residual free p-tert-butylphenol concentration of <5 ppm; however, cured epoxy systems may still contain significant amounts of unreacted p-tert-butylphenol (up to 5-10%)(1).

According to the 2016 TSCA Inventory Update Reporting data, 16 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of p-tert-butylphenol in the United States may be as low as <10 workers and as high as 100-500; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 97,601 workers (19,779 of these are female) were potentially exposed to p-tert-butylphenol in the US(1). Occupational exposure to p-tert-butylphenol may occur through inhalation and dermal contact with this compound at workplaces where p-tert-butylphenol is produced or used(2). Monitoring and use data indicate that the general population may be exposed to p-tert-butylphenol via inhalation of ambient air and dermal contact with consumer products containing p-tert-butylphenol(SRC). Potential consumer exposure is via use of products with phenolic resins or epoxy resins containing residual p-tert-butylphenol(2). Consumers may be exposed to p-tert-butylphenol in drinking water from drinking water reservoirs coated with epoxy-based paints or from pipelines(2). Consumers may also be exposed to p-tert-butylphenol from polycarbonate used for food contact material(2). p-tert-Butylphenol was identified as a compound that could potentially leach from plastic pipes and contaminate drinking water(3).

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.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product.

Corrosive

Marine pollutant.

UN Hazard Class: 8; UN Pack Group: III