Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 108-95-2 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Phenol
  • HYDROXYBENZENE
  • CARBOLIC ACID
  • PHENYL HYDROXIDE

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: Chemexfoliation (chemical peeling) is being used to obtain both therapeutic (eg, actinic keratoses) and cosmetic (eg, removal of fine facial rhytides) benefits. Phenol .../is an/ agent for inducing cutaneous exfoliation, may induce cardiac arrhythmias and is toxic to the liver and kidneys. Both phenol and trichloroacetic acid may produce hypertrophic scars and/or keloids and pigmentation irregularities, may accentuate preexisting abnormalities (eg, telangiectasias, nevi, and pores), and may be associated with a flare of latent herpes virus infection. Prolonged erythema of the treated areas and persistent rhytids have been reported with both agents. [Lober CW; J Am Acad Dermatol 17 (1): 109-12 (1987) ]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: ... Phenol damages skin, which increases the rate of penetration; therefore, it should be applied only on small areas of skin, and occlusive dressings, bandages, or diapers should not be used. [American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 1624]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Phenolic disinfectants have produced epidemics of neonatal hyperbilirubinemia when used to clean bassinets and mattresses in poorly ventilated nurseries. Fatalities have been documented in infants. ... [American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 1624]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Phenol is not a very volatile cmpd. Consequently, most toxic effects occur from dermal and oral exposure. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1093]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Phenol is nephrotoxic to humans and animals, especially following chronic exposure. ... Humans have experienced nephritis following toxic dermal exposure. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1095]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Although esophageal stricture is rare, it is a long term complication that may develop /as a result of phenol poisoning/. [Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 222]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: An oral dose of 1 g of phenol may be lethal to man; however, in exceptional cases, patients have survived the ingestion of 65 g of pure phenol or 120 g of the crude product. Roughly 50 percent of all reported cases have terminated fatally. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2573]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Phenol is toxic if absorbed and may result in death even if the exposed area is as small as that of a hand or forearm. [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V17 381 (1982)]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Undiluted /phenol/ cauterizes and whitens the skin and mucous membranes. [Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 1263]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Phenol ... employed in vaginal douche has caused local and systemic poisoning. [Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972., p. 176]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Application of moderate amounts to the skin causes epidermal separation and a severe exposure causes necrosis. [Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 969]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Toxic blood level (the concn of drug or chemical present in the blood that is associated with serious toxic symptoms in humans): 9 mg%; Lethal blood level (the concn of chemical present in blood that has been reported to cause death, or is so far above reported therapeutic or toxic concn that one can judge that it might cause death in humans): 90 u/ml /Table/ [Winek, C.L. Drug and Chemical Blood-Level Data 1985. Pittsburgh, PA: Allied Fischer Scientific, 1985., p. ]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: On human eyes, concn phenol has had severe effects ... rendering the conjunctiva chemotic, and the cornea white and hypesthetic. The lids have become edematous. ... Severe iritis ... in at least one case. Visual results have been varied from complete recovery ... to blindness and loss of one eye. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 720]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Fatal neonatal hyperbilirubinemia from inhalation of phenolic vapors has occurred in poorly ventilated nurseries in which phenol was used to disinfect mattresses and bassinets. [Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 970]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Earlier investigators reported certain signs and symptoms not found in more recent reports including abortion, acquired ochronosis, difficulty in swallowing, and tinnitus. [NIOSH; Criteria Document: Phenol p.29 (1976) DHEW Pub. NIOSH 76-196]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: The predominant acute action of a toxic dose in man appears to be to the CNS, leading to sudden collapse and unconsciousness. [USEPA; Ambient Water Quality Criteria Document: Phenol p.C-20 (1980) EPA 440/5-80-066]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Oral ingestion can result in mucocutaneous and gastrointestinal corrosion. Both oral ingestion and extensive application to the skin can cause systemic toxicity manifested by transient CNS stimulation followed by CNS and cardiovascular depression; death may result. [Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 970]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: ... Exposure by inhalation to low concn of phenol (0.004 ppm; 0.015 mg/cu m) six times for 5 minutes produced increased sensitivity to light in three volunteers adapted to the dark. Exposure to 0.006 ppm (0.02 mg/cu m) phenol for 15 seconds resulted in the formation of conditioned electrocortical reflexes in four volunteers ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V47 277 (1989)]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Repeated oral exposure for several weeks (estimated intake, 10-240 mg/day) due to contamination of groundwater after an accidental spill of phenol resulted in mouth sores (burning of the mouth), diarrhea and dark urine. Examination six months after the exposure revealed no residual effect ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V47 277 (1989)]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Topical exposure to phenol results in brown, relatively painless patches on the skin and whitish patches on the mucous membranes. Ingestion results in gastrointestinal symptoms that range from nausea, vomiting, diarrhea, and abdominal pain to hematemesis and hematochezia. Inhalation or aspiration produces coughing, stridor, and an aromatic odor of the breath. Systemic complaints from acute exposure include CNS stimulation and depression, seizures, coma, tachycardia, ventricular dysrhythmias, hypotension, hypothermia, metabolic acidosis, and acute tubular necrosis. [Ford MD, Delaney KA, Ling LJ, Erickson T; Clinical Toxicology. W.B. Saunders Company., Philadelphia, PA. 2001, p. 752]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Chronic exposure has been associated with sore throat, diarrhea, oropharyngeal sores, and dark bilirubin-free urine. The substance responsible for darkening the urine has not been identified but is probably an oxidative product of phenol metabolism. "Phenol marasmus" is a syndrome that was described in health care workers chronically exposed to nebulized phenol (5-10 percent) applied as a disinfectant in the 1800s. They developed anorexia, weight loss, headache, vertigo, salivation, muscle aches and weakness, dark urine, and hepatitis. [Ford MD, Delaney KA, Ling LJ, Erickson T; Clinical Toxicology. W.B. Saunders Company., Philadelphia, PA. 2001, p. 753]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: SYMPTOMATOLOGY: Burning pain in mouth and throat. White necrotic lesions in mouth, esophagus and stomach. Abdominal pain, vomiting ... and bloody diarrhea. Pallor, sweating, weakness, headache, dizziness, tinnitus. Shock: Weak irregular pulse, hypotension, shallow respirations, cyanosis, pallor, and a profound fall in body temperature. Possibly fleeting excitement and confusion, followed by unconsciousness ... Stentorous breathing, mucous rales, rhonchi, frothing at nose and mouth and other signs of pulmonary edema are sometimes seen. Characteristic odor of phenol on the breath. Scanty, dark-colored ... urine ... moderately severe renal insufficiency may appear. Methemoglobinemia, Heinz body hemolytic anemia and hyperbilirubinemia have been reported ... Death from respiratory, circulatory or cardiac failure. If spilled on skin, pain is followed promptly by numbness. The skin becomes blanched, and a dry opaque eschar forms over the burn. When the eschar sloughs off, a brown stain remains. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-346]**PEER REVIEWED**
  • CASE REPORTS: Several cases of sudden death or intra- or postoperative complications have been reported after phenol face peels ... . [Marzulli, F.N., H.I. Maibach. Dermatotoxicology 4th ed. New York, NY: Hemisphere Publishing Corp., 1991., p. 857]**PEER REVIEWED**
  • CASE REPORTS: Major cardiac arrhythmias were noted ... in 10 out of 43 patients during phenol face peels. [Marzulli, F.N., H.I. Maibach. Dermatotoxicology 4th ed. New York, NY: Hemisphere Publishing Corp., 1991., p. 858]**PEER REVIEWED**
  • CASE REPORTS: ... A spray of 12.5% phenol dissolved in 25% glycerol in water struck both eyes of a patient, and induced faint haze in the corneal epithelium, associated with fine gray stippling visible by slit-lamp biomicroscope, causing temporary impairment of vision to 6/12 and 6/18. The corneas cleared within 4 days, and vision returned to normal. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 720]**PEER REVIEWED**
  • CASE REPORTS: 14 mg/kg resulted in GI effects, and ingestion of 140 mg/kg caused death. [Cleland, J.G., G.L. Kingsbury. Multimedia Environmental Goals for Environmental Assessment. Volume 1. EPA-600/7-77-136a. Research Triangle Park, NC: EPA, Nov. 1977., p. E-182]**PEER REVIEWED**
  • CASE REPORTS: ... 1 ounce of 89% phenol was mistakenly given in a measured container to an outpatient. ... The patient immediately ... collapsed. Within 30 min she had an unrecordable blood pressure and sustained respiratory arrest. ... The patient experienced ventricular tachycardia 1 hr post-ingestion, and resuscitation was effected ... over first 24 hr ... ventricular arrhythmias, seizures, and metabolic acidosis. ... Subsequent esophagitis and gastrointestinal bleeding occurred. The patient survived. ... [Haddad, L.M. and Winchester, J.F. Clinical Management of Poisoning and Drug Overdosage. Philadelphia, PA: W.B. Saunders Co., 1983., p. 810]**PEER REVIEWED**
  • CASE REPORTS: ... A 32 yr old male ... spilled a solution of phenol over his scalp, face, neck, shoulders and back. The victim died 10 min later. There was coagulation necrosis of the skin and left eye and acute dermatitis veneta with acute passive congestion of the lungs, liver, spleen, and kidneys. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 1]**PEER REVIEWED**
  • CASE REPORTS: An employee accidentally spilled 4-5 liters of 78% aq phenol on himself. Following immediate irrigation with alcohol, he exhibited superficial skin burns, became comatose and died shortly thereafter. [NIOSH; Criteria Document: Phenol p.41 (1976) DHEW Pub NIOSH 76-196]**PEER REVIEWED**
  • CASE REPORTS: An industrial employee spraying weeds with effluent of a chemical plant, containing 43% phenol, 20% water, 14% cresols, 11.5% low-boiling organics, and 11% high-boiling organics suffered burns on thighs and genitalia. The affected sites were washed with large amounts of warm water (30 min) followed by ethanol (10 min). Washing and scrubbing were repeated. Within 30 min the employee developed symptoms of shock. Reduced body temp, weak and irregular pulse, accelerated respiratory rate, stertorous breathing, and constricted pupils which showed a slow response to light and slow accommodation. His left leg had convulsive movements for 30 minutes. Tests for a liver function were normal. Urine was not analyzed for phenol until 4 days after exposure at which time it was negative. Recovery was complete and the patient was released 7 days later from the hospital. [NIOSH; Criteria Document: Phenol p.830-833 (1976) DHEW Pub. NIOSH 76-196]**PEER REVIEWED**
  • CASE REPORTS: A woman committed suicide by ingesting 10-20 g of phenol. She became comatose with partial absence of reflexes, pallor of the skin, accelerated respiration, weak and rapid pulse, and dilated pupils which did not react to light. Almost one hr after the ingestion, her heart and respiration stopped and, in spite of repeated attempts at resuscitation for 2 hr, she died. Autopsy revealed marked hyperemia of the tracheal and bronchial mucous membranes. Histologic exam revealed pulmonary and liver edema as well as hyperemia of the intestines. [Stajduhar-Caric Z; J Forensic Med 15: 41-2 (1968)]**PEER REVIEWED**
  • CASE REPORTS: A 19 yr old female ingested 15 ml of phenol and complained of severe nausea, burning in the throat, and epigastrium. Laryngoscopic exam revealed superficial burns and slight edema of the hypopharynx. Despite gastric lavage with olive oil and iv saline admin, she continued to be nauseated. One hr later she began to vomit blood and to have diarrhea, passing copious amounts of blood with clots. She gradually became cyanotic and stuporous. Her blood pressure decreased markedly and her extremities became cold. She experienced periods of relapse and recovery during treatment but died 17.5 hr after ingestion. [Bennett IL; Ann Intern Med 32: 324-7 (1950)]**PEER REVIEWED**
  • CASE REPORTS: Chronic systemic absorption of phenol has caused gray coloration of the sclera with brown spots near the insertion of rectus muscle tendons, associated with blue or brown discoloration of the tendons over the knuckles of the hands. This is a form of ochronosis, known as carbolochronosis, of which 20 cases ... /were reported/ up to 1942... . [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 720]**PEER REVIEWED**
  • CASE REPORTS: An elderly Japanese woman ingested a massive quantity of phenol in a suicide attempt. She was admitted to the Emergency Department in respiratory arrest and deep coma. Duodenogastritis was evident endoscopically. With the return of spontaneous respiration and consciousness, fine, rapid rhythmic perioral movements developed together with Parkinsonian findings. The abnormal movements were aggravated by admin of a neuroleptic and ameliorated by discontinuing the drug; they disappeared completely by hospital day 15. ... [Kamijo Y et al; J Toxicol Clin Toxicol 37 (4): 509-11 (1999)]**PEER REVIEWED**
  • CASE REPORTS: After an acute percutaneous intoxication of a chemical worker with phenol, local effects on the skin were seen in conjunction with several effects due to systemic intoxication, including massive intravascular hemolysis, tachycardia, respiratory depression, and renal and liver damage. The latter was concluded from the increased activities of liver enzymes in the serum ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V47 277 (1989)]**PEER REVIEWED**
  • CASE REPORTS: A 47-yr-old male had 90% phenol spilled over his left foot and shoe (3% of body surface area). After a 4 1/2-hr exposure, manifestations included confusion, vertigo, faintness, hypotension, ventricular premature beats, atrial fibrillation, dark-green urine, and tense swelling, blue-black discoloration, hypalgesia, and hypoesthesia of the affected area. [Bentur Y et al; J Toxicol Clin Toxicol 36 (7): 707-11 (1998)]**PEER REVIEWED**
  • CASE REPORTS: Application of a bandage containing 2% phenol to the umbilicus of a newborn baby resulted in death after 11 hr. Another newborn baby treated with 30% phenol:60% camphor for a skin ulcer experienced circulatory failure, cerebral intoxication and methemoglobinemia but recovered after a blood transfusion ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V47 277 (1989)]**PEER REVIEWED**
  • EPIDEMIOLOGY STUDIES: We conducted a follow-up study to evaluate mortality among 14,861 workers employed in five facilities producing or using phenol and formaldehyde. More than 360,000 person-years of follow-up accrued. Mortality rates from all causes of death combined were similar to those in the general U.S. population. We observed excesses of cancer of the esophagus, cancer of the kidney, and Hodgkin's disease among workers exposed to phenol, but none of these excesses showed a dose-response relation with exposure to phenol. Excess lung cancer mortality (SMR=1.2) showed no consistent pattern by any exposure index. Workers exposed to phenol had lower mortality ratios for cancer of the buccal cavity and pharynx, cancer of the stomach, cancer of the brain, arteriosclerotic heart disease, emphysema, disease of the digestive system, and cirrhosis of the liver. Of these, arteriosclerotic heart disease, emphysema, and cirrhosis of the liver were inversely related to duration of phenol exposure and to cumulative phenol exposure levels. Although these inverse associations may be due to chance or uncontrolled confounders, the ability of phenol to interfere with the generation of oxidants in experimental systems suggests that the pattern may have biologic plausibility. [Dosemeci M et al; Epidemiology 2 (3): 188-93 (1991)]**PEER REVIEWED**
  • EPIDEMIOLOGY STUDIES: An accidental spill of phenol (100%) into the Nakdong river with subsequent contamination of the tap water for about two million consumers in Teagu city of Korea occurred in March 1991. A historical cohort study of 6,913 individuals was undertaken to determine association with illness. Population subjects were divided into two groups of exposed and unexposed. Exposed subjects were reported to have significantly more phenol associated symptoms than those in a nearby unexposed area (39.6% vs. 9.4%, p<0.01). Especially, in the related symptoms, highly significant differences were noted in the number of subjects reporting GI illness such as nausea, vomiting, diarrhea, or abdominal pain. During the accident, study subjects who experienced peculiar taste or odor in the tap water were significantly more in the exposed areas (92% vs. 34.3%). [Kim DH et al; J Korean Med Sci 9 (3): 218-23 (1994)]**PEER REVIEWED**
  • EPIDEMIOLOGY STUDIES: A 5 yr retrospective review of all exposures to a high concn phenol disinfectant (Creolin Disinfectant 26% phenol) reported to a regional poison center located 96 cases, with 16 cases lost to follow up. There were 60 oral-only exposures, 7 dermal-only exposures and 12 oral/dermal exposure. One patient was an inhalation exposure. Fifty-two cases (65%) were evaluated in a hospital. Eleven patients with oral exposures (14%) experienced rapid CNS depression, but no seizures occurred. Vomiting, coughing, and stridor was noted in 14, 7 and 4 patients respectively. Burns were noted in 17 of 72 (24%) patients with oral exposure and 5 of 19 (26%) with dermal exposure. Seventeen patients underwent endoscopy. Tissue sloughing was noted in one case. All other burns were first degree. No cardiovascular complications occurred. Twenty-eight patients (35%) were followed at home via telephone with one episode of vomiting and one episode of dermal irritation occurring. CNS toxicity from exposure to a high concn phenol containing cleaning product appears to be rapid in onset. The absence of serious toxicity and major chemical burns in this series does not eliminate concern with the corrosive and systemic risks of phenol poisoning. [Spiller HA et al; J Toxicol Clin Toxicol 31 (2): 307-13 (1993)]**PEER REVIEWED**
  • SPECIAL STUDIES: ...Primary human colonic epithelial cell cultures or HT-29 cell cultures were exposed to ...phenol (0.1-5 mM) for 24 hr. ...Phenol (>1.25 mM) significantly impaired the viability of primary colonic epithelial cell cultures. No differences between cell cultures from ulcerative colitis and control patients were observed. ...Glucuronidation was the preferred conjugation pathway in both cell models, despite the presence of /phenol glucuronidase/ and /sulphotransferase/ activity. Phenols have a direct toxic effect on human colonic epithelial cells in vitro, which supports the view that dietary fermentation metabolites may be involved in the modulation of chronic bowel inflammation. [Pedersen G et al; Scand J Gastroenterol 37 (1): 74-9 (2002)]**PEER REVIEWED**
  • BIOMONITORING: ... Exposures to airborne phenol and the associated urinary phenol concns from employees in a Bakelite factory /were measured/. Airborne concns of phenol ranged from 0-12.5 mg/cu m (3.3 ppm). Urine samples were collected before and after exposure and analyzed for total, free, and conjugated phenol and for ethereal glucuronides and sulfates; the concn of free phenol varied little with the changes in airborne phenol concns. Ethereal sulfates in the urine generally increased with increasing airborne phenol concns. Increases in urine phenol fractions were observed during the work shift, but these concns decreased to pre-exposure levels within 16 hours. There were no ill effects in any of the workers surveyed. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 1]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: Inhalation of phenol was related to stimulation of central nervous system, followed by severe depression. Exposure of animals to phenol resulted in paralysis in some animal species, but not in others. [O'Donoghue JL; Phenol and Related Substances. In: Neurotoxicity of Industrial and Commercial Chemicals CRC Press pp. 739-53 (1985) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Poisoning from prep containing phenol is occasionally seen in domestic animals, but especially in cats. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 205]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Glaucoma has been induced experimentally in rabbits by injecting 5% phenol in almond oil subconjunctivally in all four quadrants. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 720]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In animals, the pathological changes produced by phenol vary with the route of absorption, vehicle employed, concentration, and duration of exposure. Local skin disorders include eczema, inflammation, discoloration, papillomas, necrosis, sloughing, and gangrene. After oral ingestion, the mucous membranes of the throat and esophagus may show swelling, corrosions, and necrosis, with hemorrhage and serous infiltration of the surrounding areas. In severe intoxication, the lungs may show hyperemia, infarcts, bronchopneumonia, purulent bronchitis, and hyperplasia of the peribronchial tissues. Myocardial degeneration and necrosis can be present. The hepatic cells may be enlarged, pale, and coarsely granular with swollen fragmented and pyknotic nuclei. Prolonged administration of phenol may cause parenchymatous nephritis, hyperemia, edema of the convoluted tubules, and degenerative changes of the glomeruli. Blood cells become hyaline, with granules. Marked striation of the muscle fibers is also seen. [USEPA; Ambient Water Quality Criteria Doc: Phenol p.C-23-6 (1980) EPA 440/5-80-066 ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In Sprague-Dawley rats, 1/2 of the animals became deeply comatose with 540 uM of ip phenol and 100% with 600 uM. Five stages of encephalopathy were readily distinguished with symptoms of increased and decreased muscle tonus, righting reflex, and body tremor until recovery or death of animals. [Windus-Podehl G et al; J Lab Clin Med 101 (4): 586 (1983) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: On rabbit eyes, crystalline or concn aq phenol causees almost instantaneous white opacification of the corneal epithelium. Eight hr after application the cornea is anesthetic, the surface ulcerated, and the stroma opaque. In 5 wk there is entropion, scarring of the conjunctiva, and opacity of the cornea. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 720]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ...Guinea pigs were severely injured due to inhalation for 20 days of phenol vapor at concentrations of from 25 to 50 ppm. Post mortem evidence of acute toxicity to lung, heart, liver, and kidneys was found. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 469]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Death immediately after poisoning usually occurs from respiratory depression. [Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 222]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Three adult dogs were evaluated following oral admin of phenol by the owner. All three dogs experienced severe oral and gastric ulceration. Hematological abnormalities included neutropenia with the presence of toxic neutrophils, thrombocytopenia, and increased muscle enzymes. Endoscopic exam was performed, and biopsies yielded a diagnosis of gastric mucosal necrosis in two of the dogs. Following supportive care, the dogs recovered completely. Phenol is a caustic, highly poisonous derivative of coal tar. The dogs of this report were poisoned inadvertently by their owner who received misinformation concerning the use of this chemical via the Internet. [Gieger TL et al; J Am Anim Hosp Assoc 36 (4): 317-21 (2000) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: At high bolus doses in rats, phenol causes a characteristic muscular twitching behavior; this has been characterized as a neuromuscular effect, and is readily reversible when blood levels of free phenol decr below about 3 ug/ml. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V4 392]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: A dog bathed in a phenolic disinfectant developed signs including an anorexia, excessive salivation, muscular twitching, vomiting, cutaneous erythema, pruritis and necrosis and a rectal temperature of 40.0 deg C. Topical and parenteral antibiotic treatment resulted in recovery within one week. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 206]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The post-mortem changes associated with ingestion of phenol or cresol are those that would be expected following exposure to any extremely irritant and corrosive poison. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 205]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: The toxicity of phenol vapor was evaluated in male and female Fischer 344 rats (20/sex/group) via flow-past nose-only inhalation exposure. The test animals were exposed to target concns of 0 (air control), 0.5, 5.0, or 25 ppm of phenol in air for 6 hr/day, 5 days/wk, for 2 weeks. High pressure liquid chromatography (HPLC) measurement of phenol test atmospheres determined mean (+/- standard deviation) analytical concns of 0.0 +/- 0.0, 0.52 +/- 0.078, 4.9 +/- 0.57, and 25 +/- 2.2 ppm, respectively. After 2 weeks of exposure, 10 test animals/sex/group were sampled for clinical chemistry and hematology parameters, and then sacrificed. Histopathological exam included the nasopharyngeal tissues, larynx, trachea, lungs with mainstem bronchi, kidney, liver, and spleen. The remaining 10 animals/sex/group were retained for a 2-wk recovery period. Recovery groups of animals were evaluated as described previously and then sacrificed. No signs of toxicity in clinical observations (including overt neurological signs), body weights, food consumption, clinical pathology, organ weights, macroscopic pathology or microscopic pathology were seen during the exposures or at either sacrifice interval. In conclusion, 2-wk inhalation exposures to phenol vapor at concns up to and including 25 ppm did not produce any adverse effects. [Hoffman GM et al; Int J Toxicol 20 (1): 45-52 (2001) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Rats were exposed to 100 mg/cu m (25 ppm) phenol vapors continuously for 15 days. Numerous signs of neurological impairment, including muscle twitching and disturbed walking rhythm and posture, were noted after 3-5 days, although these effects were reversible. There was also clinical chemical evidence of liver damage. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V4 388]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... Under the conditions of this bioassay, phenol was not carcinogenic for either male or female F344 rats or male and female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative; Female Rats: Negative; Male Mice: Negative; Female Mice: Negative. [Bioassay of Phenol for Possible Carcinogenicity (1980) Technical Rpt Series No. 203 DHEW Pub No. (NIH) 80-#1759, U.S. Department of Health Education and Welfare, National Cancer Institute, Bethesda, MD 20014 ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... Phenol was administered to rats or mice at 0, 2500, or 5000 ppm in drinking water for 103 weeks. An increased incidence of leukemia and lymphomas was detected only in the low dose male rats. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 1]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: The S strain albino mice showed strong promoting activity for tumor formation after initiation with 0.3 mg 9,10-dimethyl-1,2-benzanthracene (DMBA) followed by repeated skin applications of 20% phenol. 20% phenol soln produced significant damage to the skin and was weakly carcinogenic when applied alone. Phenol in a 5% soln had moderate promoting activity, but was not carcinogenic without previous initiation. [USEPA; Ambient Water Quality Criteria Doc: Phenol p.32 (1980) EPA 440/5-80-066 ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Following initiation with 9,10-dimethyl-1-2,-benzanthracene (DMBA) and promotion by croton oil through skin painting, mice received 2 wk dermal applications of 2.5 mg phenol (as a 10% solution in benzene). Mice exhibited severe skin damage, decreased body weight and increased mortality. After 13 weeks, 22/23 mice had developed papillomas, and 13% had carcinomas of the skin. In mice treated with DMBA only, 3/21 survivors exhibited papillomas after 42 weeks. Through skin painting with 10% phenol, 5/14 survivors (36%) had papillomas after 52 weeks. In this group, skin painting was continued to 72 weeks at which time one fibrosarcoma was diagnosed. [USEPA; Ambient Water Quality Criteria Doc: Phenol p.31 (1980) EPA 440/5-80-066 ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Several studies of promotional effects of phenol on polycyclic hydrocarbon-induced skin carcinogenesis showed slight promotional effect. For example, papillomas, but not carcinomas, were observed on the skin of mice dosed repeatedly with 20% phenol in acetone, and none with 5% phenol, for 32 weeks. However, prior treatment with 7,12-dimethylbenzanthracene (DMBA) followed by phenol treatment caused a dose-related incr in malignant tumors. The 20% soln caused ulceration and scarring of the skin; the 5% soln caused slight transient crusting. ... /It was concluded/ that phenol at ulcerative concns promoted tumor development of known mouse skin carcinogens. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V4 391]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: This study evaluated the potential reproductive toxicity of phenol in a rat two-generation reproduction study, which included additional study endpoints, such as sperm count and motility, developmental landmarks, histological evaluation of suspect target organs (liver, kidneys, spleen, and thymus), weanling reproductive organ weights, and an immunotoxicity screening plaque assay. Phenol was administered to 30 Sprague-Dawley rats/sex/group in the drinking water at concns of 0, 200, 1,000, or 5,000 ppm. Parental (P1) animals were treated for 10 weeks prior to mating, during mating, gestation, lactation, and until sacrifice. The F1 generation (P1 offspring) was treated using a similar regimen, while the F2 generation was not treated. After mating, 10 P1 males/group were evaluated using standard clinical pathology parameters and an immunotoxicity screening plaque assay. Significant reductions in water and food consumption were observed in the 5,000-ppm group in both generations; corollary reductions in body weight/body weight gain were also observed. Mating performance and fertility in both generations were similar to controls, and no adverse effects on vaginal cytology or male reproductive function were observed. Vaginal opening and preputial separation were delayed in the 5,000-ppm group, and were considered to be secondary to the reduction in F1 body weight. Litter survival of both generations was reduced in the 5,000-ppm group. Absolute uterus and prostate weights were decreased in the F1 generation at all dose levels; however, no underlying pathology was observed and there was no functional deficit in reproductive performance. Therefore, these findings were not considered to be adverse. No evidence of immunotoxicity was noted in the 5,000-ppm group. The effects noted at the high concn were presumed to be associated with flavor aversion to phenol in the drinking water. Based on a comprehensive exam of all parameters, the no-observable-adverse-effect level (NOAEL) for reproductive toxicity of phenol administered in drinking water to rats is 1,000 ppm. The corresponding daily intake of phenol for an adult rat at the NOAEL of 1,000 ppm is equivalent to about 70 mg/kg/day for males and 93 mg/kg/day for females. [Ryan BM et al; Int J Toxicol 20 (3): 121-42 (2001)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: The weight of evidence indicates that phenol is not a developmental toxicant, except perhaps at maternally toxic concns. ... In a ... study conducted in the Swiss albino (CD1) mice, doses of 140 or 280 mg/kg were administered daily by gavage through days 6-15 of gestation. There were no effects at the middle dose, but the high dose was both maternally toxic (11%, tremors, ataxia, decreased body weight gain) and developmentally toxic (20% decr in fetal body weight; slight incr in cleft palate from 0-4%). [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V4 390]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: ...Rats /were injected/ ip on days 8-10 or 11-15 /of gestation/ with up to 200 mg/kg. No adverse fetal effects were observed. [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 448]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: ...The purpose of this study was to examine the time course of denervation and recovery in several hindlimb muscles following application of a 5% aq soln of phenol to the sciatic nerve. Phenol was applied to the sciatic nerve of adult female rats either by intraneural or perineural injection. Axonal degeneration was evident within the sciatic nerve 2 days following phenol application, although variable amounts of damage were observed. By 2 weeks, the soleus and tibialis anterior had atrophied to 63% and 51% of control. Reinnervation of hindlimb muscles occurred between 2 and 4 weeks following the nerve block. Following denervation, the soleus became slower in that all of the fibers expressed the slow myosin heavy chain (MHC). At 5 months, maximum tension of the soleus was 74% of control and the muscle consisted of more fast fibers on average, some of which expressed IIx MHC. These data suggest that 5% phenol causes an injury to the nerve that is more severe than a crush injury, and that reinnervation of denervated muscles may be by motoneurons other than those that originally innervated the muscles. [Bodine-Fowler SC et al; Muscle Nerve 19 (4): 497-504 (1996) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: ...Sometimes there is only mild pain or discomfort because phenol demyelinates or otherwise destroys many types of nerve fibers. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-344]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Excessive doses of phenol in animals have been shown to depress the vasomotor center of the brain producing motor disturbances and blood changes of sufficient magnitude to induce cardiac arrest, respiratory failure, and coma followed by death. [NIOSH; Criteria Document: Phenol p.62 (1976) DHEW Pub NIOSH 76-196 ]**PEER REVIEWED**
  • GENOTOXICITY: Possible interactions between hydroquinone (HQ) and phenol (PHE), 2 known benzene metabolites, in inducing micronuclei in mouse bone marrow cells were investigated. HQ and PHE administered alone gave weak and negative results, respectively, at the doses tested. However, simultaneous admin of both compounds caused a considerable incr in the induction of micronuclei as well as an incr in bone marrow toxicity. Using 3 different statistical methods, it was shown that the observed joint effect was significantly higher than additive interaction, and was close to multiplicative interaction. These findings bring further support to the hypothesis that the toxic and genotoxic effects of benzene are produced by several metabolites acting synergistically. [Barale R et al; Mutat Res 244 (1): 15-20 (1990)]**PEER REVIEWED**
  • GENOTOXICITY: Phenol tested positive for mutagenicity in L5178Y Mouse Lymphoma cells. [NTP; Fiscal Year 1987 Annual Plan p.82 (1987) NTP-87-001]**PEER REVIEWED**
  • GENOTOXICITY: Phenol was evaluated for the induction of sex-linked recessive lethal mutations in Drosophila melanogaster by the National Toxicology Program. Canton-S wild-type males were treated with concentrations of phenol that result in approximately 30% mortality. Following treatment, males were mated individually to 3 harems of Basc virgin females to produce 3 broods for analysis. The concentrations of phenol tested by injection (5250 ppm) or feeding (2000 ppm) were negative in this assay. [Woodruff RC et al; Environ Mutagen 7: 677-702 (1985)]**PEER REVIEWED**
  • GENOTOXICITY: Experiments with Drosophila have shown phenol to be highly mutagenic. [Cleland, J.G., G.L. Kingsbury. Multimedia Environmental Goals for Environmental Assessment. Volume 1. EPA-600/7-77-136a. Research Triangle Park, NC: EPA, Nov. 1977., p. E-182]**PEER REVIEWED**
  • GENOTOXICITY: ... Phenol is metabolized to DNA reactants at a low rate by human lymphocytes; the addition of S9 amplifies the rate of metabolism. [Dean BJ; Mutat Res 154 (3): 153-81 (1985) ]**PEER REVIEWED**
  • GENOTOXICITY: Phenol induced /sister chromatid exchanges/ and mutations in cultured human cells. Positive results were noted in mouse lymphoma cells test. Phenol showed weak capability to induce micronuclei in bone marrow cells of pregnant mice and, transplacentally, in fetal liver cells. it did not produce DNA damage in cultured animal cells. Phenol was negative in Salmonella mutagenicity assay. [Sheftel, V.O.; Indirect Food Additives and Polymers. Migration and Toxicology. Lewis Publishers, Boca Raton, FL. 2000., p. 135]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: Male B6C3F1 mouse bone marrow adherent stromal cells were plated at 4X10+6 cells per 2 ml of DMEM medium in 35 mm tissue culture dishes. The growing stromal cell cultures were exposed to log 2 doses of phenol for 7 days. The doses which caused a 50% decrease in colony formation (TD50) was 190x10-6 M for phenol. [Gaido K, Wierda D; Toxicol Appl Pharmacol 76 (1): 45-55 (1984) ]**PEER REVIEWED**

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Human Toxicity Values

  • ... Summarized oral lethality data from numerous case reports... estimated 140 mg/kg to be the minimal human oral dose at which death occurs. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V4 393]**PEER REVIEWED**

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Non-Human Toxicity Values

  • LD50 Rat oral 530 mg/kg [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1299]**PEER REVIEWED**
  • LD50 Cat oral 0.1 g/kg [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 982]**PEER REVIEWED**
  • LD50 Dog oral 0.5 g/kg [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 982]**PEER REVIEWED**
  • LD50 Rat oral 317 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2630]**PEER REVIEWED**
  • LD50 Rat dermal 669 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2630]**PEER REVIEWED**
  • LD50 Rat sc 460 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2630]**PEER REVIEWED**
  • LD50 Mouse oral 270 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2630]**PEER REVIEWED**
  • LD50 Mouse iv 112 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2630]**PEER REVIEWED**
  • LD50 Rabbit dermal 850 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2630]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • Phenol is absorbed by all routes of administration and can reach circulation even when applied to intact skin. [Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 967]**PEER REVIEWED**
  • Absorption of 2 g of phenol could result from 8 hr inhalation at about 50 ppm. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values, 4th ed., 1980. Cincinnati, Ohio: American Conference of Governmmental Industrial Hygienists, Inc., 1980., p. 328]**PEER REVIEWED**
  • The extent of absorption of phenol through rabbit skin is more strongly influenced by the area of the skin exposed than by the concentration of the applied solution in water. [WHO; Environ Health Criteria 161: Phenol (1994). Available from http://www.inchem.org/documents/ehc/ehc/ehc161.htm#PartNumber:6 as of April 1, 2003.]**PEER REVIEWED**
  • Renal excretion is principal route of elimination. ... In man 90% of non-toxic oral dose (0.01 mg/kg) of (14)C-labeled phenol was excreted in 24 hr, principally as sulfate (77% of the excreted label) and as glucuronide (16%), with small amt of sulfate and glucuronide conjugates of ... hydroquinone. With larger doses, free (unmetabolized) phenol can presumably be found in urine. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-346]**PEER REVIEWED**
  • After absorption into body ... Traces of "free" phenol are eliminated with feces and expired air. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2571]**PEER REVIEWED**
  • In volunteers exposed to phenol vapor (5-25 mg/cu m) the retention of vapor in the lung decreased from ... 80 to 70% in the course of an 8 hr exposure. The absorption of vapor through the whole skin was approximately proportional to the concentration of vapor used, the absorption rate being somewhat lower than in the lung. Almost 100% of the excretion of phenol occured in the urine within 1 day. [Piotrowski JK; Br J Ind Med 28: 172 (1971)]**PEER REVIEWED**
  • In man and all mammals that have been tested, nearly all of the phenol and its metabolites are excreted in the urine. Only minor amounts are excreted in air and in the feces. [USEPA; Ambient Water Quality Criteria Doc: Phenol p.C-19 (1980) EPA 440/5-80-066]**PEER REVIEWED**
  • The skin represents a primary route of entry for phenol vapor, liquid phenol, and solid phenol. Phenol vapor readily penetrates the skin with an absorption efficiency approximately equal to that of inhalation. Skin absorption can occur at low vapor concentrations. [NIOSH; Criteria Document: Phenol p.138 (1976) DHEW Pub NIOSH 76-196]**PEER REVIEWED**
  • Data are presented which correlate phenol levels in human urine with inhalation and dermal exposures. Normal phenol levels in human urine are compared with urine levels resulting from exposure to phenol. A correlation is made between urine phenol levels and potential human toxicity. [BRANCATO DJ; VET HUMAN TOXICOL 24 (FEB): 29-30 (1982) ]**PEER REVIEWED**
  • Phenol is absorbed from the gastrointestinal tract and through the skin and mucous membranes. ... The metabolites are excreted in the urine. [Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 571]**PEER REVIEWED**
  • Subjects exposed to phenol vapor (without skin contact) in concn of 5-25 mg/cu m for a total of 7 hr daily retained 60-88% of the inhaled quantity. Retention ranged from 17.8-62.8 mg and an avg of 99% of this dose was excreted in the urine in 24 hr. [Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 571]**PEER REVIEWED**
  • A fraction of phenol may be excreted by the lung and imparts an aromatic odor to the breath. [Haddad, L.M. and Winchester, J.F. Clinical Management of Poisoning and Drug Overdosage. Philadelphia, PA: W.B. Saunders Co., 1983., p. 810]**PEER REVIEWED**
  • Studies in flow-through diffusion cells showed that full-thickness rat skin absorbed (14)C-phenol at a slightly faster rate than human skin, which absorbs phenol reasonably well. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 753 (1999)]**PEER REVIEWED**
  • In a case of lethal human phenol intoxication (a phenol-containing disinfectant was ingested), the phenol concentration in brain, kidney, liver and muscle was determined several hours after death. The concentration in the brain was highest, followed by the kidney; the concentrations in liver and muscle were half that in the brain. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 753 (1999)]**PEER REVIEWED**
  • Phenol is absorbed rapidly through the lungs and through the skin... Dilution of phenol may incr absorption and does incr toxicity in the rat model. The lungs of human volunteers absorbed 60 to 80% of an inhaled phenol dose. [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1228]**PEER REVIEWED**
  • ...An inhalation study with seven men and one woman, who were exposed for 8 hr to phenol vapors /is reported/. To avoid skin exposure, these subjects remained outside the chamber and inhaled the phenol vapors, ranging from 6-20 mg/cu m (2-5 ppm), through a face mask connected to the exposure chamber. The retention of phenol in the respiratory tract was related to the duration of exposure. Retention decreased from about 80% at initiation of the exposure to approx 70% at the conclusion of the exposure period. The urinary excretion rate rose rapidly during the exposure, with max excretion "directly after the end of the exposure," and returned to the physiological level within 24 hr. Almost 100% of the phenol inhaled was excreted in the urine within 24 hr. Experimental subjects, wearing underwear or overalls, were also exposed for 6 hr to phenol vapors of 5, 10, and 25 mg/cu m (1.1, 2.2, and 6.6 ppm) while inhaling uncontaminated air. No essential differences were noted in the kinetics of phenol excretion following skin exposure when compared with inhalation. The skin absorption rate was roughly proportional to the concn of phenol vapors, characterized by an absorption coefficient of approx 0.35 cu m/hr, meaning that the subjects absorbed through the skin per hour the amount of phenol 0.35 cu m of air; the clothing worn seemed to provide no protection. These studies indicate that the dermal route is a significant route (as well as inhalation) for systemic exposure to phenol vapors, and that phenol is rapidly absorbed and excreted in the urine. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V4 394]**PEER REVIEWED**
  • Phenol is a protoplasmic toxin that disrupts cell walls and denatures proteins. These properties promote rapid pulmonary and gastrointestinal absorption. Dermal absorption is rapid even through intact skin. High concentrations of Phenol disrupt the dermal barrier and penetrate the skin effectively. [Ford MD, Delaney KA, Ling LJ, Erickson T; Clinical Toxicology. W.B. Saunders Company., Philadelphia, PA. 2001, p. 752]**PEER REVIEWED**
  • Although a small amount of phenol undergoes conjugation with glucuronic and sulfuric acids within one to two days of exposure, most is excreted unchanged in the urine. [Ford MD, Delaney KA, Ling LJ, Erickson T; Clinical Toxicology. W.B. Saunders Company., Philadelphia, PA. 2001, p. 752]**PEER REVIEWED**
  • Concn of phenol in the urine of the workers employed in the distillation of the phenolic fraction of tar and that of non-exposed male workers was found to be 87.3 and 11.7 mg/l, respectively. [Sheftel, V.O.; Indirect Food Additives and Polymers. Migration and Toxicology. Lewis Publishers, Boca Raton, FL. 2000., p. 134]**PEER REVIEWED**
  • A 47-yr-old male had 90% phenol spilled over his left foot and shoe (3% of body surface area). ...Peak serum phenol was 21.6 ug/ml, considered in the fatal range. Peak urine phenol plus urine-conjugated phenol was 13,416 mg/g creatinine, indicating a major absorption. Elimination half-life was 13.86 hours, considerably longer than previously reported. [Bentur Y et al; J Toxicol Clin Toxicol 36 (7): 707-11 (1998)]**PEER REVIEWED**
  • The use of in vivo microdialysis for the study of hepatic metabolism is demonstrated using phenol as a test system for continuous in vivo microdialysis sampling in the bile, blood, and liver extracellular fluid of anesthetized rats. The hepatic metab and biliary excretion of phenol following an iv infusion were determined while all 3 sites were simultaneously and continuously sampled to provide concn-time profiles at multiple sites in a single experimental animal. Similar patterns of metabolites were found in the bile, liver, and blood. For all of the metabolites, bile concns were higher than liver concns, indicating that the metabolites are actively excreted into the bile. [Scott DO, Lunte CE; Pharm. Res. 10 (Mar): 335-342 (1993)]**PEER REVIEWED**
  • Renal excretion of phenol (PH), phenyl glucuronide (PG), phenyl sulfate (PS), and hydroquinone (HQ) was determined in 600–900 g rainbow trout (Oncorhynchus mykiss) continuously exposed (144-hr) to waterborne PH (5 mg/l or 53.2 mol/l) in respirometer-metabolism chambers. The `free' plasma concn time course was obtained from samples withdrawn from a dorsal aortic cannulae, while the urine concn time course was acquired using a bladder catheter. Microdialysis and HPLC techniques were used to isolate and identify PH and metabolites. Plasma and urinary PH were at steady-state in 4 hr. PG and HQ in both plasma and urine continued to rise throughout 144 hr. PS values in plasma reached a max around 48 hr, while urine PS plateaued near 24 hr. Of the net PH gill uptake at steady-state (144 hr), as much as 50% was eliminated in the urine (PG=81, PS=16, PH=4%) and the rest extrarenally. PS kinetics suggested the existence of a high affinity/low capacity pathway, while PG production was suggestive of a low affinity/high capacity formation pathway. Rainbow trout glomerular filtration rate (GFR) was 6.10 ml/kg/hr, which was 30% higher than the mean urine flow rate (UFR) of 4.28 ml/kg/hr. Renal Clearance (Clx) calculated for PH, PG, PS and HQ were 4.12, 8.67, 24.33 and 1.85 ml/kg/hr, respectively. Urine Clearance Ratios (Clx/GFR) were 0.69, 1.56, 5.49 and 0.30 for PH, PG, PS and HQ, respectively. The results of this study support in vivo tubular secretion in freshwater adapted trout for both PG and PS, and suggest a possible kidney secretory transport maxima for sulfate conjugates. [McKim JM et al; Aquatic Toxicology 45 (4): 265-277 (1999)]**PEER REVIEWED**
  • Molten analytical grade phenol was applied to the intact skin of pigs at 500 mg/kg, over 35% to 40% of the total body surface area for 1.0 or 2.5 minutes. Phenol was absorbed rapidly through the intact skin. ...Peak plasma phenol concns (52.6 ppm) were achieved at 1.75 hours postexposure. Phenol was detected in plasma 8.75 hours after exposure, but it was not detectable at 23 hours. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 2]**PEER REVIEWED**

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Metabolism/Metabolites

  • Phenols are subjected to oxidative metabolism leading to ortho- and para-hydroxylated products. These metabolites are then transformed into equimolar amounts of two conjugates, sulfates and glucuronides. [Britt DL, Hushon JM; Biol Effects, Crit and Stand Haz Pollut Assoc Energy Technol p.29 (1976)]**PEER REVIEWED**
  • Metabolism in rabbits given a lethal dose of phenol (0.5 g/kg) resulted in: 47% oxidation to carbon dioxide and water plus traces of 1,4-dihydroxybenzene and ortho-dihydroxybenzene, 3% excreted in urine, 50% remaining in the carcass. Amounts were exhaled in air and excreted in in the feces. Metabolism in rabbits given a sublethal dose of phenol (0.3 g/kg) resulted in: 23% oxidation to carbon dioxide and water plus traces of 1,4-dihydroxybenzene and ortho-dihydroxybenzene, 72% excreted in the urine, 4% remaining in the carcass, 1% excreted in the feces, and trace amounts exhaled in air. Urinary route resulted in either excretion as free phenol or as conjugate. (Conjugation with sulfuric acid, glucuronic acid or other acids). /From figure/ [USEPA; Ambient Water Quality Criteria Doc: Phenol p.C-16-19 (1980) EPA 440/5-80-066]**PEER REVIEWED**
  • The cat was shown to be sensitive to phenol. In addition to sulfate conjugates, free 1,4-dihydroxybenzene was found as a major metabolite which may account for the toxicity observed in the cat. [USEPA; Ambient Water Quality Criteria Doc: Phenol p.C-19 (1980) EPA 440/5-80-066]**PEER REVIEWED**
  • Some species differences have been noted in the metabolism of phenol. Man, rat, mouse, jerboa, gerbil, hamster, lemming, and guinea pig excreted four metabolites: sulfate and glucuronic acid conjugates of phenol and of 1,4-dihydroxybenzene. The squirrel and capuchin monkeys excreted phenol glucuronide, 1,4-dihydroxybenzene glucuronide, and phenol sulfate. The ferret, dog, hedgehog, and rabbit excreted phenol sulfate, 1,4-dihydroxybenzene sulfate, and phenyl glucuronide. The Rhesus monkey, fruit bat, and chicken excreted phenyl sulfate and phenyl glucuronide but not 1,4-dihydroxybenzene conjugates. The cat excreted only phenyl sulfate and 1,4-dihydroxybenzene sulfate, and the pig excreted phenyl glucuronide as its major phenol metabolite. Relatively low doses were utilized in this study. [USEPA; Ambient Water Quality Criteria Doc: Phenol p.C-16-19 (1980) EPA 440/5-80-066]**PEER REVIEWED**
  • Concentrations of conjugated phenol in the urine increased following exposure of humans to phenol from as little as 0.6 mg/cu m (0.16 ppm) to as much as 12.5 mg/cu m (3.3 ppm) without a significant increase in the concentration of free phenol. [NIOSH; Criteria Document: Phenol p.64 (1976) DHEW Pub NIOSH 76-196]**PEER REVIEWED**
  • In humans given an oral dose of 0.01 mg/kg 14C-phenol, 90% of the radiolabeled dose appeared in the urine in 24 hr, of which 77% was present as phenyl sulfate, 16% as phenyl glucuronide with trace (>0.1%) amounts as sulfate and glucuronide conjugates of hydroquinone (1,4-dihydroxybenzene). [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V4 394]**PEER REVIEWED**
  • In man, 90% of oral dose of phenol was excreted in 24 hr, mainly as phenylsulfate (77% of 24 hr excretion) and phenylglucuronide (16%), with very small amt of quinol sulfate and glucuronide. These metabolites were also excreted by rat, mouse, jerbon, gerbil, hamster, lemming and guinea pig. /phenol/ [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 569]**PEER REVIEWED**
  • The sulfate conjugate in urine dominates at low exposure doses, and glucuronides assume greater importance at higher phenol exposure concentrations. Below 5 ppm phenol, the sulfate/glucuronide ratio is 3.7:1. [Que Hee, S. (ed.). Biological Monitoring an Introduction. New York, NY: Van Nostrand Reinhold Co., 1993., p. 471]**PEER REVIEWED**
  • A number of species differences in phenol metabolism have been documented. For example, biotransformation of phenol to hydroquinone occurs in cats, and rats produce the sulfate and glucuronide conjugates principally in the gut, as contrasted with hepatic reactions. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 2]**PEER REVIEWED**
  • The major route of phenol metabolism is conjugation with sulfate and, at high dose, with glucuronic acid. In addition, hydroquinone is formed, which is excreted as sulfate or glucuronide conjugate. Several glutathione conjugates can be formed from the reactive 1,4-benzoquinone formed from hydroquinone. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 753 (1999)]**PEER REVIEWED**
  • The major urinary metabolites of phenol were phenol sulfate, phenol glucuronide, and hydroquinone glucuronide. [Sheftel, V.O.; Indirect Food Additives and Polymers. Migration and Toxicology. Lewis Publishers, Boca Raton, FL. 2000., p. 135]**PEER REVIEWED**
  • Rainbow trout (Oncorhynchus mykiss) liver microsomes were used to study the rate of ring-hydroxylation of phenol at 11 and 25 deg C by directly measuring the production of 2 potentially toxic metabolites, hydroquinone (HQ) and catechol (CAT). ...The Michaelis-Menten saturation kinetics for the production of HQ and CAT over a range of phenol concns were determined at trout physiological pH. The apparent Km's for the production of HQ and CAT at 11 deg C were 14+/-1 and 10+/-1 mM, respectively, with Vmax's of 552+/-71 and 161+/-15 pmol/min/mg protein. The kinetic parameters for HQ and CAT at 25 deg C were 22+/-1 and 32+/-3 mM (Km) and 1752+/-175 and 940+/-73 pmol/min/mg protein (Vmax), respectively. The calculated incr in metabolic rate per 10 deg C temp rise (Q(10)) was 2.28 for HQ and 3.53 for CAT production. [Kolanczyk RC, Schmieder PK; Toxicology 176 (1-2): 77-90 (2002)]**PEER REVIEWED**
  • ...It was ...of interest to determine whether the metabolic fate of phenol (P) produced during benzene (BZ) metabolism differed from that of (P) metabolized in the absence of (BZ). Mouse livers were perfused with a solution of [14C](P) in both the orthograde (portal vein to central vein) and retrograde (central vein to portal vein) direction to investigate the metabolic zonation of enzymes involved in (P) hydroxylation and conjugation. Perfusate samples were collected, separated by HPLC, and tested for radioactivity. ...The objective was to compare and quantify the metabolites formed during the perfusion of (P) in the orthograde and retrograde directions and to compare the orthograde (P)-perfusion results with the orthograde (BZ) results reported previously. Regardless of the direction of (P) perfusion, the major compounds released from the liver were (P) phenylgucuronide, phenylsulfate, hydroquinone (HQ), and (HQ)-glucuronide. A comparison of the results of perfusing (P) in the orthograde versus the retrograde direction showed that more (P) was recovered unchanged and more (HQ) was formed during retrograde perfusion. The results suggest that enzymes involved in (P) hydroxylation are generally closer to the central vein than those involved in conjugation, and that during retrograde perfusion, (P) metabolism may be limited by the sub-optimal conditions of perfusion. Comparison of the orthograde perfusion studies of (P) and (BZ) revealed that a larger percentage of the radioactivity released from the liver was identified as unconjugated (HQ) after (BZ) perfusion than after (P) perfusion. In addition, the amount of radioactivity covalently bound to liver macromolecules was measured after each perfusion and determined to be proportional to the amount of (HQ) and (HQ)-glucuronide detected in the perfusate samples. [Hoffmann MJ et al; Toxicol Sci 49 (1): 40-7 (1999) ]**PEER REVIEWED**
  • ...The major urinary metabolites of phenol were phenol sulfate (PS), phenol glucuronide (PG), and hydroquinone glucuronide (HQG). Sulfation was the dominant pathway at all dose levels, but decreased as a % of the excreted dose with a concomitant incr in glucuronidation as the dose level increased. Male mice consistently excreted a higher proportion of phenol as the oxidized conjugated metabolite, HQG, compared to female mice, suggesting that male mice oxidize phenol to hydroquinone more rapidly than female mice. Increased oxidation of phenol to hydroquinone by male mice compared to female mice is consistent with both the greater sensitivity of male mice to the genotoxic effects of benzene and the greater potency of hydroquinone compared to phenol as a genotoxicant. Intestinal conjugation of phenol prior to absorption was significant only at low doses and thus alone does not provide an explanation for the lack of carcinogenicity of phenol in bioassays conducted at much higher dose levels. [Kenyon EM et al; J Toxicol Environ Health 44 (2): 219-33 (1995)]**PEER REVIEWED**
  • ...The cytochrome P450 isozymes involved in the metab of phenol were examined in hepatic and pulmonary microsomes utilizing chemical inhibitors of CYP2E1, CYP2B, and CYP2F2 and using CYP2E1 knockout mice. CYP2E1 was found to be responsible for only ~50% of 20 uM phenol metab in the liver. This suggests another isozyme(s) is involved in hepatic phenol metabolism. In pulmonary microsomes both CYP2E1 and CYP2F2 were significantly involved. [Powley MW, Carlson GP; Toxicology Letters 125 (1-3): 117-123 (2001)]**PEER REVIEWED**
  • ... Phenol is metabolized to DNA reactants at a low rate by human lymphocytes; the addition of S9 amplifies the rate of metabolism. [Dean BJ; Mutat Res 154 (3): 153-81 (1985) ]**PEER REVIEWED**

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TSCA Test Submissions

  • Phenol (CAS # 108-95-2) was evaluated for subchronic dietary toxicity. The test substance was administered to male albino rats (10/group) for 28-days at a concentration level of 100 ppm (8.22 mg/kg/day); 500 ppm (42.8 mg/kg/day); and 1000 ppm (86.2 mg/kg/day). No deaths or signs of intoxication were noted among any of the animals. At autopsy, no significant gross pathologic lesions were found.[MONSANTO CO; Acute Oral, Eye, Skin, and Inhalation Toxicity, Preliminary Ground Water Assessment, and Characterization of Plant Effluents of Phenol with Cover Letter Dated 072787; 05/29/86; EPA Doc No. 86-870000940; Fiche No. OTS0515378]**UNREVIEWED**
  • Phenol (CAS # 108-95-2) was evaluated for subchronic oral toxicity. The test substance was administered by gavage to rabbits (sex and strain not indicated) in a 10% alcohol solution at a dosage level of 0.5 g/kg (1 rabbit, 2 doses); 0.1 g/kg (2 rabbits, 20 doses each); 0.05 g/kg (1 rabbit, 20 doses); and 0.01 g/kg (1 rabbit, 20 doses). At 0.5 g/kg, the rabbit died and necropsy revealed a swelled, congested liver, and desquamation of the stomach. At 0.1 g/kg, 1 rabbit had kidney irritation and the other rabbit had slight liver degeneration.[DOW CHEM CO; Toxicity of Phenol; 12/15/44; EPA Doc No. 86-870002216; Fiche No. OTS0517006]**UNREVIEWED**
  • Phenol (CAS # 108-95-2) was evaluated for subchronic oral toxicity. The test substance was administered by gavage to rats (sex and strain not indicated) at a dosage level of 0.5 g/kg (1 rat, 1 dose); 0.3 g/kg (1 rat, 17 doses); 0.2 g/kg (1 rat, 20 doses); 0.1 g/kg (2 rats, 20 doses each); and 0.01 g/kg (1 rat, 20 doses). At 0.5 g/kg the rat died and at 0.2 g/kg the rat had pneumonia and died. At 0.2 and 0.1 g/kg, the rats had areas of liver degeneration.[DOW CHEM CO; Toxicity of Phenol; 12/15/44; EPA Doc No. 86-870002216; Fiche No. OTS0517006]**UNREVIEWED**
  • Phenol (CAS # 108-95-2) was evaluated for subchronic oral toxicity. The test substance was administered to rabbits (number, sex, and strain not indicated) at dosage levels of 0.001 or 0.1 g/kg for 20 doses. At 0.1 g/kg, slight kidney change was noted and at 0.001 g/kg, there was no observable change.[DOW CHEM CO; Physiological Effect of Phenol in Dowell Paraffin Solvent; 02/15/35; EPA Doc No. 86-870002218; Fiche No. OTS0517008]**UNREVIEWED**
  • Phenol (CAS # 108-95-2) was evaluated for chronic oral toxicity. In the first experiment, the test substance was administered by gavage to groups of 3 rats (sex and strain not indicated) at dosage levels of 0.2, 0.1, 0.05, or 0.01 g/kg for 6 months. At 0.2 g/kg, the animals died or were sacrificed after 1, 6, and 16 doses; all animals had tremors. The animals receiving 1 and 6 doses had stomach irritation; liver congestion and degeneration; and kidney congestion and slight hemorrhage. The animal that received 16 doses was moribund when sacrificed, but no toxicity was detected microscopically. Two animals at 0.1 g/kg, 2 animals at 0.05 g/kg, and 1 animals at 0.01 g/kg survived 136 doses with no pathological findings. In the second experiment, the test substance was administered by gavage to groups of 10 rats (sex and strain not indicated) at dosage levels of 0.1 or 0.05 g/kg for 6 months (5 days a week until 135 or 136 doses had been given). Four rats from each group died; there was no indication that death was treatment-related. At 0.1 g/kg, there was a cloudy swelling of the livers and damage to the kidneys with a cloudy swelling of the tubular epithelium. There was also a slight increase in the weights of the liver and kidneys. At 0.05 g/kg, 2 animals had injured kidneys, distention of the pelvis, slight tubular degeneration and a few casts. Blood chemistry indicated a slight decrease in lymphocytes and bone marrow count was normal.[DOW CHEM CO; Toxicity of Phenol; 12/15/44; EPA Doc No. 86- 870002216; Fiche No. OTS0517006]**UNREVIEWED**
  • Phenol (CAS # 108-95-2) was evaluated for reproductive oral toxicity. The test substance was administered by gavage to mated Charles River Crl:CD VAF/Plus female rats (10/group) at dosage levels of 0 mg/kg/day (Control); 3 groups at 60 mg/kg/day; 3 groups at 120 mg/kg/day; or 180 mg/kg/day on gestation days 6 through 14. At 120 mg/kg/day, maternal toxicity included reduced body weight gain and feed consumption. There were treatment-related findings in regards to clinical signs, developmental toxicity, necropsy findings, organ weights, or pathology results.[Procter & Gamble Co; Range Finding Maternal Toxicity Study with Phenol in Rats with Cover Letter 072992; 06/25/93; EPA Doc No. 86-930000341; Fiche No. OTS0537777]**UNREVIEWED**

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008