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Toxicity Effects

CAS Registry Number: 1319-77-3

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • Cresol
  • Cresols (Mixed Isomers Of Ortho, Meta, Para)
  • Cryslol
  • Hydroxytoluene
  • Meta/Para-Cresol
  • Methylphenol (9ci)
  • Tricresol

Human Toxicity Excerpts

  • BIOMONITORING: Phenol concentrations, as well as cresol concentrations, serve as markers of exposure /to these chemicals/.[Goldfrank, L.R., Goldfrank's Toxicologic Emergencies 9th Ed. 2011., McGraw-Hill, New York, N.Y., p. 1351] **PEER REVIEWED**
  • CASE REPORTS: ... Two cases of transitional cell sarcoma of the bladder and a case of squamous cell carcinoma of the vocal cords have been found in workers occupationally exposed to cresols and other chemicals.[USEPA/ECAO; Health and Environmental Effects Profile: Cresols p.38 (1985) ECAO-CIN-P138] **PEER REVIEWED**
  • CASE REPORTS: A 26-year-old woman developed marked increases in levels of aminotransferases about 24 hours after ingestion of 70 mL of 50% cresol. Responding to supportive measures, the patient recovered without any significant complications. Cresol and/or its metabolite may have caused transient hepato-cellular injury in this patient. In cresol poisoning, hepato-cellular injury can manifest even after a 24-hour asymptomatic period.[Hashimoto T et al; Am J Emerg Med 16 (7): 667-8 (1998)] **PEER REVIEWED** PubMed Abstract
  • CASE REPORTS: A 42-year-old man attempted suicide by ingesting about 150 mL of a saponated cresol solution containing about 50% cresol. His serum aminotransferase concentrations were elevated, and a coagulopathy was present at the time of admission, 15 hours after ingestion. The hyperaminotransferasemia and coagulopathy worsened on the second day, but resolved thereafter with supportive therapy. Histologic examination of a biopsy specimen obtained on the 14th day demonstrated focal dropout of hepatocytes (which were replaced by reticulin and collagen fibers), ballooning or hydropic degeneration of hepatocytes, and rapid regeneration with small hepatocytes in the periportal zones as well as in the centrilobular zones. A rapid onset of illness with periportal hepatocellular injury is inconsistent with damage due to a hepatotoxic metabolite of p-cresol produced by cytochrome P450, which has been suggested by studies in vitro. A direct transient noxious effect mediated via the portal or arterial circulation may be involved in hepatic injury after cresol ingestion.[Kamijo Y et al; Arch Pathol Lab Med 127 (3): 364-6 (2003)] **PEER REVIEWED** PubMed Abstract
  • CASE REPORTS: A case of systemic sclerosis is reported in which the pathogen is probably inhaled cresol, a phenolic derivate of toluene, administered as a disinfectant in an unventilated office. In treatment, corticotherapy did not have any effect and improvement was only seen after factor XIII therapy.[Cevallos R et al; Archives Des Maladies Professionnelles De Medecine DU Travail 55 (1): 43-45 (1994)] **PEER REVIEWED**
  • CASE REPORTS: ...A 40% /total body surface area/ (TBSA) cresol chemical burn that subsequently developed systemic intoxication and multiple organ failure is reported. The patient survived after intensive general supportive treatment, repeated hemodialysis and wound care.[Lin CH, Yang JY; Burns 18 (2): 162-166 (1992)] **PEER REVIEWED** PubMed Abstract
  • CASE REPORTS: /Investigators/ reported a case of acute cresol burn and poisoning in a 18-year-old woman accidentally exposed to cresol. Exposure of face, hand, feet, thighs and perineum occurred. Face, hand and feet were immediately irrigated with water, but contaminated trousers were not taken off and thighs and perineum were not washed. Burns were first and second degree in severity and covered 20% of the body. After 10 min she exhibited erythema, discoloration of the skin, and became delirious followed by coma. Pulmonary edema and hemoglobinuria were reported after treatment with a diuretic and intravenous infusion. Additional therapy included peritoneal dialysis, strict control of intravenous fluids, intravenous rogitine, oral nitroglycerin and nifedipine etc. Peritoneal dialysis was continued for 20 days. The patient was discharged 38 days later. No scarring of the skin occurred.[WHO; Environmental Health Criteria Document No. 168: Cresols (1995). Available from, as of February 4, 2006: http://www.inchem.org/pages/ehc.html] **PEER REVIEWED**
  • CASE REPORTS: /Investigators/ reported a case of acute renal failure in a healthy 50-year-old male technician accidentally exposed to a mixture of cresols. The burned area was immediately irrigated with water. The patient experienced dizziness, pain and numbness of burnt skin and abdominal pain followed by oliguria and vomiting 8 hr later. He developed severe abdominal pain and vomiting and lesser oliguria 1 day after the exposure. The patient was admitted to hospital 3 days after exposure. A follow-up examination revealed decreased pulse rate, urinary volume (70-190 mL/24 hr), blood urea nitrogen (440-1240 mg/liter), combining power of CO2 (40-42 vol %). Burnt skin was light brown in color and there was slight swelling and tactile pain. The patient was treated for acute renal failure, and complete recovery occurred within 27 days following exposure.[WHO; Environmental Health Criteria Document No. 168: Cresols (1995). Available from, as of February 4, 2006: http://www.inchem.org/pages/ehc.html] **PEER REVIEWED**
  • CASE REPORTS: /Investigators/ reported symptoms of cresol poisoning in 52 patients who ingested 4-120 mL of disinfectant containing 25-50% cresols. Mouth and throat burns, abdominal pain and vomiting were common symptoms of cresol poisoning. Coma was also a frequent occurrence; in some cases, unconsciousness occurred very soon after exposure and lasted 14 hr or more. Renal irritation and reduced phenolsulfonephthalein output indicated the occurrence of kidney effects in some patients. Darkly colored urine was produced in most cases and may have been due to hemoglobinuria. Blood abnormalities were not detected, but details regarding blood analyses were not reported; it is possible that some hematological changes (e.g., methemoglobinemia, Heinz body formation) may have been overlooked. Only two of the 52 patients died; both deaths occurred within 30 min of cresol ingestion.[WHO; Environmental Health Criteria Document No. 168: Cresols (1995). Available from, as of February 4, 2006: http://www.inchem.org/pages/ehc.html] **PEER REVIEWED**
  • CASE REPORTS: A 32-year-old man ingested 50 mL of a solution containing 90% cresols (1.035 g/vol). He remained conscious, became dyspneic, and developed a tachycardia, systolic hypotension and respiratory failure, myocardial failure, and pulmonary edema. He died on the fourth day after he had been hemodialyzed and had been given sodium bicarbonate, intravenous potassium, dextrose and insulin, a dopamine drip, and a forced diuresis with furosemide. Total serum phenols were 90 ug/mL. (A total phenol level of 10 ug/mL has been suggested to be of serious prognostic significance.)[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. 1210] **PEER REVIEWED**
  • CASE REPORTS: A 37-year-old woman died 4 days after swallowing about 250 mL of a disinfectant described as 50% cresols in a mixture of linseed oil, potassium hydroxide, and water. ... /The patient/ exhibited tachycardia with polymorphic ventricular extrasystoles shortly after exposure. This was followed within 26 hours by ventricular fibrillation and cardiac arrest. ... Death was caused by acute intravascular hemolysis, which resulted in multiple thrombosis and renal failure. The lethal dose was roughly 2 g/kg of cresols (only about one-half of which was actually absorbed). The same report described the case of a woman who recovered after drinking a smaller amount of the same disinfectant (approximately 100 mL). The urine of both women contained glucuronides of cresol metabolism. /Mixture with linseed oil, potassium hydroxide, and water/[DHHS/ATSDR; Toxicological Profile for Cresols (PB/93/110732/AS) (July 1992). Available from, as of August 7, 2006: http://www.atsdr.cdc.gov/toxprofiles/tp34.html] **PEER REVIEWED**
  • CASE REPORTS: A case of methemoglobinemia with massive hemolysis & Heinz bodies complicated by anuria & irreversible shock is described. ... Leads to suspect acute cresyl poisoning. Comparable cases reported in literature & in vitro tests demonstrate the toxic action of cresols on red blood cells.[LARCAN A ET AL; EUR J TOXICOL ENVIRON HYG 7 (1): 5-8 (1974)] **PEER REVIEWED** PubMed Abstract
  • CASE REPORTS: A patient with massive intravascular Heinz-body hemolytic anemia associated with the presence of bizarre looking erythrocytes following the oral ingestion of approx 100 mL of penetrating oil, a petroleum distillate /product/ containing 85% kerosene, 12% cresol and 2% surfactant, is described. /The patient/ was treated successfully with immediate erythrocytapheresis and forced diuresis. /Mixture of kerosene, cresol, and surfactant/[Cote MA et al; Can Med Assoc J 130 (10): 1319-22 (1984)] **PEER REVIEWED** PubMed Abstract Full text: PMC1483498
  • CASE REPORTS: A woman who swallowed between 500 and 750 mL of a concentrated cresol mixture died from cardiac arrest after 26 hours. Among 52 cases of cresol poisoning reported, two patients died, both within 0.5 hours of drinking a disinfectant purported to contain 25%-50% cresols.[DHHS/ATSDR; Toxicological Profile for Cresols (PB/93/110732/AS) (July 1992). Available from, as of August 7, 2006: http://www.atsdr.cdc.gov/toxprofiles/tp34.html] **PEER REVIEWED**
  • CASE REPORTS: Anuria was also observed in a man who worked with an antiseptic solution containing concentrated mixed cresols for 2 days before becoming ill. Other significant observations in this patient were hematological changes similar to those observed after oral exposure, including methemoglobinemia, Heinz body formation and massive hemolysis. The man died 3 days after admission to the hospital.[WHO; Environmental Health Criteria Document No. 168: Cresols (1995). Available from, as of February 4, 2006: http://www.inchem.org/pages/ehc.html] **PEER REVIEWED**
  • CASE REPORTS: In one case, coma occurred within 2 hours of ingestion of 250 mL of a 50% cresol solution. In another case, hypotension occurred within 12 hours of ingestion of 45 mL cresol, followed by death in 4 days from pulmonary edema.[Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1259] **PEER REVIEWED**
  • CASE REPORTS: Nonoccupational dermal exposure to cresol has resulted in injury and death. In 1975, ... a male infant had about 20 mL of a 90% cresol solution in water accidentally poured over his head. Within 5 minutes, the baby was unconscious and cyanotic. He died 4 hours later. Chemical burns were evident on about 7% of his skin. Examination of the internal organs revealed edema, hemorrhagic effusions from the peritoneum, pleura, and pericardium, and congestion in the brain and kidneys. The blood contained 12 mg of cresol/100 mL. Microscopic examination of the tissues revealed destruction of the epidermis with loss of the stratum corneum, extensive centrilobular and midzonal necrosis of the liver, edema of the brain, and signs of early acute tubular necrosis of the kidneys.[Green MA; Med Sci Law 15: 65-6 (1975) as cited in NIOSH; Criteria Document: Cresol p.28 (1978) DHEW Pub. NIOSH 78-133] **PEER REVIEWED**
  • CASE REPORTS: The authors report a case of a 43-year-old woman who presented with second degree chemical burns to 9% of the total body surface area due to cutaneous contact with cresol. This was associated with acute oliguric kidney injury requiring haemodialysis. In contrast to previous reports of cresol ingestion, the patient did not have evidence of hepatic dysfunction, possibly due to a low cresol concentration in the portal vein and liver. Renal histopathology showed regional accentuated tubular necrosis and disruption of the tubular basement membrane. Renal toxicity was thought to be due to direct tubular toxicity and impaired renal blood flow.[Okamoto K et al; BMJ Case Rep (2011)] **PEER REVIEWED** PubMed Abstract Full text: PMC3062832
  • CASE REPORTS: The smallest amount of cresol that produced death was 4 mL of a 25% to 50% cresol solution in an 11-month-old child.[Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 704] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Abdominal pain, coma, aspiration, dyspnea, hypoactivity, drowsiness, tremor, cough with bloody sputum, facial paralysis, seizures, vomiting.[Lelkin, J.B., Paloucek, F.P., Poisoning & Toxicology Compendium. LEXI-COMP Inc. & American Pharmaceutical Association, Hudson, OH 1998., p. 669] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Cresol in contact with skin can cause serious burns. The skin, at first red, becomes white & blisters form, & according to the concentration & length of contact, there is eczema or ulceration. The white patches can turn brown or black (signs of gangrene).[Lefaux, R. Practical Toxicology of Plastics. Cleveland: CRC Press Inc., 1968., p. 123] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Cresol introduced into the uteri of pregnant women has produced abortion, extensive hemolysis, erosion of blood vessels, damage to the kidney tubules, necrosis of the liver, and death.[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995., p. 703] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Cresol is a strong dermal irritant and causes frequent dermatitis. Serious or even fatal poisoning may result if large areas of skin are wet with cresol and not removed immediately.[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Cresol is slightly more corrosive /to the skin or eyes/ than phenol, but systemic effects may be a little milder because of slower absorption.[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-192] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Exposure to concentrated cresol may result in significant local tissue injury, hemolysis, renal injury, hepatic injury, and CNS and respiratory depression.[Goldfrank, L.R., Goldfrank's Toxicologic Emergencies 9th Ed. 2011., McGraw-Hill, New York, N.Y., p. 1351] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: In humans ... lung showed hyperemia, emphysema, edema, bronchopneumonia with petechial hemorrhages in pleura. Liver showed turbidity, inflammatory reactions, fatty degeneration; kidney showed parenchymatous, hemorrhagic nephritis; myocardial ... degeneration ... hemorrhages in epicardium & endocardium.[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. 2599] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: In some cases, cresols have been injected intentionally into the vagina and uterus for the illegal purpose of inducing abortion. Signs and symptoms in women exposed to cresols in this manner include vaginal bleeding, abdominal cramps, severe burning pain, coma, massive hemolysis, severe kidney nephrosis and failure, severe pulmonary edema with oil emboli, and death.[WHO; Environmental Health Criteria Document No. 168: Cresols (1995). Available from, as of February 4, 2006: http://www.inchem.org/pages/ehc.html] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Ingestions of 4-120 mL of 25-50% cresol result, immediately or within 10 min, in a feeling of nausea; within 15 min, a burning sensation is felt in the mouth, throat, esophagus, and epigastrium. On the skin cresol leaves a red burn. Burns and scalding with cresol are potentially lethal. Burns are seen on the lips, gums, tongue, cheeks, pharynx, and tonsils. Blisters may form followed by a painful sloughing of the mucous membrane. Hoarseness or aphonia may develop. Coma comes on quickly and may last for over 12 hr, accompanied by hypothermia. Stricture rarely forms in the gastrointestinal tract. Acute pancreatitis may be seen.[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. 1211] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Main hazard accompanying its use in industry lies in its action on skin & mucous membranes, with production of severe chemical burns & dermatitis.[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1003] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Prolonged or repeated absorption of low concentrations of cresol through the skin, mucous membranes, or respiratory tract may cause chronic systemic poisoning. Symptoms and signs of chronic poisoning include vomiting, difficulty in swallowing, salivation, diarrhea, loss of appetite, headache, fainting, dizziness, mental disturbances, and skin rash. Death may result if there has been severe damage to the liver and kidneys.[Sittig, M. Handbook of Toxic And Hazardous Chemicals. Park Ridge, NJ: Noyes Data Corporation, 1981., p. 192] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Skin contact with cresols has resulted in skin peeling on the hands, facial peripheral neuritis, severe facial burns, and damage to internal organs, including loss of kidney function and necrosis of the liver and kidneys.[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995., p. 703] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Systemic effects observed after cresol ingestion reflected those observed after its use as an abortifacient and included elevated blood pressure, damage to the vascular system and kidneys, and acute pancreatitis.[Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 704] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: When cresol contacts the skin, it may not produce any sensation immediately. After a few moments, prickling and intensive burning occur. This is followed by loss of sensory feeling. The affected skin shows wrinkling, white discoloration, and softening. Later gangrene may occur. If cresol contacts the eyes, it may cause extensive damage and blindness. A skin rash may result from repeated or prolonged exposure of the skin to low concentrations of cresol; discoloration of the skin may also occur.[Sittig, M. Handbook of Toxic And Hazardous Chemicals. Park Ridge, NJ: Noyes Data Corporation, 1981., p. 192] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: When cresol is absorbed into the body either through the lung, through the skin, mucous membranes, or by swallowing, it may cause systemic poisoning. The signs and symptoms of systemic poisoning may develop in 20 or 30 minutes. These toxic effects include weakness of the muscles, headache, dizziness, dimness of vision, ringing of the ears, rapid breathing, mental confusion, loss of consciousness, and sometimes death.[Sittig, M. Handbook of Toxic And Hazardous Chemicals. Park Ridge, NJ: Noyes Data Corporation, 1981., p. 192] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ALTERNATIVE and IN VITRO TESTS: In cell transformation assays using BALB/3T3 cells, a mixture of 3 cresol isomers was positive, and o-cresol was negative. Positive mutagenic responses were found at noncytotoxic doses.[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on 3-Methylphenol (108-39-4). Available from, as of December 17, 2014. http://www.epa.gov/iris/subst/index.html] **PEER REVIEWED**
  • GENOTOXICITY: In all Ames tests, Cresol ingredients were nongenotoxic. Mixed Cresols were not genotoxic in the fruit fly, two in vitro studies were negative for SCE production and one was positive, positive results were seen with a mammalian forward mutation assay with metabolic activation (but not without), and a transformation assay was positive only at the highest dose level.[Cosmetic Ingredient Review; Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol; Int J Toxicol 25 Suppl 1: 29-127 (2006) http://www.cir-safety.org/ingredients] **PEER REVIEWED**
  • GENOTOXICITY: No isomer, when tested individually, induced sister chromatid exchanges (SCEs) in vivo, but the mixture of the three isomers induced SCEs in Chinese hamster ovary (CHO) cells in vitro. Only o-cresol induced SCEs in human lung fibroblasts and CHO cells.[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on 3-Methylphenol (108-39-4). Available from, as of December 17, 2014. http://www.epa.gov/iris/subst/index.html] **PEER REVIEWED**
  • GENOTOXICITY: Studies on the induction of unscheduled DNA synthesis showed p-cresol to be positive in human lung fibroblast cells in the presence of hepatic homogenates, the mixture of the three isomers to be weakly positive in primary rat hepatocytes, and o-cresol to be negative in rat hepatocytes.[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on 3-Methylphenol (108-39-4). Available from, as of December 17, 2014. http://www.epa.gov/iris/subst/index.html] **PEER REVIEWED**
  • GENOTOXICITY: The ability of Mixed Cresols to induce unscheduled DNA synthesis (UDS) in primary rat hepatocytes /was examined/ ... Mixed Cresols induced detectable UDS in primary rat hepatocytes at applied concentrations of 0.5 and 1.0 nL/mL ... A smaller response was observed at 5.0 nL/mL and UDS was not detectable for treatments from 10 to 50 nL/mL. Treatment with 100 nL/mL Mixed Cresols was toxic. Mixed Cresols was considered weakly active in the primary rat hepatocyte UDS assay.[Cosmetic Ingredient Review; Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol; Int J Toxicol 25 Suppl 1: 29-127 (2006) http://www.cir-safety.org/ingredients] **PEER REVIEWED**
  • GENOTOXICITY: There is no evidence that cresols are mutagenic to Salmonella typhimurium. None of the individual isomers induced mutations at the tk locus of L5178Y mouse lymphoma cells, whereas the o/m/p mixture of isomers was active in the presence of S9 mix.[WHO; Environmental Health Criteria Document No. 168: Cresols (1995). Available from, as of February 4, 2006: http://www.inchem.org/pages/ehc.html] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: /Investigators/ reported that rats survived an 8-hour exposure to substantially saturated cresol vapors at room temperature; the liquid penetrated the skin to a dangerous extent and caused severe skin and corneal injury.[American Conference of Governmental Industrial Hygienists. Documentation of the TLV's and BEI's with Other World Wide Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 2005., p. 1] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Concentrated cresols instilled into the eyes of rabbits caused permanent opacification and vascularization. A drop of a 33% solution of cresol applied to rabbit eyes and removed with irrigation within 60 seconds caused only moderate injury, which was reversible.[American Conference of Governmental Industrial Hygienists. Documentation of the TLV's and BEI's with Other World Wide Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 2005., p. 2] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Corrosion to the GI tract and mouth is expected following cresol exposure with similar effects as phenol. Following oral administration, kidney tubule damage, nodular pneumonia, and congestion of the liver with pallor and necrosis of the hepatic cells is seen. Acute exposure can cause muscular weakness, GI disturbances, severe depression, collapse, and death.[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 440] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In rats, dermal exposure with 1.0-1.7 mL/kg for 1-2 hr caused skin discoloration, death.[Campbell J; Soap Sanit Chem 17: 103-11, 121 (1941) as cited in NIOSH; Criteria Document: Cresol p.59 (1978) DHEW Pub. NIOSH 78-133] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Mixed Cresols was applied and secured to abraded and intact skin of six albino rabbits. Dose was not stated. After 24 hr, the skin was severely red and swollen. The primary irritation score was 6.58, which classified Mixed Cresols as a primary irritant. At 72 hr, moderate to severe redness and swelling were observed./From table/[Cosmetic Ingredient Review; Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol; Int J Toxicol 25 Suppl 1: 29-127 (2006) http://www.cir-safety.org/ingredients] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Pure cresols ... have caused permanent opacification & vascularization when applied full strength to rabbit eyes. ... A drop of 33% solution applied to rabbit eyes & removed by irrigation within 60 seconds caused only moderate injury, from which the corneas recovered.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 283] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The mean lethal concentration of the /cresol/ vapor/aerosol mixture was 178 mg/cu m (duration of exposure not specified). Clinical signs of toxicity included irritation of mucous membranes and neuromuscular excitation that progressed from twitching of individual muscles to clonic convulsions. Hematuria was reported at very high concentrations. Microscopic examination revealed edematous changes in the lung and necrotic and degenerative changes in the liver (fatty degeneration, centrilobular necrosis) and kidneys (edema, swelling of the glomeruli, degeneration of the tubular epithelium, and perivascular hemorrhage).[WHO; Environmental Health Criteria Document No. 168: Cresols (1995). Available from, as of February 4, 2006: http://www.inchem.org/pages/ehc.html] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity:... Carcinogenesis studies were conducted in groups of 50 male F344/N rats and 50 female B6C3F1 mice exposed to a 60:40 mixture of m- and p-cresols (m-/p-cresol) in feed. Rats and mice were fed diets containing 0, 1500, 5000, or 15,000 ppm and 0, 1000, 3000, or 10,000 ppm, respectively. Survival of each exposed group was similar to that of their respective control group. Mean body weight gains were depressed in rats exposed to 15,000 ppm and in mice exposed to 3000 ppm and higher. A decrease of 25% over that of controls for the final mean body weight in mice exposed to 10,000 ppm appeared to be associated with lack of palatability of the feed. A marginally increased incidence of renal tubule adenoma was observed in the 15,000-ppm-exposed rats. The increased incidence was not statistically significant, but did exceed the range of historical controls. No increased incidence of hyperplasia of the renal tubules was observed; however, a significantly increased incidence of hyperplasia of the transitional epithelium associated with an increased incidence of nephropathy was observed at the high exposure concentration. The only significantly increased incidence of a neoplastic lesion related to cresol exposure observed in these studies was that of squamous cell papilloma in the forestomach of 10,000-ppm-exposed mice. A definitive association with irritation at the site-of-contact could not be made because of limited evidence of injury to the gastric mucosa at the time of necropsy. However, given the minimal chemical-related neoplastic response in these studies, it was concluded that there was no clear evidence of carcinogenicity in male rats or female mice exposed to the cresol mixture. /60:40 mixture of m-cresol and p-cresol/[Sanders JM et al; Toxicology 257(1-2): 33-9 (2009)] **PEER REVIEWED** PubMed Abstract Full text: PMC2826171
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: /Investigators/ reported that mice appeared to tolerate single, brief exposures of saturated vapors of cresol (cresylic acid), but repeated exposures to saturated concentrations for 1 hour/day for 10 days caused irritation of the nose and eyes and death of some mice.[American Conference of Governmental Industrial Hygienists. Documentation of the TLV's and BEI's with Other World Wide Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 2005., p. 1] **PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: /It has been/ concluded that o-Cresol is the most toxic isomer, followed by p-Cresol and then m-Cresol. It appeared that the three isomers are more toxic to mice (three to four times) than rats by oral administration and that toxicity was dose-dependent. Cresols in oil were more toxic than Cresols in water.[Cosmetic Ingredient Review; Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol; Int J Toxicol 25 Suppl 1: 29-127 (2006) http://www.cir-safety.org/ingredients] **PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Acute poisoning with Cresol vapor is unlikely due to the low vapor pressure of these compounds. Inhalation of an aerosol and vapor mixture, however, may cause death.[Cosmetic Ingredient Review; Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol; Int J Toxicol 25 Suppl 1: 29-127 (2006) http://www.cir-safety.org/ingredients] **PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Cresols are also strong skin irritants in animals. All three cresol isomers, either alone or in combination, are severely irritating to rabbit skin, producing visible and irreversible tissue destruction.[DHHS/ATSDR; Toxicological Profile for Cresols (PB/93/110732/AS) (July 1992). Available from, as of August 7, 2006: http://www.atsdr.cdc.gov/toxprofiles/tp34.html] **PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Cresols were previously widely used for disinfection of poultry houses, but this use was discontinued because of their toxicity; they cause respiratory problems and abdominal edema in young chicks.[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 434] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Mouse oral 760 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1003] **PEER REVIEWED**
  • LD50 Rabbit single skin penetration 2,000 (700-5,900) mg/kg with skin corrosion.[Vernot EH et al; Toxicol and Appl Pharm 42: 417-23 (1977)] **PEER REVIEWED**
  • LD50 Rat oral 1454 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1003] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • All 6 hydrocarbons tested were excreted from the gills of Dolly Varden (Salvelinus malma), although less of the largest and least polar cmpd was excreted. Approx equal amounts of the administered (14)C-labeled cresol (28.9%) was excreted from the gills. A large amt of administered (14)C-labeled cresol (38%) was recovered from the cloacal chamber.[Thomas RE, Rice SD; Physiol Mech Mar Pollut Toxic, (Proc Symp Pollut Mar Org) p.161-76 (1982)] **PEER REVIEWED**
  • An in vitro study of the permeability of human skin to cresols found that these substances had permeability coefficients greater than that for phenol, which is known to be readily absorbed across the skin in humans.[DHHS/ATSDR; Toxicological Profile for Cresols (PB/93/110732/AS) (July 1992). Available from, as of August 7, 2006: http://www.atsdr.cdc.gov/toxprofiles/tp34.html] **PEER REVIEWED**
  • Animal studies showed that 70% of cresol doses were absorbed within 6 hours.[Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1259] **PEER REVIEWED**
  • Cresol is absorbed through the skin, open wounds, and mucous membranes of gastroenteric and respiratory tracts. The rate of absorption through the skin depends on the size of the area exposed rather than the concentration of the material applied. The ... rate of absorption ... and excretion of the cresols are much like those for phenol; they are oxidized and excreted as glucuronide and sulfate conjugates.[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 436] **PEER REVIEWED**
  • Cresol slightly more corrosive /to the skin or eyes/ than phenol, but systemic effects may be a little milder because of slower absorption.[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-192] **PEER REVIEWED**
  • Cresols are normally present in human 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 437] **PEER REVIEWED**
  • Cresols can be absorbed through the skin, respiratory tract, and digestive tract. Cresols can penetrate deeply into tissues that are exposed. After Cresols are absorbed, most of the chemical is metabolized by the liver and either the metabolites or the unchanged chemical are excreted by the kidney with trace amounts excreted via the lungs. In vivo, the Cresol isomers are conjugated and excreted as glucuronides and sulfates. Significant amounts of Cresols are secreted in the bile and undergo enterohepatic recirculation. The kidney is the main route for removing Cresols.[Cosmetic Ingredient Review; Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol; Int J Toxicol 25 Suppl 1: 29-127 (2006) http://www.cir-safety.org/ingredients] **PEER REVIEWED**
  • Cresols undergo enterohepatic circulation and are excreted in bile and then reabsorbed from the intestine. However, renal elimination is the primary route of excretion.[Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins, Philadelphia, Pennsylvania 1999., p. 1259] **PEER REVIEWED**
  • Following oral exposure to cresols in rabbits, 65%-84% of the dose was excreted in the urine within 24 hours, mostly as ethereal glucuronides and sulfates.[DHHS/ATSDR; Toxicological Profile for Cresols (PB/93/110732/AS) (July 1992). Available from, as of August 7, 2006: http://www.atsdr.cdc.gov/toxprofiles/tp34.html] **PEER REVIEWED**
  • Major route of excretion ... is urine, but considerable amounts may be excreted in bile and traces in exhaled air.[Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1600] **PEER REVIEWED**
  • Oral exposure studies in dogs indicate that cresols in the body concentrate in the blood, liver and brain initially, but soon become more widespread, appearing in the lungs, kidneys and other organs.[WHO; Environ Health Criteria 168: Cresols p.34 (1995)] **PEER REVIEWED**

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Metabolism/Metabolites

  • ... Cresols are excreted by rabbit primarily as oxygen conjugates; 60-72% as ether glucuronides, 10-15% as ethereal sulfates. ... meta-cresols are hydroxylated to small extent ...[Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1600] **PEER REVIEWED**
  • Cresols in the urine are found primarily as sulfate and glucuronide conjugates. In the urine of rabbits, 60%-72% of the orally administered dose was recovered as ether glucuronide, and 10%-15% was recovered as ethereal sulfate A similar result was obtained in an earlier study in rabbits in which 14.5%-23.5% of the orally administered dose was found conjugated with sulfate in the urine. For simple phenols such as cresols, the proportions of the conjugates are known to vary with dose and to differ from one species to the next. ... Hydroxylation of a small percentage (3%) of the administered dose to 2,5-dihydroxytoluene (conjugated) occurred for both o- and m-cresol. No hydroxylation occurred for p-cresol, but p-hydroxybenzoic acid (both free and conjugated) was detected in the urine. Only 1%-2% of the administered dose was found as unconjugated free cresol in the urine.[DHHS/ATSDR; Toxicological Profile for Cresols (PB/93/110732/AS) (July 1992). Available from, as of August 7, 2006: http://www.atsdr.cdc.gov/toxprofiles/tp34.html] **PEER REVIEWED**
  • In the body, some of it is oxidized to hydroquinone and pyrocatechin, and remainder and largest proportion is excreted unchanged or conjugated with glycuronic and sulfuric acids.[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 569] **PEER REVIEWED**
  • The phenols /including cresols/ ... are partly detoxicated by liver, excreted by kidney as ethereal sulfates and glycuronates and as unchanged compound. A trace is excreted by lung.[Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972., p. 166] **PEER REVIEWED**

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Tsca Test Submissions

  • The test material, designated as "Wash Solvent (#591)", and reported as containing a "significant" amount of cresol isomers (o-, p-, and m -cresol; CAS Nos. 95-48-7, 106-44-5, 108-39-4, respectively), was applied to the shaved backs of pregnant New Zealand albino rabbits on days 6 - 18 (inclusive) of gestation. The test material was weighed out daily at dosages of 30, 100, and 200 mg/kg bw/day and blended in 5 ml of 1% methylcellulose, applied to the backs of the does, and allowed to remain in contact for 4 hours. It was then washed off with warm water and mild detergent and dried. A control group was treated with 1% methylcellulose only in a similar fashion. All animals were sacrificed on gestational day 29. There were no mortalities or abnormal behavior throughout the study. All treatment groups exhibited unspecified "dermal reactions" to the test material. Does receiving 200 mg/kg showed the most severe reactions. Reproductive parameters, including the number of resorption sites per 100 implantation sites and the number of live young per 100 implantation sites were comparable among the treatment and control groups. No treatment-related external or internal fetal abnormalities were seen. Application of the test material to the dams had no affect on the 24-hour survivability of the young.[Industrial Bio-Test Labs, Inc.; Report to the Pittsburg and Midway Mining Co.: Pilot Teratogenic Study with Wash Solvent (#591) in Albino Rabbits (1978); EPA DCN 40-8360166; Fiche No. OTS0507480] **UNREVIEWED**

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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