National Toxicology Program

National Toxicology Program

CAS Registry Number: 62-44-2 Toxicity Effects

http://ntp.niehs.nih.gov/go/23366

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

Names (NTP)

  • Phenacetin
  • N-(4-ETHOXYPHENYL)-ACETAMIDE
  • P-ACETOPHENETIDIDE

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: Group of 623 women known regularly to ingest phenacetin-containing analgesics were compared over 4-yr period with group of 621 controls. High intake of phenacetin analgesics was assoc with increased serum creatinine levels & low urine specific gravity ... . /Phenacetin analgesics/[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). Available at: http://monographs.iarc.fr/index.php, p. V13 146] **PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Chronic ingestion of large doses of analgesics (e.g., 1 kg or more of phenacetin [no longer commercially available in the US] and/or salicylate over any period of time) has been associated with analgesic nephropathy which is characterized by papillary necrosis and subsequent chronic interstitial nephritis, with or without pyelonephritis. Analgesic nephropathy frequently has been associated with ingestion of large amounts of combinations of aspirin, phenacetin, and caffeine (combinations containing phenacetin no longer are commercially available in the US). Because phenacetin previously was a component of many analgesic drug mixtures, this drug has been implicated as the causative agent of renal damage. Many clinicians, however, believe that nephropathy may be caused by a combination of several analgesics rather than a single drug. Cancer of the renal pelvis has been reported in patients with analgesic nephropathy and in patients following chronic ingestion of phenacetin-containing analgesic mixtures. Splenomegaly has also been associated with abuse of phenacetin-containing mixtures.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2184] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Renal tubular necrosis ... may ... occur. Phenacetin may cause methemoglobinemia & hemolytic anemia as form of acute toxicity, but more commonly as a consequence of chronic overdosage. Lethal doses of phenacetin are ... associated ... with cyanosis, respiratory depression, and cardiac arrest.[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 658] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: The /hemolytic/ anemia /assoc with chronic ingestion/ is usually mild, with slight reticulocytosis, but may be progressive & severe in presence of uremia or other exacerbating factors. Splenomegaly has been reported. Methemoglobinemia, sulfhemoglobin formation, & heinz bodies are not consistently present ... .[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. 704] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Hemolytic anemia may also occur following acute admin ... The anemia is usually severe & may be accompanied by intravascular hemolysis, hemoglobinuria, & acute anuria. These reactions may occur in patient with glucose-6-phosphate dehydrogenase deficiency in erythrocytes or as immunological reaction ... .[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 658] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: ... Light-headedness, dizziness, & sense of unreality & detachment, have ... been noted during pharmacokinetic studies.[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. 702] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Poisoning & death may occur from chronic abuse. ... Chronic toxicity is usually associated with a high incidence of anemia, renal damage, & GI disturbances including peptic ulcer.[ASHP. American Hospital Formulary Service -Drug Information 87. Bethesda, MD: American Society of Hospital Pharmacists, 1987. (Plus Supplements, 1987), p. 999] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Analgesic mixtures containing aspirin and phenacetin taken by humans in large doses over prolonged periods produce a classic picture of medullary interstitial nephritis, papillary damage, and chronic renal failure with loss of concentrating ability. Histologically, the kidney demonstrates a loss of renal papillae, a medullary inflammatory response with interstitial fibrosis. Proximal tubular damage may also be seen.[Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986., p. 321] **PEER REVIEWED**
  • CASE REPORTS: A 79-year-old male with phenacetin abuse was admitted to our University Hospital for treatment of asymptomatic gross hematuria. Intravenous urograpdy and computed tomography revealed synchronous right renal pelvic carcinoma and bladder carcinoma. Right nephroureterectomy and transurethral resection of bladder tumor (TUR-Bt) were performed. Histologically, right renal pelvic tumor and bladder tumor were both transitional cell carcinomas of grade 2, pT1, and grade 1 = 2, Ta, respectively. Additionally, pathological examination revealed two distal ureteral tumors, which were transitional cell carcinomas of grade 2, pTa. He also had a history of heavy tobacco-smoking (20 cigarettes per day for 50 years). The relationship between transitional cell carcinoma and phenacetin abuse as well as the influence of tobacco-smoking, and review the literature /is discussed/.[Onozawa M et al; Hinyokika Kiyo 45 (4): 257-60 (1999)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10363146?dopt=Abstract" target=new>PubMed Abstract</a>
  • CASE REPORTS: ... 31 cases /were described/ in Federal Republic of Germany of carcinoma of renal pelvis, 5 carcinomas of ureter & 106 carcinomas of bladder; only 1 case of papillary carcinoma of renal pelvis assoc with benign papilloma of ureter & 2 cases of carcinoma of bladder were found in heavy users of phenacetin.[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). Available at: http://monographs.iarc.fr/index.php, p. V13 148] **PEER REVIEWED**
  • CASE REPORTS: The carcinogenic effect of analgesic abuse involving phenacetin was studied in 88 cases of renal parenchymal disease and carcinoma of kidney and ureters. Thirty-one patients had malignant urothelial tumors of the renal pelvis or ureter. Forty-two percent of these transitional cell carcinomas occurred in patients with renal papillary necrosis following prolonged and heavy analgesic ingestion.[Mahony J et al; Aust NZ J Med 7 (OCT): 463 (1977)] **PEER REVIEWED**
  • CASE REPORTS: Phenacetin ... was under suspicion in the case of a man who had yellow vision for two days after taking 2 g, while the headache for which the medication had been taken disappeared. The visual acuity and fundi remained normal.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 716] **PEER REVIEWED**
  • CASE REPORTS: An elderly man who was addicted for years to a mixture of phenacetin and aminopyrine had poor central vision for several years, associated with large central scotomas, many scattered drusen of both fundi, and slightly pale discs. Autopsy after a cerebrovascular accident showed essentially normal optic nerves, but marked demyelination of the central core of both optic tracts.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 716] **PEER REVIEWED**
  • CASE REPORTS: Phenacetin induced sulfhemoglobinemia in 40-yr-old woman with cyanosis & 10 yr history of taking 10-20 empirin #2/day (phenacetin, aspirin, caffeine & codeine). Review of literature suggests cyanosis of chronic phenacetin use generally due to sulfhemoglobinemia.[Kneezel L et al; Johns Hopkins Med J 139 (OCT): 175 (1976)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/978859?dopt=Abstract" target=new>PubMed Abstract</a>
  • CASE REPORTS: A 65-year-old female had been taking analgesics containing phenacetin, because of severe headaches since 1958. The total dose of phenacetin that she had taken was calculated to be 8.0 kg. She visited the department of urology in our hospital in August, 1999 complaining of gross hematuria. A solid mass was detected in her left renal pelvis on the abdominal computed tomographic (CT) scan. Under the diagnosis of a left renal pelvic tumor, nephrouretectomy was performed in September, 1999. Histopathological diagnosis was grade 2 transitional cell carcinoma. Interstitial nephritis was also observed. Our case is the twenty-second report of an urinary tract tumor associated with phenacetin abuse in Japan.[Kojima K et al; Hinyokika Kiyo 48 (5): 293-6 (2002)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12094713?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: The Collaborative Perinatal Project monitored 50282 mother-child pairs, 5546 of which had 1st trimester exposure to phenacetin. Although no evidence was found to suggest a relationship to large categories of major or minor malformations, possible associations were found with several individual defects: Craniosynostosis (six cases); Adrenal syndromes (five cases); Anal atresia (seven cases); Accessory spleen (five cases). The statistical significance of these associations is unknown and independent confirmation is required.[Briggs, G.G, R.K. Freeman, S.J. Yaffe. A Reference Guide to Fetal and Neonatal Risk. Drugs in Pregnancy and Lactation. 4th ed. Baltimore, MD: Williams & Wilkins 1994., p. 672] **PEER REVIEWED**
  • EPIDEMIOLOGY STUDIES: Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. ...[Buckalew V; Am J Kidney Dis 28 (1 Suppl 1): S7-13 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8669433?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: Analgesic intake was investigated for 96 patients with cancer of the renal pelvis and ureter (including papillomas) and 294 hospital controls. In comparison with persons who never used analgesics, increased relative risks were seen for users of phenacetin-containing drugs after adjustment for smoking and high-risk occupational exposure (men: relative risks= 2.4; women: relative risks= 4.2). A significant relative risk for aspirin use among women was also observed. There was an indication of a dose-effect relationship for both types of analgesics. The influence of phenacetin and aspirin on the development of renal pelvis and ureter tumors could not be separated since in this study the two compounds occurred so frequently in the same formulation. Experimental studies and phenacetin metabolism makes it biologically most relevant to attribute the observed association in the present study to the phenacetin component of the drugs.[Jensen OM et al; Int J Cancer 44 (6): 965-8 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2606581?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: A population-based case-control of cancer of the urinary bladder was carried out in New York State women aged 20 to 49 years (173 matched pairs). Known and suspected risk factors for bladder cancer were examined for these rare, early onset female cases. More cases than controls reported heavy use of pharmaceutical products that contained phenacetin (odds ratio from 6.5, confidence interval from 1.5 to 59.2). More cases than controls reported that ... /they had a/ thyroid uptake procedure with (131)I (odds ratio from 3.7, confidence interval from 1.4 to 11.0). Analyses with the conditional multiple logistic regression model done to take into account the effects of confounding and interacting variables. The odds ratios for these factors remained elevated.[Piper JM et al; Am J Epidemiol 123 (6): 1033-42 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3706274?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: A case-control study was conducted to estimate the relative risks of end-stage renal failure after regular analgesic intake (defined as consumption of 15 or more analgesic doses per month for a continuous period of at least 1 year) for cumulative drug intake, single-ingredient analgesics, combinations, and specific compounds. The case group included all patients with end-stage renal failure undergoing renal replacement therapy in the area of West Berlin (1984-1986, n= 921). Control subjects, matched to cases by sex, age, and nationality, were selected from a group of patients in outpatient clinics. Matching was possible for 517 cases. The relative risks of end-stage after regular analgesic intake of any analgesic was 2.44 (95% confidence interval: 1.77-3.39) and after regular analgesic intake of combination drugs 2.65 (95% confidence interval 1.91-3.67). No significant increase was found, however, after regular analgesic intake of single-ingredient analgesics. The relative risk after regular analgesic intake of combination drugs and for the most preferred analgesic ingredients (phenacetin, paracetamol, acetylsalicylic acid, phenazones, caffeine) increased with dose. Furthermore, a dose-time-related relative risks and regular analgesic intake of the longest used preparation was found. Thus, the results clearly show an increased relative risks of end-stage renal failure after regular analgesic intake related to both dose and exposure time of mixed analgesic compounds, but not for the use of only single-ingredient analgesics.[Pommers W et al; Am J Nephrol 9 (5): 403-12 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2801788?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: A multicenter case-control study of 554 adults with newly diagnosed chronic renal disease (serum creatinine >= 130 mumol/L) and 516 control subjects randomly selected and matched for sex, race, age and proximity was performed to examine the use of the analgesics phenacetin, acetaminophen, and aspirin as a cause of chronic renal disease. Daily users of analgesics had significantly more renal disease than infrequent users (odds ratio, 2.79). Those using phenacetin daily had the highest risk of renal disease (odds ratio 5.11). Adjusting for other analgesics, the risk of renal disease was also increased in daily users of acetaminophen (odds ratio 3.21). No increased risk in daily users of aspirin was found. The risks with daily use of phenacetin and acetaminophen changed little after adjustment for diabetes, hypertension, and the indication for analgesic use. It was concluded tht long-term, regular use of phenacetin may increase the risk of chronic renal disease and the long-term, daily use of acetaminophen, the major metabolite of phenacetin, is associated independently with an increased risk of chronic renal disease, but there is no increased risk in daily users of aspirin.[Sandler DP et al; N Engl J Med 320 (May 11): 1238-43 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2651928?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: A case-control study /was conducted/, of 325 men ages 30-69 who were diagnosed with end-stage renal disease between 1976 and 1984, and resided in four urban areas of Michigan in 1984. Cases were selected from the Michigan Kidney Registry and excluded men with diabetic, congenital, and obstructive nephropathies. Controls were selected by random-digit dialing and were pair-matched to cases for age, race, and area of residence. Telephone interviews were conducted with 69% of eligible cases and 79% of eligible controls. Risk of end-stage renal disease was significantly related to phenacetin or acetaminophen consumption (odds ratio= 2.66) ... .[Steenland NK et al; AM J Public Health 80 (2): 153-57 (1990)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2153349?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: In a survey of the literature, phenacetin appears to be responsible for an increased risk of urothelial tumours in humans, especially renal pelvis tumour. Few observations have suggested an association between bladder cancer and phenacetin containing analgesics however. To assess this association in France, a case-control study of bladder cancer (143 cases, 120 controls) was undertaken. We point at some methodological difficulties, such as difficulties of recall, definition of a control group, non-responses, possible French distinctive features of analgesics use. Results are not able to confirm the suspected relationship between bladder cancer and phenacetin use.[Berleur M et al; Therapie 47 (3): 231-8 (1992)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/1295123?dopt=Abstract" target=new>PubMed Abstract</a>
  • OTHER TOXICITY INFORMATION: In 1961, Denmark imposed restrictions upon sale of drugs containing phenacetin because there was a marked increased in mortality from chronic interstitial nephritis among women consuming such preparations. Statistics show gradual decreased in mortality since 1960.[MABECK CE, WICHMANN B; ACTA MED SCAND 205 (7): 599 (1979)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/474188?dopt=Abstract" target=new>PubMed Abstract</a>
  • SURVEILLANCE: In a surveillance study of Michigan Medicaid recipients involving 229101 completed pregnancies conducted between 1985 and 1992, 368 newborns had been exposed to phenacetin during the 1st trimester. A total of 24 (6.5%) major birth defects were observed (16 expected), including (observed/expected) 6/4 cardiovascular defects, 1/1 polydactyly, and 2/1 hypospadias. No anomalies were observed in three other defect categories (oral clefts, spina bifida, and limb reduction defects) for which specific data were available. These data do not support an association between the drug and congenital defects.[Briggs, G.G, R.K. Freeman, S.J. Yaffe. A Reference Guide to Fetal and Neonatal Risk. Drugs in Pregnancy and Lactation. 4th ed. Baltimore, MD: Williams & Wilkins 1994., p. 673] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: ... PHENACETIN GIVEN TO CATS @ RATE OF 50 MG/KG DAILY FOR 22 WK, CAUSED SOME LIVER DEGENERATION ... .[Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 92] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... 30 BD I and BD III rats, 100 days of age ... received 40-50 mg/animal phenacetin daily in diet (avg total dose, 22 g). 1 rat died after total dose of 10 g & was found to have osteochondroma. Mean age at death was 770 days, compared with 750 days in unspecified number of controls. No tumors related to treatment were observed ... .[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). Available at: http://monographs.iarc.fr/index.php, p. V24 145] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... Male albino rats (150-180 g) were fed diets containing 0 (control), 0.05, 0.1 or 0.5% n-hydroxyphenacetin (a putative metabolite of phenacetin) for up to 73 wk. ... 1 animal fed 0.1% in diet developed transitional-cell carcinoma of renal pelvis. Of treated animals 11, 13 & 15 rats ... alive at time of appearance of 1st tumor ... 8/11, 13/13 & 15/15 developed liver tumor (... hepatocellular carcinomas), compared with 0/15 controls ... . /N-Hydroxyphenacetin/[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). Available at: http://monographs.iarc.fr/index.php, p. V13 144] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Two groups of 50 male and 50 female 9-week-old sprague-dawley rats were fed, respectively, with 1.25% or 2.5% phenacetin (japan pharmacopeia grade) in pelleted diet for 18 months and fed thereafter with basal diet for 6 months; 65 male and 65 female control animals were fed basal diet. Among animals surviving for 24 months or dying within 24 months with tumor(s), neoplasms were detected in 26/27 males and 21/27 females fed 2.5%, in 20/22 males and 19/25 females fed 1.25% and in 1/19 males and 6/25 females of the control group. Tumors (benign and malignant) of the nasal cavity were found in 16/27 males and 7/27 females fed 2.5% and in 16/22 males and 6/25 females fed 1.25%. Malignant tumors of the urinary tract were detected in 13/27 males and 4/27 females fed the high dose and in 1/22 males and 0/25 females fed the low dose; 2 papillomas were found in females given the high dose. No nasal cavity or urinary-tract tumors were seen in controls.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 141] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Female Sprague-Dawley rats were given 0 or 0.535% phenacetin in pelleted diet for 86 or 110 weeks. In the 86-week study, epithelial hyperplasia of the kidney was found in 2/24 controls and in 21/38 treated animals. In the 110-week study, the following changes were observed; urothelial hyperplasia of renal papillae in 26, and epithelial hyperplasia in 1. In addition, carcinomas of the mammary gland (5/30) and ear duct (4/30; P> 0.05) were found in the treated group. In the control group, uroepithelial hyperplasia was found in 5 animals, dilatation of vasa recta in 8 and a mammary carcinoma in 1 animal.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 140] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: The oral analgesic drug phenacetin is known to cause nasal and renal tumors in rats when fed in the diet for 2 years at 1.25 or 2.5%. Long-term exposure to chemicals at cytotoxic concentrations may lead to tumor formation secondary to chronic restorative cell proliferation. In the present experiments, cell proliferative and cytotoxic effects on the nasal mucosa were examined after short-term phenacetin administration. One week of daily gavage treatment of rats with phenacetin at doses comparable to those used in oncogenicity studies resulted in dose-related increases in DNA synthesis in both respiratory and olfactory mucosa. The increase in respiratory mucosa was due to inflammatory cells in the lamina propria and not proliferation of the respiratory epithelial cells. This observation demonstrates a potentially serious artifact in analytical approaches to DNA sysnthesis using tissue homogenates. One or two weeks of daily phenacetin treatment resulted in degenerative changes in the olfactory epithelium and necrosis of Bowman's glands. These changes were associated with increases in cell proliferation only in the olfactory epithelium. Two-week daily gavage treatment of rats with phenacetin at 100, 625, or 1250 mg/kg/day increased olfactory epithelial cell replication 62.4, 174, or 763%, respectively. The dose-response relationships for cell proliferation was similar to that of nasal tumor formation. These data suggest that the primary site of phenacetin toxicity within the nose is the olfactory mucosa, with restorative cell proliferation being confined to the epithelial cell layer. The data indicated that early cell proliferative responses may be important in the genesis of nasal tumors and that cell proliferation data may be useful for setting dose levels for oncogenicity studies.[Bogdanffy MS et al; Toxicol Appl Pharmacol 98 (1): 100-12 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2929018?dopt=Abstract" target=new>PubMed Abstract</a>
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... In the present study, the dose-related effect on the cell proliferation of the urothelium was evaluated in male Sprague-Dawley rats by autoradiography. Nine groups of twenty, 6-week old rats were treated with 0.5%, 1.0% or 1.5% of acetaminophen, antipyrine or phenacetin in the diet. A tenth group of rats received control diet without added chemicals. Ten rats from each group were killed after each of 6 and 12 weeks of feeding. There was a dose-related increase in the labeling index in the urothelium of the bladder and kidney, particularly after 6 weeks of drug administration. In particular, the 1.0% and 1.5% dose levels of antipyrine and phenacetin showed a marked proliferative effect on the urothelium. In the bladder after 6 weeks, the labeling indices were significantly increased. After 12 weeks, although numerically increased, the indices were not statistically significant. In the renal pelvic urothelium the labeling index was significantly increased in antipyrine and phenacetin treated rats at doses of 1.0% and 1.5%. After 12 weeks the majority of rats treated with 1.5% antipyrine and phenacetin had labeling indices greater than or equal to 2-fold than the control rats both in the kidney and bladder. The increased labeling indices were associated with urothelial hyperplasia, in particular after 6 weeks. ...[Johansson SL et al; Carcinogenesis 10 (1): 105-11 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2910518?dopt=Abstract" target=new>PubMed Abstract</a>
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: When phenacetin-treated female rats were exposed to males, a decreased incidence of pregnancy was seen. Reduced fetal weight was found with oral doses of 600-1200 mg/kg bw per day phenacetin given from day 0 to 20 of gestation. No increase in defect rate but some retardation in skeletal growth and an increase in supernumerary ribs occurred with doses of 150 mg/kg bw and over.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 143] **PEER REVIEWED**
  • GENOTOXICITY: Phenacetin is mutagenic in salmonella typhimurium TA100 when liver 9000 g supernatant fractions from pcb-treated hamsters instead of rats are used. Phenacetin is activated to direct-acting mutagens by deacetylation, which occurred at rates 9 to 150 times greater in hamsters than in rats. The species difference in phenacetin mutagenicity is apparently due to the difference in deacetylation activity between rat and hamster liver microsomes.[Nohimi T et al; Biochem Biophys Res Commun 110 (3): 746 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6404262?dopt=Abstract" target=new>PubMed Abstract</a>
  • GENOTOXICITY: The results of studies on the induction of chromosomal aberrations, sister chromatid exchanges and micronuclei in rodents treated with phenacetin in vivo were equivocal. Phenacetin induced chromosomal aberrations in Chinese hamster cells in vitro but not DNA strand breaks in rat hepatocytes. It did not induce sex-linked recessive lethal mutations in Drosophila. Phenacetin was mutagenic to bacteria when tested in the presence of a metabolic system derived from hamster but not mouse or rat liver. The urine from phenacetin-treated Chinese hamsters, but not that from rats, was mutagenic to bacteria.[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). Available at: http://monographs.iarc.fr/index.php, p. S6 448 (1987)] **PEER REVIEWED**
  • GENOTOXICITY: Phenacetin was negative in an intrasanguineous host-mediated assay with E coli K 12 in NMRl mice given 2 mmol/kg intraperitoneally. It induced neither an increased frequency of sex-linked recessive lethals in Drosophila melanogaster nor an enhanced number of micronucleated erythrocytes in the bone marrow of NMRl mice given 2 x 5 mol/kg bw intraperitoneally.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 145 (1980)] **PEER REVIEWED**
  • GENOTOXICITY: Phenacetin produced a borderline positive result in an in vitro chromosome aberration test in Chinese hamster fibroblasts; gaps were observed in 8.8% of the metaphases of treated cells as compared with 1% in controls. However, when combined with a rat liver metabolic activation system, the compound induced breaks, rings and translocations in up to 51% of the metaphases.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 145 (1980)] **PEER REVIEWED**
  • GENOTOXICITY: Several analgesic compounds and mixtures of analgesics were examined for both cytotoxicity and ability to induce chromosomal damage in the normal rat kidney cell line NRK-49F. Chromosomal damage was assessed using an in vitro micronucleus assay. Of all the compounds tested, only N-hydroxyparacetamol caused a high degree of cell death at the concentrations used. Four analgesic compounds were found to be inducers of micronuclei in NRK cells; in order of decreasing potency these were: N-hydroxyparacetamol, N-hydroxyphenacetin, caffeine and paracetamol. An aspirin, phenacetin, caffeine mixture failed to induce micronuclei above the background level, and a paracetamol-codeine combination did not increase the level of micronuclei induction above that induced by paracetamol alone.[Dunn TL et al; Mut Res 189 (3): 299-306 (1987)] **PEER REVIEWED**
  • GENOTOXICITY: The extent and time course of induction of micronucleated polychromatic erythrocytes in mouse bone marrow were examined after administration of phenacetin as an insoluble suspension in olive oil by intraperitoneal injection or gastric intubation to 2 strains of mice, MS/Ae and CD-1, at doses up to 1200 mg/kg. The toxicity of phenacetin and the sensitivity of micronucleus induction differed in the 2 strains, but there was little difference in the extent of micronucleated polychromatic erythrocytes induced by the 2 administration routes.[Hachiya N et al; Mut Res 223 (4): 365-8 (1989)] **PEER REVIEWED**
  • GENOTOXICITY: Cytotoxic and genotoxic effects of phenacetin and paracetamol were examined in monolayer cultures of hepatocytes isolated from the mouse, hamster, rat and guinea pig. No marked increase in unscheduled DNA synthesis (UDS) after exposing hepatocytes from any of the species to phenacetin was observed.[Holme JA, Soderlund E; Mut Res 164 (3): 167-75 (1986)] **PEER REVIEWED**
  • GENOTOXICITY: Hepatic microsomal mixed-function oxidase activities and the metabolic activation of chemcial carcinogens to mutagens in the Ames test were investigated using Aroclor 1254-induced rat and hamster preparation. Benzphetamine N-demethylase, NADPH-cytochrome c reductase and cytochromes p450 and b5 were induced in both animals to the same extent by pre-treatment with Aroclor. Phenacetin ... /was/ more efficiently activated by the hamster preparations.[Hyde R et al; Mutagenesis 2 (6): 477-82 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3127658?dopt=Abstract" target=new>PubMed Abstract</a>
  • IMMUNOTOXICITY: /Phenacetin/ was examined for ... /its/ effect on interferon induction and delayed type hypersensitivity responses in mice. Phenacetin ... suppressed the delayed type hypersensitivity response, and suppressed the serum interferon titers induced by virus infection. However, /it/ did not affect the interferon titers which were induced by tilorone, a chemical inducer. The peak of interferon titer was 12 hours after infection with herpes simplex virus type 2 (HSV-2). Therefore, ... phenacetin ... /was/ given to mice intraperitoneally 24 hours before, and 2 and 18 hours after infection with HSV-2. ... Phenacetin /shortened the mean survival time of HSV-2 infected mice when they were given 2 hours after virus inoculation/. However it was not definite statistically. In biochemical and hematogical tests, ... /phenacetine/ ... did not affect the functions of liver, kidney and carbohydrate metabolism in normal mice.[Fukuma M et al; J Toxicol Sci 11 (3): 169-77 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2432279?dopt=Abstract" target=new>PubMed Abstract</a>

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Wistar rat (male) oral about 4 g/kg[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). Available at: http://monographs.iarc.fr/index.php, p. V24 142] **PEER REVIEWED**
  • LD50 Guinea pig oral 2.6 g/kg[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). Available at: http://monographs.iarc.fr/index.php, p. V24 142] **PEER REVIEWED**
  • LD50 Rat oral 1.65 g/kg[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1244] **PEER REVIEWED**

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Absorption, Distribution and Excretion

  • ... Oral absorption of phenacetin is markedly influenced by particle size in the preparation, & plasma concentration of phenacetin & acetaminophen are correspondingly variable.[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. 703] **PEER REVIEWED**
  • Peak concentration of phenacetin in plasma usually occurs in about 1 hr, & that of acetaminophen derived there from in 1-2 hr.[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 657] **PEER REVIEWED**
  • Absorption following oral administration is rapid ... duration of effect is about 4 hr.[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 1060] **PEER REVIEWED**
  • Up to 45% of (14)C was recovered in 16 hr urine & 1% in feces of rats given [acetyl-(14)C]phenacetin per oral.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 75] **PEER REVIEWED**
  • After oral administration of 250 mg of phenacetin to two male subjects, phenacetin was detected in plasma for 12 hr, with peak concentration of 222 & 92 ng/mL occurring at 1.0 and 1.67 hr in two persons, respectively.[Findlay J et al; J Pharmacol Exp Ther 210 (1): 127 (1979)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/448640?dopt=Abstract" target=new>PubMed Abstract</a>
  • Phenacetin is excreted into breast milk, appearing along with its major metabolite, acetaminophen.[Briggs, G.G, R.K. Freeman, S.J. Yaffe. A Reference Guide to Fetal and Neonatal Risk. Drugs in Pregnancy and Lactation. 4th ed. Baltimore, MD: Williams & Wilkins 1994., p. 673] **PEER REVIEWED**
  • ... Less than 1% of phenacetin is excreted unchanged in urine.[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 657] **PEER REVIEWED**
  • No transient increase in renal clearance of phenacetin was observed in dogs following onset of diuresis induced by rapid injection of mannitol, which is consistent with failure of drug to accumulate within medulla.[Duggin G et al; J Pharmacol Exp Ther 207 (2): 584 (1978)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/712640?dopt=Abstract" target=new>PubMed Abstract</a>
  • The pharmacokinetic characteristics of the analgesic phenacetin have been determined in six healthy adults. After rapid i.v. injection of 250 mg phenacetin, the log plasma concentrations versus time curves were evaluated according to the rules of a two-compartment open model. The elimination half-life (t1/2)beta varied from 37 to 74 minutes. The volume of distribution (Vd)beta ranged from 1.0 to 2.1 L per kg body weight. The total clearance of the drug was high and approximated the average value of hepatic blood flow in normal adults. In agreement with this finding, the bioavailability of a small oral dose of phenacetin (0.25 g) was almost nil, as the bulk of the drug was cleared during its first pass through the liver. With large oral doses (1.0 g) the first-pass effect decreased and availability increased. The results are discussed and related to current general views of the liver-first-pass phenomenon.[Raaflaub J et al; Eur J Clin Pharmacol 8 (3-4): 261-5 (1975)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/1233222?dopt=Abstract" target=new>PubMed Abstract</a>

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Metabolism/Metabolites

  • Acetaminophen & phenacetin are metabolized primarily by hepatic microsomal enzymes. ... In normal individual, 75 to 80% of administered phenacetin is rapidly metabolized to acetaminophen.[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 657] **PEER REVIEWED**
  • ... Phenacetin is converted to at least a dozen other metabolites, by n-deacetylation to para-phenetidin & by hydroxylation & further metabolism of phenacetin & para-phenetidin. An unknown metabolite, but an oxidizing agent, is responsible for methemoglobin formation & hemolysis of red blood cells ... .[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 657] **PEER REVIEWED**
  • Phenacetin is metabolized ... to p-acetamidophenol, which is excreted as glucuronide and sulfate conjugate ... .[Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 176] **PEER REVIEWED**
  • ... N-hydroxyphenacetin has been identified as metabolite in ... man.[Testa, B. and P. Jenner. Drug Metabolism: Chemical & Biochemical Aspects. New York: Marcel Dekker, Inc., 1976., p. 63] **PEER REVIEWED**
  • In man cysteine conjugate, s-(1-acetamido-4-hydroxyphenyl)-cysteine (2% of dose), & corresponding mercapturic acid (a trace) are also formed.[Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 176] **PEER REVIEWED**
  • Besides previously described urinary metabolites of phenacetin.../an investigator/ using [ethyl-(14)C]phenacetin & [acetyl-(3)H]-phenacetin in rats, has described 4 other, N-acetyl-s-ethylcysteine, quinol, acetamide, and a substance which is probably N-acetyl-s-2-(4-ethoxyacetanilido)cysteine-s-oxide.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 183] **PEER REVIEWED**
  • 3-methylthio-4-hydroxyacetanilide was found in the urine of dogs and humans treated with phenacetin. About 1 to 3% of the administered dose was excreted as this thiomethyl metabolite after administration of phenacetin to dogs. An average of 0.39% of the dose was excreted in the urine as 3-methylthio-4- hydroxyacetanilide conjugates after administration of phenacetin to several subjects.[Kluch A et al; Clin Pharmacol Ther 24 (3): 287 (1978)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/688722?dopt=Abstract" target=new>PubMed Abstract</a>
  • Among volunteers tested, the poor metabolizers who received 1 g phenacetin excreted less paracetamol and more 2-hydroxylation products than the extensive metabolizers. The ratio of O-deethylation products/2-hydroxylation products was correlated with the debrisoquine metabolic ratio of each of the individuals studied. Both maximum methemoglobin formation and total methemoglobin formation were higher in the poor metabolizer group than in the extensive metabolizer group. No interphenotype differences were found in the blood levels of methemoglobin reductase.[Kong I et al; Br J Clin Pharmacol 13 (2): 275 (1982)] **PEER REVIEWED**
  • Metabolic pathways for phenacetin involve de-ethylation, N-deacetylation and ring hydroxylation. The main route is oxidative de-ethylation, giving rise to n-acetyl-para-aminophenol, which is excreted in the urine as the sulphate or as the glucuronide. In rats, rabbits, guinea pigs and ferrets given 125 mg/kg bw by oral intubation or mixed with food, 63, 57, 81 and 47% of the dose, respectively, were excreted as N-acetyl-para-aminophenol (free or conjugated). Metabolism by the second pathway, N-deacetylation, was greatest in rats (21% of the dose) and least in guinea pigs and rabbits (7 and 4% of the dose). The para-phenetidine resulting from N-deacetylation can be converted to 2-hydroxy-para-phenetidine, which in rats is excreted as the sulphate in increasing amounts with increasing doses of phenacetin. Other metabolites that have been found in urine of rats, guinea pigs and rabbits are 2-hydroxyphenacetin and 3-((5-acetamido-2-hydroxyphenyl)thio)alanine. Another thiomethyl metabolite, 3-methylthio-4-hydroxyacetanilide, representing 1-3% of the administered dose, has been identified in the urine of dogs; the 2-hydroxycetophenetidine glucuronide conjugate has been found in the urine of dogs and cats given phenacetin orally. In rats and dogs given 200 mg/kg bw phenacetin, 1% of the total dose was excreted as 4-acetaminophenoxyacetic acid in the urine of rats, and 0.13% in dogs. Intestinal microflora in rats have been shown to deconjugate the metabolite N-acetyl-para-aminophenyl glucuronide, excreted partly in bile, to the N-acetyl-para-amino-phenol.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 144] **PEER REVIEWED**
  • After 2 subjects were given an oral dose of 8.3 mg/kg bw (500 mg) 14C-phenacetin the major proportion of the dose (74 and 70%, respectively) was excreted in the urine within 24 hours as N-acetyl-para-aminophenol, either conjugated (~67%) or free (~3%). Small amounts of 2-hydroxyphenacetin, 3((5-acetamido-2-hydroxyphenyl)thio)alanine and unchanged phenacetin were also found.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 146] **PEER REVIEWED**
  • In three male volunteers given 2 g phenacetin orally, about 2% of the dose was found to be excreted as S-(1-acetamido-4-hyroxphenyl)cysteine in the urine. Other metabolites have been detected in the urine in more recent studies. 3-Methyl-thio-4-hydroxyacetanilide represented 0.13-0.72% of an administered dose of 1000-1800 mg phenacetin. 4-Acetaminophenoxyacetic acid represented 0.04% of 3 ingested doses of 500 mg phenacetin.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 146] **PEER REVIEWED**
  • Following a single oral dose of 420 mg phenacetin, no N-hydroxyphenacetin could be detected in urine, however, after a dose of 1.8 g/day for 4 days to a different subject, 0.8% N-hydroxy-phenacetin was found in urine after 24 hours and 0.7% after 96 hours.[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). Available at: http://monographs.iarc.fr/index.php, p. V24 146] **PEER REVIEWED**
  • In the present study, /the authors/ investigated the substrate specificity of CYP2A13. It was shown that CYP2A13 could catalyze ethoxyresorufin O-deethylation, methoxyresorufin O-demethylation, and phenacetin O-deethylation, which are used as marker activities for human CYP1A2. Although the intrinsic clearances (V(max)/K(m)) of the two former reactions by CYP2A13 were much lower than that of CYP1A2, the value of the last reaction by CYP2A13 was 2-fold higher than that of CYP1A2. Of particular interest was that CYP2A13 has higher affinity toward phenacetin than CYP1A2. In contrast, CYP2A6 hardly catalyzed these reactions, although the amino acid identity with CYP2A13 is as high as 93.5%. …[Fukami T et al; Drug Metab Dispos 35 (3): 335-9 (2007)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17178771?dopt=Abstract" target=new>PubMed Abstract</a>
  • In this paper, the metabolism of phenacetin has been studied in patients with chronic hepatitis B or cirrhosis secondary to a hepatitis B virus infection. The possibility of using the phenacetin test in the evaluation of liver function in these subjects has also been tested. Phenacetin pharmacokinetics and the recovery of its urinary metabolites were studied in 8 normal subjects, 16 patients with chronic hepatitis B and 12 patients with cirrhosis. The phenacetin test was performed in 18 normal subjects and 52 hepatocellular carcinoma (HCC) patients. The test was repeated in HCC patients after treatment with transcatheter arterial chemoembolization (TACE). Compared with normal controls, phenacetin apparent clearance decreased by 47.0% (p < 0.05) and 78.7% (p < 0.01) in patients with chronic hepatitis B and cirrhosis, respectively. The recovery of phenacetin O-de-ethylated metabolites decreased by 24.6 and 72.4% (p < 0.01). 46 of 52 HCC patients (88.4%) had an abnormal phenacetin test before TACE, where the ratio of plasma total acetaminophen to phenacetin was below the lower limit of the normal control range. The ratio was less than 50% of normal controls in 6 HCC patients who had a deterioration in liver function from Child-Pugh class A to Child-Pugh class B after TACE. The metabolism of phenacetin is impaired in patients with chronic hepatitis B and cirrhosis. The phenacetin test can predict the susceptibility of liver function to TACE in HCC patients.[Qu ZQ et al; Int J Clin Pharmacol Ther 45 (1): 55-62 (2007)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17256451?dopt=Abstract" target=new>PubMed Abstract</a>
  • The metabolism of [ethyl-14C]phenacetin in the rat and rabbit respiratory tract was studied. As shown by whole-body autoradiography, a selective binding of radioactivity occurred in the mucosa of the rat respiratory tract 5 min after an i.v. injection of [ethyl-14C]phenacetin. Microautoradiography showed that tissue-bound radioactivity was present in the epithelium of the nasal and tracheo-bronchial mucosa and in subepithelial glands in the olfactory mucosa. In vitro experiments showed that the mucosa of the rat and rabbit respiratory tract had a marked ability to metabolize [ethyl-14C]phenacetin, as determined by 14CO2 formation and binding of radioactivity to the mucosa. The results indicate that in situ metabolism of phenacetin in the nasal mucosa may play a role in the pathogenesis of phenacetin-induced tumors in the nasal region of rats.[Brittebo E et al; Chem Biol Interact 50 (2): 233-45 (1984)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6744467?dopt=Abstract" target=new>PubMed Abstract</a>

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 11/28/2012.

The NTP is administratively located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.

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