National Toxicology Program

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

Human Toxicity Excerpts

• TOXIC BY INGESTION AND SKIN ABSORPTION. /COMMERCIAL MIXTURES/ [Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987., p. 1244]**PEER REVIEWED**
  
• LISTED AS A TUMOR PROMOTER. /FROM TABLE/ [Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 356]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• ... DIMETHYLPHENOLS WERE AS POTENT IN PROMOTING PAPILLOMAS AS PHENOL ITSELF (WITH THE EXCEPTION OF 2,6-DIMETHYLPHENOL, WHICH WAS INACTIVE) ... IT APPEARS THAT THERE MUST BE AT LEAST ONE UNSUBSTITUTED POSITION ORTHO TO THE PHENOLIC GROUP FOR PAPILLOMA-PROMOTING ACTIVITY /IN MICE/. /DIMETHYLPHENOLS/ [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. 2583]**PEER REVIEWED**
  
• TO ENSURE LONG TERM SURVIVAL OF SALMONIDS IN PRESENCE OF PHENOLIC WASTES WHERE 2,5-XYLENOL IS THE MAIN CONSTITUENT, THE CONCN SHOULD NOT EXCEED 0.5 MG/L. [FOOD AND AGRICULTURE ORGANIZATION; WATER RES 7 (6): 929-41 (1973)]**PEER REVIEWED**
  
• 2,5-DIMETHYLPHENOL WAS NONMUTAGENIC IN TA98 AND TA100 STRAINS OF THE SALMONELLA TYPHIMURIUM HISTIDINE-REVERSION TEST SYSTEM. [EPLER JL ET AL; ENVIRON HEALTH PERSPECT 30: 179-84 (1979)]**PEER REVIEWED**
  
• THE CILIOTOXICITY OF COMPOUNDS (INCLUDING 2,5-DIMETHYLPHENOL) REPRESENTATIVE OF THE GASEOUS AND SEMIVOLATILE PHASES OF TOBACCO SMOKE WAS INVESTIGATED USING CHICKEN TRACHEAL ORGAN CULTURES. THE ALKYLATED PHENOLS EXHIBITED GREATER CILIOSTATIC EFFECTS THAN PHENOL ITSELF. [PETTERSSON B ET AL; TOXICOLOGY 23 (1): 41-55 (1982)]**PEER REVIEWED**
  
• Phenol, three cresols, and 2,5-, 2,4-, 3,5-, and 3,4-dimethylphenols were detected in ether extract of black fermented tea. ... Six of the 15 mice of Group 1 developed epithelial-cell carcinoma in the neck region after one painting of 3,4-benzopyrene followed by 55 paintings of brewed tea /over 110 days/. All other mice in this group developed pre-carcinogenic or carcinogenic stages of squamous-cell tumors. The mice of Group 2 after one painting of 3,4-benzopyrene only, developed no pathologic legions. [KAISER HE; CANCER (PHILADELPHIA) 20 (5): 614-6 (1967)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Rat oral 444 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. 3406]**PEER REVIEWED**
  
• LD50 Mouse oral 383 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. 3406]**PEER REVIEWED**
  
• LD50 Rabbit oral 938 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. 3406]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• Associations between o-cresol, p-cresol, m-cresol, 2,4-xylenol, 2,5-xylenol, 3,4-xylenol, and 3,5-xylenol exposure levels and urinary phenol excretion were examined in the coke facility industry. The subjects consisted of 76 exposed workers employed in the tar distillation process and 34 controls. ... Urinary metabolite levels were corrected for specific gravity and creatinine. The time weighted average exposure concentrations in the breathing zones of the tar distillation workers were ... 0.02 to 0.04 mg/cu m for xylenols. ... The urinary xylenol levels of exposed workers ranged from 0.12 to 0.97 mg/l with specific gravity correction. In control urine samples, the specific gravity corrected xylenol concentrations ranged from 25 x 10(-3) to 43 x 10(-3) mg/l. Significant correlations were observed between the ambient levels and urinary concentrations of phenol, o-cresol, and the xylenols, with coefficients ranging from 0.45 to 0.82. The author concludes that the biological monitoring of urinary xylenols may be used as a means of measuring xylenol exposure in coke facility workers. [Bieniek G; International Archives of Occupational and Environmental Health 70 (5): 334-40 (1997)]**PEER REVIEWED**
  
• Phenol (87.3 mg/l), p-cresol (58.6 mg/l), o-cresol (76.9 mg/l), and 2,5-xylenol (36.7 mg/l) were detected in the urine of workers employed in the distillation of the high temperature phenolic fraction of tar (carbolic oil). The concentrations of these compounds in the urine of non-exposed male workers was 11.7 mg/l, 25.7 mg/l, 68.1 ug/l, and 69 ug/l respectively. The excretion rates were 4.20 mg/hr for phenol, 2.4 mg/hr for p-cresol, 3.3 mg/hr for o-cresol; and 1.5 mg/hr for 2,5-xylenol. The highest concentrations of the ... compounds were detected in urine collected between eight and 10 hr from the beginning of exposure. ... [Bieniek G; Occup Environ Med 51 (5): 354-6 (1994)]**PEER REVIEWED**
  

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Metabolism/Metabolites

• YIELDS 2,5-DIMETHYLPHENYL-BETA-D-GLUCURONIDE AND 2,5-DIMETHYLPHENYL SULFATE IN RABBITS; 3-HYDROXY-4-METHYLBENZOIC ACID IN PSEUDOMONAS. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. D-92]**PEER REVIEWED**
  
• HYDROXYLATION OF AROMATIC HYDROCARBONS WAS STUDIED FOLLOWING THEIR ORAL ADMINISTRATION TO RATS THAT ALSO RECEIVED A PURIFIED DIET CONTAINING NEOMYCIN TO REDUCE THE LEVELS OF NORMALLY OCCURRING SIMPLE URINARY PHENOLS. PHENOLIC METABOLITES WERE QUANTITATIVELY ESTIMATED IN HYDROLYZED URINE SAMPLES BY GAS CHROMATOGRAPHY. P-XYLENE ADMINISTERED AT A DOSE OF 100 MG/KG WAS METABOLIZED TO 2,5-DIMETHYLPHENOL TO THE EXTENT OF 1.0% OF THE DOSE GIVEN. [BAKKE OM, SCHELINE RR; TOXICOL APPL PHARMACOL 16 (3): 691-700 (1970)]**PEER REVIEWED**
  
• FOUR PERSONS WERE EXPOSED TO XYLENES. 2,3- AND 3,4-XYLENOL WERE OBSERVED IN URINE OF THOSE EXPOSED TO O-XYLENE. 2,4-XYLENOL OBSERVED AFTER M-XYLENE AND 2,5-XYLENOL AFTER P-XYLENE. [SEDIVEC V, FLEK J; INT ARCH OCCUP ENVIRON HEALTH 37 (3): 205-17 (1976)]**PEER REVIEWED**
  
• Pulmonary metabolites of p-xylene, p-methylbenzyl alcohol and 2,5-dimethylphenol, were employed to investigate the divergent effects of p-xylene on pulmonary and hepatic metabolism. Rats were given p-methylbenzyl alcohol, 2,5-dimethylphenol, or 10% cremophore (control) ip daily for 3 days, and effects on hepatic and pulmonary microsomal metabolism were determined 12 hours later. Both p-methylbenzyl alcohol and 2,5-dimethylphenol mimic the decrease in pulmonary benzyloxyresorufin-O-debenzylase activity previously reported for p-xylene, but neither could account for the potent induction of cytochrome P450 in the liver. Only p-methylbenzyl alcohol had a consistent effect on P450IIB apoprotein levels, decreasing them in both the liver and lung. These data suggest that p-methylbenzyl alcohol may have a significant role in the inhibition of pulmonary P450 caused by p-xylene. [Day BJ, Carlson GP; Research Communications in Chemical Pathology and Pharmacology 76 (1): 117-20 (1992)]**PEER REVIEWED**
  

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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, 10/28/2007.