Hazardous Chemical Information System (HCIS)

Phenol

Skin absorption notice: Absorption through the skin may be a significant source of exposure. SeeChapter 11 of the Guidance Note on the Interpretation of Exposure Standards for Atmospheric Contaminants inthe Occupational Environment, published by Worksafe Australia.

Documentation notice: National Occupational Health and Safety Commission documentation available for these values.

No standard should be applied without reference to Guidance on the interpretation of Workplace exposure standards for airborne contaminants.

1. IDENTITY

2. CHEMICAL AND PHYSICAL PROPERTIES

Phenol is a colourless or white crystal with a characteristic odour. It reddens on exposure to air and light, particularly under alkaline conditions. Its chemical and physical properties include the following:

3. MAJOR INDUSTRIAL USES

Phenol is used as a general disinfectant, as a reagent in chemical analysis and for the manufacture of artificial resins, medical and industrial organic compounds and dyes. It is also used in the manufacture of fertilisers, explosives, paints and paint removers, drugs, pharmaceuticals, textiles and coke.

4. ANIMAL STUDIES

4.1 Inhalation Exposure

There are several reports of exposure to phenol vapour that have caused observable effects.

Sandage ⁽²⁾ reported a slight weight gain in rats and monkeys but not mice exposed to 5 ppm for 8 h/day, 5 days/week for 90 days. Mice exhibited positive stress tests over controls. Mukhitov (cited in Ref 3) reported elevated blood cholinesterase activity and changes in time of excitation of extensor muscles in rats exposed to 0.03 ppm and 1.4 ppm of phenol 24 h/day for 61 days.

The lowest vapour concentration shown to have 'severe' effects was reported by Deichmann et al ⁽⁴⁾ . Five of twelve guinea pigs exposed to 26-52 ppm of phenol for 7 h/day, 5 days/week died after 29 exposures. Post-mortems revealed liver, lung, heart and kidney damage. Rabbits given the same exposure regime showed no external symptoms, but similar pathological changes to guinea pigs were observed at post mortem. Rats exhibited no signs of toxicity after 53 exposures.

4.2 Teratology and Foetotoxicity

The only data relevant to inhalation were found in an abstract by Korshunov (cited in Ref 1), who described an increase in pre-implantation loss and early postnatal death in offspring of rats exposed to 1.3 ppm and 0.13 ppm of an undescribed regime. Minor and Becker ⁽⁵⁾ also described foetotoxicity but not teratogenicity. Jones et al (cited in Ref 1) treated rats with 0-120 mg/kg/day phenol by gavage and mice with 0-280 mg/kg/day orally on days 6-15 of gestation. Foetal toxicity was observed below the maternal toxicity range. In contrast to the in vivo results, in vitro assays by Freese et al ⁽⁶⁾ and Braun et al ⁽⁷⁾ suggested that phenol may be teratogenic.

Thus, phenol has been shown to be foetotoxic but not teratogenic in whole animals; no data were available with regard to the ability of phenol to cross the placenta.

4.3 Carcinogenicity

Several authors have tested the carcinogenicity of phenol by skin painting studies. Boutwell and Bosch ⁽⁸⁾ applied 5 or 10% phenol to the skin of tumour-susceptible mice after pre-treatment with the carcinogen 9,10-dimethyl-1,2-benzanthracene (DMBA), and found phenol to be a tumour-promoting agent. Salaman and Glendenning ⁽⁹⁾ demonstrated that DMBA was not necessary for the development of papillomas and carcinomas but reduced the time required for their appearance.

When phenol and the carcinogen benzo(a)pyrene were applied simultaneously, phenol was observed to inhibit the skin carcinogenicity of benzo(a)pyrene, and thus could not be a co-carcinogen ^(10,11) .

The National Cancer Institute ⁽¹²⁾ gave phenol in drinking water to rats and mice for 103 weeks. An increased incidence of carcinomas was observed in male rats. However, a definite association with phenol could not be established because only those animals treated with a lower dose were significantly different to controls. No treatment-related tumours were observed in mice.

4.4 Genotoxicity

Results of the studies on mutagenicity of phenol have been equivocal ⁽⁴⁾ . Studies by several authors, including Gocke et al ⁽¹³⁾ , Paschin and Bahitova ⁽¹⁴⁾ Morimoto et al ⁽¹⁵⁾ , and Painter and Howard ⁽¹⁶⁾ , have found phenol to cause genetic damage. Phenol has been observed to be non-mutagenic by others - in particular, it has been found negative in the Ames test by numerous authors including Florin et al ⁽¹⁷⁾ , Pool and Lin ⁽¹⁸⁾ , Haworth et al ⁽¹⁹⁾ and Kazmer et al ⁽²⁰⁾ .

5. HUMAN STUDIES

Phenol causes local and systemic toxic effects upon entering the body via ingestion, skin absorption (of any phase) or inhalation. Locally, phenol may result in irritation of the nose, throat and eyes and skin burns. There is inadequate evidence for the carcinogenicity of phenol in humans and it is therefore not classifiable in this regard ⁽²¹⁾ .

Acute poisoning (as summarised by Deichmann and Keplinger ⁽²²⁾ ) causes an increased followed by a decreased respiration rate, decreased body temperature, cyanosis, muscular weakness, weak or occasionally rapid pulse and coma. Death is usually the result of respiratory failure.

Chronic exposure to phenol is typified by systemic problems. These include vertigo, digestive difficulties, skin eruptions, nervous problems and headaches. Death may occur when liver or kidney problems become severe ⁽²²⁾ . It has been recommended that no person with known kidney or liver damage be exposed to phenol vapour at any concentration.

There is a lack of chronic studies on humans although several uncontrolled incidences have been reported.

The lowest inhaled dose reported to have observable effects was described by Mukhitov (cited in Ref 3). Exposure to 0.006 ppm for 15 seconds altered the reflexes in four of four subjects tested. An increased sensitivity to light in three dark-adapted people was observed after exposure to 0.004 ppm for 5 minutes.

No toxic effects were mentioned in a study of factory workers exposed daily to 3.2 ppm ⁽²³⁾ . However, workers concurrently exposed to up to 0.26 ppm of phenol and 0.08 ppm of pyrocatechol complained of eye irritation ⁽²⁴⁾ .

The oral LD₅₀, based on estimates only, is approximately 10 mg/kg and the lowest estimated dose found to cause death was 0.140 mg/kg (cited in Ref 9). Deaths have resulted from short-term skin contact with concentrated phenol.

6. TOXICOKINETICS

Phenol is absorbed rapidly after direct contact with the skin, inhalation of vapour, skin absorption of vapour, or through the alimentary canal (summarised in Ref 22).

Piotrowski ⁽²⁵⁾ showed that throughout an eight-hour shift, 70-80% of phenol is retained in the lungs. Lung and skin absorption is at a rate roughly proportional to the vapour concentration. Absorption of vapour through the skin was found to be equivalent to the amount of phenol in 0.35 m³/h up to 25 mg/m³, and cotton overalls were observed to provide no protection.

Aqueous phenol enters the skin at 0.08 - 0.30 mg/cm²/h. The absorption rate is temperature and concentration dependent ⁽²⁶⁾ . The total amount absorbed over a 30 minute exposure to one hand is of the same order as that of vapour absorbed by the skin over a six-hour shift ⁽²⁵⁾ .

Excretion of phenol is rapid and predominantly via the urine. Almost 100% of the absorbed phenol vapour was excreted within 24 hours after a broken eight-hour shift with exposure to 25 mg/m ³⁽²⁵⁾ , and after a six-day working week with exposure to a maximum of 9.6 mg/m ³⁽²³⁾ . After a two-day holiday following the six-day working week, phenol levels were normal ⁽²³⁾ .

Upon exposure, phenol is quickly distributed throughout the body ⁽²⁷⁾ ; it is then metabolised, mainly in the liver, intestines and lungs ⁽²⁸⁾ .

Metabolism begins immediately. The step of primary importance is generally conjugation with sulphates and glucuronides. Reactions producing dihydroxy products are of secondary importance followed by primary excretion of free phenol.

7. OVERSEAS EXPOSURE STANDARDS

8. CONCLUSION

Phenol is rapidly absorbed into the body through all routes and rapidly excreted. It may cause severe irritation, neurosis, central nervous system effects, and liver and kidney damage in experimental animals and humans. Sandage ⁽²⁾ reported mild liver and kidney effects in rats and rhesus monkeys exposed to phenol at 5 ppm. In guinea pigs, 5/12 animals died after exposure to 26-52 ppm of vapour for 7 hours/day, 5 days/week for 6 weeks, and extensive heart, lung, vascular, liver and kidney damage was observed, although exposure of rats to phenol under similar conditions was without observable effects. Increased light sensitivity and altered reflexes have been observed in volunteers exposed to phenol at less than 0.1 ppm. Exposure data for chronic ill effects in humans are lacking.

Phenol appears to be a tumour promoter in experimental animals but there is inadequate evidence for it to be a carcinogen in experimental animals or humans. It causes genetic damage in some tests but does not induce mutation in bacteria.

9. RECOMMENDATION FOR EXPOSURE STANDARD

After reviewing the relevant literature, the Exposure Standards Expert Working Group recommends a time-weighted average exposure standard of 1 ppm for phenol based on liver and kidney effects in rats and monkeys and systemic effects in guinea pigs exposed to phenol at 5 ppm and 26 ppm respectively. This standard should provide adequate protection for most workers but may not be adequate for individuals with kidney or liver damage. The Working Group is also of the view that there is ample evidence of absorption through the intact skin and recommends that the skin notation be maintained. There is not adequate evidence to assign a carcinogen category to this substance at this time.

1. Bruce RM et al, "Summary review of the health effects associated with phenol", Toxicol Ind Health, 3: 535-568, 1987.

2. Sandage C, "Tolerance criteria for continuous inhalation exposure to toxic material. I. Effects on animals of 90-day exposure to phenol, CC1₄ and a mixture of indole skatole, H₂S and metylmercaptan". Dayton Ohio, Wright-Patterson Air Base, US Air Force Systems Command, Aeronautical Systems Division, ASD Technical Report 61-519 (I), NTIS AD-268783, 1961.

3. NIOSH, "Criteria for a Recommended Standard: Occupational Exposure to Phenol", DHEW Publication  No. 76-196, National Institute for Occupational Safety and Health, US Dept. of Health, Education and Welfare, Cincinnati, Ohio, 1976.

4. Deichmann WB et al, "Phenol studies - VII. Chronic phenol poisoning, with special references to the effects upon experimental animals of the inhalation of phenol vapour", Am J  Clin Pathol, 14: 273-77, 1944.

5. Minor JL & Becker BA, "A comparison of the teratogenic properties of sodium salicylate, sodium benzoate, and phenol", Toxicol Appl Pharmacol, 19: 373, 1971.

6. Freese E et al, "Correlation between the growth inhibitory effects, partition coefficients and teratogenic effects of lipophilic acids", Teratol, 20: 413-439, 1979.

7. Braun AG et al, "Quantitative correspondence between the in vivo and in vitro activity of teratogenic agents", Proc Natl Acad Sci USA, 79: 2056-2060, 1982.

8. Boutwell RK & Bosch DK, "The tumor-promoting action of phenol and related compounds for mouse skin", Cancer Res, 19: 413-424, 1959.

9. Salaman MH & Glendenning OM, "Tumour promotion in mouse skin by sclerosing agents", Brit J Cancer, 11: 434-444, 1957.

10. Van Duuren BL & Goldschmidt BM, "Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis", J Natl Cancer Inst (US), 56: 1237-1242, 1976.

11. Van Duuren BL et al, "Cocarcinogenesis studies on mouse skin and inhibition of tumor induction", J Natl Cancer Inst (US), 46: 1039-1044, 1971.

12. NCI, "Bioassay of Phenol for Possible Carcinogenicity", Technical Report Series No NCI-CG-TR-203, National Cancer Institute, US Department of Health and Human Services, Bethesda, Maryland, 1980. Available from NTIS, Springfield, Virginia, PB80-217946.

13. Gocke E et al, "Mutagenicity of cosmetics ingredients licensed by the European communities", Mutat Res, 90: 91-109, 1981.

14. Paschin YV & Bahitova LM, "Mutagenicity of benzo(a)pyrene and the antioxidant phenol at the HGPRT locus of V79 Chinese hamster cells", Mutat Res, 104: 389-393, 1982.

15. Morimoto K et al, "Induction of sister-chromatid exchanges in human lymphocytes by microsomal activation of benzene metabolites", Mutat Res, 119: 355-360, 1983.

16. Painter RB & Howard R, "The HeLa DNA-synthesis inhibition test as a rapid screen for mutagenic carcinogens", Mutat Res, 92: 427-437, 1982.

17. Florin I et al, "Screening of tobacco smoke constituents for mutagenicity using the Ames test", Toxicol, 18: 219-232, 1980.

18. Pool BL & Lin PZ, "Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates", Food Chem Toxicol, 20: 383-391, 1982.

19. Haworth S et al, "Salmonella mutagenicity test results for 250 chemicals", Environ Mol Mutag, 5: Suppl 1, 3-142, 1983.

20. Kazmer S et al, "The effect of culture conditions and toxicity on the Ames Salmonella/microsome agar incorporation mutagenicity assay", Environ Mol Mutag, 5: 541-551, 1983.

21. IARC, "Some Organic Solvents, Resin Monomers and Related Compounds, Pigments and Occupational Exposures in Paint Manufacture and Painting", IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 47: 263-287, International Agency for Research on Cancer, Lyon, France, 1989.

22. Deichmann WB & Keplinger ML, "Phenols and Phenolic compounds", In: (Clayton GD & Clayton FE eds), Patty's Industrial Hygiene and Toxicology, 3rd ed., Vol. 2B, Toxicology, p 2567-2627, Wiley and Sons, New York, 1981.

23. Ohtsuji H & Ikeda M, "Quantitative relationship between atmospheric phenol vapour and phenol in the urine of workers in Bakelite factories", Brit J Industr Med, 29: 70-73, 1972.

24. Hirosawa I et al, "Effects of catechol on human subjects", Int Arch Occup Environ Health, 37: 107-114, 1976.

25. Piotrowski JK, "Evaluation of exposure to phenol: absorption of phenol vapour in the lungs and through the skin and excretion of phenol in urine", Brit J Industr Med, 28: 172-178, 1971.

26. Baranowska-Dutkiewicz B, "Skin absorption of phenol from aqueous solutions in men", Int Arch Occup Environ Health, 49: 99-104, 1981.

27. Liao TF & Oehme FW, "Tissue distribution and plasma protein binding of [¹⁴C]phenol in rats", Toxicol Appl Pharmacol, 57: 220-225, 1981.

28. Cassidy MK & Houston JB, "In vivo capacity of hepatic and extrahepatic enzymes to conjugate phenol", Drug Metab Dispos, 12: 619-624, 1984.

Documentation notice:
Entries carrying a notice for National Occupational Health and Safety Commission documentation indicate that these substances have been reviewed in detail by the Exposure Standards Expert Working Group and that documentation supporting the adopted national values is available in the National Commission's Documentation of the Exposure Standards [NOHSC:10003(1995)].Cited in Ref 1

1. Bruce RM et al, "Summary review of the health effects associated with phenol", Toxicol Ind Health, 3: 535-568, 1987.