Meeting report: summary of IARC monographs on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol

Vincent James Cogliano, Yann Grosse, Robert A Baan, Kurt Straif, Marie Béatrice Secretan, Fatiha El Ghissassi, Working Group for Volume 88, Vincent James Cogliano, Yann Grosse, Robert A Baan, Kurt Straif, Marie Béatrice Secretan, Fatiha El Ghissassi, Working Group for Volume 88

Abstract

An international, interdisciplinary working group of expert scientists met in June 2004 to develop IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. Each IARC Monograph includes a critical review of the pertinent scientific literature and an evaluation of an agent's potential to cause cancer in humans. After a thorough discussion of the epidemiologic, experimental, and other relevant data, the working group concluded that formaldehyde is carcinogenic to humans, based on sufficient evidence in humans and in experimental animals. In the epidemiologic studies, there was sufficient evidence that formaldehyde causes nasopharyngeal cancer, "strong but not sufficient" evidence of leukemia, and limited evidence of sinonasal cancer. The working group also concluded that 2-butoxyethanol and 1-tert-butoxy-2-propanol are not classifiable as to their carcinogenicity to humans, each having limited evidence in experimental animals and inadequate evidence in humans. These three evaluations and the supporting data will be published as Volume 88 of the IARC Monographs.

References

    1. Agency for Toxic Substances and Disease Registry 1999. Toxicological Profile for Formaldehyde. Atlanta, GA:Agency for Toxic Substances and Disease Registry. Available: [accessed 20 July 2005].
    1. Albert RE, Sellakumar AR, Laskin S, Kuschner M, Nelson N, Snyder CA. Gaseous formaldehyde and hydrogen chloride induction of nasal cancer in the rat. J Natl Cancer Inst. 1982;68:597–603.
    1. Armstrong RW, Imrey PB, Lye MS, Armstrong MJ, Yu MC, Sani S. Nasopharyngeal carcinoma in Malaysian Chinese: occupational exposures to particles, formaldehyde and heat. Int J Epidemiol. 2000;29:991–998.
    1. Casanova M, Heck HD, Everitt JI, Harrington WW, Jr, Popp JA. Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure. Food Chem Toxicol. 1988;26:715–716.
    1. Coggon D, Harris EC, Poole J, Palmer KT. Extended follow-up of a cohort of British chemical workers exposed to formaldehyde. J Natl Cancer Inst. 2003;21:1608–1614.
    1. Cogliano VJ, Baan RA, Straif K, Grosse Y, Secretan MB, El Ghissassi F, et al. The science and practice of carcinogen identification and evaluation. Environ Health Perspect. 2004;112:1269–1274.
    1. Collins JJ, Lineker GA. A review and meta-analysis of formaldehyde exposure and leukemia. Regul Toxicol Pharmacol. 2004;40L:81–91.
    1. Dalbey WE. Formaldehyde and tumors in hamster respiratory tract. Toxicology. 1982;24:9–14.
    1. Doi AM, Roycroft JH, Herbert RA, Haseman JK, Hailey JR, Chou BJ, et al. Inhalation toxicology and carcinogenesis studies of propylene glycol mono-t-butyl ether in rats and mice. Toxicology. 2004;199:1–22.
    1. Feron VJ, Bruyntjes JP, Woutersen RA, Immel HR, Appelman LM. Nasal tumours in rats after short-term exposure to a cytotoxic concentration of formaldehyde. Cancer Lett. 1988;39:101–111.
    1. Galli CL, Ragusa C, Resmini P, Marinovich M. Toxicological evaluation in rats and mice of the ingestion of a cheese made from milk with added formaldehyde. Food Chem Toxicol. 1983;21:313–317.
    1. Gibson JE. Coordinated toxicology: an example study with formaldehyde. Concepts Toxicol. 1984;1:276–282.
    1. Hall A, Harrington JM, Aw T-C. Mortality study of British pathologists. Am J Ind Med. 1991;20:83–89.
    1. Hansen J, Olsen JH. Formaldehyde and cancer morbidity among male employees in Denmark. Cancer Causes Control. 1995;6:354–360.
    1. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries. J Natl Cancer Inst. 2003;95:1615–1623.
    1. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from solid cancers among workers in formaldehyde industries. Am J Epidemiol. 2004;159:1117–1130.
    1. Hayes RB, Blair A, Stewart PA, Herrick RF, Mahar H. Mortality of US embalmers and funeral directors. Am J Ind Med. 1990;18:641–652.
    1. Heck Hd’A, Casanova-Schmitz M, Dodd PB, Schachter EN, Witek TJ, Tosun T. Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed to CH2O under controlled conditions. Am Ind Hyg Assoc J. 1985;46:1–3.
    1. Heck Hd’A, Chin TY, Schmitz MC. 1983. Distribution of [14C] formaldehyde in rats after inhalation exposure. In: Formaldehyde Toxicity (Gibson JE, ed). Washington, DC:Hemisphere Publishing Corporation, 26–37.
    1. Hildesheim A, Dosemeci M, Chan CC, Chen CJ, Cheng YJ, Hsu MM, et al. Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2001;10:1145–1153.
    1. IARC Formaldehyde. IARC Monogr Eval Carcinog Risks Hum. 1982;29:345–389.
    1. IARC 1987. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl. 7.
    1. IARC Wood dust and formaldehyde. IARC Monogr Eval Carcinog Risks Hum. 1995;62:217–375.
    1. IARC 2005. Preamble to the IARC Monographs. International Agency for Research on Cancer. Lyon, France:International Agency for Research on Cancer. Available: [accessed 8 April 2005].
    1. IARC In press. Formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. IARC Monogr Eval Carcinog Risks Hum 88.
    1. Iverson OH. Formaldehyde and skin carcinogenesis. Environ Int. 1986;12:541–544.
    1. Jeffcoat AR, Chasalow F, Feldman DB. 1983. Disposition of [14C] formaldehyde after topical exposure to rats, guinea pigs, and monkeys. In: Formaldehyde Toxicity (Gibson JE, ed). Washington, DC:Hemisphere Publishing Corporation, 38–50.
    1. Kamata E, Nakadate E, Uchida O, Ogawa Y, Suzuki S, Kaneko T, et al. Results of a 28-month chronic inhalation toxicity study of formaldehyde in male Fisher-344 rats. J Toxicol Sci. 1997;22:239–254.
    1. Kerns WD, Pavkov KL, Donofrio DJ, Gralla EJ, Swenberg JA. Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res. 1983;43:4382–4392.
    1. Kitaeva LV, Kitaev EM, Pimenova MN. The cytopathic and cytogenetic sequelae of chronic inhalational exposure to formaldehyde on female germ cells and bone marrow cells in rats [in Russian] Tsitologiia. 1990;32(12):1212–1216.
    1. Levine RJ, Andjelkovich DA, Shaw LK. The mortality of Ontario undertakers and a review of formaldehyde-related mortality studies. J Occup Med. 1984;26:740–746.
    1. Logue JN, Barrick MK, Jessup GL., Jr Mortality of radiologists and pathologists in the radiation registry of physicians. J Occup Med. 1986;28:91–99.
    1. Luce D, Leclerc A, Begin D, Demers PA, Gerin M, Orlowski E, et al. Sinonasal cancer and occupational exposures: a pooled analysis of 12 case-control studies. Cancer Causes Control. 2002;13:147–157.
    1. Monticello TM, Swenberg JA, Gross EA, Leiniger JR, Kimbell JS, Seilkop S, et al. Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells. Cancer Res. 1996;56:1012–1022.
    1. Morgan KT, Jiang X-Z, Starr TB, Kerns WD. More precise localization of nasal tumors associated with chronic exposure of F-344 rats to formaldehyde gas. Toxicol Appl Pharmacol. 1986;82:264–271.
    1. NTP 2000. Toxicology and Carcinogenesis Studies of 2-Butoxyethanol (CAS No. 111-76-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). TR 484. Research Triangle Park, NC:National Toxicology Program.
    1. NTP 2003. Toxicology and Carcinogenesis Studies of Propylene Glycol Mono-t-butyl Ether (CAS No. 57018-52-7) in F344/N Rats and B6C3F1 Mice and a Toxicology Study of Propylene Glycol Mono-t-butyl Ether in Male NBR Rats (Inhalation Studies). TR 515. Research Triangle Park, NC:National Toxicology Program.
    1. Olsen JH, Asnaes S. Formaldehyde and the risk of squamous cell carcinoma of the sinonasal cavities. Br J Ind Med. 1986;43:769–774.
    1. Olsen JH, Jensen SP, Hink M, Faurbo K, Breum NO, Jensen OM. Occupational formaldehyde exposure and increased nasal cancer risk in man. Int J Cancer. 1984;34:639–644.
    1. Pinkerton L, Hein M, Stayner L. Mortality among a cohort of garment workers exposed to formaldehyde: an update. Occup Environ Med. 2004;61:193–200.
    1. Rietbrock N. Formaldehyde oxidation in the rat [in German] Naunyn-Schmiedeberg’s Arch Exp Pathol Phamakol. 1965;251:189–190.
    1. Roush GC, Walrath J, Stayner LT, Kaplan SA, Flannery JT, Blair A. Nasopharyngeal cancer, sinonasal cancer, and occupations related to formaldehyde: a case–control study. J Natl Cancer Inst. 1987;79:1221–1224.
    1. Sellakumar AR, Snyder CA, Solomon JJ, Albert RE. Carcinogenicity of formaldehyde and hydrogen chloride in rats. Toxicol Appl Pharmacol. 1985;81:401–406.
    1. Shaham J, Bomstein Y, Gurvich R, Rashkovsky M, Kaufman Z. DNA–protein crosslinks and p53 protein expression in relation to occupational exposure to formaldehyde. Occup Environ Med. 2003;60:403–409.
    1. Shaham J, Bomstein Y, Meltzer A, Kaufman Z, Palma E, Ribak J. DNA–protein crosslinks, a biomarker of exposure to formaldehyde—in vitro and in vivo studies. Carcinogenesis. 1996;17(1):121–125.
    1. Soffritti M, Belpoggi F, Lambertini L, Lauriola M, Padovani M, Maltoni C. Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats. Ann NY Acad Sci. 2002;982:87–105.
    1. Soffritti M, Maltoni C, Maffei F, Biagi R. Formaldehyde: an experimental multipotential carcinogen. Toxicol Ind Health. 1989;5:699–730.
    1. Stroup NE, Blair A, Erikson GE. Brain cancer and other causes of death in anatomists. J Natl Cancer Inst. 1986;77:1217–1224.
    1. Takahashi M, Hasegawa R, Furukawa F, Toyoda K, Sato H, Hayashi Y. Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric carcino-genesis in rats after initiation with N-methyl-N′-nitro-N-nitrosoguanidine. Jpn J Cancer Res. 1986;77:118–124.
    1. Til HP, Woutersen RA, Feron VJ, Hollanders VHM, Falke HE. Two-year drinking-water study of formaldehyde in rats. Food Chem Toxicol. 1989;27:77–87.
    1. Vaughan TL, Stewart PA, Teschke K, Lynch CF, Swanson GM, Lyon JL, et al. Occupational exposure to formaldehyde and wood dust and nasopharyngeal carcinoma. Occup Environ Med. 2000;57:376–384.
    1. Vaughan TL, Strader C, Davis S, Daling JR. Formaldehyde and cancers of the pharynx, sinus and nasal cavity. I. Occupational exposures. Int J Cancer. 1986;38:677–683.
    1. Walrath J, Fraumeni JF., Jr Mortality patterns among embalmers. Int J Cancer. 1983;31:407–411.
    1. Walrath J, Fraumeni JF., Jr Cancer and other causes of death among embalmers. Cancer Res. 1984;44:4638–4641.
    1. West S, Hildesheim A, Dosemeci M. Non-viral risk factors for nasopharyngeal carcinoma in the Philippines: results from a case–control study. Int J Cancer. 1993;55:722–727.
    1. WHO 2005. Declaration of Interests for WHO Experts. Geneva:World Health Organization. Available: [accessed 8 April 2005].
    1. Woutersen RA, van Garderen-Hoetmer A, Bruijntjes JP, Zwart A, Feron VJ. Nasal tumours in rats after severe injury to the nasal mucosa and prolonged exposure to 10 ppm formaldehyde. J Appl Toxicol. 1989;9:39–46.

Source: PubMed

3
Sottoscrivi