Abstract
The Federal Panel on Formaldehyde concluded that definitive experiments exist which demonstrate the mutagenicity and carcinogenicity of formaldehyde under laboratory conditions. Formaldehyde induces both gene mutations and chromosomal aberrations in a variety of test systems. Inhalation of formaldehyde causes cancer of the nose in rats. The concentrations of formaldehyde in inhaled air that caused nasal cancer in Fisher 344 rats are within the same order of magnitude as those to which humans may be exposed. The data presently available do not permit a direct assessment of the carcinogenicity of formaldehyde to man. Epidemiologic studies on exposed human populations are in progress and may further clarify the situation. Other experimental and human studies on toxic effects such as teratogenicity and reproductive disorders are as yet inadequate for a health risk assessment. The CIIT 24 month study on animal carcinogenicity has not yet been completely evaluated. Additional data are expected on the effects of prolonged exposure to lower doses of formaldehyde and on the possible carcinogenicity of formaldehyde in the mouse. The panel recommends that, for a comprehensive health risk assessment, further experiments be conducted on the effects of other modes of exposure (ingestion and skin penetration), the effects in humans, and on the pharmacokinetics of formaldehyde in man and animals and the possible role for formaldehyde in reproductive and chronic respiratory disorders. It is the conclusion of the panel that formaldehyde should be presumed to pose a carcinogenic risk to humans.
Full text
PDF





























Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- AEBI H., ROGGEN G. Enzymatische Demethylierung von Dimethyl-14C-aminoantipyrin. Pharm Acta Helv. 1958 Aug-Oct;33(8-10):413–428. [PubMed] [Google Scholar]
- Argyris T. S. Tumor promotion by abrasion induced epidermal hyperplasia in the skin of mice. J Invest Dermatol. 1980 Oct;75(4):360–362. doi: 10.1111/1523-1747.ep12531153. [DOI] [PubMed] [Google Scholar]
- Auerbach C., Moutschen-Dahmen M., Moutschen J. Genetic and cytogenetical effects of formaldehyde and related compounds. Mutat Res. 1977;39(3-4):317–361. doi: 10.1016/0165-1110(77)90011-2. [DOI] [PubMed] [Google Scholar]
- Auerbach C. The Mutagenic Mode of Action of Formalin. Science. 1949 Oct 21;110(2860):419–420. doi: 10.1126/science.110.2860.419. [DOI] [PubMed] [Google Scholar]
- BERG P. Synthesis of labile methyl groups by guinea pig tissue in vitro. J Biol Chem. 1951 May;190(1):31–38. [PubMed] [Google Scholar]
- BOUTWELL R. K. SOME BIOLOGICAL ASPECTS OF SKIN CARCINOGENISIS. Prog Exp Tumor Res. 1964;4:207–250. doi: 10.1159/000385978. [DOI] [PubMed] [Google Scholar]
- BRENDEL R. UNTERSUCHUNGEN AN RATTEN ZUR VERTRAEGLICHKEIT VON HEXAMETHYLENTETRAMIN. Arzneimittelforschung. 1964 Jan;14:51–53. [PubMed] [Google Scholar]
- Bertram J. S., Heidelberger C. Cell cycle dependency of oncogenic transformation induced by N-methyl-N'-nitro-N-nitrosoquanidine in culture. Cancer Res. 1974 Mar;34(3):526–537. [PubMed] [Google Scholar]
- Boutwell R. K. The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol. 1974 Jan;2(4):419–443. doi: 10.3109/10408447309025704. [DOI] [PubMed] [Google Scholar]
- Bross I. D., Viadana E., Hooten L. Occupational cancer in men exposed to dust and other environmental hazards. Arch Environ Health. 1978 Nov-Dec;33(6):300–307. doi: 10.1080/00039896.1978.10667352. [DOI] [PubMed] [Google Scholar]
- Chanet R., Izard C., Moustacchi E. Genetic effects of formaldehyde in yeast. II. Influence of ploidly and of mutations affecting radiosensitivity on its lethal effect. Mutat Res. 1976 Apr;35(1):29–38. doi: 10.1016/0027-5107(76)90166-4. [DOI] [PubMed] [Google Scholar]
- Cohen A. Réponse des surrénales du faetus de rat à une agression par le formol à différents stades du développement. C R Acad Sci Hebd Seances Acad Sci D. 1972 Aug 21;275(8):921–924. [PubMed] [Google Scholar]
- Conner E. A., Blake D. A., Parmley T. H., Burnett L. S., King T. M. Efficacy of various locally applied chemicals as contragestational agents in rats. Contraception. 1976 May;13(5):571–582. doi: 10.1016/0010-7824(76)90013-5. [DOI] [PubMed] [Google Scholar]
- Cooper E. R., Jones A. R., Jackson H. Effects of alpha-chlorohydrin and related compounds on the reproductive organs and fertility of the male rat. J Reprod Fertil. 1974 Jun;38(2):379–386. doi: 10.1530/jrf.0.0380379. [DOI] [PubMed] [Google Scholar]
- Cooper P. Genetic effects of formaldehyde. Food Cosmet Toxicol. 1979 Jun;17(3):300–301. doi: 10.1016/0015-6264(79)90304-3. [DOI] [PubMed] [Google Scholar]
- Crump K. S., Guess H. A., Deal K. L. Confidence intervals and test of hypotheses concerning dose response relations inferred from animal carcinogenicity data. Biometrics. 1977 Sep;33(3):437–451. [PubMed] [Google Scholar]
- DICKEY F. H., CLELAND G. H., LOTZ C. The role of organic peroxides in the induction of mutations. Proc Natl Acad Sci U S A. 1949 Oct;35(10):581–586. doi: 10.1073/pnas.35.10.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Decoufle P. Cancer risks associated with employment in the leather and leather products industry. Arch Environ Health. 1979 Jan-Feb;34(1):33–37. doi: 10.1080/00039896.1979.10667364. [DOI] [PubMed] [Google Scholar]
- Della Porta G., Cabral J. R., Parmiani G. Studio della tosicità transplacentare e di cancerogenesi in ratti trattati con esametilentetramina. Tumori. 1970 Nov-Dec;56(6):325–334. doi: 10.1177/030089167005600602. [DOI] [PubMed] [Google Scholar]
- Della Porta G., Colnaghi M. I., Parmiani G. Non-carcinogenicity of hexamethylenetetramine in mice and rats. Food Cosmet Toxicol. 1968 Dec;6(6):707–715. doi: 10.1016/0015-6264(68)90235-6. [DOI] [PubMed] [Google Scholar]
- Egle J. L., Jr Retention of inhaled formaldehyde, propionaldehyde, and acrolein in the dog. Arch Environ Health. 1972 Aug;25(2):119–124. doi: 10.1080/00039896.1972.10666147. [DOI] [PubMed] [Google Scholar]
- Einbrodt H. J., Prajsnar D., Erpenbeck J. Der Formaldehyd- und Ameisensäurespiegel im Blut und Urin beim Menschen nach Formaldehydexposition. Zentralbl Arbeitsmed Arbeitsschutz Prophyl. 1976 Aug;26(8):154–158. [PubMed] [Google Scholar]
- Engel H. O., Calnan C. D. Resin dermatitis in a car factory. Br J Ind Med. 1966 Jan;23(1):62–66. doi: 10.1136/oem.23.1.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Epstein S. S., Arnold E., Andrea J., Bass W., Bishop Y. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol Appl Pharmacol. 1972 Oct;23(2):288–325. doi: 10.1016/0041-008x(72)90192-5. [DOI] [PubMed] [Google Scholar]
- Epstein S. S., Arnold E., Andrea J., Bass W., Bishop Y. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol Appl Pharmacol. 1972 Oct;23(2):288–325. doi: 10.1016/0041-008x(72)90192-5. [DOI] [PubMed] [Google Scholar]
- Gamble J. F., McMichael A. J., Williams T., Battigelli M. Respiratory function and symptoms: an environmental-epidemiological study of rubber workers exposed to a phenolformaldehyde type resin. Am Ind Hyg Assoc J. 1976 Sep;37(9):499–513. doi: 10.1080/0002889768507508. [DOI] [PubMed] [Google Scholar]
- Garry V. F., Oatman L., Pleus R., Gray D. Formaldehyde in the home--some environmental disease perspectives. Minn Med. 1980 Feb;63(2):107–111. [PubMed] [Google Scholar]
- Gescher A., Hickman J. A., Stevens M. F. Oxidative metabolism of some N-methyl containing xenobiotics can lead to stable progenitors of formaldehyde. Biochem Pharmacol. 1979 Nov 1;28(21):3235–3238. doi: 10.1016/0006-2952(79)90069-8. [DOI] [PubMed] [Google Scholar]
- Goodman J. I., Tephly T. R. A comparison of rat and human liver formaldehyde dehydrogenase. Biochim Biophys Acta. 1971 Dec 21;252(3):489–505. doi: 10.1016/0304-4165(71)90152-8. [DOI] [PubMed] [Google Scholar]
- Guseva V. A. Izuchenie gonadotropnogo éffekta u krys-samtsov pod vozdeistviem formal'edgida pri odnovremennom ego postuplenii s vozdukhom i vodoi. Gig Sanit. 1972 Oct;37(10):102–103. [PubMed] [Google Scholar]
- HARRIS D. K. Health problems in the manufacture and use of plastics. Br J Ind Med. 1953 Oct;10(4):255–268. doi: 10.1136/oem.10.4.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HILL A. B. THE ENVIRONMENT AND DISEASE: ASSOCIATION OR CAUSATION? Proc R Soc Med. 1965 May;58:295–300. doi: 10.1177/003591576505800503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HORTON A. W., TYE R., STEMMER K. L. Experimental carcinogenesis of the lung. Inhalation of gaseous formaldehyde or an aerosol of coal tar by C3H mice. J Natl Cancer Inst. 1963 Jan;30:31–43. [PubMed] [Google Scholar]
- Hendrick D. J., Lane D. J. Occupational formalin asthma. Br J Ind Med. 1977 Feb;34(1):11–18. doi: 10.1136/oem.34.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hennings H., Boutwell R. K. Studies on the mechanism of skin tumor promotion. Cancer Res. 1970 Feb;30(2):312–320. [PubMed] [Google Scholar]
- Hurni H., Ohder H. Reproduction study with formaldehyde and hexamethylenetetramine in beagle dogs. Food Cosmet Toxicol. 1973 Jun;11(3):459–462. doi: 10.1016/0015-6264(73)90010-2. [DOI] [PubMed] [Google Scholar]
- Ishchenko V. N., Pushkina I. K. Otsenka uslovii truda v proizvodstve i pri pererabotke fenol-formal'degidnykh smol. Gig Sanit. 1978 Nov;(11):98–100. [PubMed] [Google Scholar]
- JENSEN K. A., KIRK I., KØLMARK G., WESTERGAARD M. Chemically induced mutations in Neurospora. Cold Spring Harb Symp Quant Biol. 1951;16:245–261. doi: 10.1101/sqb.1951.016.01.020. [DOI] [PubMed] [Google Scholar]
- Jones A. R., Davies P., Edwards K., Jackson H. Antifertility effects and metabolism of alpha and epi-chlorhydrins in the rat. Nature. 1969 Oct 4;224(5214):83–83. doi: 10.1038/224083a0. [DOI] [PubMed] [Google Scholar]
- Kakunaga T. The role of cell division in the malignant transformation of mouse cells treated with 3-methylcholanthrene. Cancer Res. 1975 Jul;35(7):1637–1642. [PubMed] [Google Scholar]
- Kerfoot E. J., Mooney T. F. Formaldehyde and paraformaldehyde study in funeral homes. Am Ind Hyg Assoc J. 1975 Jul;36(7):533–537. doi: 10.1080/0002889758507286. [DOI] [PubMed] [Google Scholar]
- Kuschner M., Laskin S., Drew R. T., Cappiello V., Nelson N. Inhalation carcinogenicity of alpha halo ethers. III. Lifetime and limited period inhalation studies with bis(chloromethyl)ether at 0.1 ppm. Arch Environ Health. 1975 Feb;30(2):73–77. doi: 10.1080/00039896.1975.10666646. [DOI] [PubMed] [Google Scholar]
- Laduron P., Leysen J. Enzymatic formaldehyde production from 5-methyltetrahydrofolic acid: prior step to alkaloid formation. Biochem Pharmacol. 1975 Apr 15;24(8):929–932. doi: 10.1016/0006-2952(75)90171-9. [DOI] [PubMed] [Google Scholar]
- Loomis T. A. Formaldehyde toxicity. Arch Pathol Lab Med. 1979 Jul;103(7):321–324. [PubMed] [Google Scholar]
- MALLING H., MILTENBURGER H., WESTERGAARD M., ZIMMER K. G. Differential response of a double mutant--adenineless, inositolless-in neurospora crassa to combined treatment by ultra-violet radiation and chemicals. Int J Radiat Biol Relat Stud Phys Chem Med. 1959 Oct;1:328–343. doi: 10.1080/09553005914550451. [DOI] [PubMed] [Google Scholar]
- MALORNY G., RIETBROCK N., SCHNEIDER M. DIE OXYDATION DES FORMALDEHYDS ZU AMEISENSAEURE IM BLUT, EIN BEITRAG ZUM STOFFWECHSEL DES FORMALDEHYDS. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1965 Apr 29;250:419–436. doi: 10.1007/BF00246893. [DOI] [PubMed] [Google Scholar]
- Magaña-Schwencke N., Ekert B., Moustacchi E. Biochemical analysis of damage induced in yeast by formaldehyde. I. Induction of single-strand breaks in DNA and their repair. Mutat Res. 1978 May;50(2):181–193. doi: 10.1016/0027-5107(78)90023-4. [DOI] [PubMed] [Google Scholar]
- Marks T. A., Worthy W. C., Staples R. E. Influence of formaldehyde and Sonacide (potentiated acid glutaraldehyde) on embryo and fetal development in mice. Teratology. 1980 Aug;22(1):51–58. doi: 10.1002/tera.1420220108. [DOI] [PubMed] [Google Scholar]
- Martin C. N., McDermid A. C., Garner R. C. Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res. 1978 Aug;38(8):2621–2627. [PubMed] [Google Scholar]
- McMartin K. E., Martin-Amat G., Makar A. B., Tephly T. R. Methanol poisoning. V. Role of formate metabolism in the monkey. J Pharmacol Exp Ther. 1977 Jun;201(3):564–572. [PubMed] [Google Scholar]
- McMartin K. E., Martin-Amat G., Noker P. E., Tephly T. R. Lack of a role for formaldehyde in methanol poisoning in the monkey. Biochem Pharmacol. 1979 Mar 1;28(5):645–649. doi: 10.1016/0006-2952(79)90149-7. [DOI] [PubMed] [Google Scholar]
- Moss E., Lee W. R. Occurrence of oral and pharyngeal cancers in textile workers. Br J Ind Med. 1974 Jul;31(3):224–232. doi: 10.1136/oem.31.3.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller P., Raabe G., Schumann D. Leukoplakia induced by repeated deposition of formalin in rabbit oral mucosa. Long-term experiments with a new "oral tank". Exp Pathol (Jena) 1978;16(1-6):36–42. doi: 10.103/00006450-03000-00006. [DOI] [PubMed] [Google Scholar]
- NEELY W. B. THE METABOLIC FATE OF FORMALDEHYDE-14-C INTRAPERITONEALLY ADMINISTERED TO THE RAT. Biochem Pharmacol. 1964 Aug;13:1137–1142. doi: 10.1016/0006-2952(64)90114-5. [DOI] [PubMed] [Google Scholar]
- Natvig H., Andersen J., Rasmussen E. W. A contribution to the toxicological evaluation of hexamethylenetetramine. Food Cosmet Toxicol. 1971 Aug;9(4):491–500. doi: 10.1016/0015-6264(71)90079-4. [DOI] [PubMed] [Google Scholar]
- Nishioka H. Lethal and mutagenic action of formaldehyde in Hcr + and Hcr - strains of Escherichia coli. Mutat Res. 1973 Feb;17(2):261–265. doi: 10.1016/0027-5107(73)90175-9. [DOI] [PubMed] [Google Scholar]
- Obe G., Beek B. Mutagenic activity of aldehydes. Drug Alcohol Depend. 1979 Jan-Mar;4(1-2):91–94. doi: 10.1016/0376-8716(79)90044-9. [DOI] [PubMed] [Google Scholar]
- Orringer E. P., Mattern W. D. Formaldehyde-induced hemolysis during chronic hemodialysis. N Engl J Med. 1976 Jun 24;294(26):1416–1420. doi: 10.1056/NEJM197606242942602. [DOI] [PubMed] [Google Scholar]
- Palese M., Tephly T. R. Metabolism of formate in the rat. J Toxicol Environ Health. 1975 Sep;1(1):13–24. doi: 10.1080/15287397509529305. [DOI] [PubMed] [Google Scholar]
- Palkovits M., Mitro A. Morphological changes in the hypothalamo-pituitary-adrenal system during early postnatal period in rats. Gen Comp Endocrinol. 1968 Apr;10(2):253–262. doi: 10.1016/0016-6480(68)90033-6. [DOI] [PubMed] [Google Scholar]
- Plunkett E. R., Barbela T. Are embalmer's at risk? Am Ind Hyg Assoc J. 1977 Jan;38(1):61–62. doi: 10.1080/0002889778507913. [DOI] [PubMed] [Google Scholar]
- Poverenny A. M., Siomin Y. A., Saenko A. S., Sinzinis B. I. Possible mechanisms of lethal and mutagenic action of formaldehyde. Mutat Res. 1975 Jan;27(1):123–126. doi: 10.1016/0027-5107(75)90280-8. [DOI] [PubMed] [Google Scholar]
- Pruett J. J., Nevo Z., Scheuenstuhl H., Michaeli D. The incorporation and localization of aldehydes (highly reactive cigarette smoke components) into cellular fractions of cultured human lung cells. Arch Environ Health. 1980 Jan-Feb;35(1):15–20. doi: 10.1080/00039896.1980.10667456. [DOI] [PubMed] [Google Scholar]
- Rietbrock N. Kinetik und Wege des Methanolumsatzes. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1969;263(1):88–105. [PubMed] [Google Scholar]
- STRITTMATTER P., BALL E. G. Formaldehyde dehydrogenase, a glutathionedependent enzyme system. J Biol Chem. 1955 Mar;213(1):445–461. [PubMed] [Google Scholar]
- Sanotskii I. V., Fomenko V. N., Sheveleva G. A., Sal'nikova L. S., Nakoriakova M. V. Izuchenie vliianiia beremennosti na chuvstvitel'nost' zhivotnykh k khimicheskim agentam. Gig Tr Prof Zabol. 1976 Jan;(1):25–28. [PubMed] [Google Scholar]
- Schoenberg J. B., Mitchell C. A. Airway disease caused by phenolic (phenol-formaldehyde) resin exposure. Arch Environ Health. 1975 Dec;30(12):574–577. doi: 10.1080/00039896.1975.10666782. [DOI] [PubMed] [Google Scholar]
- Schuck E. A., Stephens E. R., Middleton J. T. Eye irritation response at low concentrations of irritants. Arch Environ Health. 1966 Nov;13(5):570–575. doi: 10.1080/00039896.1966.10664620. [DOI] [PubMed] [Google Scholar]
- Shumilina A. V. Menstrual'naia i detorodnaia funktsii rabotnits, imeiushchikh po usloviiam proizvodstva kontakt s formal 'degidom. Gig Tr Prof Zabol. 1975 Dec;(12):18–21. [PubMed] [Google Scholar]
- Shumilina A. V. Menstrual'naia i detorodnaia funktsii rabotnits, imeiushchikh po usloviiam proizvodstva kontakt s formal 'degidom. Gig Tr Prof Zabol. 1975 Dec;(12):18–21. [PubMed] [Google Scholar]
- Slaga T. J., Bowden G. T., Boutwell R. K. Acetic acid, a potent stimulator of mouse epidermal macromolecular synthesis and hyperplasia but with weak tumor-promoting ability. J Natl Cancer Inst. 1975 Oct;55(4):983–987. doi: 10.1093/jnci/55.4.983. [DOI] [PubMed] [Google Scholar]
- Swenberg J. A., Kerns W. D., Mitchell R. I., Gralla E. J., Pavkov K. L. Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. Cancer Res. 1980 Sep;40(9):3398–3402. [PubMed] [Google Scholar]
- Thorndike J., Beck W. S. Production of formaldehyde from N5-methyltetrahydrofolate by normal and leukemic leukocytes. Cancer Res. 1977 Apr;37(4):1125–1132. [PubMed] [Google Scholar]
- Uotila L., Koivusalo M. Formaldehyde dehydrogenase from human liver. Purification, properties, and evidence for the formation of glutathione thiol esters by the enzyme. J Biol Chem. 1974 Dec 10;249(23):7653–7663. [PubMed] [Google Scholar]
- WATANABE F., MATSUNAGA T., SOEJIMA T., IWATA Y. [Study on the carcinogenicity of aldehyde. I. Experimentally produced rat sarcomas by repeated injections of aqueous solution of formaldehyde]. Gan. 1954 Sep;45(2-3):451–452. [PubMed] [Google Scholar]
- WATANABE F., SUGIMOTO S. [Study on the carcinogenicity of aldehyde. II. Seven cases of transplantable sarcomas of rats appearing in the areas of repeated subcutaneous injections of urotropin]. Gan. 1955 Sep;46(2-3):365–367. [PubMed] [Google Scholar]
- Waydhas C., Weigl K., Sies H. The disposition of formaldehyde and formate arising from drug N-demethylations dependent on cytochrome P-450 in hepatocytes and in perfused rat liver. Eur J Biochem. 1978 Aug 15;89(1):143–150. doi: 10.1111/j.1432-1033.1978.tb20906.x. [DOI] [PubMed] [Google Scholar]
- Weber-Tschopp A., Fischer T., Grandjean E. Reizwirkungen des Formaldehyds (HCHO) auf den Menschen. Int Arch Occup Environ Health. 1977 Sep 15;39(4):207–218. doi: 10.1007/BF00409367. [DOI] [PubMed] [Google Scholar]
- den Engelse L., Gebbink M., Emmelot P. Studies on lung tumours. III. Oxidative metabolism of dimethylnitrosamine by rodent and human lung tissue. Chem Biol Interact. 1975 Dec;11(6):535–544. doi: 10.1016/0009-2797(75)90029-0. [DOI] [PubMed] [Google Scholar]
