Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1995 Jun;103(6):568–573. doi: 10.1289/ehp.95103568

Ethylenebisdithiocarbamates and ethylenethiourea: possible human health hazards.

P Houeto 1, G Bindoula 1, J R Hoffman 1
PMCID: PMC1519130  PMID: 7556009

Abstract

Humans are exposed to ethylenebisdithiocarbamates (EBDCs) from environmental sources. Exposure to EBDCs is chronic for workers in a variety of industries, where EBDCs are used for their properties as slimicides, vulcanization accelerators, antioxidants, and scavengers in waste-water treatment. EBDCs, and particularly the EBDC metabolite ethylenethiourea, have clearly defined, important toxic effects in various animal species, and there is reason to suspect they are carcinogenic in humans. In the absence of definitive information regarding human risk, further studies need to be done. In the interim, regular surveillance of workers with high levels of exposure to EBDCs, with specific attention to markers of thyroid and hepatic pathology, should be considered.

Full text

PDF
569

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams R. M., Manchester R. D. Allergic contact dermatitis to Maneb in a housewife. Contact Dermatitis. 1982 Jul;8(4):271–271. doi: 10.1111/j.1600-0536.1982.tb04217.x. [DOI] [PubMed] [Google Scholar]
  2. Allen J. R., Van Miller J. P., Seymour J. L. Absorption, tissue distribution and excretion of 14C ethylenethiourea by the rhesus monkey and rat. Res Commun Chem Pathol Pharmacol. 1978 Apr;20(1):109–115. [PubMed] [Google Scholar]
  3. Babini G. Su un caso di eritrodermia da ditiocarbammato di zinco. Arch Ital Dermatol Venereol Sessuol. 1966;34(3):230–238. [PubMed] [Google Scholar]
  4. Blazquez C. H. Residue determination of ethylenethiourea (2-imidazolidinethione) from tomato foliage, soil, and water. J Agric Food Chem. 1973 May-Jun;21(3):330–332. doi: 10.1021/jf60187a051. [DOI] [PubMed] [Google Scholar]
  5. Bruze M., Fregert S. Allergic contact dermatitis from ethylene thiourea. Contact Dermatitis. 1983 May;9(3):208–212. doi: 10.1111/j.1600-0536.1983.tb04360.x. [DOI] [PubMed] [Google Scholar]
  6. Burry J. N. Contact dermatitis from agricultural fungicide in South Australia. Contact Dermatitis. 1976 Oct;2(5):289–289. doi: 10.1111/j.1600-0536.1976.tb03054.x. [DOI] [PubMed] [Google Scholar]
  7. Camoni I., Cicero A. M., Di Muccio A., Dommarco R. Verifica della escrezione urinaria di etilentiourea (ETU) in ratti trattati con zineb. Med Lav. 1984 May-Jun;75(3):207–214. [PubMed] [Google Scholar]
  8. Canossa E., Angiuli G., Garasto G., Buzzoni A., De Rosa E. Indicatori di dose in agricoltori esposti a mancozeb. Med Lav. 1993 Jan-Feb;84(1):42–50. [PubMed] [Google Scholar]
  9. Capen C. C., Martin S. L. The effects of xenobiotics on the structure and function of thyroid follicular and C-cells. Toxicol Pathol. 1989;17(2):266–293. doi: 10.1177/019262338901700205. [DOI] [PubMed] [Google Scholar]
  10. Chhabra R. S., Eustis S., Haseman J. K., Kurtz P. J., Carlton B. D. Comparative carcinogenicity of ethylene thiourea with or without perinatal exposure in rats and mice. Fundam Appl Toxicol. 1992 Apr;18(3):405–417. doi: 10.1016/0272-0590(92)90139-9. [DOI] [PubMed] [Google Scholar]
  11. Chvapil M., Ludwig J. C., Sipes I. G., Misiorowski R. L. Inhibition of NADPH oxidation and related drug oxidation in liver microsomes by zinc. Biochem Pharmacol. 1976 Aug 1;25(15):1787–1791. doi: 10.1016/0006-2952(76)90417-2. [DOI] [PubMed] [Google Scholar]
  12. Crippa M., Misquith L., Lonati A., Pasolini G. Dyshidrotic eczema and sensitization to dithiocarbamates in a florist. Contact Dermatitis. 1990 Sep;23(3):203–204. doi: 10.1111/j.1600-0536.1990.tb04796.x. [DOI] [PubMed] [Google Scholar]
  13. Cruickshank P. A., Jarrow H. C. Ethylenethiourea degradation. J Agric Food Chem. 1973 May-Jun;21(3):333–335. doi: 10.1021/jf60187a048. [DOI] [PubMed] [Google Scholar]
  14. Ferraz H. B., Bertolucci P. H., Pereira J. S., Lima J. G., Andrade L. A. Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication. Neurology. 1988 Apr;38(4):550–553. doi: 10.1212/wnl.38.4.550. [DOI] [PubMed] [Google Scholar]
  15. Fishbein L. Environmental health aspects of fungicides. I. Dithiocarbamtes. J Toxicol Environ Health. 1976 May;1(5):713–735. doi: 10.1080/15287397609529371. [DOI] [PubMed] [Google Scholar]
  16. Frakes R. A. Drinking water guideline for ethylene thiourea, a metabolite of ethylene bisdithiocarbamate fungicides. Regul Toxicol Pharmacol. 1988 Jun;8(2):207–218. doi: 10.1016/0273-2300(88)90029-3. [DOI] [PubMed] [Google Scholar]
  17. Gak J. C., Graillot C., Turhaut R. Différence de sensibilité du hamster et du rat vis-à-vis des effets de l'administration à long terme de l'éthylène thiourée. Eur J Toxicol Environ Hyg. 1976 Sep-Oct;9(5):303–312. [PubMed] [Google Scholar]
  18. Haines L. D., Adler I. L. Gas chromatographic determination of ethylene thiourea residues. J Assoc Off Anal Chem. 1973 Mar;56(2):333–337. [PubMed] [Google Scholar]
  19. Hedenstedt A., Rannug U., Ramel C., Wachtmeister C. A. Mutagenicity and metabolism studies on 12 thiuram and dithiocarbamate compounds used as accelerators in the Swedish rubber industry. Mutat Res. 1979 Dec;68(4):313–325. doi: 10.1016/0165-1218(79)90164-2. [DOI] [PubMed] [Google Scholar]
  20. Hill R. N., Erdreich L. S., Paynter O. E., Roberts P. A., Rosenthal S. L., Wilkinson C. F. Thyroid follicular cell carcinogenesis. Fundam Appl Toxicol. 1989 May;12(4):629–697. [PubMed] [Google Scholar]
  21. Hui Q. Y., Armstrong C., Laver G., Iverson F. Monooxygenase-mediated metabolism and binding of ethylene thiourea to mouse liver microsomal protein. Toxicol Lett. 1988 Jun;41(3):231–237. doi: 10.1016/0378-4274(88)90059-8. [DOI] [PubMed] [Google Scholar]
  22. Innes J. R., Ulland B. M., Valerio M. G., Petrucelli L., Fishbein L., Hart E. R., Pallotta A. J., Bates R. R., Falk H. L., Gart J. J. Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a preliminary note. J Natl Cancer Inst. 1969 Jun;42(6):1101–1114. [PubMed] [Google Scholar]
  23. Israeli R., Sculsky M., Tiberin P. Acute intoxication due to exposure to maneb and zineb. A case with behavioral and central nervous system changes. Scand J Work Environ Health. 1983 Feb;9(1):47–51. doi: 10.5271/sjweh.2443. [DOI] [PubMed] [Google Scholar]
  24. Ivanova-chemishanska L., Petrova-vergieva T., Mirkova E. Embriotoksichno i teratogenno deistvie na niakoi pestitsidi. Eksp Med Morfol. 1975;14(1):29–33. [PubMed] [Google Scholar]
  25. Iverson F., Khera K. S., Hierlihy S. L. In vivo and in vitro metabolism of ethylenethiourea in the rat and the cat. Toxicol Appl Pharmacol. 1980 Jan;52(1):16–21. doi: 10.1016/0041-008x(80)90242-2. [DOI] [PubMed] [Google Scholar]
  26. Jordan L. W., Neal R. A. Examination of the in vivo metabolism of maneb and zineb to ethylenethiourea (ETU) in mice. Bull Environ Contam Toxicol. 1979 May;22(1-2):271–277. doi: 10.1007/BF02026941. [DOI] [PubMed] [Google Scholar]
  27. Kato Y., Odanaka Y., Teramoto S., Matano O. Metabolic fate of ethylenethiourea in pregnant rats. Bull Environ Contam Toxicol. 1976 Nov;16(5):546–555. doi: 10.1007/BF01685362. [DOI] [PubMed] [Google Scholar]
  28. Khera K. S., Iverson F. Toxicity of ethylenethiourea in pregnant cats. Teratology. 1978 Dec;18(3):311–313. doi: 10.1002/tera.1420180304. [DOI] [PubMed] [Google Scholar]
  29. Kleibl K., Rácková M. Cutaneous allergic reactions to dithiocarbamates. Contact Dermatitis. 1980 Aug;6(5):348–349. doi: 10.1111/j.1600-0536.1980.tb04963.x. [DOI] [PubMed] [Google Scholar]
  30. Koizumi A., Shiojima S., Omiya M., Nakano S., Sato N., Ikeda M. Acute renal failure and maneb (manganous ethylenebis[dithiocarbamate]) exposure. JAMA. 1979 Dec 7;242(23):2583–2585. [PubMed] [Google Scholar]
  31. Kurttio P., Savolainen K. Ethylenethiourea in air and in urine as an indicator of exposure to ethylenebisdithiocarbamate fungicides. Scand J Work Environ Health. 1990 Jun;16(3):203–207. doi: 10.5271/sjweh.1793. [DOI] [PubMed] [Google Scholar]
  32. Lentza-Rizos C. Ethylenethiourea (ETU) in relation to use of ethylenebisdithiocarbamate (EBDC) fungicides. Rev Environ Contam Toxicol. 1990;115:1–37. doi: 10.1007/978-1-4612-3416-6_1. [DOI] [PubMed] [Google Scholar]
  33. Lewerenz H. J., Plass R. Contrasting effects of ethylenethiourea on hepatic monooxygenases in rats and mice. Arch Toxicol. 1984 Dec;56(2):92–95. doi: 10.1007/BF00349078. [DOI] [PubMed] [Google Scholar]
  34. Lewerenz H. J., Plass R. Effect of ethylenethiourea on hepatic microsomal enzymes in the rat. Arch Toxicol Suppl. 1978;(1):189–192. doi: 10.1007/978-3-642-66896-8_28. [DOI] [PubMed] [Google Scholar]
  35. Lisi P., Caraffini S. Pellagroid dermatitis from mancozeb with vitiligo. Contact Dermatitis. 1985 Aug;13(2):124–125. doi: 10.1111/j.1600-0536.1985.tb02520.x. [DOI] [PubMed] [Google Scholar]
  36. MALOOF F., SPECTOR L. The desulfuration of thiourea by thyroid cytoplasmic particulate fractions. J Biol Chem. 1959 Apr;234(4):949–954. [PubMed] [Google Scholar]
  37. Massey R. C., Key P. E., McWeeny D. J. Analysis of ethylenethiourea in beer by high-performance liquid chromatography. J Chromatogr. 1982 May 7;240(1):254–256. doi: 10.1016/s0021-9673(01)84033-4. [DOI] [PubMed] [Google Scholar]
  38. McClain R. M., Posch R. C., Bosakowski T., Armstrong J. M. Studies on the mode of action for thyroid gland tumor promotion in rats by phenobarbital. Toxicol Appl Pharmacol. 1988 Jun 30;94(2):254–265. doi: 10.1016/0041-008x(88)90267-0. [DOI] [PubMed] [Google Scholar]
  39. McClain R. M. The significance of hepatic microsomal enzyme induction and altered thyroid function in rats: implications for thyroid gland neoplasia. Toxicol Pathol. 1989;17(2):294–306. doi: 10.1177/019262338901700206. [DOI] [PubMed] [Google Scholar]
  40. Nash R. G. Pesticide residues. Improved gas-liquid chromatographic method for determining ethylenethiourea in plants. J Assoc Off Anal Chem. 1974 Sep;57(5):1015–1021. [PubMed] [Google Scholar]
  41. Nater J. P., Terpstra H., Bleumink E. Allergic contact sensitization to the fungicide Maneb. Contact Dermatitis. 1979 Jan;5(1):24–26. doi: 10.1111/j.1600-0536.1979.tb05530.x. [DOI] [PubMed] [Google Scholar]
  42. Newsome W. H. Determination of ethylenethiourea residues in apples. J Agric Food Chem. 1972 Sep-Oct;20(5):967–969. doi: 10.1021/jf60183a008. [DOI] [PubMed] [Google Scholar]
  43. Newsome W. H. The excretion of ethylenethiourea by rat and guinea pig. Bull Environ Contam Toxicol. 1974 Feb;11(2):174–176. doi: 10.1007/BF01684600. [DOI] [PubMed] [Google Scholar]
  44. Nitz S., Moza P., Korte F. A capillary gas-liquid chromatographic method for determination of ethylenethiourea and prophylenethiourea in hops, beer, and grapes. J Agric Food Chem. 1982 May-Jun;30(3):593–596. doi: 10.1021/jf00111a044. [DOI] [PubMed] [Google Scholar]
  45. Onley J. H., Giuffrida L., Ives N. F., Watts R. R., Storherr R. W. Gas-liquid chromatography and liquid chromatography of ethylenethiourea in fresh vegetable crops, fruits, milk, and cooked foods. J Assoc Off Anal Chem. 1977 Sep;60(5):1105–1110. [PubMed] [Google Scholar]
  46. Onley J. H., Yip G. Determination of ethylene thiourea residues in foods, using thin layer and gas chromatography. J Assoc Off Anal Chem. 1971 Jan;54(1):165–169. [PubMed] [Google Scholar]
  47. Padgett E. L., Barnes D. B., Pruett S. B. Disparate effects of representative dithiocarbamates on selected immunological parameters in vivo and cell survival in vitro in female B6C3F1 mice. J Toxicol Environ Health. 1992 Dec;37(4):559–571. doi: 10.1080/15287399209531693. [DOI] [PubMed] [Google Scholar]
  48. Pease H. L., Holt R. F. Managanese ethylenebis (dithiocarbamate) (maneb)/ethylenethiourea (ETU) residue studies on five crops treated with ethylenebis(dithiocarbamate) (EBDC) fungicides. J Agric Food Chem. 1977 May-Jun;25(3):561–567. doi: 10.1021/jf60211a043. [DOI] [PubMed] [Google Scholar]
  49. Piraccini B. M., Cameli N., Peluso A. M., Tardio M. A case of allergic contact dermatitis due to the pesticide maneb. Contact Dermatitis. 1991 May;24(5):381–382. doi: 10.1111/j.1600-0536.1991.tb01763.x. [DOI] [PubMed] [Google Scholar]
  50. Ruddick J. A., Newsome W. H., Iverson F. A comparison of the distribution, metabolism and excretion of ethylenethiourea in the pregnant mouse and rat. Teratology. 1977 Oct;16(2):159–162. doi: 10.1002/tera.1420160208. [DOI] [PubMed] [Google Scholar]
  51. Schnell R. C., Deimling M. J. Effect of manganese on hepatic drug metabolism in male and female rats. Res Commun Chem Pathol Pharmacol. 1984 Feb;43(2):307–315. [PubMed] [Google Scholar]
  52. Seiler J. P. A survey on the mutagenicity of various pesticides. Experientia. 1973 May 15;29(5):622–623. doi: 10.1007/BF01926706. [DOI] [PubMed] [Google Scholar]
  53. Seiler J. P. Ethylenethiourea (ETU), a carcinogenic and mutagenic metabolite of ethylene bis-dithiocarbamate. Mutat Res. 1974 Jun;26(3):189–191. doi: 10.1016/s0027-5107(74)80073-4. [DOI] [PubMed] [Google Scholar]
  54. Siddiqui A., Ali B., Srivastava S. P. Heterogeneous effects of ethylenebisdithiocarbamate (EBDC) pesticides on oxidative metabolism of xenobiotics. Pharmacol Toxicol. 1991 Jul;69(1):13–16. doi: 10.1111/j.1600-0773.1991.tb00401.x. [DOI] [PubMed] [Google Scholar]
  55. Smith D. M. Ethylene thiourea: thyroid function in two groups of exposed workers. Br J Ind Med. 1984 Aug;41(3):362–366. doi: 10.1136/oem.41.3.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Ulland B. M., Weisburger J. H., Weisburger E. K., Rice J. M., Cypher R. Thyroid cancer in rats from ethylene thiourea intake. J Natl Cancer Inst. 1972 Aug;49(2):583–584. [PubMed] [Google Scholar]
  57. Wang H. P., Pacáková V., Stulík K. Determination of ethylenethiourea in beverages without sample pretreatment using high-performance liquid chromatography and amperometric detection on a copper electrode. J Chromatogr. 1988 Dec 21;457:398–402. doi: 10.1016/s0021-9673(01)82091-4. [DOI] [PubMed] [Google Scholar]
  58. Weisburger E. K., Ulland B. M., Nam J., Gart J. J., Weisburger J. H. Carcinogenicity tests of certain environmental and industrial chemicals. J Natl Cancer Inst. 1981 Jul;67(1):75–88. [PubMed] [Google Scholar]
  59. Zorin P. M. Allergicheskii dermatit, vozhnikshii v rezul'tate kontakta s tsinebom. Vestn Dermatol Venerol. 1970 Feb;44(2):65–68. [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES