Abstract
Ethylenebis(dithiocarbamate) (EBDC) fungicides are used heavily in the United States. EBDCs (e.g., mancozeb, maneb) are metabolized to ethylene thiourea (ETU). The EPA classifies ETU as a carcinogen, based on thyroid and other cancers in rodents, and has restricted the use of EBDCs, while requiring workers to use protective equipment. There are no data on the potential carcinogenicity of EBDCs in humans, and there is only one study on human genotoxicity. ETU is known to cause decreases of thyroxine (T4) and increases in thyroid-stimulating hormone (TSH) in rodents. We have studied cytogenetic outcomes and serum thyroid hormone levels among 49 heavily exposed workers without protective equipment spraying EBDC on tomatoes in Mexico. We also studied 14 lightly exposed landowners and 31 nonexposed controls. Urinary ETU was used to compare exposure between groups. We found an increase in TSH (p = 0.05) among applicators compared to controls, but no decrease in thyroid hormone (T4). We found increases in sister chromatid exchange (p = 0.03) and in chromosome translocations (chromosome aberrations that persist through cell division) for applicators compared to controls (p = 0.05). However, the subset of reciprocal translocations showed a lesser increase (p = 0.24). Our data suggest that EBDCs affect the thyroid gland and the lymphocyte genome among heavily exposed workers. However, our data are limited to subclinical outcomes, are of borderline statistical significance, and should be interpreted with caution.
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- Bayer M. F. Effective laboratory evaluation of thyroid status. Med Clin North Am. 1991 Jan;75(1):1–26. doi: 10.1016/s0025-7125(16)30469-2. [DOI] [PubMed] [Google Scholar]
- Bonassi S., Abbondandolo A., Camurri L., Dal Prá L., De Ferrari M., Degrassi F., Forni A., Lamberti L., Lando C., Padovani P. Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study. Cancer Genet Cytogenet. 1995 Feb;79(2):133–135. doi: 10.1016/0165-4608(94)00131-t. [DOI] [PubMed] [Google Scholar]
- Hagmar L., Brøgger A., Hansteen I. L., Heim S., Högstedt B., Knudsen L., Lambert B., Linnainmaa K., Mitelman F., Nordenson I. Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage. Cancer Res. 1994 Jun 1;54(11):2919–2922. [PubMed] [Google Scholar]
- Hershman J. M., Pekary A. E., Berg L., Solomon D. H., Sawin C. T. Serum thyrotropin and thyroid hormone levels in elderly and middle-aged euthyroid persons. J Am Geriatr Soc. 1993 Aug;41(8):823–828. doi: 10.1111/j.1532-5415.1993.tb06177.x. [DOI] [PubMed] [Google Scholar]
- Houeto P., Bindoula G., Hoffman J. R. Ethylenebisdithiocarbamates and ethylenethiourea: possible human health hazards. Environ Health Perspect. 1995 Jun;103(6):568–573. doi: 10.1289/ehp.95103568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jablonická A., Poláková H., Karelová J., Vargová M. Analysis of chromosome aberrations and sister-chromatid exchanges in peripheral blood lymphocytes of workers with occupational exposure to the mancozeb-containing fungicide Novozir Mn80. Mutat Res. 1989 Oct;224(2):143–146. doi: 10.1016/0165-1218(89)90148-1. [DOI] [PubMed] [Google Scholar]
- Johnson G. D., Nogueira Araujo G. M. A simple method of reducing the fading of immunofluorescence during microscopy. J Immunol Methods. 1981;43(3):349–350. doi: 10.1016/0022-1759(81)90183-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Kurttio P., Vartiainen T., Savolainen K. Environmental and biological monitoring of exposure to ethylenebisdithiocarbamate fungicides and ethylenethiourea. Br J Ind Med. 1990 Mar;47(3):203–206. doi: 10.1136/oem.47.3.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lucas J. N., Tenjin T., Straume T., Pinkel D., Moore D., 2nd, Litt M., Gray J. W. Rapid human chromosome aberration analysis using fluorescence in situ hybridization. Int J Radiat Biol. 1989 Jul;56(1):35–44. doi: 10.1080/09553008914551161. [DOI] [PubMed] [Google Scholar]
- Mariotti S., Barbesino G., Caturegli P., Bartalena L., Sansoni P., Fagnoni F., Monti D., Fagiolo U., Franceschi C., Pinchera A. Complex alteration of thyroid function in healthy centenarians. J Clin Endocrinol Metab. 1993 Nov;77(5):1130–1134. doi: 10.1210/jcem.77.5.8077303. [DOI] [PubMed] [Google Scholar]
- Mendelsohn M. L., Mayall B. H., Bogart E., Moore D. H., 2nd, Perry B. H. DNA content and DNA-based centromeric index of the 24 human chromosomes. Science. 1973 Mar 16;179(4078):1126–1129. doi: 10.1126/science.179.4078.1126. [DOI] [PubMed] [Google Scholar]
- Minkler J., Stetka D., Jr, Carrano A. V. An ultraviolet light source for consistent differential staining of sister chromatids. Stain Technol. 1978 Nov;53(6):359–360. [PubMed] [Google Scholar]
- Perry P., Wolff S. New Giemsa method for the differential staining of sister chromatids. Nature. 1974 Sep 13;251(5471):156–158. doi: 10.1038/251156a0. [DOI] [PubMed] [Google Scholar]
- Ramsey M. J., Moore D. H., 2nd, Briner J. F., Lee D. A., Olsen L. a., Senft J. R., Tucker J. D. The effects of age and lifestyle factors on the accumulation of cytogenetic damage as measured by chromosome painting. Mutat Res. 1995 Oct;338(1-6):95–106. doi: 10.1016/0921-8734(95)00015-x. [DOI] [PubMed] [Google Scholar]
- 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]
- Spruill M. D., Ramsey M. J., Swiger R. R., Nath J., Tucker J. D. The persistence of aberrations in mice induced by gamma radiation as measured by chromosome painting. Mutat Res. 1996 Sep 23;356(2):135–145. doi: 10.1016/0027-5107(95)00218-9. [DOI] [PubMed] [Google Scholar]
- Tucker J. D., Moore D. H., 2nd The importance of age and smoking in evaluating adverse cytogenetic effects of exposure to environmental agents. Environ Health Perspect. 1996 May;104 (Suppl 3):489–492. doi: 10.1289/ehp.96104s3489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tucker J. D., Morgan W. F., Awa A. A., Bauchinger M., Blakey D., Cornforth M. N., Littlefield L. G., Natarajan A. T., Shasserre C. A proposed system for scoring structural aberrations detected by chromosome painting. Cytogenet Cell Genet. 1995;68(3-4):211–221. doi: 10.1159/000133916. [DOI] [PubMed] [Google Scholar]
- van Coevorden A., Laurent E., Decoster C., Kerkhofs M., Neve P., van Cauter E., Mockel J. Decreased basal and stimulated thyrotropin secretion in healthy elderly men. J Clin Endocrinol Metab. 1989 Jul;69(1):177–185. doi: 10.1210/jcem-69-1-177. [DOI] [PubMed] [Google Scholar]