Skip to main content
PMC home page
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2001 Mar;58(3):172–177. doi: 10.1136/oem.58.3.172

Association between serum concentrations of hexachlorobenzene and polychlorobiphenyls with thyroid hormone and liver enzymes in a sample of the general population

M Sala 1, J Sunyer 1, C Herrero 1, J To-Figueras 1, J Grimalt 1
PMCID: PMC1740109  PMID: 11171930

Abstract

OBJECTIVES—Hexachlorobenzene (HCB) is a highly lipophilic organochlorine compound of widespread environmental occurrence, that accumulates in the biological system. It affects the porphyrine metabolism, thyroid hormones, and the liver function in animals. Although HCB is one of the most common organochlorine compound in humans, little investigation on its health effects has been done. Polychlorobiphenyls (PCBs) are also widespread toxic environmental contaminants. The aim of the present study was to investigate the association of serum HCB and PCB concentrations with thyroid hormone status and liver enzymes in human.
METHODS—Thyroid stimulating hormone (TSH), total and free thyroxine (T4), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) were measured as biological markers of thyroid and liver function in a rural population sample older than 14 years (n=192, except for TSH with n=608) highly exposed to HCB. Serum concentrations of HCB were measured by gas chromatography coupled to electron capture detection.
RESULTS—After adjustment for confounding variables, there was a significant negative association between serum HCB concentrations and total T4 (a decrease of 0.32 µg/dl per each unit, ln ng/ml, of increase of HCB) and a positive association with GGT (a relative increase of 10 % per each ln unit of increase of HCB), although most subjects (92%) were within the normal range for both T4 and GGT. These associations were not modified after adjustment for total lipid content or for other organochlorine compounds. The association of T4 and GGT with PCB was smaller although significant. No association was found with the other biochemical markers.
CONCLUSIONS—These results suggest that the internal dose of HCB of this population may reflect a subtle metabolic effect on thyroid function and an enzymatic induction activity. Further studies are needed to evaluate the health impact of these effects in more susceptible populations, such as infants.


Keywords: hexachlorobenzene; environmental exposure; thyroid; liver enzymes

Full Text

The Full Text of this article is available as a PDF (149.1 KB).

Selected References

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

  1. CAN C., NIGOGOSYAN G. Acquired toxic porphyria cutanea tarda due to hexachlorobenzene. Report of 348 cases caused by this fungicide. JAMA. 1963 Jan 12;183:88–91. [PubMed] [Google Scholar]
  2. Cabral J. R., Mollner T., Raitano F., Shubik P. Carcinogenesis of hexachlorobenzene in mice. Int J Cancer. 1979 Jan 15;23(1):47–51. doi: 10.1002/ijc.2910230110. [DOI] [PubMed] [Google Scholar]
  3. Cabral J. R., Shubik P., Mollner T., Raitano F. Carcinogenic activity of hexacholorobenzene in hamsters. Nature. 1977 Oct 6;269(5628):510–511. doi: 10.1038/269510a0. [DOI] [PubMed] [Google Scholar]
  4. Calvo R., Obregón M. J., Ruiz de Oña C., Escobar del Rey F., Morreale de Escobar G. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain. J Clin Invest. 1990 Sep;86(3):889–899. doi: 10.1172/JCI114790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Colborn T. Environmental estrogens: health implications for humans and wildlife. Environ Health Perspect. 1995 Oct;103 (Suppl 7):135–136. doi: 10.1289/ehp.95103s7135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colborn T. Pesticides--how research has succeeded and failed to translate science into policy: endocrinological effects on wildlife. Environ Health Perspect. 1995 Sep;103 (Suppl 6):81–85. doi: 10.1289/ehp.95103s681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Colborn T. The wildlife/human connection: modernizing risk decisions. Environ Health Perspect. 1994 Dec;102 (Suppl 12):55–59. doi: 10.1289/ehp.94102s1255a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Courtney K. D. Hexachlorobenzene (HCB): a review. Environ Res. 1979 Dec;20(2):225–266. doi: 10.1016/0013-9351(79)90001-x. [DOI] [PubMed] [Google Scholar]
  9. Currier M. F., McClimans C. D., Barna-Lloyd G. Hexachlorobenzene blood levels and the health status of men employed in the manufacture of chlorinated solvents. J Toxicol Environ Health. 1980 Mar;6(2):367–377. doi: 10.1080/15287398009529857. [DOI] [PubMed] [Google Scholar]
  10. DeVito M., Biegel L., Brouwer A., Brown S., Brucker-Davis F., Cheek A. O., Christensen R., Colborn T., Cooke P., Crissman J. Screening methods for thyroid hormone disruptors. Environ Health Perspect. 1999 May;107(5):407–415. doi: 10.1289/ehp.99107407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Emmett E. A., Maroni M., Jefferys J., Schmith J., Levin B. K., Alvares A. Studies of transformer repair workers exposed to PCBs: II. Results of clinical laboratory investigations. Am J Ind Med. 1988;14(1):47–62. doi: 10.1002/ajim.4700140107. [DOI] [PubMed] [Google Scholar]
  12. Emmett E. A., Maroni M., Jefferys J., Schmith J., Levin B. K., Alvares A. Studies of transformer repair workers exposed to PCBs: II. Results of clinical laboratory investigations. Am J Ind Med. 1988;14(1):47–62. doi: 10.1002/ajim.4700140107. [DOI] [PubMed] [Google Scholar]
  13. Foster W. G., McMahon A., Villeneuve D. C., Jarrell J. F. Hexachlorobenzene (HCB) suppresses circulating progesterone concentrations during the luteal phase in the cynomolgus monkey. J Appl Toxicol. 1992 Feb;12(1):13–17. doi: 10.1002/jat.2550120105. [DOI] [PubMed] [Google Scholar]
  14. Foster W. G., Pentick J. A., McMahon A., Lecavalier P. R. Body distribution and endocrine toxicity of hexachlorobenzene (HCB) in the female rat. J Appl Toxicol. 1993 Mar-Apr;13(2):79–83. doi: 10.1002/jat.2550130203. [DOI] [PubMed] [Google Scholar]
  15. Gocmen A., Peters H. A., Cripps D. J., Bryan G. T., Morris C. R. Hexachlorobenzene episode in Turkey. Biomed Environ Sci. 1989 Mar;2(1):36–43. [PubMed] [Google Scholar]
  16. Grimalt J. O., Sunyer J., Moreno V., Amaral O. C., Sala M., Rosell A., Anto J. M., Albaiges J. Risk excess of soft-tissue sarcoma and thyroid cancer in a community exposed to airborne organochlorinated compound mixtures with a high hexachlorobenzene content. Int J Cancer. 1994 Jan 15;56(2):200–203. doi: 10.1002/ijc.2910560209. [DOI] [PubMed] [Google Scholar]
  17. Herrero C., Ozalla D., Sala M., Otero R., Santiago-Silva M., Lecha M., To-Figueras J., Deulofeu R., Mascaró J. M., Grimalt J. Urinary porphyrin excretion in a human population highly exposed to hexachlorobenzene. Arch Dermatol. 1999 Apr;135(4):400–404. doi: 10.1001/archderm.135.4.400. [DOI] [PubMed] [Google Scholar]
  18. Jarrell J. F., McMahon A., Villeneuve D., Franklin C., Singh A., Valli V. E., Bartlett S. Hexachlorobenzene toxicity in the monkey primordial germ cell without induced porphyria. Reprod Toxicol. 1993;7(1):41–47. doi: 10.1016/0890-6238(93)90008-u. [DOI] [PubMed] [Google Scholar]
  19. Koopman-Esseboom C., Morse D. C., Weisglas-Kuperus N., Lutkeschipholt I. J., Van der Paauw C. G., Tuinstra L. G., Brouwer A., Sauer P. J. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr Res. 1994 Oct;36(4):468–473. doi: 10.1203/00006450-199410000-00009. [DOI] [PubMed] [Google Scholar]
  20. Manson M. M., Smith A. G. Effect of hexachlorobenzene on male and female rat hepatic gamma-glutamyl transpeptidase levels. Cancer Lett. 1984 Mar;22(2):227–234. doi: 10.1016/0304-3835(84)90123-x. [DOI] [PubMed] [Google Scholar]
  21. Mazhitova Z., Jensen S., Ritzén M., Zetterström R. Chlorinated contaminants, growth and thyroid function in schoolchildren from the Aral Sea region in Kazakhstan. Acta Paediatr. 1998 Sep;87(9):991–995. doi: 10.1080/080352598750031671. [DOI] [PubMed] [Google Scholar]
  22. Nagayama J., Okamura K., Iida T., Hirakawa H., Matsueda T., Tsuji H., Hasegawa M., Sato K., Ma H. Y., Yanagawa T. Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants. Chemosphere. 1998 Oct-Nov;37(9-12):1789–1793. doi: 10.1016/s0045-6535(98)00244-6. [DOI] [PubMed] [Google Scholar]
  23. Phillips D. L., Pirkle J. L., Burse V. W., Bernert J. T., Jr, Henderson L. O., Needham L. L. Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding. Arch Environ Contam Toxicol. 1989 Jul-Aug;18(4):495–500. doi: 10.1007/BF01055015. [DOI] [PubMed] [Google Scholar]
  24. Pluim H. J., de Vijlder J. J., Olie K., Kok J. H., Vulsma T., van Tijn D. A., van der Slikke J. W., Koppe J. G. Effects of pre- and postnatal exposure to chlorinated dioxins and furans on human neonatal thyroid hormone concentrations. Environ Health Perspect. 1993 Nov;101(6):504–508. doi: 10.1289/ehp.93101504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. SCHMID R. Cutaneous porphyria in Turkey. N Engl J Med. 1960 Aug 25;263:397–398. doi: 10.1056/NEJM196008252630807. [DOI] [PubMed] [Google Scholar]
  26. Sala M., Sunyer J., Otero R., Santiago-Silva M., Camps C., Grimalt J. Organochlorine in the serum of inhabitants living near an electrochemical factory. Occup Environ Med. 1999 Mar;56(3):152–158. doi: 10.1136/oem.56.3.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sala M., Sunyer J., Otero R., Santiago-Silva M., Ozalla D., Herrero C., To-Figueras J., Kogevinas M., Anto J. M., Camps C. Health effects of chronic high exposure to hexachlorobenzene in a general population sample. Arch Environ Health. 1999 Mar-Apr;54(2):102–109. doi: 10.1080/00039899909602243. [DOI] [PubMed] [Google Scholar]
  28. Seldén A. I., Nygren Y., Westberg H. B., Bodin L. S. Hexachlorobenzene and octachlorostyrene in plasma of aluminium foundry workers using hexachloroethane for degassing. Occup Environ Med. 1997 Aug;54(8):613–618. doi: 10.1136/oem.54.8.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Smith A. B., Schloemer J., Lowry L. K., Smallwood A. W., Ligo R. N., Tanaka S., Stringer W., Jones M., Hervin R., Glueck C. J. Metabolic and health consequences of occupational exposure to polychlorinated biphenyls. Br J Ind Med. 1982 Nov;39(4):361–369. doi: 10.1136/oem.39.4.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith A. G., Carthew P., Francis J. E., Cabral J. R., Manson M. M. Enhancement by iron of hepatic neoplasia in rats caused by hexachlorobenzene. Carcinogenesis. 1993 Jul;14(7):1381–1387. doi: 10.1093/carcin/14.7.1381. [DOI] [PubMed] [Google Scholar]
  31. Smith A. G., Dinsdale D., Cabral J. R., Wright A. L. Goitre and wasting induced in hamsters by hexachlorobenzene. Arch Toxicol. 1987 Jul;60(5):343–349. doi: 10.1007/BF00295753. [DOI] [PubMed] [Google Scholar]
  32. To-Figueras J., Sala M., Otero R., Barrot C., Santiago-Silva M., Rodamilans M., Herrero C., Grimalt J., Sunyer J. Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population. Environ Health Perspect. 1997 Jan;105(1):78–83. doi: 10.1289/ehp.9710578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Visser T. J., Kaptein E., van Toor H., van Raaij J. A., van den Berg K. J., Joe C. T., van Engelen J. G., Brouwer A. Glucuronidation of thyroid hormone in rat liver: effects of in vivo treatment with microsomal enzyme inducers and in vitro assay conditions. Endocrinology. 1993 Nov;133(5):2177–2186. doi: 10.1210/endo.133.5.8404669. [DOI] [PubMed] [Google Scholar]
  34. van Birgelen A. P. Hexachlorobenzene as a possible major contributor to the dioxin activity of human milk. Environ Health Perspect. 1998 Nov;106(11):683–688. doi: 10.1289/ehp.106-1533492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. van Raaij J. A., Frijters C. M., van den Berg K. J. Hexachlorobenzene-induced hypothyroidism. Involvement of different mechanisms by parent compound and metabolite. Biochem Pharmacol. 1993 Oct 19;46(8):1385–1391. doi: 10.1016/0006-2952(93)90103-4. [DOI] [PubMed] [Google Scholar]
  36. van Raaij J. A., Frijters C. M., van den Berg K. J. Hexachlorobenzene-induced hypothyroidism. Involvement of different mechanisms by parent compound and metabolite. Biochem Pharmacol. 1993 Oct 19;46(8):1385–1391. doi: 10.1016/0006-2952(93)90103-4. [DOI] [PubMed] [Google Scholar]
  37. van Raaij J. A., Kaptein E., Visser T. J., van den Berg K. J. Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats. Biochem Pharmacol. 1993 Feb 9;45(3):627–631. doi: 10.1016/0006-2952(93)90136-k. [DOI] [PubMed] [Google Scholar]
  38. van Raaij J. A., van den Berg K. J., Notten W. R. Hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone: interaction with thyroxine binding sites of rat thyroid hormone carriers ex vivo and in vitro. Toxicol Lett. 1991 Dec;59(1-3):101–107. doi: 10.1016/0378-4274(91)90060-j. [DOI] [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES