Antiandrogenic activity of phthalate mixtures: Validity of concentration addition

Toxicology and Applied Pharmacology

Volumn 259, Issue 2, 2012, Pages 169-176

  Christen, Verena ^a   Crettaz, Pierre ^b   Oberli Schrämmli, Aurelia ^b   Fent, Karl ^a,c  

^a UNIVERSITY OF APPLIED SCIENCES AND ARTS NORTHWESTERN SWITZERLAND   (Switzerland)

^b FEDERAL OFFICE OF PUBLIC HEALTH   (Switzerland)

^c ETH ZURICH   (Switzerland)

Author keywords

Antiandrogenicity; Benzylbutylphthalate (BBP); Bisphenol A; Concentration addition; Di 2 ethylhexyl phthalate (DEHP); Dibutyl phthalate (DBP); Diethylphthalate (DEP); Dimethyl phthalate (DMP); Isobole method; Mixture activity; Phthalates; Toxic unit approach

Indexed keywords

4,4' ISOPROPYLIDENEDIPHENOL; PHTHALIC ACID;

ADDITION REACTION; ARTICLE; CONCENTRATION RESPONSE; DRUG ACTIVITY; DRUG ANTAGONISM; DRUG POTENTIATION; FEMALE; HUMAN; HUMAN CELL;

ANDROGEN ANTAGONISTS; CELL LINE, TUMOR; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; PHENOLS; PHTHALIC ACIDS; RECEPTORS, ANDROGEN; REGRESSION ANALYSIS;

EID: 84857233070     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2011.12.021     Document Type: Article

References (39)

1. Ahn K.C., Zhao B., Chen J., Cherednichenko G., Sanmarti E., Denison M.S., Lasley B., Pessah I.N., Kultz D., Chang D.P., Gee S.J., Hammock B.D. In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens. Environ. Health Perspect. 2008, 116:1203-1210.
2. Aït-Aïssa S., Laskowski S., Laville N., Porcher J.M., Brion F. Anti-androgenic activities of environmental pesticides in the MDA-kb2 reporter cell line. Toxicol. In Vitro 2010, 7:1979-1985.
3. Andersen H.R., Andersson A.M., Arnold S.F., Autrup H., Barfoed M., Beresford N.A., Bjerregaard P., Christiansen L.B., Gissel B., Hummel R., Jorgensen E.B., Korsgaard B., Le Guevel R., Leffers H., McLachlan J., Moller A., Nielsen J.B., Olea N., Oles-Karasko A., Pakdel F., Pedersen K.L., Perez P., Skakkeboek N.E., Sonnenschein C., Soto A.M. Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals. Environ. Health Perspect. 1999, 107:89-108.
4. Benson R. Hazard to the developing male reproductive system from cumulative exposure to phthalate esters - dibutyl phthalate, diisobutyl phthalate, butylbenzyl phthalate, diethylhexyl phthalate, dipentyl phthalate, and diisononyl phthalate. Regul. Toxicol. Pharmacol. 2009, 53:90-102.
5. Berenbaum M.C. What is synergism?. Pharmacol. Rev. 1995, 41:93-141.
6. Borch J., Metzdorff S.B., Vinggaard A.M., Brokken L., Dalgaard M. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Toxicology 2006, 223:144-155.
7. Borch J., Axelstad M., Vinggaard A.M., Dalgaard M. Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis. Toxicol. Lett. 2006, 163:183-190.
8. Chang C.Y., McDonnell D.P. Androgen receptor-cofactor interactions as targets for new drug discovery. Trends Pharmacol. Sci. 2005, 5:225-228.
9. Christen V., Crettaz P., Oberli-Schrämmli A., Fent K. Some flame retardants and the antimicrobials triclosan and triclocarban enhance the androgenic activity in vitro. Chemosphere 2010, 81:1245-1252.
10. Christiansen S., Scholze M., Dalgaard M., Vinggaard A.M., Axelstad M., Kortenkamp A., Hass U. Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ. Health Perspect. 2009, 117:1839-1846.
11. Ermler S., Scholz E.M., Kortenkamp A. The suitability of concentration addition for predicting the effects of multi-component mixtures of up to 17 anti-androgens with varied structural features in an in vitro AR antagonist assay. Toxicol. Appl. Pharmacol. 2011, 257(2):189-197.
12. Fisher J.S. Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. Reproduction 2004, 127:305-315.
13. Foster P.M. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int. J. Androl. 2006, 29:140-147. discussion 181-185.
14. Frederiksen H., Aksglaede L., Sorensen K., Skakkebaek N.E., Juul A., Andersson A.M. Urinary excretion of phthalate metabolites in 129 healthy Danish children and adolescents: estimation of daily phthalate intake. Environ. Res. 2011, 111:656-663.
15. Gray L.E., Ostby J., Furr J., Price M., Veeramachaneni D.N., Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol. Sci. 2000, 58:350-365.
16. Gray L.E., Wilson V.S., Stoker T., Lambright C., Furr J., Noriega N. Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. Int. J Androl. 2006, 29:96-104.
17. Hernández-Díaz S., Mitchell A.A., Kelley K.E., Calafat A.M., Hauser R. Medications as a potential source of exposure to phthalates in the U.S. population. Environ. Health Perspect. 2009, 117:185-189.
18. Howdeshell K.L., Furr J., Lambright C.R., Rider C.V., Wilson V.S., Gray L.E. Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: altered fetal steroid hormones and genes. Toxicol. Sci. 2007, 99:190-202.
19. Howdeshell K.L., Wilson V.S., Furr J., Lambright C.R., Rider C.V., Blystone C.R., Hotchkiss A.K., Gray L.E. A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague-Dawley rat in a cumulative, dose-additive manner. Toxicol. Sci. 2008, 105:153-165.
20. Jobling S., Reynolds T., White R., Parker M.G., Sumpter J.P. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ. Health Perspect. 1995, 103:582-587.
21. Körner W., Vinggaard A.M., Terouanne B., Ma R., Wieloch C., Schlumpf M., Sultan C., Soto A.M. Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals. Environ. Health Perspect. 2004, 112:695-702.
22. Kortenkamp A., Altenburger R. Synergisms with mixtures of xenoestrogens: a reevaluation using the method of isoboles. Sci. Total. Environ. 1998, 221:59-73.
23. Kortenkamp A., Faust M. Combined exposures to anti-androgenic chemicals: steps towards cumulative risk assessment. Int. J. Androl. 2010, 33:463-474.
24. Kunz P.Y., Fent K. Estrogenic activity of UV filter mixtures. Toxicol. Appl. Pharmacol. 2006, 217:86-99.
25. Kunz P.Y., Fent K. Estrogenic activity of ternary UV filter mixtures in fish (Pimephales promelas) - an analysis with nonlinear isobolograms. Toxicol. Appl. Pharmacol. 2009, 234:77-88.
26. Lambrot R., Muczynski V., Lécureuil C., Angenard G., Coffigny H., Pairault C., Moison D., Frydman R., Habert R., Rouiller-Fabre V. Phthalates impair germ cell development in the human fetal testis in vitro without change in testosterone production. Environ. Health Perspect. 2009, 117:32-37.
27. Marsee K., Woodruff T.J., Axelrad D.A., Calafat A.M., Swan S.H. Estimated daily phthalate exposures in a population of mothers of male infants exhibiting reduced anogenital distance. Environ. Health Perspect. 2006, 114:805-809.
28. Martino-Andrade A.J., Morais R.N., Botelho G.G., Muller G., Grande S.W., Carpentieri G.B., Leão G.M., Dalsenter P.R. Coadministration of active phthalates results in disruption of foetal testicular function in rats. Int. J. Androl. 2009, 32:704-712.
29. National Research Council NRC Phthalates Cumulative Risk Assessment - The Tasks Ahead 2008, Committee on Phthalates Health Risks, National Research Council, National Academy of Sciences, Board on Environmental Science and Technology, National Academy Press, Washington, DC, USA.
30. Rider C.V., Furr J., Wilson V.S., Gray L.E. A mixture of seven antiandrogens induces reproductive malformations in rats. Int. J. Androl. 2008, 31:249-262.
31. Rider C.V., Wilson V.S., Howdeshell K.L., Hotchkiss A.K., Furr J.R., Lambright C.R., Gray L.E. Cumulative effects of in utero administration of mixtures of "antiandrogens" on male rat reproductive development. Toxicol. Pathol. 2009, 37:100-113.
32. Rider C.V., Furr J.R., Wilson V.S., Gray L.E. Cumulative effects of in utero administration of mixtures of reproductive toxicants that disrupt common target tissues via diverse mechanisms of toxicity. Int. J. Androl. 2010, 33:443-462.
33. Schlumpf M., Kypke K., Wittassek M., Angerer J., Mascher H., Mascher D., Vökt C., Birchler M., Lichtensteiger W. Exposure patterns of UV filters, fragrances, parabens, phthalates, organochlor pesticides, PBDEs, and PCBs in human milk: correlation of UV filters with use of cosmetics. Chemosphere 2010, 81:1171-1183.
34. Sharpe R.M. Phthalate exposure during pregnancy and lower anogenital index in boys: wider implications for the general population?. Environ. Health Perspect. 2005, 113:504-505.
35. Stahlhut R.W., van Wijngaarden E., Dye T.D., Cook S., Swan S.H. Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ. Health Perspect. 2001, 115:876-882.
36. Stoker T.E., Cooper R.L., Lambright C.S., Wilson V.S., Furr J., Gray L.E. In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture. Toxicol. Appl. Pharmacol. 2005, 207(1):78-88.
37. Terouanne B., Tahiri B., Georget V., Belon C., Poujol N., Avances C., Orio F., Balaguer P., Sultan C. A stable prostatic bioluminescent cell line to investigate androgen and antiandrogen effects. Mol. Cell. Endocrinol. 2000, 160:39-49.
38. Wilson V.S., Bobseine K., Lambright C.R., Gray L.E. A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists. Toxicol. Sci. 2002, 66:69-81.
39. Zacharewski T. Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays. Environ. Health Perspect. 1998, 106:577-582.