Mixtures of endocrine disrupting contaminants modelled on human high end exposures: An exploratory study in rats

International Journal of Andrology

Volumn 35, Issue 3, 2012, Pages 303-316

  Christiansen, S ^a   Kortenkamp, A ^b   Axelstad, M ^a   Boberg, J ^a   Scholze, M ^b   Jacobsen, P R ^a   Faust, M ^c   Lichtensteiger, W ^d   Schlumpf, M ^d   Burdorf, A ^e   Hass, U ^a  

^a TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

^b BRUNEL UNIVERSITY   (United Kingdom)

^c F+B Environmental Consulting   (Germany)

^d UNIVERSITY OF ZURICH   (Switzerland)

^e ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Anti androgens; Bisphenol A; Combined exposure; Endocrine disrupters; Mixtures; Nipple retention; Paraben; Pesticides; Phthalates; Rat; UV filters

Indexed keywords

1,1 DICHLORO 2,2 BIS(4 CHLOROPHENYL)ETHYLENE; 4 METHOXYCINNAMIC ACID 2 ETHYLHEXYL ESTER; 4 METHYL BENZYLIDENE CAMPHOR; 4,4' ISOPROPYLIDENEDIPHENOL; BUTYL PARABEN; CAMPHOR DERIVATIVE; ENDOCRINE DISRUPTOR; EPOXICONAZOLE; LINURON; PARACETAMOL; PHTHALIC ACID BIS(2 ETHYLHEXYL) ESTER; PHTHALIC ACID DIBUTYL ESTER; PROCHLORAZ; PROCYMIDONE; TRIAZOLE; UNCLASSIFIED DRUG; VINCLOZOLIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIRTH WEIGHT; BREAST AREOLA; CONTROLLED STUDY; ENVIRONMENTAL EXPOSURE; FEMALE; IN VIVO STUDY; MALE; NAMED INVENTORIES, QUESTIONNAIRES AND RATING SCALES; NIPPLE; NONHUMAN; ORGAN WEIGHT; POINT OF DEPARTURE INDEX; POSTNATAL DEVELOPMENT; PREGNANCY OUTCOME; PRENATAL EXPOSURE; PRIORITY JOURNAL; PROSTATE; RAT; WEIGHT GAIN;

ABNORMALITIES, DRUG-INDUCED; ANDROGEN ANTAGONISTS; ANIMALS; ENDOCRINE DISRUPTORS; FEMALE; GENITALIA; HUMANS; MALE; NO-OBSERVED-ADVERSE-EFFECT LEVEL; PREGNANCY; RATS; RATS, WISTAR; SEX DIFFERENTIATION;

EID: 84861458913     PISSN: 01056263     EISSN: 13652605     Source Type: Journal    
DOI: 10.1111/j.1365-2605.2011.01242.x     Document Type: Article

References (86)

1. Andrade AJ, Grande SW, Talsness CE, Gericke C, Grote K, Golombiewski A, Sterner-Kock A & Chahoud I. (2006) A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats. Toxicology 228, 85-97.
2. Axelstad M, Boberg J, Hougaard KS, Christiansen S, Jacobsen PR, Mandrup KR, Nellemann C, Lund SP & Hass U. (2011) Effects of pre- and postnatal exposure to the UV-filter octyl methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring. Toxicol Appl Pharmacol 250, 278-290.
3. Benson R. (2009) 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. Regulatory Toxicol Pharmacol 53, 90-102.
4. Bretz F, Pinheiro JC & Branson M. (2005) Combining multiple comparisons and modelling techniques in dose-response studies. Biometrics 61, 738-748.
5. Buser HR, Balmer ME, Schmid P & Kohler M. (2006) Occurrence of UV filters 4-methylbenzylidene camphor and octocrylene in fish from various Swiss rivers with inputs from wastewater treatment plants. Environ Sci Technol 40, 1427-1431.
6. Chemical Watch. (2011) Danes cite combined exposure in REACH phthalates proposal. CHEMICAL WATCH, [Cited 06/16/2011], Available at: (accessed on 26 January 2012).
7. Chen M, Hsu I, Wolfe A, Radovick S, KuoHsiang H, Shengquiang Y, Chawnshang C, Messing EM & Shuyuan Y. (2009) Defects of prostate development and reproductive system in the estrogen receptor-α null male mice. Endocrinology 150, 251-259.
8. Christiansen S, Scholze M, Dalgaard M, Vinggaard AM, Axelstad M, Kortenkamp A & Hass U. (2009) Synergistic disruption of external male sex organ development by a mixture of four anti-androgens. Environ Health Perspect 117, 1839-1846.
9. Christiansen S, Boberg J, Axelstad M, Dalgaard M, Vinggaard AM, Metzdorff SB & Hass U. (2010) Low-dose perinatal exposure to di(2-ethylhexyl) phthalate induces anti-androgenic effects in male rats. Reprod Toxicol 30, 313-321.
10. Cousins IT, Staples CA, Klecka GM & Mackay M. (2002) A Multimedia Assessment of the Environmental Fate of Bisphenol A. Hum Ecol Risk Assess 8, 1107-1135.
11. Cross SE & Roberts MS. (2000) The effect of occlusion on epidermal penetration of parabens from a commercial allergy test ointment, acetone and ethanol vehicle. J Invest Dermatol 115, 914-918.
12. Danish Ministry of the Environment. (2011) The Danish Minister of Environment plans to introduce a ban against four dangerous phthalates. Denmark, [Cited Sep.2011], Available from: (accessed on 6 February 2012).
13. Delbes G, Levacher C, Duquenne C, Racine C, Pakarinen P & Habert R. (2005) Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor alpha. Endocrinology 146, 2454-2461.
14. Durrer S, Ehnes C, Fuetsch M, Maerkel K, Schlumpf M & Lichtensteiger W. (2007) Estrogen sensitivity of target genes and expression of nuclear receptor coregulators in rat prostate after pre- and postnatal exposure to the ultraviolet filter 4-methylbenzylidene camphor. Environ Health Perspect 115(Suppl. 1), 42-50.
15. EFSA. (2006) Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to 2, 2-BIS(4-HYDROXYPHENYL)PROPANE (Bisphenol A) Question number EFSA-Q-2005-100, Adopted on 29 November 2006. updated 29 January 2007. The EFSA J 428, 1 of 75. Available: (accessed on 30 January 2012).
16. Ellem SJ & Risbridger GP. (2010) Aromatase and regulating the estrogen:androgen ratio in the prostate gland. J Steroid Biochem Mol Biol 118, 246-251.
17. Ermler S, Scholze M & Kortenkamp A. (2010) The sensitivity of the MDA-kb2 cell in vitro assay in detecting anti-androgenic chemicals - identification of sources of variability and estimation of statistical power. Tox in vitro 24, 1845-1853.
18. Ermler S, Scholze M & Kortenkamp A. (2011) 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 257, 189-197.
19. European Food Safety Authority (EFSA). (2010) Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A. EFSA J 8, 1829.
20. Galassi S, Bettinetti R, Neri MC, Falandysz J, Kotecka W, King I, Lo S, Klingmueller D & Schulte-Oehlmann U. (2008) pp'-DDE contamination of the blood and diet in central European populations. Sci Total Environ 390, 45-52.
21. Gallavan RH, Holson JF, Stump DG, Knapp JF & Reynolds VL. (1999) Interpreting the toxicologic significance of alterations in anogenital distance: potential for confounding effects of progeny body weights. Reprod Toxicol 13, 383-390.
22. Ghanem CI, Ruiz ML, Villanueva SS, Luquita M, Llesuy S, Catania VA, Bengochea LA & Mottino AD. (2009) Effect of repeated administration with subtoxic doses of acetaminophen to rats on enterohepatic recirculation of a subsequent toxic dose. Biochem Pharmacol 77, 1621-1628.
23. Gray LE Jr, Ostby JS & Kelce WR. (1994) Developmental effects of an environmental antiandrogen: The fungicide vinclozolin alters sex differentiation of the male rat. Toxicol Appl Pharmacol 129, 46-52.
24. Gray LE Jr, Ostby J, Monosson E & Kelce WR. (1999) Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health 15, 48-64.
25. Gupta U, Malhotra N, Varma SK & Chaudhury RR. (1981) Effect of intrauterine administration of antiprostaglandin drugs on implantation in the rat. Contraception 24, 283-288.
26. Hany J & Nagel R. (1995) Nachweis von UV-Filtersubstanzen in Muttermilch. Dtsch Lebensmitt Rundsch 91, 341-345.
27. Hass U, Scholze M, Christiansen S, Dalgaard M, Vinggaard AM, Axelstad M, Metzdorff SB & Kortenkamp A. (2007) Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat. Environ Health Perspect 115(Suppl 1), 122-128.
28. Hass U, Jacobsen PR, Boberg J, Christiansen S, Nellemann C, Kristensen DM & Leffers H. (2010) Developmental exposure to paracetamol causes anti-androgenic effects in male rat offspring. Reprod Toxicol Abstract 30, 230-231.
29. Hotchkiss AK, Parks-Saldutti LG, Ostby JS, Lambright C, Furr J, Vandenbergh JG & Gray LE Jr. (2004) A mixture of the 'antiandrogens' linuron and butyl benzyl phthalate alters sexual differentiation of the male rat in a cumulative fashion. Biol Reprod 71, 1852-1861.
30. Howdeshell KL, Wilson VS, Furr J, Lambright CR, Rider CV, Blystone CR, Hotchkiss AK & Gray LE Jr. (2008) A Mixture of Five Phthalate Esters Inhibits Fetal Testicular Testosterone Production in the Sprague-Dawley Rat in a Cumulative, Dose-Additive Manner. Toxicol Sci 105, 153-165.
31. Jensen MS, Rebordosa C, Thulstrup AM, Toft G, Sørensen HT, Bonde JP, Henriksen TB & Olsen J. (2010) Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism. Epidemiology 21, 6.
32. Jensen GE, Nikolov NG, Wedebye EB, Ringsted T & Niemelä JR. (2011) QSAR models for anti-androgenic effect - a preliminary study. SAR QSAR Environ Res 22, 35-49.
33. Kang KS, Che JH, Ryu DY, Kim TW, Li GX & Lee YS. (2002) Decreased sperm number and motile activity on the F1 offspring maternally exposed to butyl p-hydroxybenzoic acid (butyl paraben). J Vet Med Sci 64, 227-235.
34. Kavlock R & Cummings A. (2005) Mode of action: Inhibition of androgen receptor function - Vinclozolin-induced malformations in reproductive development. Crit Rev Toxicol 35, 721-726.
35. Kelce WR, Monosson E, Gamcsik MP, Laws SC & Gray LE Jr. (1994) Environmental hormone disruptors: Evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicol Appl Pharmacol 126, 276-285.
36. Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA & Wilson EM. (1995) Persistent DDT metabolite p, p'-DDE is a potent androgen receptor antagonist. Nature 375, 581-585.
37. Kelce WR, Lambright CR, Gray LEJ & Roberts KP. (1997) Vinclozolin and p, p'-DDE alter androgen-dependent gene expression: in vivo confirmation of an androgen receptor-mediated mechanism. Toxicol Appl Pharmacol 142, 192-200.
38. Kohn M, Parham F, Masten S, Portier C, Shelby M, Brock J & Needham J. (2000) Human exposure estimates for phthalates. Environ Health Perspect 108, A440-A442.
39. Kojima H, Katsura E, Takeuchi S, Niiyama K & Kobayashi K. (2004) Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells. Environ Health Perspect 112, 524-531.
40. Kristensen DM, Skalkam ML, Audouze K, Lesné L, Desdoits-Lethimonier C, Frederiksen H et al. (2010) Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis. Environ Health Perspect 119, 534-541.
41. Kristensen DM, Hass U, Lesné L, Lottrup G, Jacobsen PR, Desdoits-Lethimonier C et al. (2011) Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Hum Reprod 26, 235-244.
42. Laier P, Metzdorff SB, Borch J, Hagen ML, Hass U, Christiansen S et al. (2006) Mechanisms of action underlying the antiandrogenic effects of the fungicide prochloraz. Toxicol Appl Pharmacol 213, 160-171.
43. Ma R, Cotton B, Lichtensteiger W & Schlumpf M. (2003) UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci 74, 43-50.
44. McIntyre BS, Barlow NJ & Foster PMD. (2001) Androgen-mediated development in male rat offspring exposed to fluta-mide in utero: Permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues. Toxicol Sci 62, 236-249.
45. McIntyre BS, Barlow NJ & Foster PM. (2002) Male rats exposed to linuron in utero exhibit permanent changes in anogenital distance, nipple retention, and epididymal malformations that result in subsequent testicular atrophy. Toxicol Sci 65, 62-70.
46. McPherson SJ, Ellem SJ & Risbridger GP. (2008) Estrogen-regulated development and differentiation of the prostate. Differentiation 76, 660-670.
47. Menard C, Heraud F, Nougadere A, Volatier JL & LeBlanc JC. (2008) Relevance of integrating agricultural practices in pesticide dietary intake indicator. Food Chem Toxicol 46, 3240-3253.
48. Metzdorff SB, Dalgaard M, Christiansen S, Axelstad M, Hass U, Kiersgaard MK, Scholze M, Kortenkamp A & Vinggaard AM. (2007) Dysgenesis and histological changes of genitals and perturbations of gene expression in male rats after in utero exposure to antiandrogen mixtures. Toxicol Sci 98, 87-98.
49. Milmo S. (2011) Getting to grips with combined exposure and cumulative exposures. CHEMICAL WATCH, pp 9-10, [Cited 05/30/2011], Available from: (accessed on 26 January 2012).
50. Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, Yuji H, Shimatsu A, Kuzuya H & Nakao K. (2002) Thyroid hormone action is disrupted by bisphenol A as an antagonist. J Clin Endocrinol Metab 87, 5185-5190.
51. Mylchreest E, Cattley RC & Foster PM. (1998) Male reproductive tract malformations in rats following gestational and lactational exposure to Di(n-butyl) phthalate: an antiandrogenic mechanism? Toxicol Sci 43, 47-60.
52. Mylchreest E, Wallace DG, Cattley RC & Foster PM. (2000) Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to Di(n-butyl) phthalate during late gestation. Toxicol Sci 55, 143-151.
53. NRC. (2008) Phthalates Cumulative Risk Assessment - the Task Ahead. Committee on Phthalates Health Risks, National Research Council, National Academy of Sciences, Board on Environmental Science and Technology, USA.
54. Oliveira AG, Coelho PH, Guedes FD, Mahecha GA, Hess RA & Oliveira CA. (2007) 5alpha-Androstane-3beta, 17beta-diol (3beta-diol), an estrogenic metabolite of 5alpha-dihydrotestosterone, is a potent modulator of estrogen receptor ERbeta expression in the ventral prostrate of adult rats. Steroids 72, 914-22.
55. Orton F, Rosivatz E, Scholze M & Kortenkamp A. (2011) Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Antiandrogens. Environ Health Perspect 119, 794-800.
56. Ostby J, Kelce WR, Lambright C, Wolf CJ, Mann P & Gray LE Jr. (1999) The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro. Toxicol Ind Health 15, 80-93.
57. Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ & Gray LE Jr. (2000) The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58, 339-349.
58. Prins GS & Korach KS. (2008) The role of estrogens and estrogen receptors in normal prostate growth and disease. Steroids 73, 233-244.
59. Prins GS, Tang WY, Belmonte J & Ho S-M. (2008) Perinatal exposure to oestradiol and bisphenol A alters the prostate epigenome and increases susceptibility to carcinogenesis. Basic Clin Pharmacol Toxicol 102, 134-138.
60. Rider CV, Furr J, Wilson VS & Gray LE Jr. (2008) A mixture of seven antiandrogens induces reproductive malformations in rats. Int J Androl 31, 249-262.
61. Rider CV, Furr JR, Wilson VS & Gray LE Jr. (2010) Cumulative effects of in utero administration of mixtures of reproductive toxicants that disrupt common target tissues via diverse mechanisms of toxicity. Int J Androl 33, 443-462.
62. Salian S, Doshi T & Vanage G. (2009) Perinatal exposure of rats to Bisphenol A affects the fertility of male offspring. Life Sci 85, 742-752.
63. SCCP, Scientific Committee on Consumer Products, Directorate General for Health & Consumers. (2008) Opinion on 4-methylbenzylidene camphor (4-MBC). COLIPA no. S60, p. 10.
64. Schlumpf M, Cotton B, Conscience M, Haller V, Steinmann B & Lichtensteiger W. (2001) In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect 109, 239-244.
65. Schlumpf M, Kypke K, Wittassek M, Angerer J, Mascher H, Mascher D, Vökt C, Birchler M & Lichtensteiger W. (2010) 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 81, 1171-1183.
66. Schmutzler C, Hamann I, Hofmann PJ, Kovacs G, Stemmler L, Mentrup B et al. (2004) Endocrine active compounds affect thyrotropin and thyroid hormone levels in serum as well as endpoints of thyroid hormone action in liver, heart and kidney. Toxicology 205, 95-102.
67. Schreurs R, Lauser P, Seinen W & van den Burg B. (2002) Estrogenic activity of UV filters determined by an in vitro reporter gene assay and an in vivo transgenic zebrafish assay. Arch Toxicol 76, 257-261.
68. Schreurs RH, Sonneveld E, Jansen JH, Seinen W & van der Burg B. (2005) Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays. Toxicol Sci 83, 264-272.
69. Schultz VD, Phillips S, Sar M, Foster PMD & Gaido KW. (2001) Altered gene profiles in fetal rat testes after in utero exposure to Di(n-butyl) phthalate. Toxicol Sci 64, 233-242.
70. Scialli AR, Ang R, Breitmeyer J & Royal MA. (2010) A review of the literature on the effects of acetaminophen on preg-nancy outcome. Reprod Toxicol 30, 495-507.
71. Seidlova-Wuttke D, Jarry H, Christoffel J, Rimoldi G & Wuttke W. (2006) Comparison of effects of estradiol (E2) with those of octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC) - 2 filters of UV light - on several uterine, vaginal and bone parameters. Toxicol Appl Pharmacol 210, 246-254.
72. Simard J, Luthy I, Guay J, Belanger A & Labrie F. (1986) Characteristics of interaction of the antiandrogen flutamide with the androgen receptor in various target tissues. Mol Cell Endocrinol 44, 261-270.
73. Taxvig C, Hass U, Axelstad M, Dalgaard M, Boberg J, Andeasen HR & Vinggaard AM. (2007) Endocrine-disrupting activities in vivo of the fungicides tebuconazole and epoxiconazole. Toxicol Sci 100, 464-473.
74. Timms BG, Howdeshell KL, Barton L, Bradley S, Richter CA & vom Saal FS. (2005) Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra. PNAS 102, 7014-7019.
75. Tinwell H, Lefevre PA, Moffat GJ, Burns A, Odum J, Spurway TD, Orphanides G & Ashby J. (2002) Confirmation of uterotrophic activity of 3 (4-methylbenzylidene) camphor in the immature rat. Environ Health Perspect 110, 533-536.
76. Vinggaard AM, Christiansen S, Laier P, Poulsen ME, Breinholt V, Jarfelt K, Jacobsen H, Dalgaard M, Nellemann C & Hass U. (2005) Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring. Toxicol Sci 85, 886-897.
77. Vinggaard AM, Hass U, Dalgaard M, Andersen HR, Bonefeld-Jorgensen E, Christiansen S, Laier P & Poulsen ME. (2006) Prochloraz: an imidazole fungicide with multiple mechanisms of action. Int J Androl 29, 186-192.
78. Vinggaard AM, Niemela J, Wedebye EB & Jensen GE. (2008) Screening of 397 chemicals and development of a quantitative structure-activity relationship model for androgen receptor antagonism. Chem Res Toxicol 21, 813-823.
79. VKM Vitenskapskomiteen for Mattrygghet. (2006) (Norwegian Scientific Committee for Food Safety) Opinion of the panel on food additives, flavourings, processing aids, materials in contact with food and cosmetics of the Norwegian Scientific Committee for Food Safety, Risk assessment of parabens in cosmetics. 04/408-24 final.
80. Walters KA, Simanainen IJ & Handelsman DJ. (2010) Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models. Human Reprod Update 16, 543-558.
81. Wilkinson CF, Christoph GR, Julien E, Kelley JM, Kronenberg J, McCarthy J & Reiss R. (2000) Assessing the risks of exposures to multiple chemicals with a common mechanism of toxicity: how to cumulate? Regul Toxicol Pharmacol 31, 30-43.
82. Wilson VS, Lambright C, Furr J, Ostby J, Wood C, Held G & Gray LE Jr. (2004) Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis. Toxicol Lett 146, 207-215.
83. Wolf C, Lambright C, Mann P, Price M, Cooper RL, Ostby J & Gray LE Jr. (1999) Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p, p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol Ind Health 15, 94-118.
84. You L, Casanova M, Archibeque-Engle S, Sar M, Fan L & Heck HDA. (1998) Impaired male sexual development in perinatal Sprague-Dawley and Long- Evans hooded rats exposed in utero and lactationally to p, p'-DDE. Toxicol Sci 45, 162-173.
85. Zhu Y-S & Imperato-McGinley JL. (2009) 5alpha-reductase isozymes and androgen actions in the prostate. Ann NY Acad Sci 1155, 43-56.
86. Zoeller RT, Bansal R & Parris C. (2005) Bisphenol A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology 146, 607-612.