Human and ecological risk assessment of a crop protection chemical: A case study with the azole fungicide epoxiconazole

Critical Reviews in Toxicology

Volumn 44, Issue 2, 2014, Pages 176-210

  Chambers, Janice E ^a   Greim, Helmut ^b   Kendall, Ronald J ^c   Segner, Helmut ^d   Sharpe, Richard M ^e   Van Der Kraak, Glen ^f  

^a MISSISSIPPI STATE UNIVERSITY   (United States)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c TEXAS TECH UNIVERSITY   (United States)

^d UNIVERSITY OF BERN   (Switzerland)

^e UNIVERSITY OF EDINBURGH   (United Kingdom)

^f UNIVERSITY OF GUELPH   (Canada)

Author keywords

Azole fungicides; Azoles; Endocrine disruption; Epoxiconazole; Risk assessment

Indexed keywords

AROMATASE; EPOXICONAZOLE; FUNGICIDE; GLUCOCORTICOID; PYRROLE DERIVATIVE; RETINOIC ACID; STEROL 14ALPHA DEMETHYLASE; UNCLASSIFIED DRUG; VITELLOGENIN;

ACUTE TOXICITY; ADVERSE OUTCOME; ALGA; AMPHIBIA; BIOSAFETY; BIRD; CASE STUDY; CHRONIC TOXICITY; CLEFT PALATE; CONSUMER; CROP PROTECTION; DRUG EFFECT; ENDOCRINE FUNCTION; ENVIRONMENTAL EXPOSURE; ENZYME INHIBITION; FISH; FOOD CHAIN; HAZARD ASSESSMENT; HUMAN; LEMNA; MACROPHYTE; NONHUMAN; REPRODUCTIVE TOXICITY; REPTILE; REVIEW; RISK ASSESSMENT; SENSITIVITY ANALYSIS; SKELETON MALFORMATION; STEROIDOGENESIS; TOXICITY TESTING; WILDLIFE;

ANIMALS; CROPS, AGRICULTURAL; ECOSYSTEM; ENDOCRINE DISRUPTORS; EPOXY COMPOUNDS; FUNGICIDES, INDUSTRIAL; HUMANS; LETHAL DOSE 50; RISK ASSESSMENT; TOXICITY TESTS; TRIAZOLES;

EID: 84893457734     PISSN: 10408444     EISSN: 15476898     Source Type: Journal    
DOI: 10.3109/10408444.2013.855163     Document Type: Review

References (225)

1. Abinawanto SK, Sugishima N, Shiokawa T. (1997). Sex-reversal effects of non-steroidal aromatase inhibitor on aromatase (P450arom) mRNA expression in adult chicken gonads. Jpn Poult Sci, 34, 158-68.
2. Abu-Abed S, Dolle P, Metzger D, et al. (2001). The retinoic acidmetabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures. Genes Dev, 15, 226-40. (Pubitemid 32107667)
3. Ackermans MM, Zhou H, Carels E, et al. (2011). Vitamin A and clefting: putative biological mechanisms. Nutr Rev, 69, 613-24.
4. Akcha F, Arzul G, Rousseau S, Bardouil M. (2008). Comet assay in phytoplankton as biomarker of genotoxic effects of environmental pollution. Mar Environ Res, 66, 59-61.
5. Albrecht ED, Aberdeen W, Pepe GJ. (2000). The role of estrogen in the maintenance of primate pregnancy. Am J Obstet Gynecol, 182, 432-8. (Pubitemid 30127359)
6. Amaral VC, Nunes Jr GP,. (2009). Prednisone reduces ketoconazoleinduced skeletal defects in rat fetuses. Arch Toxicol, 83, 863-71.
7. Amrani L, Zerguine K, Farine JP, et al. (2004). Imidazole derivative KK-42 reduces ecdysteroid titers and interferes with reproductive processes in adult females of Tenebrio molitor. Pest Biochem Physiol, 80, 163-72. (Pubitemid 39547808)
8. Andersen L, Kinnberg K, Holbech H, et al. (2004). Evaluation of a 40 day assay for testing endocrine disrupters: effects of an anti-estrogen and an aromatase inhibitor on sex ratio and vitellogenin concentrations in juvenile zebrafish (Danio rerio). Fish Physiol Biochem, 30, 257-66. (Pubitemid 43055343)
9. Ankley GT, Bencic DC, Breen MS, et al. (2009a). Endocrine disrupting chemicals in fish: developing exposure indicators and predictive models of effects based on mechanism of action. Aquat Toxicol, 92, 168-78.
10. Ankley GT, Bencic DC, Cavallin JE, et al. (2009b). Dynamic nature of alterations in the endocrine system of fathead minnows exposed to the fungicide prochloraz. Toxicol Sci, 112, 344-53.
11. Ankley GT, Cavallin JE, Durhan EJ, et al. (2012). A time-course analysis of effects of the steroidogenesis inhibitor ketoconazole on components of the hypothalamic-pituitary-gonadal axis of fathead minnows. Aquat Toxicol, 114-115, 88-95.
12. Ankley GT, Cebrian ME, Daston G, et al. (2003). Report of the Joint IPCS-Japan Workshop on "Endocrine Disruptors: research Needs and Future Directions".
13. Ankley GT, Daston GP, Degitz SJ, et al. (2006). Toxicogenomics in regulatory ecotoxicology. Environ Sci Technol, 40, 4055-65. (Pubitemid 44164241)
14. Ankley GT, Jensen KM, Durhan EJ, et al. (2005). Effects of two fungicides with multiple modes of action on reproductive endocrine function in the fathead minnow (Pimephales promelas). Toxicol Sci, 86, 300-8. (Pubitemid 41418643)
15. Ankley GT, Jensen KM, Kahl MD, et al. (2007). Ketoconazole in the fathead minnow (Pimephales promelas): reproductive toxicity and biological compensation. Environ Toxicol Chem, 26, 1214-23. (Pubitemid 46932682)
16. Ankley GT, Kahl MD, Jensen KM, et al. (2002). Evaluation of the aromatase inhibitor fadrozole in a short-term reproduction assay with the fathead minnow (Pimephales promelas). Toxicol Sci, 67, 21-30.
17. Baldwin WS, Marko PB & Nelson DR. (2009). The cytochrome P450 (CYP) gene superfamily in Daphnia pulex. BMC Genomics, 10, 169.
18. Bar-Oz B, Moretti ME, Bishai R, et al. (2000). Pregnancy outcome after in utero exposure to itraconazole: a prospective cohort study. Am J Obstet Gynecol, 183, 617-20.
19. Barnett CP, Chitayat D, Bradley TJ, et al. (2011). Dexamethasone normalizes aberrant elastic fiber production and collagen 1 secretion by Loeys-Dietz syndrome fibroblasts: a possible treatment? Eur J Hum Genet, 19, 624-33.
20. Baudiffier D, Hinfray N, Vosges M, et al. (2012). A critical role of follicle-stimulating hormone (Fsh) in mediating the effect of clotrimazole on testicular steroidogenesis in adult zebrafish. Toxicology, 298, 30-9.
21. Belaid B, Richard-Mercier N, Pieau C, Dorizzi M. (2001). Sex reversal and aromatase in the European pond turtle: treatment with letrozole after the thermosensitive period for sex determination. J Exp Zool, 290, 490-7. (Pubitemid 32930898)
22. Berenzen N, Hümmer S, Liess M, Schulz R. (2003). Pesticide peak discharge from wastewater treatment plants into streams during the main period of insecticide application: ecotoxicological evaluation in comparison to runoff. Bull Environ Contam Toxicol, 70, 891-7. (Pubitemid 36514406)
23. Berenzen N, Lentzen-Godding A, Probst M, et al. (2005). A comparison of predicted and measured levels of runoff-related pesticide concentrations in small lowland streams on a landscape level. Chemosphere, 58, 683-91. (Pubitemid 40023204)
24. Berg C, Gyllenhammar I, Kvarnryd M. (2009). Xenopus tropicalis as a test system for developmental and reproductive toxicity. J Toxicol Environ Health A, 72, 219-25.
25. Bergman A, Andersson A-M, Becher G, et al. (2013). Science and policy on endocrine disrupters must not be mixed: a reply to a "common sense" intervention by toxicology journal editors. Environmental Health, 12, 69.
26. Blake J, Wynn S, Maumene C, Jørgensen LN. (2011). Evaluation of the benefits provided by the azole class of compounds in wheat, and the effect of losing all azoles on wheat and potatoes in Denmark, France and the UK: report 1-Impact of the loss of all azoles.
27. Brock TCM, Arts GHP, Ten Hulscher TEM., et al. (2011). Aquatic effect assessment for plant protection products: dutch proposal that addresses the requirements of the Plant Protection Product Regulation and Water Framework Directive, Wageningen, Alterra Wageningen UR.
28. Buerge IJ, Poiger T, Muller MD, Buser HR. (2006). Influence of pH on the stereoselective degradation of the fungicides epoxiconazole and cyproconazole in soils. Environ Sci Technol, 40, 5443-50. (Pubitemid 44373111)
29. Cardone A, Comitato R, Bellini L, Angelini F. (2002). Effects of the aromatase inhibitor fadrozole on plasma sex steroid secretion, spermatogenesis and epididymis morphology in the lizard, Podarcis sicula. Mol Reprod Dev, 63, 63-70. (Pubitemid 34831315)
30. Carmichael SL, Shaw GM, Ma C, et al. (2007). Maternal corticosteroid use and orofacial clefts. Am J Obstet Gynecol, 197, 585e1-7; discussion 683-4, e1-7.
31. Carney EW, Kimmell CA. (2007). Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs. Birth Defects Res B, 80, 473-96.
32. Casper RF, Mitwally MF. (2011). Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clin Obstet Gynecol, 54, 685-95.
33. Cedergreen N, Streibig JC. (2005). The toxicity of herbicides to nontarget aquatic plants and algae: assessment of predictive factors and hazard. Pest Manag Sci, 61, 1152-60. (Pubitemid 41617500)
34. Chai X, Zhang J, Hu H, et al. (2009). Design, synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P450 14a-demethylase. Eur J Med Chem, 44, 1913-20.
35. Chardard D, Dournon C. (1999). Sex reversal by aromatase inhibitor treatment in the newt Pleurodeles waltl. J Exp Zool, 283, 43-50. (Pubitemid 29042910)
36. Ciolino HP, Dai Z, Nair V. (2011). Retinol inhibits aromatase activity and expression in vitro. J Nutr Biochem, 22, 522-6.
37. Conley A, Hinshelwood M. (2001). Mammalian aromatases. Reproduction, 121, 685-95. (Pubitemid 32472054)
38. Crespo CJ, Smit E, Snelling A, et al. (2002). Hormone replacement therapy and its relationship to lipid and glucose metabolism in diabetic and nondiabetic postmenopausal women: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care, 25, 1675-80. (Pubitemid 41071069)
39. Crews D, Bergeron J. (1994). Role of reductase and aromatase in sex determination in the red-eared slider (Trachemys scripta), a turtle with temperature-dependent sex determination. J Endocrinol, 143, 279-89. (Pubitemid 24347783)
40. Cummings AM, Hedge JL, Laskey J. (1997). Ketoconazole impairs early pregnancy and the decidual cell response via alterations in ovarian function. Fundam Appl Toxicol, 40, 238-46.
41. Czeizel A, Rockenbauer M. (1998). A population based case-control teratologic study of oral metronidazole treatment during pregnancy. Brit J Obstet Gynaec, 105, 322.
42. Czeizel AE. (1997). First 25 years of the Hungarian congenital abnormality registry. Teratology, 55, 299-305. (Pubitemid 27389919)
43. Czeizel AE, Fladung B, Vargha P. (2004a). Preterm birth reduction after clotrimazole treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol, 116, 157-63. (Pubitemid 39195126)
44. Czeizel AE, Kazy Z, Puhó E. (2004b). Population-based case-control teratologic study of topical miconazole. Congenital Anomalies, 44, 41-5.
45. Czeizel AE, Kazy Z, Vargha P. (2003). A population-based case-control teratological study of vaginal econazole treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol, 111, 135-40. (Pubitemid 37338730)
46. Czeizel AE, Rockenbauer M, Siffel C, Varga E. (2001). Description and mission evaluation of the Hungarian case-control surveillance of congenital abnormalities, 1980-1996. Teratology, 63, 176-85. (Pubitemid 32417246)
47. Czeizel AE, Tóth M, Rockenbauer M. (1999). No teratogenic effect after clotrimazole therapy during pregnancy. Epidemiology, 10, 437-40. (Pubitemid 29288244)
48. DAR. (2006a). Draft Assessment Report (DAR), public version. Initial risk assessment provided by the Rapporteur Member State Germany for the existing active substance epoxiconazole of the third stage (part A) of the review programme referred to in Article 8(2) of Council Directive (human health-toxicology exposure). In: R. M. S. GERMANY, editor. Annex B, B.1-B7.
49. DAR (2006b). Draft Assessment Report (DAR), public version. Initial risk assessment provided by the Rapporteur Member State Germany for the existing active substance epoxiconazole of the third stage (part A) of the review programme reffered to in Article 8(2) of Council Directive (ecotoxicology). In: GERMANY, R. M. S. (ed.) Annex B, B.9, parts 1 and 2.
50. Davis TD, Curry EA, Steffens GL. (1991). Chemical regulation of vegetative growth. Crit Rev Plant Sci, 10, 151-88.
51. De Santis M, Di Gianantonio E, Cesari E, et al. (2009). First-trimester itraconazole exposure and pregnancy outcome: a prospective cohort study of women contacting teratology information services in Italy. Drug Saf, 32, 239-44.
52. Deladoey J, Fluck C, Bex M, et al. (1999). Aromatase deficiency caused by a novel P450arom gene mutation: impact of absent estrogen production on serum gonadotropin concentration in a boy. J Clin Endocrinol Metab, 84, 4050-4. (Pubitemid 30644193)
53. Derfoul A, Perkins GL, Hall DJ, Tuan RS. (2006). Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes. Stem Cells, 24, 1487-95. (Pubitemid 44464665)
54. Di Renzo F, Rossi F, Bacchetta R, et al. (2011). Expression analysis of some genes regulated by retinoic acid in controls and triadimefonexposed embryos: is the amphibian Xenopus laevis a suitable model for gene-based comparative teratology? Birth Defects Res B Dev Reprod Toxicol, 92, 189-94.
55. Dijksterhuis J, Van Doorn T, Samson R, Postma J. (2011). Effects of seven fungicides on non-target aquatic fungi. Water, Air, Soil Pollution, 222, 421-5.
56. Do Rego JL, Tremblay Y, Luu-The V, et al. (2007). Immunohistochemical localization and biological activity of the steroidogenic enzyme cytochrome P450 17alpha-hydroxylase/C17, 20-lyase (P450C17) in the frog brain and pituitary. J Neurochem, 100, 251-68. (Pubitemid 46085853)
57. Dodo T, Uchida K, Hirose T, et al. (2010). Increases in discontinuous rib cartilage and fused carpal bone in rat fetuses exposed to the teratogens, busulfan, acetazolamide, vitamin A, and ketoconazole. Hum Exp Toxicol, 29, 439-50.
58. Domingues I, Oliveira R, Musso C, et al. (2013). Prochloraz effects on biomarkers activity in zebrafish early life stages and adults. Environ Toxicol, 28, 155-63.
59. Dorizzi M, Richard-Mercier N, Desvages G, et al. (1994). Masculinization of gonads by aromatase inhibitors in a turtle with temperature-dependent sex determination. Differentiation, 58, 1-8. (Pubitemid 24361121)
60. Dubrovsky EB. (2005). Hormonal cross talk in insect development. Trends Endocrin Met, 16, 6-11. (Pubitemid 40037721)
61. 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). EFSA, EFSA-Q-2005-100, 1-75.
62. EFSA (2008). Conclusion regarding the peer review of the pesticide risk assessment of the active substance epoxiconazole. EFSA Journal, 80, 1-442.
63. EFSA (2009). Scientific opinion on risk assessment for a selected group of pesticides from the triazole group to test possible methodologies to assess cumulative effects from exposure through food from these pesticides on human health1. EFSA Report. European Food Safety Commission.
64. EFSA. (2012). Reasoned opinion on the modification of the exsting MRLs for epoxiconazole in products of animal origin. EFSA Journal, 10, 2795.
65. Elbrecht A, Smith RG. (1992). Aromatase enzyme activity and sex determination in chickens. Science, 255, 467-70.
66. Fairchild J, Ruessler D, Haverland P, Carlson A. (1997). Comparative sensitivity of Selenastrum capricornutum and Lemna minor to sixteen herbicides. Arch Environ Contam Toxicol, 32, 353-7. (Pubitemid 27287531)
67. Fairchild JF, Ruessler DS, Carlson AR. (1998). Comparative sensitivity of five species of macrophytes and six species of algae to atrazine, metribuzin, alachlor, and metolachlor. Environ Toxicol Chem, 17, 1830-4. (Pubitemid 28390166)
68. Fenske M, Segner H. (2004). Aromatase modulation alters gonadal differentiation in developing zebrafish (Danio rerio). Aquat Toxicol, 67, 105-26. (Pubitemid 38299338)
69. Fisher CR, Graves KH, Parlow AF, Simpson ER. (1998). Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci USA, 95, 6965-70. (Pubitemid 28278090)
70. Frampton G, Jansch S, Scott-Fordsmand J. (2006). Effects of pesticides on soil invertebrates in laboratory studies: a review and analysis using species sensitivity distributions. Environ Toxicol Chem, 25, 2480.
71. Frampton G, Wratten S. (2000). Effects of benzimidazole and triazole fungicide use on epigeic species of Collembola in wheat. Ecotoxicol Environ Saf, 46, 64-72. (Pubitemid 30331821)
72. Frank S, Madlener M, Werner S. (1996). Transforming growth factors beta1, beta2, and beta3 and their receptors are differentially regulated during normal and impaired wound healing. J Biol Chem, 271, 10188-93. (Pubitemid 26131583)
73. Furukawa, S, Hayashi S, Usuda K, et al. (2008). Histopathological effect of ketoconazole on rat placenta. J Vet Med Sci, 70, 1179-84.
74. Georgopapadakou NH. (1998). Antifungals: mechanism of action and resistance, established and novel drugs. Curr Opin Microbiol, 1, 547-57. (Pubitemid 128433642)
75. Georgopapadakou NH, Walsh TJ. (1996). Antifungal agents: chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother, 40, 279-91. (Pubitemid 26053134)
76. Giavini E, Menegola E. (2010). Are azole fungicides a teratogenic risk for human conceptus? Toxicol Lett, 198, 106-11.
77. Giddings JM, Arts G, Hommen U. (2013). The relative sensitivity of macrophyte and algal species to herbicides and fungicides: an analysis using species sensitivity distributions. Integr Environ Assess Manag, 9, 308-18.
78. Gilbert LI. (2004). Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster. Mol Cell Endocrinol, 215, 1-10. (Pubitemid 38333237)
79. Goetz AK, Ren H, Schmid JE, et al. (2007). Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat. Toxicol Sci, 95, 227-39. (Pubitemid 44942793)
80. Groppelli S, Pennati R, De Bernardi F, et al. (2005). Teratogenic effects of two antifungal triazoles, triadimefon and triadimenol, on Xenopus laevis development: craniofacial defects. Aquat Toxicol, 73, 370-81.
81. Grote K, Niemann L, Selzsam B, et al. (2008). Epoxiconazole causes changes in testicular histology and sperm production in the Japanese quail (Coturnix coturnix japonica). Environ Toxicol Chem, 27, 2368-74.
82. Guan Z, Chai X, Yu S, et al. (2010). Synthesis, molecular docking, and biological evaluation of novel triazole derivatives as antifungal agents. Chem Biol Drug Des, 76, 496-504.
83. Gust M, Garric J, Giamberini L, et al. (2010). Sensitivity of New Zealand mudsnail Potamopyrgus antipodarum (Gray) to a specific aromatase inhibitor. Chemosphere, 79, 47-53.
84. Haeba MH, Hilscherova K, Mazurova E, Blaha L. (2008). Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna. Environ Sci Pollut Res Int, 15, 222-7.
85. Hassold E, Backhaus T. (2009). Chronic toxicity of five structurally diverse demethylase-inhibiting fungicides to the crustacean Daphnia magna: a comparative assessment. Environ Toxicol Chem, 28, 1218-26.
86. He W, Meng T, Wu M, et al. (2010). Perturbation of Fgf10 signal pathway in mouse embryonic palate by dexamethasone and vitamin B12 in vivo. J Pediatr Surg, 45, 2030-5.
87. Hermsen SA, Van Den Brandhof EJ, Van Der Ven LT, Piersma AH. (2011). Relative embryotoxicity of two classes of chemicals in a modified zebrafish embryotoxicity test and comparison with their in vivo potencies. Toxicol In Vitro, 25, 745-53.
88. Holbech H, Kinnberg KL, Brande-Lavridsen N, et al. (2012). Comparison of zebrafish (Danio rerio) and fathead minnow (Pimephales promelas) as test species in the Fish Sexual Development Test (FSDT). Comp Biochem Physiol C Toxicol Pharmacol, 155, 407-15.
89. Janer G, Porte C. (2007). Sex steroids and potential mechanisms of nongenomic endocrine disruption in invertebrates. Ecotoxicology, 16, 145-60. (Pubitemid 46292042)
90. Jensen BH, Petersen A, Christiansen S, et al. (2013). Probabilistic assessment of the cumulative dietary exposure of the population of Denmark to endocrine disrupting pesticides. Food Chem Toxicol, 55, 113-20.
91. Jensen KM, Ankley GT. (2006). Evaluation of a commercial kit for measuring vitellogenin in the fathead minnow (Pimephales promelas). Ecotoxicol Environ Saf, 64, 101-5. (Pubitemid 43766112)
92. Ji H, Zhang W, Zhou Y, et al. (2000). A three-dimensional model of lanosterol 14a-demethylase of Candida albicans and its interaction with azole antifungals. J Med Chem, 43, 2493-505. (Pubitemid 30437131)
93. Jick SS. (1999). Pregnancy outcomes after maternal exposure to fluconazole. Pharmacotherapy, 19, 221-2. (Pubitemid 29072033)
94. Johansen NS, Moen LH, Egaas E. (2007). Sterol demethylation inhibitor fungicides as disruptors of insect development and inducers of glutathione S-transferase activities in Mamestra brassicae. Comp Biochem Physiol C Toxicol Pharmacol, 145, 473-83. (Pubitemid 46501776)
95. Kale P, Johnson LB. (2005). Second-generation azole antifungal agents. Drugs Today, 41, 91-106.
96. Kazy Z, Czeizel E. (2005). [A population-based case-control study of broncho-vaxom use during pregnancy]. Orv Hetil, 146, 2359-61. (Pubitemid 46141560)
97. Kazy Z, Puho E, Czeizel AE. (2005a). Population-based case-control study of oral ketoconazole treatment for birth outcomes. Congenit Anom (Kyoto), 45, 5-8. (Pubitemid 41657747)
98. Kazy Z, Puho E, Czeizel AE. (2005b). The possible association between the combination of vaginal metronidazole and miconazole treatment and poly-syndactyly Population-based case-control teratologic study. Reprod Toxicol, 20, 89-94. (Pubitemid 40459656)
99. Kazy Z, Puho E, Czeizel AE. (2005c). Teratogenic potential of vaginal metronidazole treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol, 123, 174-8. (Pubitemid 41728361)
100. Kendall RJ, Lacher TE, Cobb GC, Cox SB. (2010). Wildlife toxicology: emerging contaminant and biodiversity issues. Boca Raton: CRC Press.
101. Kenneke JF, Mazur CS, Kellock KA, Overmyer JP. (2009). Mechanistic Approach to understanding the toxicity of the azole fungicide triadimefon to a nontarget aquatic insect and implications for exposure assessment. Environ Sci Technol, 43, 5507-13.
102. King CT, Rogers PD, Cleary JD, Chapman SW. (1998). Antifungal therapy during pregnancy. Clin Infect Dis, 27, 1151-60. (Pubitemid 29242465)
103. Kinnberg K, Holbech H, Petersen GI, Bjerregaard P. (2007). Effects of the fungicide prochloraz on the sexual development of zebrafish Danio rerio. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol, 145, 165-70. (Pubitemid 46341989)
104. Kitano T, Takamune K, Nagahama Y, Abe SI. (2000). Aromatase inhibitor and 17alpha-methyltestosterone cause sex-reversal from genetical females to phenotypic males and suppression of P450 aromatase gene expression in Japanese flounder (Paralichthys olivaceus). Mol Reprod Dev, 56, 1-5. (Pubitemid 30193856)
105. Kjærstad MB, Andersen HR, Taxvig C, et al. (2007). Effects of azole fungicides on the function of sex and thyroid hormones. Kobenhavn: Danish Ministry of the Environment/Environmental Protection Agency. Research No. 111, 75p.
106. Kjaerstad MB, Taxvig C, Nellemann C, et al. (2010). Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals. Reprod Toxicol, 30, 573-82.
107. Koltin Y, Hitchcock CA. (1997). The search for new triazole antifungal agents. Curr Opin Chem Biol, 1, 176-82. (Pubitemid 127437142)
108. Kumar PR, Kanniappan M, Mathuram LN, et al. (2011). Effect of hexaconazole on reproductive performance in female rats. ROAVS, 1, 74-7.
109. Kumar S. (2010). Effect of 2,4-D and isoproturon on chromosomal disturbances during mitotic division in root tip cells of Triticum aestivum L. Tsitol Genet, 44, 14-21.
110. Kwon JY, Haghpanah V, Kogson-Hurtado LM, et al. (2000). Masculinization of genetic female nile tilapia (Oreochromis niloticus) by dietary administration of an aromatase inhibitor during sexual differentiation. J Exp Zool, 287, 46-53. (Pubitemid 30392713)
111. Lafont R. (2000). The Endocrinology of Invertebrates. Ecotoxicology, 9, 41-57.
112. Lafont R, Mathieu M. (2007). Steroids in aquatic invertebrates. Ecotoxicology, 16, 109-30. (Pubitemid 46292044)
113. Lammer EJ, Chen DT, Hoar RM, et al. (1985). Retinoic acid embryopathy. N Engl J Med, 313, 837-41. (Pubitemid 15250197)
114. Lance VA, Bogart MH. (1992). Disruption of ovarian development in alligator embryos treated with an aromatase inhibitor. Gen Comp Endocrinol, 86, 59-71.
115. Langlois V, Duarte-Guterman P, Trudeau V. (2011). Expression profiles of reproduction-and thyroid hormone-related transcripts in the brains of chemically-induced intersex frogs. Sex Dev, 5, 26.
116. Langlois VS, Carew AC, Pauli BD, et al. (2010). Low levels of the herbicide atrazine alter sex ratios and reduce metamorphic success in Rana pipiens tadpoles raised in outdoor mesocosms. Environ Health Perspect, 118, 552-57.
117. Latrille F, Charuel C, Lodola A. (1989). A comparative study of the effects of ketoconazole and fluconazole on 17-beta estradiol production by rat ovaries in vitro. Res Commun Chem Pathol Pharmacol, 64, 173-6. (Pubitemid 19123241)
118. Le Curieux-Belfond O, Moslemi S, Mathieu M, Séralini GE. (2001). Androgen metabolism in oyster Crassostrea gigas: evidence for 17b-HSD activities and characterization of an aromatase-like activity inhibited by pharmacological compounds and a marine pollutant. J Steroid Biochem, 78, 359-66. (Pubitemid 33079111)
119. Leboucher G, Beguin N, Mauget R, Kreutzer M. (1998). Effects of fadrozole on sexual displays and reproductive activity in the female canary. Physiol Behav, 65, 233-40. (Pubitemid 28548643)
120. Lee RF. (1998). Annelid cytochrome P-450. Compar Biochem Physiol C, 121, 173-9. (Pubitemid 28529361)
121. Luster D, Miller P. (1993). Triazole plant growth regulator binding to native and detergent-solubilized plant microsomal cytochrome P450.Pest Biochem Physiol, 46, 27-39
122. Mahmood R, Flanders KC, Morriss-Kay GM. (1992). Interactions between retinoids and TGF beta s in mouse morphogenesis. Development, 115, 67-74.
123. Maldonado E, Murillo J, Barrio C, et al. (2011). Occurrence of cleftpalate and alteration of Tgf-beta(3) expression and the mechanisms leading to palatal fusion in mice following dietary folic-acid deficiency. Cells Tissues Organs, 194, 406-20.
124. Maltby L, Brock TC, Van Den Brink PJ. (2009). Fungicide risk assessment for aquatic ecosystems: importance of interspecific variation, toxic mode of action, and exposure regime. Environ Sci Technol, 43, 7556-63.
125. Markov GV, Tavares R, Dauphin-Villemant C, et al. (2009). Independent elaboration of steroid hormone signaling pathways in metazoans. Proc Natl Acad Sci USA, 106, 11913-18.
126. Marotta F, Tiboni GM. (2010). Molecular aspects of azoles-induced teratogenesis. Expert Opin Drug Metab Toxicol, 6, 461-82.
127. Mastroiacovo P, Mazzone T, Botto LD, et al. (1996). Prospective assessment of pregnancy outcomes after first-trimester exposure to fluconazole. Am J Obstet Gynecol, 175, 1645-50. (Pubitemid 27021041)
128. Matsumoto T, Osada M, Osawa Y, Mori K. (1997). Gonadal estrogen profile and immunohistochemical localization of steroidogenic enzymes in the oyster and scallop during sexual maturation. Comp Biochem Physiol B Biochem Mol Biol, 118, 811-17. (Pubitemid 28088027)
129. Mcdonald H, O'Loughlin J, Vigneswaran R, et al. (1997). Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial. Intern J Obst Gynaecol, 104, 1391-7. (Pubitemid 27517637)
130. Mellert W. (1992). Study of the potential carcinogencity of Reg. No. 205259 (Epoxiconazole) in Wistar rats: administration via the diet over 24 months. Limburgerhof, Germany: BASF.
131. Menegola E, Broccia ML, Di Renzo F, Giavini E. (2006). Postulated pathogenic pathway in triazole fungicide induced dysmorphogenic effects. Reprod Toxicol, 22, 186-95. (Pubitemid 43994387)
132. Menegola E, Broccia ML, Di Renzo F, et al. (2004). Relationship between hindbrain segmentation, neural crest cell migration and branchial arch abnormalities in rat embryos exposed to fluconazole and retinoic acid in vitro. Reprod Toxicol, 18, 121-30. (Pubitemid 38175454)
133. Menegola E, Broccia ML, Di Renzo F, et al. (2000). In vitro teratogenic potential of two antifungal triazoles: triadimefon and triadimenol. In Vitro Cell Dev Biol Anim, 36, 88-95. (Pubitemid 30141615)
134. Miller WR, Anderson TJ, Dixon JM. (2002). Anti-tumor effects of letrozole. Cancer Invest, 20, 15-21. (Pubitemid 35303439)
135. Mineshima H, Fukuta T, Kato E, et al. (2012). Malformation spectrum induced by ketoconazole after single administration to pregnant rats during the critical period-comparison with vitamin A-induced malformation spectrum. J Appl Toxicol, 32, 98-107.
136. Monod G, Rime H, Bobe J, Jalabert B. (2004). Agonistic effect of imidazole and triazole fungicides onin vitro oocyte maturation in rainbow trout (Oncorhynchus mykiss). Mar Environ Res, 58, 143-6. (Pubitemid 38738874)
137. Morales WJ, Schorr S, Albritton J. (1994). Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled double-blind study. Am J Obstet Gynecol, 171, 345.
138. Mu X, Pang S, Sun X, et al. (2013). Evaluation of acute and developmental effects of difenoconazole via multiple stage zebrafish assays. Environ Pollut, 175, 147-57.
139. Mullis PE, Yoshimura N, Kuhlmann B, et al. (1997). Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood. J Clin Endocrinol Metab, 82, 1739-45. (Pubitemid 127495177)
140. Nishikimi H, Kansaku N, Saito N. (2000). Sex differentiation and mRNA expression of P450c17, P450arom and AMH in gonads of the chicken. Mol Reprod Dev, 55, 20-30.
141. Nyman A-M, Schirmer K, Ashauer R. (2012). Toxicokinetictoxicodynamic modelling of survival of Gammarus pulex in multiple pulse exposures to propiconazole: model assumptions, calibration data requirements and predictive power. Ecotoxicology, 21, 1828-40.
142. Oestreich A, Schmid P, Schlatter C. (1997). Biological monitoring of the fungicide epoxiconazol during application. Arch Environ Contam Toxicol, 33, 329-35. (Pubitemid 27510172)
143. Ohlsson A, Cedergreen N, Oskarsson A, Ulleras E. (2010). Mixture effects of imidazole fungicides on cortisol and aldosterone secretion in human adrenocortical H295R cells. Toxicology, 275, 21-8.
144. Osada M, Tawarayama H, Mori K. (2004). Estrogen synthesis in relation to gonadal development of Japanese scallop, Patinopecten yessoensis: gonadal profile and immunolocalization of P450 aromatase and estrogen. Comp Biochem Physiol B Biochem Mol Biol, 139, 123-8. (Pubitemid 39208652)
145. Panter GH, Hutchinson TH, Hurd KS, et al. (2004). Successful detection of (anti-)androgenic and aromatase inhibitors in pre-spawning adult fathead minnows (Pimephales promelas) using easily measured endpoints of sexual development. Aquat Toxicol, 70, 11-21. (Pubitemid 39296969)
146. Papis E, Bernardini G, Gornati R, et al. (2007). Gene expression in Xenopus laevis embryos after Triadimefon exposure. Gene Expr Patterns, 7, 137-42. (Pubitemid 44712734)
147. Papis E, Bernardini G, Gornati R, Prati M. (2006). Triadimefon causes branchial arch malformations in Xenopus laevis embryos. Environ Sci Pollut Res Int, 13, 251-5. (Pubitemid 44140730)
148. Park-Wyllie L, Mazzotta P, Pastuszak A, et al. (2000). Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology, 62, 385-92.
149. Paveley ND, Sylvester-Bradley R, Scott RK, et al. (2001). Steps in
150. Pennati R, Groppelli S, Zega G, et al. (2006). Toxic effects of two pesticides, Imazalil and Triadimefon, on the early development of the ascidian Phallusia mammillata (Chordata, Ascidiacea). Aquat Toxicol, 79, 205-12. (Pubitemid 44279078)
151. Perkins EJ, Garcia-Reyero N, Villeneuve DL, et al. (2008). Perturbation of gene expression and steroidogenesis with in vitro exposure of fathead minnow ovaries to ketoconazole. Mar Environ Res, 66, 113-15.
152. Piferrer F, Zanuy S, Carrillo M, et al. (1994). Brief treatment with an aromatase inhibitor during sex differentiation causes chromosomally female salmon to develop as normal, functional males. J Exp Zool, 270, 255-62. (Pubitemid 2146767)
153. Poulsen ME, Christensen HB, Herrmann SS. (2009). Proficiency test on incurred and spiked pesticide residues in cereals. Accreditation and Quality Assurance, 14, 477-85.
154. Pradat P, Robert-Gnansia E, Di Tanna GL, et al. (2003). First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol, 67, 968-70. (Pubitemid 38018036)
155. Probst M, Berenzen N, Lentzen-Godding A, Schulz R. (2005). Scenariobased simulation of runoff-related pesticide entries into small streams on a landscape level. Ecotoxicol Environ Saf, 62, 145-59. (Pubitemid 41196112)
156. Pursley TJ, Blomquist IK, Abraham J, et al. (1996). Fluconazole-induced congenital anomalies in three infants. Clin Infect Dis, 22, 336-40. (Pubitemid 26056165)
157. Quignot N, Desmots S, Barouki R, Lemazurier E. (2012). A comparison of two human cell lines and two rat gonadal cell primary cultures as in vitro screening tools for aromatase modulation. Toxicol In Vitro, 26, 107-18.
158. Ramwell CT, Johnson PD, Boxall AB, Rimmer DA. (2005). Pesticide residues on the external surfaces of field crop sprayers: occupational exposure. Ann Occup Hyg, 49, 345-50. (Pubitemid 40806924)
159. Rasmussen JJ, Monberg RJ, Baattrup-Pedersen A, et al. (2012). Effects of a triazole fungicide and a pyrethroid insecticide on the decomposition of leaves in the presence or absence of macroinvertebrate shredders. Aquat Toxicol, 118-119, 54-61.
160. Reijntjes S, Blentic A, Gale E, Maden M. (2005). The control of morphogen signalling: regulation of the synthesis and catabolism of retinoic acid in the developing embryo. Dev Biol, 285, 224-37. (Pubitemid 41242827)
161. Reitzel AM, Tarrant AM. (2010). Correlated evolution of androgen receptor and aromatase revisited. Molecular Biol Evol, 27, 2211-15.
162. Rentz N, Hanson M. (2009). Duckweed toxicity tests are appropriate for era. Integr Environ Assess Manag, 5, 350-1.
163. Rewitz K, Rybczynski R, Warren J, Gilbert L. (2006a). The Halloween genes code for cytochrome P450 enzymes mediating synthesis of the insect moulting hormone. Biochem Soc Trans, 34, 1256-60. (Pubitemid 46769033)
164. Rewitz KF, Styrishave B, Lobner-Olsen A, Andersen O. (2006b). Marine invertebrate cytochrome P450: emerging insights from vertebrate and insects analogies. Comp Biochem Physiol C Toxicol Pharmacol, 143, 363-81. (Pubitemid 44080688)
165. Rhen T, Lang JW. (1994). Temperature-dependent sex determination in the snapping turtle: manipulation of the embryonic sex steroid environment. Gen Comp Endocrinol, 96, 243-54. (Pubitemid 24361243)
166. Rhomberg LR, Goodman JE, Foster WG, et al. (2012). A critique of the European Commission document, "State of the Art Assessment of Endocrine Disrupters". Crit Rev Toxicol, 42, 465-73.
167. Richard-Mercier N, Dorizzi M, Desvages G, Girondot M, Pieau C. (1995). Endocrine sex reversal of gonads by the aromatase inhibitor Letrozole (CGS 20267) in Emys orbicularis, a turtle with temperaturedependent sex determination. Gen Comp Endocrinol, 100, 314-26. (Pubitemid 26024999)
168. Rockett JC, Narotsky MG, Thompson KE, et al. (2006). Effect of conazole fungicides on reproductive development in the female rat. Reprod Toxicol, 22, 647-58. (Pubitemid 44548326)
169. Sancho E, Villarroel M, Andreu E, Ferrando M. (2009). Disturbances in energy metabolism of Daphnia magna after exposure to tebuconazole. Chemosphere, 74, 1171-8.
170. Sasaki J, Yamamoto T, Okada H. (1989). [The synergistic abortive effect of anti-progestogen RU 38486 and aromatase inhibitors for pregnant rat]. Nihon Sanka Fujinka Gakkai Zasshi, 41, 179-84. (Pubitemid 19059903)
171. Sechman A, Rzasa J, Paczoska-Eliasiewicz H. (2003). Effect of nonsteroidal aromatase inhibitor on blood plasma ovarian steroid and thyroid hormones in laying hen (Gallus domesticus). J Vet Med A Physiol Pathol Clin Med, 50, 333-8. (Pubitemid 41743004)
172. Segner H, Caroll K, Fenske M, et al. (2003). Identification of endocrinedisrupting effects in aquatic vertebrates and invertebrates: report from the European IDEA project. Ecotoxicol Environ Saf, 54, 302-14. (Pubitemid 36315868)
173. Sheehan TP, Cirrito J, Numan MJ, Numan M. (2000). Using c-Fos immunocytochemistry to identify forebrain regions that may inhibit maternal behavior in rats. Behav Neurosci, 114, 337-52. (Pubitemid 30488994)
174. Siegel JN, Gentile AC. (1966). Effect of 3-amino-1,2,4-triazole on histidine metabolism in algae. Plant Physiol, 41, 670-2.
175. Skolness SY, Durhan EJ, Garcia-Reyero N, et al. (2011). Effects of a short-term exposure to the fungicide prochloraz on endocrine function and gene expression in female fathead minnows (Pimephales promelas). Aquat Toxicol, 103, 170-8.
176. Snyder MJ. (2000). Cytochrome P450 enzymes in aquatic invertebrates: recent advances and future directions. Aquat Toxicol, 48, 529-47. (Pubitemid 30227219)
177. Soma KK, Alday NA, Hau M, Schlinger BA. (2004b). Dehydroepiandrosterone metabolism by 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase in adult zebra finch brain: sex difference and rapid effect of stress. Endocrinology, 145, 1668-77. (Pubitemid 38402374)
178. Soma KK, Sullivan KA, Tramontin AD, et al. (2000b). Acute and chronic effects of an aromatase inhibitor on territorial aggression in breeding and nonbreeding male song sparrows. J Comp Physiol, 186, 759-69.
179. Soma KK, Tramontin AD, Featherstone J, Brenowitz EA. (2004a). Estrogen contributes to seasonal plasticity of the adult avian song control system. J Neurobiol, 58, 413-22. (Pubitemid 38199128)
180. Soma KK, Tramontin AD, Wingfield JC. (2000a). Oestrogen regulates male aggression in the non-breeding season. Proc Biol Sci, 267, 1089-96. (Pubitemid 30389020)
181. Sorensen HT, Nielsen GL, Olesen C, et al. (1999). Risk of malformations and other outcomes in children exposed to fluconazole in utero. Br J Clin Pharmacol, 48, 234-8. (Pubitemid 29349461)
182. Stachowski-Haberkorn S, Quiniou F, et al. (2008). In-situ microcosms, a tool for assessment of pesticide impacts on oyster spat (Crassostrea gigas). Ecotoxicology, 17, 235-45.
183. Taxvig C, Hass U, Axelstad M, et al. (2007). Endocrine-disrupting activities in vivo of the fungicides tebuconazole and epoxiconazole. Toxicol Sci, 100, 464-73. (Pubitemid 350131373)
184. Taxvig C, Vinggaard AM, Hass U, et al. (2008). Endocrine-disrupting properties in vivo of widely used azole fungicides. Int J Androl, 31, 170-7.
185. Taya Y, O'kane S, Ferguson MW. (1999). Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development, 126, 3869-79. (Pubitemid 29440484)
186. Thune JJ, Hoefsten DE, Lindholm MG, et al. (2005). Simple risk stratification at admission to identify patients with reduced mortality from primary angioplasty. Circulation, 112, 2017-21. (Pubitemid 41377422)
187. Tiboni GM. (1993). Second branchial arch anomalies induced by fluconazole, a bis-triazole antifungal agent, in cultured mouse embryos. Res Commun Chem Pathol Pharmacol, 79, 381-4. (Pubitemid 23095812)
188. Tiboni GM, Marotta F, Castigliego AP, Rossi C. (2009). Impact of estrogen replacement on letrozole-induced embryopathic effects. Hum Reprod, 24, 2688-92.
189. Tiboni GM, Marotta F, Del Corso A, Giampietro F. (2006). Defining critical periods for itraconazole-induced cleft palate, limb defects and axial skeletal malformations in the mouse. Toxicol Lett, 167, 8-18. (Pubitemid 44566438)
190. Tiboni GM, Marotta F, Rossi C, Giampietro F. (2008). Effects of the aromatase inhibitor letrozole on in utero development in rats. Hum Reprod, 23, 1719-23. (Pubitemid 352019997)
191. Tiwary BK, Li W-H. (2009). Parallel evolution between aromatase and androgen receptor in the animal kingdom. Mol Biol Evol, 26, 123-9.
192. Trosken ER, Adamska M, Arand M, et al. (2006). Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles. Toxicology, 228, 24-32. (Pubitemid 44550226)
193. Trösken ER, Scholz K, Lutz RW, et al. (2004). Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans. Endocrine Res, 30, 387-94. (Pubitemid 39453086)
194. Tulandi T, Martin J, Al-Fadhli R, et al. (2006). Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril, 85, 1761-5. (Pubitemid 43816444)
195. Uchida D, Yamashita M, Kitano T, Iguchi T. (2004). An aromatase inhibitor or high water temperature induce oocyte apoptosis and depletion of P450 aromatase activity in the gonads of genetic female zebrafish during sex-reversal. Comp Biochem Physiol A Mol Integr Physiol, 137, 11-20. (Pubitemid 38081282)
196. US EPA (2005). Epoxiconazole tolerance on bananas and coffee exported to the US. EPA-HQ-2005-0071, pp 55.
197. Vaillant S, Dorizzi M, Pieau C, Richard-Mercier N. (2001a). Sex reversal and aromatase in chicken. J Exp Zool, 290, 727-40. (Pubitemid 33066405)
198. Vaillant S, Guemene D, Dorizzi M, et al. (2003). Degree of sex reversal as related to plasma steroid levels in genetic female chickens (Gallus domesticus) treated with Fadrozole. Mol Reprod Dev, 65, 420-8. (Pubitemid 36841892)
199. Vaillant S, Magre S, Dorizzi M, et al. (2001b). Expression of AMH, SF1, and SOX9 in gonads of genetic female chickens during sex reversal induced by an aromatase inhibitor. Dev Dyn, 222, 228-37. (Pubitemid 32937595)
200. Van Den Brink PJ, Blake N, Brock TC, Maltby L. (2006). Predictive value of species sensitivity distributions for effects of herbicides in freshwater ecosystems. Hum Ecol Risk Assess, 12, 645-74. (Pubitemid 44266867)
201. Vandame R, Belzunces LP. (1998). Joint actions of deltamethrin and azole fungicides on honey bee thermoregulation. Neurosci Lett, 251, 57-60. (Pubitemid 28355960)
202. Villeneuve DL, Ankley GT, Makynen EA, et al. (2007a). Comparison of fathead minnow ovary explant and H295R cell-based steroidogenesis assays for identifying endocrine-active chemicals. Ecotoxicol Environ Saf, 68, 20-32. (Pubitemid 47081183)
203. Villeneuve DL, Blake LS, Brodin JD, et al. (2007b). Transcription of key genes regulating gonadal steroidogenesis in control and ketoconazoleor vinclozolin-exposed fathead minnows. Toxicol Sci, 98, 395-407. (Pubitemid 47244810)
204. Villeneuve DL, Knoebl I, Kahl MD, et al. (2006). Relationship between brain and ovary aromatase activity and isoform-specific aromatase mRNA expression in the fathead minnow (Pimephales promelas). Aquat Toxicol, 76, 353-68. (Pubitemid 43246821)
205. Villeneuve DL, Miracle AL, Jensen KM, et al. (2007c). Development of quantitative real-time PCR assays for fathead minnow (Pimephales promelas) gonadotropin beta subunit mRNAs to support endocrine disruptor research. Comp Biochem Physiol C Toxicol Pharmacol, 145, 171-83. (Pubitemid 46350867)
206. Villeneuve DL, Mueller ND, Martinović D, et al. (2009). Direct effects, compensation, and recovery in female fathead minnows exposed to a model aromatase inhibitor. Environ Health Perspect, 117, 624.
207. Vinggaard AM, Hnida C, Breinholt V, Larsen JC. (2000). Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro, 14, 227-34. (Pubitemid 30235120)
208. Wang J, Kuliszewski M, Yee W, et al. (1995). Cloning and expression of glucocorticoid-induced genes in fetal rat lung fibroblasts. Transforming growth factor-beta 3. J Biol Chem, 270, 2722-8.
209. Wang Y, Wu S, Chen L, Wu C, et al. (2012). Toxicity assessment of 45 pesticides to the epigeic earthworm (Eisenia fetida). Chemosphere, 88, 484-91.
210. Watanabe H, Menzies JA. (1985). Depression of ovarian estradiol-17 beta following single oral dose of ketoconazole. Res Commun Chem Pathol Pharmacol, 48, 141-4. (Pubitemid 15081106)
211. Weltje L, Simpson P, Gross M, et al. (2013). Comparative acute and chronic sensitivity of fish and amphibians: a critical review of data. Environ Toxicol Chem, 32, 984-94.
212. Wennstrom KA, Crews D. (1995). Making males from females: the effects of aromatase inhibitors on a parthenogenetic species of whiptail lizard. Gen Comp Endocrinol, 99, 316-22.
213. WHO-IPCS (2002). Global assessment of the state-of-the-science of endocrine disruptors. International Programme on Chemical Safety, World Health Organization and United Nations Environment Program, Geneva.
214. Wibbels T, Crews D. (1994). Putative aromatase inhibitor induces male sex determination in a female unisexual lizard and in a turtle with temperature-dependent sex determination. J Endocrinol, 141, 295-9. (Pubitemid 24199328)
215. Wolf Jr C, Lambright C, Mann P, et al. (1999). Administration of potentially antiandrogenic pesticides (procymidone linuron iprodione chlozolinate pp'-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. (Pubitemid 30484120)
216. Wolf FT. (1962). Growth inhibition of Chlorella induced by 3-amino-1 2 4-triazole and its reversal by purines. Nature, 193, 901-2.
217. Wouters W, De Coster R, Goeminner N, et al. (1988). Aromatase inhibition by the antifungal ketoconazole. J Steroid Biochem, 30, 387-9.
218. Wuttke W, Jarry H, Knoke I, et al. (1995). Luteotropic and luteolytic effects of oxytocin in the porcine corpus luteum. Adv Exp Med Biol, 395, 495-506. (Pubitemid 26110891)
219. Wuttke W, Pitzel L, Seidlova-Wuttke D, Hinney B. (2001). LH pulses and the corpus luteum: the luteal phase deficiency LPD). Vitam Horm, 63, 131-58. (Pubitemid 33805712)
220. Zarn JA, Bruschweiler BJ, Schlatter JR. (2003). Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 alpha-demethylase and aromatase. Environ Health Perspect, 111, 255-61. (Pubitemid 36395190)
221. Zerulla M, Lange R, Steger-Hartmann T, et al. (2002). Morphological sex reversal upon short-term exposure to endocrine modulators in juvenile fathead minnow (Pimephales promelas). Toxicol Lett, 131, 51-63. (Pubitemid 34461910)
222. Zhang X, Hecker M, Tompsett AR, et al. (2008). Responses of the medaka HPG axis PCR array and reproduction to prochloraz and ketoconazole. Environ Sci Technol, 42, 6762-9.
223. Zhang Y, Mario AL. (2002). Tuberculosis drug targets. Current Drug Targets, 3, 131-54. (Pubitemid 34296204)
224. Zirilli L, Orlando G, Diazzi C, et al. (2008a). Hypopituitarism and HIV-infection: a new comorbidity in the HAART era? J Endocrinol Invest, 31, 33-8.
225. Zirilli L, Rochira V, Diazzi C, et al. (2008b). Human models of aromatase deficiency. J Steroid Biochem Mol Biol, 109, 212-18.