Possible impact of phthalates on infant reproductive health

International Journal of Andrology

Volumn 29, Issue 1, 2006, Pages 172-180

  Lottrup, G ^a   Andersson, A M ^a   Leffers, H ^a   Mortensen, G K ^a   Toppari, J ^a,b   Skakkebaek N E ^a   Main, K M ^a,c   De Muinck Keizer Schrama, S ^c   Swan, S ^c   Foster, P ^c   Astrup Jensen, A ^c  

^a Rigshospitalet   (Denmark)

^b UNIVERSITY OF TURKU   (Finland)

^c NONE

Author keywords

Anogenital distance; Breast milk; Infant; Male reproduction; phthalates; testicular dysgenesis syndrome; testosterone; virilization

Indexed keywords

ANDROGEN; ISONONYL PHTHALATE; LUTEINIZING HORMONE; PHTHALIC ACID 2 ETHYLHEXYL MONOESTER; PHTHALIC ACID DERIVATIVE; PHTHALIC ACID DIBUTYL ESTER; PHTHALIC ACID DIETHYL ESTER; PHTHALIC ACID DIMETHYL ESTER; SEX HORMONE BINDING GLOBULIN; TESTOSTERONE; UNCLASSIFIED DRUG;

BREAST MILK; CELL FUNCTION; CONFERENCE PAPER; CRYPTORCHISM; DETOXIFICATION; EXPOSURE; GENITAL MALFORMATION; HORMONE DETERMINATION; HUMAN; LEYDIG CELL; NONHUMAN; PREGNANCY; PREVALENCE; PRIORITY JOURNAL; REPRODUCTIVE HEALTH; SKIN ABSORPTION; TESTIS DEVELOPMENT; URINALYSIS; VIRILIZATION;

ENVIRONMENTAL POLLUTANTS; FEMALE; GENITALIA, MALE; HUMANS; INFANT; MALE; MATERNAL EXPOSURE; PHTHALIC ACIDS; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS;

EID: 33645233817     PISSN: 01056263     EISSN: 13652605     Source Type: Journal    
DOI: 10.1111/j.1365-2605.2005.00642.x     Document Type: Conference Paper

References (69)

1. Adami H.-O. Bergström R. Möhner M. Zatonski W. Storm H. Ekbom A. et al. 1994 Testicular cancer in nine Northern European countries. International Journal of Cancer 59 33 38.
2. ATSDR 1995 Toxicological Profile for Diethyl Phthalate. Agency for Toxic Substances and Disease Registry Atlanta, GA, USA. Available at: http://www.atsdr.cdc.gov/toxprofiles/tp73.html. Last accessed 28. 12. 05.q1
3. ATSDR 2001 Toxicological Profile for Di-n-butyl Phthalate. Agency for Toxic Substances and Disease Registry Atlanta, GA, USA. Available at: http://www.atsdr.cdc.gov/toxprofiles/tp135.html.
4. ATSDR 2002 Toxicological Profile for Di(2-ethyl)phthalate (DEHP). Agency for Toxic Substances and Disease Registry Atlanta, GA, USA. Available at: http://www.atsdr.cdc.gov/toxprofiles/tp9.html.
5. Belgorosky A. Rivarola M. A. 1985 Sex hormone binding globulin response to testosterone. An androgen sensitivity test. Acta Endocrinologica 109 130 138.
6. Boisen K. A. Kaleva M. Main K. M. Virtanen H. E. Haavisto A.-M. Schmidt I. M. Chellakooty M. Damgaard I. N. Mau C. Reunanen M. Skakkebæk N. E. Toppari J. 2004 Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet 363 1264 1269.
7. Boisen K. Chellakooty M. Schmidt I. Kai C. Damgaard I. Suomi A. M. Toppari J. Skakkebæk N. E. Main K. 2005 Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship to placental weight, anthropometrical measurements at birth, and reproductive hormone levels at 3 months of age. Journal of Clinical Endocrinology and Metabolism 90 4041 4046.
8. Bornehag C.-G. Sundell J. Weschler C. J. Sigsgaard T. Lundgren B. Hasselgran M. Hägerhed-Engman L. 2004 The association between asthma and allergic symptoms in children and phthalate in house dust: a nested case-control study. Environmental Health Perspectives 112 1393 1397.
9. Braissant O. Foufelle F. Scotto C. Dauca M. Wahli W. 1996 Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 137 354 366.
10. Calafat A. M. Needham L. L. Silva M. J. Lambert G. 2004a Exposure to di-(2-ethylhexyl)phthalate among premature neonates in a neonatal intensive care unit. Pediatrics 113 429 434.
11. Calafat A. M. Slakman A. R. Silva M. J. Herbert A. R. Needham L. L. 2004b Automated solid phase extraction and quantitative analysis of human milk for 13 phthalate metabolites. Journal of Chromatography B 805 49 56.
12. Carruthers C. M. Foster P. M. 2005 Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate. Birth Defects Research (Part B) 74 277 285.
13. David R. M. Moore M. R. Finney D. C. Guest D. 2001 Reversibility of the chronic effects of di(2-ethylhexyl)phthalate. Toxicologic Pathology 29 430 439.
14. Duty S. M. Silva M. J. Barr D. B. Brock J. W. Ryan L. Chen Z. Herrick R. F. Christiani D. C. Hauser R. 2003 Phthalate exposure and human semen parameters. Epidemiology 14 269 277.
15. European Commission 2005 Press Release 5th July 2005. Available at: http://www.europa.eu.int/rapid/pressReleasesAction.do?reference=IP/05/ 838&format=HTML&aged=1&language=EN&guiLanguage=en.
16. Faouzi M. A. Dine T. Gressier B. Kambia K. Luyckx M. Pagniez D. Brunet C. Cazin M. Belabed A. Cazin J. C. 1999 Exposure of hemodialysis patients to di-2-ethylhexyl phthalate. International Journal of Pharmaceutics 180 113 121.
17. Fisher J. S. Macpherson S. Marchetti N. Sharpe R. M. 2003 Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate. Human Reproduction 18 1383 1394.
18. Gray T. J. Rowland I. R. Foster P. M. Gangolli S. D. 1982 Species differences in the testicular toxicity of phthalate esters. Toxicology Letters 11 141 147.
19. Gray L. E. Jr. Wolf C. Lambright C. Mann P. Price M. Cooper R. L. Ostby J. 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. Toxicology and Industrial Health 15 94 118.
20. Gray L. E. Jr. Ostby J. Furr J. Price M. Veeramachaneni D. N. Parks L. 2000 Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicological Sciences 58 350 365.
21. Green R. Hauser R. Calafat A. M. Weuve J. Schettler T. Ringer S. Huttner K. Hu H. 2005 Use of di(2-ethylhexyl) phthalate-containing medical products and urinary levels of mono(2-ethylhexyl) phthalate in neonatal intensive care unit infants. Environmental Health Perspectives 113 1222 1225.
22. Handelsman D. J. 2001 Estrogens and falling sperm counts. Reproduction, Fertility and Development 13 317 324.
23. Hauser R. Meeker J. D. Park S. Silva M. J. Calafat A. M. 2004 Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environmental Health Perspectives 112 1734 1740.
24. Higuchi T. T. Palmer J. S. Gray L. E. Jr.. Veeramachaneni D. N. 2003 Effects of dibutyl phthalate in male rabbits following in utero, adolescent, or postpubertal exposure. Toxicological Sciences 72 301 313.
25. Hotchkiss A. K. Parks-Saldutti L. G. Ostby J. S. Lambright C. Furr J. Vandenbergh J. G. Gray L. E. 2004 A mixture of the 'antiandrogens' linuron and butyl benzyl phthalate alters sexual differentiation of the male rat in a cumulative fashion. Biology of Reproduction 71 1852 1861.
26. Hurst C. H. Waxman D. J. 2003 Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicological Sciences 74 297 308.
27. Ito Y. Yokota H. Wang R. Yamanoshita O. Ichihara G. Wang H. Kurata Y. Takagi K. Nakajima T. 2005 Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets. Archives of Toxicology 79 147 154.
28. Jørgensen N. Andersen A.-G. Eustache F. Irvine D. S. Suominen J. Petersen J. H. et al. 2001 Regional differences in semen quality in Europe. Human Reproduction 16 1012 1019.
29. Jørgensen N. Carlsen E. Nermoen I. Punab M. Suominen J. Andersen A.-G. et al. 2002 East-west gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland. Human Reproduction 17 2199 2208.
30. Jørgensen N. Asklund C. Carlsen E. Skakkebæk N. E. 2006 Coordinated European investigations of semen quality: results from studies of Scandinavian young men is a matter of concern. International Journal of Andrology 29 54 61.q2
31. Jones H. B. Garside D. A. Liu R. Roberts J. C. 1993 The influence of phthalate esters on Leydig cell structure and function in vitro and in vivo. Experimental and Molecular Pathology 58 179 193.
32. Kato K. Silva M. J. Reidy J. A. Hurtz D. III. Malek N. A. Needham L. L. Nakazawa H. Barr D. B. Calafat A. M. 2004 Mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxyhexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate. Environmental Health Perspectives 112 327 330.
33. Kavlock R. Boekelheide K. Chapin R. Cunningham M. Faustman E. M. Foster P. et al. 2002a NTP center for the evaluation of risks to human reproduction: phthalate expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl)phthalate. Reproductive Toxicology 16 529 653.
34. Kavlock R. Boekelheide K. Chapin R. Cunningham M. Faustman E. M. Foster P. et al. 2002b NTP center for the evaluation of risks to human reproduction: phthalate expert panel report on the reproductive and developmental toxicity of di-n-butyl phthalate. Reproductive Toxicology 16 489 527.
35. Kirk-Othmer 1996 Phthalic acids and other benzenepolycarboxylic acids. In: Kirk-Othmer Encyclopedia of Chemical Technology Vol. 18 eds Kroschwitz J. I. Howe-Grant M. pp. 991 1043. John Wiley London, UK.
36. Kleymenova E. Swanson C. Boekelheide K. Gaido K. W. 2005 Exposure in utero to Di(n-butyl) phthalate alters the vimentin cytoskeleton of fetal rat sertoli cells and disrupts sertoli cell-gonocyte contact. Biology of Reproduction 73 482 490.
37. Koch H. M. Drexler H. Angerer J. 2003 An estimation of the daily intake of di(2-ethylhexyl) phthalate (DEHP) and other phthalates in the general population. International Journal of Hygiene and Environmental Health 206 77 83.
38. Koch H. M. Bolt H. M. Angerer J. 2004a Di(2-ethylhexul) phthalate (DEHP) metabolites in human urine and serum after single oral dose of deuterium-labelled DEHP. Archives of Toxicology 78 123 130.
39. Koch H. M. Drexler H. Angerer J. 2004b Internal exposure of nursery-school children and their parents and teachers to di(2-ethylhexyl) phthalate (DEHP). International Journal of Hygiene and Environmental Health 207 15 22.
40. Koch H. M. Preuss R. Drexler H. Angerer J. 2005 Exposure of nursery school children and their parents and teachers to di-n-butylphthalate and butylbenzylphthalate. International Archives of Occupational and Environmental Health 78 223 229.
41. Latini G. DeFelice C. Presta G. DelVecchio A. Paris I. Ruggieri F. Mazzeo P. 2003 In utero exposure to di(2-ethylhexyl)phthalate and duration of human pregnancy. Environmental Health Perspectives 111 1783 1785.
42. Liu K. Lehmann K. P. Sar M. Young S. S. Gaido K. W. 2005 Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Biology of Reproduction 73 180 192.
43. Mahood I. K. Hallmark N. McKinnell C. Walker M. Fisher J. S. Sharpe R. M. 2005 Abnormal Leydig cell aggregation in the fetal testis of rats exposed to di (n-butyl) phthalate and its possible role in testicular dysgenesis. Endocrinology 146 613 623.
44. Main K. M. Mortensen G. K. Kaleva M. Boisen K. Damgaard I. Chellakooty M. et al. 2005 Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in three months old infants. Environmental Health Perspectives (DOI:10.1289/ehp.8075, available at: http://dx.doi.org/ ).
45. Marsman D. 1995 NTP technical report on the toxicity studies of dibutyl phthalate (CAS No.84-74-2) administered in feed to F344/N rats and B6C3F1 mice. Toxicity Report Series 30 1 G5.
46. McKinnell C. Sharpe R. M. Mahood K. Hallmark N. Scott H. Ivell R. et al. 2005 Expression of insulin-like factor 3 protein in the rat testis during fetal and postnatal development and in relation to cryptorchidism induced by in utero exposure to di (n-butyl) phthalate. Endocrinology 146 4536 4544.
47. Mortensen G. K. Main K. M. Andersson A.-M. Leffers H. Skakkebæk N. E. 2005 Determination of phthalate monoesters in human breast milk, consumer milk and infant formula by tandem mass spectrometry(LC/MC/MS). Analytical and Bioanalytical Chemistry 382 1084 1092.
48. Murature D. A. Tang S. Y. Steinhardt G. Dougherty R. C. 1987 Phthalate esters and semen quality parameters. Biomedical and Environmental Mass Spectrometry 14 473 477.
49. Mylchreest E. Cattley R. C. Foster P. M. 1998 Male reproductive tract malformations in rats following gestational and lactational exposure to di(n-butyl)phthalate: an antiandrogenic mechanism Toxicological Sciences 43 47 60.
50. Mylchreest E. Wallace D. G. Cattley R. C. Foster P. M. 2000 Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to di(n-butyl)phthalate during late gestation. Toxicological Sciences 55 143 151.
51. Mylchreest E. Sar M. Wallace D. G. Foster P. M. 2002 Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. Reproductive Toxicology 16 19 28.
52. Parks L. G. Ostby J. S. Lambright C. R. Abbott B. D. Klinefelter G. R. Barlow N. J. Gray L. E. Jr. 2000 The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicological Sciences 58 339 349.
53. Rajapakse N. Silva E. Kortenkamp A. 2002 Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action. Environmental Health Perspectives 110 917 921.
54. Salazar-Martinez E. Romano-Riquer P. Yanez-Marquez E. Longnecker M. P. Hernandez-Avila M. 2004 Anogenital distance in human male and female newborns: a descriptive, cross-sectional study. Environmental Health 3 8.
55. Schettler T. 2006 Human exposure to phthalates via consumer products. International Journal of Andrology 29 134 139.
56. Schultz R. Yan W. Toppari J. Volkl A. Gustafsson J. A. Pelto-Huikko M. 1999 Expression of peroxisome proliferator acrivated receptor alpha messenger ribonucleic acid and protein in human and rat testis. Endocrinology 140 2968 2975.
57. Setchell B. P. Hertel T. Söder O. 2003 Postnatal testicular development, cellular organization and paracrine regulation. In: The developing Testis Vol. 5 ed. Söder O. pp. 24 37. Karger Basel, Switzerland.
58. Silva M. J. Barr D. B. Reidy J. A. Kato K. Malek N. A. Hodge C. C. Hurtz D. III. Calafat A. M. Needham L. L. Brock J. W. 2003 Glucuronidation patterns of common urinary and serum monoester phthalate metabolites. Archives of Toxicology 77 561 567.
59. Silva M. J. Barr D. B. Reidy J. A. Malek N. A. Hodge C. C. Caudill S. P. Brock J. W. Needham L. L. Calafat A. M. 2004a Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environmental Health Perspectives 112 331 338.
60. Silva M. J. Reidy J. A. Herbert A. R. Preau J. L. Jr. Needham L. L. Calafat A. M. 2004b Detection of phthalate metabolites in human amniotic fluid. Bulletin of Environmental Contamination and Toxicology 72 1226 1231.
61. Silva M. J. Reidy J. A. Samandar E. Herbert A. R. Needham L. L. Calafat A. M. 2005 Detection of phthalate metabolites in human saliva. Archives of Toxicology 79 647 652.
62. Skakkebæk N. E. Rajpert-De Meyts E. Main K. M. 2001 Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Human Reproduction 16 972 978.
63. Swan S. H. Brazil C. Drobnis E. Z. Liu F. Kruse R. L. Hatch M. Redmon J. B. Wang C. Overstreet J. W. 2003 Geographic differences in semen quality of fertile U.S. males. Environmental Health Perspectives 111 414 420.
64. Swan S. H. Main K. M. Liu F. Stewart S. L. Kruse R. L. Calafat A. M. et al. 2005 Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environmental Health Perspectives 113 1056 1061.
65. Thompson C. J. Ross S. M. Hensley J. Liu K. Heinze S. C. Young S. S. Gaido K. W. 2005 Differential steroidogenic gene expression in the fetal adrenal gland versus the testis and rapid and dynamic response of the fetal testis to di(n-butyl) phthalate. Biology of Reproduction 73 908 917.
66. Toppari J. Larsen J. C. Christiansen P. Giwercman A. Grandjean P. Guillette L. J. et al. 1996 Male reproductive health and environmental xenoestrogens. Environmental Health Perspectives 104 741 803.
67. Williams D. T. Blanchfield B. J. 1975 The retention, distribution, excretion, and metabolism of dibutyl phthalate-7-14C in the rat. Journal of Agricultural and Food Chemistry 23 854 858.
68. Wilson V. S. Lambright C. Furr J. Ostby J. Wood C. Held G. Gray L. E. Jr. 2004 Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis. Toxicology Letters 146 207 215.
69. Wine R. N. Li L. H. Barnes L. H. Gulati D. K. Chapin R. E. 1997 Reproductive toxicity of di-n-butylphthalate in a continuous breeding protocol in Sprague-Dawley rats. Environmental Health Perspectives 105 102 107.