Use of genomic data in risk assessment case study: I. Evaluation of the dibutyl phthalate male reproductive development toxicity data set

Toxicology and Applied Pharmacology

Volumn 271, Issue 3, 2013, Pages 336-348

  Makris, Susan L ^a   Euling, Susan Y ^a   Gray, L Earl ^b   Benson, Robert ^a   Foster, Paul M D ^c  

^a U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^b U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^c NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

Dibutyl phthalate; Risk assessment; Toxicogenomic

Indexed keywords

PHTHALIC ACID DIBUTYL ESTER; TESTOSTERONE;

ANOGENITAL DISTANCE; ARTICLE; CLINICAL EVALUATION; CRYPTORCHISM; DATA BASE; DEVELOPMENTAL TOXICITY; GENOMICS; HISTOPATHOLOGY; HYPOSPADIAS; INCIDENCE; LEYDIG CELL TUMOR; MALE; MALE FERTILITY; MALE GENITAL SYSTEM; NONHUMAN; ORGAN WEIGHT; PENIS DISEASE; PHENOTYPE; PREPUTIAL GLAND; REPRODUCTIVE TOXICITY; RISK ASSESSMENT; SEMEN ABNORMALITY; SYSTEMATIC REVIEW; TESTIS ATROPHY; TESTIS WEIGHT;

AGD; ANOGENITAL DISTANCE; BENCHMARK DOSE LOWER CONFIDENCE LIMIT; BMDL; DBP; DIBUTYL PHTHALATE; GD; GESTATION DAY; INTEGRATED RISK INFORMATION SYSTEM; IRIS; LOAEL; LOEL; LOWEST-OBSERVED-ADVERSE-EFFECT LEVEL; LOWEST-OBSERVED-EFFECT LEVEL; MOA; MODE OF ACTION; NATIONAL RESEARCH COUNCIL; NATIONAL TOXICOLOGY PROGRAM; NO-OBSERVED-ADVERSE-EFFECT LEVEL; NO-OBSERVED-EFFECT LEVEL; NOAEL; NOEL; NRC; NTP; OECD; ORGANISATION OF ECONOMIC CO-OPERATION AND DEVELOPMENT; PND; POD; POINT OF DEPARTURE; POSTNATAL DAY; RACB; REFERENCE DOSE; REPRODUCTIVE ASSESSMENT BY CONTINUOUS BREEDING; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RFD; RISK ASSESSMENT; RT-PCR; T; TESTOSTERONE; TOXICOGENOMIC; U.S. ENVIRONMENTAL PROTECTION AGENCY; U.S. EPA; WEIGHT OF EVIDENCE; WOE;

ANIMALS; DIBUTYL PHTHALATE; ENVIRONMENTAL POLLUTANTS; GENITALIA, MALE; GENOMICS; MALE; PLASTICIZERS; RATS; REPRODUCTION; RISK ASSESSMENT;

EID: 84883741823     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2010.09.006     Document Type: Article

References (64)

1. Barlow N.J., Foster P.M. Pathogenesis of male reproductive tract lesions from gestation through adulthood following in utero exposure to di(n-butyl) phthalate. Toxicol. Pathol. 2003, 31(4):397-410.
2. Barlow N.J., Phillips S.L., Wallace D.G., Sar M., Gaido K.W., Foster P.M.D. Quantitative changes in gene expression in fetal rat testes following exposure to di(n-butyl) phthalate. Toxicol. Sci. 2003, 73(2):431-441.
3. Barlow N.J., McIntyre B.S., Foster P.M. Male reproductive tract lesions at 6, 12, and 18months of age following in utero exposure to di(n-butyl) phthalate. Toxicol. Pathol. 2004, 32:79-90.
4. BASF, 1992. Study on the oral toxicity of dibutyl phthalate in Wistar rats. Administration via the diet over 3months. Prepared by BASF Corporation, Ludwigshafen, Germany for Eastman Kodak Company; Project No. 31S0449//89020; Submitted under TSCA Section8D; EPA Document No. 86-920000903; NTIS OTS0535640 (As cited in NTP-CERHR, 2000).
5. Baskin L.S., Himes K., Colborn T. Hypospadias and endocrine disruption: is there a connection?. Environ. Health Perspect. 2001, 109:1175-1183.
6. Bowman C.J., Turner K.J., Sar M., Barlow N.J., Gaido K.W. Altered gene expression during rat Wolffian duct development following di(n-butyl) phthalate exposure. Toxicol. Sci. 2005, 86:161-174.
7. Carruthers C.M., Foster P. Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate. Birth Defects Res. B Dev. Reprod. Toxicol. 2005, 74(3):277-285.
8. David R.M. Proposed mode of action for in utero effects of some phthalate esters on the developing male reproductive tract. Toxicol. Pathol. 2006, 34(3):209-219. http://tpx.sagepub.com/cgi/reprint/34/3/209.pdf.
9. Ema M., Miyawaki E. Adverse effects on development of the reproductive system in male offspring of rats given monobutyl phthalate, a metabolite of dibutyl phthalate, during late pregnancy. Reprod. Toxicol. 2001, 15(2):189-194.
10. Ema M., Miyawaki E., Kawashima K. Further evaluation of developmental toxicity of di-n-butyl phthalate following administration during later pregnancy in rats. Toxicol. Lett. 1998, 98(1-2):87-93.
11. Ema M., Miyawaki E., Kawashima K. Critical period for adverse effects on development of reproductive system in male offspring of rats given di-n-butyl phthalate during later pregnancy. Toxicol. Lett. 2000, 111(3):271-278.
12. Euling S.Y., Thompson C.M., Chiu W.A., Benson R. An approach for integrating toxicogenomic data in risk assessment: The dibutyl phthalate case study. Toxicol. Appl. Pharmacol. 2013, 271(3):324-335. (this issue).
13. Euling S.Y., White L.D., Kim A.S., Sen B., Wilson V.S., Keshava C., Keshava N., Hester S., Ovacik A.M., Ierapetritou M.G., Androulakis I.P., Gaido K.W. Use of genomic data in risk assessment case study: II. Evaluation of the dibutyl phthalate toxicogenomic data set. Toxicol. Appl. Pharmacol. 2013, 271(3):349-362. (this issue).
14. Fennell T.R., Krol W.L., Sumner S.C., Snyder R.W. Pharmacokinetics of dibutylphthalate in pregnant rats. Toxicol. Sci. 2004, 82(2):407-418.
15. Ferrara D., Hallmark N., Scott H., Brown R., McKinnell C., Mahood I.K., Sharpe R.M. Acute and long-term effects of in utero exposure of rats to di(n-butyl) phthalate on testicular germ cell development and proliferation. Endocrinology 2006, 147(11):5352-5362.
16. Fisher J.S., Macpherson S., Marchetti N., Sharpe R.M. Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate. Human Reprod. 2003, 18(7):1389-1394.
17. Foster P.M.D. Mode of action: impaired fetal Leydig cell function-effects on male reproductive development produced by certain phthalate esters. Crit. Rev. Toxicol. 2005, 35(8-9):713-719.
18. Gray L.E., Wolf C., Lambright C., Mann P., Price M., Cooper R.L., Ostby J. Administration of potentially antiandrogenic pesticides (procymidone, linuron, 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. Indust. Health 1999, 15(1-2):94-118.
19. Hauser R., Meeker J.D., Duty S., Silva M.J., Calafat A.M. Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites. Epidemiology 2006, 17(6):682-691.
20. Higuchi T.T., Palmer J.S., Gray L.E., Veeramachaneni D.N.R. Effects of dibutyl phthalate in male rabbits following in utero, adolescent, or postpubertal exposure. Toxicol. Sci. 2003, 72(2):301-313.
21. Kim T., Shin J., Lee S., Moon H., Kang I., Kim I., Han S. Effects of in utero exposure of diethylstilbestrol and dibutyl phthalate on the testis descent in rat offspring. Abstract # 574. Toxicologist 2004, 78:118.
22. Kleymenova E., Dei Rossi E., Liu K., Swanson C., Pluta L., Gaido K. Developmental exposure to di-n-butyl phthalate affects cord organization and Sertoli cell-gonocyte interactions in the fetal rat testis. Abstract # 926. Toxicologist 2004, 78:190.
23. Kleymenova E., Swanson C., Gaido K.W. Low dose cellular responses in the fetal rat testis in utero exposed to di-n-butyl phthalate. Abstract #1372. Toxicologist 2005, 79:281.
24. Kleymenova E., Swanson C., Boekelheide K., Gaido K.W. Exposure in utero to di(n-butyl) phthalate alters the vimentin cytoskeleton of fetal rat Sertoli cells and disrupts Sertoli cell-gonocyte contact. Biol. Reprod. 2005, 73(3):482-490.
25. Klonisch T., Fowler P.A., Hombach-Klonisch S. Molecular and genetic regulation of testis descent and external genitalia development. Dev. Biol. 2004, 270:1-18.
26. Lee K.-Y., Shibutani M., Takagi H., Kato N., Takigami S., Uneyama C., Hirose M. Diverse developmental toxicity of di-n-butyl phthalate in both sexes of rat offspring after maternal exposure during the period from late gestation through lactation. Toxicology 2004, 203(1-3):221-238.
27. Lehmann K.P., Phillips S., Sar M., Foster P.M.D., Gaido K.W. Dose-dependent alterations in gene expression and testosterone synthesis in the fetal testes of male rats exposed to di (n-butyl) phthalate. Toxicol. Sci. 2004, 81:60-68.
28. Liu K., Lehmann K.P., Sar M., Young S.S., Gaido K.W. Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Biol. Reprod. 2005, 73(1):180-192.
29. Mahood I.K., Hallmark N., McKinnell C., Walker M., Fisher J.S., Sharpe R.M. Abnormal Leydig cell aggregation in the fetal testis of rats exposed to di (n-butyl) phthalate and its possible role in testicular dysgenesis. Endocrinology 2005, 146(2):613-623.
30. Main K.M., Mortensen G.K., Kaleva M.M., Boisen K.A., Damgaard I.N., Chellakooty M., Schmidt I.M., Suoimi A.-M., Virtanen H.E., Petersen J.H., Andersson A.-M., Toppari J., Skakkebaek N.E. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ. Health Perspect. 2006, 114(2):270-276.
31. Marty M.S., Allen B., Chapin R.E., Cooper R., Daston G.P., Flaws J.A., Foster P.M.D., Makris S.L., Mylchreest E., Sandler D., Tyl R.W. Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test. Birth Defects Res. B 2009, 86:470-489.
32. McKinnell C., Sharpe R.M., Mahood K., Hallmark N., Scott H., Ivell R., Staub C., Jegou B., Haag F., Koch-Nolte F., Hartung S. 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 2005, 146(10):4536-4544.
33. Mylchreest E., Cattley R.C., Foster P.M.D. Male reproductive tract malformations in rats following gestational and lactational exposure to di(n-butyl) phthalate: an antiandrogenic mechanism?. Toxicol. Sci. 1998, 43:47-60.
34. Mylchreest E., Sar M., Cattley R.D., Foster P.M.D. Disruption of androgen-regulated male reproductive development by di(n-butyl) phthalate during late gestation in rats is different from flutamide. Toxicol. Appl. Pharmacol. 1999, 156(2):81-95.
35. Mylchreest E., Wallace D.G., Cattley R.C., Foster P.M.D. Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to di(n-butyl) phthalate during late gestation. Toxicol. Sci. 2000, 55:143-151.
36. Mylchreest E., Sar M., Wallace D.G., Foster P.M.D. Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. Reprod. Toxicol. 2002, 16:19-28.
37. NRC Toxicity Testing in the 21st Century 2007, The National Academies Press, Washington, DC.
38. NTP Final Report on the Reproductive Toxicity of Di-n-Butyl Phthalate (Cas. No. 84-74-3) in Sprague-Dawley Rats 1991, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Toxicity Program, Research Triangle Park, NC, NTP Report # RACB89012. NTIS # PB92-111996.
39. NTP NTP Technical Report on Toxicity Studies of Dibutyl Phthalate Administered in Feed to F344/N Rats and B6C3F1 Mice. Toxicity Report Series Number 30 1995, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Toxicity Program, Research Triangle Park, NC, http://ntp.niehs.nih.gov/ntp/htdocs/ST_rpts/tox030.pdf.
40. NTP-CERHR (National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction) NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP) 2000, National Toxicology Program, U.S. Department of Health and Human Services, Research Triangle Park, NC, http://cerhr.niehs.nih.gov/chemicals/phthalates/dbp/DBP_Monograph_Final.pdf.
41. OECD Series on Testing and Assessment, Number 43: Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment 2008, Organisation for Economic Co-operation and Development, ENV/JM/MONO(2008)16, July-2008, Paris. http://www.oecd.org/document/30/0,3343,en_2649_34377_1916638_1_1_1_1,00.html.
42. Plummer S., Hallmark N., Sharpe R., Elcombe C. Identification of gene clusters and signaling pathways affected by dibutyl phthalate-nuclear receptor interactions in fetal rat testes. Abstract #2258. Toxicologist 2005, 79:463.
43. Plummer S., Sharpe R.M., Hallmark N., Mahood I.K., Elcombe C. Time-dependent and compartment-specific effects of in utero exposure to di(n-butyl) phthalate on gene/protein expression in the fetal rat testis as revealed by transcription profiling and laser capture microdissection. Toxicol. Sci. 2007, 97(2):520-532.
44. Saillenfait A.M., Payan J.P., Fabry J.P., Beydon D., Langonne I., Gallissot F., Sabate J.P. Assessment of the developmental toxicity, metabolism, and placental transfer of di-n-butyl phthalate administered to pregnant rats. Toxicol. Sci. 1998, 45(2):212-224.
45. Shultz V.D., Phillips S., Sar M., Foster P.M.D., Gaido K.W. Altered gene profiles in fetal rat testes after in utero exposure to di(n-butyl) phthalate. Toxicol. Sci. 2001, 64(2):233-242.
46. Skakkeback N.E., Rajpert-De Meyts E., Main K.M. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod. 2001, 16:972-978.
47. Srivastava S.P., Srivastava S., Saxena D.K., Chandra S.V., Seth P.K. Testicular effects of di-n-butyl phthalate (DBP): biochemical and histopathological alterations. Arch. Toxicol. 1990, 64:148-152.
48. Swan S.H. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ. Res. 2008, 108:177-184.
49. Swan S.H., Main K.M., Liu F., Stewart S.L., Kruse R.L., Calafat A.M., Mao C.S., Redmon J.B., Ternand C.L., Sullivan S., Teague J.L. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ. Health Perspect. 2005, 113:1056-1061.
50. Thompson C.J., Ross S.M., Gaido K.W. Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism. Endocrinology 2004, 145(3):1227-1237.
51. Thompson C.J., Ross S.M., Hensley J., Liu K., Heinze S.C., Young S.S., Gaido K.W. Differential steroidogenic gene expression in the fetal adrenal versus the testis and rapid and dynamic response of the fetal testis to di(n-butyl) phthalate. Biol. Reprod. 2005, 73(5):908-917.
52. U.S.EPA Guidelines for reproductive toxicity risk assessment. Risk Assessment Forum, 630/R-96/0009, Washington, DC http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=23162.
53. U.S.EPA Guidelines for carcinogen risk assessment. Risk Assessment Forum, Washington, DC. EPA/630/P-R-03/001B.003 http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_id=439797.
54. U.S.EPA Toxicological review of dibutyl phthalate (di-n-butyl phthalate). External peer review draft. Integrated Risk Information System, Washington, DC; NCEA-S-1755 http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=155707.
55. U.S. EPA, 2009a. The U.S Environmental Protection Agency's Strategic Plan for Evaluating the Toxicity of Chemicals (Final Report). March 2009, Office of the Science Advisor, Washington, DC. EPA/100/K-09/001. http://www.epa.gov/OSA/spc/toxicitytesting/docs/toxtest_strategy_032309.pdf.
56. U.S. EPA, 2009b. An Approach to Using Toxicogenomic Data in U.S. EPA Human Health Risk Assessments: a Dibutyl Phthalate (DBP) Case Study (Final Report), National Center for Environmental Assessment, Office of Research and Development, Washington, DC. EPA/600/R-09/028F. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=213405.
57. Virtanen H.E., Cortes D., Rajpert-De Meyts D., Ritzén E.M., Nordenskjöld A., Skakkebaek N.E., Toppari J. Development and descent of the testis in relation to cryptorchidism. Acta Paediatr. 2007, 96(5):622-627.
58. Welsh M., Saunders P.T.K., Fisken M., Scott H.M., Hutchison G.R., Smith L.B., Sharpe R.M. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J. Clin. Invest. 2008, 118:1479-1490.
59. Wilson V.S., Lambright C., Furr J., Ostby J., Wood C., Held G., Gray L.E. Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis. Toxicol. Lett. 2004, 146(3):207-215.
60. Wilson V.S., Keshava N., Hester S., Segal D., Chiu W., Thompson C.M., Euling S.Y. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment. Toxicol. Appl. Pharmacol. 2013, 271(3):299-308. (this issue).
61. Wine R.N., Li L.-H., Barnes L.H., Gulati D.K., Chapin R.E. Reproductive toxicity of di-n-butylphthalate in a continuous breeding protocol in Sprague-Dawley rats. Environ. Health Perspect. 1997, 105:102-107.
62. Wood H.M., Elder J.S. Cryptorchidism and testicular cancer: separating fact from fiction. J. Urol. 2009, 181(2):452-461.
63. Woodruff T.J., Zeise L., Axelrad D.A., Guyton K.Z., Janssen S., Miller M., Miller G.G., Schwartz J.M., Alexeeff G., Anderson H., Birnbaum L., Bois F., Cogliano V.J., Crofton K., Euling S.Y., Foster P.M., Germolec D.R., Gray E., Hattis D.B., Kyle A.D., Luebke R.W., Luster M.I., Portier C., Rice D.C., Solomon G., Vandenberg J., Zoeller R.T. Meeting report: moving upstream-evaluating adverse upstream end points for improved risk assessment and decision-making. Environ. Health Perspect. 2008, 116(11):1568-1575.
64. Zhang Y., Jiang X., Chen B. Reproductive and developmental toxicity in F1 Sprague-Dawley male rats exposed to di-n-butyl phthalate in utero and during lactation and determination of its NOAEL. Reprod. Toxicol. 2004, 18(5):669-676.