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Ida N. Damgaard,¹ Niels E. Skakkebæk,¹ Jorma Toppari,² Helena E. Virtanen,² Heqing Shen,³ Karl-Werner Schramm,³ Jørgen H. Petersen,^1,4 Tina K. Jensen,¹ Katharina M. Main,¹ and the Nordic Cryptorchidism Study Group

¹University Department of Growth and Reproduction, Copenhagen, Denmark; ²Departments of Physiology and Pediatrics, University of Turku, Turku, Finland; ³GSF-National Research Center for Environmental and Health, Institute for Ecological Chemistry, Neuherberg, Germany; ⁴Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

Abstract
Introduction: Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children.

Design: Within a prospective birth cohort, we performed a case–control study ; 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Milk was collected as individual pools between 1 and 3 months postpartum and analyzed for 27 organochlorine pesticides.

Results: Eight organochlorine pesticides were measurable in all samples (medians ; nanograms per gram lipid) for cases/controls: 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene (p,p´-DDE) : 97.3/83.8 ; β-hexachlorocyclohexane (β-HCH) : 13.6/12.3 ; hexachlorobenzene (HCB) : 10.6/8.8 ; -endosulfan: 7.0/6.7 ; oxychlordane: 4.5/4.1 ; 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p´-DDT) : 4.6/4.0 ; dieldrin: 4.1/3.1 ; cis-heptachloroepoxide (cis-HE) : 2.5/2.2. Five compounds [octachlorostyrene (OCS) ; pentachlorobenzene, 1,1-dichloro-2,2-bis(4-chlorophenyl) ethane(p,p´-DDD) ; o,p´-DDT ; mirex] were measurable in most samples (detection rates 90.8–99.2%) but in lower concentrations. For methoxychlor, cis-chlordane, pentachloroanisole (PCA) , -HCH, 1,1-dichloro-2-(2-chlorophenyl) -2,2(4-chlorophenyl) ethane, trans-chlordane, -HCH, and o,p´-DDE, both concentrations and detection rates were low (26.5–71.5%) . Heptachlor, HCH (, ) , aldrin, β-endosulfan and trans-heptachloroepoxide were detected at negligible concentrations and low detection rates and were not analyzed further. Seventeen of 21 organochlorine pesticides [p,p´-DDT, p,p´-DDE, p,p´-DDD, o,p´-DDT, HCH (, β, ) , HCB, PCA, -endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, OCS, and dieldrin] were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane (p = 0.012) , there were no significant differences between cryptorchid and healthy boys for individual chemicals. However, combined statistical analysis of the eight most abundant persistent pesticides showed that pesticide levels in breast milk were significantly higher in boys with cryptorchidism (p = 0.032) .

Conclusion: The association between congenital cryptorchidism and some persistent pesticides in breast milk as a proxy for maternal exposure suggests that testicular descent in the fetus may be adversely affected.

Key words: cryptorchidism, human breast milk, infants, persistent organochlorine pesticides. Environ Health Perspect 114: 1133–1138 (2006) . doi:10.1289/ehp.8741 available via http://dx.doi.org/ [Online 27 February 2006]

Address correspondence to I. Damgaard, University Department of Growth and Reproduction, GR-5064 Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Telephone: 45 35 45 43 30. Fax: 45 35 45 60 54. E-mail: ind@rh.dk

Members of the Nordic Cryptorchidism Study Group: K. Boisen, M. Chellakooty, and I. Schmidt from the University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark ; M. Kaleva and A. Suomi from the Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.

This work was supported by The University of Copenhagen, The Danish Medical Research Council (grants 9700833 and 9700909) , Svend Andersens Foundation, Novo Nordisk Foundation, The Academy of Finland, Sigrid Jusélius Foundation, Turku University Central Hospital and the European Commission (contracts BMH4-CT96-0314, QLK4-CT1999-01422, QLK4-2001-00269, and QLK4-CT2002-00603) .

The sponsors had no part in study design, data collection, analysis, interpretation, or writing of the manuscript. The article does not represent the opinion of the European Community, which is not responsible for any use that might be made of the data appearing therein.

The authors declare they have no competing financial interests.

Received 14 October 2005 ; accepted 27 February 2006.