Flame Retardants in Placenta and Breast Milk and Cryptorchidism in Newborn Boys
Main, Katharina Maria, Kiviranta, Hannu, Virtanen, Helena Eeva, Sundqvist, Erno, Tuomisto, Jouni Tapio, Tuomisto, Jouko, Vartiainen, Terttu, Skakkebaek, Niels Erik, Toppari, Jorma, Environmental Health Perspectives
Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants, and the general population is exposed through products such as upholstery, building materials, insulation, electronic equipment, and contaminated food. PBDEs are added to polymers without being chemically bound and can leach into the environment, where they settle with air particles and sludge. They are persistent, and some--BDE-47, BDE-99, and BDE-153--can accumulate in lipid-rich tissues (Agency for Toxic Substances and Disease Registry 2004; Sjodin et al. 2003).
Concentrations of PBDE in human European breast milk samples are generally low compared with those in the United States, and considered to be well below the estimated lowest observed adverse effect level (LOAEL) of 1 mg/kg/day (Darnerud et al. 2001). Two technical mixtures, penta- and octa-mixtures of PBDEs, have been banned from use in Europe since 2003 (Darnerud et al. 2001), and Swedish studies indicated a decrease in breast milk levels since the middle of the 1990s (Meironyte et al.1999; Sjodin et al. 2003). However, annual production rates of some PBDEs are still considerable in some areas (Alaee et al. 2006; Betts 2002; Law et al. 2006). Animal studies show that some PBDEs exhibit endocrine-disrupting activity, which has been studied predominantly for thyroid hormone transport and metabolism (Legler and Brouwer 2003), but data on adverse effects on reproductive outcome after gestational exposure are also emerging (Lilienthal et al. 2006).
The prevalence of cryptorchidism in newborn boys appears to have increased in some areas, such as Great Britain and Denmark, over the past decades, and its current prevalence is considerably higher in Denmark than in Finland (Anonymous 1986; Boisen et al. 2004). Although the reason for this is as yet unknown, the rapid increase in prevalence suggests that environmental factors are involved (Sharpe 2006; Skakkebaek et al. 2001). Adverse effects of fetal exposure to environmental chemicals on testicular descent and hormonal function may be detectable during the short physiologic activation of the pituitary-gonadal axis at approximately 3 months of age (Andersson et al. 1998; Main et al. 2000, 2006b; Suomi et al. 2006).
In this study we aimed to evaluate the association between exposure to 14 PBDEs (BDEs 28, 47, 66, 71, 75, 77, 85, 99, 100,119, 138, 153, 154, 183) in newborn boys and the position and function of the testes.
Materials and Methods
The study was conducted according to the Helsinki II Declaration (World Medical Association 2000) after informed oral and written consent of the parents. The ethical committees (Finland: 7/1996; Denmark: KF01-030/97) and the Danish Data Protection Agency (1997-1200-074) approved the study
Study population. We obtained breast milk samples and placentas from a joint prospective, longitudinal cohort study performed 1997-2001 at Turku University Hospital, Turku, Finland, and the National University Hospital (Rigshospitalet, Hvidovre Hospital), Copenhagen, Denmark. This binational study aimed at establishing contemporary prevalence rates for cryptorchidism and hypospadias and evaluating risk factors by means of questionnaires and biological samples (blood, placentas, breast milk). Exposure measurements were prospectively planned to include persistent and nonpersistent chemicals, some of which have been previously reported (Damgaard et al. 2006; Main et al. 2006a; Shen et al. 2005, 2006, 2007). Recruitment strategy, inclusion criteria, and clinical examination of the children (i.e., the identification of cryptorchidism) have been previously described (Boisen et al. 2004; Main et al. 2006b; Suomi et al. 2006) and were strictly standardized. Boys with normally descended testes, including retractile testes, were used as controls in this study under the terms "controls" or "healthy boys." Boys with undescended testes (nonpalpable, inguinal, suprascrotal, high scrotal), either uni- or bilaterally at birth, were included in the group of cryptorchid boys. …