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D.V. Cicchetti, A.S. Kaufman, and S.S. Sparrow (this issue) examine various technical issues related to six studies of perinatal PCB exposure and neurodevelopment and one study of adult PCB exposure and motor function. They raise questions about possible imperfections of the studies, but many of their assertions are unsupported or frankly incorrect, and they do little to assess the potential impact of the issues that they raise; we find none of their arguments about flaws in our study compelling. Their stated purpose is to scientifically evaluate the body of literature, but their narrow focus does not allow a genuine evaluation of the scientific evidence.

BACKGROUND: Early-life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula, and they result in high serum concentrations. OBJECTIVES: Our goal was to determine whether soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls. METHODS: Using the Illumina HumanMethylation450 BeadChip, we evaluated epigenome-wide DNA methylation in vaginal cells from four soy formula-fed and six cow formula-fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and 9 months of age from 50 girls (28 soy formula-fed and 22 cow formula-fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue. RESULTS: The epigenome-wide scan suggested differences in methylation between soy formula-fed and cow formula-fed infants at three CpGs in the gene proline rich 5 like (PRR5L) (p < [10.sup.4]). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein-exposed mice showed a 50% decrease in vaginal Prr5l mRNA levels compared to controls. CONCLUSIONS: Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene. http://dx.doi.org/10.1289/EHP428, Introduction Soy formula use during infancy has been associated with altered age at menarche (Adgent et al. 2012; D'Aloisio et al. 2013) and identified as a risk factor for uterine [...]

Objective. Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 [micro]g/dL (0.96-2.12 [micro]mol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years. Methods. The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured. Results. Chelation therapy with succimer lowered average blood lead levels for ~6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints. Conclusion. These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 [micro]g/dL (0.96-2.17 [micro]mol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 [micro]g/dL (0.96-2.12 [micro]mol/L). Pediatrics 2004;114:19-26; child, lead, environmental exposure, chelation therapy, succimer, cognition, clinical trials. ABBREVIATIONS. CDC, Centers for Disease Control and Prevention; TLC, Treatment of Lead-Exposed Children; NEPSY, Developmental Neuropsychological Assessment; CI, confidence interval., Before the availability of chelating drugs, as many as 45% of lead-poisoned children who presented with signs or symptoms of encephalopathy died, and more than one quarter of surviving patients [...]

Although dichlorodiphenyl trichloroethane (DDT)is being banned worldwide, countries in sub-Saharan Africa have sought exemptions for malaria control. Few studies show illness in children from the use of DDT, and the [...]

Pollutant chemicals that are widespread in the environment can affect endocrine signaling, as evidenced in laboratory experiments and in wildlife with relatively high exposures. Although humans are commonly exposed to such pollutant chemicals, the exposures are generally low, and clear effects on endocrine function from such exposures have been difficult to demonstrate. Several instances in which there are data from humans on exposure to the chemical agent and the endocrine outcome are reviewed, including age at weaning, age at puberty, and sex ratio at birth, and the strength of the evidence is discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real., ABBREVIATIONS. DDT, dichlorodiphenyltrichloroethane, PCB, polychlorinated biphenyl; DDE, dichlorodiphenyldichloroethene; ppm, parts per million. The most informative studies of the effects of environmental chemicals on the endocrine system in children concern 2 [...]

Objective. Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ. Methods. We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable. The 741 children began with blood lead levels between 20 and 44 [micro]g/dL, and were 13 to 33 months old at randomization to chelation or placebo. Blood lead levels were measured repeatedly, and cognitive tests were given at baseline, 6 months, and 36 months follow-up. Results. By 6 months after randomization, blood lead levels had fallen by similar amounts in both chelated and placebo children, despite the immediate drops in the chelated group; there was no association between change in blood lead level and change in cognitive test score. Blood lead levels continued to fall. At 36 months follow-up, in the placebo group only, cognitive test scores had increased 4.0 points per 10 [micro]g/dL fall in blood lead level from baseline to 36 months follow-up and 5.1 points from 6 to 36 months. Conclusions. The improvement in scores in the placebo group only implies that factors other than declining blood lead levels per se are responsible for cognitive improvement; it is possible but less likely that succimer, the active drug, impairs cognition. Pediatrics 2002;110: 787-791; child, preschool; environmental exposure; lead poisoning/blood/etiology; cognition/physiology; chelation therapy., ABBREVIATIONS. TLC, Treatment of Lead-Exposed Children; MDI, Mental Development Index; SD, standard deviation. Prospective data from multiple studies in several countries show that lead exposure insufficient to produce symptoms still [...]

Chelation therapy with succimer did not protect children with mild lead poisoning from developmental disabilities, according to a study of 780 children with blood lead levels between 20 and 44 micrograms per deciliter. Chelation therapy uses chemicals that can remove toxic metals from the body.