Research | Mini-Monograph Effects of Environmental Agents on the Attainment of Puberty: Considerations When Assessing Exposure to Environmental Chemicals in the National Children’s Study Richard Y. Wang, Larry L. Needham, and Dana B. Barr National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA The apparent decline in the age at puberty in the United States raises a general level of concern because of the potential clinical and social consequences of such an event. Nutritional status, genetic predisposition (race/ethnicity), and environmental chemicals are associated with altered age at puberty. The Exposure to Chemical Agents Working Group of the National Children’s Study (NCS) presents an approach to assess exposure for chemicals that may affect the age of maturity in children. The process involves conducting the assessment by life stages (i.e., in utero, postnatal, peripubertal), adopting a general categorization of the environmental chemicals by biologic persistence, and collect- ing and storing biologic specimens that are most likely to yield meaningful information. The analysis of environmental samples and use of questionnaire data are essential in the assessment of chemicals that cannot be measured in biologic specimens, and they can assist in the evaluation of exposure to nonpersistent chemicals. Food and dietary data may be used to determine the extent to which nutri- ents and chemicals from this pathway contribute to the variance in the timing of puberty. Additional research is necessary in several of these areas and is ongoing. The NCS is uniquely poised to evaluate the effects of environmental chemicals on the age at puberty, and the above approach will allow the NCS to accomplish this task. Key words: children, environmental chemicals, exposure assessment, hor- monally active agents, National Children’s Study, puberty. Environ Health Perspect 113:1100–1107 (2005). doi:10.1289/ehp.7615 available via http://dx.doi.org/ [Online 12 May 2005] The purpose of the National Children’s Study (NCS) is to evaluate the health risks to chil- dren in this country from environmental exposures by using a longitudinal cohort design (Children’s Health Act of 2000). This effort is expected to improve our children’s health by mitigating these health risks in our society. The approach of the NCS is to cen- tralize its activities around hypotheses that evaluate the relationship between a wide array of environmental exposures (i.e., chemical, biologic, physical, and psychosocial factors) and priority health outcomes. The list of pri- ority outcomes includes pregnancy, neuro- developmental injury, asthma, and obesity and physical development. One of several NCS hypotheses addressing these concerns seeks to evaluate the effects of environmental agents on the age at puberty, which was dis- cussed at an inter-work group meeting co- chaired by the Nutrition, Growth, and Pubertal Development Working Group and the Exposure to Chemical Agents Working Group (Baltimore, Maryland, 17–18 December 2002). This article presents a brief back- ground on the factors associated with the age of maturity and discusses the assessment for exposure to environmental chemical agents in the developing child by using a life-stage approach. The articles in this mini-mono- graph describe the roles and efforts of the Exposure to Chemical Agents Working Group in the NCS. Portions of this discussion may refer the reader to these other articles for additional information. 1100 Recent evidence suggests that puberty in U.S. children is starting at an earlier age com- pared with previous years (Anderson et al. 2003; Freedman et al. 2003; Herman- Giddens et al. 1997, 2001). This is of general interest because the extent to which this is occurring in this population has not been well characterized and because such ﬁndings have potential influences within our society. In cross-sectional studies of populations in the United States from 1988 through 1994, it is reported that the mean age of onset for breast development for girls was 9.5–9.7 years, which is approximately 1–2 years earlier than the observations of previous investigators (Lee et al. 2001). This approximates to 14% of the population achieving Tanner stage 2 or greater for breast development at the age of 8 years (Lee et al. 2001). In U.S. boys sampled from 1988 through 1994, the median age of onset for genital development ranged from 9.5 to 10.4 years, depending on race/ethnicity, which is about 1 year earlier than that previ- ously described (Herman-Giddens et al. 2001). This corresponded to about 32–58% of the boys attaining Tanner stage 2 at 9 years of age. These observed changes in pubertal development are not unique to the United States but also have been noted in other coun- tries (Huen et al. 1997; Karlberg 2002; Parent et al. 2003; Proos et al. 1993; Viner 2002). To define properly the significance of these findings to the population, more refined investigations are needed to characterize the time trend in pubertal development because of the limitations in study design of these prior reports (Lee et al. 2001; Reiter and Lee 2001; Viner 2002). Nutrition, genetic pre- disposition, and environmental chemical exposure are factors associated with pubertal change that can be evaluated during this process. The factors associated with altered puber- tal development are numerous (Parent et al. 2003). When early onset of puberty was origi- nally noted in immigrant children, it was attributed to improved nutrition and well- being. Although these remain the primary fac- tors determining the onset and progression of puberty, there are other considerations. These include genetic predisposition or host suscep- tibility, and environmental chemical exposure. Certain populations may be susceptible to variations in pubertal development base on observations among racial/ethnic groups (Anderson et al. 2003; Freedman et al. 2002; Sun et al. 2002; Wu et al. 2002). African- American girls were reported to develop either thelarche or pubarche at about the mean age of 8.8 years, 1–2 years earlier than non- Hispanic white girls (Herman-Giddens et al. 1997). This trend in race/ethnic groups for the age of onset for puberty was noted in boys as well (Herman-Giddens et al. 2001; Sun et al. 2002). Although obesity was associated with the early onset of puberty in these racial/ethnic groups, it was less of a determin- ing variable in African-American girls, sug- gesting the involvement of other factors (Kaplowitz et al. 2001). In a study of serum leptin levels in girls 8–17 years of age, African- Americans girls were noted to have higher lep- tin levels than Caucasians after controlling for obesity, age, and serum insulin levels (Wong et al. 1998). Although serum leptin was shown to increase before gonadotropin levels in girls and boys (Garcia-Mayor et al. 1997), This article is part of the mini-monograph “Assessing Exposures to Environmental Agents during the National Children’s Study.” Address correspondence to R. Wang, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway, MS-F17, Atlanta, GA 30341 USA. Telephone: (770) 488-7950. Fax: (770) 488-4546. E-mail: RYWang@cdc.gov The authors declare they have no competing ﬁnancial interests. Received 20 September 2004; accepted 14 March 2005. VOLUME 113 | NUMBER 8 | August 2005 • Environmental Health Perspectives