Wang et al. commonly found in personal care products (e.g., cosmetics, shampoos); therefore, researchers should ask specific questions regarding the use of these products (Tiwary and Ward 2003). Similarly, changes in loca- tion throughout the life stages (home, school, work site) may warrant adjustments of these assessment tools. In the design of these expo- sure assessment tools, it is important to vali- date them before applying them to health effect studies. Biologic markers of health effect. These measurements will be used to monitor the onset and completion of puberty. Various tools can be used, including biochemical measures (e.g., hormones), physical examina- tion, and diagnostic scans (Rockett et al. 2004) (Table 3). Dual-energy X-ray absorp- tiometry is a noninvasive method to assess body fat mass, body fat-free mass, and bone mineral mass and density for skeletal maturity. Potential Risk Factors for Altered Pubertal Development Several factors are known to cause or are associ- ated with altered pubertal development that need to be considered in the study because they may bias the estimate of the relationship between chemical exposure and the age of onset of puberty. Some of these items are listed in Table 4. Conclusion Evidence exists that nutritional status, genetic predisposition (race/ethnicity), and environ- mental chemical exposure are associated with altered age at puberty. The assessment for exposure to environmental chemicals that may affect the attainment of puberty in the develop- ing child is challenged by several factors, includ- ing the various developmental periods when an exposure can affect the maturation process, lim- ited access to certain biologic specimens during select periods of human development, and the many chemicals with varying properties. The recommended approach is to conduct the assessment by life stages (i.e., in utero, postnatal, pre- and peripubertal). Study participants need to be recruited at preconception to ensure that the “critical window” of gestation, that is, the first trimester, is included in the exposure assessment process. Chemicals should be cate- gorized by biologic persistence, and biologic specimens that are most likely to yield mean- ingful information should be collected and stored. The latter will allow for the judicious use of specimens of limited quantity for special investigations (e.g., nested case–control studies) and time to develop new and improved analyti- cal methods. For chemicals that either cannot be measured in biologic specimens or have short biologic half-lives, the analysis of environ- mental samples and use of questionnaire data are necessary to complete the assessment for exposure. Food and dietary data may assist in determining the extent to which nutrients and chemicals from this pathway contribute to the variance in the timing of puberty. Factors that are either known causes of, or associated with, altered pubertal development need to be con- trolled for during the assessment of health out- comes. The National Children’s Study is uniquely poised to evaluate the effects of envi- ronmental chemicals on the age at puberty, and the above approach will allow the NCS to accomplish this task. Table 4. Potential risk factors affecting pubertal development. Precocious Gonadotropin-dependent (central precocious puberty) Brain pathology (e.g., hypothalamic hamartoma, tumors, hydocephalus, severe head trauma) Hypothyroidism, untreated Gonadotropin-independent precocious puberty McCune-Albright syndrome in girls Familial male precocious puberty (testotoxicosis) Tumors (ovarian, adrenocortical, Leydig cell, chorionic gonadotropin-secreting tumors) Exogenous pharmaceutical estrogen or androgen use Isolated premature thelarche, premature pubarche/adrenarche, premature menarche Delayed Poor nutrition Chronic illness Constitutional growth delay Intense physical training General categories associated with altered pubertal development General nutrition General health Brain injury Obesity Socioeconomic status Immigration/adoption Race/ethnicity Pharmaceuticals [estrogenic, androgenic, estrogen blocker (i.e., aromatase inhibitors), and androgen blocker (e.g., ﬁnasteride, ﬂutamide)] Genetics Gestational age REFERENCES Anderson SE, Dallal GE, Must A. 2003. 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