Wang et al. these earlier findings because of either their small sample sizes or the current availability of improved methodology (e.g., biomonitoring) in exposure assessment. Despite the ﬁndings of the various studies presented in the preceding section, the extent to which environmental chemicals contribute to changes in human pubertal development remains largely unknown. This is because of limitations in the designs of the investigations from which these observations were made, the various approaches used in conducting expo- sure assessment, and the few number of chemicals studied to date that are related to populations. A focused investigation could attempt to answer some of the questions regarding environmental chemical exposure and maturation. For example, what is the sig- niﬁcance to pubertal development of the tim- ing of exposure to a chemical during a child’s growth? Current studies in this area do not allow for such conclusions because of cross- sectional or retrospective design. The observations from either cross- sectional or retrospective study designs are dif- ﬁcult to interpret as to the timing of chemical exposure during a child’s development, and use less than perfect models to assess for overall exposure when a single level of a chemical in a biologic matrix is available. An example of when the latter situation becomes challenging is with human milk. When infant exposure is assessed from human milk consumption, both the changing level of the chemical in the milk during the breast-feeding period and the duration of breast-feeding must be considered. The timing of exposure to a chemical is extremely difficult to ascertain from these study designs. This is because the random sam- pling of blood or urine from an individual does not allow for a determination of when the exposure occurred, which could have been at any time before the procurement of the speci- men. However, exposures to apparent events (e.g., the industrial chemical explosion in Table 1. Human studies on the effects of environmental chemical exposure on pubertal development. Chemical p,p’-DDE Reference Gladen et al. 2000 Exposure measure Milk level at birth Level of exposure Median, 2.4 µg/g lipids Range, 0.3–23.8 µg/g lipids Dioxin-like compounds Endosulfan Lead PBBs 1102 Krstevska- Konstantinova et al. 2001 Den Hond et al. 2002 Saiyed et al. 2003 Selevan et al. 2003 Wu et al. 2003 Blanck et al. 2000 Developmental window or route of exposure assessed Intrauterine Postnatal (breastfeeding) Puberty Puberty Puberty Puberty Lactational exposure index Serum level at or postpuberty Serum level at puberty Serum level at puberty Blood level at puberty Puberty Intrauterine Blood level at puberty Extrapolated maternal serum level posteventb Immigrant/adopted, 1.04 µg/L (median) Immigrant/nonadopted, 1.20 µg/L (median) Native, 0.13 µg/L (median) Exposures: range of means, 0.11–0.21 ng TEQ/L Exposed, 7.47 ± 1.19 µg/L (mean ± SD) Nonexposed, 1.37 ± 0.40 µg/L (mean ± SD) Non-Hispanic whites: geometric mean, 1.4 µg/dL; 95% CI, 1.2–1.5 African Americans: geometric mean, 2.1 µg/dL; 95% CI, 1.9–2.3 Mexican Americans: geometric mean, 1.7 µg/dL, 95% CI, 1.6–1.9 Range, 0.7–21.7 µg/dL Mean ± SD, 17.3 µg/L ± 107.8; range, NDa to 1,142 µg/L Associated health effects Males Females No effect on attainment No effect on time of of puberty by DDE level onset, height, or body from intrauterine weight at puberty by exposure DDE level from Increased height and intrauterine exposure body weight at puberty with increasing DDE level from intrauterine exposure No effect on attainment of puberty by DDE level from lactational exposure Immigrant children with idiopathic precocious puberty had higher DDE levels than native children with precocious puberty; adoption status was not associated with DDE level No effect on likelihood to attain either genital maturity or pubarche by TEQ level Delayed pubarche and genital maturity with exposure Decreased likelihood to attain thelarche with increasing TEQ level No effect on pubarche, menarche, or thelarche by lead level for non- Hispanic whites Delayed pubarche, thelarche, and menarche with increasing lead level for African Americans Delayed pubarche and thelarche with increasing lead level for Mexican Americans Decreased height with increasing lead level, regardless of race/ethnicity Delayed pubarche and menarche with increasing lead level, no effect on attainment of thelarche by lead level Accelerated attainment of menarche with increasing intrauterine PBB level and breast-feeding Continued, next page VOLUME 113 | NUMBER 8 | August 2005 • Environmental Health Perspectives