the aforementioned designs, but this can be reduced by constructing nested case–control studies. Nutrition and genetic predisposition are important contributors to growth and maturity, which require further investigations. Although it is generally accepted that nutrition affects pubertal development, unresolved issues remain because this association is variable among studies, and recent evidence suggests that birth size contributes to puberty as well (Luo et al. 2003). The extent to which birth height and body mass index relate to nutritional status in determining the timing of puberty is not known. As more work is done to resolve such questions, it would be important to con- trol for environmental chemical exposure. Strategies for Testing Hypotheses Sampling Periods The timing for the collection of exposure data (environmental, questionnaire, and biologic) depends on two general factors: the health Exposure measure Maternal serum level posteventb Serum level at puberty Intrauterine Milk level at birth Postnatal (breastfeeding) Lactational exposure index Puberty Puberty Serum level at puberty Questionnaire Level of exposure Mean ± SD, 5.6 µg/L ± 5.5; range, NDc to 78 µg/L Exposures: range of PCB-138 means, 94–227 ng/L Exposures: range of PCB-153 means, 166–332 ng/L Exposures: range of PCB-180 means, 95–202 ng/L Median, 1.7 µg/g lipids, Range, 0.5–5.5 µg/g lipids Cases: DEHP, 450 µg/L (mean ± SD not given) Controls: DEHP, 70 µg/L (mean ± SD not given) Seveso, Italy, in 1976) in combination with elevated levels are exceptions. Timing is more of a problem for a persistent chemical with a long half-life than for a nonpersistent chemical. This problem can make it difficult to assess either the occurrence of subacute exposures or the source of the exposure when location has changed. The lack of consideration for these concerns can lead to either misclassiﬁcation of a study participant for a critical window of exposure, or increased variance in the popula- tion for a given effect. Additional concerns with these types of designs for investigating health effects include the difﬁculty in establish- ing a temporal relation between exposure and effect and the introduction of recall bias when collecting information from the participants. These study design issues are best resolved with a prospective longitudinal design, which can be accomplished for environmental chem- icals during the evaluation of other factors more closely associated with pubertal develop- ment. The assessment for exposure in this set- ting may be more resource intensive than in Table 1. Continued Chemical PCBs Developmental window or route of exposure assessed Intrauterine Puberty Reference Blanck et al. 2000 Den Hond et al. 2002 Gladen et al. 2000 Phthalates Colon et al. 2000 Phytoestrogens Freni-Titulaer et al. 1986 Abbreviations: DEHP, di-(2-ethylhexyl) phthalate; ND, not detected; p,p’-DDE, p,p', dichlorodiphenyldichloroethylene; TEQ, toxic equivalent. aPBB limit of detection, 1 µg/L. bCows contaminated by feed containing PBB in 1973. cPCB limit of detection, 5 µg/L. Environmental Health Perspectives • VOLUME 113 | NUMBER 8 | August 2005 effect being monitored and the environmental chemical that is under evaluation. In the evaluation of sexual maturation, it is important to monitor for the formative periods of the sex- ual organs (in utero) when a signiﬁcant amount of chemical exposure is expected, that is, post- natal (breast-feeding), pre- and peripuberty, and the completion of puberty. These are dis- cussed to a greater extent elsewhere (Pryor et al. 2000). Recruitment of participants dur- ing preconception will ensure that exposures in the ﬁrst trimester of gestation will be character- ized, and data collected at this time may serve as a baseline comparison throughout the pregnancy and the postpartum period. The successful completion of sexual matu- ration is dependent on proper anatomic devel- opment of the organs and hormonal regulation leading to their function. The anatomic devel- opment of organs and sexual differentiation of the fetus occurs during pregnancy or the in utero period. Organogenesis takes place in the ﬁrst trimester (weeks 4–8) of gestation, and disruption during this time can lead to Associated health effects Males Females Decreased likelihood to attain genital maturity with increasing PCB-138 level Decreased likelihood to attain pubarche with increasing PCB-153 level No effect on likelihood to attain either genital maturity or pubarche by PCB-180 level No effect on time of onset of puberty or height or body weight at puberty by PCB level from intrauterine exposure No effect on time of onset of puberty or height or body weight at puberty by PCB level from lactational exposure Assessment of environmental chemicals affecting puberty No effect on age at menarche or attainment of thelarche or pubarche by intrauterine PCB level No effect on likelihood to attain either thelarche or pubarche by PCB-138 level No effect on likelihood to attain either thelarche or pubarche by PCB-153 level No effect on likelihood to attain either thelarche or pubarche by PCB-180 level No effect on time of onset of puberty by PCB level from intrauterine exposure Increased body weight at puberty with increasing PCB level from intrauterine exposure in Caucasian girls No effect on time of onset, height, or body weight at puberty by PCB level from lactational exposure Premature thelarche Use of soy-based formula increased likelihood for onset of premature thelarche before 2 years of age 1103