Relationship of Lead, Mercury, Mirex, Dichlorodiphenyldichloroethylene, Hexachlorobenzene, and Polychlorinated Biphenyls to Timing of Menarche Among Akwesasne Mohawk Girls

Background. Children are commonly ex- posed at background levels to several ubiquitous envi- ronmental pollutants, such as lead and persistent organic pollutants, that have been linked to neurologic and en- docrine effects. These effects have prompted concern about alterations in human reproductive development. Few studies have examined the effects of these toxicants on human sexual maturation at levels commonly found in the general population, and none has been able to examine multiple toxicant exposures. The aim of the current investigation was to examine the relationship between attainment of menarche and levels of 6 envi- ronmental pollutants to which children are commonly exposed at low levels, ie, dichlorodiphenyldichloroeth- ylene (p,p-DDE), hexachlorobenzene (HCB), polychlori- nated biphenyls (PCBs), mirex, lead, and mercury. Methods. This study was conducted with residents of the Akwesasne Mohawk Nation, a sovereign territory that spans the St Lawrence River and the boundaries of New York State and Ontario and Quebec, Canada. Since the 1950s, the St Lawrence River has been a site of sub- stantial industrial development, and the Nation is cur- rently adjacent to a US National Priority Superfund site. PCB, p,p-DDE, HCB, and mirex levels exceeding the US Food and Drug Administration recommended tolerance limits for human consumption have been found in local animal species. The present analysis included 138 Akwe- sasne Mohawk Nation girls 10 to 16.9 years of age. Blood samples and sociodemographic data were collected by Akwesasne community members, without prior knowl- edge of participants' exposure status. Attainment of men- ses (menarche) was assessed as present or absent at the time of the interview. Congener-specific PCB analysis was available, and all 16 PCB congeners detected in >50% of the sample were included in analyses (Interna- tional Union of Pure and Applied Chemistry numbers 52, 70, 74, 84, 87, 95, 99, 101 (90), 105, 110, 118, 138 (163 and 164), 149 (123), 153, 180, and 187). Probit analysis was used to determine the median age at menarche for the sample. Binary logistic regression analysis was used to determine predictors of menarcheal status. Six toxicants (p,p-DDE, HCB, PCBs, mirex, lead, and mercury) were entered into the logistic regression model. Age, socioeco- nomic status (SES), and BMI were tested as potential cofounders and were included in the model at P < .05. Interactions among toxicants were also evaluated. Results. Toxicant levels were measured in blood for this sample and were consistent with long-term exposure to a variety of toxicants in multiple media. Mercury lev- els were at or below background levels, all lead levels were well below the Centers for Disease Control and Prevention action limit of 10 g/dL, and PCB levels were consistent with a cumulative, continuing exposure pat- tern. The median age at menarche for the total sample was 12.2 years. The predicted age at menarche for girls with lead levels above the median (1.2 g/dL) was 10.5 months later than that for girls with lead levels below the median. In the logistic regression analysis, age was the strongest predictor of menarcheal status and SES was also a significant predictor but BMI was not. The logistic regression analysis that corrected for age, SES, and other pollutants (p,p-DDE, HCB, mirex, and mercury) indi- cated that, at their respective geometric means, lead (geo- metric mean: 0.49 g/dL) was associated with a signifi- cantly lower probability of having reached menarche ( 1.29) and a group of 4 potentially estrogenic PCB congeners (E-PCB) (geometric mean: 0.12 ppb; Interna- tional Union of Pure and Applied Chemistry numbers 52, 70, 101 (90), and 187) was associated with a significantly greater probability of having reached menarche ( 2.13). Predicted probabilities at different levels of lead and PCBs were calculated on the basis of the logistic regression model. At the respective means of all toxicants and SES, 69% of 12-year-old girls were predicted to have reached menarche. However, at the 75th percentile of lead levels, only 10% of 12-year-old Mohawk girls were predicted to have reached menarche; at the 75th percen- tile of E-PCB levels, 86% of 12-year-old Mohawk girls were predicted to have reached menarche. No association was observed between mirex, p,p-DDE, or HCB and menarcheal status. Although BMI was not a significant predictor, we tested BMI in the logistic regression model; it had little effect on the relationships between menar- cheal status and either lead or E-PCB. In models testing toxicant interactions, age, SES, lead levels, and PCB lev- els continued to be significant predictors of menarcheal status. When each toxicant was tested in a logistic regres- sion model correcting only for age and SES, we observed little change in the effects of lead or E-PCB on menar- cheal status. Conclusions. The analysis of multichemical exposure among Akwesasne Mohawk Nation adolescent girls sug- gests that the attainment of menarche may be sensitive to relatively low levels of lead and certain PCB congeners. This study is distinguished by the ability to test many toxicants simultaneously and thus to exclude effects from unmeasured but coexisting exposures. By testing several