title: Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls.
abstract: BACKGROUND
  Children are commonly exposed at background levels to several ubiquitous environmental pollutants, such as lead and persistent organic pollutants, that have been linked to neurologic and endocrine 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 environmental pollutants to which children are commonly exposed at low levels, ie, dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), polychlorinated 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 substantial industrial development, and the Nation is currently 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 Akwesasne Mohawk Nation girls 10 to 16.9 years of age. Blood samples and sociodemographic data were collected by Akwesasne community members, without prior knowledge of participants' exposure status. Attainment of menses (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 (International 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, socioeconomic 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 levels were at or below background levels, all lead levels were well below the Centers for Disease Control and Prevention action limit of 10 microg/dL, and PCB levels were consistent with a cumulative, continuing exposure pattern. 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 microg/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) indicated that, at their respective geometric means, lead (geometric mean: 0.49 microg/dL) was associated with a significantly lower probability of having reached menarche (beta = -1.29) and a group of 4 potentially estrogenic PCB congeners (E-PCB) (geometric mean: 0.12 ppb; International Union of Pure and Applied Chemistry numbers 52, 70, 101 [+90], and 187) was associated with a significantly greater probability of having reached menarche (beta = 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 percentile 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 menarcheal status and either lead or E-PCB. In models testing toxicant interactions, age, SES, lead levels, and PCB levels continued to be significant predictors of menarcheal status. When each toxicant was tested in a logistic regression model correcting only for age and SES, we observed little change in the effects of lead or E-PCB on menarcheal status.
  
  
  CONCLUSIONS
  The analysis of multichemical exposure among Akwesasne Mohawk Nation adolescent girls suggests 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 PCB congener groupings, we were able to determine that specifically a group of potentially estrogenic PCB congeners affected the odds of reaching menarche. The lead and PCB findings are consistent with the literature and are biologically plausible. The sample size, cross-sectional study design, and possible occurrence of confounders beyond those tested suggest that results should be interpreted cautiously. Additional investigation to determine whether such low toxicant levels may affect reproduction and disorders of the reproductive system is warranted.
authors.affiliation: University at Albany, State University of New York, Albany, New York 12222, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Denham
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Schell
authors.forename: Glenn
authors.initials: G
authors.lastname: Deane
authors.forename: Mia V
authors.initials: MV
authors.lastname: Gallo
authors.forename: Julia
authors.initials: J
authors.lastname: Ravenscroft
authors.forename: Anthony P
authors.initials: AP
authors.lastname: DeCaprio
mesh_terms: D000293:Adolescent; D002648:Child; D003430:Cross-Sectional Studies; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006581:Hexachlorobenzene / Q000097:blood / Q000494:pharmacology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood / Q000494:pharmacology*; D007198:Indians, North American; D007854:Lead / Q000097:blood / Q000494:pharmacology*; D016015:Logistic Models; D008572:Menarche / Q000187:drug effects*; D008628:Mercury / Q000097:blood / Q000494:pharmacology; D008917:Mirex / Q000097:blood / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000494:pharmacology; D012923:Social Class
chemical_list: D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D007854:Lead; D003633:Dichlorodiphenyl Dichloroethylene; D006581:Hexachlorobenzene; D011078:Polychlorinated Biphenyls; D008628:Mercury; D008917:Mirex