text: Discussion
  Among adolescent boys in Chapaevsk, Russia, higher serum levels of sum of dioxin-like compounds and sum of dioxin TEQs were positively associated with increased age, consumption of fish, local meats other than chicken, and inversely with weeks of gestation. The age association was found despite a narrow age range of slightly over two years in our study. Although not statistically significant, the distance the boy lived from the Khimprom factory at the time of blood draw was inversely associated with serum levels of sum of dioxin-like compounds and sum of dioxin TEQs. As expected, serum PCBs, specifically PCB 118, were strongly associated with both sum of dioxin-like compounds and sum of dioxin TEQs.
  There was no association between the distance of the residence from the Khimprom plant during the pregnancy and subsequent serum dioxin levels. One potential explanation for the lack of association may include misclassification of distance since the mother was asked to recall a time period more than 14 years prior to the study. However, we would expect that the mother would be able to recall residential history at the time of the birth of their son. Mother's self-reported estimates of current residential distance from Khimprom was generally accurate; twenty-one of twenty-nine mothers correctly categorized their current residential distance from the Khimprom plants based on cross-referencing using GIS mapping. Other explanations include that prenatal exposure 14 or more years prior to the current serum sample is not as strong a predictor as are exposures resulting from present residential location. Although there was no association of case status (cryptorchidism or hypospadias) with dioxin levels, we did not have sufficient power to definitively assess this relationship.
  Perinatal history (e.g. weeks of breastfeeding) was generally not associated with exposure measures in this population; this may be a function of older age of the children. However, there are limited data on the relationship of perinatal factors with organochlorine exposures in this age group so a null finding is of interest given reports that differences in organochlorine levels among breastfed and non-breastfed are generally no longer discernable by early school age [24,25] and, furthermore, that dietary intake after this age contributes significantly to total dioxin intake [26]. In prior studies, substantial emphasis has been placed on pre- and early postnatal (via breastfeeding) exposures because of particular vulnerability during fetal and early infant development. The exposure risk factors during peri-adolescence, another period of potential developmental vulnerability, has not been studied in-detail, therefore, the identification of exposure risk factors specific to this period will enhance our understanding of this critical period.
  Although data on levels of PCDD/PCDFs in children is limited, our results suggest that the mean total TEQs among Chapaevsk adolescents were higher than most values previously reported in non-occupationally exposed populations of comparable or even older ages. Figure 2 shows a comparison of the mean PCDD/PCDFs TEQ levels in Chapaevsk boys with other populations (TEQ from dioxin-like PCBs was not included, since some of these studies did not report them). The mean TEQs of pooled blood samples from 10 year-old German boys in rural and urban settings was 8.2 pg TEQ/g lipid for an urban industrial area, 9.0 pg TEQ/g lipid for an industrial area within a rural setting, and 10.1 pg TEQ/g lipid for a rural area [27]. In comparison, the mean TEQ in the Chapevsk boys was 19.3 pg TEQ/g lipid. With the exception of children described by Wuthe et al. [27], subjects in the other studies in Figure 2 were significantly older than the Chapaevsk boys. Despite age differences, the mean TEQ in Chapaevsk boys was comparable to or even higher than the mean TEQ in older populations from other countries. For example, they were higher than mean TEQs of 18.4 pg TEQ/g lipid in adults (40.6 years old average) from South Germany [27] or 16.4 pg TEQ/g lipid from 20 year old Japanese women [28] or pooled samples from randomly selected males and females 18-69 years of age from the Spanish city of Mataro [29], which were 12.5 and 14.7 pg TEQ/g lipid respectively. The mean levels in adult female (mean age 41 years) non-factory workers in the Russian city of Shelekhovo were also lower at 14.5 pg TEQ/g lipid [30]. Mean TEQs for the general population (mean age 44.2 years) in Germany, collected in 1997-98 [31], and median TEQs for long-term workers of pulp and paper mill and non-workers in the U.S. in 1996 [32] were similar to levels found in the Chapaevsk boys. The mean levels in the study in Germany were 20.71 pg TEQ/g lipid and in the U.S. the median levels were 19.1 pg TEQ/g lipid for community residents and 21.2 pg TEQ/g lipid for low exposure workers.
  Figure 2
  Mean PCDD/PCDFs TEQ levels in Chapaevsk boys in comparison with other populations.
  Although TCDD was largely below the detection limits in this small pilot sample, the two boys with detectable values had high TCDD levels (17.9 and 21.7 pg/g lipid), suggesting that exposure for at least some portion of this population is substantially higher than typical of this age group. In comparison, in a cohort of adult (mean age of 58 years) fishermen from a polluted region of Finland, the mean TCDD concentration was 19 pg/g lipid [33]. In adult (mean age of 53 years) residents from Calcasieu Parish, Louisiana, which is near a chemical industrial complex, the mean TCDD level was 7.6 pg/g lipid [34]. Not only were the dioxin levels in these two children higher than those found in these studies, but the adults in the previous studies were several decades older and therefore would be expected to have higher dioxin body burdens than younger children [35]. Potential explanations for the large number of non-detectable samples for TCDD include the small sample volume and young age of the subjects. In our future studies in this population, we will collect larger volumes of serum for dioxin analysis.
  In one of the few studies on dioxin-like compounds in which children were included, Eskenazi and coworkers [36] evaluated the relationship between serum TCDD concentrations and age at exposure of female residents of Seveso, Italy. Residents near the ICMESA chemical plant in Seveso were exposed to some of the highest known residential levels of 2,3,7,8-TCDD as a result of an explosion at the plant. Archived serum collected near the time of the accident was used to measure exposures. Residents closest to the plant had a median 2,3,7,8-TCDD level of 272 ppt (IQR 92 - 883 ppt). Residential proximity to the plant and younger age (up to 13 years old) were the strongest predictors of an individual's serum 2,3,7,8-TCDD level. Other predictors included being outdoors at the time of explosion and consumption of homegrown food. The higher levels found in children were most likely a result of increased exposure as a result of activity patterns and a greater proportionate consumption of food, water and air than adults [37].
  Although the exposure scenario (an acute high exposure event) is different than the chronic low/moderate exposure occurring in Chapaevsk, the results from Seveso suggest that children may be at increased risk for high dioxin exposure from environmental contamination. In our study, although distance from the Khimprom plants was a weak predictor of serum dioxin-like compounds, consumption of local foods (specifically meat and fish), as in the Seveso study, was a strong predictor of sum of dioxin-like compounds and dioxin TEQs. This finding is notable given concerns regarding environmental dioxin contamination in the community and suggests that food may be one of the more, if not most, important routes of environmental contaminant exposure for residents in this setting. In other settings, contaminated food generally contributes much more substantially to human organochlorine burden than air or soil (which may be related to residential proximity to pollutant sources) [6]. We will investigate this issue in more detail in our ongoing study.
  
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