Pharmacokinetic Variability and Modern Epidemiology—The Example of Dichlorodiphenyltrichloroethane, Body Mass Index, and Birth Cohort

We investigated cross-sectional associations of body composition and weight change with polychlorinated biphenyls (PCB) and organochlorine pesticides/pesticide metabolites measured in blood collected at the baseline of the Physical Activity for Total Health study of postmenopausal, overweight women living in the Seattle, Washington metropolitan area. Indicators of greater adiposity were associated with lower plasma concentrations of most PCBs with six or more chlorine atoms. This pattern was observed for current weight, body mass index, fat mass percent, subcutaneous abdominal fat, intra-abdominal fat, waist circumference, hip circumference, waist-to-hip ratio, and maximum adult weight. Conversely, PCB 105, PCB 118, and p,p 0 -DDE were generally increased or showed no association with these variables. Weight gain since age 35 was associated with lower concentrations of almost every organochlorine we studied, and past weight loss episodes of at least 20 pounds (Z9.1 kg) were associated with higher concentrations. Our results have implications for epidemiologic studies of organochlorines in terms of covariates that may be important to consider in statistical analyses, particularly as such considerations may differ importantly by specific analyte. Our finding of increased organochlorine concentrations with past weight loss episodes may have public health significance; however, this association requires confirmation in longitudinal studies.

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Adiposity, body composition, and weight change in relation to organochlorine pollutant plasma concentrations

Roos

Ulrich

Sjödin

et al. 2012

“…Although gender differences have been reported for some of the chemicals evaluated in the present study, we did not find any major differences between men and women regarding the co-variation of the environmental pollutants evaluated in the present study (data not shown). With levels of contaminants in human tissue over time being possibly influenced by BMI, under the assumption of a similar total body uptake, 25 clustering patterns could also differ depending on BMI.…”

Section: Metalsmentioning

confidence: 99%

An investigation of the co-variation in circulating levels of a large number of environmental contaminants

Lampa

Lind

Bornefalk-Hermansson

et al. 2012

We are daily exposed to many different environmental contaminants. Mixtures of these contaminants could act together to induce more pronounced effects than the sum of the individual contaminants. To evaluate the effects of such mixtures, it is of importance to assess the co-variance amongst the contaminants. Thirty-seven environmental contaminants representing different classes were measured in blood samples from 1016 individuals aged 70 years. Hierarchical cluster analysis and principal component analysis were used to assess the co-variation among the contaminants. Within each identified cluster, possible marker contaminants were sought for. We validated our findings using data from the National Health and Nutrition Examination Survey (NHANES) 2003--2004 study. Two large clusters could be identified, one representing low/medium chlorinated polychlorinated biphenyls (PCBs) (r6 chlorine atoms), as well as two pesticides and one representing medium/high chlorinated PCBs (Z6 chlorine atoms). PCBs 118 and 153 could be used as markers for the low/medium chlorinated cluster and PCBs 170 and 209 could be used as markers for the medium/high chlorinated cluster. This pattern was similar to data from the NHANES study. Apart from the PCBs, little co-variation was seen among the contaminants. Thus, a large number of chemicals have to be measured to adequately identify mixtures of environmental contaminants.

“…The findings of other studies, with regard to BMI are, however, mixed with some investigators reporting positive correlations Fitzgerald et al, 2007a), whereas others have found either inverse associations (Wolff et al, 2000) or none . For a review, the issues surrounding associations with BMI, see Wolff et al (2005Wolff et al ( , 2007.…”

mentioning

confidence: 99%

Estimating the half-lives of PCB congeners in former capacitor workers measured over a 28-year interval

Seegal

Fitzgerald

Hills

et al. 2010

To date, most estimates of the half-life of polychlorinated biphenyls (PCBs) in humans have been based on relatively short follow-up periods. To address this issue, we determined the half-lives of PCB congeners of occupational origin in the serum of former capacitor workers as part of a study conducted in [2003][2004][2005][2006] F approximately 28 years after their last occupational exposure. A total of 241 persons from a source population of 6798 former capacitor workers were interviewed and asked to donate a blood sample for serum PCB congener analysis. A subgroup of 45 participants also had serum archived from 1976 and reanalyzed for the same 27 PCB congeners by the same laboratory. Our estimates of the half-lives of the congeners among these 45 persons were longer than those reported by Wolff et al. (1992), due primarily to the much longer interval between exposure and determination of serum PCB concentrations. Half-lives were significantly greater for the heavy versus light occupational congeners, for women versus men and for those with low versus high initial exposure. Current serum total PCB concentrations, expressed as the geometric mean of wet weight data, averaged 6.7 ng/g for the entire 241-person cohort, which represents a 10-fold decrease from values reported in the late 1970s, but is still nearly twice the average for persons of similar age residing in the same area, but without occupational exposure. In addition, current serum PCB concentrations remained significantly and positively associated with earlier occupational exposure, but were not associated with fresh water fish consumption. In general, the results support a consistent and long-duration trend of increased PCB body burden in this cohort of former capacitor workers compared with non-occupationally exposed individuals. The results may aid in further understanding the toxicological/epidemiological consequences of exposure to PCBs in humans.