A decay model to assess paternal levels of polybrominated biphenyls among men in the Michigan long-term PBB study at the time of their sons' conception. Público

Abstract

The continual use of synthetic chemicals with hormonal or anti-hormonal properties in consumer products has raised concerns for human health in the scientific community. The Michigan Long-Term PBB Study was established in 1976, after more than 4,000 Michigan residents consumed polybrominated biphenyl (PBB)-contaminated farm products in the early 1970s. Between 1976 and 1993, serum samples were collected from cohort members and analyzed for PBB. Measurable levels of PBB were detectable even 20 years after the industrial incident. The creation of this cohort provides an unprecedented opportunity to study the elimination and long-term effects of PBBs and their congeners. This study investigates the effect of covariates on the rates of serum PBB decay among 904 male participants. A general linear mixed model approach was used to develop the decay model which was ultimately used to estimate in utero PBB levels of offspring born to father's in the study. Time-independent covariates retained in the decay model were BMI at enrollment and having had a weight change of greater than 10lbs from 1973 (exposure) to enrollment. Time since exposure, an interaction variable between BMI and time and a time-squared (Time²) variable were the time-dependent covariates retained in the decay model. Higher initial BMI was associated with a slower rate of decay; having had a weight change of greater than 10lbs since 1973 (exposure) to enrollment was associated with a faster rate of decay compared to those who did not have this fluctuation in weight since exposure. The predictive performance of the decay model was evaluated by comparing results derived from this decay model to observed participant serum PBB levels collected in 1991-1993. There was a strong association between the predicted and observed log(PBB) levels (Spearman Correlation Coefficient, ρs = 0.80). Serum PBB concentration levels were predicted for 134 offspring at the time of their conception. The median estimated in utero PBB concentration level was predicted to be 6.7 ppb and ranged from 1.0 ppb to 1535.5ppb.

Table of Contents

Table of Contents

I. Introduction 1

II. Methods 6

Study Population 6

Serum PBB Samples 6

Data Description 8

Statistical Analysis 10

Building the Decay Model 11

Validating the Decay Model 12

Prediction of Offspring's Paternal in utero PBB exposure 13

III. Results 14

IV. Discussion 18

V. Conclusion 22

VI. References 23

VII. Tables 27

VIII. Figures 32

List of Tables

Table

1. Demographic characteristics of men included in the mixed-effects decay model

2. Results of the mixed effects decay model for males in the Michigan Long-Term PBB Study using measurements between 1974 and 1993

3. Results of the mixed effects decay model that includes a time-dependent BMI variable

4. Results of the mixed effects decay model that includes an interaction variable between time and having lost at least 10% of body weight since enrollment to follow-up

5. Results of the validation of the mixed effects decay model

6. Summary of Validation study: Comparison of observed and predicted serum PBB

List of Figures

Figure

1. Flow chart of inclusion criteria for male participants included in the mixed-effects decay model.

2. Individual profile for male participants included in the mixed-effects decay model

3. Results of the mixed effects decay model that includes a time-dependent BMI variable

4. Observed and predicted serum PBB concentrations levels between 1991 and 1993 for male participants of the Michigan Long-Term PBB Study.

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Biology, Biostatistics Chemistry, General
Palavra-chave	polybrominated biphenyl
Committee Chair / Thesis Advisor	Marcus, Michele, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

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