Development of a pooled-sample framework for a large-scale human biomonitoring program using urinary phthalate data from NHANES 公开

Wang, Wen-Li (Spring 2023)

Permanent URL: https://etd.library.emory.edu/concern/etds/bk128c25d?locale=zh
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Abstract

Background: Biomonitoring is an approach to assess human exposure to a chemical via its metabolite or reaction product in human tissues. To assess chemical exposure among a specific population, biological samples must be strategically taken from a sufficient number of subjects. However, not all studies can afford to measure levels of compounds in hundreds or thousands of subjects. Additionally, some samples may be below the limit of detection (LOD) due to extremely low exposure levels or insufficient quantity of biological samples. The pooled sample approach may be useful to address both problems above. However, one of the key considerations is the ambiguous pooled samples formulation strategy. The goal of this study is to investigate an optimal pooled sample framework that could be used for a large-scale human biomonitoring program aiming to assess exposure to phthalates.

Methods: We developed algorithms to address our pooled sample designs to achieve two aims: 1) recommend the number of samples per pool needed to obtain a grand mean phthalate metabolite concentration that is comparable to the average concentration of individual samples in the pools. 2) recommend a minimum sample size that can produce consistent grand mean concentrations of each phthalate metabolite.

Results: There was no significant differences in arithmetic mean (AM) concentrations between individual and pooled samples for all phthalate metabolites in each pool type. Majority of the pooled phthalate metabolites have no significant differences in the AMs across different pool types. The AMs, SDs, and corresponding CVs for all pooled phthalate metabolite concentrations are similar across sample sizes regardless of the pool type.

Conclusions: Our study suggests that using pooled urinary phthalate metabolite samples is a feasible approach for large-scale human biomonitoring to obtain the AM concentrations of individual urinary phthalates, regardless of the number of samples per pool. Taking into account the cost and time constraints, we recommend a minimum sample size of approximately 1500 to produce consistent AM and GM concentrations for MCPP, MEP, MiBP, and MEHP. For MBzP and MBP, a minimum sample size of approximately 1000 is recommended to produce consistent AM and GM concentrations.

Table of Contents

1. Background and significance ................................................................................................... 1

1.1. Phthalates ............................................................................................................................. 1

1.2. Biomonitoring ...................................................................................................................... 1

1.3. Pooled sample approach ...................................................................................................... 2

1.4. Pooled sample framework ................................................................................................... 4

2. Methods...................................................................................................................................... 4

2.1. Target analytes ..................................................................................................................... 4

2.2. Pooled sample designs ......................................................................................................... 5

2.3. Statistical analysis ................................................................................................................ 7

3. Results ........................................................................................................................................ 8

3.1. Individual phthalate metabolites .......................................................................................... 8

3.2. Pooled phthalate metabolites ............................................................................................. 10

4. Discussions ............................................................................................................................... 30

4.1. Individual phthalate metabolites ........................................................................................ 30

4.2. Pooled sample design 1...................................................................................................... 30

4.3. Pooled sample design 2...................................................................................................... 31

4.4. Limitations and Strengths .................................................................................................. 32

4.5 Future study recommendations ........................................................................................... 32

5. Conclusions.............................................................................................................................. 33

6. References ................................................................................................................................ 34

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