Upstream adverse effects in risk assessment: A model of polychlorinated biphenyls, thyroid hormone disruption and neurological outcomes in humans

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• 作者：Amber Wise ; Fred Parham ; Daniel A. Axelrad ; Kathryn Z. Guyton ; Christopher Portier ; Lauren Zeise ; R. Thomas Zoeller ; Tracey J. Woodruff
• 关键词：CI ; confidence interval ; FT4 ; free thyroxine ; g lipid/L ; grams of lipid per liter ; IQ ; intelligence quotient ; ln ; natural log ; ng/dL ; nanograms per deciliter ; OH-PCB ; hydroxylated polychlorinated biphenyl ; PBDEs ; polybrominated diphenyl ethers ; PCBs ; poly
• 刊名：Environmental Research
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：117
• 期：Complete
• 页码：90-99
• 全文大小：286 K

文摘

Background

Increasing data on early biological changes from chemical exposures requires new interpretation tools to support decision-making.

Objectives

To test the possibility of applying a quantitative approach using human data linking chemical exposures and upstream biological perturbations to overt downstream outcomes.

Methods

Using polychlorinated biphenyl (PCB) exposures and maternal thyroid hormone (TH) perturbations as a case study, we model three relationships: (1) prenatal PCB exposures and TH changes, using free T₄ (FT₄); (2) prenatal TH and childhood neurodevelopmental outcomes; and (3) prenatal PCB exposures and childhood neurodevelopmental outcomes (IQ). We surveyed the epidemiological literature; extracted relevant quantitative data; and developed models for each relationship, applying meta-analysis where appropriate.

Results

For relationship 1, a meta-analysis of 3 studies gives a coefficient of ?0.27 pg/mL FT₄ per ln(sum of PCBs) (95 % confidence interval [CI] ?0.82 to 0.27). For relationship 2, regression coefficients from three studies of maternal FT₄ levels and cognitive scores ranged between 0.99 IQ points/(pg/mL FT₄) (95 % CI ?0.31 to 2.2) and 7.6 points/(pg/mL FT₄) (95 % CI 1.2 to 16.3). For relationship 3, a meta-analysis of five studies produces a coefficient of ?1.98 IQ points (95 % CI ?4.46 to 0.50) per unit increase in ln(sum of PCBs). Combining relationships 1 and 2 yields an estimate of ?2.0 to ?0.27 points of IQ per unit increase in ln(sum of PCBs).

Conclusions

Combining analysis of chemical exposures and early biological perturbations (PCBs and FT₄) with analysis of early biological perturbations and downstream overt effects (FT₄ and IQ) yields estimates within the range of studies of exposures and overt effects (PCBs and IQ). This is an example approach using upstream biological perturbations for effect prediction.