US EPA

1510266 

Journal Article 

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

Wise, A; Parham, F; Axelrad, DA; Guyton, KZ; Portier, C; Zeise, L; Zoeller, RT; Woodruff, TJ 

2012 

Yes 

Environmental Research
ISSN: 0013-9351
EISSN: 1096-0953 

ACADEMIC PRESS INC ELSEVIER SCIENCE 

SAN DIEGO 

117 

90-99 

English 

22770859 

10.1016/j.envres.2012.05.013 

WOS:000307912900012 

https://linkinghub.elsevier.com/retrieve/pii/S0013935112001843
Exit
 

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. 

Environmental chemical exposure; Neurodevelopmental outcomes; Polychlorinated biphenyls; Quantitative risk assessment; Thyroid hormone