Clewell HJ, Peeples CR, Song G, Yoon M, Wu H, Verner M-A, Andersen ME, Longnecker MP. Evaluating epidemiological associations between high blood concentrations of polybrominated diphenyl ethers (PBDEs) and altered timing of menarche: Are they meaningful? [abstract 740]. Presented at the Society of Toxicology Annual Meeting, San Diego, CA, March 21, 2015.
Reported associations between blood PBDEs and altered time of menarche in the general population has raised concerns for potential health effects of PBDE exposure in early ages. However, individual differences in growth patterns and the resulting body types are often associated with their timing of puberty, which can also affect the chemical disposition substantially. In this study we evaluated the impact of kinetic variability during puberty on the reported epidemiological association of BDE-47, one of the most abundant PBDE congeners, with earlier menarche. A probabilistic PBPK modeling approach was used to simulate a hypothetical population that resembles that of NHANES. The simulated average blood concentrations of BDE-47 and its distribution were comparable to those in NHANES and the simulated population was matched to the study population in terms of growth physiology and markers of pubertal events. Model sensitivity analysis revealed that variability of individual exposure as a function of age and body weight and natural correlations between physiological body type and an individual’s lipid metabolism status are the two most influential factors affecting the strength and direction of blood BDE-47 associations with age at menarche; these two factors were also identified as the major data daps in the current analysis. Our study demonstrates that a Monte Carlo PBPK modeling approach can provide a tool to critically assess the role of pharmacokinetic variation in chemical-health effect associations in epidemiological studies (supported by the ACC-LRI).