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Dataset for Predicted versus observed activity of PCB mixtures toward the ryanodine receptor
Dataset   Open access

Dataset for Predicted versus observed activity of PCB mixtures toward the ryanodine receptor

Justin A. Griffin, Xueshu Li, Hans-Joachim Lehmler and Erika B. Holland
University of Iowa
08/05/2025
DOI: 10.25820/data.007911
txt
01_ReadMe_PredObs_PCB-RyR18.15 kBDownloadView
READMECC BY V4.0 Open Access
csv
02_Data_dictionary_RyR Binding Assay926.00 byteDownloadView
Data DictionaryCC BY V4.0 Open Access
csv
03_PCB95,149,95+149_BindingAssay7.19 kBDownloadView
CC BY V4.0 Open Access
csv
04_PCB95,52,95+52_BindingAssay7.00 kBDownloadView
CC BY V4.0 Open Access
csv
05_PCB95,126,95+126_BindingAssay4.67 kBDownloadView
CC BY V4.0 Open Access

Abstract

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs, and similar compounds, towards RyR1 activation and related neurotoxicity. \
Ryanodine receptor Polychlorinated biphenyls PCBs Neurotoxicity Neurotoxic equivalents California Addition Model

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