You are here:
EFFECT OF ORGANOPHOSPHORUS FLAME RETARDANTS ON NEURONAL DEVELOPMENT IN VITRO
Citation:
Mundy, W., T. Freudenrich, K. Wallace, AND M. Behl. EFFECT OF ORGANOPHOSPHORUS FLAME RETARDANTS ON NEURONAL DEVELOPMENT IN VITRO. Presented at Society of Toxicology, March 10 - 14, 2013.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX
Description:
The increased use of organophosphorus compounds as alternatives to brominated flame retardants (BFRs) has led to widespread human exposure, There is, however, limited information on their potential health effects. This study compared the effects of nii ne organophosphorus flame retardants (OPFs) with the BFR tetrabromobisphenol A and the known developmental neurotoxicants Pb and t-retinoic acid on neuronal proliferation and neurite outgrowth in vitro. Proliferation was assessed in human stem cell-derived neuroprogenitor (hNPl) cells after a 24 hr exposure by counting the number of cells incorporating BrdU. Neurite outgrowth was assessed in human stem cell-derived (hN2) neurons and rat primary cortical neurons after 48 hr of exposure by measuring the length and branching of neurites labeled with III-tubulin antibody. Cytotoxicity was estimated by total cell counts. Cells were cultured and exposed to chemicals (0.003 to 30 uM) in 96-well plates and endpoints quantified using the Cellomics ArrayScan high content imager. In hNPl cells, Pb, t-retinoic acid, tetrabromobisphenol A and a majority of the OPFs were cytotoxic at concentrations > 3 uM; however, tricresyl phosphate and triphenyl phosphate both decreased proliferation at 30 uM in the absence of cytotoxicity. In hN2 cells OPFs, tetrabromobisphenol A and t-retinoic acid decreased neurite outgrowth only at cytotoxic concentrations, while Pb decreased neurite outgrowth in the absence of cytotoxicity. Rat neurons were less sensitive than hN2 cells in that no chemical was cytotoxic at the concentrations tested; however, tricresyl phosphate, t-butylphenyl diphenyl phosphate, isodecyl diphenyl phosphate, and isopropylated phenyl phosphate decreased neurite outgrowth at 30 uM. These data suggest that some OPFs have the ability to affect neurodevelopmental processes in vitro at micromolar concentrations, and that human neurons may be more sensitive compared to rats. This abstract does not necessarily reflect US. EPA policy.