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Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays
Shafer, T., K. Wallace, W. Mundy, AND M. Behl. Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays. Presented at Soceity of Toxicology, Phoenix, AZ, March 23 - 27, 2014.
EFFECTS OF ORGANOPHOSPHORUS FLAME RETARDANTS ON SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS TJ Shafer1, K Wallace1, WR Mundy1, M Behl2,. 1Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, USA, 2National Toxicology Program, NIEHS, RTP, NC, USA. Organophosphorus compounds are increasingly used as alternatives to brominated flame retardants (BFRs) and thus are commonly found in house air and dust. However, there is limited information on their potential health effects. Assessment of spontaneous neural network activity using microelectrode arrays has been shown to be a sensitive method to screen chemicals for potential neuroactivity/toxicity. Therefore, this study compared the effects of nine organophosphorus flame retardants (OPFs) with the BFR tetrabromobisphenol A to determine their ability to alter network function in primary cultures of rat cortical neurons grown on 48 well microelectrode array (MEAs) plates. On day 13 or 14 in vitro, 1 hr of baseline activity was recorded prior to exposure to flame retardants (0.1 to 30 µM). Changes in spontaneous mean firing rate (MFR) relative to the vehicle control were assessed 1hr after exposure. The BFR tetrabromobisphenol A and the OPF tris (2-chloroethyl) phosphate did not alter the spontaneous activity at any concentration tested. The remaining 8 OPFs decreased spontaneous activity in a concentration-dependent manner, with EC50 values ranging from 6.6 to 18.6 µM in the following order: t-butylphenyl diphenyl phosphate ≥ tricresyl phosphate ≥ 2-ethylhexyl diphenyl phosphate ≥ isopropylated phenyl phosphate ≥ isodecyl diphenyl phosphate ≥ ortho-tricresyl phosphate ≥ triphenyl phosphate ≥ tris (1,3-dichloroisopropyl) phosphate. None of the flame retardants decreased the viability of cortical cells at any concentration tested. This data indicates that some OPFs have the ability to alter the spontaneous activity in neuronal networks in vitro at micromolar concentrations. This abstract does not necessarily reflect U.S. EPA policy.
Abstract will be presented at the Society of Toxicology Meeting, March 23-27, 2014, Phoenix, AZ.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
SYSTEMS BIOLOGY BRANCH