A recent chemical spill of 4-Methylcyclohexanemethanol (4-MCHM) in West Virginia left 300,000 people without water. Officials claimed that this compound is not lethally toxic, but potentially harmful if swallowed or inhaled, and can cause eye and skin irritation. Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens reports high exposures from skin contact or inhalation may cause damage to the heart, liver, kidneys, and lungs, and may result in death. However, no quantitative data seem to exist and no references can be found on neurotoxicity. We have investigated the neurotoxicity of 4-MCHM using mammalian nerve cell networks grown on microelectrode arrays. Network spontaneous activity from multiple units (range 48 – 120 per network) were used as the primary readout. Individual units were followed based on spike waveforms digitized at 40 kHz (Plexon MNAP system). Dose response curves show the effective inhibitory concentration at 50 percent decrease (EC50) to average 27.4 microM SD±6.17. However, in the presence of 40 microM bicuculline, a competitive GABAA antagonist, the EC50 shifts to 70.63uM SD ±4.3; implying that early, low concentration exposures to 4-MCHM involve GABA activation. Initial activity loss occurs without active unit loss (defined as 10 or more template threshold crossing per min), indicating functional interference with spike production. Full recovery has not been seen at concentrations above 130 microM, unless the culture was given bicuculline. Direct exposure to 400uM results in immediate, irreversible loss of spike production, followed by necrosis of glia and neurons.
| Identifer | oai:union.ndltd.org:unt.edu/info:ark/67531/metadc799542 |
| Date | 05 1900 |
| Creators | Gibson, Jason (Jason Robert) |
| Contributors | Gross, Guenter W., Gopal, Kamakshi V., Huggett, Duane B. |
| Publisher | University of North Texas |
| Source Sets | University of North Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Format | iv, 46 pages : illustrations (some color), Text |
| Rights | Public, Gibson, Jason (Jason Robert), Copyright, Copyright is held by the author, unless otherwise noted. All rights reserved. |
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