In vitro cytotoxicity assessment of a West Virginia chemical spill mixture involving 4-methylcyclohexanemethanol and propylene glycol phenyl ether

Abstract

Thousands of gallons of industrial chemicals, crude 4-methylcyclohexanemethanol (MCHM) and propylene glycol phenyl ether (PPh), leaked from industrial tanks into the Elk River in Charleston, West Virginia, USA, on January 9, 2014. A considerable number of people were reported to exhibit symptoms of chemical exposure and an estimated 300,000 residents were advised not to use or drink tap water. At the time of the spill, the existing toxicological data of the chemicals were limited for a full evaluation of the health risks, resulting in concern among those in the impacted regions. In this preliminary study, we assessed cell viability and plasma membrane degradation following a 24-h exposure to varying concentrations (0-1000 μM) of the two compounds, alone and in combination. Evaluation of different cell lines, HEK-293 (kidney), HepG2 (liver), H9c2 (heart), and GT1-7 (brain), provided insight regarding altered cellular responses in varying organ systems. Single exposure to MCHM or PPh did not affect cell viability, except at doses much higher than the estimated exposure levels. Certain co-exposures significantly reduced metabolic activity and increased plasma membrane degradation in GT1-7, HepG2, and H9c2 cells. These findings highlight the importance of examining co-exposures to fully understand the potential toxic effects.

Supramolecular Luminescent Sensors

“…The first responders in this case relied on the chemical company responsible for the spill to accurately disclose the nature of the contamination and then screened large numbers of samples only for the reported contaminant. When accurate information was not forthcoming until several days after the initial contamination event, residents were inadvertently exposed to additional contaminants, first responders were unable to develop effective remediation strategies, and the development of an effective containment response was delayed . Similar gaps in current state-of-the art detection methods explain why consumers were initially unaware of the presence of bisphenol A (BPA) analogues, including bisphenol S (BPS) and bisphenol F (BPF), in the presence of products labeled “BPA-free,” and were inadvertently exposed to these BPA derivatives .…”

“…When accurate information was not forthcoming until several days after the initial contamination event, residents were inadvertently exposed to additional contaminants, first responders were unable to develop effective remediation strategies, and the development of an effective containment response was delayed. 1845 Similar gaps in current state-of-the art detection methods explain why consumers were initially unaware of the presence of bisphenol A (BPA) analogues, including bisphenol S (BPS) and bisphenol F (BPF), in the presence of products labeled "BPA-free," and were inadvertently exposed to these BPA derivatives. 1846 Detection methods for BPA relied on mass spectral methods; 1847 because the BPA analogues have slightly different molar masses, they remained undetected in the products for an as-yet undetermined amount of time.…”

Effects of MCHM on yeast metabolism

“…Crude MCHM is not a dermal irritant to humans at the concentrations in the water reported after the spill [7]. In the evaluation of different cell lines, HEK-293, HepG2, H9c2, and GT1-7 only the highest dose of MCHM (128 ppm or 1 mM) elicited a statistically significant decrease in cell viability, when compared to the control (1% DMSO) [8]. MCHM induced DNA damage-related biomarkers in human A549 cells, indicating that it is related to genotoxicity [9].…”

The Polymorphic PolyQ Tail Protein of the Mediator Complex, Med15, Regulates the Variable Response to Diverse Stresses

“…It was shown that amino acids [32], inositol [32], zinc [27], and phosphate [27] levels are increased. Since the 2014 MCHM spill, several studies have measured the toxicological effects of MCHM on diverse species but have not addressed the mechanism of toxicity during acute exposure [64][65][66][67][68][69][70][71]. One possible explanation of MCHM's diverse effects is, as a stable hydrotrope, MCHM changes the structure of nutrient sensors so they no longer sense extracellular compounds.…”