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ARS Home » Northeast Area » Wyndmoor, Pennsylvania » Eastern Regional Research Center » Sustainable Biofuels and Co-products Research » Research » Publications at this Location » Publication #396949
Research Project: Chemical Conversion of Biomass into High Value Products

Location: Sustainable Biofuels and Co-products Research

Title: Developmental toxicity and estrogenic activity of antimicrobial phenolic-branched fatty acids using in silico simulations and in vivo and in vitro bioassay

Author
item ZHANG, XINWEN - University Of Delaware
item Lew, Helen
item Wagner, Karen
item Fan, Xuetong
item WU, CHANGQING - University Of Delaware

Submitted to: Frontiers in Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2024
Publication Date: 9/2/2024
Citation: Zhang, X., Lew, H.N., Wagner, K., Fan, X., Wu, C. 2024. Developmental toxicity and estrogenic activity of antimicrobial phenolic-branched fatty acids using in silico simulations and in vivo and in vitro bioassay. Frontiers in Toxicology. 6. https://doi.org/10.3389/ftox.2024.1380485.
DOI: https://doi.org/10.3389/ftox.2024.1380485

Interpretive Summary: Chemicals are frequently encountered on a daily basis, but even naturally occurring substances may negatively impact health or the environment. For example, natural compounds such as essential oils are widely used in food and for non-food purposes and may be acutely toxic above certain concentrations. We have created bioactive lipid-essential oil products from natural compounds, and it is critical to evaluate their toxicity in order to aid in product design and determine safe and appropriate applications for the products. In this study, general guidelines of FDA and NIH toxicology programs were followed to evaluate the potential toxicity of designed products. Results show that the tested compounds were non-mutagenic developmental toxins, but some did show minor side effects in chick embryogenesis studies. This knowledge helps to design safer compounds with minimal negative effects on health and the environment.

Technical Abstract: Phenolic-branched chain fatty acids (phenolic BCFAs) have been synthesized as new bio-based antimicrobials. Little is known about their developmental toxicity and estrogenic activity (EA). This study was initiated to enhance our insights into the potential safety of four phenolic BCFAs (with phenol, thymol, carvacrol or creosote branches). Methyl-branched iso-oleic acid, phenol and creosote were included in the study as controls. An in silico simulation Toxicity Estimation Software Tool (T.E.S.T) predicted that the phenolic BCFAs had much higher toxicities to aquatic organisms than free phenolics did. Curiously, the opposite was predicted for rats, where toxicity of phenolic BCFAs was lower than that of phenolics. The developmental toxicity of four test phenolic BCFAs was assessed using an in vivo chicken embryonic assay. A non-monotonic dose response was observed in creosote or creosote-soy BCFA treatments. Creosote-soy BCFA had much lower mortality rates than that of creosote at the same dosages. TBARs values were significantly increased (p < 0.05) in the carvacrol-soy BCFA treatments. The other three phenolic BCFAs had comparable levels to that of the vehicle control. Additionally, the MCF-7 cell proliferation assay findings revealed that phenol-stearic BCFA showed EA while the phenol treatment had little EA at 10 µM.