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Due to their reported variable composition of components, they might be acutely toxic to humans and animals in small amounts. Despite the necessity, rigorous toxicity testing in terms of safety evaluation has not been reported so far, especially using alternatives to animal models. Here, we provide a strategy by use of alternative in vitro (cell cultures) and in vivo (\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , hen\u2019s egg test) approaches for detailed investigation of the impact of commonly used rosemary, citrus and eucalyptus essential oil on acute, developmental and reproductive toxicity as well as on mucous membrane irritation. In general, all EOs under study exhibited a comparable impact on measured parameters, with a slightly increased toxic potential of rosemary oil. In vitro cell culture results indicated a concentration-dependent decrease of cell viability for all EOs, with mean IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 0.08 to 0.17% [v\/v]. Similar results were obtained for the\n                    <jats:italic>C. elegans<\/jats:italic>\n                    model when using a sensitized\n                    <jats:italic>bus-5<\/jats:italic>\n                    mutant strain, with a mean LC\n                    <jats:sub>50<\/jats:sub>\n                    value of 0.42% [v\/v]. In wild-type nematodes, approximately tenfold higher LC\n                    <jats:sub>50<\/jats:sub>\n                    values were detected.\n                    <jats:italic>C. elegans<\/jats:italic>\n                    development and reproduction was already significantly inhibited at concentrations of 0.5% (wild-type) and 0.1%\n                    <jats:italic>(bus-5)<\/jats:italic>\n                    [v\/v] of EO, respectively. Gene expression analysis revealed a significant upregulation of xenobiotic and oxidative stress genes such as\n                    <jats:italic>cyp-14a3<\/jats:italic>\n                    ,\n                    <jats:italic>gst-4<\/jats:italic>\n                    ,\n                    <jats:italic>gpx-6<\/jats:italic>\n                    and\n                    <jats:italic>sod-3<\/jats:italic>\n                    . Furthermore, all three EOs under study showed an increased short-time mucous membrane irritation potential, already at 0.5% [v\/v] of EO. Finally, GC\u2013MS analysis was performed to quantitate the relative concentration of the most prominent EO compounds. In conclusion, our results demonstrate that EOs can exhibit severe toxic properties, already at low concentrations. Therefore, a detailed toxicological assessment is highly recommended for each EO and single intended application.\n                  <\/jats:p>","DOI":"10.1007\/s00204-020-02945-6","type":"journal-article","created":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T10:02:44Z","timestamp":1604743364000},"page":"673-691","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Acute, reproductive, and developmental toxicity of essential oils assessed with alternative in vitro and in vivo systems"],"prefix":"10.1007","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-7964","authenticated-orcid":false,"given":"Peter","family":"Lanzerstorfer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Sandner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Pitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Mascher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Aumiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Weghuber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,7]]},"reference":[{"key":"2945_CR1","doi-asserted-by":"publisher","unstructured":"Abbas S, Wink M (2010) Epigallocatechin gallate inhibits beta amyloid oligomerization in Caenorhabditis elegans and affects the daf-2\/insulin-like signaling pathway Phytomedicine 17:902\u2013909 doi:https:\/\/doi.org\/10.1016\/j.phymed.2010.03.008","DOI":"10.1016\/j.phymed.2010.03.008"},{"key":"2945_CR2","doi-asserted-by":"publisher","unstructured":"Akhoon BA, Pandey S, Tiwari S, Pandey R (2016) Withanolide A offers neuroprotection, ameliorates stress resistance and prolongs the life expectancy of Caenorhabditis elegans Exp Gerontol 78:47\u201356 doi:https:\/\/doi.org\/10.1016\/j.exger.2016.03.004","DOI":"10.1016\/j.exger.2016.03.004"},{"key":"2945_CR3","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.apjtb.2015.05.007","volume":"5","author":"B Ali","year":"2015","unstructured":"Ali B, Al-Wabel NA, Shams S, Ahamad A, Khan SA, Anwar F (2015) Essential oils used in aromatherapy: A systemic review. 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