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Among these blooms, <jats:italic>Heterosigma akashiwo<\/jats:italic>, a golden\u2010brown phytoflagellate, is one of the 40 species with a high potential to form harmful blooms, leading to significant fish mortality. Climate change leads to rising atmospheric and ocean temperatures. These changes, along with altered rainfall patterns and meltwater input, can cause fluctuations in ocean salinity. Elevated atmospheric carbon dioxide (CO<jats:sub>2<\/jats:sub>) levels increase water acidity as oceans absorb CO<jats:sub>2<\/jats:sub>. This study investigated the effects of temperature, salinity, and CO<jats:sub>2<\/jats:sub> levels on lipid production, hemolytic activity, and toxicity of <jats:italic>H. akashiwo<\/jats:italic> using the design of experiment approach, which can be used to investigate the effect of two or more factors on the same response simultaneously in a precise manner with fewer experiments and materials but in a larger region of the factor space. The lipid content was measured using a high\u2010throughput Nile Red method, and the highest level of lipid content was detected at 25\u00b0C, a salinity of 30, and a CO<jats:sub>2<\/jats:sub> concentration of 400\u2009ppm. Hemolytic activity was assessed using rabbit blood erythrocytes in a 96\u2010well plate, and the optimal conditions for achieving the highest hemolytic activity were determined at 15\u00b0C, a salinity of 10, and a CO<jats:sub>2<\/jats:sub> concentration of 400\u2009ppm. As the chemical structure of the toxin is not known, we used the toxicity against the cell line RTgill\u2010W1 as the cell toxicity proxy. The maximum toxicity was identified at 15\u00b0C, a salinity of 10, and a CO<jats:sub>2<\/jats:sub> level of 700\u2009ppm.<\/jats:p>","DOI":"10.1111\/jpy.13481","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T15:28:36Z","timestamp":1720798116000},"page":"1001-1020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Influence of multi\u2010stressor combinations of <scp><i>p<\/i>CO<sub>2<\/sub><\/scp>, temperature, and salinity on the toxicity of <i>Heterosigma akashiwo<\/i> (Raphidophyceae), a fish\u2010killing flagellate"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6351-9393","authenticated-orcid":false,"given":"Malihe Mehdizadeh","family":"Allaf","sequence":"first","affiliation":[{"name":"Department of Chemical and Biochemical Engineering Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Trick","sequence":"additional","affiliation":[{"name":"Chemical and Biochemical Engineering Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010marine\u2010120308\u2010081121"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hal.2015.04.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-7642-2_9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-7494-0_1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2216\/i0031\u20108884\u201043\u20101\u201026.1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05317"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2008.05.019"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2016.07.119"},{"key":"e_1_2_9_10_1","first-page":"407","volume-title":"Harmful marine algal blooms. 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