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While TIS holds promise for a variety of clinical and nonclinical applications, little data is yet available regarding its effects in humans and its mechanisms of action. To inform the design and safe conduct of experiments involving TIS, researchers require quantitative guidance regarding safe exposure limits and other safety considerations. To this end, we undertook a two\u2010part effort to determine frequency\u2010dependent thresholds for applied currents below which TIS is unlikely to pose risk to humans in terms of heating or unwanted stimulation. In Part II of this effort, described here, we draw on a previously compiled list (see Part I) of adverse effects (AEs) reported for transcranial direct\/alternating current stimulation (tDCS\/ACS), deep brain stimulation (DBS), and TIS to determine biophysics\u2010informed exposure metrics for assessing safety. Using an in silico approach, we conduct multiphysics simulations of various tACS, DBS, and TIS exposure scenarios in an anatomically detailed head and brain model. By matching the stimulation in terms of the identified exposure metrics, we infer frequency\u2010dependent TIS parameters that produce exposure conditions equivalent to those known to be safe for tACS and DBS. Based on the results of our simulations and existing knowledge regarding tES and DBS safety, we propose frequency\u2010dependent thresholds below which TIS voltages and currents are unlikely to pose a risk to humans. Safety\u2010related data from ongoing and future human studies are required to verify and refine the thresholds proposed here.<\/jats:p>","DOI":"10.1002\/bem.22536","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T03:40:51Z","timestamp":1736912451000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Recommendations for the Safe Application of Temporal Interference Stimulation in the Human Brain Part II: Biophysics, Dosimetry, and Safety Recommendations"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-7440","authenticated-orcid":false,"given":"Antonino M.","family":"Cassar\u00e0","sequence":"first","affiliation":[{"name":"Foundation for Research on Information Technologies in Society Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-8702","authenticated-orcid":false,"given":"Taylor H.","family":"Newton","sequence":"additional","affiliation":[{"name":"Foundation for Research on Information Technologies in Society Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Foundation for Research on Information Technologies in Society Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine J.","family":"Regel","sequence":"additional","affiliation":[{"name":"TI Solutions AG Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Achermann","sequence":"additional","affiliation":[{"name":"Foundation for Research on Information Technologies in Society Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Pascual\u2010Leone","sequence":"additional","affiliation":[{"name":"TI Solutions AG Zurich Switzerland"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts USA"},{"name":"Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Kuster","sequence":"additional","affiliation":[{"name":"Foundation for Research on Information Technologies in Society Zurich Switzerland"},{"name":"TI Solutions AG Zurich Switzerland"},{"name":"Department of Information Technology and Electrical Engineering ETH Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Neufeld","sequence":"additional","affiliation":[{"name":"Foundation for Research on Information Technologies in Society Zurich Switzerland"},{"name":"TI Solutions AG Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2017.06.001"},{"key":"e_1_2_10_3_1","article-title":"Evaluation of Human Exposure to Low Frequency Fields","volume":"138","author":"Bernhardt J.","year":"1985","journal-title":"AGARD Lecture Series"},{"key":"e_1_2_10_4_1","first-page":"157","volume-title":"Biological Effects of Static and Extremely Low Frequency Magnetic Fields","author":"Bernhardt J.H.","year":"1986"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2560\/3\/1\/001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.23.051870"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurom.2023.04.139"},{"key":"e_1_2_10_8_1","unstructured":"Center for Devices and Radiological Health.2019.MIDA\u2014A Multimodal Imaging\u2010Based Model of the Human Head and Neck. 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