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  <front>
    <journal-meta>
      <journal-id journal-id-type="iso-abbrev">Pharmacophore</journal-id>
      <journal-id journal-id-type="publisher-id">pharmacophorejournal.com</journal-id>
      <journal-id journal-id-type="publisher-id">Pharmacophore</journal-id>
      <journal-title-group>
        <journal-title>Pharmacophore</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2229-5402</issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">pharmacophorejournal.com-6998</article-id>
      <article-id pub-id-type="doi">10.51847/94Dy3t5G9p</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>From Toxicity Scores to Defensible Safety Judgments: A Conceptual Framework for Integrating Exposure, Biological Mechanisms, Species Differences, and Uncertainty in Artificial Intelligence–Supported Toxicology</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Silva</surname>
                <given-names>Ana</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Al-Farsi</surname>
                <given-names>Mohamed</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Moretti</surname>
                <given-names>Luca</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Okafor</surname>
                <given-names>Grace</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Computational Toxicology and AI-Based Safety Assessment, University of Lisbon, Lisbon, Portugal.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Toxicological Sciences and Risk Assessment, Sultan Qaboos University, Muscat, Oman.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Pharmaceutical Toxicology and Mechanistic Safety, University of Milan, Milan, Italy.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Regulatory Toxicology and Safety Evaluation, University of Ibadan, Ibadan, Nigeria.
          </aff>
                          <author-notes>
            <corresp id="cor1">
              <bold>Address for correspondence:</bold> Prof. Wael Abu Dayyih, Department of
              Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak 61710, Jordan.
                              E-mail: <email xlink:href="ana.silva@ulisboa.pt">ana.silva@ulisboa.pt</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>10</month>
        <year>2026</year>
      </pub-date>
      <volume>17</volume>
      <issue>5</issue>
      <fpage>151</fpage>
      <lpage>158</lpage>
      <permissions>
        <copyright-statement>
          Copyright: &#x000a9; 2026 Pharmacophore
        </copyright-statement>
        <copyright-year>2026</copyright-year>
        <license>
          <ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/"
            specific-use="textmining" content-type="ccbyncsalicense">
            https://creativecommons.org/licenses/by-nc-sa/4.0/</ali:license_ref>
          <license-p>This is an open access journal, and articles are distributed under the terms of
            the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
            others to remix, tweak, and build upon the work non-commercially, as long as appropriate
            credit is given and the new creations are licensed under the identical terms.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>A<sc>BSTRACT</sc></title>
        <p>Artificial intelligence is increasingly used to predict toxicological endpoints, prioritize chemicals, integrate high-dimensional biological data, and support alternatives to conventional testing. Yet a toxicity score is not itself a safety judgment. A predictive output usually characterizes the probability, class, or magnitude of a hazard-related endpoint under a particular model and data domain, whereas safety assessment requires an inference about biological significance under specified exposure conditions, mechanistic plausibility, species relevance, population variability, uncertainty, and decision context. This article develops a conceptual account of how those evidentiary dimensions should be combined without converting predictive performance into unwarranted claims of safety or harm. The analysis distinguishes hazard prediction from exposure-conditioned interpretation, examines how mechanistic evidence and cross-species biology can strengthen or weaken transfer, and treats uncertainty as a structured property of the evidence rather than a residual confidence score. The resulting approach positions AI output as one evidentiary input within an iterative safety judgment in which concordant evidence may increase confidence, discordant evidence may redirect interpretation, and unresolved limitations may block downstream inference. The central implication is that defensible AI-supported toxicology depends less on whether a model produces an accurate toxicity score in isolation than on whether the complete evidentiary configuration justifies the decision being made.</p>
      </abstract>
      <kwd-group>
                <kwd>Artificial intelligence</kwd>
                <kwd>Toxicology</kwd>
                <kwd>Safety assessment</kwd>
                <kwd>Exposure</kwd>
                <kwd>Species differences</kwd>
                <kwd>Uncertainty</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>
