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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Public Health</journal-id>
<journal-title>Frontiers in Public Health</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Public Health</abbrev-journal-title>
<issn pub-type="epub">2296-2565</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fpubh.2025.1652017</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Public Health</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Internal and external silica dust exposure threshold as an early screening index for silicosis: a cross-sectional study</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Liu</surname><given-names>Shupeng</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>He</surname><given-names>Hailan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Chu</surname><given-names>Lei</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Song</surname><given-names>Qiong</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Zhai</surname><given-names>Yuesong</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Yang</surname><given-names>Fang</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c002"><sup>&#x002A;</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Liu</surname><given-names>Heliang</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c003"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/3109260/overview"/>
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<aff id="aff1"><sup>1</sup><institution>School of Public Health, North China University of Science and Technology</institution>, <addr-line>Tangshan</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Hebei Key Laboratory of Organ Fibrosis, North China University of Science and Technology</institution>, <addr-line>Tangshan</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Zibo Infectious Diseases Hospital</institution>, <addr-line>Zibo</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/281574/overview">Angela Gambelunghe</ext-link>, University of Bologna, Italy</p></fn>
<fn fn-type="edited-by" id="fn0002">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/709155/overview">Francesca Borghi</ext-link>, University of Bologna, Italy</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2854024/overview">Irina-Luciana Gurzu</ext-link>, Grigore T. Popa University of Medicine and Pharmacy, Romania</p></fn>
<corresp id="c001">&#x002A;Correspondence: Yuesong Zhai, <email>depp56667@163.com</email></corresp>
<corresp id="c002">Fang Yang, <email>fangyang@ncst.edu.cn</email></corresp>
<corresp id="c003">Heliang Liu, <email>liuheliang@ncst.edu.cn</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>24</day>
<month>09</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>13</volume>
<elocation-id>1652017</elocation-id>
<history>
<date date-type="received">
<day>23</day>
<month>06</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>09</day>
<month>09</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2025 Liu, He, Chu, Song, Zhai, Yang and Liu.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Liu, He, Chu, Song, Zhai, Yang and Liu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Introduction</title>
<p>Common occupational hazards such as lead, chromium, and mercury have clear biological detection thresholds, but silicon dioxide does not. Therefore, this study aims to determine silica dust exposure thresholds internal and external exposure to identify early screening markers and help screening for susceptible individuals and prevent silicosis.</p>
</sec>
<sec id="sec2">
<title>Methods</title>
<p>Basic information, including physical examination data and questionnaires, was collected from the study participants. Blood and urine samples from iron mine workers were also collected as biological specimens. Silicon levels in these samples were measured using ICP-MS, and cumulative dust exposure was calculated based on an on-site hygiene investigation of the mine.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>Overall, 1,964 participants were included in the study: 1,823 in the dust exposure group (without illness) and 141 in the silicosis group (with illness). Analysis revealed that the silicosis group had higher cumulative dust exposure, indicating an elevated external exposure index. Internal exposure indicators, such as elevated blood and urine silicon levels, were identified as risk factors for silicosis. Screening thresholds were determined using receiver operating characteristic curves and restricted cubic splines. The results showed that workers had an average dust exposure duration of 8.5&#x202F;years. The threshold values were 8.02&#x202F;&#x03BC;g/L for blood silicon with an area under the curve (AUC) of 0.557, 9.51&#x202F;&#x03BC;g/L for urine silicon with AUC of 0.647, and 3728.50&#x202F;mg&#x00B7;years for cumulative dust exposure with AUC of 0.658. When validated with external data from silica-exposed workers, blood silicon had the highest accuracy as an early screening indicator for silicosis.</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>Blood silicon, urine silicon, and cumulative dust exposure were initially proposed as early screening indicators for silicosis. Validation with external worker data showed that blood silicon had relatively high threshol reliability as a screening marker.</p>
</sec>
</abstract>
<kwd-group>
<kwd>silicosis</kwd>
<kwd>cumulative dust exposure</kwd>
<kwd>blood silicon</kwd>
<kwd>urinary silicon</kwd>
<kwd>biological detection threshold</kwd>
</kwd-group>
<counts>
<fig-count count="5"/>
<table-count count="9"/>
<equation-count count="1"/>
<ref-count count="29"/>
<page-count count="10"/>
<word-count count="6265"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Occupational Health and Safety</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<label>1</label>
<title>Introduction</title>
<p>Silicosis is a systemic disease characterized by nodular lung fibrosis, mainly caused by prolonged inhalation of dust particles rich in free silicon dioxide (SiO<sub>2</sub>). It is a common form of pneumoconiosis. The pathogenesis of silicosis remains unclear, and no effective treatment exists (<xref ref-type="bibr" rid="ref1 ref2 ref3 ref4">1&#x2013;4</xref>). Therefore, early screening of susceptible populations and prompt removal from dusty environments are crucial for preventing and treating silicosis (<xref ref-type="bibr" rid="ref5">5</xref>).</p>
<p>According to the Chinese occupational exposure limits for hazardous agents in the workplace - Part 1: Chemical hazardous agents (GBZ 2.1&#x2013;2019), clear biological detection thresholds exist for common occupational hazards, such as blood lead, blood chromium, urine chromium, and urine mercury. However, no such threshold exists for silicosis. Previous research shows that silicon levels in the blood and urine of workers exposed to silica dust rise rapidly during the early stages of exposure, peak within 4&#x2013;6&#x202F;years, and then decline before stabilizing (<xref ref-type="bibr" rid="ref6">6</xref>). These changes in silicon content reflects the direct manifestation of silicon dioxide in the body, it naturally precedes indirect reactions such as those of cytokines, highlighting the value of blood and urine silicon as early indicators of silicosis (<xref ref-type="bibr" rid="ref6 ref7 ref8">6&#x2013;8</xref>). Additionally, studies show that cumulative silica exposure (mg&#x00B7;a) is significantly and positively correlated with the cumulative incidence of pneumoconiosis (%), underscoring its significance in early diagnosis and screening of high-risk populations (<xref ref-type="bibr" rid="ref9">9</xref>). However, the specific exposure threshold remains to be determined.</p>
<p>In this study, the silicon content was measured to represent internal exposure, and the cumulative dust exposure (CDE) was calculated to represent external exposure. Restricted cubic splines (RCS) and receiver operating characteristic (ROC) curves were used to determine the threshold for each screening indicator. So, this study aims to preliminarily identify early screening indicators and biological thresholds for silicosis, providing a theoretical basis for screening high-risk populations and preventing the disease among dust-exposed workers.</p>
</sec>
<sec sec-type="materials|methods" id="sec6">
<label>2</label>
<title>Materials and methods</title>
<sec id="sec7">
<label>2.1</label>
<title>Study participants</title>
<p>In total, 2,119 workers exposed to silica dust who underwent occupational health examinations between March 2023 and June 2024 were initially recruited. After excluding individuals with other lung, endocrine, or metabolic diseases, and those who have taken antioxidant drugs such as vitamin C 1&#x202F;month before the physical examination, prior exposure to other toxic agents before employment at the iron mine, and incomplete responses, 1,964 participants met the inclusion criteria, yielding a response rate of 92.69%. Of these, 1,823 did not have silicosis (102 in the silica dust-free control group and 1,721 in the exposed non-silicosis group). The remaining 141 had silicosis (stage I, II, or III), resulting in a prevalence rate of 7.18%. All participants provided written informed consent. The study was approved by the Ethics Committee of North China University of Science and Technology (Approval Number: 2021041).</p>
</sec>
<sec id="sec8">
<label>2.2</label>
<title>Data collection</title>
<p>Sociodemographic data, including sex, age, marital status, and educational level, were collected, along with information on behaviors and lifestyle (e.g., alcohol use and smoking), personal and family medical history, and detailed occupational history (e.g., job type, work location, position, employment date, working hours, and exposure to harmful occupational factors). Physical examination results (e.g., height, weight, lung function, blood tests, and urinalysis) were also recorded. In addition, enterprise-level information such as production processes, environmental monitoring, and general company conditions was collected.</p>
</sec>
<sec id="sec9">
<label>2.3</label>
<title>Determination of silicon content</title>
<p>Silicon levels in blood and urine samples were measured using ICP-MS, following procedures detailed in our previous study (<xref ref-type="bibr" rid="ref6">6</xref>). All operations were conducted under silicon-free conditions.</p>
</sec>
<sec id="sec10">
<label>2.4</label>
<title>Determination of dust concentration</title>
<p>Total dust concentration, particle dispersion, and free silica content in settled workplace dust were measured using the filter membrane gravimetric method, in accordance with Chinese standard GBZ/T192.1&#x2013;2007.</p>
</sec>
<sec id="sec11">
<label>2.5</label>
<title>Sampling methods of air dust sample</title>
<p>Sampling methods of air dust sample adopts a combination of personal sampling and fixed-point sampling. In accordance with the requirements of Chinese &#x201C;Sampling Specifications for the Detection of Hazardous Substances in the Air of Workplaces,&#x201D; sampling should be conducted separately based on the type, nature, fluctuation situation and degree of hazard. Dust concentration determination: Set up dust detection points. Each detection point should be measured 1 to 3 times per shift for 2 consecutive days. The workers wore individual dust samplers and measured for two work shifts. Fixed-point sampling was carried out using the AKFC-92A dust sampler (Shanghai Yichang Industrial Co., Ltd. China). The sampling filter membrane was a mixed cellulose ester filter membrane with a diameter of 37&#x202F;mm and a pore size of 0.8&#x202F;&#x03BC;m, with a flow rate of 5&#x202F;L/min. The flow rate of the individual sampler is 2&#x202F;L/min, collecting air samples from the entire shift of the workers (8&#x202F;h). As shown in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table 1</xref>.</p>
</sec>
<sec id="sec12">
<label>2.6</label>
<title>Calculation of cumulative dust exposure</title>
<p>Each worker&#x2019;s dust exposure years were calculated based on the start and end dates (employment time) of each job type and associated exposure to harmful factors recorded in their occupational history. CDE was then estimated by job type using the following formula:</p><disp-formula id="E1">
<mml:math id="M1">
<mml:mi>CDE</mml:mi>
<mml:mo>=</mml:mo>
<mml:msub>
<mml:mo>&#x2211;</mml:mo>
<mml:mi mathvariant="normal">j</mml:mi>
</mml:msub>
<mml:mspace width="0.25em"/>
<mml:msubsup>
<mml:mo>&#x2211;</mml:mo>
<mml:mi>ds</mml:mi>
<mml:mi>de</mml:mi>
</mml:msubsup>
<mml:mspace width="0.25em"/>
<mml:msub>
<mml:mi mathvariant="normal">S</mml:mi>
<mml:mi>jt</mml:mi>
</mml:msub>
</mml:math>
</disp-formula>
<p>The unit of CDE is mg/m<sup>3</sup>&#x00B7;years. S<sub>jt</sub> is the average annual exposure measurement for job type <italic>t</italic> in workshop <italic>j</italic> during year <italic>TTH</italic>, ds is the year the worker began job type <italic>t</italic> in workshop <italic>j</italic>, and de is the year the worker ended certain job type <italic>t</italic> in workshop <italic>j</italic> (For silicosis patients, <italic>de</italic> is the year diagnosed with silicosis). CDE reflects both the duration and intensity of dust exposure (<xref ref-type="bibr" rid="ref10">10</xref>).</p>
</sec>
<sec id="sec13">
<label>2.7</label>
<title>Statistical analysis</title>
<p>Statistical analyses were conducted using SPSS 23.0 and SAS 9.4. Normally distributed quantitative data are expressed as mean &#x00B1; standard deviation, while categorical variables are described as composition ratios. Pearson correlation, Spearman correlation, and chi-square test were used for correlation analyses of normally distributed, non-normally distributed, and categorical data, respectively. ROC curves and RCS were used to identify screening thresholds. All hypothesis tests were two-sided, with a significance level of <italic>&#x03B1;</italic>&#x202F;=&#x202F;0.05.</p>
</sec>
</sec>
<sec sec-type="results" id="sec14">
<label>3</label>
<title>Results</title>
<sec id="sec15">
<label>3.1</label>
<title>Basic characteristics of the study participants</title>
<p>All participants were male and were classified into non-silicosis and silicosis groups based on disease status. Potential risk factors for silicosis in dust-exposed workers, including age, smoking, alcohol consumption, body mass index (BMI), and forced expiratory volume in 1&#x202F;s (FEV1%), were described and compared. Significant differences were observed between the two groups regarding age, drinking, BMI, FEV1%, and years of dust exposure (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05), while no difference was found in smoking status (<xref ref-type="table" rid="tab1">Table 1</xref>).</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Characteristics of the study participants.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" colspan="2">Variable</th>
<th align="center" valign="top">Total (<italic>n</italic>, %)</th>
<th align="center" valign="top">Non-silicosis group (<italic>n</italic>, %)</th>
<th align="center" valign="top">Silicosis group (<italic>n</italic>, %)</th>
<th align="center" valign="top"><italic>p-</italic>value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="4">Age (years)</td>
<td align="left" valign="top">&#x003C;30</td>
<td align="center" valign="top">78 (3.97)</td>
<td align="center" valign="top">77 (4.21)</td>
<td align="center" valign="top">1 (0.70)</td>
<td align="center" valign="top" rowspan="4">&#x003C;0.05</td>
</tr>
<tr>
<td align="left" valign="top">30&#x2013;40</td>
<td align="center" valign="top">402 (20.47)</td>
<td align="center" valign="top">389 (21.32)</td>
<td align="center" valign="top">13 (9.21)</td>
</tr>
<tr>
<td align="left" valign="top">40&#x2013;50</td>
<td align="center" valign="top">719 (36.61)</td>
<td align="center" valign="top">672 (36.88)</td>
<td align="center" valign="top">47 (33.32)</td>
</tr>
<tr>
<td align="left" valign="top">&#x003E;50</td>
<td align="center" valign="top">765 (38.95)</td>
<td align="center" valign="top">685 (37.19)</td>
<td align="center" valign="top">80 (56.67)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="3">Smoking</td>
<td align="left" valign="top">Non-smoker</td>
<td align="center" valign="top">726 (36.97)</td>
<td align="center" valign="top">672 (36.88)</td>
<td align="center" valign="top">54 (38.32)</td>
<td align="center" valign="top" rowspan="3">0.26</td>
</tr>
<tr>
<td align="left" valign="top">Smoker</td>
<td align="center" valign="top">1,084 (55.19)</td>
<td align="center" valign="top">1,003 (55.01)</td>
<td align="center" valign="top">81 (57.41)</td>
</tr>
<tr>
<td align="left" valign="top">Quit smoking</td>
<td align="center" valign="top">154 (7.84)</td>
<td align="center" valign="top">148 (8.11)</td>
<td align="center" valign="top">6 (4.27)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="3">Drinking</td>
<td align="left" valign="top">No drinking</td>
<td align="center" valign="top">596 (30.35)</td>
<td align="center" valign="top">530 (29.11)</td>
<td align="center" valign="top">66 (46.76)</td>
<td align="center" valign="top" rowspan="3">&#x003C;0.05</td>
</tr>
<tr>
<td align="left" valign="top">Drinking</td>
<td align="center" valign="top">1,292 (65.78)</td>
<td align="center" valign="top">1,221 (67.02)</td>
<td align="center" valign="top">71 (50.42)</td>
</tr>
<tr>
<td align="left" valign="top">Stop drinking</td>
<td align="center" valign="top">76 (3.87)</td>
<td align="center" valign="top">72 (3.87)</td>
<td align="center" valign="top">4 (2.82)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="4">BMI (kg/m<sup>2</sup>)</td>
<td align="left" valign="top">Underweight</td>
<td align="center" valign="top">3 (0.15)</td>
<td align="center" valign="top">3 (0.21)</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top" rowspan="4">&#x003C;0.05</td>
</tr>
<tr>
<td align="left" valign="top">Normal</td>
<td align="center" valign="top">738 (37.58)</td>
<td align="center" valign="top">699 (38.31)</td>
<td align="center" valign="top">39 (27.68)</td>
</tr>
<tr>
<td align="left" valign="top">Overweight</td>
<td align="center" valign="top">883 (44.96)</td>
<td align="center" valign="top">821 (45.88)</td>
<td align="center" valign="top">62 (44.01)</td>
</tr>
<tr>
<td align="left" valign="top">Obese</td>
<td align="center" valign="top">340 (17.31)</td>
<td align="center" valign="top">300 (16.50)</td>
<td align="center" valign="top">40 (28.41)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="3">FEV1%</td>
<td align="left" valign="top">80%</td>
<td align="center" valign="top">1788 (91.04)</td>
<td align="center" valign="top">1,680 (92.21)</td>
<td align="center" valign="top">108 (76.62)</td>
<td align="center" valign="top" rowspan="3">&#x003C;0.05</td>
</tr>
<tr>
<td align="left" valign="top">70&#x2013;80%</td>
<td align="center" valign="top">140 (7.13)</td>
<td align="center" valign="top">109 (6.00)</td>
<td align="center" valign="top">31 (22.02)</td>
</tr>
<tr>
<td align="left" valign="top">70%</td>
<td align="center" valign="top">36 (1.83)</td>
<td align="center" valign="top">34 (1.89)</td>
<td align="center" valign="top">2 (1.36)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="4">Dust exposure years (years)</td>
<td align="left" valign="top">10</td>
<td align="center" valign="top">783 (39.87)</td>
<td align="center" valign="top">757 (41.51)</td>
<td align="center" valign="top">26 (18.44)</td>
<td align="center" valign="top">&#x003C;0.05</td>
</tr>
<tr>
<td align="left" valign="top">10&#x2013;20</td>
<td align="center" valign="top">674 (34.31)</td>
<td align="center" valign="top">637 (34.91)</td>
<td align="center" valign="top">37 (26.21)</td>
<td rowspan="3"/>
</tr>
<tr>
<td align="left" valign="top">20&#x2013;30</td>
<td align="center" valign="top">333 (16.96)</td>
<td align="center" valign="top">305 (16.68)</td>
<td align="center" valign="top">28 (19.87)</td>
</tr>
<tr>
<td align="left" valign="top">30</td>
<td align="center" valign="top">174 (8.86)</td>
<td align="center" valign="top">124 (6.80)</td>
<td align="center" valign="top">50 (35.46)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>BMI, body mass index; FEV1%, forced expiratory volume in 1&#x202F;s.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec16">
<label>3.2</label>
<title>Dust exposure overview</title>
<p>The primary job categories in the mine include mining, crushing, grinding and selection, as well as auxiliary operations. Based on dust exposure data from 2021 to 2024, an analysis of variance revealed significant differences among job types, except for auxiliary roles (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01; <xref ref-type="table" rid="tab2">Table 2</xref>).</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Silica dust exposure from 2021 to 2024 (mg/m<sup>3</sup>&#x00B7;day).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Job type</th>
<th align="center" valign="top">2021</th>
<th align="center" valign="top">2022</th>
<th align="center" valign="top">2023</th>
<th align="center" valign="top">2024</th>
<th align="center" valign="top"><italic>p-</italic>value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Mining</td>
<td align="center" valign="middle">1.88&#x202F;&#x00B1;&#x202F;0.15</td>
<td align="center" valign="middle">0.71&#x202F;&#x00B1;&#x202F;0.13</td>
<td align="center" valign="middle">0.44&#x202F;&#x00B1;&#x202F;0.04</td>
<td align="center" valign="middle">0.7&#x202F;&#x00B1;&#x202F;0.25</td>
<td align="center" valign="middle">0.004</td>
</tr>
<tr>
<td align="left" valign="middle">Crushing</td>
<td align="center" valign="middle">4.6&#x202F;&#x00B1;&#x202F;0.95</td>
<td align="center" valign="middle">0.81&#x202F;&#x00B1;&#x202F;0.16</td>
<td align="center" valign="middle">0.86&#x202F;&#x00B1;&#x202F;0.2</td>
<td align="center" valign="middle">0.82&#x202F;&#x00B1;&#x202F;0.25</td>
<td align="center" valign="middle">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="middle">Grinding and selection</td>
<td align="center" valign="middle">1.22&#x202F;&#x00B1;&#x202F;0.3</td>
<td align="center" valign="middle">0.91&#x202F;&#x00B1;&#x202F;0.09</td>
<td align="center" valign="middle">0.85&#x202F;&#x00B1;&#x202F;0.11</td>
<td align="center" valign="middle">0.35&#x202F;&#x00B1;&#x202F;0.02</td>
<td align="center" valign="middle">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="middle">Auxiliary</td>
<td align="center" valign="middle">0.28&#x202F;&#x00B1;&#x202F;0.04</td>
<td align="center" valign="middle">0.2&#x202F;&#x00B1;&#x202F;0.77</td>
<td align="center" valign="middle">0.13&#x202F;&#x00B1;&#x202F;0.03</td>
<td align="center" valign="middle">0.25&#x202F;&#x00B1;&#x202F;0.06</td>
<td align="center" valign="middle">0.174</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec17">
<label>3.3</label>
<title>Comparison of cumulative dust exposure and silicon levels</title>
<p>CDE, blood silicon, and urine silicon levels were compared among the dust-free control, dust exposure, and silicosis groups. Analysis of variance revealed significant differences across all groups (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01; <xref ref-type="table" rid="tab3">Table 3</xref>).</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Comparison of internal and external exposure levels under different silica dust exposure conditions.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th>Item</th>
<th align="center" valign="top">Control group (<italic>n</italic>&#x202F;=&#x202F;102)</th>
<th align="center" valign="top">Dust exposure group (<italic>n</italic>&#x202F;=&#x202F;1721)</th>
<th align="center" valign="top">Silicosis group (<italic>n</italic>&#x202F;=&#x202F;141)</th>
<th align="center" valign="top"><italic>p</italic></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Cumulative dust exposure (mg&#x00B7;years)</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">2487.23&#x202F;&#x00B1;&#x202F;235.75<sup>a</sup></td>
<td align="center" valign="middle">2926.46&#x202F;&#x00B1;&#x202F;240.03<sup>a</sup></td>
<td align="center" valign="middle">&#x003C;0.01</td>
</tr>
<tr>
<td align="left" valign="middle">Blood silicon value (&#x03BC;g/mL)</td>
<td align="center" valign="middle">5.28&#x202F;&#x00B1;&#x202F;1.68</td>
<td align="center" valign="middle">9.80&#x202F;&#x00B1;&#x202F;1.67<sup>a</sup></td>
<td align="center" valign="middle">9.55&#x202F;&#x00B1;&#x202F;3.55<sup>a</sup></td>
<td align="center" valign="middle">&#x003C;0.01</td>
</tr>
<tr>
<td align="left" valign="middle">Urine silicon value (&#x03BC;g/mL)</td>
<td align="center" valign="middle">6.24&#x202F;&#x00B1;&#x202F;1.70</td>
<td align="center" valign="middle">12.29&#x202F;&#x00B1;&#x202F;1.86<sup>a</sup></td>
<td align="center" valign="middle">13.39&#x202F;&#x00B1;&#x202F;4.80<sup>ab</sup></td>
<td align="center" valign="middle">&#x003C;0.01</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><sup>a</sup> Compared with the control group, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05; <sup>b</sup> Compared with the silica dust-exposed group, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05; <sup>c</sup> Compared with the silicosis group, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec18">
<label>3.4</label>
<title>Correlation between cumulative dust exposure and silicon levels</title>
<p>Correlation analysis was conducted between internal exposure indicators (blood and urine silicon levels) and the external exposure indicator (CDE). Both blood and urine silicon levels showed a significant positive correlation with CDE (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01). The correlation with urine silicon was strong, while that with blood silicon was moderate (<xref ref-type="table" rid="tab4">Table 4</xref>).</p>
<table-wrap position="float" id="tab4">
<label>Table 4</label>
<caption>
<p>Cumulative dust exposure and urinary and blood silicon levels.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Cumulative dust exposure</th>
<th align="center" valign="top"><italic>n</italic></th>
<th align="center" valign="top"><italic>r</italic></th>
<th align="center" valign="top"><italic>p</italic></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Blood silicon value (&#x03BC;g/mL)</td>
<td align="center" valign="middle">1964</td>
<td align="center" valign="middle">0.42</td>
<td align="center" valign="middle">&#x003C;0.01</td>
</tr>
<tr>
<td align="left" valign="middle">Urine silicon value (&#x03BC;g/mL)</td>
<td align="center" valign="middle">1964</td>
<td align="center" valign="middle">0.66</td>
<td align="center" valign="middle">&#x003C;0.01</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec19">
<label>3.5</label>
<title>Analysis results of early screening indicators for silicosis</title>
<p>Blood and urine silicon levels (internal exposure), CDE (external exposure), and years of dust-exposed work were selected as early screening markers for silicosis. Thresholds for each screening index were identified using RCS and ROC curves. According to the relationship curves, blood and urine silicon levels rose rapidly within the first 1&#x2013;6&#x202F;years of exposure, stabilized between years 6 and 10, and then declined. Urine silicon levels peaked around year 9, while blood silicon levels peaked around year 10. These findings suggest that the highest risk period for developing silicosis occurs between 6 and 10&#x202F;years after initial silica-dust exposure (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Relationship between dust exposure years and blood/urine silicon levels.</p>
</caption>
<graphic xlink:href="fpubh-13-1652017-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Line graph showing silicon content in micrograms per liter over exposure years to silicon dioxide. Urine silicon, indicated in red, starts at about 10, peaks at 14, and then fluctuates slightly downward. Blood silicon, in blue, starts near 8, peaks at 12, and gradually decreases. The x-axis represents exposure years from one to over twenty.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec20">
<label>3.6</label>
<title>Silicon levels as an indicator of silicosis</title>
<p>RCS and the ROC curves were jointly used to determine thresholds for blood and urine silicon as screening indicators for silicosis. Since RCS did not identify clear thresholds, only the points corresponding to the maximum kappa values from the ROC curves were selected.</p>
<p>For blood silicon, the ROC analysis showed statistical significance (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05), with an area under the curve (AUC) of 0.557. Analysis showed that the optimal blood silicon threshold was 8.015&#x202F;&#x03BC;g/L, corresponding to the highest kappa value, with sensitivity and specificity of 0.776 and 0.455, respectively (<xref ref-type="table" rid="tab5">Table 5</xref>; <xref ref-type="fig" rid="fig2">Figure 2A</xref>).</p>
<table-wrap position="float" id="tab5">
<label>Table 5</label>
<caption>
<p>ROC curve results of blood silicon levels and silicosis.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">AUC</th>
<th align="center" valign="top" rowspan="2">SE</th>
<th align="center" valign="top" rowspan="2"><italic>p-</italic>value</th>
<th align="center" valign="top" colspan="2">95% CI</th>
</tr>
<tr>
<th align="center" valign="top">Lower limit</th>
<th align="center" valign="top">Upper limit</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">0.56</td>
<td align="center" valign="middle">0.03</td>
<td align="center" valign="middle">0.01</td>
<td align="center" valign="middle">0.5</td>
<td align="center" valign="middle">0.62</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>AUC, area under the curve; ROC, receiver operating characteristics; CI, confidence interval; SE, Sensitivity.</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>ROC curves of blood and urine silicon levels for silicosis screening. ROC curves for <bold>(A)</bold> blood; <bold>(B)</bold> urine silicon.</p>
</caption>
<graphic xlink:href="fpubh-13-1652017-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Two ROC curves labeled A and B are displayed. Each graph shows sensitivity on the y-axis and 1-specificity on the x-axis. Both curves increase and approach the upper left corner, indicating varying diagnostic accuracy. Curve B appears to perform better than curve A.</alt-text>
</graphic>
</fig>
<p>For urinary silicon, ROC analysis revealed statistical significance (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05), with an AUC of 0.647. The optimal urinary silicon threshold was 9.51&#x202F;&#x03BC;g/L, yielding the highest kappa value, with sensitivity and specificity of 0.917 and 0.444, respectively (<xref ref-type="table" rid="tab6">Table 6</xref>; <xref ref-type="fig" rid="fig2">Figure 2B</xref>).</p>
<table-wrap position="float" id="tab6">
<label>Table 6</label>
<caption>
<p>ROC curve results of urine silicon levels and silicosis.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">AUC</th>
<th align="center" valign="top" rowspan="2">SE</th>
<th align="center" valign="top" rowspan="2"><italic>p-</italic>value</th>
<th align="center" valign="top" colspan="2">95% CI</th>
</tr>
<tr>
<th align="center" valign="top">Lower limit</th>
<th align="center" valign="top">Upper limit</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">0.65</td>
<td align="center" valign="middle">0.02</td>
<td align="center" valign="middle">&#x003C;0.01</td>
<td align="center" valign="middle">0.60</td>
<td align="center" valign="middle">0.69</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>AUC, area under the curve; ROC, receiver operating characteristics; CI, confidence interval; SE, Sensitivity.</p>
</table-wrap-foot>
</table-wrap>
<p>The AUC of both blood silicon and urine silicon is relatively low, especially blood silicon with 0.56 AUC is marginal at best. Although it within the scope of statistics, external validation is still required to obtain the corresponding threshold.</p>
</sec>
<sec id="sec21">
<label>3.7</label>
<title>External cumulative dust exposure as an indicator of silicosis</title>
<p>The ROC curve and RCS were used to determine the threshold for CDE as a screening indicator for silicosis, yielding values of 3207.235&#x202F;mg&#x00B7;years and 4,250&#x202F;mg&#x00B7;years, respectively. The average threshold was 3728.5&#x202F;mg&#x00B7;years. Accordingly, the CDE among workers in this iron mine should not exceed 3728.5&#x202F;mg&#x00B7;years.</p>
</sec>
<sec id="sec22">
<label>3.8</label>
<title>ROC curve of cumulative dust exposure and silicosis</title>
<p>The ROC curve was used to determine the threshold of CDE as a screening indicator for silicosis. The results were statistically significant (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05) with an AUC of 0.658, indicating acceptable screening performance. The optimal CDE threshold, corresponding to the kappa value, was 3207.235&#x202F;mg&#x00B7;years, with sensitivity and specificity of 0.569 and 0.735, respectively (<xref ref-type="table" rid="tab7">Table 7</xref>; <xref ref-type="fig" rid="fig3">Figure 3</xref>).</p>
<table-wrap position="float" id="tab7">
<label>Table 7</label>
<caption>
<p>ROC curve results of cumulative dust exposure and silicosis.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">AUC</th>
<th align="center" valign="top" rowspan="2">SE</th>
<th align="center" valign="top" rowspan="2"><italic>p</italic>-value</th>
<th align="center" valign="top" colspan="2">95% CI</th>
</tr>
<tr>
<th align="center" valign="top">Lower limit</th>
<th align="center" valign="top">Upper limit</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">0.658</td>
<td align="center" valign="middle">0.019</td>
<td align="center" valign="middle">&#x003C;0.001</td>
<td align="center" valign="middle">0.622</td>
<td align="center" valign="middle">0.694</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>AUC, area under the curve; ROC, receiver operating characteristics; CI, confidence interval; SE, Sensitivity.</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p><bold>(A)</bold> ROC and <bold>(B)</bold> restricted cubic spline curves for cumulative dust exposure and silicosis.</p>
</caption>
<graphic xlink:href="fpubh-13-1652017-g003.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Panel A shows an ROC curve graph with sensitivity on the y-axis and one minus specificity on the x-axis, indicating diagnostic performance. Panel B displays a graph of the association between silicosis and CDE using restricted cubic splines with four knots. The red line represents estimation, and dashed lines denote confidence limits, highlighting the relationship across CDE values.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec23">
<label>3.9</label>
<title>Restrictive cubic splines of cumulative dust exposure and silicosis</title>
<p>Using an RCS model with four knots, the Akaike Information Criterion (AIC) of the model was 1090.70. CDE showed a nonlinear dose&#x2013;response relationship with silicosis. The overall association was significant (<italic>&#x03C7;<sup>2</sup></italic> =&#x202F;102.54, <italic>p</italic> &#x003C;&#x202F;0.01), as was the test for nonlinearity (<italic>&#x03C7;<sup>2</sup></italic> =&#x202F;71.62, <italic>p</italic> &#x003C;&#x202F;0.01). Based on the odds ratio (OR) confidence interval, CDE between 1750 and 7,250&#x202F;mg&#x00B7;years was associated with an increased risk of silicosis (OR &#x003E;1). The risk peaked at approximately 4,250&#x202F;mg&#x00B7;years, indicating a rapid increase in risk from 1750 to 4,250&#x202F;mg&#x00B7;years, followed by a gradual decline between 4,250 and 7,250&#x202F;mg&#x00B7;years (<xref ref-type="fig" rid="fig3">Figure 3</xref>). This phenomenon is quite interesting and seems contrary to common sense, it should be that the OR value increases with the increase of the CDE. However, as shown in this chart, the OR value does indeed decline after exceeding the peak of 4,250&#x202F;mg&#x00B7;years. It is speculated that this is related to the susceptibility to silicosis. Before the peak, the risk of developing the disease is relatively high, while after the peak, since those who should have developed the disease have already done so, the remaining population is less susceptible to silicosis. Therefore, the OR value keeps decreasing. This phenomenon also deserves further study in the future.</p>
<p>Using CDE as a screening indicator for silicosis, thresholds identified by the ROC curve and RCS were 3207.235 and 4,250&#x202F;mg&#x00B7;years, respectively. The average value of 3728.5&#x202F;mg&#x00B7;years was adopted as 3728.5&#x202F;mg&#x00B7;years as the screening threshold.</p>
</sec>
<sec id="sec24">
<label>3.10</label>
<title>Dust exposure duration as a screening indicator for silicosis</title>
<p>Years of dust exposure are a simple, practical, and effective indicator for early screening of silicosis. Therefore, they were evaluated as a screening threshold using both the ROC curve and RCS, which yielded thresholds of 8.915 and 8&#x202F;years, respectively. The average, 8.5&#x202F;years, was adopted as the screening threshold. Accordingly, dust exposure among workers in this iron mine should not exceed 8.5&#x202F;years.</p>
</sec>
<sec id="sec25">
<label>3.11</label>
<title>ROC curve of dust exposure years and silicosis</title>
<p>The ROC curve was used to identify the threshold of dust exposure years for silicosis screening. Results showed statistical significance (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05) with an AUC of 0.689, indicating acceptable screening performance. The optimal dust exposure threshold was 8.915&#x202F;years, corresponding to the kappa&#x2019;s highest value, with sensitivity and specificity of 0.73 and 0.54, respectively (<xref ref-type="table" rid="tab8">Table 8</xref>; <xref ref-type="fig" rid="fig4">Figure 4</xref>).</p>
<table-wrap position="float" id="tab8">
<label>Table 8</label>
<caption>
<p>ROC curve results of dust exposure years and silicosis.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">AUC</th>
<th align="center" valign="top" rowspan="2">SE</th>
<th align="center" valign="top" rowspan="2"><italic>p</italic></th>
<th align="center" valign="top" colspan="2">95% CI</th>
</tr>
<tr>
<th align="center" valign="top">Lower limit</th>
<th align="center" valign="top">Upper limit</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">0.69</td>
<td align="center" valign="middle">0.02</td>
<td align="center" valign="middle">&#x003C;0.01</td>
<td align="center" valign="middle">0.65</td>
<td align="center" valign="middle">0.73</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>AUC, area under the curve; ROC, receiver operating characteristics; CI, confidence interval; SE, Sensitivity.</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p><bold>(A)</bold> ROC and <bold>(B)</bold> restricted cubic spline curves for dust exposure years and silicosis.</p>
</caption>
<graphic xlink:href="fpubh-13-1652017-g004.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Panel A shows a ROC curve with the x-axis labeled "1-Specificity" and the y-axis labeled "Sensitivity." Panel B presents a graph of the association between silicosis and exposure years, using restricted cubic splines with four knots. The x-axis represents exposure years, and the y-axis indicates odds ratios, with estimation in red, confidence limits in black dashed lines, and knots in blue.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec26">
<label>3.12</label>
<title>Restricted cubic spline of dust exposure years and silicosis</title>
<p>Using the RCS model with four nodes, the AIC of the model was 1094.47. Dust exposure years showed a nonlinear dose&#x2013;response relationship with silicosis. The overall association was significant (<italic>&#x03C7;<sup>2</sup></italic>&#x202F;=&#x202F;82.50, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01), as was the test for nonlinearity (<italic>&#x03C7;<sup>2</sup></italic>&#x202F;=&#x202F;10.19, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01). When the dust exposure period exceeds 8&#x202F;years, the OR is greater than 1, indicating increased risk of silicosis. The OR remained stable between 8 and 15&#x202F;years, then rose sharply beyond 15&#x202F;years, suggesting a higher risk of silicosis (<xref ref-type="fig" rid="fig4">Figure 4</xref>).</p>
</sec>
<sec id="sec27">
<label>3.13</label>
<title>Validation of external data</title>
<p>In total, 330 individuals were included in the validation set: 79 from a coal mine control group, 112 silica-exposed tunneling workers, and 139 cases of silicosis. ROC curve analysis of blood and urine silicon levels was conducted to assess the accuracy of previously identified screening indicators. Results showed that the blood silicon threshold slightly differed from that of iron mine workers but remained a relatively reliable screening marker for silicosis. In contrast, urine silicon levels showed greater variability, and their threshold requires further validation (<xref ref-type="table" rid="tab9">Table 9</xref>).</p>
<table-wrap position="float" id="tab9">
<label>Table 9</label>
<caption>
<p>Blood and urine silicon concentration in the validation set/<italic>M</italic> (<italic>P<sub>25</sub></italic>, <italic>P<sub>75</sub></italic>).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Silica content /(&#x03BC;g/mL)</th>
<th align="center" valign="top" colspan="3">Groups</th>
<th align="center" valign="top" rowspan="2"><italic>H</italic></th>
<th align="center" valign="top" rowspan="2"><italic>p</italic></th>
</tr>
<tr>
<th align="center" valign="top">Control group (<italic>n</italic>&#x202F;=&#x202F;79)</th>
<th align="center" valign="top">Dust exposure group (<italic>n</italic>&#x202F;=&#x202F;112)</th>
<th align="center" valign="top">Silicosis group (<italic>n</italic>&#x202F;=&#x202F;139)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Blood silicon</td>
<td align="center" valign="middle">7.04 (6.4, 7.90)</td>
<td align="center" valign="middle">11.69 (10.33, 13.44)</td>
<td align="center" valign="middle">10.98 (10.24, 11.99)</td>
<td align="center" valign="middle">70.75</td>
<td align="center" valign="middle">&#x003C;0.05</td>
</tr>
<tr>
<td align="left" valign="middle">Urine silicon</td>
<td align="center" valign="middle">8.03 (6.83, 9.03)</td>
<td align="center" valign="middle">12.50 (9.88, 14.57)</td>
<td align="center" valign="middle">10.16 (9.29, 11.69)</td>
<td align="center" valign="middle">41.71</td>
<td align="center" valign="middle">&#x003C;0.05</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Validation of the blood silicon threshold using the ROC curve showed statistical significance (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05), with an AUC of 0.63. The optimal threshold, based on the highest kappa value, was 8.81&#x202F;&#x03BC;g/L, with sensitivity and specificity of 0.99 and 0.37, respectively. This closely aligns with the previously identified threshold of 8.02&#x202F;&#x03BC;g/L for iron ore dust-exposed workers, supporting the reliability of blood silicon as a screening marker for silicosis (<xref ref-type="fig" rid="fig5">Figure 5A</xref>).</p>
<fig position="float" id="fig5">
<label>Figure 5</label>
<caption>
<p>ROC curves of blood and urine silicon levels in the validation set for silicosis. ROC curves for <bold>(A)</bold> blood silicon and <bold>(B)</bold> urine silicon.</p>
</caption>
<graphic xlink:href="fpubh-13-1652017-g005.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Two ROC curve graphs labeled A and B show the relationship between sensitivity and 1-specificity. Graph A has a steep initial increase and reaches near the top right, indicating good classifier performance. Graph B rises more steadily and similarly reaches near the top, also indicating robust performance. Gridlines are present in both graphs.</alt-text>
</graphic>
</fig>
<p>Validation of the urine silicon threshold using the ROC curve showed significance (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05), with an AUC of 0.70. The optimal threshold, based on the highest kappa value, was 11.05&#x202F;&#x03BC;g/L, with a sensitivity of 0.63 and specificity of 0.97. This value is notably higher than the 9.51&#x202F;&#x03BC;g/mL threshold identified in iron ore dust-exposed workers, indicating that further validation is needed for urine silicon as a screening marker (<xref ref-type="fig" rid="fig5">Figure 5B</xref>).</p>
</sec>
</sec>
<sec sec-type="discussion" id="sec28">
<label>4</label>
<title>Discussion</title>
<p>Silicosis, the most common type of pneumoconiosis, is the most prevalent occupational disease in China and among the most serious worldwide (<xref ref-type="bibr" rid="ref11 ref12 ref13">11&#x2013;13</xref>). The World Health Organization and International Labor Organization aim to eliminate pneumoconiosis by 2030 (<xref ref-type="bibr" rid="ref14">14</xref>). Achieving this goal requires effective prevention of silica dust exposure and the identification of early biological screening thresholds. However, the Occupational Exposure Limits for Hazardous Factors in the Workplace: Part 1 of the Occupational Health Standards of the People&#x2019;s Republic of China (GBZ 2.1&#x2013;2019) provides no guidance on biological monitoring indicators or occupational exposure biological limits. Therefore, establishing biological monitoring indicators and occupational exposure limits for silica dust is urgently needed to guide occupational health standards.</p>
<p>Silicosis is progressive and irreversible, often leading to severe morbidity and mortality even after exposure ends. Clinical studies show that early diagnosis significantly improves survival in patients with silicosis, while advanced stages are associated with sharply increased mortality. The findings underscore the urgent need for systematic early screening, such as high-resolution computed tomography, and stricter occupational health regulations to reduce silica exposure (<xref ref-type="bibr" rid="ref15">15</xref>, <xref ref-type="bibr" rid="ref16">16</xref>).</p>
<p>Several potential biomarkers for silicosis have been proposed, but none have been validated for clinical use. For example, IL-8 shows promise in detecting silicosis and predicting mortality (<xref ref-type="bibr" rid="ref17">17</xref>), while serum CC16 and L-selectin levels may serve as viable alternatives. Neopterin levels in urine and serum have been linked to dust exposure, and lactate dehydrogenase may indicate silica-induced toxicity in agate workers. CXCL16 has emerged as a potential biomarker for distinguishing between silica exposure and silicosis (<xref ref-type="bibr" rid="ref18 ref19 ref20 ref21">18&#x2013;21</xref>). Blood inflammatory markers also correlate with silicosis and impaired lung function (<xref ref-type="bibr" rid="ref22">22</xref>). Additionally, certain VOCs in exhaled breath appear suitable for identifying silica exposure (<xref ref-type="bibr" rid="ref23">23</xref>, <xref ref-type="bibr" rid="ref24">24</xref>). Based on biological rationality, these biomarkers have good statistical significance in some studies. However, most initial biomarker studies suffer from limited and non-representative cohorts. While statistically significant results can be found in small groups, these findings may not be generalizable to the entire population at risk. In the meantime, due to limitations such as small sample size, specificity and sensitivity, and the high cost and difficulty in promotion of instruments and equipment, they have not yet been widely promoted in clinical practice and practical applications. Thus, further research with representative samples is needed to confirm their clinical utility.</p>
<p>We focus on SiO<sub>2</sub>, the primary hazard in silicosis. Traditionally, SiO<sub>2</sub> is considered biologically inert. Once it enters the lungs, it remains deposited in the lesion or phagocytosed by alveolar macrophages without undergoing metabolism. However, studies show that trace amounts of silicon can enter the bloodstream and tissues, undergo metabolism, and exert toxic effects (<xref ref-type="bibr" rid="ref6">6</xref>). Thus, silicon may indicate systemic SiO<sub>2</sub> accumulation. Our previous research found that both blood and urine silicon levels reflect internal silicon burden. After exposure to silica dust, the silicon levels in the body change at an early stage, often before other recognized early biomarkers of silicosis (<xref ref-type="bibr" rid="ref7">7</xref>, <xref ref-type="bibr" rid="ref8">8</xref>). Epidemiological studies suggest that silicosis can develop or progress even after exposure ends, indicating a threshold lung burden above which the disease progresses without further exposure (<xref ref-type="bibr" rid="ref25">25</xref>). However, this threshold remains undefined.</p>
<p>Our previous measurements of silicon levels in workers exposed to silica dust showed a rapid increase during the first 1&#x2013;5&#x202F;years, followed by a decline in serum and urine silicon with prolonged exposure (<xref ref-type="bibr" rid="ref6">6</xref>, <xref ref-type="bibr" rid="ref8">8</xref>). Similarly, animal studies found significantly elevated serum silicon levels in rats exposed to silica dust (<xref ref-type="bibr" rid="ref7">7</xref>). After SiO<sub>2</sub> enters the body, a compensatory clearance mechanism is triggered, increasing silicon metabolism and leading to an early metabolic peak. As exposure continues over time, the capacity of the body to metabolize SiO<sub>2</sub> becomes saturated, entering a decompensated phase. Therefore, silicon levels gradually decline in the later stages of exposure, although the precise metabolic mechanism remains unclear.</p>
<p>Recent studies have identified a link between blood and urine silicon levels and the development of pulmonary fibrosis in both animals and humans. These findings suggest that blood and urine silicon may reflect early-stage pulmonary fibrosis and show changes earlier than traditional inflammatory markers such as TGF-&#x03B2;1, TNF-<italic>&#x03B1;</italic>, and CC16, highlighting their potential for early screening (<xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref27">27</xref>). In addition, Fan et al. examined the dose&#x2013;response relationship of pneumoconiosis using cumulative free silica exposure as an indicator across various dust types with different silica content (<xref ref-type="bibr" rid="ref9">9</xref>). The results showed a significant positive correlation between cumulative silica exposure (mg&#x00B7;years) and the cumulative incidence of pneumoconiosis (%), underscoring the role of free silica content in pneumoconiosis pathogenesis. However, despite decades of research, few studies have examined the link between cumulative silica exposure and silicosis. Most have focused on immediate exposure limits, such as permissible exposure limits, which represent the average RCS exposure over an 8-h shift and vary from 0.05 (USA) to 0.35&#x202F;mg/m<sup>3</sup> (China) (<xref ref-type="bibr" rid="ref28">28</xref>). Moreover, the average intensity of RCS exposure remains debated (<xref ref-type="bibr" rid="ref2">2</xref>) and annual cumulative exposure thresholds were not addressed. Therefore, the existing CDE research mainly focuses on the dose&#x2013;response relationship with silicosis but rarely involves the CDE threshold.</p>
<p>This study used CDE as the external exposure indicator and blood and urine silicon levels as internal exposure indicators. Thresholds were identified using the RCS and ROC curves. Both regression models for CDE were statistically significant, establishing 3728.5&#x202F;mg&#x00B7;years as the preliminary screening threshold. Although RCS results for blood and urine silicon lacked statistical significance, external validation (<xref ref-type="bibr" rid="ref29">29</xref>) confirmed blood silicon as a reliable indicator for early screening of silicosis. Theoretically, it is speculated that blood silicon should be more stable and reliable than urine silicon, urinary silicon is more susceptible to the influence of metabolism in the body, but the detection of urine silicon is simpler. In view of this study AUCs for blood and urine silicon are low, therefore these thresholds are preliminary and require prospective validation. It should also be emphasized that the determination of silicon requires strict &#x201C;silicon-free&#x201D; conditions. Additionally, better instruments and equipment are needed to eliminate determination bias.</p>
<p>This cross-sectional study analyzes silicosis among workers undergoing physical examinations from 2023 to 2024. However, due to the small sample size, this study did not conduct further analysis on factors such as age, educational level, smoking and drinking, and type of work. In the meantime, it lacks longitudinal data and is limited to a single iron mine without a large, multicenter sample and difficult to generalize to other scenarios and situations. So, this study merely made a preliminary attempt, providing a model for similar research in the future and playing a leading and exemplary role. When the sample size is expanded and different scenarios are applied in the future, more convincing results may be obtained.</p>
<p>In conclusion, blood and urine silicon levels can serve as early screening indicators for silicosis. CDE can be estimated using job type, exposure type, and duration of dust exposure. Years of dust exposure also offer predictive value. Once workers reach a high-risk exposure period, they should be reassigned from silica-exposed roles. Notably, these thresholds are intended solely for screening for susceptible individuals and not for diagnosing or assessing silicosis prognosis.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec29">
<title>Data availability statement</title>
<p>The data analyzed in this study is subject to the following licenses/restrictions: the health check data of the enterprise staff cannot be made public. Requests to access these datasets should be directed to <email>liuheliang@ncst.edu.cn</email>.</p>
</sec>
<sec sec-type="ethics-statement" id="sec30">
<title>Ethics statement</title>
<p>The studies involving humans were approved by Ethics Committee of North China University of Science and Technology. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.</p>
</sec>
<sec sec-type="author-contributions" id="sec31">
<title>Author contributions</title>
<p>SL: Data curation, Formal analysis, Investigation, Writing &#x2013; original draft. HH: Formal analysis, Validation, Writing &#x2013; review &#x0026; editing. LC: Methodology, Software, Writing &#x2013; review &#x0026; editing. QS: Conceptualization, Data curation, Writing &#x2013; review &#x0026; editing. YZ: Conceptualization, Data curation, Software, Writing &#x2013; review &#x0026; editing. FY: Resources, Validation, Writing &#x2013; review &#x0026; editing. HL: Funding acquisition, Supervision, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec sec-type="funding-information" id="sec32">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by the Project of National Natural Science Foundation of China (U21A20334), Hebei Province Natural Science Foundation of China (H2025209083, H2025209038), and Hebei Province graduate student innovation ability training funding project (CXZZBS2024140).</p>
</sec>
<ack>
<p>We are very grateful for the participation of the managers and workers of the two mines.</p>
</ack>
<sec sec-type="COI-statement" id="sec33">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec34">
<title>Generative AI statement</title>
<p>The authors declare that no Gen AI was used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="sec35">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec36">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fpubh.2025.1652017/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fpubh.2025.1652017/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.DOCX" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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