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Styrene lung cancer risk assessment: an alternative evaluation of human lung cancer risk assuming mouse lung tumors are potentially human relevant and operating by a threshold-based non-genotoxic mode of action
Rodent inhalation studies indicate styrene is a mouse lung-specific carcinogen. Mode-of-action (MOA) analyses indicate that the lung tumors cannot be excluded as weakly quantitatively relevant to humans due to shared oxidative metabolites detected in rodents and humans. However, styrene also is not...
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| Published in: | Journal of toxicology and environmental health. Part B, Critical reviews Critical reviews, 2024-10, Vol.27 (7), p.264-286 |
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| container_end_page | 286 |
| container_issue | 7 |
| container_start_page | 264 |
| container_title | Journal of toxicology and environmental health. Part B, Critical reviews |
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| creator | Bus, J. S. Su, S. Li, W. Goodman, J. E. |
| description | Rodent inhalation studies indicate styrene is a mouse lung-specific carcinogen. Mode-of-action (MOA) analyses indicate that the lung tumors cannot be excluded as weakly quantitatively relevant to humans due to shared oxidative metabolites detected in rodents and humans. However, styrene also is not genotoxic following in vivo dosing. The objective of this review was to characterize occupational and general population cancer risks by conservatively assuming mouse lung tumors were relevant to humans but operating by a non-genotoxic MOA. Inhalation cancer values reference concentrations for respective occupational and general population exposures (RfC
car-occup
and RfC
car-genpop
) were derived from initial benchmark dose (BMD) modeling of mouse inhalation tumor dose-response data. An overall lowest BMDL
10
of 4.7 ppm was modeled for lung tumors, which was further duration- and dose-adjusted by physiologically based pharmacokinetic (PBPK) modeling to derive RfC
car-occup/genpop
values of 6.2 ppm and 0.8 ppm, respectively. With the exception of open-mold fiber reinforced composite workers not using personal protective equipment (PPE), the RfC
car-occup/genpop
values are greater than typical occupational and general population human exposures, thus indicating styrene exposures represent a low potential for human lung cancer risk. Consistent with this conclusion, a review of styrene occupational epidemiology did not support a conclusion of an association between styrene exposure and lung cancer occurrence, and further supports a conclusion that the conservatively derived RfC
car-occup
is lung cancer protective. |
| doi_str_mv | 10.1080/10937404.2024.2380449 |
| format | article |
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car-occup
and RfC
car-genpop
) were derived from initial benchmark dose (BMD) modeling of mouse inhalation tumor dose-response data. An overall lowest BMDL
10
of 4.7 ppm was modeled for lung tumors, which was further duration- and dose-adjusted by physiologically based pharmacokinetic (PBPK) modeling to derive RfC
car-occup/genpop
values of 6.2 ppm and 0.8 ppm, respectively. With the exception of open-mold fiber reinforced composite workers not using personal protective equipment (PPE), the RfC
car-occup/genpop
values are greater than typical occupational and general population human exposures, thus indicating styrene exposures represent a low potential for human lung cancer risk. Consistent with this conclusion, a review of styrene occupational epidemiology did not support a conclusion of an association between styrene exposure and lung cancer occurrence, and further supports a conclusion that the conservatively derived RfC
car-occup
is lung cancer protective.</description><identifier>ISSN: 1093-7404</identifier><identifier>ISSN: 1521-6950</identifier><identifier>EISSN: 1521-6950</identifier><identifier>DOI: 10.1080/10937404.2024.2380449</identifier><identifier>PMID: 39056307</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Animals ; Carcinogens ; Carcinogens - toxicity ; Dosage ; Dose-Response Relationship, Drug ; Epidemiology ; Exposure ; Fiber composites ; Genotoxicity ; Health risks ; Humans ; In vivo methods and tests ; Inhalation ; Inhalation Exposure - adverse effects ; Inhalation Exposure - analysis ; Lung cancer ; lung cancer risk assessment ; Lung Neoplasms - chemically induced ; Lung Neoplasms - epidemiology ; Metabolites ; Mice ; Mode of action ; Modelling ; non-genotoxic mode-of-action ; Occupational exposure ; Occupational Exposure - adverse effects ; Occupational Exposure - analysis ; Pharmacokinetics ; physiologically based pharmacokinetic (PBPK) modeling ; Protective equipment ; Respiration ; Risk Assessment ; Rodents ; Styrene ; Styrene - toxicity ; styrene oxide ; Styrenes ; Tumors</subject><ispartof>Journal of toxicology and environmental health. Part B, Critical reviews, 2024-10, Vol.27 (7), p.264-286</ispartof><rights>2024 Gradient. Published with license by Taylor & Francis Group, LLC. 2024</rights><rights>2024 Gradient. Published with license by Taylor & Francis Group, LLC. This work is licensed under the Creative Commons Attribution – Non-Commercial – No Derivatives License http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c272t-d8351f87ca99435d0c5740ea2728b0dc755ad55188c419714fb7e248d70626ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39056307$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bus, J. S.</creatorcontrib><creatorcontrib>Su, S.</creatorcontrib><creatorcontrib>Li, W.</creatorcontrib><creatorcontrib>Goodman, J. E.</creatorcontrib><title>Styrene lung cancer risk assessment: an alternative evaluation of human lung cancer risk assuming mouse lung tumors are potentially human relevant and operating by a threshold-based non-genotoxic mode of action</title><title>Journal of toxicology and environmental health. Part B, Critical reviews</title><addtitle>J Toxicol Environ Health B Crit Rev</addtitle><description>Rodent inhalation studies indicate styrene is a mouse lung-specific carcinogen. Mode-of-action (MOA) analyses indicate that the lung tumors cannot be excluded as weakly quantitatively relevant to humans due to shared oxidative metabolites detected in rodents and humans. However, styrene also is not genotoxic following in vivo dosing. The objective of this review was to characterize occupational and general population cancer risks by conservatively assuming mouse lung tumors were relevant to humans but operating by a non-genotoxic MOA. Inhalation cancer values reference concentrations for respective occupational and general population exposures (RfC
car-occup
and RfC
car-genpop
) were derived from initial benchmark dose (BMD) modeling of mouse inhalation tumor dose-response data. An overall lowest BMDL
10
of 4.7 ppm was modeled for lung tumors, which was further duration- and dose-adjusted by physiologically based pharmacokinetic (PBPK) modeling to derive RfC
car-occup/genpop
values of 6.2 ppm and 0.8 ppm, respectively. With the exception of open-mold fiber reinforced composite workers not using personal protective equipment (PPE), the RfC
car-occup/genpop
values are greater than typical occupational and general population human exposures, thus indicating styrene exposures represent a low potential for human lung cancer risk. Consistent with this conclusion, a review of styrene occupational epidemiology did not support a conclusion of an association between styrene exposure and lung cancer occurrence, and further supports a conclusion that the conservatively derived RfC
car-occup
is lung cancer protective.</description><subject>Animals</subject><subject>Carcinogens</subject><subject>Carcinogens - toxicity</subject><subject>Dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epidemiology</subject><subject>Exposure</subject><subject>Fiber composites</subject><subject>Genotoxicity</subject><subject>Health risks</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Inhalation</subject><subject>Inhalation Exposure - adverse effects</subject><subject>Inhalation Exposure - analysis</subject><subject>Lung cancer</subject><subject>lung cancer risk assessment</subject><subject>Lung Neoplasms - chemically induced</subject><subject>Lung Neoplasms - epidemiology</subject><subject>Metabolites</subject><subject>Mice</subject><subject>Mode of action</subject><subject>Modelling</subject><subject>non-genotoxic mode-of-action</subject><subject>Occupational exposure</subject><subject>Occupational Exposure - adverse effects</subject><subject>Occupational Exposure - analysis</subject><subject>Pharmacokinetics</subject><subject>physiologically based pharmacokinetic (PBPK) modeling</subject><subject>Protective equipment</subject><subject>Respiration</subject><subject>Risk Assessment</subject><subject>Rodents</subject><subject>Styrene</subject><subject>Styrene - toxicity</subject><subject>styrene oxide</subject><subject>Styrenes</subject><subject>Tumors</subject><issn>1093-7404</issn><issn>1521-6950</issn><issn>1521-6950</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><recordid>eNp9kd-O1SAQxhujcf_oI2hIvPGmKxQo1CvNRleTTbxQrxsOTPd0pXAEutrX9Imc5nS9MEYuYML85puBr6qeMXrBqKavGO24ElRcNLTBjWsqRPegOmWyYXXbSfoQY2TqFTqpznK-pbhkpx9XJ7yjsuVUnVa_PpclQQDi53BDrAkWEklj_kZMzpDzBKG8JiYQ4wukYMp4BwTujJ8xjIHEgeznCfP_qp-nES-nOOdNv8xTTJmYBOQQC0qPxvtlU0jgUTgU7OZIPEDCDlizW4ghZZ8g76N39c5kcCTEUN9AiCX-HC12cLBOYuw605Pq0WB8hqfbeV59ff_uy-WH-vrT1cfLt9e1bVRTaqe5ZINW1nSd4NJRK_GrwGBS76izSkrjpGRaW8E6xcSwU9AI7RRtm9YAP69eHnUPKX6fIZd-GrMF700AfHLPqRZKtbwViL74C72NM_6mX6mu46JlokFKHimbYs4Jhv6QxsmkpWe0X03v703vV9P7zXSse76pz7sJ3J-qe5cReHMExjDENJkfMXnXF7P4mIaEno04x_97_AaLfb_u</recordid><startdate>20241002</startdate><enddate>20241002</enddate><creator>Bus, J. S.</creator><creator>Su, S.</creator><creator>Li, W.</creator><creator>Goodman, J. 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S. ; Su, S. ; Li, W. ; Goodman, J. 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S.</creatorcontrib><creatorcontrib>Su, S.</creatorcontrib><creatorcontrib>Li, W.</creatorcontrib><creatorcontrib>Goodman, J. 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Part B, Critical reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bus, J. S.</au><au>Su, S.</au><au>Li, W.</au><au>Goodman, J. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Styrene lung cancer risk assessment: an alternative evaluation of human lung cancer risk assuming mouse lung tumors are potentially human relevant and operating by a threshold-based non-genotoxic mode of action</atitle><jtitle>Journal of toxicology and environmental health. Part B, Critical reviews</jtitle><addtitle>J Toxicol Environ Health B Crit Rev</addtitle><date>2024-10-02</date><risdate>2024</risdate><volume>27</volume><issue>7</issue><spage>264</spage><epage>286</epage><pages>264-286</pages><issn>1093-7404</issn><issn>1521-6950</issn><eissn>1521-6950</eissn><abstract>Rodent inhalation studies indicate styrene is a mouse lung-specific carcinogen. Mode-of-action (MOA) analyses indicate that the lung tumors cannot be excluded as weakly quantitatively relevant to humans due to shared oxidative metabolites detected in rodents and humans. However, styrene also is not genotoxic following in vivo dosing. The objective of this review was to characterize occupational and general population cancer risks by conservatively assuming mouse lung tumors were relevant to humans but operating by a non-genotoxic MOA. Inhalation cancer values reference concentrations for respective occupational and general population exposures (RfC
car-occup
and RfC
car-genpop
) were derived from initial benchmark dose (BMD) modeling of mouse inhalation tumor dose-response data. An overall lowest BMDL
10
of 4.7 ppm was modeled for lung tumors, which was further duration- and dose-adjusted by physiologically based pharmacokinetic (PBPK) modeling to derive RfC
car-occup/genpop
values of 6.2 ppm and 0.8 ppm, respectively. With the exception of open-mold fiber reinforced composite workers not using personal protective equipment (PPE), the RfC
car-occup/genpop
values are greater than typical occupational and general population human exposures, thus indicating styrene exposures represent a low potential for human lung cancer risk. Consistent with this conclusion, a review of styrene occupational epidemiology did not support a conclusion of an association between styrene exposure and lung cancer occurrence, and further supports a conclusion that the conservatively derived RfC
car-occup
is lung cancer protective.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>39056307</pmid><doi>10.1080/10937404.2024.2380449</doi><tpages>23</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1093-7404 |
| ispartof | Journal of toxicology and environmental health. Part B, Critical reviews, 2024-10, Vol.27 (7), p.264-286 |
| issn | 1093-7404 1521-6950 1521-6950 |
| language | eng |
| recordid | cdi_pubmed_primary_39056307 |
| source | Taylor and Francis Science and Technology Collection |
| subjects | Animals Carcinogens Carcinogens - toxicity Dosage Dose-Response Relationship, Drug Epidemiology Exposure Fiber composites Genotoxicity Health risks Humans In vivo methods and tests Inhalation Inhalation Exposure - adverse effects Inhalation Exposure - analysis Lung cancer lung cancer risk assessment Lung Neoplasms - chemically induced Lung Neoplasms - epidemiology Metabolites Mice Mode of action Modelling non-genotoxic mode-of-action Occupational exposure Occupational Exposure - adverse effects Occupational Exposure - analysis Pharmacokinetics physiologically based pharmacokinetic (PBPK) modeling Protective equipment Respiration Risk Assessment Rodents Styrene Styrene - toxicity styrene oxide Styrenes Tumors |
| title | Styrene lung cancer risk assessment: an alternative evaluation of human lung cancer risk assuming mouse lung tumors are potentially human relevant and operating by a threshold-based non-genotoxic mode of action |
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