In vivo mutagenicity assessment of styrene in MutaMouse liver and lung

Abstract Background Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile–butadiene–styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. St...

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Main Authors: Yasumasa Murata, Masakatsu Natsume, Takako Iso, Yoshiyuki Shigeta, Nozomu Hirose, Takaaki Umano, Katsuyoshi Horibata, Kei-ichi Sugiyama, Kenichi Masumura, Akihiko Hirose, Mariko Matsumoto
Format: Article
Language:English
Published: BMC 2023-04-01
Series:Genes and Environment
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Online Access:https://doi.org/10.1186/s41021-023-00270-9
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author Yasumasa Murata
Masakatsu Natsume
Takako Iso
Yoshiyuki Shigeta
Nozomu Hirose
Takaaki Umano
Katsuyoshi Horibata
Kei-ichi Sugiyama
Kenichi Masumura
Akihiko Hirose
Mariko Matsumoto
author_facet Yasumasa Murata
Masakatsu Natsume
Takako Iso
Yoshiyuki Shigeta
Nozomu Hirose
Takaaki Umano
Katsuyoshi Horibata
Kei-ichi Sugiyama
Kenichi Masumura
Akihiko Hirose
Mariko Matsumoto
author_sort Yasumasa Murata
collection DOAJ
description Abstract Background Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile–butadiene–styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. Styrene is metabolized into styrene 7,8-oxide (SO). SO is mutagenic in bacteria and mouse lymphoma assays. It is clastogenic in cultured mammalian cells. However, styrene and SO are not clastogenic/aneugenic in rodents, and no rodent in vivo gene mutation studies were identified. Methods To investigate the mutagenicity of orally administered styrene, we used the transgenic rodent gene mutation assay to perform an in vivo mutagenicity test (OECD TG488). The transgenic MutaMouse was given styrene orally at doses of 0 (corn oil; negative control), 75, 150, and 300 mg/kg/day for 28 days, and mutant frequencies (MFs) were determined using the lacZ assay in the liver and lung (five male mice/group). Results There were no significant differences in the MFs of the liver and lung up to 300 mg/kg/day (close to maximum tolerable dose (MTD)), when one animal with extremely high MFs that were attributed to an incidental clonal mutation was omitted. Positive and negative controls produced the expected results. Conclusions These findings show that styrene is not mutagenic in the liver and lung of MutaMouse under this experimental condition.
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spelling doaj.art-2ba5467ff8fc457fa0a44d7e1fe3d0592023-04-16T11:25:17ZengBMCGenes and Environment1880-70622023-04-0145111110.1186/s41021-023-00270-9In vivo mutagenicity assessment of styrene in MutaMouse liver and lungYasumasa Murata0Masakatsu Natsume1Takako Iso2Yoshiyuki Shigeta3Nozomu Hirose4Takaaki Umano5Katsuyoshi Horibata6Kei-ichi Sugiyama7Kenichi Masumura8Akihiko Hirose9Mariko Matsumoto10Division of Risk Assessment, National Institute of Health SciencesGenotoxicology Laboratory, BioSafety Research Center IncDivision of Risk Assessment, National Institute of Health SciencesDivision of Risk Assessment, National Institute of Health SciencesDivision of Risk Assessment, National Institute of Health SciencesDivision of Risk Assessment, National Institute of Health SciencesDivision of Genetics and Mutagenesis, National Institute of Health SciencesDivision of Genetics and Mutagenesis, National Institute of Health SciencesDivision of Risk Assessment, National Institute of Health SciencesDivision of Risk Assessment, National Institute of Health SciencesDivision of Risk Assessment, National Institute of Health SciencesAbstract Background Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile–butadiene–styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. Styrene is metabolized into styrene 7,8-oxide (SO). SO is mutagenic in bacteria and mouse lymphoma assays. It is clastogenic in cultured mammalian cells. However, styrene and SO are not clastogenic/aneugenic in rodents, and no rodent in vivo gene mutation studies were identified. Methods To investigate the mutagenicity of orally administered styrene, we used the transgenic rodent gene mutation assay to perform an in vivo mutagenicity test (OECD TG488). The transgenic MutaMouse was given styrene orally at doses of 0 (corn oil; negative control), 75, 150, and 300 mg/kg/day for 28 days, and mutant frequencies (MFs) were determined using the lacZ assay in the liver and lung (five male mice/group). Results There were no significant differences in the MFs of the liver and lung up to 300 mg/kg/day (close to maximum tolerable dose (MTD)), when one animal with extremely high MFs that were attributed to an incidental clonal mutation was omitted. Positive and negative controls produced the expected results. Conclusions These findings show that styrene is not mutagenic in the liver and lung of MutaMouse under this experimental condition.https://doi.org/10.1186/s41021-023-00270-9TG488MutaMouseStyreneIn vivo mutagenicityAnd transgenic rodent gene mutation assay
spellingShingle Yasumasa Murata
Masakatsu Natsume
Takako Iso
Yoshiyuki Shigeta
Nozomu Hirose
Takaaki Umano
Katsuyoshi Horibata
Kei-ichi Sugiyama
Kenichi Masumura
Akihiko Hirose
Mariko Matsumoto
In vivo mutagenicity assessment of styrene in MutaMouse liver and lung
Genes and Environment
TG488
MutaMouse
Styrene
In vivo mutagenicity
And transgenic rodent gene mutation assay
title In vivo mutagenicity assessment of styrene in MutaMouse liver and lung
title_full In vivo mutagenicity assessment of styrene in MutaMouse liver and lung
title_fullStr In vivo mutagenicity assessment of styrene in MutaMouse liver and lung
title_full_unstemmed In vivo mutagenicity assessment of styrene in MutaMouse liver and lung
title_short In vivo mutagenicity assessment of styrene in MutaMouse liver and lung
title_sort in vivo mutagenicity assessment of styrene in mutamouse liver and lung
topic TG488
MutaMouse
Styrene
In vivo mutagenicity
And transgenic rodent gene mutation assay
url https://doi.org/10.1186/s41021-023-00270-9
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