Human plasma and liver concentrations of styrene estimated by combining a simple physiologically based pharmacokinetic model with rodent data
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- Miura Tomonori
- Showa Pharmaceutical University
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- Uehara Shotaro
- Central Institute for Experimental Animals
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- Nakazato Mayuko
- Showa Pharmaceutical University
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- Kusama Takashi
- Showa Pharmaceutical University
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- Toda Akiko
- Shin Nippon Biomedical Laboratories, Ltd.
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- Kamiya Yusuke
- Showa Pharmaceutical University
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- Murayama Norie
- Showa Pharmaceutical University
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- Shimizu Makiko
- Showa Pharmaceutical University
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- Suemizu Hiroshi
- Central Institute for Experimental Animals
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- Yamazaki Hiroshi
- Showa Pharmaceutical University
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<p>Long-term exposure to certain volatile organic compounds is a significant public health concern. A variety of food containers and drinking cups prepared from polystyrene or polystyrene-related plastics could contain styrene monomer. In the current study, the concentrations of styrene in plasma and liver were surveyed and determined after oral doses of 25 mg/kg to rats and 200 mg/kg to control and humanized-liver mice. Plasma concentrations of styrene in rats were still detected 2 hr after 10-25 mg/kg oral doses. In contrast, after an order of magnitude higher oral dose of styrene (200 mg/kg) to mice, styrene in mouse plasma was rapidly cleared within 15 min to the limit-of-detection level. However, unmetabolized styrene was detected in mouse liver 24 hr after oral treatment. A simple physiologically based pharmacokinetic (PBPK) model capable of estimating blood and liver concentrations of styrene was established for rats. A human PBPK model was then set up for styrene by using the same intrinsic hepatic clearances in rats and humans and by applying allometric scaling to rat parameters obtained from the plasma concentrations of styrene in rats. By reverse dosimetry analysis (from concentrations to doses), we found that the 95th percentile values of styrene concentrations (0.132 ng/mL) reported in United States biomonitoring data of more than 1000 human blood samples may imply exposure to repeated oral doses of styrene of 2.89 µg/kg/day. These results suggest that styrene biomonitoring data in human blood samples imply exposures roughly similar to or lower than the established tolerable daily intake level of 7.7 μg/kg/day.</p>
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 44 (8), 543-548, 2019
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001288155146368
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- NII論文ID
- 130007687325
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- NII書誌ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 030049180
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- PubMed
- 31378765
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可