In vitro-in silico-based probabilistic risk assessment of combined exposure to bisphenol A and its analogues by integrating ToxCast high-throughput in vitro assays with in vitro to in vivo extrapolation (IVIVE) via physiologically based pharmacokinetic (PBPK) modeling

被引:25
作者
Lin, Yi-Jun [1 ,2 ]
Lin, Zhoumeng [2 ]
机构
[1] Natl Yang Ming Univ, Inst Food Safety & Hlth Risk Assessment, Taipei 11221, Taiwan
[2] Kansas State Univ, Coll Vet Med, Inst Computat Comparat Med ICCM, Dept Anat & Physiol, 1800 Denison Ave,P200 Mosier Hall, Manhattan, KS 66506 USA
关键词
Bisphenol AF; Bisphenol F; Bisphenol S; Combined risk assessment; In vitro to in vivo extrapolation (IVIVE); UNITED-STATES; TOXICITY; FOODSTUFFS; DOSIMETRY; CHEMICALS; HEALTH; BPA; PRINCIPLES; TOXICOLOGY; PROGRESS;
D O I
10.1016/j.jhazmat.2020.122856
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Combined risk assessment of endocrine effects of bisphenol A (BPA) and its analogues, such as bisphenols S, F, and AF (BPS, BPF, and BPAF), is challenging due to lack of related common toxicity metrics. This study conducted a population-based in vitro-to-in vivo extrapolation using physiologically based pharmacokinetic (PBPK) models coupled with Monte Carlo simulations to convert ToxCast in vitro estrogen receptor (ER) assays to human equivalent doses (HEDs). The ER pathway-based HEDs were compared with HEDs from animal studies and used to assess the combined risks for different populations across different countries/regions in a probabilistic manner. The estimated ER pathway-based HEDs for the four bisphenols (BPs) matched the animal-derived HEDs. The HEDs for the ER gene transcription (the common biological process target among BPs) were 0.40 (2.5th-97.5th percentiles: 0.06-5.42), 4.43 (0.69-53.84), 3.30 (0.51-626.57), and 1.12 (0.16-9.73) mg/kg/day for BPA, BPS, BPF, and BPAF, respectively. Results suggest a potentially moderate concern for combined risks of activating the ER pathway for toddlers and adults with high dietary exposures. This study presents in vitro-based credible HEDs for the four BPs and represents an advancement in the application of in vitro-in silico-based alternative approaches in human health risk assessment.
引用
收藏
页数:13
相关论文
共 62 条
  • [1] Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment
    Adeleye, Yeyejide
    Andersen, Melvin
    Clewell, Rebecca
    Davies, Michael
    Dent, Matthew
    Edwards, Sue
    Fowler, Paul
    Malcomber, Sophie
    Nicol, Beate
    Scott, Andrew
    Scott, Sharon
    Sun, Bin
    Westmoreland, Carl
    White, Andrew
    Zhang, Qiang
    Carmichael, Paul L.
    [J]. TOXICOLOGY, 2015, 332 : 102 - 111
  • [3] Developing Context Appropriate Toxicity Testing Approaches Using New Alternative Methods (NAMs)
    Andersen, Melvin E.
    McMullen, Patrick D.
    Phillips, Martin B.
    Yoon, Miyoung
    Pendse, Salil N.
    Clewell, Harvey J.
    Hartman, Jessica K.
    Moreau, Marjory
    Becker, Richard A.
    Clewell, Rebecca A.
    [J]. ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION, 2019, 36 (04) : 523 - 534
  • [4] Bisphenol A Analogues in Food and Their Hormonal and Obesogenic Effects: A Review
    Andujar, Natalia
    Galvez-Ontiveros, Yolanda
    Zafra-Gomez, Alberto
    Rodrigo, Lourdes
    Jesus Alvarez-Cubero, Maria
    Aguilera, Margarita
    Monteagudo, Celia
    Rivas, Ana
    [J]. NUTRIENTS, 2019, 11 (09)
  • [5] [Anonymous], 2014, Bisphenol A (BPA): Use in Food Contact Application
  • [6] In vitro to in vivo extrapolation for high throughput prioritization and decision making
    Bell, Shannon M.
    Chang, Xiaoqing
    Wambaugh, John F.
    Allen, David G.
    Bartels, Mike
    Brouwer, Kim L. R.
    Casey, Warren M.
    Choksi, Neepa
    Ferguson, Stephen S.
    Fraczkiewicz, Grazyna
    Jarabek, Annie M.
    Ke, Alice
    Lumen, Annie
    Lynn, Scott G.
    Paini, Alicia
    Price, Paul S.
    Ring, Caroline
    Simon, Ted W.
    Sipes, Nisha S.
    Sprankle, Catherine S.
    Strickland, Judy
    Troutman, John
    Wetmore, Barbara A.
    Kleinstreuer, Nicole C.
    [J]. TOXICOLOGY IN VITRO, 2018, 47 : 213 - 227
  • [7] Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review
    Chen, Da
    Kannan, Kurunthachalam
    Tan, Hongli
    Zheng, Zhengui
    Feng, Yong-Lai
    Wu, Yan
    Widelka, Margaret
    [J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY, 2016, 50 (11) : 5438 - 5453
  • [8] Probabilistic human health risk assessment of perfluorooctane sulfonate (PFOS) by integrating in vitro, in vivo toxicity, and human epidemiological studies using a Bayesian-based dose-response assessment coupled with physiologically based pharmacokinetic (PBPK) modeling approach
    Chou, Wei-Chun
    Lin, Zhoumeng
    [J]. ENVIRONMENT INTERNATIONAL, 2020, 137
  • [9] From bisphenol A to bisphenol F and a ban of mustard due to chronic low-dose exposures?
    Dietrich, Daniel R.
    Hengstler, Jan G.
    [J]. ARCHIVES OF TOXICOLOGY, 2016, 90 (02) : 489 - 491
  • [10] ECHA (European Chemicals Agency), 2020, INF CHEM