基于贝叶斯的苯并(α)芘PBPK模型优化与健康风险评估应用

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Abstract The physiologically based pharmacokinetic(PBPK) model was used to predict the human internal dose of benzo(α)pyrene(BaP) exposure. The parameters of the model were optimized based on bayes statistics and Markov Chain Monte Carlo simulation (MCMC), and the optimized model was adopted to derive the reference value regarding the internal dose of BaP. It was found that the accuracy of the model was significantly improved after calibrating the posterior parameters by Monte Carlo simulation, and the validation results of two datasets showed that the sums of squared residuals were reduced by 72% and 94%. The PBPK model was based on the pharmacokinetic of BaP and its metabolite 3-hydroxybenzo(α)pyrene(3-OHBaP). The internal concentration distribution of BaP followed the order of fat>kidney>skin>slowly perfused tissue>richly perfused tissue>venous blood>liver, while that of 3-OHBaP was in the order of kidney>richly perfused tissue>fat>lung >venous blood >slowly perfused tissue> liver>skin. Besides, the sensitivity analysis indicated that the rich perfused tissue-blood distribution coefficients showed the strongest influence on the model output, which sensitivity coefficient exceeded 200%. While the coefficients related to excretion showed the weakest influence, and only sensitivity coefficient of glomerular filtration rate K_BR exceeded 1%. According to the reference concentration 2.0×10^-6mg/m³ recommended by U.S. Environmental Protection Agency, the biomonitoring equivalent of BaP was derived based on the optimized PBPK model. The results showed that the reference value for the occupational populations was 0.405pmol/mol creatinine (i.e., the mean concentration of 3-OHBaP in urine), which lays a foundation for the quantitative health risk assessment based on the human internal dose.

Key words： benzo(α)pyrene bayes statistics Markov Chain Monte Carlo(MCMC) physiologically based pharmacokinetic (PBPK) model 3-OHBaP biomonitoring equivalents

Received: 26 September 2021

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X592

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	Articles by authors
	MENG Xiang-hui
	WANG Hong-yang
	SUN Yu-wei
	ZHANG Ming-hui
	ZHU Guang-can
	SHEN Ya-qin
	LIU Hui-fang

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MENG Xiang-hui,WANG Hong-yang,SUN Yu-wei等. Optimization of benzo (α) pyrene PBPK model based on bayes and its application in health risk assessment[J]. CHINA ENVIRONMENTAL SCIENCECE, 2022, 42(5): 2370-2378.

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http://www.zghjkx.com.cn/EN/ OR http://www.zghjkx.com.cn/EN/Y2022/V42/I5/2370

[1]	Kim K H, Jahan S A, Kabir E, et al. A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects [J]. Environment International, 2013,60:71–80.
[2]	Dimitriou K, Kassomenos P. The influence of specific atmospheric circulation types on PM10-bound benzo(a)pyrene inhalation related lung cancer risk in Barcelona, Spain [J]. Environment International, 2018,112:107–114.
[3]	周煜,沈毅,王姝婷,等.杭州市居民谷物和烧烤油炸类食品多环芳烃暴露风险评估 [J]. 预防医学, 2019,31(3):260-264,270. Zhou Y, Shen Y, Wang S T, et al. Risk assessment of polycyclic aromatic hydrocarbons exposed from cereal, fried and grilled food in Hangzhou [J]. Preventive Medicine, 2019,31(3):260-264,270.
[4]	孟祥帅,陈鸿汉,郑从奇,等.焦化厂不同污染源作用下土壤PAHs污染特征 [J]. 中国环境科学, 2020,40(11):4857-4864. Meng X S, Chen H H, Zhen C Q, et al. Pollution characteristics of PAHs in soil at an abandoned coking plant affected by different sources [J]. China Environmental Science, 2020,40(11):4857-4864.
[5]	康杰,胡健,朱兆洲,等.太湖及周边河流表层沉积物中PAHs的分布、来源与风险评价 [J]. 中国环境科学, 2017,37(3):1162-1170. Kang J, Hu J, Zhu Z Z, et al. Distribution, source and risk assessment of PAHs in surface sediments from Taihu Lake and its surrounding rivers [J]. China Environmental Science, 2017,37(3):1162-1170.
[6]	刘晓晨.苯并[a]芘暴露生物标志物的研究 [J]. 大连:大连医科大学, 2013. Liu X C. Study on exposure biomakers of benzo(a)pyrene [D]. Dalian: Dalian Medical University, 2013.
[7]	Richter B S, Dettbarn G, Jessel S, et al. Ultra-high sensitive analysis of 3-hydroxybenzo[a]pyrene in human urine using GC-APLI-MS [J]. Journal of Chromatography B, 2019,1118–1119:187–193.
[8]	Zając J, Dziedzina S, Zając A, et al. Relationship between variants of detoxification genes and 3-hydroxybenzo[a]pyrene concentration in urine of coke plant workers [J]. Polycyclic Aromatic Compounds, 2020,40(1):1–12.
[9]	Fernández S F, Pardo O, Hernández C S, et al. Children’s exposure to polycyclic aromatic hydrocarbons in the Valencian Region (Spain): Urinary levels, predictors of exposure and risk assessment [J]. Environment International, 2021,153:106535.
[10]	Oliveira M, Capelas S, Delerue-Matos C, et al. Grill workers exposure to polycyclic aromatic hydrocarbons: Levels and excretion profiles of the urinary biomarkers [J]. International Journal of Environmental Research and Public Health, 2020,18(1):230.
[11]	EPA, 2019. Guidelines for human exposure assessment [J]. Risk Assessment Forum U.S. Environmental Protection Agency: 223.EPA/ 100/B-19/001.
[12]	侯荣,阿依博塔·吐尔逊别克,秦宁,等.室内空气中苯并[a]芘的健康限值研究 [J]. 中国环境科学, 2020,40(5):434–441. Hou R, Ayibota T, Qin N, et al. Research on benzo[a]pyrene criteria in indoor air [J]. China Environmental Science, 2020,40(5):2287-2294.
[13]	EPA, 2017. Toxicological review of benzo[a]pyrene [R]. Integrated Risk Information System National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency. Washington, DC:EPA/635/R-17/003Fa.
[14]	Louro H, Heinälä M, Bessems J, et al. Human biomonitoring in health risk assessment in Europe: Current practices and recommendations for the future [J]. International Journal of Hygiene and Environmental Health, 2019,222(5):727–737.
[15]	刘远,王中钰,陈景文,等.基于PBPK模型评价三氯乙烯的职业暴露健康风险 [J]. 生态毒理学报, 2019,14(4):83-91. Liu Y, Wang Z Y, Chen J W, et al. Health risk assessment of occupational exposure to trichloroethylene based on PBPK model [J]. Asian Journal of Ecotoxicology, 2019,14(4):83-91.
[16]	Zhang Y, Han X, Niu Z. Health risk assessment of haloacetonitriles in drinking water based on internal dose [J]. Environmental Pollution, 2018,236:899–906.
[17]	Ortiz H R, Maître A, Barbeau D, et al. Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3- hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons [J]. PLoS ONE, 2014,9(7):e102570.
[18]	茆诗松,汤银才.贝叶斯统计 [M]. 2版.北京:中国统计出版社, 2012:237-241. Mao S S, Tang Y C. The Bayesian statistics [M]. 2nd edition. Beijing: China Statistics Press, 2012:237-241.
[19]	Chou W C, Lin Z. Bayesian evaluation of a physiologically based pharmacokinetic (PBPK) model for perfluorooctane sulfonate (PFOS) to characterize the interspecies uncertainty between mice, rats, monkeys, and humans: Development and performance verification [J]. Environment International, 2019,129:408–422.
[20]	Ratier A, Lopes C, Labadie P, et al. A Bayesian framework for estimating parameters of a generic toxicokinetic model for the bioaccumulation of organic chemicals by benthic invertebrates: Proof of concept with PCB153 and two freshwater species [J]. Ecotoxicology and Environmental Safety, 2019,180:33–42.
[21]	宋韬.基于PBPK模型的多环芳烃暴露人群剂量与健康风险研究 [D]. 广州:暨南大学, 2018. Song T. Populational Dose and health risk assessment on polycyclic aromatic hydrocarbons based on PBPK model [D]. Guangzhou: Jinan University, 2018.
[22]	Brown R P, Delp M D, Lindstedt S L, et al. Physiological parameter values for physiologically based pharmacokinetic models [J]. Toxicology and Industrial Health, 1997,13(4):407–484.
[23]	Smith J N, Mehinagic D, Nag S, et al. In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes [J]. Toxicology Letters, 2017,269:23–32.
[24]	Deng L, Liu H, Deng Q. Physiologically-based pharmacokinetic modeling of benzo(a)pyrene and the metabolite in humans of different ages [J]. International Journal of Environmental Health Research, 2019,31(2):202–214.
[25]	Gelman D, Koch C P, Kosloff R. Dissipative quantum dynamics with the surrogate Hamiltonian approach. A comparison between spin and harmonic baths [J]. The Journal of Chemical Physics, 2004,121(2): 661–671.
[26]	Barbeau D, Lutier S, Bonneterre V, et al. Occupational exposure to polycyclic aromatic hydrocarbons: relations between atmospheric mixtures, urinary metabolites and sampling times [J]. International Archives of Occupational and Environmental Health, 2015,88(8): 1119–1129.
[27]	Lin Z, Fisher J W, Ross M K, et al. A physiologically based pharmacokinetic model for atrazine and its main metabolites in the adult male C57BL/6mouse [J]. Toxicology and Applied Pharmacology, 2011,251(1):16–31.
[28]	Pletz J, Blakeman S, Paini A, et al. Physiologically based kinetic (PBK) modelling and human biomonitoring data for mixture risk assessment [J]. Environment International, 2020,143:105978.
[29]	Apel P, Rousselle C, Lange R, et al. Human biomonitoring initiative (HBM4EU) - Strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment [J]. International Journal of Hygiene and Environmental Health, 2020,230:113622.
[30]	刘柳,张岚,李琳,等.健康风险评估研究进展 [J]. 首都公共卫生, 2013,(6):264–268. LIU L, ZHANG L, LI L, et al. Research progress on health risk assessment [J]. Capital Journal of Public Health, 2013,(6):264–268.
[31]	Angerer J, Aylward L L, Hays S M, et al. Human biomonitoring assessment values: Approaches and data requirements [J]. International Journal of Hygiene and Environmental Health, 2011,214 (5):348–360.
[32]	Hays S M, Becker R A, Leung H W, et al. Biomonitoring equivalents: A screening approach for interpreting biomonitoring results from a public health risk perspective [J]. Regulatory Toxicology and Pharmacology, 2007,47(1):96–109.
[33]	Lafontaine M. Polycyclic aromatic hydrocarbon exposure in an artificial shooting target factory: Assessment of 1-hydroxypyrene urinary excretion as a biological indicator of exposure [J]. The Annals of Occupational Hygiene, 2000,44(2):89–100.
[34]	Gendre C, Lafontaine M, Delsaut P, et al. Exposure to polycyclic aromatic hydrocarbons and excretion of urinary 3-hydroxybenzo[a] pyrene: assessment of an appropriate sampling time [J]. Polycyclic Aromatic Compounds, 2004,24(4/5):433–439.
[35]	Kondo K, Wakasone Y, Iijima K, et al. Inverse analysis to estimate site-specific parameters of a mathematical model for simulating pesticide dissipations in paddy test systems [J]. Pest Management Science, 2019,75(6):1594–1605.
[36]	Heredia O R, Bouchard M. Understanding the linked kinetics of benzo(a)pyrene and 3-hydroxybenzo(a)pyrene biomarker of exposure using physiologically-based pharmacokinetic modelling in rats [J]. Journal of Pharmacokinetics and Pharmacodynamics, 2013,40(6):669– 682.
[37]	Péry A R R, Brochot C, Desmots S, et al. Predicting in vivo gene expression in macrophages after exposure to benzo(a)pyrene based on in vitro assays and toxicokinetic/toxicodynamic models [J]. Toxicology Letters, 2011,201(1):8–14.
[38]	张昭勇,欧莉莉,罗嘉莹,等.空气中多环芳烃在人体中的代谢反应及其对吸入性过敏性疾病的影响机制 [J]. 环境卫生学杂志, 2017, 1(v.7):75–80. Zhang Z Y, Ou L L, Luo J Y, et al. Metabolic Response in Human Body to Air Polycyclic Aromatic Hydrocarbons and their Effects on Inhalant Allergic Diseases [J]. Journal of Environmental Hygiene, 2017,1(v.7):75–80.
[39]	Crowell S R, Hanson-Drury S, Williams D E, et al. In vitro metabolism of benzo[a]pyrene and dibenzo[def,p]chrysene in rodent and human hepatic microsomes [J]. Toxicology Letters, 2014,228(1): 48–55.
[40]	Payan J-P, Lafontaine M, Simon P, et al. 3-Hydroxybenzo(a)pyrene as a biomarker of dermal exposure to benzo(a)pyrene [J]. Archives of Toxicology, 2009,83(9):873–883.
[41]	Lutier S, Maître A, Bonneterre V, et al. Urinary elimination kinetics of 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene of workers in a prebake aluminum electrode production plant: Evaluation of diuresis correction methods for routine biological monitoring [J]. Environmental Research, 2016,147:469–479.
[42]	Marie C, Bouchard M, Heredia O R, et al. A toxicokinetic study to elucidate 3-hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats [J]. Journal of Applied Toxicology, 2010,30:402–410.
[43]	Boogaard P J, Hays S M, Aylward L L. Human biomonitoring as a pragmatic tool to support health risk management of chemicals – Examples under the EU REACH programme [J]. Regulatory Toxicology and Pharmacology, 2011,59(1):125–132.