IEG 환경지질연구정보센터

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(1)]æ~>Æ·~ã²æ. òY. Vol. 9, No. 1, pp. 28~38, 2004. `"æ~ æ~>ÒÏö* F¾ Ê.~ W«Âö & ÿ£Ò Î~ ®{ 9 ª+. Bç& Á*^ Á;æ ÁFê ÁFÿR Á·æö 1. 2. 1. 1. 3. 1. "8Fö «z" ~ãö. LG ~ãn*ö ö¶K². 1. 2. 3. Uncertainty Analysis of a Pharmacokinetic Modeling for Inhalation Exposure of Benzene from the Use of Groundwater at Dwelling. Á. Á. Á. Á. Á. Sang-Joon Kim1 Hyun-Ho Lee2 Ji-Yeon Park1 You-Jin Lee1 Donghan Yu3 Ji-Won Yang1 1. Environmental Remediation Engineering Laboratory, Department of Chemical and Biomolecular Engineering, KAIST 2 LG Institute of Environment, Safety & Health 3 Korea Atomic Energy Institute. ABSTRACT This study presents the result of uncertainty and sensitivity analysis of a pharmacokinetic model which describes the distribution and removal of benzene at each organ when an indivisual inhales indoor contaminated air with benzene originated from groundwater. The pharmacokinetic model simulates the distribution of benzene deposited in organs of human body through inhalation of contaminated indoor air as well as degradation-metabolism in liver. This study focused on the uncertainty problem induced from the use of the single values for blood flow, partition coefficient, degradation constant, volume, etc. of each organ which was due to a lack of knowledge about these parameters or their measurements. To solve this problem, uncertainty analysis on the pharmacokinetic model was conducted simultaneously which would help understanding the risk assessment associated with VOCs. Key words : Indoor air pollution, Benzene, Physiologically based pharmacokinetic model, Uncertainty analysis, Sensitivity analysis. º £ ^. º æ~>¦V F¾ ÊF Ú8ö >B>Ú ^j Û~ Úö F«Fr ' Ë8ö ª

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(14) /. ªVç>ö çw~ ; ." B*' 2.2.. 12). ERinhal(t) = [OFs(t)Cs(t) + OFa(t)Ca(t)]BR(t). (3). VB ER(exposure rate, ng/hr)f * J"b~ Â ï, OF(occupancy factor, *ìr)º B ‘ ò ’ _f ‘ <~ ÷n’ö *~~ ®j &ËW ¯, 6FN j ~ . .¢ Ú, ò¢ B 7f 8 Òö zË j 10ª ÿn ÒÏ r OF º 0.167(=10/ 60) OF º 0.833(=1-OF )~ 8j <æò ß® ÿ' £Ò ÎöBº B' *ö ²Ö~º «" ÊF ³ê¢ ÒÏ~² >æ ÿ¢ ãÖö &B OF º 7 f 8 Ò~ ;ê 10ª ÿnò 1~ 8j &æ r OF º 0(=1-OF )~ 8j <º . ÚÂ Îj Ï ÿ' ÎÒ¢ Matlab-simulinkj Ï ~ >¯~& . BR(breath rate)f * ^ï W êö V¢ ÿçö V¢ 8j 'Ï~& . Fig. 2º B ~ ÿn «~º ÊF~ Â³ê s. a. s. s. a. s. Fig. 2. Inhalation rate of benzene in base case. Journal of KoSSGE Vol. 9, No. 1, pp. 28~38, 2004. 8). Fig. 3. Conceptual representation of PBPK model for benzene (f: adipose tissue, s: slowly perfused tissues, r: rapidly perfused tissues, and l: liver)..

(15) `"æ~ æ~>ÒÏö* F¾ Ê.~ W«Âö & ÿ£Ò Î~ ®{ 9 ª+. 31. Table 1. Compartment and parameter definitions for PBPK model8). Table 2. Physiological parameters used in PBPK model for benzene18,12). Abbreviation Definition Cin Concentration in air inhaled Ca Concentration in alveolar air Cexh Measured concentration in expired breath Qa Alveolar ventilation rate Qb Cardiac output Pb Blood/air partition coefficient Ba Arterial blood concentration Venous blood concentration B Am Amount metabolized in liver Qi Blood flow rate to compartment i Vi Volume of compartment i Ci Concentration in compartment i Bi Concentration in venous blood leaving compartment i Ai Amount in compartment i Pi Tissue/blood partition coefficient for compartment i Vmax Maximum metabolic rate Km Michaelis constant. Parameters Values Alveolar ventilation rate (L/min) active inactive Man (65.42 kg) 796.2 442.8 Woman (54.66 kg) 529.2 330.6 Cardiac output (L/hr) 390 Blood flow rate (fraction of cardiac output) Fat 0.05 Slowly perfused tissues 0.25 Richly perfused tissues 0.44 Liver 0.26 Volume (fraction of body weight) Fat 0.19 Slowly perfused tissues 0.62 Richly perfused tissues 0.05 Liver 0.026 Partition coefficient Blood:air 7.4 Fat:air 406.0 SPT:air 15.0 RPT:air 11.0 Liver:air 11.0 Metabolic constant 17.1 Vmax (mg/h/kg) 0.35 Km (mg/L). ï;çö ®º ©b &;~& . (4)º æO^

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(19) 32. BçÁ*^Á;æÁFêÁFÿÁ·æö. Fig. 4. Profile distribution of benzene concentration in blood stream leaving from each organ derived from uncertainty analysis of 24 hrsimulation. Journal of KoSSGE Vol. 9, No. 1, pp. 28~38, 2004.

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(32) ~ ; .~ ÊF³êº ¦¾" *Ú æ pº . >ö SPT, RPT,. Fig. 5. Profile distribution of benzene removed by metabolization and exhalation from 24 hr-simulation. Journal of KoSSGE Vol. 9, No. 1, pp. 28~38, 2004.

(33) 34. Bç&Á*^Á;æÁFêÁFÿÁ·æö. Fig. 6. Profile distribution of benzene concentration in blood stream leaving from each organ derived from uncertainty analysis of 12 dayssimulation. Journal of KoSSGE Vol. 9, No. 1, pp. 28~38, 2004.

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(58) BçÁ*^Á;æÁFêÁFÿÁ·æö. 36. Fig. 8. Profile distribution of benzene removed by metabolization and exhalation from 12 days-simulation.. öBº &Ë z® ÒÏ>º Spearman rank-order correlation j Ï~&b r" ? ;~B . 6 ∑ (xi – yi ) ρ=1 –---------------------------2 n( n –1 ) 2. (11). VB x , y º X, Y æ>~ i®~ B*(rank) n f þ2~ >¢ ~ . -² áÚê ρ 8f −1öB 1ræ æ~º −1ö &rÖ r~ ç&&ê& ®rj ~ . ρ ~ .&8 º ©f «K¶ò~ ®{ W « Ö"~ö 'Ëj "º ©j ~ . V¢B Spearman rank-order correlationj ê ¢ B*z~ « Ö"ö 'Ë j "º 7º«K¶ò ~ B*¢ áj > ® . Fig. 9f B >¯ ®{ WªCÖ"¢ :ûb Î «K¶~ 7ºê¢ Spearman rank-order correlation b R~ " ® . ~ ÿn~ ÂÖ"öB ^(BR)" Michaelis ç>(K )& &Òªf ^VÂ ö Ûb ¸f 7ºê¢ ¾æÚ ® . ^ïf «Â~ Âïö ç7 &ê~º ¶ *ÚBï" i. i. m. Journal of KoSSGE Vol. 9, No. 1, pp. 28~38, 2004. jf~² B . Michaelis ç>º *öB~ ÊF~ &Òª ³êf &ê~² B . ¯ Michaelis ç>8 Ã&~ ò¢ ª³ê& 'Úæ² >æ &Òª(metabolism) fº r~ ç&&ê¢ &æ >& ^VÂ~ 'Ë ² ¾æ¾² >æ ^VÂï"º ·~ ç&&ê¢ <² B . öB ÒÏ ÿ'£Ò Î~ êÖöB Ë V¦bº ªVç>~ *~f B ?bæ ®{ Wj

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