4 / 46
Notes:
Volume 2
Journal of Environmental Research
Page 51
JOINT EVENT
July 26-27, 2018 Rome, Italy
&
6
th
Edition of International Conference on
Water Pollution & Sewage Management
4
th
International Conference on
Pollution Control & Sustainable Environment
Development and evaluation of PBPK model of perfluorodecanoic acid: Application to human
exposure assessment
Yong Bok Lee
1
and
Hea Young Cho
2
1
Chonnam National University, South Korea
2
CHA University, South Korea
T
he aim of present study was to develop a physiologically-based pharmacokinetic (PBPK) model of perfluorodecanoic acid
(PFDA) in rats for applying its human exposure assessment. We constructed the PBPK model based on
in vivo
study after
the oral or intravenous administration of PFDA in female rats (at dose of 1 mg/kg). The biological samples consisted of plasma,
nine tissues (kidney, liver, lung, heart, spleen, adipose tissue, muscle, GI tract, and brain), urine, and feces were analyzed using
UPLC-MS/MS with liquid-liquid extraction after protein precipitation. The PBPK model was fitted and simulated as changing
the key parameters such as the transporter maximum (Tm), the transporter affinity constant (Kt), the rate constant to storage
compartment (Kst), and the urinary elimination rate constant (Ku). The tissue-plasma partition coefficient was the highest
in the liver (0.607), followed by kidney (0.233), lung (0.100), and spleen (0.052). The model simulation was fitted well with
the observed values. The parameters of T
m
, K
t
, K
st
, and K
u
were 199.5 µg/h, 201.5 µg/L, 0.19 h
-1
, and 0.13 h
-1
, respectively. A
PBPK model was extrapolated to humans by taking the interspecies differences in physiological parameters into account. The
reference dose of 22.98 µg/kg/day and external dose of 5.54 ng/kg/day for human risk assessment were estimated using Korean
biomonitoring values. The developed PBPK model in rats can be a foundation for the development of human model for PFDA
and used as a tool in assessing human exposure of PFDA.
Biography
Yong Bok Lee is currently a Professor of the College of Pharmacy, the former Vice-President of Chonnam National University and the Ex-President of The Korean
Society of Pharmaceutical Sciences and Technology. He received his PhD degree in Pharmaceutics from Seoul National University. His research interests are
focused on the lymphatic delivery of immunosuppressants and the application of population PK/PD models associated with genetic differences in drug transporters
and enzymes. He won many prestigious awards and honors including the KSPs Progress Prize and Academic Prize, the KFDC Academic Prize, the CNU Yongbong
Academic Prize and the MEST official commendation.
leeyb@chonnam.ac.krYong Bok Lee et al., J Environ Res 2018, Volume: 2