PMID- 30024383
OWN - NLM
STAT- MEDLINE
DCOM- 20190329
LR  - 20190329
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 126
IP  - 7
DP  - 2018 Jul
TI  - Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic 
      Arsenic Exposure Using Data from Two Diverse Human Populations.
PG  - 077004
LID - 10.1289/EHP3096 [doi]
LID - 077004
AB  - BACKGROUND: Multiple epidemiological studies exist for some of the well-studied 
      health endpoints associated with inorganic arsenic (iAs) exposure; however, 
      results are usually expressed in terms of different exposure/dose metrics. 
      Physiologically based pharmacokinetic (PBPK) models may be used to obtain a 
      common exposure metric for application in dose-response meta-analysis. OBJECTIVE: 
      A previously published PBPK model for inorganic arsenic (iAs) was evaluated using 
      data sets for arsenic-exposed populations from Bangladesh and the United States. 
      METHODS: The first data set was provided by the Health Effects of Arsenic 
      Longitudinal Study cohort in Bangladesh. The second data set was provided by a 
      study conducted in Churchill County, Nevada, USA. The PBPK model consisted of 
      submodels describing the absorption, distribution, metabolism and excretion 
      (ADME) of iAs and its metabolites monomethylarsenic (MMA) and dimethylarsenic 
      (DMA) acids. The model was used to estimate total arsenic levels in urine in 
      response to oral ingestion of iAs. To compare predictions of the PBPK model 
      against observations, urinary arsenic concentration and creatinine-adjusted 
      urinary arsenic concentration were simulated. As part of the evaluation, both 
      water and dietary intakes of arsenic were estimated and used to generate the 
      associated urine concentrations of the chemical in exposed populations. RESULTS: 
      When arsenic intake from water alone was considered, the results of the PBPK 
      model underpredicted urinary arsenic concentrations for individuals with low 
      levels of arsenic in drinking water and slightly overpredicted urinary arsenic 
      concentrations in individuals with higher levels of arsenic in drinking water. 
      When population-specific estimates of dietary intakes of iAs were included in 
      exposures, the predictive value of the PBPK model was markedly improved, 
      particularly at lower levels of arsenic intake. CONCLUSIONS: Evaluations of this 
      PBPK model illustrate its adequacy and usefulness for oral exposure 
      reconstructions in human health risk assessment, particularly in individuals who 
      are exposed to relatively low levels of arsenic in water or food. 
      https://doi.org/10.1289/EHP3096.
FAU - El-Masri, Hisham A
AU  - El-Masri HA
AD  - National Health and Environmental Effects Research Laboratory, Office of Research 
      and Development (ORD), U.S. Environmental Protection Agency (EPA), Durham, North 
      Carolina, USA.
FAU - Hong, Tao
AU  - Hong T
AD  - ICF International, Inc., Durham, North Carolina, USA.
FAU - Henning, Cara
AU  - Henning C
AD  - ICF International, Inc., Durham, North Carolina, USA.
FAU - Mendez, William Jr
AU  - Mendez W Jr
AD  - ICF International Inc., Fairfax, Virginia, USA.
FAU - Hudgens, Edward E
AU  - Hudgens EE
AD  - National Health and Environmental Effects Research Laboratory, Office of Research 
      and Development (ORD), U.S. Environmental Protection Agency (EPA), Durham, North 
      Carolina, USA.
FAU - Thomas, David J
AU  - Thomas DJ
AD  - National Health and Environmental Effects Research Laboratory, Office of Research 
      and Development (ORD), U.S. Environmental Protection Agency (EPA), Durham, North 
      Carolina, USA.
FAU - Lee, Janice S
AU  - Lee JS
AD  - National Center for Environmental Assessment, ORD, EPA, Durham, North Carolina, 
      USA.
LA  - eng
GR  - P42 ES010349/ES/NIEHS NIH HHS/United States
GR  - R24 ES028532/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20180716
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Arsenicals)
RN  - 0 (Drinking Water)
RN  - 0 (Water Pollutants, Chemical)
RN  - N712M78A8G (Arsenic)
SB  - IM
EIN - Environ Health Perspect. 2018 Sep;126(9):99002. PMID: 30392381
MH  - Adult
MH  - Aged
MH  - Arsenic/*pharmacokinetics/urine
MH  - Arsenicals/*pharmacokinetics/urine
MH  - Bangladesh
MH  - Drinking Water/analysis
MH  - Environmental Exposure/*analysis
MH  - Female
MH  - Food Contamination/analysis
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Models, Theoretical
MH  - Nevada
MH  - Risk Assessment
MH  - Water Pollutants, Chemical/*pharmacokinetics/urine
MH  - Young Adult
PMC - PMC6108830
EDAT- 2018/07/20 06:00
MHDA- 2019/03/30 06:00
PMCR- 2018/07/16
CRDT- 2018/07/20 06:00
PHST- 2017/11/13 00:00 [received]
PHST- 2018/05/24 00:00 [revised]
PHST- 2018/06/08 00:00 [accepted]
PHST- 2018/07/20 06:00 [entrez]
PHST- 2018/07/20 06:00 [pubmed]
PHST- 2019/03/30 06:00 [medline]
PHST- 2018/07/16 00:00 [pmc-release]
AID - EHP3096 [pii]
AID - 10.1289/EHP3096 [doi]
PST - epublish
SO  - Environ Health Perspect. 2018 Jul 16;126(7):077004. doi: 10.1289/EHP3096. 
      eCollection 2018 Jul.