PMID- 19337526
OWN - NLM
STAT- MEDLINE
DCOM- 20090716
LR  - 20240419
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 117
IP  - 3
DP  - 2009 Mar
TI  - A physiologically based pharmacokinetic model for the assessment of infant 
      exposure to persistent organic pollutants in epidemiologic studies.
PG  - 481-7
LID - 10.1289/ehp.0800047 [doi]
AB  - BACKGROUND: It has been suggested that pre- and postnatal exposure to persistent 
      organic pollutants (POPs) can promote several adverse effects in children, such 
      as altered neurodevelopment. Epidemiologic studies to date have relied on the 
      analysis of biological samples drawn pre- or post-natally for exposure 
      assessment, an approach that might not capture some key events in the 
      toxicokinetics of POPs. OBJECTIVES: We aimed to build a generic physiologically 
      based pharmacokinetic (PBPK) modeling framework for neutral POPs to assess infant 
      toxicokinetic profiles and to validate the model using data on POP levels 
      measured in mothers and infants from a Northern Quebec Inuit population. METHODS: 
      The PBPK model developed herein was based upon a previously published model to 
      which an infant submodel was added. Using the model and maternal blood levels at 
      the time of delivery, exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene 
      (p,p'-DDE), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), 
      hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), 
      2,2',3,4,4',5'-hexachlorobiphenyl (PCB-138), 2,2',4,4',5,5'-hexachlorobiphenyl 
      (PCB-153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB-180) in mothers was 
      estimated to subsequently simulate infant blood, breast milk, and cord blood POP 
      concentration. Simulations were then compared with corresponding measured levels 
      through Spearman correlation analyses. RESULTS: Predictions were highly 
      correlated with measured concentrations for PCB-153, PCB-180, PCB-138, HCB, and 
      p,p'-DDE (r = 0.83-0.96). Weaker correlations were observed for p,p'-DDT and 
      beta-HCH for which levels were near the limits of detection. CONCLUSION: This is 
      the first study to validate a PBPK model of POPs in infants on an individual 
      basis. This approach will reduce sampling efforts and enable the use of 
      individualized POP toxicokinetic profiles in the epidemiologic studies of POP 
      adverse effects on child development.
FAU - Verner, Marc-Andre
AU  - Verner MA
AD  - Departement des sciences biologiques, Centre Toxen, Universite du Quebec a 
      Montreal, and Centre de recherche du Hospitalier Universitaire de Quebec, 
      Montreal, Quebec, Canada.
FAU - Ayotte, Pierre
AU  - Ayotte P
FAU - Muckle, Gina
AU  - Muckle G
FAU - Charbonneau, Michel
AU  - Charbonneau M
FAU - Haddad, Sami
AU  - Haddad S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081110
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Environmental Pollutants)
RN  - 0 (Organic Chemicals)
SB  - IM
EIN - Environ Health Perspect. 2013 Jul;121(7):A209
MH  - Adult
MH  - Computer Simulation
MH  - Environmental Pollutants/blood/*pharmacokinetics
MH  - *Epidemiologic Methods
MH  - Female
MH  - Humans
MH  - Infant
MH  - Inuit
MH  - *Maternal Exposure
MH  - *Models, Biological
MH  - Organic Chemicals/blood/*pharmacokinetics
MH  - Quebec
PMC - PMC2661921
OTO - NOTNLM
OT  - epidemiology
OT  - exposure assessment
OT  - infants
OT  - persistent organic pollutants
OT  - physiologically based pharmacokinetic modeling
EDAT- 2009/04/02 09:00
MHDA- 2009/07/17 09:00
PMCR- 2009/03/01
CRDT- 2009/04/02 09:00
PHST- 2008/07/28 00:00 [received]
PHST- 2008/11/10 00:00 [accepted]
PHST- 2009/04/02 09:00 [entrez]
PHST- 2009/04/02 09:00 [pubmed]
PHST- 2009/07/17 09:00 [medline]
PHST- 2009/03/01 00:00 [pmc-release]
AID - ehp-117-481 [pii]
AID - 10.1289/ehp.0800047 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2009 Mar;117(3):481-7. doi: 10.1289/ehp.0800047. Epub 
      2008 Nov 10.