PMID- 27161441
OWN - NLM
STAT- MEDLINE
DCOM- 20170220
LR  - 20181113
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 90
IP  - 6
DP  - 2016 Jun
TI  - Evaluation of relative effect potencies (REPs) for dioxin-like compounds to 
      derive systemic or human-specific TEFs to improve human risk assessment.
PG  - 1293-305
LID - 10.1007/s00204-016-1724-9 [doi]
AB  - Toxic equivalency factors (TEFs) are generally applied for estimating human risk 
      of dioxins and dioxin-like compounds using systemic (e.g., blood) levels, even 
      though these TEFs are established based on intake doses in rodent studies. This 
      review shows that systemic relative effect potencies (REPs) can deviate 
      substantially from intake REPs, but are similar to in vitro-derived REPs. 
      Interestingly, the in vitro REPs for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin 
      (HpCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) are up to one order of 
      magnitude higher than their in vivo REPs and WHO-TEFs, based on oral intake. In 
      addition, clear species-differences in in vitro REPs were apparent for some 
      congeners. Especially the human-derived REP for polychlorinated biphenyl 126 is 
      one to two orders of magnitude lower than rodent REPs and its current WHO-TEF. 
      Next, suggested adapted systemic or human-specific TEFs for these congeners were 
      applied to calculate changes in systemic TEQ concentrations in studies from the 
      USA, Germany and Japan and compared with either the JECFA TDI or USEPA RfD of 
      TCDD. Overall, the effect of such TEF changes for these three congeners on total 
      TEQ roughly balances each other out in the general population. However, results 
      may be different for situations in which a specific group of congeners dominates. 
      For those congeners that show a distinct deviation between either intake and 
      systemic REPs or between rodent- and human-based in vitro REPs, we propose that 
      especially REPs derived from human-based in vitro models are weighted more 
      heavily in establishing systemic or human-specific TEF values to improve human 
      health risk assessment.
FAU - van Ede, Karin I
AU  - van Ede KI
AD  - Division of Toxicology and Veterinary Pharmacology, Institute for Risk Assessment 
      Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The 
      Netherlands. k.i.vanede@uu.nl.
FAU - van Duursen, Majorie B M
AU  - van Duursen MB
AD  - Division of Toxicology and Veterinary Pharmacology, Institute for Risk Assessment 
      Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The 
      Netherlands.
FAU - van den Berg, Martin
AU  - van den Berg M
AD  - Division of Toxicology and Veterinary Pharmacology, Institute for Risk Assessment 
      Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160509
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Dioxins and Dioxin-like Compounds)
RN  - 0 (Hazardous Substances)
SB  - IM
MH  - Animals
MH  - Dioxins and Dioxin-like Compounds/chemistry/*toxicity
MH  - Environmental Exposure/*analysis
MH  - Hazardous Substances/chemistry/*toxicity
MH  - Humans
MH  - Models, Theoretical
MH  - Risk Assessment
MH  - Species Specificity
PMC - PMC4873528
OTO - NOTNLM
OT  - Dibenzofurans
OT  - Dioxins
OT  - Human risk assessment
OT  - PCBs
OT  - TEF-concept
EDAT- 2016/05/11 06:00
MHDA- 2017/08/18 06:00
PMCR- 2016/05/09
CRDT- 2016/05/11 06:00
PHST- 2016/02/09 00:00 [received]
PHST- 2016/04/21 00:00 [accepted]
PHST- 2016/05/11 06:00 [entrez]
PHST- 2016/05/11 06:00 [pubmed]
PHST- 2017/08/18 06:00 [medline]
PHST- 2016/05/09 00:00 [pmc-release]
AID - 10.1007/s00204-016-1724-9 [pii]
AID - 1724 [pii]
AID - 10.1007/s00204-016-1724-9 [doi]
PST - ppublish
SO  - Arch Toxicol. 2016 Jun;90(6):1293-305. doi: 10.1007/s00204-016-1724-9. Epub 2016 
      May 9.