• Je něco špatně v tomto záznamu ?

Consensus toxicity factors for polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls combining in silico models and extensive in vitro screening of AhR-mediated effects in human and rodent cells

M. Larsson, M. van den Berg, P. Brenerová, MB. van Duursen, KI. van Ede, C. Lohr, S. Luecke-Johansson, M. Machala, S. Neser, K. Pěnčíková, L. Poellinger, D. Schrenk, S. Strapáčová, J. Vondráček, PL. Andersson,

. 2015 ; 28 (4) : 641-50. [pub] 20150213

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc16010580

Consensus toxicity factors (CTFs) were developed as a novel approach to establish toxicity factors for risk assessment of dioxin-like compounds (DLCs). Eighteen polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs), and biphenyls (PCBs) with assigned World Health Organization toxic equivalency factors (WHO-TEFs) and two additional PCBs were screened in 17 human and rodent bioassays to assess their induction of aryl hydrocarbon receptor-related responses. For each bioassay and compound, relative effect potency values (REPs) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin were calculated and analyzed. The responses in the human and rodent cell bioassays generally differed. Most notably, the human cell models responded only weakly to PCBs, with 3,3',4,4',5-pentachlorobiphenyl (PCB126) being the only PCB that frequently evoked sufficiently strong responses in human cells to permit us to calculate REP values. Calculated REPs for PCB126 were more than 30 times lower than the WHO-TEF value for PCB126. CTFs were calculated using score and loading vectors from a principal component analysis to establish the ranking of the compounds and, by rescaling, also to provide numerical differences between the different congeners corresponding to the TEF scheme. The CTFs were based on rat and human bioassay data and indicated a significant deviation for PCBs but also for certain PCDD/Fs from the WHO-TEF values. The human CTFs for 2,3,4,7,8-pentachlorodibenzofuran, 1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, and 1,2,3,4,7,8,9-heptachlorodibenzofuran were up to 10 times greater than their WHO-TEF values. Quantitative structure-activity relationship models were used to predict CTFs for untested WHO-TEF compounds, suggesting that the WHO-TEF value for 1,2,3,7,8-pentachlorodibenzofuran could be underestimated by an order of magnitude for both human and rodent models. Our results indicate that the CTF approach provides a powerful tool for condensing data from batteries of screening tests using compounds with similar mechanisms of action, which can be used to improve risk assessment of DLCs.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc16010580
003      
CZ-PrNML
005      
20160414103532.0
007      
ta
008      
160408s2015 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1021/tx500434j $2 doi
024    7_
$a 10.1021/tx500434j $2 doi
035    __
$a (PubMed)25654323
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Larsson, Malin $u †Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
245    10
$a Consensus toxicity factors for polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls combining in silico models and extensive in vitro screening of AhR-mediated effects in human and rodent cells / $c M. Larsson, M. van den Berg, P. Brenerová, MB. van Duursen, KI. van Ede, C. Lohr, S. Luecke-Johansson, M. Machala, S. Neser, K. Pěnčíková, L. Poellinger, D. Schrenk, S. Strapáčová, J. Vondráček, PL. Andersson,
520    9_
$a Consensus toxicity factors (CTFs) were developed as a novel approach to establish toxicity factors for risk assessment of dioxin-like compounds (DLCs). Eighteen polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs), and biphenyls (PCBs) with assigned World Health Organization toxic equivalency factors (WHO-TEFs) and two additional PCBs were screened in 17 human and rodent bioassays to assess their induction of aryl hydrocarbon receptor-related responses. For each bioassay and compound, relative effect potency values (REPs) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin were calculated and analyzed. The responses in the human and rodent cell bioassays generally differed. Most notably, the human cell models responded only weakly to PCBs, with 3,3',4,4',5-pentachlorobiphenyl (PCB126) being the only PCB that frequently evoked sufficiently strong responses in human cells to permit us to calculate REP values. Calculated REPs for PCB126 were more than 30 times lower than the WHO-TEF value for PCB126. CTFs were calculated using score and loading vectors from a principal component analysis to establish the ranking of the compounds and, by rescaling, also to provide numerical differences between the different congeners corresponding to the TEF scheme. The CTFs were based on rat and human bioassay data and indicated a significant deviation for PCBs but also for certain PCDD/Fs from the WHO-TEF values. The human CTFs for 2,3,4,7,8-pentachlorodibenzofuran, 1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, and 1,2,3,4,7,8,9-heptachlorodibenzofuran were up to 10 times greater than their WHO-TEF values. Quantitative structure-activity relationship models were used to predict CTFs for untested WHO-TEF compounds, suggesting that the WHO-TEF value for 1,2,3,7,8-pentachlorodibenzofuran could be underestimated by an order of magnitude for both human and rodent models. Our results indicate that the CTF approach provides a powerful tool for condensing data from batteries of screening tests using compounds with similar mechanisms of action, which can be used to improve risk assessment of DLCs.
650    _2
$a zvířata $7 D000818
650    _2
$a benzofurany $x chemie $x toxicita $7 D001572
650    _2
$a počítačová simulace $7 D003198
650    _2
$a lidé $7 D006801
650    _2
$a techniky in vitro $7 D066298
650    _2
$a polychlorované bifenyly $x chemie $x toxicita $7 D011078
650    _2
$a kvantitativní vztahy mezi strukturou a aktivitou $7 D021281
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a receptory aromatických uhlovodíků $x fyziologie $7 D018336
650    _2
$a hlodavci $7 D012377
650    _2
$a polychlorované dibenzodioxiny $x analogy a deriváty $x chemie $x toxicita $7 D000072317
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a van den Berg, Martin $u ‡Endocrine Toxicology Group, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, NL-3508 TD Utrecht, The Netherlands.
700    1_
$a Brenerová, Petra $u #Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno, Czech Republic.
700    1_
$a van Duursen, Majorie B M $u ‡Endocrine Toxicology Group, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, NL-3508 TD Utrecht, The Netherlands.
700    1_
$a van Ede, Karin I $u ‡Endocrine Toxicology Group, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, NL-3508 TD Utrecht, The Netherlands.
700    1_
$a Lohr, Christiane $u ⊥Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Kaiserslautern 67663, Germany.
700    1_
$a Luecke-Johansson, Sandra $u §Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
700    1_
$a Machala, Miroslav $u #Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno, Czech Republic.
700    1_
$a Neser, Sylke $u ⊥Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Kaiserslautern 67663, Germany.
700    1_
$a Pěnčíková, Kateřina $u #Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno, Czech Republic.
700    1_
$a Poellinger, Lorenz $u §Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
700    1_
$a Schrenk, Dieter $u ⊥Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Kaiserslautern 67663, Germany.
700    1_
$a Strapáčová, Simona $u #Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno, Czech Republic.
700    1_
$a Vondráček, Jan $u #Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno, Czech Republic. ∥Department of Cytokinetics, Institute of Biophysics AS CR, 612 65 Brno, Czech Republic.
700    1_
$a Andersson, Patrik L $u †Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden. $7 gn_A_00006215
773    0_
$w MED00002106 $t Chemical research in toxicology $x 1520-5010 $g Roč. 28, č. 4 (2015), s. 641-50
856    41
$u https://pubmed.ncbi.nlm.nih.gov/25654323 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20160408 $b ABA008
991    __
$a 20160414103616 $b ABA008
999    __
$a ok $b bmc $g 1114009 $s 934948
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2015 $b 28 $c 4 $d 641-50 $e 20150213 $i 1520-5010 $m Chemical research in toxicology $n Chem Res Toxicol $x MED00002106
LZP    __
$a Pubmed-20160408
Zpět

Najít záznam

Citační ukazatele

Možnosti archivace