1. Paper review 2015.01.07 MIYEON SHIN

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3. Intro- 1.PBDEs have been banned in several countries. 2.There are sig. corr b/w intake of food and body burdens (USA, North EU etc). 3.No association between two var. in Swedish women. 4.Blood conc. >> 3 ?

4. Intro- 5. Indoor dust??? (UK, Singapore, Canada) 6. More susceptible in Child than adult 7. Other uncertainties (Estimating exposure from dust); Bioavailability 8. Usually Bioav.of PBDEs is assumed to be 100%. 4

5. Intro- 10. 5 Subchronic low-level exposures (21 days) ADME Compare b/w groups Retained PBDEs Excreted PBDEs Retained PBDEs Bioav. by congener

6. Materials and Methods 6 Sac. Time Dust Low (4 rats) 24 h after last feeding High (4 rats) Corn Oil Low (4 rats) High (13 rats) 3 rats (3 day), 3 rats (7 day), 3 rats (14 day), 4 rats (24 h after last feeding) Total 29 rats To investigate steady state time point

7. Daily intake amount 7

8. Collected samples Epididymal fat Liver (for both bioav. And mRNA assay) Kidney Brain GI tract Remaining carcass Feces (daily) & Fecal pellets in GI tract Urine (4 day intervals) 8 Materials and Methods

9. Analysis (1) Tissues, feces and urine were homogenized and spiked with ten 13 C-labeled recovery standards and extracted. Rat chow, NIST dust, corn oil were extracted. DE-71, DE79 and DE83R was also analyzed. High resolution GC/MS Column: DB5-MS (30m) 9 Materials and Methods

10. Analysis (2) Hydroxylated metabolites from the feces were analyzed by a GC/MS method as MeO-PBDEs (tetra- to hexa BDEs). To investigate gene expression of Cyp2b1 and Cyp2b, RT-PCR was performed (ABI Prism 7700). 10 Materials and Methods

11. Calculation (3) Bioconcentration factors (BCFs) - ratio b/w conc. in tissues and in diet. Statistical- -ANOVA (var 1:vehicle, var 2: dose, dependent var: PBDE level) -1way ANOVA for Steady state (compare among sac. days). 11 Materials and Methods

12. Results and Discussion Dose level (low and high) were studied to determine uptake degree. Determine enzyme modulation at relatively low levels (7-9 p.p.b, slightly above the ave.conc. in other countries for salmon and breast milk) 12

13. Dosed amount/Steady state The rat chow had measurable amounts of several PBDEs leading to body burdens in the control rat tissues. ->subtracted from the dosed rat levels To explore the steady state, epididymal fat was analyzed (3, 7, 14 and 21 days). 13 Results and Discussion

14. BCFs 14 Results and Discussion 1) Epididymal fat 2) Liver Tri- to hexa BDE Hepta- to Deca BDE

15. Conclusion (1) No differences in BCFs were consistently observed for either the high- or low-dose levels or the dust or corn oil dose vehicles; - the majority of PBDEs concentrate to similar degree in rat tissues after injestion of either dust or oil over the given dose range. 15 Results and Discussion

16. Cytochrome P450 (Cyp) 16 Results and Discussion

17. 17 Results and Discussion

18. Debromination There is a sig. degradation mechanism for BDE99, 183, 209 in fish species. But minor mechanism in rats. -> Because they used PBDE mixture in their study, it Is impossible to investigate about PBDE debromination. 18 Results and Discussion

19. Absorption Absorption was investigated in a manner that accounts for these metabolic transformations. Fecal excretion was the major route of elimination 19 Results and Discussion

20. 20 Results and Discussion

21. Metabolism difference Feces were analyzed for monohydroxylated BDEs. 4’-MeO-BDE49 (0.3 % of the total tetra- to hexa-BDE dose), 4’MeO-BDE-101 (0.5 % of the total tetra- to hexa-BDE dose), a methoxy-hexaBDE (0.1 %) No difference in the % between two high dose groups (p>0.05) 21 Results and Discussion

22. Other The mechanism of formation and the characterization of these bound residues are unknown. The involvement of enzyme systems other than those investigated in this study or gut microbial metabolism of PBDEs may also be of significance (CYP isozymes, mercapturic acid pathway enzimes, or deiodinases etc.). 22 Results and Discussion

23. Grand conclusion PBDEs in dust bioconcentrate into rat tissues to the same or greater degree as PBDE administered in an oil matrix. -> Household dust is a likely source of PBDE intake and must be taken into account when human exposure assessment. 23 Results and Discussion

24. Thank you for listening! 24