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Table 4 In vitro procedures applied to Pb particles and compared with in vivo data for subsequent calibration (2 pages)

From: Experimental determination of the oral bioavailability and bioaccessibility of lead particles

References Substrate Oral phase Gastric phase Intestinal phase Comparison with in vivo data
Ruby et al. 1993 PBET-GI[55] Mine wastes   1/10 g.mL-1 2 h @ pH 7.0 · In vivo results on rabbits (1 sample): 10.7% (blood based RBA at t = 1 h), and 9±4 % (gastric solubility,t = 1.5 h)
    2 h @ pH 1.3 Pepsin; organic acids; HCl NaHCO3; pancreatin; bile  
Ruby et al. 1996 PBET-GI[74] Mine wastes Residential soils Tailings   1/100 g.mL-1 4 h @ pH 7.0 · In vivo relative Pb bioavailability in rats (based on BLLs, Y axis) correlation to IVBA results from the G phase (X axis): R2 = 0.93, n=7, intercept 3.2, slope 1.4
    1 h @ pH 2.5 Pepsin; organic acids; HCl NaHCO3; pancreatin; bile  
      · Correlation with I phase: R2 = 0.76
Medlin 1997
PBET-G[88]
15 soils or soil-like materials (EPA Region VIII)   1/111 g.mL-1   · In vivo point estimates in piglets (Y-axis) correlated to in vitro results (X-axis):
    1 h @ pH 1.5 Pepsin; organic acids; acetic acids; HCl   
      R2=0.63, n=15, intercept −8.21, slope 0.90, p < 0.001*
      · Extensive QA/QC protocol
Brown et al. 2003 PBET-G[58] Urban soil treated with various biosolids (n=9)   1/100 g.mL-1   · In vivo bone bioavailability reduction % in rats correlated to in vitro bioaccessibility reduction with the treatment of soils (R=0.9)
    1 h @ pH 2.3 Pepsin; organic acids; HCl   
Hettiarachchi et al. 2003 PBET-GI[59] Joplin soil treated or not with Mn, P, or CRYP (n=15)   1/100 g.mL-1 1 h @ pH 6.5 · In vivo point estimate RBA in rats (Y-axis) correlated to in vitro results (X-axis)
    1 h @ pH 2.0 Pepsin; organic acids; HCl NaHCO3; pancreatin; bile  
      G phase: R2=0.95, intercept 11, slope 0.82
      I phase: R2=0.77, intercept 12, slope 1.87
Schroder et al. 2004 IVG[70] 18 soils (EPA Region VIII)   1/150 g.mL-1 1 h @ pH 1.8 Pepsin; NaCl; HCl 1 h @ pH 5.5 Pancreatin; bile; NaHCO3; decanol · In vivo blood RBA (X-axis) in piglets correlated (p < 0.001) to in vitro data (Y-axis):
      - G (R=0.93) & I (R=0.80) results, with dough
      - G results no dough (R=0.89)
      · Best correlation for G phase with dough: R2=0.86, n=18, intercept 2.97, slope 0.39
Marschner et al. 2006 IVG[62] 5 soils, with or without milk powder   1/40 g.mL-1 6 h @ pH 7.5 · Absence of correlation between in vivo bioavailability in piglets and in vitro results
    2 h @ pH 2.0 Pepsin; NaCl; HCl NaHCO3; trypsin; bile; pancreatin; urea; inorganics  
Oomen et al. 2006
RIVM[86]
11 soils or soil-like material (EPA Region VIII) 5 min @ pH 6.5 1/37.5 or 1/375 g.mL-1 2 h @ pH 5.5-6.5 · In vivo point estimates in piglets (X-axis) correlated to relative in vitro fasted model results (Y-axis):
    2 h @ pH 1.0-2.0 (in)organics, pancreatin, bile, BSA, lipase, CaCl2 G phase: R2=0.68-0.79, intercept 0, slope 0.79-1.08
   (in)organics, mucin, uric acid, alpha-amylase    
      I phase: R2=0.66-0.81, intercept 0, slope 0.69-1.16
    (in)organics, pepsin, mucin, BSA   
Drexler and Brattin 2007; USEPA 2007 RBALP[43, 84] 19 soil-like materials from EPA region VIII,   1/100 g.mL-1   · In vivo RBA point estimates in piglets (Y-axis) correlated to in vitro results (X-axis) : weighted R2=0.924, n=19, intercept −0.028, slope 0.878, p < 0.001
    1 h @ pH 1.5   
    Glycine; HCl   
      · Extensive QA/QC protocol and statistical analyses
      · Precision 7% within samples, and 4-6% within laboratories (round robin testing)
Bannon et al. 2009
RBALP[64]
8 small arms range soils   1/100 g.mL-1 1 h @ pH 1.5   · In vivo point estimates on piglets: 108±18% · In vitro results: 83±1-100±3%
    Glycine; HCl   
Caboche 2009 Denys et al. 2012 UBM[65, 66] 14 mining and smelting soils 5 min @ pH 6.5 1/37.5 g.mL-1
1 h @ pH 1.2-1.7
4 h @ pH 5.8-6.8 · In vivo kidney RBA in piglets (X-axis) correlated to in vitro results adjusted by PbAc solubility in the G and I phases (Y-axis):
     (in)organics, pancreatin, bile, BSA, lipase, CaCl2  
      G phase: R2=0.93, intercept 1.10, slope 1.86, p < 0.01
   (in)organics, mucin, uric acid, alpha-amylase    
      I phase: R2=0.89, intercept 1.09, slope 1.09, p < 0.01
    (in)organics, pepsin, mucin, BSA   
Juhasz et al. 2009 SBRC[67] 5 incinerator & urban soils; 5 soils from Marschner et al.[62]   1/100 g.mL-1 1 h @ pH 1.5 Glycine, HCl 4 h @ pH 6.5NaOH, pancreatin, bile · In vivo blood RBA in piglets (Y-axis) correlated to relative in vitro data for the I phase (X-axis):
R2=0.53, intercept 1.98, slope 0.58 (urban & incinerator soils)
      R2=0.47, intercept 29.5, slope 0.42 (soils from Marschner et al., 2006 study)
Wragg et al. 2011 UBM[95] 12 soils (mining, composite, phosphate-treated), 1 dust 5 min @ pH 6.5 (in)organics, mucin, uric acid, alpha-amylase 1/100 g.mL-1 2 h @ pH 1.2-1.4 4 h @ pH 6.3±0.5 (in)organics, pancreatin, bile, BSA, lipase, CaCl2 · In vivo RBA in piglets (X-axis) correlated to in vitro results adjusted by PbAc solubility in the G and I phases (Y-axis):
    (in)organics, pepsin, mucin, BSA   
      G phase: R2=0.61, slope 0.78, median RSD 4% within samples, 33% within laboratories
      I phase: R2=0.57, slope 0.38, median RSD 15% within samples, 81% within laboratories
Smith et al. 2011 RBALP[68] 12 soils impacted from a variety of Pb sources   1/100 g.mL-1 1 h @ pH 1.5 Glycine, HCl   · In vivo blood RBA in mice (X-axis) correlated to relative in vitro data (Y-axis):
      R2=0.78, intercept 30.207, slope 0.69
Smith et al. 2011 SBRC[68] 12 soils impacted from a variety of Pb sources   1/100 g.mL-1 1 h @ pH 1.5 Glycine, HCl 4 h @ pH 6.5 NaOH, pancreatin, bile · In vivo blood RBA in mice (X-axis) correlated to relative in vitro data (Y-axis):
      R2=0.88, intercept −7.02, slope 1.06 (SBRC, I phase results)
  1. IVBA–in vitro bioaccessibility; RBA–relative bioavailability; G–gastric; I–intestinal; RSD–relative standard deviation; *relationship with corrected EPA in vivo data from [84]; in vitro-in vivo relationship not performed with EPA corrected data (in vivo bioavailability or bulk Pb concentrations).