Table 6 Examples of variants of physiologically based in vitro procedures (not calibrated) applied to Pb particles (2 pages)

Sheppard et al. 1995[116]

Centrifugation, filtration 0.2 μm

4 h, pH 2.0

NaCl; pepsin; HCl

18 h, pH 7.5

NaHCO₃; NaCl; bile; pancreatin; α-amylase

Berti and Cunningham 1997[125]

Stir bar

1/100

1 h, pH 2.5

Pepsin; organic acids; HCl

2 h, pH 7.0

NaHCO₃; pancreatin; bile

Davis et al. 1997[126]

Wrist action shaker

Centrifugation (2,100 g; 25 min)

1/10

2 h, pH 1.3

Pepsin; organic acids; HCl

2 h, pH 7.0

NaHCO₃; pancreatin; bile

Hamel et al. 1998[92]

Shaking water bath

Centrifugation (1,380 g; 10 min)

1/100 to 1/5000

2 h

NaCl; pepsin; HCl

Hamel et al. 1999[102]

Water bath, 90 cyc/min

Centrifugation (906 g; 10 min), filtration 0.45 μm

5 s, pH 5.5

Mucin; urea; KCl; NaCl; Na₂HPO₄; CaCl₂.4H₂O

1/2160

2 h

NaCl; pepsin; HCl

2 h

NaHCO₃

Oliver et al. 1999[89]

Wrist action shaker

Filtration 0.45 μm

1/10

2 h, pH 1.3 to 3.0

Organic acids; HCl; with(out) pepsin

16 h, pH 7.0

NaHCO₃ with(out) bile & pancreatin

Ellickson et al. 2001[57]

Bath set, 90 cyc/min

Centrifugation (200 g; 20 min) & (906 g; 15 min); HNO₃, 48 h; filtration 0.45 μm

Mucin; urea; CaCl₂.H₂O; NaCl; KCl; Na₂HPO₄

1/2160

2 h, pH 1.4

Pepsin; NaCl; HCl

4 h, pH 6.5

NaHCO₃

Oomen et al. 2002, Van De Wiele et al. 2007[82, 87]; DIN test

Agitator, 200 rpm

Centrifugation (7,000 g; 10 min)

1/50

2 h, pH 2.0

HCl; [pepsin; mucin]^*

6 h, pH 7.5

Phosphate buffer; [bile; trypsin; pancreatin]^*

Oomen et al. 2002, Van De Wiele et al. 2007[82, 87]; SHIME test

Stirring, 150 rpm

Centrifugation (7,000 g; 10 min)

1/2.5 to 1/40

3 h, pH 2.0 (fast) or 4.0 (fed)

Nutrilon plus; pectin; mucin; cellobiose; proteose peptone; starch; glucose

5 h, pH 6.5

NaHCO₃; pancreatin; bile

Oomen et al. 2002, Van De Wiele et al. 2007[82, 87]; TIM test

Peristaltic

Ultrafiltration

5 min, pH 5.0

Fast: 40 min, pH 4.5 to 1.8

HCl; lipase; pepsin^* 0.5 mL/min

Fast: 5.3 h, pH 6.5 to 7.2

NaHCO₃; pancreatin; bile^* 1 mL/min

Fed: 4.5 h, pH 6.5 to 7.2

Fed: 1.5 h, pH 5.0 to 2.0

Yu et al. 2006[113]

Water bath, 90 rpm

Filtration 0.45 μm

Mucin; urea; KH₂PO₄; CaCl₂.H₂O; NaCl, KCl

1/400

2 h, pH 1.4

NaCl; pepsin; HCl

2 h, pH 6.5

NaHCO₃

Bruce et al. 2007[94]

Ar

Centrifugation (10,000 g; 15 min), filtration 0.22 μm

1/100

1 h pH 1.3 (fast) to 4 (fed)

Pepsin; HCl; organic acids

3 h pH 7.0

NaHCO₃; bile; pancreatin

Saikat et al. 2007[104]

Centrifugation (2,100 g; 25 min)

1/38-1/100

1 h pH 1.1 or 2.5

Pepsin; organic acids; HCl

4 h, pH 5.5 or 7.0

NaHCO₃; pancreatin; bile

Triantafyllidou et al. 2007[26]

Gentle mixing

No separation

1/16,667

3 h, pH 1.2

NaCl; pepsin; HCl

Turner and Ip 2007[127]

End-over-end

Centrifugation (2,100 g;10 min)

1/200

2 h, pH 2.5

Pepsin; HCl; Na malate & citrate; lactic & acetic acids

4 h, pH 7.0

NaHCO₃; bile; pancreatin

Van De Wiele et al. 2007[87]

Water rotator set

Filtration 0.45 μm

1/100

1 h pH 2.5

Pepsin; HCl; Na citrate & malate; lactate, acetate

4 h, pH 7.0

NaHCO_3; bile; pancreatin

Bosso and Enzweiler 2008; Bosso et al. 2008[107, 114]

Slow orbital + Ar flux

Centrifugation (5,000 rpm; 20 min)

1/100

1 h, pH 1.7

Pepsin; HCl; citric, malic, acetic, & lactic acids

2 h, pH 7.0

NaHCO_3; bile; pancreatin

Turner et al. 2009[128]

Constant, lateral

Centrifugation (2,000 g; 10 min)

1/100-1/143

1 h, pH 2.5

Pepsin; HCl; Na malate, citrate; lactic & acetic acids

4 h, pH 7.0

NaHCO₃; bile; pancreatin

Sialelli et al. 2010[115]

Orbital, 150 rpm

1/100

1 h, pH 1.5

Pepsin; HCl; Na citrate; malic & lactic acids

3.5 h, pH 7.0

Pancreatin, NaHCO₃