Table 2.
Selected animal models of isocyanate asthma: sensitization via skin.
| Sensitization via skin
|
Inhalation challenge
|
|||||
|---|---|---|---|---|---|---|
| Compound, reference | Animal | Frequency/form | Dose (μmol NCO) | Frequency/form/route/timing | Dose | End points (inflammation, airway responsiveness, isocyanate antibodies, other) |
| TDI | ||||||
| Karol et al. 1981 | Guinea pig | Single; 1/day × 50 μL 1, 10, 25, 100% in OO | Various; ~ 7, 70, 174, 1,390 | Once/inhalation/TDI vapor and TDI-GSA conjugate aerosol, 2 weeks later | 5 ppb TDI vapor and 12 μg/L air TDI-GSA | ↑ Respiratory rate, ↑ TDI-IgE antibodies |
| Erjefält and Persson 1992 | Guinea pig | Twice; days 1 and 8; 1/day × 2 days × 100 μL 20% TDI in EA/OO | 2 × ~ 278 = 556 | Once; tracheal, TDI, day 15 | ~ 1.4–4 pmol NCO | ↑ Plasma exudation in lungs (131I-albumin) |
| Scheerens et al. 1999 | Mice BALB/c | Short exp: 2/day × 2 days; long exp: 1/week × 6 weeks; both: × 200 μL 1% TDI in Ace/OO | Short exp: 2 × 55.6 = 111 Long exp: 6 × ~ 28 = 167 | Once; intranasal, 20 μL 1% TDI in EA/OO and ear 20 μL 0.5% in Ace; day 8 or day 42 | Intranasal 2.8 μmol NCO + ear 1.4 μmol NCO | Short: ↑ TDI-IgG, long: ↑ TDI-IgE and TDI-IgG, ↑ in vivo tracheal hyperresponsiveness |
| Vanoirbeek et al. 2004 | Mice BALB/c | Variable; once (1% TDI) or 1/day × 3 days (1, 2, 3); 40 μL 0.3% or 3% TDI in Ace/OO, + repeat on day 7 | 1% TDI: 5.6 × (1+1) = 11.2; 0.3% TDI: ~ 1.7 × (3 + 1) = 6.7; 3% TDI: 16.7 × (3 + 1) = 66.8 | Once; intranasal, 20 μL 0.1% TDI in Ace/OO, day 10 | 0.28 μmol NCO | ↑ Airway responsiveness, ↑ mixed Th1/Th2 lung inflammation, ↑ total IgE, greater response with lower skin dose; timing and freq skin exposure important |
| Ban et al. 2006 | Mice BALB/c | Single; 50 μL 1% TDI in Ace/OO on day 0, then tracheal instillation with 50 μL 0.2% TDI in OO on day 5 | 7 on skin + 1.4 tracheal instillation | Trachea instillation with 50 μL 0.1% TDI in OO, on days 18, 28, 31 | 3 × 0.7 = 2.1 μmol NCO | Lung Th2 inflammation, ↑ TDI-IgE, only skin sensit induced Th2 asthma-like responses |
| HDI | ||||||
| Herrick et al. 2002 | Mice BALB/c | Twice; 50 μL 0.01 or 1% HDI in 4:1 A:OO on days 0 and 7 | 1.2 and 12.4 | Intranasal; 50 μL HDI-MSA (2 μg/μL) on days 14, 15, 18, 19 | 100 μg | Lung and BAL Th2 inflammation, ↑ IgE, ↑ HDI-IgG, lower sensit dose, more lung inflammation |
| MDI | ||||||
| Rattray et al. 1994 | Guinea pig | Single, variable; 400 μL of 10, 30, or 100% MDI in CO | 320, 959, 3,195 | Once; inhalation of MDI aerosol on day 21 | 26–36 mg/m3 | ↑ Respiratory rate, ↑ MDI-IgG1, inhalation failed to induce sensit |
Abbreviations: ↑, increase; Ace, acetone; Alb, albumin; BAL, bronchoalveolar lavage; CO, corn oil; EA, ethyl acetate; exp, exposure; Freq, frequency; GSA, guinea pig serum albumin; MSA, mouse serum albumin; OO, olive oil; sensit, sensitization.