Critique Table 1.
Study Designa
| Specific Aim |
Test System | Exposures: Concentration and Duration |
Endpoints (Timing of Post-Exposure Measurement) |
|---|---|---|---|
| 1 | NEP knockout and control (wild-type) mice | Intratracheally instilled with 0, 10, or 100 µg resuspended DEP (SRM 2975) | NEP and cytokine levels in BAL fluid, NEP expression in lung (in wild-type only), and airway epithelial cell proliferation (day 7) |
| 2 | BEAS-2B (transformed epithelial human cell line) | Treated for 24 hr with 0, 1, or 10 µg/cm2 particles: DEP (SRM 2975), cDEP, sDEP, control (SRM 1649a) | NEP mRNA levels (24 hr) |
| 3 | BEAS-2B human cells: untreated or treated with NEP-specific siRNA to knock down NEP expression | Treated for 24 hr with 0, 10, or 40 µg/cm2 DEP (SRM 2975) | RNA expression, measured by microarray and RT-PCR, of multiple genes (and molecular pathways) affected by either DEP treatment or NEP knockdown (24 hr) |
| 4 | 11 Healthy human volunteers (ages 19–33 yr) | Single inhalation exposure to DEE. Individual exposure concentrations ranged from 0.09 to 1.80 mg/m3 EC and 56 to 134 min duration | NEP activity, and differential cell count and protein content in induced sputum (baseline pre-exposure and 1 hr post-exposure [at least 1 wk after baseline]) |
a
cDEP indicates SRM 2975 treated with the chelator Chelex-100; sDEP indicates SRM 2975 treated with dichloromethane; RT-PCR indicates real-time polymerase chain reaction.