Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation.
NASA is contemplating sending humans to Mars and to the moon for further exploration. Volcanic ashes from Arizona and Hawaii with mineral properties similar to those of lunar and Martian soils, respectively, are used to simulate lunar and Martian environments for instrument testing. Martian soil is highly oxidative; this property is not found in Earth's volcanic ashes. NASA is concerned about the health risk from potential exposure of workers in the test facilities. Fine lunar soil simulant (LSS), Martian soil simulant (MSS), titanium dioxide, or quartz in saline was intratracheally instilled into groups of 4 mice (C57BL/6J) at 0.1 mg/mouse (low dose, LD) or 1 mg/mouse (high dose, HD). Separate groups of mice were exposed to ozone (0.5 ppm for 3 h) prior to MSS instillation. Lungs were harvested for histopathological examination 7 or 90 days after the single dust treatment. The lungs of the LSS-LD groups showed no evidence of inflammation, edema, or fibrosis; clumps of particles and an increased number of macrophages were visible after 7 days but not 90 days. In the LSS-HD-7d group, the lungs showed mild to moderate alveolitis, and perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of mild chronic pulmonary inflammation, septal thickening, and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lung lesions in the MSS-LD-7d group were similar to those observed in the LSS-HD-7d group. The MSS-LD-90d group had PLMs and scattered foci of mild fibrosis in the lungs. The MSS-HD-7d group showed large foci of PLMs, intra-alveolar debris, mild-to-moderate focal alveolitis, and perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild-to-moderate alveolitis and fibrosis. The findings in the O(3)-MSS-HD-90d group included widespread intra-alveolar debris, focal moderate alveolitis, and fibrosis. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The effects of O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.
Lam
Chiu-Wing
CW
Wyle Laboratories, NASA Johnson Space Center, Houston, Texas 77058, USA. Chiu-wing.Lam@jsc.nasa.gov
James
John T
JT
McCluskey
Richard
R
Cowper
Shawn
S
Balis
John
J
Muro-Cacho
Carlos
C
D000280:Administration, Inhalation; D000818:Animals; D019443:Cosmic Dust / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000008:administration & dosage / Q000009:adverse effects; D012822:Silicon Dioxide / Q000009:adverse effects; D013997:Time Factors; D014025:Titanium / Q000009:adverse effects
D019443:Cosmic Dust; C009495:titanium dioxide; D010126:Ozone; D012822:Silicon Dioxide; D014025:Titanium