TABLE 2.
Experimental Animal Studies Using Talc Inhalation Exposure Relevant for STOT-RE and Carcinogenicity Classification
| Study Description and Findings | Type of Talc | Exposure Details | Reference |
|---|---|---|---|
| Rat inhalation study: The study noted mild fibrosis in exposed rats, as well as one case of lung adenoma. Lung burdens (2.8, 4.5, and 12.3 mg) suggest saturation of lung clearance over time. | Italian 00000 grade | 10.8 mg/m3 (MMAD missing); exposure of 3, 6, and 12 months. Follow-up at 12 months after exposure. | Wagner et al12 |
| Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc | MP 10–52 | Exposure: 6 hr/day, 5 days/week for 4 weeks Rats: 2.3, 4.3, and 17 mg/m3 Mice: 2.2, 5.7, and 20.4 mg/m3 MMAD: 3 μm ± 1.9 aerosol |
Pickrell et al19 |
| Syrian golden hamsters' exposure to respirable talc showed little to no pathology compared with controls. Animals however did not survive to lifetime. | J & J BP | 9.8 mg/m3 (MMAD, 4.9 μm); exposure of 3, 30, or 150 minutes for 30 days, 300 days of follow-up | Wehner et al10 |
| Pulmonary clearance in 10-week-old Syrian golden hamsters exposed to respirable talc. The clearance half-life was 7–10 days; pulmonary clearance was completed in 4 months. | J & J BP | 40–75 mg/m3 (MMAD, 6.6 μm); single exposure of 120 minutes, 300 days of follow-up | Wehner et al11 |
| NTP lifetime inhalation study in rats and mice. In rats, the inhalation of talc resulted in a range of inflammatory, reparative, and proliferative lung responses. Lung tumor formation and reduced clearance are evident at high doses in female rats (AA, BA, CA) only. In mice, there was no evidence of hyperplasia or interstitial fibrosis, although clearance was reduced at the higher dose. |
MP 10–52 | 6 and 18 mg/m3 (rats: MMAD of 2.7 and 3.2 μm; mice: MMAD of 3.3 and 3.6 μm) | NTP14 |
| Critical review of NTP (1993) dose selection and outcome interpretation | MP 10–52 | Exposure described in NTP (1993) | Oberdorster17 |
| Lung burden study of talc in rats and mice after 20 days of inhalation exposure (Pickrell et al14) Rats: 2.3, 4.3, and 17 mg/m3 Mice: 2.2, 5.7, and 20.4 mg/m3 |
MP 10–52 | Mean lung burdens in rats were 77, 187, and 806 μg of talc per gram of lung (n = 10) for exposures at 2.3, 4.3, and 17 mg/m3 of talc, respectively. Mean lung burdens in mice were 114, 325, and 1150 μg talc per gram of lung (n = 10) for exposures at 2.2, 6.3, and 20.6 mg/m3 of talc | Hanson et al20 |
| An animal model for inhalation exposure to talc. Respirable fraction contained 1300 particles/mL larger than 1 μm. Between 1% and 2% of these particles were fibrous. | Italian 00000 | 10.8 mg/m3 (MMAD missing); exposure of 3, 6, and 12 months. Follow-up at 12 months after exposure. | Wagner et al13 |
AA, alveolar adenoma; BA, bronchiolar adenoma; CA, carcinoma (combined); MMAD, mass medium aerodynamic diameter; NTP, National Toxicology program; STOT-RE, specific target organ toxicity arising from repeated exposure.