Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc

Our plain-English summary of Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc, by J.A. Pickrell, M.B. Snipes, J.M. Benson, et al (Environmental Research, 1989).

The study

• Authors: J.A. Pickrell, M.B. Snipes, J.M. Benson, R.L. Hanson, R.K. Jones, R.L. Carpenter, J.J. Thompson, C.H. Hobbs, S.C. Brown
• Journal: Environmental Research
• Published: 1989;49(2):233-45
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The relationship between the inhalation exposure concentration of talc and the resulting lung burdens and histologic lesions was studied using groups of 20 F344/Crl rats and 20 B6C3F mice (10 male and 10 female) exposed to one of three concentrations of asbestos-free talc for 6 hr/day, 5 days/week for 4 weeks. Controls were exposed to filtered air using the same schedule. The pulmonary retention of talc and the development of pulmonary pathology were evaluated. The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 microns with a geometric standard deviation (sigma g) of 1.9. The mean exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus, the amount retained in the lung per unit of exposure concentration increased with increasing concentration. Mean exposure concentrations for the mice were 0, 2.2, 5.7, and 20.4 mg of talc/m3, which resulted in lung burdens of 0, 0.10, 0.29, and 1.0 mg talc/g lung; thus, the relationship between exposure concentration and the amount retained in the lung was approximately constant. Lung burdens from this study were used to project lung burdens that would result from longer exposures of rodents and man. No clinical signs were observed in the rats or mice prior to sacrifice 24 hr after the last exposure day. Histologic alterations in lung tissue consisted of only a modest, diffuse increase of talc-containing, free macrophages within alveolar spaces in both rat and mouse groups exposed to the highest level of talc for 20 days. A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens of 2-3 mg talc/g lung (wet wt) if animals were exposed to 17 mg talc/m3 for 2 years, and deposition and clearance of talc were unchanged by continued exposure. A potential limitation in this modeling is that if clearance of talc is delayed by continued exposure, the accumulated talc lung burdens would be higher than those projected by the simulation model. Humans exposed to aerosols of respirable talc are projected to accumulate much higher lung burdens than would occur in rodents exposed to the same aerosol, because humans have a higher estimated deposition fraction and slower estimated clearance of the deposited talc dust. Equilibrium lung burdens of greater than or equal to 2 mg talc/g lung were predicted for human exposures at or near the TLV for talc.

In plain English

In this animal experiment, groups of 20 F344/Crl rats and 20 B6C3F1 mice breathed asbestos-free talc or filtered air 6 hours a day, 5 days a week, for 20 exposure days. Average concentrations were 2.3, 4.3 and 17 mg talc/m3 for rats and 2.2, 5.7 and 20.4 mg/m3 for mice. Exposed rats averaged 0.07, 0.17 and 0.72 mg talc per gram of lung. Exposed mice retained 0.10, 0.29 and 1.0 mg per gram. Microscopy of the highest-exposure rats and mice showed only a modest, diffuse increase in free macrophages (scavenger cells) in the air sacs. Lower-exposure groups were not examined microscopically. The authors' model projected people breathing respirable talc at the 2 mg/m3 occupational limit (TLV), 7 hours a day, 5 days a week, would reach an equilibrium lung burden of about 2 mg talc per gram of lung after about 4 years, if deposition and clearance stayed unchanged. The authors concluded the current TLV for talc might not be safe for chronic occupational exposures. They noted the projections relied on one time point and could underestimate burdens if clearance slowed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal inhalation experiment (short-term repeated exposure) with computer modeling to project long-term lung burdens in rodents and humans
• Who was studied: F344/Crl rats and B6C3F1 mice, 6 to 7 weeks old at the start of exposures; groups of 20 rats and 20 mice (10 males and 10 females each) per exposure level, at the Lovelace Inhalation Toxicology Research Institute, Albuquerque, New Mexico
• Exposure: Asbestos-free talc, reported free of asbestos by electron microscopic examination and dispersion staining. Target concentrations were 0, 2, 6 or 18 mg/m3, for 6 hr/day, 5 days/week, for 20 exposure days. Mean measured concentrations were 2.3, 4.3 and 17 mg/m3 for rats and 2.2, 5.7 and 20.4 mg/m3 for mice. Controls breathed filtered air.
• Main results:
  • Rats exposed to 2.3, 4.3 and 17 mg talc/m3 had average lung burdens of 0.07, 0.17 and 0.72 mg talc/g lung after the 20-day exposure
  • Mice exposed to 2.2, 5.7 and 20.4 mg talc/m3 had lung burdens of 0.10, 0.29 and 1.0 mg talc/g lung
  • Lung burdens normalized for lung weight and exposure concentration were 30 to 65% higher in mice than in rats
  • In rats, normalized lung burdens at the medium and high exposure levels were about 35% higher than at the lowest level. A similar trend in mice was not statistically significant.
  • The only exposure-related lung finding was a modest, diffuse increase in free macrophages within the air spaces of rats and mice exposed to the highest concentration. Talc particles were seen inside the macrophages.
  • Because the response was minimal at the high exposure level, tissues from the lower exposure groups were not examined histologically
  • The model projected that rats exposed for 24 months would reach 0.27 mg talc/g lung at 2.3 mg talc/m3
  • The model projected that rats exposed for 24 months would reach at least 2 mg talc/g lung at 17 mg talc/m3, assuming no change in deposition and clearance
  • For humans exposed to 2 mg of respirable talc/m3 (described as the TLV for talc) for 7 hr/day, 5 days/week, the model projected an equilibrium lung burden of approximately 2 mg talc/g lung (wet weight). This assumed that deposition and clearance of talc are unchanged by continued exposure.
  • The projected human equilibrium lung burden was reached after approximately 4 years of exposure
• The authors' conclusion: The authors concluded that the predicted human talc lung burdens, which correspond to those producing lesions in rodents, together with epidemiological evidence, suggest that the current TLV for talc might not be safe for chronic occupational exposures.
• Limitations the authors state:
  • The projections used lung burdens measured at only one time point, after 20 days of exposure
  • The simulations may underestimate actual lung burdens if talc clearance slows with continued exposure and accumulation

Topics

The National Library of Medicine indexes this study under subjects our site covers: Talc and vermiculite.

Medical terms in this study, explained in our Lexicon: Talc, Deposition, Asbestos-Free Talc, Pathology, Macrophage.

Related studies

• Inhalation toxicity study of disk-shaped potassium octatitanate particles (terracess TF) in rats following 90 days of aerosol exposure — S. Sakai, K. Inada, et al. (2010)
• Deposition pattern of inorganic particles at the alveolar level in the lungs of rats and mice — A.R. Brody, M.W. Roe (1983)
• Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats — M. Yokohira, Y. Nakano-Narusawa, et al. (2016)
• Inhalation Toxicity of Talc — N.F. Johnson (2021)
• Additional histopathologic examination of the lungs from a 3-month inhalation toxicity study with multiwall carbon nanotubes in rats — S. Treumann, L. Ma-Hock, et al. (2013)
• Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos — K.E. Pinkerton, P.C. Pratt, et al. (1984)

Browse more research in Environmental Research, or return to medical research.