Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz

Our plain-English summary of Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz, by J.M. Davis, A.D. Jones, B.G. Miller (International Journal of Experimental Pathology, 1991).

The study

• Authors: J.M. Davis, A.D. Jones, B.G. Miller
• Journal: International Journal of Experimental Pathology
• Published: 1991;72(5):501-25
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Rats were exposed for 1 year, with a 2-year follow-up, to dust clouds consisting of a mixture of amosite or chrysotile asbestos with either titanium dioxide or quartz. The addition of titanium dioxide to asbestos did not increase levels of pulmonary fibrosis above the amounts produced by chrysotile or amosite alone. Quartz, however, greatly increased fibrosis above that produced by the asbestos types alone. Both particulate dusts caused an increase in the numbers of pulmonary tumours and mesotheliomas compared to asbestos alone but while tumours in animals treated with asbestos and quartz tended to occur earlier than tumours with asbestos alone, in animals treated with dusts containing titanium dioxide, tumour production occurred later than with asbestos alone. In animals treated with mixtures of asbestos and quartz, there was evidence of increased transport of fibres across the visceral pleural surface and this may be associated with the finding of a higher proportion of pleural mesotheliomas than previously reported in experimental inhalation studies from any laboratory using the main asbestos varieties. The presence of particulate dusts made little difference to the amounts of amosite fibre retained in the lung tissue but, with chrysotile, titanium dioxide appeared to increase retention while quartz reduced it.

In plain English

This was an animal experiment at the Institute of Occupational Medicine, Edinburgh. Four groups of 48 rats breathed dust for one year, with a two-year follow-up. Each day they breathed chrysotile or amosite asbestos for five hours and titanium dioxide or quartz for two hours, one dust at a time; planned daily averages were 10 mg/m3 asbestos plus 10 mg/m3 titanium dioxide or 2 mg/m3 quartz. Results were compared with controls and with asbestos-alone groups from the institute's earlier studies. Adding titanium dioxide made no difference to lung scarring (fibrosis), while adding quartz increased it with both asbestos types. All four mixed-dust groups had more lung tumours than asbestos alone. With quartz, tumour deaths came earlier; with titanium dioxide, the tumours occurred at slower rates. Pleural mesotheliomas occurred in 6 of 38 rats examined after chrysotile plus quartz and in 8 of 39 after amosite plus quartz. Granulomas containing dust on the lung surface were very common with quartz and quite rare with titanium dioxide. The authors suggested that particulate dusts, especially quartz, made it easier for asbestos fibres to cross the pleural surface.

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 in rats (1-year exposure, 2-year follow-up), compared with controls and with asbestos-alone groups from the institute's previous studies
• Who was studied: Four groups of 48 AF/Han strain rats, Institute of Occupational Medicine, Edinburgh, UK. Groups of four rats were killed at the end of dusting and 6 months later; the rest lived out their life span
• Exposure: UICC chrysotile (A) or a long-fibre amosite sample, combined with either titanium dioxide (rutile) or quartz. Planned levels were 10 mg/m3 respirable asbestos and either 10 mg/m3 titanium dioxide or 2 mg/m3 quartz, as means over the 7-hour exposure day. Asbestos was generated for 5 hours and the particulate dust for the remaining 2 hours, so the rats inhaled a single dust at any one time
• Main results:
  • Titanium dioxide did not change fibrosis. Mean advanced fibrosis was 12.9% with chrysotile plus titanium dioxide vs 12.2% with chrysotile alone, and 9.4% with amosite plus titanium dioxide vs 10.0% with amosite alone. Quartz increased fibrosis with both asbestos types: 23.5% with chrysotile plus quartz and 17.8% with amosite plus quartz (P less than 0.0001). Controls had 0.1%.
  • Fibrosis was higher with chrysotile plus quartz than with amosite plus quartz, but this difference was not statistically significant
  • Adding either particulate dust increased tumour production compared with asbestos alone; the asbestos-alone figures came from previous studies. Total pulmonary tumours and mesotheliomas, with rats with tumours out of rats examined: controls 2 (2 of 47); chrysotile 14 (13 of 37); chrysotile plus titanium dioxide 27 (26 of 41); chrysotile plus quartz 27 (22 of 38); amosite 14 (14 of 40); amosite plus titanium dioxide 21 (20 of 40); amosite plus quartz 28 (26 of 39)
  • Pleural mesotheliomas: six in the chrysotile plus quartz group (16%) and eight in the amosite plus quartz group (21%), compared with two per group with asbestos plus titanium dioxide or amosite alone
  • Mortality from pulmonary tumours was higher in the groups given quartz with asbestos. In the titanium dioxide groups, tumour numbers were similar to the quartz groups but occurred at slower rates, leading to higher estimated survival than even asbestos alone
  • Lung chrysotile burden 6 months after dusting was 315 micrograms with chrysotile alone. It was significantly higher with titanium dioxide (711 micrograms) and significantly lower with quartz (183 micrograms) (P less than 0.03 in each case)
  • Lung amosite burden was similar with or without particulate dust: 3083 micrograms with amosite alone, 3294 with titanium dioxide, 2766 with quartz
  • Small granulomas containing dust outside the lung's external elastic lamina, on the pleural surface, were quite rare with asbestos plus titanium dioxide and very common with asbestos plus quartz
• The authors' conclusion: The authors concluded that particulate dusts, and particularly quartz, appear able to penetrate the pleural surfaces more readily than asbestos fibres and to make fibre penetration easier. They associated this with the relatively high numbers of pleural mesotheliomas in the quartz groups.
• Limitations the authors state:
  • The amosite clouds for the mixed-dust exposures had more fibres for the same respirable mass than the earlier pure amosite cloud (3648 and 4150 vs 2060 fibres longer than 5 micrometres per ml)
  • Lung amosite content for the amosite plus quartz group was based on only two animals
  • Chrysotile cannot be seen by light microscopy, so its presence in pleural granulomas could not be confirmed
  • Late survival patterns were based on small numbers of surviving animals and are least reliable

Topics

Medical terms in this study, explained in our Lexicon: Amosite, Chrysotile, Pulmonary Fibrosis, Fibrosis, Mesothelioma, Pleural Mesothelioma.

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