Ann. occup. Hyg., Vol. 41, Supplement 1, pp. 210-212, 1997
© 1997 British Occupational Hygiene Society
Published by Elsevier Science Ltd. All rights reserved
Printed in Great Britain
0003-4878/97 $17.00 + 0.00
Inhaled Particles VIII
PII: S0003-4878(96)00065-8
EFFECTS OF EXPOSURE PERIOD AND LUNG BURDEN ON
CLEARANCE RATE OF INHALED ALUMINIUM-SILICATE
CERAMIC FIBRE FROM RAT LUNG
T. Oyabu, I. Tanaka, S. Ishimatsu*, H. Yamato, Y. Morimoto, T. Tsuda,
H. Hori* and T. Higashi
Institute of Industrial Ecological Sciences, * School of Health Sciences, University of Occupational
and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi, Kitakyushu 807, Japan
INTRODUCTION
It has been shown that occupational exposure to various types of asbestos may lead
to asbestosis, bronchial cancer, pleural and peritoneal mesotheliomas. Recently the
production of man-made fibres (MMFs) has increased as asbestos substitutes.
Therefore, the effects of MMFs on health should be investigated because the health
effects are not always clear for many MMFs.
In general, asbestosis and fibrosis occur after long retention of asbestos in the
lung. Therefore, the clearance rate of deposited particles is considered to be a very
important factor of these diseases. The lower the clearance rate, the higher the
possibility of disease. In our previous study (Tanaka et al., 1994) the clearance rate
of glass fibre in rat lungs after a 12 month exposure experiment became slower than
that after 1 month exposure.
In this study, the effect of exposure period on the clearance rate of aluminiumsilicate ceramic fibre is examined by inhalation studies. In addition, the relationship
between lung burden and clearance rate is discussed.
MATERIALS AND METHODS
The exposure system and the experimental procedure have been shown in a
previous paper (Tanaka and Akiyama, 1990). Exposure concentration in the
chamber was monitored continuously by a light scattering method (Dust Monitor
AP-632, Shibata Sci. Tech. Japan). The mass concentration of RCF was measured
gravimetrically each day by the isokinetic sampling of air through a glass fibre filter.
The mass median aerodynamic diameter (MMAD) and the geometric standard
deviation (GSD) of RCF in the exposure chamber were measured by using an
Andersen cascade impactor (AN-200 Sibata Sci. Tech. Japan). The RCF in the
chamber were collected by an asbestos-sampler, which conformed to the asbestos
measurement method of NIOSH. The diameter and the length of the RCF were
measured by a scanning electron microscope (S-700, Hitachi, Japan) and a digitizer
(KD3030L, Graphtec, Japan).
Experimental conditions are summarised in Table 1. The Wistar male rats were
randomly allocated to control and test groups. Eighty Wistar male rats in the test
210
Effects of exposure period of inhaled aluminium-silicate ceramic fibre
211
Table 1. Experimental conditions of RCF inhalation
Exposure period (months)
Number of exposed rats
Number of control rats
Exposure concentration (mg m~3)
MMAD (GSD) (jun)
GMD (\im)
GML (urn)
Sacrifice time after exposure
(months)
1
3
6
12
21
22
20 ± 3
4.0(1. 9)
15
15
15
16
27
27
2.6 ± 1.3
4.6 (1.8)
2.6 ± 1.1
4.6 (1.8)
2.8 ± 1.0
4.6 (1.8)
1.1
8.2
1.3
9.2
1.3
9.2
1.3
9.2
3 days, 3,6,9
3 days, 3,6
3 days, 3, 6
3 days, 12
groups were divided into four groups depending on the exposure period and were
exposed to aluminium-silicate ceramic fibre (RCF, content: SiO2 52% and A12O3
48%) for 6 h day"1, 5 days week"1 by inhalation. The exposure period was 1, 3, 6
and 12 months. Control rats were exposed to clean air in identical, adjacent
chambers under similar conditions of flow, temperature and humidity. The exposed
rats were sacrificed at 3 days after each exposure period. The controls were also
sacrificed at the same time.
At each sacrifice time the body and the wet lung were weighed and then the lungs
were ashed by a low temperature asher (PR-503, Yamato Sci. Co., Japan). Ashed
samples were digested with phosphoric acid in a teflon flask and the silicon and
aluminium were measured by an inductively coupled plasma—atomic emission
spectroscopy (SPS-1500R, Seiko Instruments Inc., Japan). The wavelengths of the
detector were 251.611 nm for silicon and 396.152 nm for aluminium.
RESULTS AND DISCUSSION
Figure 1 shows the measured lung burden of the RCF with the clearance time.
The solid lines in Fig. 1 are regression lines based on a single compartment model.
1000
12M (BHT:3.7M)
1
.a
j
2
4
6
8
10
Clearance Time (months)
Fig. 1. Clearance of inhaled RCF from rat lungs.
12
14
T. Oyabu et al.
212
16
m
14
12
p
10
I
8
•a
6
I
4
S
2
i
• GF
• TW
• RCF (This work)
i
0
0.5
1.0
1.5
i
2.0
i
2.5
Deposited amount of fibers (mg)
Fig. 2. Relationship between biological half time and deposited amount of fibres in rat lungs.
This figure shows that the biological half times (BHTs) of four groups have almost
the same value in spite of the difference in the exposure period.
In the previous papers (Tanaka et al., 1994; Fujino et al., 1995), the BHTs in a 12
month exposure period [glass fibres (GF): 9.2 months and potassium titanate
whisker (TW): 15 months] were much longer than those in a 1 month exposure
period (GF: 1.5 months and TW: 3.5 months).
One possible reason for this discrepancy may be the different amounts of the
deposited fibres. Figure 2 shows the relationship between the BHTs and the
deposited amounts of fibres just after the termination of the exposure periods in
our previous studies. The BHTs show almost the same level (1.5-4 months) when
the lung burden is lower than 0.65 mg. On the other hand, the BHTs increase
significantly with the lung burden which is over 1.5 mg.
Morrow (1992) indicated that when the volume of the particles phagocytized by
alveolar macrophages is over the limitation, macrophage-medicated clearance is
impaired and finally ceases. The limited amount is not exactly estimated but it is
probable that when the deposited amount is over a threshold value, BHT will
become longer.
We suggest that the BHTs show almost the same time in spite of the different
exposure periods (1, 3, 6 and 12 months), as the deposited amount of fibres in rat
lungs may be less than the threshold.
REFERENCES
Fujino, A., Hori, H., Higashi, T. etal. (1995) In vitro biological study to evaluate the toxic potentials of
fibrous materials. Int. J. occup. Environ. Health 1 (1), 21-28.
Morrow, P. E. (1992) Dust overloading of the lungs: update and appraisal. Toxicol. appl. Pharmacol.
113, 1-12.
Tanaka, I. and Akiyama, T. (1990) Pulmonary deposition fraction of a glass fibre in rats by inhalation.
In Aerosols: Sci., Ind., Health and Environ. (Edited by S. Masuda and K. Takahashi) pp. 1242—
1245. Pergamon Press, Oxford
Tanaka, I., Oyabu, T., Ishimatsu, S. et al. (1994) Pulmonary deposition and clearance of glass fibre in
rat lungs after long-term inhalation. Environ. Health Perspect. 102 (S5), 215-216.