Pulmonary Endpoints (Lung Carcinomas and Asbestosis) Following Inhalation Exposure to Asbestos

Figures & data

FIGURE 1. Fiber deposition in the lung. Lines within the airways show net axial core flow through the trachea (site of impaction), bronchi, and bronchioles (Lippmann & Schlesinger 1984).

TABLE 1. Respiratory and Physiological Parameters in the Rat and Human and Their Influence on Fiber Deposition

Parameter	Rat	Human	Rat/human ratio
Minute ventilation ^a (ml/min)	100	7000	0.014
Volume inhaled/6 h/d (ml)	36,000	2,520,000	0.014
Lung volume ^a (ml)	13	4341	0.003
Alveolar surface area ^a (μm^2)	463,000,000,000	143,000,000,000,000	0.003
Number alveoli/lung ^a	40,000,000	1,000,000,000	0.04
Number alveolar cells/lung ^a	130,000,000	56,000,000,000	0.002
Fiber exposure concentration (f/ml)	100	0.2	500
Number fibers inhaled/d	3,600,000	504,000	7
Number fibers alveoli/d	0.09	0.0005	179
Number fibers alveolar cell/d	0.03	0.000009	3077
Number fibers/μm^2 of alveolar surface/d	0.0000078	0.000000004	2206
Fiber exposure concentration (f/ml)	1,000	0.2	5,000
Number fibers inhaled/d	36,000,000	504,000	71
Number fibers alveoli/d	0.9	0.0005	1786
Number fibers alveolar cell/d	0.28	0.000009	30,769
Number fibers/μm^2 of alveolar surface/d	0.000078	0.000000004	22,061
Fiber exposure concentration (f/ml)	100,000	0.2	500,000
Number fibers inhaled/d	3,6000,000,000	504,000	7142
Number fibers alveoli/d	90	0.0005	178,571
Number fibers alveolar cell/d	28	0.000009	3,076,923
Number fibers/μm^2 of alveolar surface/d	0.0078	0.000000004	2,206,109
^a Pinkerton (1992).

TABLE 2. Molecular and Phenotypic Markers Measured in Subchronic Rat Inhalation Studies Using Asbestos

	Crocidolite		Chrysotile
	High*	Low	High	Low
Endpoints	8.25* {2800}	0.16 {60}	8.23 {2457}	0.18 {32}
5’BrdU (proliferation)
Bronchial epithelial cells	>(5 d)	N.D.	>(5 d)	–
Mesothelial cells	>(20 d)	N.D.	>(5 d)	–
c-jun Oncogene	>	–	–	–
odc (Ornithine decarboxylase)	>	–	–	–
Hydroxyproline (fibrosis)	>(20 d)	–	− (20 d)	–
Note. Modified from Shukla, Vacek, and Mossman (2004b).Asterisk indicates time-weighted average concentration (mg/m^3 air). { } = Average number of fibers >5 μm/cc air (PCOM). N.D., not done. ( ) = Time of observed change. Endpoints of cell proliferation including incorporation of 5’BrdU in individual cells by histochemistry, mRNA levels of the early response protooncogene, c-jun, and odc, a marker of tumor promotion, and hydroxyproline levels, a marker of increased collagen production, in lung homogenates, were measured after 5 and 20 d of exposure to asbestos types at 2 concentrations.

TABLE 3. Clearance Half-Times of Fibers

Fiber	Type	Weighted T1/2 fibers, L > 20 μm (d)	Reference
Calidria chrysotile	Serpentine asbestos	0.3	(Bernstein et al., 2003a)
Brazilian chrysotile	Serpentine asbestos	2.3	(Bernstein et al., 2004)
Fiber B	B01.9	2.4	(Bernstein et al., 1996)
Fiber A	Glasswool	3.5	(Bernstein et al., 1996)
Fiber C	Glasswool	4.1	(Bernstein et al., 1996)
Fiber G	Stonewool	5.4	(Bernstein et al., 1996)
MMVF34	HT stonewool	6.0	(Hesterberg et al., 1998b)
MMVF22	Slagwool	8.0	(Bernstein et al., 1996)
Fiber F	Stonewool	8.5	(Bernstein et al., 1996)
MMVF11	Glasswool	9.0	(Bernstein et al., 1996)
Fiber J	X607	9.8	(Bernstein et al., 1996)
MMVF 11	Glasswool	13	(Bernstein et al., 1996)
Fiber H	Stonewool	13	(Bernstein et al., 1996)
Canadian chrysotile	Serpentine asbestos	11.4	(Bernstein et al., 2003b)
MMVF10	Glasswool	39	(Bernstein et al., 1996)
Fiber L	Stonewool	45	(Bernstein et al., 1996)
MMVF33	Special purpose glass	49	(Hesterberg et al., 1998a)
RCF1a	Refractory ceramic	55	(Hesterberg et al., 1998b)
MMVF21	Stonewool	67	(Hesterberg et al., 1998b)
MMVF32	Special purpose glass	79	(Hesterberg et al., 1998a)
MMVF21	Stonewool	85	(Bernstein et al., 1996)
Amosite	Amphibole asbestos	418	(Hesterberg et al., 1998a)
Crocidolite	Amphibole asbestos	536	(Bernstein et al., 1996)

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