Document baRQ8JwXgBE3v2nK71jy7B1mo
Confidential Special Report 34-70 7 Pages
R: 9-3-71
Chemical Hygiene Fellowship MELLON INSTITUTE
Carnegie-Mellon University
Calidria Asbestos-Resin Grads RG 244 Tracheal Insufflation of Rat Lungs with Interpretation
of Pathology after 30, 60, 90 and 180 Days
Editor: C. P. Carpenter
Contributors! D. L. Geary, Jr*, E. R. Kinkead,
R, C. Myers, D. J, Nachreiner
For: UNION CARBIDE CORPORATION, Chemicals and Plastics Operations Division
Sanrole
A 500-gram sample of Resin Grade RG 244 UCC Calidria Asbestos was received 11-30-70, from King City, California, pursuant to arrangements made by Paul McDaniel of the New York Office, The sample was identified by the Chemical Hygiene Fellowship *33-251.
Tracheal Insufflation
A 1% (V:/V) suspension of the RG 244 sample was prepared in 0,85% saline. All needles, syringes and suspensions were sterilized prior to use. Either 1 ml . or 0.5 ml amounts of the 6terile IX suspension were injected into the rat lung through the trachea, exposed by blunt dissection, after a midline cervical Incision, Following injection of these 200 to 300 gram, male albino, Harlan Wistar rats the incisions were closed with Michael wound clamps until healing ensued.
A total of 13 rats were dosed with 1 ml and 15 with 0.5 ml of the,IX suspension while 11 control ratB received 1 ml of sterile 0,85% NaCl, Three rats from each asbestos do9ed group and 2 controls were killed for histopathologic examination of the lung after intervals of 30, 60 and 90 days which left groups of 4, 6 and 5 rats on the 1 ml, 0.5 ml asbestos and control for the 180 day sacrifice.
Summary of Microscopic Pathology Found 30, 60, 90 and 180 Days
Following Tracheal Insufflation of Rats
The 30-day pathology was narked by the presence of granulation tissue with thickening of the structural elements of the lung (stroma) and the accumulation of giant cells often associated with foreign bodies.
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Report 34-70 Page 2
After 60 days one rat on the 0.5 cl dosage level had inflammation and in growth of connective tissue which blocked a terminal bronchus. Two of 3 rats on both the 1.0 and 0.5 cl dosage level had atelectasis (collapse) of one or more lobes of the lung. Fibrotic foreign body nodules were present in all cases.
After 90 days there was chronic foreign body pneumonia in 2 of 3 rats at both dosaga levels, fibrotic foreign nodules in 3 of 3 and emphysema in 2 of 3. Chronic inflammatory cell foci and atelectasis were present. Bronchioles were dilated in 2 of 3 rats on both dosage levels and all but one on both dosage levels had 6ome lung hemorrhage.
The final 180 day sacrifice revealed interstitial pneumonia in 4 rats on the 0.5 cl dose. ThiB is a chronic form of pneumonia of interstitial tissue with decrease of the normal lung tissue* Atelectasis was present in the 4 rats on 1 cl and on 1 rat on the 0.5 ml dose of asbestos with the 5 controls normal. Fibrotic foreign body tissue was present in all dosed lungs with none in the controls. Pink hyalin material was found in 2 of 4 lungs from rats on the 1 cl dose while in 3 of 4 there was a bluish homogeneous material evident.
In essence, a total of 10 of 13 rats on the 1 ml dose and 12 of 15 on the 0.5 ml dose had fibrotic foreign body nodules or tissue. There were 3 cases of emphysema on the high dose and 4 on the low dose and 1 in the control. Atelectasis (essentially collapse of lung alveoli) was present in 9 rats on 1 cl and 6 on 0.5 cl of asbestos with none reported in the controls. In general, because of the over whelming preponderance of effect in the asbestos dosed lungs versus the controls, we have sufficient evidence of damage to warn us to do our best to prevent inhalation of concentrations of asbestos in excess of the Threshold Limit Value proposed for 1970, (Threshold Limit Values of Airborne Contaminants and Intended Changes. Adopted by ACGI1I for 1970, American Conference of Governmental Hygienists, 1014 Broadway, Cincinnati, Ohio 45202).
Summary Tables for each of the four sacrifices are Included. Detailed pathology reports on each animal are available and copies can be furnished if the need for them arises, A literature review prepared in connection with another request for Information is attached although not requested.
Acknowledgments: Inhalation Studies
Typed: September 7, 1971 - md
CS!
Charles P, Carpenter, Ph.D. Administrative Fellow
Daniel L. Geary, Jr,, M.Ed. Research Associate Edwin R, Kinkead, B.S. Fellow Roy C. Myers, B.S. Research Assistant Donald J, Nachreiner, B.S. Research Assistant
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Report 34-70 Page 3
Table 34-19 Tracheal Insufflation to Rate Sacrificed 30 Days After Dosing
TOTAL NUMBER EXAMINED CROSSLY: LUNG: Number Examined
Pneumonia Hemorrhage Pleural adhesions Stromal thickening Foam cell accumulations Granulation tissue foci Kultinucleated giant cells Abscess bronchopneumonia Round cell accumulations TRACHEA: Number Examined Chronic tracheitis
Ml of 1" Solution
1 0.5 0.0
33
(M) 3 3 (G) 3 3 (G)` 1 0 (G) 1 2 (M) 3 2 (M) 3 2 (M) 3 3 (M) 3 2 (M) 0 1 (M) 0 0
(M) 3 3 (M) 0 0
2 2 0 0 0 0 0 0 0 0 1 2 1
The following tissues were examined microscopically on all animals: Lung,
Liver, Kidney, Heart, Spleen, Adrenal , Thyroid, Parathyroid, Trachea and
Esophagus.
G Gross
M - Microscopic
Table 34-20 Tracheal'insufflation to Rats Sacrificed 60 Days After Dosing
TOTAL NUMBER EXAMINED GROSSLY :A O O -7 n ^
LUNG: Number Examined
U
Hemorrhage
Pneumonia
Atelectasis
Edema
Hemorrhage
Atelectasis
Fibrotic foreign body nodules
Bronchiolitis fibrosa obliterans
KIDNEY: Number Examined
Round cell accumulations
HEART: Number Examined
Focal myocarditis
fHJSCLE: Number Exanined
Purulent mass
Large suppurative process, striated muscle
CM) (G) (G) (G) (G) (M)
(M) (M) (M) (M) (M) CM) (M) (M) (G) CM)
Ml of 1% Solution
1_ 0.5
0.0
33 33 00
2
2 1
33 02 12 10 22
0 0 0 0
0
33 01
0 0
33 10
2 0
33 01 10 10 1-
2 0 0 0 -
The following tissues were examined microscopically on all animals: Lung,
Liver, Kidney, Heart, Spleen, Adrenal, Thyroid, Parathyroid, Trachea and
Esophagus.
G Gross
M Microscopic
Report 34-70 Page 4
Table 34-21 Tracheal Insufflation to Rata Sacrificed 90 Days After Dosing
TOTAL NUMBER EXAMINED CROSSLY* LUNG: Number Examined
Pleural adhesions Hemorrhage Edema Pneumonia Chronic foreign body pneumonia Fibrotic foreign body nodules Emphysema Chronic inflammatory cell foci Round cell foci Atelectasis Bronchiectasis Stromal thickening Hemorrhage Inhaled blood KIDNEY: Number Examined Hydronephrosis Hydronephrosis Round cell focus TRACHEA: Number Examined Chronic tracheitis HEART: Number Examined Myxoid change, interstitium
Ml of 12 Solution
1_ 0,5 0.0
33
2
00
33
2
(G) 0 2 0
(G) 0 2 0
(G) 3 3 0
(G)
33
0
(M) 2 2 0
(M)
33
0
(M) 2 2 0
(M) 3 3 0
(M) 0 1 1
CM) 3 3 0
00 2 2 0
CM)
10
0
(M)
32
0
(M) 0 1 0
(M) 3 3 3
(G) 0 0 1
(M) 0 0 1
(M) 0 1 0
(M) 3 3 3
(M) 2 1 2
00 '3 3
3
00 0 1 0
The following tissues were examined nicroscopi cally on all animals: Lung,
Liver, Kidney, Heart, Spleen, Adrenal, Thyroid , Parathyroid, Trachea and
Esophagus.
G * Gross
M - Microscopic
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Report 34-70 Page 5
Table 34-22 Tracheal Insufflation to Rats Sacrificed 180 Days After Dosing
TOTAL NUMBER EXAMINED GROSSLY: LUNG: Number Examined
Edema Pneumonia Atelectasis Emphysema Emphysema Atelectasis Inhalation pneumonia Interstitial pneumonia Abscess bronchopneumonia Suppurative bronchiectasis Acute bronchitis Lymphoid cell accumulations Foam cell accumulations Fibrotic foreign body tissue Granulation tissue foci Pink hyalin material Bluish homogeneous material Numerous mononuclear cells Mucoid infiltration Proliferation bronchiole epithelium LIVER: Number Examined Eile duct proliferation Round cell foci KIDNEY: Number Examined Hydronephrosis Sand calculi Hydronephrosis Sand calculi Dilated tubules Pink casts Interstitial nephritis Cellular infiltration Slight tubular regeneration Moderate tubular regeneration TRACHEA: Number Examined Acute tracheitis Chronic tracheitis
Ml of 12 Solution
1_ 0.5
0.0
46
5
00 4 6 5
(G) 2 0 1
(G) 4 5 1
(G) 2 0 1
(G) 0 0 1
(M) 1 2 1
00 4 1 0
00
10
0
00 0 4 0
00 0 0 1
00 1 0 0
00 0 0 1
00 3 0 0
(M) 2 1 3
00 4 6 0
00 0 1 0
00 2 0 0
(M)
31
0
(M) 1 0 0
00 2 0 0
(M) 0 0 1
<M) 4 6 5
00 0 2 1
00 1 0 0
00 4 6 5 (G) 0 1 0
(G) 0 1 0
00 0 1 0
00 0 1 0
(M) G 2 2
oo 0 2 1
00 0 1 0 (M) 0 1 0
(to 0 1 3
(M) 0 0 1
(M) 4 6 5
(M) 1 0 0
00 0 4 0
The following tissues were examined microscopically on all animals: Lung,
Liver, Kidneys, Heart, Spleen, Adrenal, Thyroid, Parathyroid , Trachea and
Esophagus.
G - Cross
M - Microscopic
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Report 34-70 Page 6
Asbestos
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Enterline, P. E. Asbestos-Dust Exposures at Various Levels and Mortality. Arch. Environ. Health, 15, p. 181, (1967).
Kogan, F, M; Svirskll, E L,; Belobragina, G. V. Gig. Tr, Prof. Zabol. 13. pp. 9-12 (Russ) (1969), Hygienic Characteristics of the Dust Generated in the Production of Asbestos-containing Thermal Insulating Materials Asbestos Vermiculite and Asbestos Perlite. As cited in C.A. V. 72(26). p, 253(136090y) 1970.
Parazzi, Elena, et al. Cytotoxicity of Asbestos Dusts. Med, Lav. 1968, 59(10). 561-76 (Eng). As cited in C.A. Vol. 71# #2, p. 256(6374n) (1969).
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~
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McDonald, J. C., et al. Mortality in Chrysotlle Asbestos Mines and Mills of Quebec. Arch. Environ. Health, 22, 677-86, June 1971, As reported in the JAMA p. 1658, June 7, 1971, Vol. 216 No. 10.
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Dust
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Marr, William T, Asbestos Exposure During Naval Vessel'Overhaul. AI1LAJ, 25 (3), pp. 264-268, May-June 1964.
Thomson, J. G., and W. M, Graves, Asbestos as an Urban Air Contaminant, Arch. Pathol. 81; 45b (1966).
Westlake, George E., Harlan J. Spjut, and Marilyn N, Smith. Penetration of Colonic Mucosa by Asbestos Particles. An Electron Microscopic Study in Rats Fed Asbestos Dust* Lab. Investigation, 14: 2029 (1965).
Analytical
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