Document KJ0EJjJNvJgKo55ar1gNyeKvK
FILE NAME: Union Carbide (UC)
DATE: 1966 July 8
DOC#: UC201
DOCUMENT DESCRIPTION: Unpublished Report - The Fibrogenic Potential of Asbestos Products via Intraperitoneal Injection in Guinea Pigs, Rats & Rabbits and by the Intratracheal Route in the Rat
Confidential Report 29-55
P r ec eiv ed ' JULI 81966
Bidg. 701 Li b r a r y
P lease DO NOT REMOVE FROM LIBRARY
MELLON INSTITUTE Special Report
The Fibroeenlc Potential of Asbestos Products
R: 7-8-66
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1- pages
PtAWn???
lb EXHIBIT
Uruon Carbide 98
via Intraperitoneal Injection in Guinea Pigs. Rats and Rabbits
and by the Intratracheal Route in the Rat
Chemicals Division. Union Carbide Corporation_____ Industrial Fellowship 274-29
The results of intraperitoneal administration indicate that the asbestos products studied produced fibrotic lesions of the visceral organs in rats and guinea pigs regardless of fiber length. Of the three products, CMS-100 (refined fiber), produces the most severe reaction. JT-100 (standard fiber) and JM-3K (Johns Kanville screened fiber) produced similar but less severe reactions. The results on rabbits were inconclusive.
Both JT-100 and CMS-100 produced specific lesions in rats by the intra tracheal route but with JT-100 they were more severe. No lesions were found in the rats which received JM-3K. fibers.
These results indicate that these three asbestos fibers may be fibrogenic by either route. No specific lesions were observed in the lungs of the JM-3K intratracheal rats, but only two rats survived to be examined.
Samples
The following samples were shipped to Mellon Institute at the request of Mr. Paul W. McDaniel who furnished the descriptive information.*
Designation of Asbestos Product
Soarce
Quan tity
Date Received
M. I. Sample Number
`CTS-100 Fiber (same as JT-100 Fiber) "Standard Fiber" containing impuri ties in the form of clay and magne tite. A short fiber.
Sterling
Forest
8 02.
8-14-63
26-220
*CMS-100 Fiber "Refined Fiber" with lesser impurities than JT-100. A short fiber.
Sterling Forest
8 oz.
8-14-63
26-219
* The individual fibers for most part had lengths of 0.9 to 10 microns, but there were some as long as 30 microns and some th.t were less chan 0.5 micron. The diameters of the fiber were generally 0.3 to 1.2 microns, but there were smaller sizes noted. The clay-magnetite particles were mostly 0.5 to 3.0 microns in diameter but there were some present as small as 0.08 micron (by electron microscope).
i
Designation of Asbestos Product
JM-3K Fiber. Long Fiber" (Brushed through screen to reduce fiber length to 1 nm. or less before injecting.)
Source Manville, N.J.
Report 29-55 Page 2
Quan-
Date
City Received
M. I.
Sample Number
8 oz. 8-26-63 26-22?
Methods
Intraperitoneal Injections
JM"3K asbestos as brushed through a 1 mm. screen to reduce its
andCJT-100`asbest "?*** (1* " *> ln rder t0 facilitate dosing. The CMS-100
pared as a
f reCeived* Each asbestos product was pre
pared as a 2.52 (W/V) suspension in 0.852 saline. All needles, syringes and
suspensions were sterilized prior to use. The animals were divided into three
S ? s P(R)eaaidCtwo i"8 f.elVen Bale albino guinea pigs (P), six male albino rats (R), and two male albino New Zealand rabbits (H). The guinea pigs and rab-
(25 m g T n r ? h intraperl<t0neal
2 1- (50 mg.) and the Lts, f m l
( 5 mg.) of the respective asbestos suspensions. Eleven guinea pigs and six
lntraperitoneal injections of salinf. TM . i e we" ,o
ra bit controls. All injections were made in the lower right auadrant of the
abdomen. T.U.s 29-92 through 29-95 cont.ln the ,, . 1 ? "
.file.
Results
giant cellSMiii1s L Pir1th!d ^
SeVere reaction in the form of granulomas with
giant cells in six of the seven guinea pigs examined mieropatholoeicallv Tvniral
granulomas with giant cells oar. observed*! three of f o u ^ i .
Shu.
8
,,ill100 as*?stos fiber Produced a granulomatous reaction in all of the
Thf iabbits hadSincid 5 ? T ^ subJected t0 mcropathological examination. The rabbits had incidental lesions unrelated to the asbestos fibers,
five of ttJhf<i!!~3V SbeS,C0S fibrS produced granulomas with fibers visible in wwhhiicchh wLass vvi/sJibmleUon grosPs83exaemxianmaltnieodn'. 0ne of two rats had granuloma formation
Methods
Intratracheal Injection
One per cent (W/V) suspensions of JT-100, CMS-100 JM-3K. and a 0 52
" ;" i" . c"s-100 v" e pre!,*rc'i in -85,;
i h. m t " ; . : ; , !
Page 3 Feaale albino rats weighing in excess of 200 grans were elver, 1 ,,1
a V X 2 `:rSS sip? - 2SE^L'StZZL
-- - j . X r S t . ^ L i ' i s s - S e 1 f ; i ofo*
<" *
TOe" eMdWH,
" ' f ? " 1" f CMS- 10 "S" ' y three rate
I S is i
Results
if l"
d' " = !
s - " shiJ "
ously a b s ^ in theri W * granulomas of the JT-100 rats but were conspicu-
on only S T r a ^ e c e ^ n g M T s t l t t T
f ic-Phology was performed
similar to JT-100 or cis-?00
aSbeSt0S' Neither f hese i l s had lesions
Approved :
Acknowledgments: Technical Assistance Pathological Examination Data in Book 868, pp. 63 to 90 and 99-109.
Typed: July u , 1966 - aid
Edwin R. Kinkead, B.S. Research Associate
L & Yk/yf 'TU'
Urbano C. Pozzanii,, m Ts . L. Senior Fellow
i4-*>(^?.Y..r5Charles P. Carpenter
Assistant Administr.
Fellow
Charles C. Haun, B.S., Junior Fellow John M. King, Ph.D,, DVM, Fellow
Dose of Asbestos
Animal Number
50 mg. (2 ml. of 2.j7. suspension)
P. 96813 P. 96803
P. 96815 P. 96806 P. 96802
-
P. 96807
P. 96810
P. 96811
P. 96812
P. 96814
P. 96821
H. 96737 H. 96574
Ta b 1- 29'92
Intraperitoneal Injections of Asbestos CMS-100
Days to Death or Sacrifice
___________ Gross P a t h o l o g y ________
20 D
75 D
240 D 270 D 286 S
Peritonitis; asbestos scattered throughout abdominal cavity.
Peritonitis; adhesions of intestines to liver.
Autolyzed.
No asbestos in abdominal cavity. Multiple small adhesions of the omentum
to the mesentery.
286 S 286 S
Adhesions of liver to stomach. Deposits scattered In the intestinal mesentery.
Omentumal adhesions to liver with deposits in the omentum.
286 S
Intestinal adhesions to midline and seminal vessels.
286 S
Areas of fibrosis in most of left liver lobes.
286 S
Adhesions-- liver to stomach and intestines.
286 S
Adhesions of abdominal wall to liver, stomach and omentum with deposits.
60 D 270 S
Numerous deposita of asbestos adherred to intestines.
Multiple adhesions, ventral colon and urinary bladder.
_______ Micropatholoev_________
Not examined.
Not examined.
Not examined. Not examined. Several small, well marked granu
lomas with giant cells on the serosal surface of colon. Liver-- marked granulomatous re action on the surface. Granulomas-- serosal wall. Liver-- well marked granulomas. Marked chronic granulomas in the intestine and diaphragm. Intestinal, liver, skeletal muscle-- adhesions to each other. Areas of giant cell formation. Colon-- large cystic masses filled with debris. Lined by columnar epithelium. Liver-- fibrosis and granuloma formation. Foreign body granu lomas on abdominal wall. Granulomatous lesions of the stomach, liver and skeletal m u s c l e . _______________
Not examined.
Multiple well encapsulated granu lomas present with innumerable giant cells.
(Continued)
V !*) 0
09
0 O M
ft
N> vO
>ose of Asbestos
Animal Number
'5 mg. One ml. of 2.5% uspension)
R. 9571 R. 9678
R. 9629
R. 9631
-
R. 9639
R. 9660
Table 29-9-
(Continued)
Days to Death or Sacrifice .
______ Cross Pathology__________
20 D 170 D 258 S 258 S 258 S 258 S
Congested lungs and liver; asbestos scattered throughout abdominal cavity.
Asbestos deposits throughout abdominal area.
Nodules of white material in mesentery, ventral and abdominal wall.
Deposits in the mesentery and ligaments of the testicle.
Chronic abscess pneumonia. Scattered deposits in mesentery and wall
of small intestines. Adhesion of testes to intestines.
________ Micropatholoev___________
Not examined.
Not examined.
Scattered granulomas in intestine and skeletal muscle.
Multiple granulomas with giant cells and asbestos deposits.
Chronic bronchopneumonia. Large granulomas, well encapsulated.
v Jg>
09 U
& o O,i Hrt
NJ VO VIn In
I
Dose of Asbestos
Animal Number
50 mg. (2 ml. of 2.5% suspension)
P. 96844 P. 96851
P. 96849
P. 96834
** P. 96835 P. 96837 P. 96839 P. 96840 P. 96841 P. 96847
P. 96848
Table 29
Intraperitoneal Injections of Asbestos JT-100
Days to Death or Sacrifice
Gross Pathology
_________ Mlcropathology________
11 D 150 D 185 D 286 S
286 S 286 S 286 S 286 S 286 S 286 S
286 S
Peritonitis, asbestos scattered throughout abdominal cavity.
Entire gut adherred together. Liver adherred to ventral wall and diaphragm.
Multiple visceral adhesions of the asbestos to the ventral abdominal wall.
Gray deposits in the ventral abdominal wall.
Severe multiple adhesions with pus in corporated.
Multiple intestinal adhesions. Gray deposits in the abdominal wall.
Omental adhesions to the liver with tiny deposits in this mesentery.
Spleen adherred to ventral wall, stomach to diaphragm.
Multiple tiny deposits on left liver lobes and left abdominal wall.
Omental adhesions to the ventral tips of the liver.
Deposits on the intestinal mesentery and abdominal wall with omental adhesions.
Not examined.
Not examined.
Not examined.
Scattered foreign body granulo ias with slightly elongated fibers of asbestos in them.
Typical granulomas.
Adherred masses with many granu
lomas on the serosal surface.
Typical connective tissue granu lomas.
Typical connective tissue granu
lomas .
'
Numerous granulomas with foreign
bodies present in them.
Typical granulomas with foreign
bodies, giant cells, fibrosis
present.
Typical connective tissue granu les .
H. 96729 H. 96734
270 S 270 S
Heart covered by chronic connective tissue.
Multiple serosal deposits scattered pri marily on the colon and ventral wall.
Essentially normal. Essentially normal.
(Continued)
V fc > it oo u ft o
ON f t
K> \o iIn Un
Dose of Asbestos
Animal Number
25 mg. (One ml. of 2.5X suspension)
R. 4576 R. 4536 R. 4534
R. 4617
R. 4596
Table 29-y3
(Continued)
Days to Death or Sacrifice
Cross Patholoev
36 D 160 D 200 D
242 D
258 S
Cannibalized. Autolyzed.
Peritonitis, pleuritis, some fibrosis in plMural cavity.
Pneumonia. Asbestos particles scattered throughout entire abdominal cavity.
Slight deposits in the mesentery and omentum.
Microoathol. cv
Not examined Not examined. Not examined.
Not examined.
Intestine-- typical granulomas with foreign bodies.
Report 29-55 Page 7
Table 2e 4 Intraperitoneal Injections of Asbestos JM-3K
Report 29-55, Page 8
Q CO
Dose of Asbestos
Animal Number
50 mg. (2 ml. of 2.5% suspens ion)
P. 96829
P. 96833 P. 96830
P. 96826
-
P. 96828
P. 96832
P. 96822
P. 96823
P. 96824 P. 96827 P. 96831
Days to Death or Sacrifice
____________ Gross Pathology
43 D 64 D 76 D 78 D 86 D 286 S
286 S
Peritonitis, asbestos adherred to ven tral wall and small intestine.
Intestines adherred to ventral wall. Scattered adhesions to ventral abdominal
wall. Peritonitis, liver and stomach adhbrred
to ventral abdominal wall. Peritonitis, asbestos scattered through
out abdominal cavity. Intestines adherred to ventral abdominal
wall. Abscessed at point of adhesion. Multiple adhesions of the liver to the
stomach, omentum, and intestines.
Deposits on right seminal vessel.
286 S 286 S 286 S
Greenish deposits in the ventral abdominal wall and omentum with adhesions to liver.
Midline omental adhesions to greenish deposits.
Liver adherred to ventral abdominal wall.
________ Mlc ropathology______ _
Not examined.
Not examined. Not examined.
Not examined.
Not examined.
Not examined.
Foreign bodies. Granuloma attached to intestinal wall. Some granu lomas in liver.
Seminal vessel-- granulomatous re action with foreign material in soft tissue and mesentery.
Foreign body granulomas with foreign material present.
Deposits of foreign material and large granulomas on muscle.
Tip of liver infectious; abscess formation, granuloma formation.
H. 96764 H. 96697
25 mg. (One ml. of 2.5% suspension)
R. 4628 R. 4622
R. 4623 R. 4615 R. 4578 R. 4583
60 D 270 S
35 D
230 D
234 D 241 D 258 3 258 S
No asbestos in peritoneal cavity. Asbestos at site of injection.
Not examined. Essentially normal.
Pneumonia. Intestine adherred to the ventral wall.
Pasturella Pneumonia. Intestines ad herred to abdominal wall with each other.
Autolyzed. Pasturella Pneumonia.
Adhesions of the omentum and mesentery. Middle ear Infection.
Not examined.
Not examined.
Not examined. Not examined, Essentially normal. Essentially normal.
Dose of Saline 2 ml.
Table 29-95 Intraperitoneal Inlections of Saline Control
Animal Number
P. 96857 P. 96856 P. 96853 P. 96858 P. 96852 P. 96859
P. 96860
P. 96861 P. 96862 P. 96863 P. 96869
Days to Death or Sacrifice
___________ Gross Pathology______ ____
88 D 156 D 170 D 207 D 286 S 286 S
Pneumonia. Pneumonia. Pneumonia. Pneumonia. Essentially Essentially
normal. normal.
286 S
286 S 286 S 286 S 286 S
Emaciated. Liver massively reduced in size.
Essentially normal. Essentially normal. Chronic nephritis in both kidneys. Essentially normal.
One ml.
R. 9489 R. 4483 R. 4531 R. 4540 R. 4542 R. 4557
12 D 258 S 258 S 258 S 258 S 258 S
Pneumonia. Chronic abscessed pneumonia. Essentially normal. Essentially normal. Essentially normal. Essentially normal.
_______ Micropathology_________
Mot examined. Mot examined. Mot examined. Mot examined. Essentially normal. Scattered areas of interstitial
pneumonia. Liver necrosed and abscessed.
Essentially normal. Essentially normal. Chronic interstitial nephritis. Essentially normal.
Not examined. Massive abscessed pneumonia. Essentially normal. Essentially normal. Essentially normal. Essentially normal.
Report 29-55 Page 9
Dose of Asbestos
10 mg. (One ml. of 17. suspension)
Rat Number
84636
84645
*
84702
5 mg. (One ml. of 0.57. suspension)
72531 81427
81433
81440
72528 77679
77680 81600
Table 29-96 Intratracheal Injections of Asbestos CMS-100 to Rats
Days to Death or Sacrifice
30 S
Pneumonia.
90 S
Pneumonia.
Cross Patholoav
180 S
Chronic pneumonia.
12 D 30 S
90 S
90 S 180 S 180 S 180 S 180"S
Cannibalized. Lung-- appeared normal.
No lesions.
Chronic pneumonia. Not recorded. Lipid foci in lungs. Gray foci in lungs. Pneumonia.
Pneumonia, numerous granulomas scattered throughout lung.
Pneumonia, lesions of bronchiolitis obliterans 16 several bronchi' and btonchioles.
Scattered granulomas; lesions of bronchiolitis obliterans with foreign material and thromboticlike areas.
Not examined. Multiple granulomas; bluish ma-
terlal present in all granu lomas . Scattered small granulomas. Some bronchiolitis obliterans also apparent. Pneumonia; scattered granulomas; bronchiolitis obliterans. Scattered small granulomas. Bronchiolitis obliterans. Chronic granulomas sans giant cells. Numerous scattered granulomas. Multiple granulomas scattered throughout lung. Bronchiolitis obliterans.
d 5*J OPQ *XJ A O
to \> I
I
U1
Dose of Asbestos
10 mg. (One ml. of 17. suspension)
Rat Number
84629
84672 84669 84633
84659
84674
84676 84631
Table 2( / Intratracheal Injections of Asbestos JT-100 to Rats
Days to Death or Sacrifice
__________ Grosa Pathology__________
60 D
123 D 151 D 30 S
Large white areas on lung* of the right lung. ,
Pneumonia. Pasturella Pneumonia. Chronic pneumonia.
atelectasis
30 S
Chronic pneumonia.
90 S
90 S 180 S
Pneumonia.
Chronic abscessed pneumonia. Not recorded.
._________ Micropatholoay
Bronchiectasis. Areas of acute bronchopneumonia.
Not examined. Not examined. Multiple granulomas and bronchi
olitis obliterans. Pneumonia; granulomas, large
lesions of bronchiolitis obliterans. Numerous granulomas, well marked bronchiolitis obliterans. Scattered granulomas. Cr'anulomas, some bronchiolitis obliterans.
Dose of Asbestos
10 mg. (One ml. of 17. suspension)
Rat Number
84695 84635 81214 81171
81161 84660
Table 29-98 Intratracheal Injections of Asbestos JM-3K to Rats
Days to Death or Sacrifice
Gross Pathology
10 D 13 D 15 D 50 D
30 S 180 S
Entire lung was dark red.
Chronic pneumonia.
Pneumonia and emphysema.
Chronic pneumonia; bronchial lymph nodes,
enlarged and gray.
*
Chronic pneumonia.
Chronic pneumonia and enlarged lymph
nodes.
________ Mlcropathology_____
Not examined. Not examined. Not examined. Not examined.
Chronic bronchopneumonia. Chronic bronchopneumonia, a few
scattered granulomas.
Dose of Saline One ml.
Rat Number
78253 78273 78302 78717 34639 84646 8*651 84677
Table 29-99 Intratracheal Injections of Saline to Rata
Days to Death or Sacrifice
Gross Patholoav
30 S 30 S 90 S 90 S 180 S 180 S 180 S 180 S
Essentially normal. Essentially normal. Essentially normal. Azygous Abscessed. Essentially normal. Essentially normal. Essentially normal. Essentially normal.
Essentially normal. Essentially normal. Essentially normal. Few areas of chronic Essentially normal. Essentially normal. Essentially normal. Essentially normal.
pneumonia.
Report 29-55 Page 12
t
MAILING U S X
Medical Departments
4 - C. U. Demehl 1 - E. Q. Hull 1 - R. E. Joyner 1 - R. J. Sexton 1 - F. E. Medford
2 - R & D Department Library S. Charleston, W. Va.
10 - P. McDaniel 1 - N. H. Ketcham