Document nm3QwdGYepGnmg7m5RJDGLBe1
FILE NAME: Union Carbide (UC)
DATE: 1966 July 8
DOC#: UC028
DOCUMENT DESCRIPTION: Special Report from Mellon Institute - The Fibrogenic Potential of Asbestos Products
PLAINTIFF'S EXHIBIT
Confidential Report 29-55
MELLON INSTITUTE Special Report
R: 7-8-66
/ fr J 7~t>-I (o 12 page
The Fibrocenlc Potential of Asbestos Products via Introneritoneal Injection In Guinea Pies. Rats and Rabbits
and bv the Intratracheal Route In the Rat
Chemicals Division. Union Carbide Corporation
.
.
Summary
Industrial Fellowship 274-29
The results of Intraperitoneal administration Indicate that the asbestos
-products studied produced flbrotlc lesions of the visceral.^organs In rata 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 Manville screened fiber) produced similar hut less severe reactions. The
results, on rabbits were inconclusive.
- '
'
Roth JT-100 and CMS-100 produced specific lesions In rs by (the Intra tracheal route but with JT-100 they were more severe. Mo lesions were found In the rats which received JM-3K fibers'. . .
These results Indicate that these three asbestos fibers ay he flbrogenic by either route. Mo specific lesions were observed in the lungs of the JM-3R Intratracheal rats, but only.two rats survived to he examined.
Samples
The following samples were shipped to Mellon Institute lit th request of
Mr. Paul V. McDaniel who furnished the descriptive information.
'
Designation of Asbestos Product
,, *CTS-100 Fiber (same as JT-100 Fiber) "Standard Fiber" containing impurities in the form of clay and magne-
j, tlte. A short fiber.
Soorce Sterling Forest
Quantltv
6 os.
`
M. I.
Mate Sample
, Mectlved / Number
-
,
8-14-63 26-220
-
'
*CMS-100 Fiber "Refined Fiber" with
lesser Impurities than JT-100. A ' short fiber.
Sterling Forest
8 os.
'
8-14-63
26-219
:
t
* The individual fibers for most part had lengths of 0.9*to 10 microns, but there were some os long as 30 microns and some that were lesa than 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
Designation of Asbestos Product .
Source
JM-3K Fiber. "Long Fiber" (Brushed through screen to reduce fiber length to 1 son. or less before injecting.)
Manville, N.J. *
Report 29-55 .Page 2
QuantitJL.
8 os.
Date Received
8-26-63
M. 1. Sample Number
26-227
Intraperitoneal Injections
Methods
The JH-3K asbestos was brushed through a 1 atm. screen to reduce. Its fiber length to < 1000 micra (1.0 am.) in order to facilitate dosing. The CMS-100 and JT-100 asbestos samples were used as received. Each asbestos product was pre pared as a 2.52 (W/V) suspension in 0.852 saline. All needles syringes and suspensions were sterilised prior to use. The anlstals were divided into three groups-- each consisting of eleven stale albino guinea pigs (P), six sale albino rats (R), and two stale albino Mew Zealand rabbits (H). The guinea pigs and rab bits received intraperltoneal injections of 2 si. (50 sg.) and the rats 1 si. (25 sg.) of the respective asbestos suspensions. Eleven guinea pigs and six rats received control intraperltoneal injections of saline. There vers no rabbit controls. All Injections were made in the lower right quadrant of the abdomen. Tobies 29-92 through 29-95 contain the results oq individual animals.
Eesults .
CMS-100 produced the sost severe reaction in the form of granulomas with
giant cells in six of the seven guinea pigs examined slcropathologlcally. Typical
granulomas with giant cells were observed in three of four rats and the one rabbit.
JT-100 asbestos fiber produced a granulomatous reaction in all of the * 8 guinea pigs as well as the one rat subjected to sicropathologleal examination. The rabbits bod incidental lesions unrelated to the asbestos fibers.' ''
The JM-3K asbestos fibers produced granulomas with fibers visible in five of the five guineo pigs examined. One of two rati had granuloma formation which was visible on gross examination.
Intratracheal Inlectlons
Methods
*
One per cent (W/V) suspensions of JT--100 CMS--100 JM--3K and a 0.52
suspension of CMS-100 were prepared In 0.852 sqline as for the Intraperltoneal
injections.
'
.
.
* s
'
.
Report 29-55 '
*
; . ;
Page 3
Female albino rots weighing in excess of 200 grams wr given 1 ml. of ; the respective asbestos suspensions by intratracheal injection. Th rats were anesthetized with saturated vapor of anhydrous diethyl*ether. The trahea w exposed by blunt dissection and the injection was made directly.and the incision
closed with a Michael Wound Clamp.
.
Eight rots were injected with 1* *1. of a IX JT-100 suspension <10 mg.
asbestos). Eight rots were injected with 1 1. of a IX
Jurats
mg. asbestos). Because of the flocculeut properties of C M S - r4t*
were dosed with 1 ml. of a IX suspension (10 mg. asbestos). f ^ t rats "*r*
injected with 1 ml. of a IX CMS-100 suspension (5 mg. asbestos), fix rats injected
with physiological saline served as controls. Tables 29-96 through 29-99 contain
results on Individual animals *
Results
*
.
Specific lesions were found in most of the rats given CMS-100 and^JT-100
that consisted of'marked granuloma formation with bluish foreign body material
bron.hl.llti. .bllt.r.n. w.. M t W t e . t r . t . .1..
with bluish foreign body material within the l**lns.
t^ila
severe fibrotic reaction to this foreign material. Multinudeata giant calls
!!r!" conmon futur. with th. ,r.ouloM. ol th. JT-100 r.t. bot w.r. ton.,len-
.i.ly ab.ont in th. lung, of th. r.t. lv.n CHS-100. HUrop.tholMy w.. .rtorl
on only two rot. rcivin, JH-3K >>b.to.. K.lth.r of th... .nlnol. hid l.lon>
similar to JT-100 or CMS-100.
*
Edwin R. Kinkead,' B.S.
Research Associate
Approved:
Acknowledgmentsi Technical Assistance Pathological Examination Data in Book 868, pp. 63 to 90 and 99-109.
Typed:* July 11, 1966 - aid
Urbano C. Pozzani, H.I Senior fallow
Charles P. Carpenter,/rh.p. Assistant Administrative fellow
Charles C. Baun, B.S., Junior Fellow John M. King, Ph.D., DVM, Fellow
ud^ /r
Twtraoeritonesl Inlection ofAsbestos CH3-100
Dose of Asbestos 50 mg. (2 ml. of 2.52 suspension)
-
Animal Number
Days to Death or Sacrifice
P. 96813 20 D
P. 96803 75 D
P. 96815
p. 96806
P. 96802
260 D
270 D
286 S
P. 96807 286 S
P. 96810 286 8
P. 96811 286 8
P. 96812 286 8.
P. 96816 . 286 0
P. 96821 286 8
* Croat Pathology
Mtcronathologv
Peritonitis; beato catterei throughout Not examined.
abdominal cavity. Peritonitis; adhesion of intestine to.
Not examined.
liver.
.
Aotolysed. . No asbestos in abdominal cavity. *
Multiple snail adhesions of the omentun
to the mesentery.
Adhesions of liver to stomach. Deposit scattered in the intestinal, mesentery
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.
Omentonal adhesions to liver vith deposits
in the omentun.
.
Intestinal adhesions to midline and
seminal vessels..
.
. *
Arsis of fibrosis in most of left liver
'lobes.
.
*
.. ... .)}.
Adhesions-- liver to stotbach and intestines.
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.
Adhesions of abdominal usili to liver* stomaeh and omentum with ^epoalti.
Granulomatous lesions of the stomach, liver and skeletal muscle.
H. 96737 H. 96576
60 D 270 8
Numerous deposits of asbestos adherred.
to intestines. *
.
Multiple adhesions* venreal colon and
urinary bladder.
Not examined. '
Multiple well encapsulated granu
lomas present with Innumerable
giant cells.
.
(Continued)
*V SB
W *5
* 8 rt
is*
e of Asbestos
-< a. if
Days to Death o Sacrlfl
mg.
*. 4571
te ml. of 2.52
-.pension)
R. *678
20 D 170 D
R. *629
258 S
R. *631 %
R. 463* R. *660
258 S
258 S 258 S
Tabla 29-91
(Continued)
Cross Pathology
Congested longs and liver; asbestos scattered throughout abdominal cavity.
Asbestos deposits throughout abdominal
area. Modules 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.
.
*
Micronsthology
Sot examined.
Kot examined.
Scattered granulomas in intestine and skeletal nuscle.
Multiple granulomas with giant cells and asbestos deposits.
Chronic bronchopneumonia. Large granulomas, well encapsulated.
Table 29* Intraperitoneal Injection ofAsbesto JT-100
noea of Aabestoa
I
50 mg. . (2 ml. of 2.5% suspension)
Animal Humber
P. 96844
P. 96851
P. 96849
P. 96834
P. 96835
- P. 96837
P. 96839
P. 96840
P. 96841
P. 96847
P. 96848
Dayp to Death or Sacrifie
Greg Pathology
11 D 150 D . 185 D 286 S '
286 S 286 S ' 286 S 286 S 286 8 286 S
Peritonitis asbestos scattered throughout
abdominal cavity. Entire gut. adherred together. Liver ad-
herred to ventral wall and diaphragm.
Multiple visceral adhesions of the asbestos
to the ventral abdominal vail.
Gray deposits in the ventral abdominal
wall.
. ,,V" .V -
SePtrt Multiple adhesions with pus In
corporated.
* .
Multiple Intestinal adhesions. Cray
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 deposite on left liver
. lobes and left abdominal wall.
Omental adhesions to the ventral tips of
~ the liver.
286 $
Oepotiti on the intestinal mesentery and abdominal wall with omental adhesions.
Mlcrooathologv
Mot examined.
Mot examined.
Mot examined.
Scattered foreign body granulomas 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.
'
.-i
Typical connective tissue granu
les.
It. 96729 H. 96734
270 S 270 S
Smart covered by chronic connective
tisane. Multiple serosal depocit* scattered pri
marily on the colon and ventral wall.
Essentially normal. Essentially normal.
(Continued?
Animi
Dos of Asbesto Number
25 mg
* *576
(On al* of 2,31 R, 4536
suspension)
.R *534
R. 4617
R. 4596
tabi -*3 (Continued)
Days to Death or* Sacrifie
Cross Pathology
36 D ' Cannibalised.
.
160 0 * Autolytedr
' -'
200 D Peritonitis, pleuritis, owe fibrosis in
pltSural cavity.
*
242 D
Pneumonia. Asbestos particles scattered
throughout entire abdominal cavity.
258 S Slight deposits in the mesentery and
onentue.
Mlcrooatholoffv
Rot examined. Rot examined. Not examined.
Rot examined.
Intestine-- typical granulomas with foreign bodies.
&
I
|
i
?
1
.
r. . v-.
4
Report 29-55 Page 7
h ,.
i
Tabla V '6
Intraperitoneal Injections of Asbestos JH-3K
Animal Number
Days to . Death or. Sacrlflei
Croaa Patholotv
Micronstholorr
0 g.
P. 96829 18 D . Peritonitis, asbestos adherred to ven
Kot examined.
,
2 1. of 2.58
tral vail and small intestine.
uspension)
P. 96833 63 D
Intestines adherred to ventral vail.
Mot examined.
P. 96830 66 D
Scattered adhesions to ventral abdominal
Not examined.
"
P. 96826 P. 96828 P. 96832 P. 96822
76 D 78 D 86 D 286 S
P. 96823 286 S
vail. Peritonitis* liver and stomach adherred
to ventral abdominal vail.
Peritonitis* asbestos scattered through
out abdominal cavity.
,
Intestines adherred to ventral abdominal
vail. Abscessed at point of adhesion.
Multiple adhesions of the liver to the
stomach* omentum* and intestines.
'
Deposits on right seminal vessel.
Kot examined.
.
Not examined,
' * '
Not examined.
Foreign bodies. Granuloma attached to intestinal vail. Some granu lomas in liver.
Seminal vessel-- granulomatous re action with foreign material in
soft tissue and mesentery.
P. 96826 P. 96827 P. 96831
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 vail.
<
Foreign body granulomas vith foreign material present.
Deposits of foreign material and large granulomas on muscle.
Tip of liver infectious;, abscess formation, granuloma formation, v X) o H
N. 96766 '60 D * No asbestos in peritoneal cavity.
Not examined.
M
H. 96697 270 8
Asbestos at site of Injection.
Essentially normal <
VO
I
V
5 ogf.'.'li^v'.
: ju:,6628 .;;r.33o;: $
Pneumonia. Intestine adhered to the ' \ ( iNot examined.
i . ventral mall. >
. .` .'
One ml?;of. 2,58 > i
uspensldn)
1. 6622
' J -4M. *.230 D.; w Pasturalla Pneumonia. Intestinea ad-
..v Not examined*
0I9
..herred to abdominal vail vith each other.
;
< i;l
V
1*6623 236 d : Autolyred. .
. yA .Not examined.
-
.
.\1* 6615 ...V.261 D - Pasturalla Pneumonia.
.
. .
Not examined.
i
1.6578 ' ; 258 8.' Adheaions of the omentum and mesentery.;
Essentially normal.
1. 6583 . ! 258 8
Middle ear infection.
Essentially normal.
*
Titbit 29-^95
Iiitraoerltonaal Injection of Online Control
' lose of Saline l ml.
*
Animal Number
P. 96857 P. 96856 * P. 96853 P. 96858 P. 96852 P. 96859
P. 96860
P. 96861 P. 96862 P. 96863 P. 96864
Days to Death or Sacrifice
Cross Pstholoev
88 D
Pneumonia.
. .
156 0
Pneumonia.
170 D
Pneumonia.
207 D
Pneumonia.
..
286 S
Essentially normal.
286 S
Essentially normal.
286 S
286 S 286 S 286 S 286 S
Emaciated. Liver massively reduced in
sire.
'
Essentially normal.
Essentially normal;
<
Chronic nephritis in both kidneys.
Essentially normal.
tie ml.
1 4484 R. 4483 R. 4531 ' R. 4540 R. 4542 R.'4557
12 0 258 8 258 8 258 8 258 8 258 S
Pneumonia.
. .
.
Chronic abscessed pneumonia.
v
Essentially normal.
Essentially normal.
Essentially normal.
Essentially normal.
a
r`
N
Micropathology_______
Not examined. Not examined* Not examined* Not examined. Essentially normal. Scattered areas of interstltlnl
pneumonia. Liver necrosed and abscessed.
Essentially normal. Essentially normal. Chronic interstitial c.. uriti s . Essentially normal.
Not examined*
Massive abscessed pneumonia.
Essentially normal.
Essentially normal.
;
Essentially normal.
Essentially normal. .
Report 29-55 Page 9
' ' V. >
V ->.-\
v '
..
9
Tabi 29-9
*
Intratracheal Injections of Asbesto CHS-100 to tata
Rat
se of Asbesto* Kunber
n*e* of.I-X
spanatoti)
84636 8464S
84702
Days to Death or Sacrifica
Cross Pathology
30 S
Pneumonia.'
90 S
Pneumonia.
180 S Chronic pneumonia
>ne ml. of .5Z suspension)
72531 81427
81433
81440
72528 77679
77680 81600
12 D
Cannibalised.
30 8
90 8
Ho lenient*
' \ ' .
- ,
90 S
180 S 180 8
180 8 180^8
UnTyluC pHvmRniis
,
not recorded.
. .
lipid foci in lungs.
Cray foci in lungs. - / ; ' Pneumonia. '
'4 ! *r>'i - -N-.% .,V"
Mlcronethology
Pneumonia, numerous granulomas
scattered throughout lung.
Pneumonia, lesions of bronchiolitis obliterans in several bronehi
and bronchioles.
i
Scattered granulomas; lesions of
bronchiolitis obliterans with
foreign material and.thrombotic-
like areas.
;
Rot examined. Multiple granulomas; bluish ma
terial present In all granu
lomas.
i
Scattered small granulomas; Some
bronchiolitis obliterans also
apparent.
'
Pneunonia; scattered granulomas;
bronchiolitis obliterans*
Scattered small granulomas. .
Bronchiolitis obliterans. Chronic
granulomas sans giant cells,
numerous scattered granulomas.
Multiple granulomas scattered
" throughout lung. Bronchiolitis
obliterans.
1 i
.
#
.. .'
??
0 u
9 O
H M O I
Ut
,
Table {..* 7
Intratracheal Infections of Asbestos JT-100 to Rats
Bat
l-o-s-e--of Asbestos! Number'
10 mg.
84629
(One ml. of 11
suspension)
. 84672
84669
84633
84659
Days to Death or Sacrifice
Cross 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 8
Chronic pneumonia.
'
84674
90 S
Pneumonia.
'
84676
90 S'
Chronic ibteeesed pneumonia.
84631
180 S
Kot recorded.
.
Mlcrcoatholocr
Bronchiectasis. Areas of acute
bronchopneumonia.
Not examined.
Not examined. Multiple granulomas and bronchi
olitis obliterans.
Pneumonia; granulomas, large
lesions of bronchiolitis
* obliterans.
' u
Numerous granulomas, well marked
bronchiolitis obliterans.
Scattered granulomas.
Granulomas, some bronchiolitis
obliterans.
* Table *9-98
Intratracheal injections of Asbestos JM-3R to Pats.
lose of Asbestos
10 mg. [One ml. of It mspenalon)
Rat Number
84695 84635 81214 81171
.81161 84660
Days to Death or Sacrifice
Cross Pathology
10 D 13 D 15 D 50 D
30 8 * 180 3
Entire long mat dark red.
Chronic pneumonia. .
Pneumonia and emphysema % Chronic pneumonia; bronchial lymph nodes,
enlarged and gray.
Chronic pneumonia.
Chronic pneumonia and enlarged lymph
nodes.
' ..
Micropathology
Not examined. Not examined. Not examined. Not examined.
Chronic btonchopneumonia. Chronic bronchopneumonia, a few
scattered granulomas. .
$ k*
Table 29-99
Tntratracheal Injections of Selina to 9ata_
none of Salina One ad*
. ..... Rat Number
78253 . 78273
78302 78717 84639 84646 8*651 84677
Days to Death or Sacrifice
CtoasfathelgBL
30 8 30 S 90 S 90 S 180 S 180 S 180 S 180 S
Essentially normal. Essentially nomai. Essentially nomai. Azygoos Cbecessed. Essentially normal. Essentially normal. Essentially normal. Essentially normal.
t^ X
Mlcronathologv-
Essentlally normal. Essentially normal. Essentially normal. fetr areas of chronic
Essentially normal Essentially normal. Essentially nomal. Essentially normal.
pneumonia.
Report 29-55
' HM