Document zN0dz07jn0mqMrGqd8K3zrMR
#
ETHYL CORPORATION
TOJ'COWOr UNO IMOUVTmAl hTQKNI (IffAKfUfKI
Ethyl Tower. 451 Kuirioa Baton Koook, Loui.srA.rsvv 7<Hut
504/388-7858
July 1G, 1971)
T.R. Torkolson 1603 Building Dow Chemical, USA Midland, Michigan
40640
Dear Ted:
Enclosed is a copy of a research proposal from the University of Tennessee, Materials Science Toxicology Laboratories, for studying pulmonary o.fi'ucts by PVC dust.
This proposal is a result of our initial conversation?; concerning the potential hazards associated with PVC dust exposure in the workplace.
Dr. AuLiati has considerable expor L i
in the on. .1 cl
plastic toxicology studies and is qui .< interested in jus-
suing the PVC dust problem.
I would appreciate receiving your comments and those of the Vinyl Chloride Research Coordinators - CMA regarding this proposal.
Thank you for your assistance in forwarding copies to the coordinators as discussed during our telephone conversation.
Best regards,
Sincerely
TJBisbb Attach. cc: G.L. Ter Ilaar
J. Autian
TheodoreVJ. Benya, Ph.D. Tox.i cologis t
SCC
1-0619
Of. John Auli.in, Director (901) S28-6020
Ds. W. Homer Lawrence Associate Director and Head. Animal Toxicology (901) 528-6068
Materials Science Toxicology Laboratories
COLLEGE OF DENTISTRY & COLLEGE OF PHARMACY
UNIVERSITY OF TENNESSEE CENTER FOR THE HEALTH SCIENCES MEMPHIS, TENNESSEE 38163
Dr. Elwood O. Dillingham F/r\h!. Cellular Toxicology (0011 528-6072
Dr, Inyt |. Nunez Biofnj(crr.il'
(*<01} 528-6073
Dr. |.nv\ Turner Head. Pathology (901J 528-636-1
June 13, 1979
Dr. Theodore J. Benya, Toxicologist Ethyl Corporation Toxicology and Industrial Hygiene Department Ethyl Tower, 451 Florida Baton Rouge, Louisiana 70801
Dear Ted:
I am a little late in sending you the Informal proposal developed by Dr. W. H. Lawrence and myself, and I hope this has not inconven ienced you. Please review what we have said and then let us know if it can be developed into a full-fledged proposal. I will be out-oftown for the next two weeks, and thus you may wish to talk to Dr. Homer Lawrence (SOI: 528-6068) if questions arise.
Hoping to hear from you soon.
cc Dr. W. H. Lawrence JA/rw
see
1-0620
Hmi Aulian, Director (901) 520-6020
r W. Homr Lawrence Oiretior and
Hvjti. Anitrul Toxicology (901) 528-6068
Materials Science Toxicology Laboratories
COLLEGE OF DENTISTRY & COLLEGE OF PHARMACY
UNIVERSITY OF TENNESSEE CENTCR FOR THE HEALTH SCIENCES MEMPHIS, TENNESSEE 38163
Or. IKvnu'l O. OiliinxSjrn
C.f'ilitln 1 !! I`f. 'y
rnn *v;a
Of L..^ J
I lr.ii/, .'Im.
(9.11, i^a-60'H
Dr. /,irri(.s r. Fulfil I Hvj'l yjih<il>`tcy
run s.m-sjm
TO: FROM: OATH: SUBJECT:
Dr. Theodore J. Benya, Toxicologist Ethyl Corporation
Prs . John Autian and W.H. Lawrence? M;itcrials Science Toxicology Lnh-i rn : o i i e r.
Juno 12, 1 SI 79
Proposed Carcinogenic Study of PVC Oust
PROPOSAL FOR A FEASIBILITY STUDY TO EXAMi CARCINOGENICITY OF PVC DUST
TUI: POTUNiiU.
1 ntroduction
Because of the possible relationship between exposure to
PVC dust and lung disorders, it became desirable to initiate a
short-term feasibility study to assess the possibility that PVC
dust might be implicated in pulmonary tumorgenesis. The latent
period for such tumors, if induced by PVC dust, is unknown but
tumor induct k:js often is not observed until after a considerable
lapse of time.
This proposal is designed as a six-months study, but sufficient
animals will be treated to provide for a number of animals
remaining nftvi completion of the six-month design to pcnJ :
extending the study, without the delay ol starting over f: or? < ).
beginning, for a longer period of time if results from the ~
see
1-0621
2- -
i x- months study would surest it might Ik* fruitful. Titer.* 'extra* animals will be held until the histological cva1uat mu:s of the six-month tissues have been completed; at this time a decision will be made whether or not to continue the obser v.. i Lon period, and if so, the schedule to employ.
General Procedure The PVC dust to be evaluated will be supplied by the Ethyl
Corporation (Dr. Benya). A specified quantity of the dust will be administered by intratracheal instillation in a manner similar to that described by Davis, et al. (Br. .1. Cancer, 31:129, 19 7:'.) A similar procedure was used by Stenback and Rowland (Scand. J. Resp. Pis. , ^_:130, 1978) to study talc and benzo (a) pyrene in Syrian golden hamsters.
Male rats of the Wistar strain, weighing lou to 150 gram.; at. the initiation of the study, are recommended. The test sample is prepared for administration by suspending it in normal saline, by sonication immediately prior to administration, so that 0.2 mi. of the suspension will contain the desired quantity of PVC dust (about 3 to 5 mg.). Bach rat is anesthetized and a cannula is passed through the larynx and the 'dose* (0.2 ml. of the suspen sion) is given by intratracheal instillation. In order to produce maximum exposure in a minimum period of time, it is proposed that this procedure be repeated three (3) times per week for five (5) weeks for a total of fifteen (15) 'doses'. Control rats will be administered 0.2 ml. of saline in the same manner.
see
1-0622
3- -
It is recommended that 10 rats from the PVC dust treatment group and 10 of the controls be sacrificed, autopsied and tissue, taken for histopathology at the following times (from date of initiation of treatments): (a) six weeks, (b) three mouths, fc) four months, (d) five mouths, and (e) six months. The remaining rats will be held until the tis.ues from the six month*, sacrifices arc examined histologically, at which time a decision will be made as to whether to continue the study or not. At autopsy, the trachea, lungs, liver, and kidneys will be removed and preserved in 10% buffered formalin for histological processing and evaluation. In addition, if suspicious lesions of other tissues or organs are observed during the autopsy, they will be removed and preserved for histological examination.
To conduct the study as envisioned in this outline, it is desired to have about 100 rats which have been treated with the IS intratracheal instillations of the PVC dust suspensions, plus 100 saline-treated controls. Tn-as-much-ns Ishinishi, et a 1. (Environ. Health Perspect., 1:191, 1977) reported a survival of 30% to 71% of the rats in their various groups after 15 weekly instillations of this type (mean of all groups was 41% survival), it is suggested that each group be initially composed of 200 rats to provide approximately 100 at the end of the 15 'dose' treatment schedule.
Comments There arc many modifications or variations of this procedure
which could bo employed. This particular procedure is suggested
see
1-0623
4- because this methodology of administering a powder or similar material into the lung area is reasonably well established. The rather frequent treatment of rats proposed here is an attempt to demonstrate in a rather brief period, if possible, a reaction which might occur much more slowly from a more conservative treatment schedule.
A six-months study is rather'short for assessing a material for its ability or tendency to produce rumors. The experimental design, however, provides the flexibility of extending the observation period, without a loss of time, should it appear desirable.
see
1-0624
6-27-7?
ns'o
P. F. DEISLER
Vinyl Chloride
I have just discovered this reasonably complete summary of Maltoni's studies up to 1977. The numbers are suspect, e.g., ''corrected numbers'5 and there is little in the way of data for separate sexes. Also, the exposures are atypical in that four-hour exposures were studied for periods ranging from 17-52 weeks. A more typical exposure would have been about twice this amount. Table 13 suggests that exposure time has an effect on tumor incidence.
X have taken the results of experiment BT1 (Table 8) and plotted them on semi-log paper. If a straight line relation is obtained, then a no-effect level would be predicted at around 20 ppm. However, experiment BT15 (Table 12) gives data for lower exposures and results to 87 weeks (final results not yet located). Inspection suggests that there are effects at lower levels, possibly even 1 ppm.
Table 13, like Table 8, suggests that the dose response for angiosarcomas is not straight forward. 30,000 ppm (Table 10) really did give a good response!
Table 21 is important, since it is clear from animal stuides that VCM is a multi site carcinogen - one obvious site to investigate would be cutaneous/subcutaneous tumors.
The Maltoni experiments could have been better designed since the doses have been chosen unevenly and are concentrated at the highest exposure levels. It seems unlikely that we could get individual animal results which would have enabled us to do some very interesting analyses of relative risk.
2)^
D. E. Stevenson
DES:sas
Attachments
cc:
R. E. Joyner H. L. Kusnetz M.!. B. Slomka
n
os
<-n
tic* o ro CO d
6/27/79
see
1-0625
- --O--
_VL
M,
I'htn the [*.'.perimenU i*n VijivI ( hhvide O ko:1 "ij-.-.U: i'il-.x'!-; of luhaiali.. nl
Dillerer.t
lor J Year
A nimtds:
rets
Exp.
Tixatewi::*
<}~C
P "
no.
i!< i.f'S re
( ' < </. s) 2
c to:-d
.C'-
{;
HI
BT1
10.000, 6000, 2500, 500,
13 263 300 577
64-06
250. 50 ppm: untreated
controls: treated con
BT2
trols: VA 2500 ppm 200. 150, 100 ppm: ur.-
13 2.S0 265 545 120-165
treated controls
BT6
30.000 ppm
17 30 30 60 -60
BT9
50 ppm; untreated controls
u
200 200 400
100-300
BT15 25, 10. 5. 1 ppm: untreated 13 300 300 600
120
controls
" The duration of treatment in each case was 4 hr daily. 5 days weekly.
Table 2 Plan of the E:\pcnments on Vinyl Chloride On.'oa'enc'is: EtiVats of Lendl-. or Exposure hv Inhalation
Attiiti.tls: .S';>rwy?/tf-/)a*Wfy re:<
Expno.
Trcau nent
----
----- --------------------------- eve
dmts VC
duration (:-viaV> 9
O
total
pt'r ?ro:tp
|
UT3
10.000, 6000. 25011, 4 hr daily, 5 days 2i 262 2'S 550 611-WO
500, 250, 50
weekly, 17
ppm; untreated
weeks
controls
BTI0 10,000, 6000 ppm; 4 hr daily, 5 days ll 420 420 840
120
'
<7
untreated controls
weekly, 5 weeks;
; 4 hr daily. 1 day
*i
i
weekly, 25 weeks;
i |I
i 1 hr daily, 4 days
weekly, 25
weeks
124
see
1-0627
* Th; route in both cases m;is by inhalation. uv.J ih; daih, 5 days weekly, 52 weeks.
v::j~ >f
4 hr
Table 5 Plan of the Experiments on Vinyl Chloride Gncocene'.U: KiTects of Species
A vu-
- if'.
Exp. r.o.
Treatments doses i 'C
species
C\*'" strain ( . . < -. i :
/"<
+ to:.:! -roup
BT4 BT$
10,000. 6000, 2500. 500, 250. 50 ppm; untreated controls
10.00'J. 600, 2500, 500, 250. 50 ppm; untreated controls
mouse Swiss hamster Golden
1 1 25-J 260 510 60-150 I l - - ?s v, s 3 2 -70
4 The route in both cases was bv inhala: ion, ar.J the du .'avion of tre:itrr.eitt daily. 5 days weekly, 30 weeks.
4 hr
Table 6 Plan of the Experiments on Vinyl Chloride Oncogenesis: Experiments by Ingestion
Ar.lfuS.v Spra^iii'-Pty-i'-y rets
I Treatment
i r..xp.
err ru-r
r.o. doses VC
duration
total group
iI
BT11 50 mg. 16.65 mg, 3.33 mg/ kg body weight in
5 times weekly 52 weeks
13 1*0 16<! 320 SO
i olive oil; controls:
olive oil
BT27 ! mg. 0.3 mg. 0.03
5 times weekly
10 300 300 600 150
mg/kg body weight in
52 weeks or
olive oil; controls:
more
olive oil
126
see
1-0629
EH3 S3 10
v
5o* u
3C-
"3
3or o
I zon -o
I i
i
o
~"3 3 O
H c=ar. M
m
3
n
o o O
3
V6o3 3f>
rn
"o3
o
>c
3
oft'
5`
3
)
rcon
Table 8 Experiment T5T1: Results after 135 Weeks (End of Experiment)
Croup, treatment
I
VA 2500 ppm It
VC 10,000 ppm 111
VC 6000 ppm IV
VC 2500 ppm V
VC 500 ppm VI
VC 250 ppm VI)
VC 50 ppm VIII
No treatment Total
Animats with tumors
A tiitnals (S-D mix)
total
correcteii
no."
y.yitihnl /;lnnit carrinotiwx*'
n\<.
lit-
fe/tcy tin. % (If('riy)
nephrn-
anviosnrromox ------------ ------------- -- --
hUtMomus''
liver*
sub-
muni* other
C-tllll- skin
brain
1 \-pe
nv.
nv.
ncon.t car-
tirttro- car- ami/
latr/iry
Intr/icy
other an- ciito- hrpn- hlttsia eitiit or
sites ttinmns mat tiunrt.r inns mas .w\v,;
no. % (xi'rr/:.r) no. % (weeks) no.
no. no. tin.
no. no. no.
total* no.
96 AO 69 61 72 60 74 59 67 59 67 59 64 59 6tt 58 577 464
16 26 50 7 12 62 -> 3 33 A 7 79 ------ ------
29 -- --
5 8 59
4 7 65
6 i() 4T
74 S3
6 10
SO
1 135
26 -- --
9 15
64
13 22
70
13 22
7;:
7 12
XI
4 7 79
1 2 135
47 --
--
31, 4 3-* .) yA
.V
-n. l "
ul
31 7 113 1 25 1 4-- 1 " | ----
14 12 11 X 15
3 P 3S S'" 31
1 32 1 >*! 1 1V 16 2 7'1 10
10r 6 X 37 155
see
>y
I
Table 9 Experiment HT 2: Results a: tor 143 We cks (fit: d of i: xp.-nmo:::!
Xo. of
j h !,J: tumors
Group, treatment
Zvrtthal
g/ii/tt!
A nii'-.rJ {
cur-
(S-D ret>) fft:r>uui.\
1'.ephrovia nomas
(./! ^tauircori:; t
-- ---------
Other
liver
Sltt s
other tvpe tout/
or site
Oita!
I-
VC 200 ppm
120 1
3 12
1- 23':
30
11
VC 150 ppm
120 2
7
5
3" 17- 29
1(1
VC 100 ppm 12U 1 10
1--
12r 20
a IV
No treatment
I S3
1
--
--
1* 20-
21
$
`i
Total
545 5 20
IS
5
72 100
3 Exposure by inhalation to VC in air at 200. 150. a ud 100 ppm, hr daily. 5 days
weekly, for 52 weeks.
* One ir.tra-abdominal angiosarcoma.
bTuo subcutaneous angiosarcomas; l mera-abdoninal ajvio.'arotirna.
,
e One sti`*e::.i:isv *:s ar.ciosnreorua.
`i rive skin carcinoma*: I subcutaneous fibroanuioni.:; .5 rv.tnirrr.ey carcinomas; 2 iiver
fibroangionas: 3 5r-er argiomu*: 3 liver hepatomas: l liver .o'.ir.y.yjmu; l imru-;:NUr.iir.:'l
fibre-angioma: 1 leiinso-vafconm cf uterus: l neurilemmoma: 1 orbital fibrosarcoma.
"Three skin carcinomas; 5 mammary carcinoma:; I th\mu* angioma; 1 nasal o-.Jeo-
i
sarcoma: l cranial osteosarcoma; 1 liver colurtgiatna; 2 adenocarcinomas of uterus; 1
J
fibromixosarcomr. of uterus: 1 fibrosarcoma of lung: 1 lymphoma.
t One skin carcinoma: 1 subcutaneous fibrosarcoma: 3 mammary carcinomas; 1 intra-
;
abdominal angioma: 3 forestomach papillomas; 1 adenocarcinoma of uterus; 1 intra-
abdominal r:bdonyo*a.-coma: l kidney adenoma.
j
e One Zymbal gland adenoma; l skin adenocarcinoma: l skin sebaceous adenoma; l
;
subcutaneous fibrosarcoma; 2 subcutaneous fibrnnuxosafconvi*: l mammary carcinoma;
1 intrathoracic rabdomjosarcoma; 3 forcstomach papillomas: I adrenal carcinoma; 3
adenocarcinomas of uterus; l fibrosarcoma of uterus; i fibrosarcoma of scrotum; 3
lymphomas.
> Several animals with two or more tumors.
J
S3
130
1 Si
see i-0633
Table 10 l-A;vrmu:nt !3T6: fie-mlii niter CO Weeks
of K\pcrimcrtt)
.1 efm.jfv ii1: utiiiur.\
Group,
tr^Ktouviii
{.S'-/) r<ns\ Cor-
torn! rn>."
V.\ni t:! ?!.::>! c.trcb:uin,;\
it-
tew? no. r,i (n.r.A
iO'.CtO-
'iUtwttxo
phro- ----------------in- other />* xt:c<
ro. tt-i. /!'.
tr
/*</.
i
VC 30.000 ppm
60
60 31 52 43
-- 17 lh 27"
5!
Exposure by inhalation to VC in air at 30.(M> ppnt. A hr daily, 5 days \?-A!y. for 52
v. ecks.
a Animals alive1 after 2-1 weeks. when the tir>: tumor (a V.yni'tal glattd curciiivnnal observed. The percentages refer to the corrected r.ve.nter.
ll One lur-s anciO'arcoma. Seven Zvmbnl gland ader.orrv.ts: l shin carcinoma: I subcutaneous f-broarviotna: 7 n:.::;wtMrv eareinom *: 1 liver ane.ioitu: l hvpaumta: II forestomack p.spilioniai; 1 ov.-.ri;ui angioma; 1 brain ttcuroXiisContu: l HarJerian glanJ carcinoma. ! Several animals u jih iwo or mure tumors.
131
SCC 1.-0634
i.'.UMiirfWS
*,, /*.51
l;i t?^` |!! I|3t hiijHuij
i|!p!
!I.;M
Table 12 Experiment UT15: Results after S7 Weeks
N, S'o, of animcls with nmor*
Group. treatment
Animals (S-P ran)
total
Mir-
vivnrs
Other
y.ymbal * an^io><ircortu:s
type
plctt-i phro-
acAI
a:r- Nust.t.
other car or
ciiumuis mas liver sites cinott:y* site
total
I
VC 25 ppm
U
VC 10 ppm
ilu 45 no 51
3--
3 -- 10
1
--
--
--
11
7 20 5 16
Hi VC 5 ppm
IV
VC l ppm
no
62 -- -- -- --
13
5 17
no 49 -- -- -- -- 8 4 12
V No treatment
no
49 _
- ir - - -- 2 4
6
Total
600 256
4--
3 -- 44 25 71
lalation to VC in air at 25, 10, 5, and 1 ppm. 4 hr daily. 5 days weekly, for 52 weeks.
im Miip1
I
Ji'lp-:
yifer.--
&
t*rferei
133
see
1-0636
Exposure by inhalation to VC in air t 10,000, 6000, 2500, 500, 250, imd 50 ppm, 4 hr daily, 5 days weekly, for 17 weeks. The number of tumors found in experiment UT1 after 135 weeks is shown in parentheses.
i One subcutaneous angiosarcoma. One intra-abdominal angiosarcoma. <* One subcutaneous angiosarcoma; t intra-abdominal angiosarcoma.
One intra-abdominal angiosarcoma. f One subcutaneous ossifying angiosarcoma; I orbital angiosarcoma,
s One ovarian angiosarcoma. '`Three skin carcinomas; t skin papilloma (nose); 1 renal adenoma; 1 lung angioma; I parauricukir fibrosarcoma. 'One Zyrnbal gland fibroangioma; 5 skin carcinomas; 1 subcutaneous angioma; I mammary carcinoma; 1 forcstomacb papilloma; 1 adenocarcinoma of
uterus; 1 cranial osteoma. JTwo skin carcinomas; I subcutaneous angioma; I mammary carcinoma; 1 hepatoma; l adenocarcinoma of uterus.
* One ovarian enreinomu; 2 lymphomas. One Zymbal gland adenoma; 1 mammary carcinoma; I adenocarcinoma of uterus; I l.cvdig cells tumor; I retrobulbar fibroma.
One skin papilloma lno.se); l mammary carcinoma; 3 adenocarcinomas of uterus, "One Zymbal gland adenoma; 1 skin carcinoma; 3 subcutaneous fibrosarcomas: I subcutaneous leiomyosarcoma; f mammary carcinoma; f ovarian pyn*
androblastoma*, 1 fibrosarcoma of uterus; ! salivary adenocarcinoma; 2 lymphomas. o Several animals with (wo or more tumors.
t-*
\
O (A
O' n (A n
u
cn
Table 14 r.NpcrinK*nt Ij I 5: Rc>ii!i-, alter 143 kkeoks (I-:*.! ' I \peri:;V:al)
,V' oi <:rt>::::'\ v.Uh tW'>f>r*
Croup, treatment
A ttir?i.:l
(S-D rats)
tout
Correctal
no.
1'/y !>.
hhm.l : A--,/far- :
cittomc o:'.i\
tingiosarcomas
h\>-r
oilier sita
other
M /'i'
a-ul; Or
litre
to;,;!
r
VC 10.000 ppm
30 30
1
-- 1*- 2" 3 -
breeders
11 VC 6000 ppm
30 30 -- -- -- -- -- --
breeders
III VC 10,000 ppm
54 51 3 1 __ nr 2f S
offspring
: i IV ~
VC 6000 ppm
32 32
1 -- __
o.i 4' Cr-
V offspring:
Total
146 143 5 1 -- 5 H 17
. *
Exposure cj in:halation to VC in air at 10,000 J fidfl0 peril of breeds rs, 4 hr daily, for 1 week I. from 12th to Istth day of pregnancy).
"Animals alive after 22 weeks, when the first tumor (a subcutaneous ansuj>ctrestt?.0 arose in an offspring.
11
t'One intra-abdominal angiosarcoma.
* One subcutaneous angiosarcoma; I angiosarcoma of the leg.
rtOne subcutaneous angiosarcoma; l intra-abdom:.-..*.! angiosarcoma.
One liver fibroangioma; 1 liver angioma.
( One Zymbal gland fibrosarcoma; 1 ovarian leionv.o*;..rcon::i.
c One Z.yn;b:ii gland adenoma; 1 skin carcinoma; I subcutaneous fibroangioma; 1
mammary carcinoma.
h One animal with two tumors.
136
T-et-Tjas* i
SCC 1 --0638
t 'rs^^r
Table 15 Incidence of Hepatic Tumors among Sprague-Dawle\ Results after 104 Weeks
Ru'.n I'.xpoi-.'-i to VC:
Exp, no.
Group
;V<*. of IDtlll
Sttrfl'rnn
G'.'S-*, uirt
r.-putiifllC*
total
V.r.iiuuts with liver
tumors
DT10
!
VC 10,000 ppm 120 16 --
J
i!
VC 6000 pptn
120 15 -- --
111
no treatment
240 55 -- --
BT14
I
VC 10.000 ppm 46 S U) 15 19
I!
VC 6000 pp:n
43 5 10 13 17
Exposure in ,iir :ii 10.000 and 6000 ppm. 4 hr daily. 5 d-n-> v.-.--*.. fur < wv-i.5, at different ages: 13 uek* (B1 10) and 1 day (liTl4).
see
1-0640
No treatment Total
-?l) 3 --
--
--
--
-- 4V
!
220
3
I (17)
5 (15)
IN ( !5 )
3 (7)
2 (M
19 (17)
39 fOV
C
U-- e c
n
C
V.
CO
Vi
C--
Gco __ Gw 2O c e *
- j -C
E
O5
ui C
Eoi= -: o ^ i o
_yi -u
> c
s *--
.5uC2.~O- -5C cot:
&?*=
C
_o
| ^C -- UC ^^s3 ,. s c ..
2
r. o i: * K v! <
~ c
^
.25 TOJ oW n -5,
O
K
'J
oV n. e
CX
.,, o
<->
>. 5 -o b
Boca o o 2
* =
e 9C
*Ee CcO
e
$J *C*r
o> c--
C."5
rt
OC.-CoCUCoCo>O2O;C'E.iu=oE'juC^>
^hOoC'r-.-CCCCO^
mr-<K*Vi?wsiy^
L
Exposure by inhalation to VC in air at 10,000, 6000, 2500, 500, 250, and 50 ppm, 4 hr daily, 5 days weekly, for 30 weeks. * Animals alive after 16 weeks, when the first tumor (a mammary carcinoma) was observed. The percentages refer to the corrected number.
l> Adenomas, some of which undergoing malignant transformation.
c In females. Three subcutaneous angiomas; 4 liver fibroangiomnx; 1 heart fibroangiomn; 1 ossifying inlet-scapular angioma. * One subcutaneous angiosarcoma; 1 liver fibroungiomas; 4 liver angiomas; 1 renal fihroang.iuma; 1 thymus angioma. * Three subcutaneous angiosarcomas; I subcutaneous angioma; 3 liver angiomas; 2 intra-abdominal angiosarcomas; 2 renal angiosarcomas; ! lung angioma, f Two subcutaneous angiosarcomas; 1 subcutaneous fibronngi'oma; I subcutaneous aitgionia; 4 liver lihroaugiomas; f liver angioma; 3 inlrn-abdomii'al angio sarcomas; J inlrn-abdominal libroangionut; f renal angiosarcoma; 1 testicular libroanrioma; l angioma of the caecum; I lung lihroangioma; I lung angioma. li One subeulimeons angioma; 6 liver nbroangiomas; If) liver angiomas; 2 imra abdominal angiosarcomas: I ovarian angioma; 1 scrota) angioma; 1 lung
angioma. ' One subcutaneous angiosarcoma; I subcutaneous fibroangiomn: 2 subcutaneous angiomas; 2 liver libroangiomas; 3 liver angiomas; f intni-nbdomm:i! angioma;
1 ovarian angioma; 1 mliathoracic librnangioma; I angioma of |be intor.H-npulur fat pail. J One angiosarcoma of uterus. * Two squamous carcinomas; I invasive acanthoma, i Tive squamous carcinomas; 1 acanthoma. m One squamous carcinoma; 2 acanthomas. " One acanthoma. `One skin adenocarcinoma; I basalioma. t* One Zyinhal gland adenoma; I forcstomnch papilloma. n One subcutaneous leiomyosarcoma; 1 forcstomnch papilloma; / Ifarderian gland adenoma: I lymphoma. rOnc forcstomach papilloma; 1 parotid gland mixed tumor. * One Zymbal gland adenoma. I One 2ymbnl gland adenoma; I t.cydig cells tutnor; 1 lymphoma. II One parotid gland adenocarcinoma, One subcuiancous leiomyosarcoma; 1 adenoma of colon; t ovarian carcinoma; I leiomyosarcoma of uterus; 3 lymphomas.
w Several eases with two or more minors.
Table 16 . Experiment UTS: Results after 109 Weeks (End of Experiment)
.Vo. a! animals with tumors
Croup, treatment
Animats (Golden
sters)
liver angiosarco
mas
sr::n
tri-
cho-
Cpi-
Iile'li-
<?/>:<: i
and
bet-
tym-
satio- nmiaitn plus-
mas*
mas
for*S'.O-
f.'jac/i
cpithe. liar'
tumors
other tvpe and.'"
or site soud'
I VC 10,000 ppm
II VC 6000 ppm
III VC 2500 ppm
IV VC 500 ppm
V VC 250 pom
VI VC 50 ppm
VII No treatment Total
35 32 33 33 32 33 70 268
--6
1
122
'--
1
1
2 4--
-- 3--
--6
1
-- 2--
3 24
5
4 2e 10
27
71 10
1 11
3* 13
1 7 or 12
l
2--
6
_1 4
10
2 2-- 7 8 37 ` 14 68
Exposure by inhalation to VC in air at 10.000, GOon. 2500, 500. 250, and 50 ppm, 4
*5
hr daily, 5 days weekly, for 30 weeks. Several cases with acanthosis and some undergoing malignant transformation.
h Papillomas, acanthomas, some of which undergoing malignant transformation.
< One subcutaneous angioma; I gall bladder adenocarcinoma.
i Two hepatomas; 2 User fibroangiomas; 2 liver angiomas: l biliJucts adenocar
cinoma.
* One hepatoma; I liver fibroaneioma: I liver ancioma.
* One subcutaneous angioma; l bronchial carcinoma,
s Several animals with two or more tumors.
142
see 1-0644
o (/) on .... 4* n u>
Table 19 Experiment DT11: Results after 120 Weeks
No. of animals with tumors
Croup, treatment
VC 50.00 mg/kg 1 )1
VC 16.65 mg/kg III
VC 3.33 mg/kg . IV
Control: olive oil Total
Animats (S-D rats)
total
sur vivors
SO 2
R0 2
R0 4
SO 4 320 12
Zyinha! ylaiitf ear- urphro. rlnomns bUtsuannx
mi^/Vwirronm.f
liver
other sites
\ 2 16 2
t 3 9 --*
------
2''
1 ---- -- 4 5 25 4
nut/ntuary ear* einntnas
5
6
4
4 19
other type ami/
nr site
7C
3*1
3"
5f IK
totalit
29 21
9 9 68
Exposure by ingestion (stomach lube) to VC in olive oil, at 50.00, 16.65, and 5.33 mg/kg body weight, once daily,
4-5 days weekly, for 52 week:;. * One thymus angiosarcoma; l intra-abdominal angiosarcoma (next to spleen). 'One limy angiosarcoma: I intra-abdominal angiosarcoma (next lo kidney). eOnc skin sebaceous carcinoma*, 1 hepatoma; 1 liver angioma; 2 forevtornneh papillomas: 1 intestinal adenocar
cinoma; I lymphoma. * One liver angioma; I adrenal carcinoma: I lymphoma. One subcutaneous sarcoma with nngjobtnsiic component*, t in(ra-nblomin:l ossifying sarcoma with ang.iohlnsltc com
ponent; I bladder papilloma. t One skin carcinoma; 1 papilloma of the auditory duct; l bladder caictiumia; I adrenal carcinoma-, f redouloxar-
coma. R .Several animals wilb two tumors.
m
see
i~0646
+ -r
*3
a: n
cu _c Voax. ui co oc
X c t>
+ 4-
oaX. W
a
c 5 ""
++
>
cS . C
+
c o
OS
i_
rS sW t) 4- 4- 4- 4-
X
o
X--
a.
t
O
OL/>.
Jf33 3
_ =o p Co
:
b- 5-
a<s^
V
145
see \ 1-0647
iMF
Table 22
Reported Ca\c> of Angiosarcoma liXpo.\ed to Vinyl Chloride
Belgium Canada Czechoslovakia
Federal Republic of Germany Franco Great Britain Italy Japan Norway Rumania Sweden
Switzerland U.S.A. Yugoslavia Total
To.\:!
10 10
6
SCC 1-0648