Document 93xK7moNB597MMb4OzLOmr436
9nduMAiai BIO -TEST JlaLbombyiieA, 9m.
1910 frontage road NORTHBROOK. ILLINOIS 60062
)/C+-
SEVEN-MONTH STATUS SUMMARY TO
MANUFACTURING CHEMISTS ASSOCIATION
CHRONIC VAPOR INHALATION TOXICITY STUDY WITH VINYL CHLORIDE (ETHYLENE DERIVED) IN ALBINO RATS, ALBINO MICE AND GOLDEN HAMSTERS
JUNE 19, 1974
IBT NO. 663-03222
CMA 001953
DnduiiAied B I O - T E S T loJtanaltyUed,, !)*vz.
30
TABLE VI continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Cln-ohic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Tumors Observed Among Mice
Group Animal Number and Sex
Lung
Neoplastic Findings Liver
Skin
Date of Death
T-III continued 1505 Female 1565 Female 1409 Male 1543 Female 1544 Female 1546 Female
1535 Female 1432 Male 1577 Female
AA (s) AA (s) AA (s) AA (s) AA (s) AA (s)
HS (s) HS (s) HS (s) HS (s) HS HS (s)
AA (s)
HS (s)
AA (s)
AA (s)
HS (s)
Metastatic
Mammary Tumor
4-3-74
4-3-74
4-5-74
4-5-74
4-5-74
MT (Axillary region)
4-5-74
4-7-74
4-8-74
MT (Para-aural)
4-9-74
MT (Abdomen)
MT (Pelvic region)
Key to Symbols
AA = Multiple Alveologenic Adenomas of Lung HS = Hemangiosarcoma of Liver MT = Malignant Mammary Tumor (s) = Multiple Lesions
CMA 001954
UrtduAhial B I O - T E S T J.alt&U2i(ytie4., 9nc.
29
TABLE VI
TEJSflliWlAlFERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Tumors Observed Among Mice
Group Animal Number and Sex
Lung
Neoplastic Findings Liver
Skin
Date of Death
T-I 1123 Male 1110 Female
1119 Female 1200 Female
AA (s)
HS (s)
AA (s), Metastatic
Mammary Tumor HS (s)
Metastatic
Mammary Tumor
MT (Para-aural)
3-15-74 3-20-74
3-24-74
MT (Femoral region) 3-30-74
T-II 1347 Female
1309 Female 1289 Male 1382 Female 1350 Female 1399 Female
Metastatic
Mammary Tumor HS (s)
AA (s)
HS
HS (s)
AA (s)
HS (s)
AA (s)
MT (Abdomen)
3-5-74
3-18-74 3-25-74 4-2-74 4-5-74
MT (Inguinal region) 4-9-74
T-III 1538 Female 1532 Female 1562 Female 1598 Female 1405 Male 1494 Male 1574 Female 1531 Female
1588 Female 1593 Female
AA (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (s)
AA (s)
HS (s)
HS (s) HS (s) HS (s) HS (s) HS (s) HS (s)
HS (s) HS (s)
3-6-74 3-7-74 3-8-74 3-18-74 2-25-74 3-22-74 3-22-74
MT (Femoral region) 3-23-74 3-25-74 3-30-74
CMA 001955
Group T-I T-II T-III
TABLE V
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Summary of Tumor Data Among Mice
I
No. Mortalities with Neoplasms
4 (1 Male, 3 Females)
6 (1 Male, 5 Females)
Location of Tumors
Lung
Liver
2 (50%)
2 (50%)
3 (50%)
4 (66.7%)
Skin 2 (50%) 2 (33%)
Metastasis to Lung 2 1
19 (4 Males, 15 Females)
17 (89.5%)
17 (89.5%)
3 (15.8%)
o
to
Q o o J--1 Lsn0 <T\
oo
Dnduilual B I O - T E S T laltonahyii&L, 9hc,
27
VII. Histopathology Histopathologic examinations were conducted on all mice which showed
grossly visible lesions through the end of the seventh month of inhalation exposures. All mice which showed neoplastic findings are presented in Tables V and VI.
CMA 001957
DtuLubuaL B I O - T E S T J.alt&ialvue, 3nc.
26
TABLE IV continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex
Gross Pathologic Findings
Grade
T-III Mice
1535-F 1432-M 1477-F
1494-M
Multiple small (1-2 mm) white foci in all
lobes of the lung. Dark red focus (3 cm)
involving most of one major lobe of liver
and smaller (1-3 mm) lesions in other lobes.
Adhesions between lobes of affected liver and
between liver and mesentery.
Congestion of all lobes of lung
4
Multiple small (1-3 mm) white foci in all lobes
of lung
Left diaphragmatic lobe of lung congested, multiple
white parenchymal foci in all lobes of lung
ranging from 1 mm to 1 cm in size.
Liver has small (1-5 mm) dark red foci in all
lobes. Some liver lesions are raised and some
depressed.
Subcutaneous multi-lobular fibrotic mass (5x5x3
cm) in inguinal region with retroperitoneal invasion.
Several areas filled with brown fluid
Two similar masses in left axillary region
extending into para-aural region, each approxi
mately 1.5 cm in diameter.
Two small subcutaneous masses (1 cm dia.) in
right abdominal region filled with dark red fluid
Large mass (2.5 cm) located in left axillary
region
Multiple small (1-2 mm) white foci in all lobes of
lung. Small (1-5 mm) dark red foci in all
lobes of liver. Abdominal cavity contains dark
red fluid.
CMA 001958
DniudiiaL B I O - T E S T
9nc.
26
TABLE IV continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex
Gross Pathologic Findings
Grade
T-III Mice
1535-F 1432-M 1477-F
1494-M
Multiple small (1-2 mm) white foci in all
lobes of the lung. Dark red focus (3 cm)
involving most of one major lobe of liver
and smaller (1-3 mm) lesions in other lobes.
Adhesions between lobes of affected liver and
between liver and mesentery.
Congestion of all lobes of lung
4
Multiple small (1-3 mm) white foci in all lobes
of lung
Left diaphragmatic lobe of lung congested, multiple
white parenchymal foci in all lobes of lung
ranging from 1 mm to 1 cm in size.
Liver has small (1-5 mm) dark red foci in all
lobes. Some liver lesions are raised and some
depressed.
Subcutaneous multi-lobular fibrotic mass (5x5x3
cm) in inguinal region with retroperitoneal invasion.
Several areas filled with brown fluid
Two similar masses in left axillary region
extending into para-aural region, each approxi
mately 1.5 cm in diameter.
Two small subcutaneous masses (1 cm dia.) in
right abdominal region filled with dark red fluid
Large mass (2.5 cm) located in left axillary
region
Multiple small (1-2 mm) white foci in all lobes of
lung. Small (1-5 mm) dark red foci in all
lobes of liver. Abdominal cavity contains dark
red fluid.
CMA 001959
B I O * T E S T 2abonaivue<l, 9nc,
25
TABLE IV continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex
Gross Pathologic Findings
Grade
T-III Mice
1565-F 1409-M 1543-F
1544-F 1546-F
Few small (1 mm) white foci in all lobes of lung. Diffuse dark red discoloration of one entire lobe of liver with adhesions to mesentery. Small (1-2 mm) dark red foci in other lobes of liver. Multiple small (1-3 mm) white foci in all lobes of lung. Small (1-4 mm) dark red foci in all lobes of liver. Some liver lesions on surface had depressed centers. Abdominal cavity filled with dark red fluid Multiple 1 mm - 2 cm white foci involving all
lobes of lung, Hepatomegaly with multiple dark red foci (1-3 mm) in all lobes and adhesions between diaphragm and surface of liver. Also adhesions between liver lobes, liver to intestine, liver to mesentery. Abdominal cavity filled with dark red fluid Multiple small (1-2 mm) white foci in all lobes of lung. Diffuse dark red discoloration of one lobe of liver with smaller (1-3 mm) dark red foci in other lobes. Adhesions between surface of liver lesions and mesentery. Abdominal cavity filled with dark red fluid Several 1-5 mm white foci involving all lobes of lung. Large (3x3x3 cm) focus in one lobe of liver which involved almost the entire lobe with smaller (1-5 mm) similar lesions in all other lobes of liver. There are adhesions between the surface of the larger liver lesion and mesentery. Abdominal cavity filled with dark red fluid.
CMA 001960
DwLubiial B I O - T E S T 2aJM>\at&ued-, 9*tc.
24
TABLE IV continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex______ Gross Pathologic FindingsGrade
TE-HI Mice
1531-F
1588-F
1593-F 1505-F
Congestion of all lobes of lung Large (5x3x5 cm) subcutaneous mass in right femoral region extending into musculature of limb and abdomen.
1
Few small (1 mm) white foci in all lobes of lung. Large (2-3 cm) dark red raised foci in two lobes of liver with smaller (1-3 mm) lesions in other lobes. Adhesions between larger lesions and mesentery. Spleen enlarged 3 times normal. Abdominal cavity filled with dark red fluid Few sm&ll (1 mm) white foci in all lobes of lung. Small (1-3 mm) dark red foci in all lobes of the liver. Some of the lesions on the surface were raised while others had depressed centers.
Spleen enlarged li times normal
Abdominal cavity filled with dark red fluid Several 1-5 mm white foci involving all lobes of lung. Large (3x3x3 cm) dark red focus in one lobe of liver which involved almost the entire lobe with smaller (1-5 mm) similar lesions in all other lobes of liver. There are adhesions between the surface of the larger liver lesion and* mesentery. Abdominal cavity filled with dark red fluid.
CMA 001961
jWWW B I O - T E S T laJwatvwi., 9*tc.
TABLE IV continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex
TE-II Mice
1299-F
Gross Pathologic Findings
Multiple small (1-2 mm) white foci in all lobes of lung. Large (2x2x2 cm) subcutaneous tumor mass in inguinal region.
Grade 3
TE-III Mice
1405-M 1538-F
1532-F
1562-F
1598-F
1574-F
Irregular surface on right kidney Multiple small to large (1 mm - 1 cm) dark red foci in all lobes of the liver some of which are slightly raised and others have depressed centers Multiple white foci (1-3 mm) in all lobes of lung.
Enlarged thymus Congestion of all lobes of lung Multiple small (1-2 mm) white foci in all lobes of lung Multiple small (1 mm) dark red foci in all lobes of liver. Large (1 cm) raised lesion in one lobe of liver with adhesions between surface of lesion and adjacent mesentery and abdominal fat. Abdominal cavity filled with dark red fluid. Multiple small (1-2 mm) white foci in all lobes of lung. Diffuse dark red discoloration of one lobe of liver which was enlarged and smaller (1-3 mm) lesions in all other lobes. Adhesions between surface of lesions and mesenteric fat. Abdominal cavity filled with dark red fluid. Small (1-2 mm) white foci in all lobes of lung Large (2.5 cm) dark red nodular focus in one small lobe of liver. The lesion involved almost the entire lobe. The other lobes of liver were pale in color. Abdominal cavity filled with dark red fluid
-- -
3
--
CMA 001962
HtvJUiMal B I O - T E S T laJmatiyu&s,, 9nc.
22
TABLE IV continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex
Gross Pathologic Findings
Grade
TE-I Mice
1200-F 1071-M
Dark red raised focus (1 cm) in major lobe of liver with adhesions to diaphragm. Multiple small (1-2 mm) white to dark foci in all lobes of lungs. Large subcutaneous tumor mass (4x4x2 cm) in right femoral region. Abdominal cavity contained moderate amount of dark red fluid. All lobes of lung congested
2
TE-II Mice
I301-F 1268-M 1309-F 1341-F 1289-M
1382-F
1350-F
Gall bladder distended with bile
-
Enlarged gall bladder
-
Congestion of all lobes of lung
4
Large (6 mm) nodular red focus in major lobe
of liver with adhesions between capsular surface
and mesenteric fat.
Congestion of all lobes of lung
3
Enlarged spleen, 3 times normal
-
Multiple small (1-3 mm) white foci in all lobes
of lung. Large (2x2x2 cm) dark red focus
in one lobe of liver. Abdominal cavity contains
moderate amount of dark red fluid.
Large (3x2x3 cm) dark red focus in one
lobe of liver and smaller foci (0.5 cm) in other
lobes. Abdominal cavity contains moderate
amount of dark red fluid.
Small (1-2 mm) white foci in all lobes of the
lungs. Large (3 cm) nodular focus in major
lobe of liver with adhesions between capsular
surface and mesentery. All lobes of liver have
small depressed red foci. Abdominal cavity contains
moderate amount of dark red fluid.
CMA 001963
9ndu6iAiai B 1 O * T E S T lah&uit&ueA., Jnc.
21
TABLE IV continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex
Gross Pathologic Findings
Grade
TE-II
2189-F
Hamsters 2004-M
2180-F
2166-F
2155-F
Congestion of all lobes of lung Congestion of all lobes of lung Congestion of all lobes of lung Congestion of all lobes of lung Congestion of all lobes of lung
3 4 4 5 2
TE-III 2220-M Hamsters 2312-F
2311-F
Congestion of all lobes of lung Congestion of all lobes of lung Right kidney has focus of white discoloration extending from capsule into cortex
4 3
-
Control Mice
835-M 859-M
TE-I Mice
1033-M 1048-M 1023-F
1110-F 119-F
Focal consolidation of all lobes of lung Enlarged kidney 1/ 2 times normal, w/ granular surface
1 -
Pale kidneys Enlarged seminal vesicle, 5 times normal Small (1-3 mm) dark red foci in all lobes of
* -
liver. One small lobe has large (2 cm) dark
focus which is slightly raised. There are also
discolored foci with depressed centers. A small
(5 mm) yellow nodule is also attached to the
larger mass. Multiple, small (2-4 mm) white foci
in all lobes of lungs. Several small (2 mm) dark red to white foci in
right anterior lobe of lung. Large (5x5x7 cm)
firm subcutaneous mass on right side of head in
para-aural region which encircles neck and extends
dorsally on other side of head toward left ear.
Small (1-20 mm) dark red foci in all lobes of the liver and dark red fluid in abdominal cavity.
-
CMA 1964
!)ndudtual B I O - T E S T J.olia>\at&Uii,
20
TABLE IV
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Gross Pathologic Data
Group Animal and Number
Species and Sex
Gross Pathologic Findings
Grade
Control Rats
32-M 173-F
75-M 51-M
Focal consolidation of all lobes of lung Focal consolidation of all lobes of lung Focal consolidation of all lobes of lung 6x4x5 cm subcutaneous multilobular fibrotic mass in abdominal region
5 3 5
-
TE-1 Rats
215-M 211-M
283-M
Dark red discoloration of all lobes of lung Congestion of lung Small consolidated foci in all lobes of lung Congestion of all lobes of lung Spleen enlarged, 2 times normal
1 5
-
4
TE-II Rats
499-M 521-F
518-F
Diffuse red discoloration of all lobes of lung Spleen enlarged, 3 times normal Draining abscess in inguinal region Congestion of all lobes of lung
1 -
4
TE-III Rats
657-M 635-M 721-F
Congestion of lung with small consolidated foci Consolidation of all lobes of lung Congestion of all lobes of lung
3 3 4
Control 1750-F Hamsters 1773-F
1784-F
Congestion of all lobes of lung Congestion of all lobes of lung Congestion of all lobes of lung
4 4 3
TE-I
1861-M
Hamsters 1912-F
1910-F
Congestion of all lobes of lung Congestion of all lobes of lung Dilatation of both uterine horns with clear fluid (hydrometra)
5 4
CMA 00196S
BI O * T E S T 2oJ>&iat<vUe4; 9*tc.
19
VI, Gross Pathology Noteworthy gross pathologic findings are presented in Table IV.
Animals not listed showed only postmortem changes or were too badly cannabalized or decomposed for valid examination.
CMA 001966
BIO-TEST JlaltoAaiosUei,
18
TABLE III
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Summary of Mortality Data
Month Noi.
Cumulative Number of Mortalities at End of Month
ALBINO RATS
Control
T-I
T-II
T-III
MF
MF
MF
MF
1 00 00 00 00 2 00 20 10 00 3 01 20 10 14 4 02 41 30 14 5 23 51 61 34 6 34 62 6 1 54 7 4 4 8 6 6 2 65
Control
Month No. M
F
ALBINO MICE
T-I T--II
MF
MF
T--III MF
1 00 00
2 00 03
3 20 64
4
51
19 5
5
82
26 6
6 12 2 30 6
7 18 5 31 11
00 00 30 41 42 83 9 12
00 00 10 47 87 10 9 13 23
Control
Month No. M
F
GOLDEN HAMSTERS
T-I T--II
MF
MF
T--III MF
1 54 44 75 25
2
8 11
10 12
9 16
10 11
3
8 13
12 14
12 18
14 13
4
9 15
16 16
15 19
15 13
5
9 18
16 16
16 20
15 15
6 13 18 16 16 20 21 16 16
7 13 28 24 19 22 33 18 26
T-IV F
0 0 0 0 0 0 0
CMA 001967
)*uh<dtUal B I O - T E S T Jabyialvu&i, !)hc.
17
V. Mortality Data The cumulative monthly mortality data are presented in Table III.
No definite dos related trends have been observed.
CM* 01968
TABLE II continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters
Summary of Mean Body Weights - Golden Hamsters
1
Sex Males
Group
0
Control TE-I TE-II TE-III
73 71 63 60
Week Number
12
3
74 86 99 72 79 89 61 82 83 66 83 86
Mean Body Weights (grams) 4 23
Month Number 456
98 110 120 129 130 133 90 101 114 120 121 122 89 94 99 119 108 120 87 91 93 91 88 112
Overall Weight 7 Gain
130 57 128 57 118 55
no 50
Females Control 77 80 91 102 104
TE-I 78 78 85 96 95
TE-II
74
75
82
95
94
TE-III
69
70
87
95
92
108 118 120 121 124 125 48 102 112 118 118 122 130 52
99 ' 108 107 106 114 112 38 100 106 106 104 110 118 49
DO
o
m to
n
o o t-1 cr\ vo
O'
TABLE II continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Summary of Mean Body Weights - Albino Mice
I
Sex
Group
0
Males
Control TE-I TE-II TE-III
35 33 36 36
Females
Control TE-I TE-II TE-11I
29 30 28 28
Week Number 123
36 37 39 34 35 37 37 37 40 35 35 38
29 29 30 29 31 31 29 29 31 28 27 30
Mean Body Weights (grams) 4 23
Month Number 456
40 41 43 46 43 46 39 39 43 44 42 47 40 38 42 44 42 45 38 40 43 44 38 45
32 33 35 36 35 38 34 34 37 39 38 40 31 34 35 37 36 38 31 34 35 36 37 37
Overall Weight 7 Gain
52 17 45 12 43 7 41 5
37 8 41 11 36 8 34 6
O
o o 'O o
TABLE II TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Sex
Group
0
Males
Control TE-I TE-II TE-III
205 209 201 200
Females
Control TE-I TE-II TE-III TE-IV
160 168 171 165 181
Summary of Mean Body Weights - Albino Rats
Week Number 1 23
258 294 335 246 286 331 261 301 335 245 302 326
188 214 223 184 207 223 200 208 228 185 216 228 209 223 236
Mean Body Weights (grams) 4 23
Month Number 456
363 456 498 517 537 543 346 448 491 526 545 554 360 457 490 522 549 567 351 453 499 529 550 567
235 275 299 315 320 326 232 274 297 310 308 323 242 289 302 313 316 329 240 287 303 312 321 329 251 282 288 291 314 324
I
Overall Weight 7 Gain
550 345 567 358 565 364 576 376
344 184 348 180 342 171 346 181 338 157
00 O m ut
r
#
oo 4
9nduAVtial B I O - T E S T Ja&yiadyuei, Unc,
13
Hamsters: Mean body weights oi namsters inrougn me sixm"'month
of the inhalation period revealed dose related decreases in body weight
for both sexes_frpm control down to TE-III animals. However, evaluation
of body weight gains for all groups between the fifth. sixth and seventh
months of the investigation indicated that gains of all test groupsi were
nearly as great or greater than the control group gains. Below is a
table showing average gains of each group of hamsters during the third,
fourth, fifth and sixth months of the study.
Mean Gain During Month Indicated (grams)
Sex
Group
Third
Fourth
Fifth
Sixth
Males
Control
9
1
3 -3
TE-I
6
1
1
6
TE-II
20
-11
12
-2
TE-III
-2
-3
24
-2
Females
Control TE-I TE-II TE-III
2 6 -1 0
1 0 -1 -2
31 48 8 -2 68
CMA 001972
UndtutiiaL B I O * T E S T ^u^O'iaia'Uei, 9*tc.
12
IV . Body Wei 14lit Data
The mean body weight and weight gain data are presented in Table II, Below is a discussion of the data from each species.
Rats: The average seven-month weight gain of the TE-IV rats was found to be less than the control or other test group animals. This difference was attributed to the greater initial weights of the TE-IV group at the start of inhalation exposures. There were no other abnormalities or dose related trends in the other test groups.
Mice: There are no adverse body weight effects among the mice which can definitely be attributed to inhalation of the test material. Although the seven-month body weights and weight gains of the highest test level are less than the lower dose groups and the control mice, the differences are only slight.
QOl^3
BIO -TEST
Day Number
197 198 199 200 201 204 205 206 207 208 211 212
TABLE I continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
Exposure Number
TE-I Rang e
141 142
143* 144 145 146 147 148 149 150 151 152
40.0 29-0
-
38.5 37.5 41.5 41.5 40.5 47.0 48.0 42.5 36.0
55.0 64.5
-
56.0 55.5 61.0 52.5 51.5 56.5 54.5 51.0 64.5
Mean
45.1 57.4
49.0 48.0 51.0 47.0 49.2 51.6 51.4 47.0 48.1
Chamber Concentration (ppm)
TE-II
TE-III
Range
Mean
Rang e
Mean
178 216 196
170 220 177
--
-
178 310 223
174 212 197
188 248 218
184 234 207
178 272 223
180 206 193
170 242 200
160 230 189
154 282 194
2400 2460
2340 2340 2320 2280 2500 2300 2260 2320 2160
2700 2800
3120 2740 2700 2840 2800 2820 3420 2520 3200
2535 2594
2561 2500 2552 2541 2613 2444 2627 2413 2583
TE-IV
Range
Mean
2320 2400
2100 1980 1980 2420 2260 2200 2600 2200 2200
2480 2520
3200 2740 2800 2600 2420 2720 2700 2660 2600
2391 2440
_
2480 2553 2352 2523 2352 2524 2654 2440 2435
* Equipment failure, exposures not conducted.
n
o o V5 -J
BIO -TEST
QN
r-i
Day Number
170 171 172 173 176 177 178 179 180 183 184 185 186 187 190 191
193 194
TABLE I continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
1
Exposure Number
TE-I Rang e
122 123 124 125 126 127 128 129 130 131* 132 133 134 135 136 137 138 139 140
45.0 35.0 17.5 39.5 35.0 43.0 42.0 41.0 37.5
48.5 39.5 47.0 46.5 46.0 43.0 46.0 43.0 35.0
51.0 55.0 57.5 51.5 66.5 62.5 60.0 65.0 60.0
57.5 57.5 53.0 55.5 50-0 51-0 52.0 54-0 61.0
Mean
48.5 48.0 37.5 48.7 54.2 52.9 48.2 53.3 50.1
52.9 52.0 49.6 50.7 48.0 47.6 49.7 48.9 54.3
Chamber Concentration (ppm)
TE-II
TE-III
Range
Mean
Rang e
Mean
180 208 192 186 210 197 148 248 198 178 204 197 190 222 211 174 214 195 184 214 195 192 228 210 190 206 198
2260 2320 2000 2360 2360 2360 2400 2520 2340
2440 3020 2800 2620 3060 2860 2800 2800 2560
2461 2708 2488 2505 2787 2739 2512 2671 2467
170 206 196 186 220 206 184 224 209 180 262 194 170 220 201 196 212 202 178 206 197 174 200 187 158 246 205
2280 2320 2040 2180 2480 2460 2300 2340 2160
2580 2800 2680 3400 2800 2620 2640 2520 2700
2452 2551 2419 2515 2575 2512 2462
2424 2537
TE-IV Range
Mean
2200 2080 2400 2460 3060 2140 2440 2500 2400
2440 3140 2920 2620 3100 2880 2900 2740 2600
2355 2347 2640 2543 3080 2551 2644 2657 2500
2380 2220 2380 2400 2480 2340 2360
2220 2020
2540 2800 2580 2540 3280 2540 2540
2460 3900
2453 2434 2480 2472 2753 2445 2440
2343 2590
ooi^5 CHA
Day Number
137
138
141
142
143
144
145
148
149
150
151 o 152
155 156
oo
H
157
158 <X\
159
162
163
164
165
166
169
TABLE I continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
Exposure Number
TE-I Range
Mean
Chamber Concentration (ppm)
TE -II
TE-III
Range
Mean
Range
Mean
TE-IV Range
Mean
99
41.0
63.0
50.0
176 252 222
1600
3840
2745
1920
3600
2875
100
31.9
37.4
35.2
158 200 187
2000
2643
2354
1200
3440
2352
101
19.0 100.0
46.3
152 266 189
1860
2620
2346
1740
2600
2046
102
32.5
52.0
48.8
104 306 202
2620
3540
3100
2400
3320
2676
103
42.0
49-0
47.8
180 296 222
2080
2900
2580
1820
2620
2306
104
31.5
55.5
51.0
190 224 205
2340
2920
2546
2200
2820
2494
105
38.5
70-0
49.0
154 240 196
2320
2980
2408
2220
3160
2542
106
22.0
32.5
29.6
180 212 193
2240
2640
2393
2120
2270
2245
107
29.5
70.0
49.9
156 314 220
2140
3460
2614
1880
2040
1946
108
35.0
58.0
49.3
90 288 200
1780
2920
2566
2080
2860
2534
109
32.0
62.0
44.0
150 234 193
1280
2800
2349
2060
3000
2529
110
41.5 110.0
58.9
170 252 198
2300
2800
2497
2140
2700
2357
111
45.0
66.0
52.3
178 260 216
2620
2800
2683
2300
2900
2700
112
43.0
61.0
49.7
164 246 198
2300
2900
2573
2400
3240
2706
113
35.0
58.0
54.1
160 258 222
2220
2700
2519
2420
2560
2467
114
38.0
60.5
57.7
176 212 200
2220
2820
2392
2340
2680
2502
115
47.0
60.0
54.3
160 210 195
2180
2700
2538
1960
2660
2408
116
42.5
67.0
57.1
104 252 203
1460
2840
2592
2340
3080
2642
117
28.0
60.5
46.1
178 260 202
2240
3020
2535
2100
2400
2360
118
40.0
58.0
49.4
164 214 197
2280
2920
2922
2370
2540
2455
119
37.0
55.5
50.3
178 214 184
2280
2640
2428
2120
2740
2361
120
25.0
66.5
53.0
172 194 187
2400
2740
2529
2380
2480
2428
121
39.5
51 .0
48.0
158 264 213
2400
2740
2543
2100
3020
25o4
b io - test
Day Number
113 114 115 116 117 120 121 122
123 3
124 ^
127 128 129 3 130 131 134 135 136
TABLE I continued
*
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
I
Exposure Number
TE-I Rang e
81 21 50 82 Holiday 83 37 54 84 26 55 85 Equip - failure 86 45 46 87 32 54 88 48 60 89 20 58 90 39 52 91 37 55 92 39 58 93 43 55 94 42 63 95 35 70 96 52 77 97 25 48 98 40 43
Mean
42
-
47 47 45 44 54 44 46 47 51 50 53 53 68 38 41
Chamber Concentration (ppm)
TE-II
TE-III
Range
Mean
Rang e
Mean
180 244 211
-- -
164 260 201 178 214 200
--168 232 199 160 250 184 140 204 173 202 388 295 124 180 175 196 200 197 186 226 200 136 266 230 180 228 201 190 250 220 208 262 230 135 248 186 118 200 172
1620
-
2180 1980
1960 2200 2500 2410 1980 1600 1660 1600 2680 1740 2180 1560 2080
2520
-
2500 2780
2960 2820 2920 3960 2600 2560 2500 2620 3100 2800 2960 3480 2800
2306
-
2385 2393
2565 2513 2664 3090 2396 2414 2191 2145 2883 2259 2624 2983 2410
TE-IV Range
Mean
Equip .failure
_
--
1780
2240
2006
2100
2380
2176
--
2200
2840
2529
2040
2800
2390
1040
1120
1083
2000
2780
2377
2120
2280
2236
Equip .failure
-
Equip .failure
-
Equip .failure
-
One sample on Iy2900
1940
3000
2333
1700
2180
2180
2080
3660
3513
1860
2700
2170
co
09 n k iu lu a L B I - T E S T JaJwiaJtyiied., 9*
7" IS 3 1 -0 1 9 7*W *?6
Day Number
85 86 87 88 89 92 93 94 95 96 99 100 101 102 103 106 107 108 109 110
TABLE I continued
7
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
)
Exposure Number
TE-I Range
61
62
63
64
65
66
67
68
69
Q 70
71
o 72
o
H
73
74
00 75
76
77
78
79
80
29 47 47 54 46 80 35 50 50 61 28 53 37 56 40 45 32 46 37 47 29 31 27 52
*-
*-
38 55 Holiday Holiday 3? 55 36 47 36 50
Mean
43 49 60 48 53 42 48 42 39 43 29 36
-
-
51
-
~
46 43 44
Chamber Concentration (ppm)
TE-II
TE-III
Range
Mean
Rang e
Mean
148 200
98 174 208 136 110 206 170 170 258 168
-
-
180
-
228 158 166
216 220 224 220 232 192 302 238 216 230 310 310
-
"
230
-
-
260 248 242
191 210 185 211 214 172 209 216 190 199 277 256
-
203
-
247 235 201
1620 2160
400 2080 2220 1200 1600 2080 2000 1880 2740 1900
1680
-
--
1800 2120 1960
2280 2560 1960 2380 2540 2980 2900 3500 2840 2810 3940 3340
-
2620
-
2580 2600 3020
2077 2380 1659 2246 2394 1963 2401 2722 2367 2448 3185 2499
--
2585
--
--
2397 2409 1448
TE-IV
Range
Mean
1220
2500
2500
2940
2320
2720
2520
2680
2320
2520
Equip,.failure
2000
2680
Equip .failure
2220
2500
1880
2810
3280
3680
2440
3340
--
2210
2640
"~
2306 2725 2457 2506 2428
-
2503
-
2328 2448 3516 2578
2470
2360 2240 2200
2900 2560 2680
2633 2464 2400
Unable to run exposures due to weather.
Day Number
57 58 59 60 61 64 65 66 67 68 Q 71 72 O 73 o 74 \> 75 KD 78 79 80 81 82
TABLE I continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
I
o
tn
Exposure Number
TE-I Range
41 47 59 42 48 56 43 51 59 44 46 80 45 43 61 46 42 58 47 114 136 48 48 114 49 43 60 50 24 39 51 Equip - failed 52 42 51 53 45 58 54 Holiday 55 Holiday 56 44 60 57 48 74 58 45 60 59 28 49 60 42 47
Mean
53 54 56 63 52 53 119 84 52 32
-
48 49
-
-
48 56 54 46 45
Chamber Concentration (ppm)
TE-II
TE-II1
Rang e
Mean
Rang e
Mean
96 188 128 148 248 219 196 262 238 200 240 211 178 220 195 188 210 199 172 452 298 146 416 255 178 240 206
96 124 105
- --
194 226 210 178 211 202
- --
-"
180 229 196 304 390 347 220 364 243 198 248 218 214 262 240
1950 2240 2400 2110 2040 1690 1140 2240 2280 2180
*
2380 2310
-
--
2190 1740 2020 2060 2080
2900 2660 3100 2680 2780 2690 1750 4000 2590 2460
-
2700 2650
-
2700 2400 2760 2500 2580
2686 2579 2835 2344 2640 1968 1659 2910 2498 2348
2565 2516
-
2445 2141 2404 2333 2229
TE-IV Range
2210 2610 2900 1560 1920 2040 2550 1160 2500 1520
2630 3220 3310 1990 2340 2660 2670 1940 2610 1700
2410 2340
--
-
2320 1375 1940 1940 2100
2560 2590
~
2620 1870 2580 2560 2800
Mean
2310 2616 3203 1752 2149 2281 2569 1754 2573 1612
"
2528 2460
--
r
2525 1576 2231 2306 2388
CT'
Day Number
29 30 31 32 33 36 37 38 39 40 43 Q 44 > 45 9 46 hVO 47 ooo 50 51 52 53 54
TABLE I continued
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
*
Exposure Number
TE-I Range
21 48 66 22 47 63 23 31 51 24 42 47 25 29 58
45 60
27 46 58 28 48 58 29 42 55 30 45 52 31 45 60 32 41 58 33 39 56 34 47 53 35 46 55 36 40 62 37 43 51 38 28 55 39 38 49 40 45 57
Mean
58 56 46 45 51 47 55 52 43 50 52 48 44 50 54 60 50 38 45 49
Chamber Concentration (ppm)
TE-II
TE-III
Range
Mean
Rang e
Mean
192 248 219 216 340 265 200 256 220 196 232 106 172 232 212
92 280 203 210 242 225 168 190 184 188 216 209 204 212 209 106 238 180
98 190 177 178 240 215 168 206 200 210 224 217 166 198 171 172 214 190 190 220 198 182 212 193 134 238 278
1090 2000 1900 2120 2200 1680 1600 2210 1970 1740 2070 1810 1900 1850 2180 1670 2220 2010 1980 1610
2490 2870 2770 3960 2840 2640 2600 2830 2770 2800 2900 2570 3010 2790 2600 2510 2610 2750 2460 2590
1561 2567 2659 2855 2496 1899 2337 2587 2474 2141
2659 1920 2190 2002 2377 2083 2451 2225 2208 2018
TE-IV Range
Mean
2400 2030 1960 2020 1360 1530 2670 2070 2590 2600 2610 2250 1890 1980 2050 2310 3160 3090 2530 2070
1560 2710 2600 2900 1920 2000 3350 3510 2890 2930 3040 2610 2190 2560 2350 2920 3670 4090 2740 2540
2488 2105 2295 2441 1655 1799 2998 3356 2686 2750 2891 2564 1920 2379 2213 2692 3307 3688 2638 2525
*C
1 S 3 1 * I H0
Day Number
1
2
3
4
5
8
9
10
11
12
15
16
17
18 n
19
22
23
O o
24
h4 VO
25 00
26
TABLE I
TEST MATERIAL: Vinyl Chloride (Ethylene Derived)
Chronic Vfcpor Inhalation Toxicity Study - Albino Rats, Albino Mice, and Golden Hamsters
Chamber Concentration Data
I
Exposure Number
TE-I Range
1 39 55 2 42 51 3 45 53 4 45 54 5 50 56 6 40 62 7 51 63 8 41 61 9 49 65 10 38 77 11 45 69 12 42 63 13 52 61 14 56 64 15 41 66 16 43 62 17 47 78 18 44 55 19 43 54 20 55 69
Mean
43 48 50 51 52 57 53 56 58 62 60 60 58 59 47 49 60 51 50 62
Chamber Concentration (ppm)
TE-II
TE-III
Rang e
Mean
Rang e
Mean
130 180 173
164 190 181
170 214 207
24 162
87
182 237 218
128 332 194
186 260 199
115 280 164
188 274 242
174 198 186
160 224 202
54 266 156
170 228 207
84 200 162
96 178 160
196 222 211
202 224 219
178 208 201
194 220 214
200 264 242
1820 1700 1290 1190 1160 1600 1990 2240 2010 1150 2230 2400 2750 1870 2200 1990 2470 2220 1610 1690
2610 2600 2550 3600 3100 2850 2610 2840 2650 2900 2690 3100 2480 2666 2630 2510 3000 25310 2830 2740
2510 2548 2098 2540 2202 2401 2475 2555 2283 1770 2510 2653 1972 2544 2556 2391 2922 2356 2690 2488
TE-IV Range
Mean
2030 2240 2140 1980 1900 2000 2300 1850 1970 2390 3010 2430 1160 1150 2320 2540 2370 2570 1810 2390
2880 2600 2590 2490 2580 2480 2980 2310 2690 2930 3570 2920 1920 2400 2610 2640 2560 2980 2150 2650
2355 2467 2261 2293 2330 2329 2675 1915 2192' 2481 3236 2733 1664 1794 2545 2612 2531 2777 1969 2510
`tmvcpnvfDp X S 3 1 * O 1a^
Dtuluilual B I O - T E 5 T loltonalvu&i, 9*tc.
3
III, Chamber Concentration Data The daily range and mean of the Vinyl Chloride concentrations in
each test chamEer are shown in Table I. The overall average daily vapor concentrations were calculated to be 49.5, 201, 2548 and 2487 ppm for the TE-I through TE-IV chambers, respectively.
CMA 001982
JIndtuiiial B I O - T E S T ^alwato-'ii&l, 9mc.
2
II. Summary After seven months of inhalation exposures, dose related gross and
histopathologie-findings have been observed in all test levels of the mice. These findings have included test material related lesions consisting of alveologenic adenomas of the lung, hemangiosarcomas of the liver and malignant mammary tumors.
Studies of other parameters including behavioral reactions, body.weights and mortality have not revealed definite dose related responses to inhalation of Vinyl Chloride.
Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC.
Report prepared by :
// * f jJ
44
Kenneth J. /Sdhadeberg
J-
Senior Group Leader
Inhalation and Pharmacology
Report approved by:
,1
(John W. Goode, Ph.D. mager
Decatur Research Laboratories
Manager, Toxicology lb
CMA 001983
9nda.it-u.jl B I O - T E S T lakyxatvu&i., 9hc.
SEVEN-MONTH STATUS SUMMARY TO MANUFACTURING CHEMISTS ASSOCIATION CHRONIC VAPOR INHALATION TOXICITY STUDY WITH
VINYL CHLORIDE (ETHYLENE DERIVED) IN ALBINO RATS, ALBINO MICE AND GOLDEN HAMSTERS JUNE 19, 1974 IBT NO. 663-03222
I. Introduction A chronic vapor inhalation toxicity study with Vinyl Chloride (Ethylene
Derived) was initiated on September 10, 1974. A summary of all data ob tained through the seventh month of exposures is reported herein.
CMA 001984
TOXICOLOGY
ENVIRONMENTAL SCIENCES CHEMISTY
plant sciences
medical sciences
9nduAt/wal BI O - T E S T
1810 FRONTAGE ROAD NORTHBROOK, ILLINOIS 60062
June 19, 1974
9m.
AREA CODE 312 TELEPHONE 272-3030
Dr. Kenneth D, Johnson Manufacturing Chemists Association 1825 Connecticut Avenue, N. W. Washington, D. C. 20009
Dear Dr. Johnson:
Re: IBT No. 663-03222 - Chronic Vapor Inhalation Toxicity Study with Vinyl Chloride (Ethylene Derived) in Albino Rats, Albino Mice and Golden Hamsters - Seven-Month Status
We are submitting herewith our laboratory report dated
June 19, 1974, prepared in connection with the above study.
Very truly yours
^v
J. C. Calandra President
JCC:bp
CMA 001985