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1 TOXICOLOGY ENVIRONMENTAL SCIENCES CHEMISTRY PLANT SCIENCES MEDICAL SCIENCES SnduAt'ual BIO - T E $ T Jlalb&icLjxyu/id', Dnc. DECATUR RESEARCH 1800 EAST PERSHING ROAD DECATUR. ILLINOIS 62526 August 16, 1974 s AREA CODE 217 TELEPHONE 677-9254 Dr. Kenneth D, Johnson Manufacturing Chemists Association 1825 Connecticut Avenue N. W. Washington, D. C. 20009 Dear Dr. Johnson: Enclosed are tables summarizing mortality, body weight and gross pathologic findings through the eleventh month of inhalation exposures on the chronic inhalation toxicity study with Vinyl Chloride. I've also included a table giving daily concentration data from the seven-month point to the end of the eleventh month. Preceding each table is a brief discussion of the data. A complete and formal eleven-month status summary with full evaluation of this data plus histopathologic data will be submitted shortly. Sincerely Ken JLimueuerg, u.l? Senior Group Leader Inhalation Toxicity KS/dm enc. cc - Dr. T. R. Torkelson J. W. Goode M. L. Keplinger RSV 0003204 Ondust/iial B I O - T E S T ^aL&taiiyu&i, Ohc. 1 . I, Analytical Concentration Data The daily range and mean of the Vinyl Chloride concentrations in each chamber from exposure 153 (data previous to this exposure given in seven-month status report) through the end of the eleventh testing month are reported in Table I. The overall average daily vapor concen trations were calculated to be 49.9, 198, 2501 and 2489 ppm for the T-I through T-IV chambers, respectively. RSV 0003205 TABLE I TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats. Albino Mice and Golden Hamsters Chamber Concentration Data )ay Tiber RSV 0003206 Exposure NumberRange Chamber Concentration (ppm) T-I T- MeanRange Mean T-1II Ran Re 153 45.5 48.5 47.5 176 214 197 1820 2680 154 50.5 55.0 51.5 180 242 206 2300 2820 155 Holiday , no exposures 156 43.5 53.5 46.5 180 242 202 2180 3000 157 46.5 52.5 50.4 154 194 184 2320 2600 158 36.5 52.5 45.0 138 250 192 1440 2600 159 44.5 55.0 49.2 130 138 134 2460 2620 lfaO 38.0 67 .5 45.1 124 260 196 2000 3120 161 47.0 61.0 53.1 130 200 179 2380 2920 162 47.5 53.0 57.8 150 232 181 2380 2700 163 50.0 53.5 51.5 180 210 195 2440 2800 164 47.0 53.0 52.1 184 202 187 2200 2660 165 46.5 56.0 49.4 190 216 200 2420 2800 166 47.0 71.0 52.3 184 228 201 2100 2820 167 42.5 53.0 47.9 180 204 199 2300 . 2740 168 38.0 55.5 49.4 180 226 193 2160 2800 169 44.0 51.0 47.6 196 215 207 2440 3710 170 48.0 56.5 53.6 184 216 205 2120 3100 171 46.0 51.5 49.3 186 198 191 2260 2620 172 47.0 50.5 48.5 202 214 209 2180 2600 Mean 2467 2459 2554 2457 2240 2540 2687 2384 2484 2580 2488 2583 2520 2479 2472 2932 2528 2487 2478 T-IV Range 2340 2400 2500 2640 2140 2160 2500 2600 1100 2500 2340 2740 2600 2660 2160 2480 2200* 2500 2460 2400 2140 2380 2400 3020 2510 3000 2700 3040 2900 2800 2500 2940 2800 2900 2980 2580 2460 Mean 2409 2493 2231 2294 2760 2600 2264 2664 2456 2815 2669 2755 2353 2667 2545 2729 2668 2488 2339 CO O to r r-n . ms i Jr.. .-'<ir*y. TABLE I continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats. Albino Mice and Golden Hamsters Chamber Concentration Data iy ber Exposure Number 173 174 175 176 177* 178 179 180 181*** 182 183 184 185 < 186 187 O 188 o o 189 u 190 191 1 Q? 193 T-i Rang;e Mean Chamber Concentration (ppm) T-II T-I1I Ranee Mean Range 44.5 55.5 50.4 46.5 53.0 47.9 48.5 52.5 50.5 45.0 54.5 48.8 47.5 55.0 51 -0 47.5 52.5 51.2 44.0 56.0 49 A Equipment malfunction, 45.5 57.0 51.4 44.0 51.5 50.0 43.0 75.0 57.4 47.0 55.0 50.9 39.0 57.5 48.0 35.0 66.0 48.6 38.0 75.5 49.9 43.0 50.0 47.4 Holiday,, no exposures 41.0 50.5 47.5 45.5 58.5 50.2 46.0 41.0 57.0 55.5 50.5 50.5 154 220 180 222 194 206 182 210 -- 186 222 164 236 no exposures 188 218 184 212 88 222 172 230 180 214 182 250 170 266 196 224 192 210 192 251 182 214 186 234 197 194 199 198 - 203 201 204 193 171 203 199 209 202 205 198 196 20Q 215 1500 2100 2380 2320 2440 2420 2560 1900 2320 2000 2300 2140 2140 2140 2160 2300 2160 2320 2380 3340 2560 2780 2760 2780 2700 2740 2760 2500 2640 2720 2400 2888 3240 2560 2620 2540 2620 2880 Mean T-IV Range 2468 2367 2487 2534 2618 2573** 2645 2340 2480 2460 2320 2560 2580 - 2760 2600 2520 2660 2820 2700 - 2347 2396 2364 2501 2328 2397 2537 2400 1900 2420 2100 2040 2280 2200 2500 2460 ^ / bU 2500 2620 2460 2500 2600 2560 2560 2431 2350 2452 2633 2240 2380 2420 2320 2440 2760 Mean 2532 2512 2496 2536 2673 2640 " 2347 2464 2280 2355 2380 2392 2545** 2524 2272 2400 2540 o m iSI r LO iV - i TABLE I continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Chamber Concentration Data Day Exposure Number ?70 194 271 195 274 196 275 197 276 198 277 199 278 200 281 201 282 202 283 203 284 204 X 285 Co 205 288 < 206 289 207 290 o 208 291 u> 209 fv 292 o 210 295 00 211 296 212 297 213 T-I Range Mean Chamber Concentration (ppm) T-II T-IIi Range Mean Ran Re______ Mean 48.0 43.5. 44.5 38.0 45.5 47.0 54.5 50.5 51.0 56.0 52.5 56.0 50.1 47.3 47.9 49.5 48.9 50.3 172 190 188 174 188 170 214 208 216 242 214 220 204 2260 200 2140 202 2180 198 2160 199 2320 201 ,2280 37.0 52.5 48.3 176 226 200 2220 40.0 56.0 47.5 168 232 204 2360 43.5 54.0 48.2 176 236 202 2120 43.0 54.0 49.7 188 216 206 2340 47.0 57.0 52.5 144 220 194 3400 43.0 58.5 50.3 154 224 199 2100 Equipment malfunction. but animals were exposed 42.5 59.0 48.5 194 206 200 2360 40.0 53.5 45.9 204 218 209 2280 45.5 51.5 . 49.3 166 220 203 2380 Equipment malfunction, no exposure 46.5 54.5 47.6 186 230 207 2280 43.5 53.0 49.3 200 210 205 2480 Vinyl Chloride: gas regulator broken, no exposures 2660 2560 2580 2640 2720 2860 2700 2740 2940 2920 3420 2980 2820 2820 2680 3200 2660 2447 2439 2377 2386 2457 2585 2473 2515 2459 2550 2620 2504 2593 2482 2521 2577 2613 T-IV R anSe______ Mean 2.140 2380 2400 2440 2340 2300 2580 2520 2280 2540 2210 2140 2400 2500 2460 2440 2740 2920 2900 2720 2520 2780 2600 2560 2270 2408 2440 2440 2564 2656 2672 2600 2413 2640 2478 2397 2480 2280 2440 2620 2560 2560 2528 2424 2516 2280 2520 2520 2680 2428 2585 t 1 0 <n o .i. r.t- **# TABLE I continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Chamber Concentration Data Day Number Exposure Number 298 214 299 215 302 216 303 217 304 218 305 219 306 220 309 221 310 222 311 223 312 224 315 30 225 316 < 226 317 227* 318 o 228 319 c w 229 322 t\) o 230 323 sC 231 324 232 325 233 T-I Range Mean Chamber Concentration (ppm) T-II T-III Range Mean Rang_______ Mean Holiday, no exposures Holiday, no exposures Vinyl Chloride gas regu lator broken, no exposures Vinyl Chloride 45.5 50.5 44.5 52.5 45.0 57.5 41.5 49.5 47.5 55.0 44.5 57.5 39.0 46.0 37.0 52.5 46.0 55.0 46.5 55.5 46.5 52.0 44.5 52.0 49.5 56.5 49.5 62.0 gas regulator 48.2 202 48.6 186 42.3 190 45.9 168 51.0 186 51.3 160 42.8 148 44.2 146 54.0 182 50.6 152 49.2 49.1 52.0 170 192 198 54.9 176 broken, 226 210 218 192 196 226 172 196 220 242 280 222 222 250 no exposures 218 2140 2460 204 2280 2740 203 2360 2660 185 2080 2500 193 2280 2500 184 1 sampl e only 160 1800 2040 174 1800 2440 208 2080 2500 205 2040 2800 192 1960 2380 201 2440 2620 210 2500 2680 208 2160 2840 49-5 54.5 50.7 200 208 204 2220 2620 45.5 56.5 49-7 190 206 196 2400 2840 2288 2565 2481 2258 2380 2280 1920 2073 2473 2558 2022 2542 2699 2475 2405 2597 T-IV Range_________ Mean 2400 2500 2400 2520 2400 2500 2360 2500 2280 2500 1 sample only 2640 2960 2500 31GG 2400 2620 2480 2445 2440 2410 2364 2440 2800 2680 2480 2240 2500 2300 2260 2200 2220 2580 2720 2620 2380 2460 2500 2400 2640 2460 2333 2348 2370 8 1 0 - T S T V U Day Number 326 329 330 331 332 333 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 T-I Rang e Mean Chamber Concentration (ppm) T-II T-III Range Mean Range Mean T-1V Range Mean 234 235 236* 237* 238 239 48.0 62.0 54.0 Equipment malfunction, - - 58.0 53.5 58.5 55.5 56.0 56.0 56.0 47.5 55.0 51.3 170 238 202 but animals exposed 200 204 202 186 198 191 206 208 208 185 210 202 2300 2500 2220 2260 2160 2760 2580 2500 2380 2600 2576 2540 2376 2300 2556 2520 2760 2576 - - 1 sample only 1700 2300 - - 2420 2084 * No exposure in group indicated; animal cages repaired. ** Exposures cut to 51 hours; animal cages repaired. *** Exposures cut to 41 hours; gas chromatograph repaired. Note: In exposures noted above, the equipment malfunction is referring to a breakdown in the gas chromatograph or sequential sampler valve system-chamber concentrations were believed to be near targets. CP 0 c* K. to < o o o tv fsj *-- O BIO-TEST J.a&osuUo'ue&. One. 7 II. Mortality Data The cumulative monthly mortality data are presented in Table II. Below is a brief discussion of the data for each species. Rats: With the exception of the T-IV rats (composed of females only and permitted food ati libitum) there is a dose related mortality effect in both sexes at the eleven month point. Although the total number of rats which died in the T-IV group is not as great as in the T--HI female group, there was a rapid increase in mortality during the eleventh month in the T-IV group. Mice: Dose related mortality effects were observed in both male and female mice at the eleven month point. Hamsters: A significant increase in mortality rate was observed among male and female T-III hamsters during the eleventh month of the investigation. There were no other significant mortality findings. RSV 0003211 r, 9*uiu<lt\ial B I O - T E S T 9*tc. 8 Month Number 1 2 3 4 5 6 7 8 9 10 11 TABLE II TEST MATERIAL: Vinyl Chloride (Ethylene' Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary of Mortality Data - Albino Rats Accumulative Number of Mortalities at End of Month Control T-I T-II T- III MF MF MF M F 0 00 0 00 0 0 0 02 01 00 0 0 1 2 0 1. 0 1 4 '0 2 4 1 3 0 1 . 4 2 35 161 3 4 346 2 6 1 5 4 448 6 626 5 4 5 9 7 10 5 10 8 4 6 10 8 11 5 16 15 5 7 11 11 12 9 24 28 7 8 13 13 14 19 34 52 T-IV F 0 0 0 0 _Q 0 0 1 4 7 17 RSV 0003212 --" E r * y .i h t -.i t ' r w .u r a r r M ir ) r it f tt i 9ndu&bual B I O - T E S T JaJiAJisifateA j?,*- Month dumber 1 2 3 4 5 6 7 8 9 10 11 TABLE II continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary of Mortality Data - Albino Mice Accumulative Number of Mortalities at End of Month Control T-I T-II T-III MF MF MF M F 000 00000 000 30000 2 0 6 4 3 0 1 -0 5 1 19 5 4 1 4 7 8 2 26 6 4 2 8 7 12 2 30 6 8 3 10 9 18 5 31 11 9 12 13 23 18 5 32 14 16 30 30 46 23 8 38 24 37 58 56 75 28 10 42 31 78 82 76 98 30 15 54 46 96 94 100* 100* * All surviving mice sacrificed r? fr ? \ - t - i ~TTH TTm ~l II I I IT - RSV 0003213 0ndM.it/ual B I O - T E S T dcdt&iattyu&i., One. TABLE II continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary of Mortality Data - Golden Hamsters Accumulative Number of Mortalities at End of Month Month Control T-I T-II T-III Number _____ M F M F MF M F 1 544 47 52 5 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 8 14 28 24 19 23 35 19 28 9 14 29 24 20 25 36 20 28 10 14 30 26 20 26 37 23 29 11 15 31 28 21 26 38 28 36 10 003214 9nduA&ual B I O - T E S T J.\ib&uztosu&i., 9*c. 11 III. Body Weight Data The mean body weight and weight gain data are presented in Tables III through V. Below is a brief discussion of the data for each species. Rats: There are no dose related findings. Mice: There appeared to be a drop in body weights of both the males and females of the T-III group during the tenth month of testing. These mice were sacrificed during the eleventh testing month. The other test levels do not indicate any definite adverse effecs. Hamsters: Except for th T-III female hamsters, which revealed a low mean body weight for the eleventh month, there are no significant findings . RSV 0003215 BIO -TEST A RSV 0 0 0 3 2 1 6 Group e Control T-I T-II T-11I iale Control T-I T-II T-1II T-1V TABLE 111 TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden JlamsLers Summary of Mean Body Weights - Albino Rats Mean Body Weights (grams) Month Number: 0 1 2 3 4 5 6 7 8 9* 10 11 205 363 456 498 517 537 543 550 559 697 677 689 209 346' 448 491 526 545 554 567 593 651 640 670 201 360 457 490 522 549 567 565 585 681 663 696 200 351 453 499 529 550 567 576 581 627 629 680 160 235 275 299 315 320 326 344 356 392 366 380 168- 232 274 297 310 308 323 348 367 357 363 374 171 242 289 302 313 316 329 342 358 368 362 386 165 240 287 303 312 321 329 346 359 359 356 374 181 251 282 288 291 314 324 338 348 363 363 384 Gain 484 461 495 480 220 206 215 209 203 ^parent malfunction of animal weighing machine during month indicated. a*\ - - - ** nr iL ..Jt 1 TABLE IV 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 Mean Body Weights (grams) Month Number: 0 1 2 3 4 5 6 7 8 9* 10 11 & Control 35 40 41 43 46 43 46 52 49 47 43 47 T-I 33 39 ' 39 43 44 42 47 45 47 47 38 48 T-II 36 40 38 42 44 42 45 43 44 46 37 44 T-III 36 38 40 43 44 38 45 41 41 43 31 ale Control 29 32 33 35 36 35 38 37 41 40 37 40 . T-I 30 ` 34 34 37 39 38 40 41 40 40 42 43 T-II T-III 28 31 34 35 37 36 38 36 40 39 30 40 28 31 34 35 36 37 37 34 37 39 27 ** Cain 12 15 8 ** 11 13 12 ** H b* Exposures were terminated for all mice at the end of the ninth month of the investigation. U1 surviving T-III mice were sacrificed during the eleventh month of the investigation. 5t/0> < O O UJ N U> - sj .. ... -------- >T inn - ----------------mi---------n----------------i~f ' mi I III I lll'"l i iif 'ilia Hi............... Tiir^MmiillVHinrmini|~|iTiT~i iTl'r I HIIW mi Sex Male Female Group Control T-I T-U T-1II Control T-I T-Il T-III TABLE V TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary o Mean Body Weights - Golden Hamsters 01 73 98 71 90 63 89 60 87 77 104 78 95 74 94 69 92 Mean Body Weights (grams) Month Number: 2 3 4 5 6 7 8 9 10 11 110 120 129 130 133 130 138 141 129 126 101 114 120 121 122 128 126 118 115 110 94 99 119 108 120 118 122 117 115 115 91 93 91 88 112 110 115 115 115 114 108 118 120 121 124 125 128 133 119 116 102 112 118 118 122 130 126 125 118 no 99 108 107 106 114 112 116 118 112 112 100 106 106 104 110 118 105 107 103 99 Gain 53 39 52 54 39 32 38 30 tP o -H m in r RSV 0 0 0 3 2 1 8 '-'W ' ~ f- j. OnduiUiial B I O - T E S T 9kc. 15 IV. Gross Pathology A summary of tumor data based on gross pathologic findings among all species is presented in Table VI. This table does not take into account animals that died and postmortem autolysis or cannibalism precluded gross pathologic examination. f. .4 j RSV 0003219 r~ Oncbiifrual B I O - T E S T a&o/iatosUe&, One. 16 TABLE VI TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary of Tumor Data Based on Gross Pathologic Findings Among All Species Through 8/14/74 Species Group Number of Animals Examined Total Male Female Tissue Involved (Male/Female) Liver Lung Skin* Kidney Mice Control 4 3 1 0/0 1/1 0/0 0/0 T-I 36 12 24 4/9 5/16 2/7 0/1 #- T-II 133 67 66 45/57 52/39 7/26 5/9 v T-ni 121 58 63 48/47 44/45 4/20 7/3 Rats Control T-I T-II T-III T-IV 0 3 11 52 7 0 3 4 18 0 0 0 7 34 7 0/0 2/0 0/5 7/24' 0/5 0/0 2/0 0/4 0/6 0/0 0/0 0/0 0/1 0/8 0/5 0/0 0/0 0/0 0/2 0/0 Hamsters Control 0 0 0 0/0 0/0 0/0 0/0 T-I 0 0 0 0/0 0/0 0/0 0/0 T-II 0 0 0 0/0 0/0 0/0 0/0 T-III 10 7 3 2/2 4/1 1/0 0/0 * Mammary Tumors RSV 0003220 L