Document x1bez2pDQ2jv0x4j9Yyw1DYaG

DEPAfv.JlENT OF HEALTH. EDUCATION. ANL PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH BCTHESOA. MARVLANO 20014 Welfare February 21, 1975 NATIONAL CANCER INSTITUTE Bear Colleague: Enclosed Is the latest revision of the Guidelines for Carcinogen Bloassay in Small Rodents, Although the material contained In this document describes many of the areas that need to be considered whenever a carcinogen bloassay Is planned or undertaken, it does not cover them all. Thus, future revisions of the "Guidelines" will be Issued as new sections are developed and changes are made in existing ones. We would appreciate your comments as to how the "Guidelines" might be further developed. Your name has been placed on the mailing list to receive new editions of the "Guidelines" as they become available. Thank you for your interest. Sincerely n - Enclosure James M. Sontag, Ph.D. * Manager, Bloassay Operations Segment Carcinogenesis, DCCP, NCI Landow Building, Room A-306 Bethesda, Maryland 20014 see 5-0197 (Admit trative Document) GUIDELINES FOR CARCINOGEN BIOASSAY IN SMALL RODENTS James M. Sontag, Ph.D. Manager, Bioassay Operations Segment Norbert P. Page, D.V.M. Chief, Carcinogen Bioassay and Program Resources Branch February 21, 1975 CARCINOGENESIS, DIVISION OF CANCER CAUSE & PREVENTION NATIONAL CANCER INSTITUTE BETHESDA, MARYLAND See 5~019S  r Cj f* , *2-382 (2D *2-383 1 <> /*. - / qJ' qMApg^-j c~*-$<7 fjys \j^S-^. 42-383 42-363 --------------------------------i Sir i ex ,A*x*._______2 _ cT rd X~tln. Mfi ~i^ro i _/ , - ./iWri 1 </f'S- (Wfo - H* 7 ! /S *! .. 3T _^jQ. c*=c '^9r- U>4 *4L-, ^kJ:r> #> iUi> 4k i A . AC J >! If ~ll A Q ' (2* r* nmft A i tr^- -- [ Q~/u &ju /-- / f Aa< <1 H/ rec OA A \i V c \? s< i M. ' 6) c r/t-o-twr rTM A la- <OU : , Ja A_P^ i / i Pa ytx^iAjiri' *.(*uh -^Ti --<r - cA<La. JLC r-.x (f*((o >/*$ -Osf/ ~0 Lr / ! \ ................................. i -- 1... i Ti: ii i i i ^ i n |i! I ........... 1 ' ^|t * 1 j \ -- -- ----------------- \ i ____ . J . .. I r" see 5-0205 A W * B i u - I CO Day Number 213 214 215 218 219 220 221 222 225 226 227 228 229 232 233 234 235 236 TABLE I TEST MATERIAL; Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study ~ Albino Rats, Albino Mice and Golden Hamsters Chamber Concentration Data Exposure Number 153 154 155 156 157 158 159 . 160 161 162 163 164 165 166 167 168 169 170 T-I Rang;e Mean Chamber Concentration (ppm) T-II T-III Range Mean Range ` Mean 45.5 48.5 47.5 176 214 197 1820 2680 2467 50.5 55.0 51.5 180 242 206 2300 2820 2459 Holiday,, no exposures 43.5 53.5 46.5 180 242 202 2180 3000 2554 46.5 52.5 50.4 ' 154 194 184 2320 2600 2457 36.5 52.5 45.0 138 250 192 1440 2600 2240 44.5 55.0 49.2 130 138 134 2460 2620 2540 38.6 . 67.5 45,1 124 260 196 2000 3120 2687 47.0 61.0 53.1 130 200 179 2380 2920 2384 47.5 53.0 57.8 150 232 }81 2380 2700 2484 50.0 53.5 51.5 180 210 195 2440 2800 2580 47.0 53.0 52.1 164 202 187 2200 2660 2488 46.5 56.0 49.4 =.190 . 216 200 2420 2800 2583 47.0 71.0 52.3 184 228 201 2100 2820 2520 42.5 53.0 47.9 180 . 204 199 2300 2740 2479 38.0 55.5 49.4 180 226 193 2160 2800 2472 44.0 51.0 47.6 196 215 207 2440 3710 2932 48.0 56.5 53.6 184 216 205 2120 3100 2528 V. _________________ T-IV Range 2340 2400 2500 2640 2140 2160 2500 2600* 1100 2500 2340 2740 2600 2660 2160 2480 2200 2500 2460 2380 2400 3020 * 2510 3000 2700 3040 2900 2800 2500 2940 2800 2900 2980 Mean 2409 2493 2231 2294 2760 2600* 2264 2664 2456 . 2815 2669 2755 2353 2667 2545 2729 2668 see 5-0206 v & LTi () a ia - t &s t Day 239 240 241 242 243 246 247 248 249 250 253 254 255 256 257 260 261 262 TABLE 1 continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rata, Albino Mice and Golden Hamsters Chamber Concentration Data Exposure Number 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 T-I Ratige Mean Chamber Concentration (ppm) T-II T-III Ranee Mean Range 46.0 51.5 49.3 186 198 47.0 50.5 48.5 202 214 44.5 55.5 50.4 154 220 46.5 53.0 47.9 180 222 48.5 52.5 50.5 194 206 45.0 47.5 54.5 55.0 48.8 51.0 182 210 - 47.5 52.5 51.2 186 222 44.0 56.0 49.4 164 236 Equipment malfunction, no exposures 45.5 57.0 51.4 188 218 44.0 43.0 51.5 75.0 50.0 184 57.4 ' 88 212 22 47.0 55.0 50.9 172 230 39.0 35.0 57.5 66.0 48.0 48.6 180 182 214 .250 38.0 75.5 49.9 170 266 43.0 50.0 47.4 196 224 191 209 197 194 199 198 - 203 201 /. 204 193 171 203 199 209 202 205 2260 2180 1500 2100 2380 2320 2440 2420 2560 2620 2600 3340 2560 2780 2760 2780 2700 2740 1900 2320 2000 2300 2140 2140 2140 2160 / \ 2760 2500 2640 2720 2400 2888 3240 2560 Mean 2487 2478 2468 2367 2487 2534 2618 2573 2645 2347 2396 2364 2501 2328 2397 2537 2400 T-IV Range 2400 2140 2340 2480 2460 2320 2560 2580 ** 2580 2460 2760 2600 2520 2660 2820 2700 ** 1900 2420 2100 2040 2280 2200 2500 2460 2760 2500 2620 2460 2500 2600 2560 2560 Mean 2488 2339 2532 2512 2496 2536 2673 2640 2347 2464 2580 2355 2380 2392 2545 2524 see 5-0207 s cr 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 263 264 267 268 269 270 271 274 275 276 277 27 8 281 282 283 284 285 288 Exposure Number 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 T-I Ranee Mean Chamber Concentration (ppm) T-Il T-III Ranee Mean Range Holiday , no exposures 41.0 50.5 47.5 192 210 198 2300 45.5 58.5 50.2 192 251 196 2160 46.0 57.0 50.5 182 214 200 2320 41.0 55.5 50.5 186 234 215 2380 48.0 54.5 50.1 172 214 204 2260 43.5 50.5 47.3 190 208 2QQ 2140 44.5 51.0 47.9 188 216 202 2180 38.0 56.0 49.5 174 242 198 2160 45.5 52.5 48.9 188 214 .199 2320 47.0 56.0 50.3 170 220 201 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 1400 43.0 58.5 50.3 154 224 199 2100 Equipment malfunction. but animals were exposed / 2620 2540 2620 2880 2660 2560 2580 2640 2720 2860 2700 2740 2940 2920 3420 2980 Mean 2431 2350 2452 2633 2447 2439 2377 2386 2457 2585 2473 2515 2459 2550 2620 2504 T-IV Rangg______ Mean ** 2240 2380 2420 2140 2380 2400 2440 2340 2300 2580 2520 2280 2540 2210 2140 ** 2320 2440 2760 2400 2500 2460 2440 2740 2920 2900 2720 2520 2780 2600 2560 2272 2400 2540 2270 2408 2440 2440 2504 2656 2672 2600 2413 2640 2478 2397 see 5-0208 I t < r*//- `T&nvrrywrrDT 1C 3 l - r> l a Day Number 289 290 291 292 295 296 29? 298 299 302 303 304 305 306 309 310 311 312 TABLE I continued TEST MATERIA^: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice an<2 Golden Hamsters Chamber Concentration Data Exposure Number 207 108 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 T-I Range Mean Chamber Concentration (ppm) T-II T-III Range Mean Range 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 Holiday, no exposures Holiday, no exposures Vinyl Chloride gas regulator broken, no ^pxposures Vinyl Chloride gas regulator broken. no exposures 45.5 50.5 48.2 202 226 218 2140 44.5 52.5 48.6 . 186 210 204 2280 45.0 57.5 42.3 190 218 203 2360 41.5 49.5 45.9 168 192 185 2080 47.5 55.0 51.0 186 196 193 2280 44.5 57.5 51.3 160 226 184 * 39.0 46.0 42.8 148 172 160 1800 2820 2820 2680 3200 2660 2460 . 2740 2660 2500 2500 *' 2040 Mean 2593 2482 2521 2577 2613 T-1V Ran ge 2480 2280 2440 2620 2560 2560 2280 2520 2520 2680 Mean 2528 2424 2516 2428 2585 2288 2565 2481 2258 2380* 2280* 1920 2400 2400 2400 2360 2280 * 2640 2500 2520 2500 2500 2500 * 2960 2480 2445 2440 . 2410 2364 2440* 2800 see 5-0209 Day Number 315 316 317 318 319 322 323 324 325 326 329 330 331 332 333 336 337 338 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 225 226 227 228 229 230 231 . 232 233 234 235 236 237 238 239 240 241 242 T-I Ran ge Mean Chamber Concentration (ppm) T-II T-III Range Mean Range' 37.0 52.5 44.2 146 196 174 46.0 55.0 54.0 46.5 55.5 5Q.6 46.5 52.0 49.2 44.5 52.0 49.1 49.5 56.5 52.0 49.4 62.0 54.9 49.5 . 54.5 50.7 45.5 56.5 49.7 48.0 62.0 54.0 Equipment malfunction. 182 220 208 152 242 205 170 280 192 192 222 201 198 222 210 176 250 208 200 208 204 190 206 196 170 238 ,202 but animals exposed **** **** 58.0 200 204 202 53.5 56.0 47.5 41.0 40.0 43.0 58.5 56.0 55.0 44.5 48.5 53.5 55.5 56.0 51.3 42.8 46.0 49.6 ,186 206 185 164 172 168 198 208 . 210 182 200 200 191 208 202 168 184 190 1800 2080 2040 1960 2440 2500 2160 2220 2400 2300 2440 2500 2800 2380 2620 2660 2840 2620 2840 2760 2500 2220 2260 2160 2280 2500 1980 2580 2500 2380 2600 . 2620 2860 2580 Mean 2073 2473 2558 2022 2542 2699 2475 2405 2597 2576 2540 2376 2300 2556 2481 2685 2366 T-IV Range 2500 2400 *** 2240 2500 2300 2260 2200 2220 2520 *** *** ** 1700 2420 3100 2620 *** 2580 2720 2620 2380 2460 2500 2760 *** *** ** 2300 2700 2300 2500 Mean 2680 2480 *** 2400 2640 2460 2333 2348 2370 2576 ** ** 2420 2084 2584 2380 TABbE 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 -- """ ---- Chamber Concentration (ppm) Exposure T-I T-II Number___________Range________ Mean________ Range________ Mean________ T II 339 243 340 244 343 245 344 246 345 247 346 248 347 249 350 250 351 251 352 252 353 253 354 254 357 255 358 256 359 257 360 cn i 258 361 364 o in tIn-) nn 259 260 365 261 40.0 29.0 60.0 53.0 48.9 50.7 46.5 43.5 49.5 55.0 52.0 51.0 50.7 47.6 50.0 00 un 52.5 50.1 49.0 _ 53.0 - 50.8 - 35.0 34.5 54.5 45.5 64.0 70.0 39.5 44.3 59.0 53.0 70.0 58.7 Holiday,, no exposures, 21.5 54.0 43.5 46.0 71.0 56.0 44.5 59.5 50.7 44.5 40.0 46.5 54.0 53.0 55.0 49.7 46.8 51.6 184 182 198 186 190 194 194 180 180 216 206 192 214 202 170 202 196 190 234 203 2380 2960 210 199 2300 2560 210 203 2420 2720 204 195 2300 2560 210 203 2140 2620 206 200 2420 2580 200 197 2240 2520 250 213 .2700 2940 246 228 2640 2900 228 219 . 2560 2820 214 7207 2340 2560 202 199 2330 2940 240 225 2420 2800 208 206 2420 2560 216 202 2360 2840 212 206 2340 2600 212 204 2300 2800 200 197 2620 i' 2840 Mean 2607 2420 2638 2458 2525 2528 2422 2800 2783 2680 2490 2635 2654 2487 2602 2480 2597 2718 T-IV Rang e 2380 2380 2420 2400 2420 2400 2320 2180 2100 2280 2280 2420 2440 2500 2640 2500 2480 2460 2460 2280 2260 2500 2480 2500 2420 2320 2460 2380 2560 2440 2500 2380 2640 2460 2860 2540 Mean 2413 2428 2536 2467 2436 2435 2375 2240 2176 2395 2372 2447 2460 2350 2512 2440 2730 2484 - no exposure * only 1 sample taken ** no sample taken *** equipment failure, no exposure **** eoLiimnent failure, animals exposed i ( i i ii \ \ 2*tcLi<itaiaL BIO-TEST Jtalvy>'itcyiied., 9*tc. j. j. IV. Body Weight Data The mean body weight data for albino rats, albino mice and hamsters are presented in Tables II, m and IV, respectively. see 5-0212 O TABLE II TEST MATBWAUi Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rain, Albino Mice and Golden Humstere Summary u/ Moan Body Weights ' Albino Ruts Moan Body Weights (grama) Month Numbers Sox Group 0 12 1 4 S 6 7 fl 9 10 II >2 13 14 IS 16 17 16 Chanue uc T-l T-fl T-11I 205 209 201 200 363 316 360 351 456 448 457 453 498 491 490 499 517 521. 522 529 537 545 549 500 543 554 567 567 550 567 565 576 559 593 585 581 697 651 6B1 627 6/7 640 663 629 689 670 696 680 692 696 736 718 708 704 740 729 739 732 764 764 769 782 754 765 786 795 768 758 779 773 781 " 763 784 781 578 575 . 580 UC T-l T-ii T-III T-1V no 168 171 165 181 235 232 212 210 251 275 274 289 287 282 299 297 302 303 288 315 310 313 312 291 320 326 308 323 316 329 321 329 314 324 344 348 342 346 338 356 367 358 359 348 392 357 368 359 363 366 380 398 363 374 384 362 386 393 356 374 378 363 384 NA 397 395 414 420 395 424 425 441 450 NA 444 463 446 458 479 462 -- 393 421 475 457 440 - 491 472 450 - - 331 304 279 - - = No more animals remaining In group. NA * Not available. / Ui u 1 - 0S2eei; 1 ft u.c. T-I T-ll T-I 11 35 33 36 36 UC T-I T-Il T-Ili 29 30 28 28 TABLE 111 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: 1 2 3 4 5 6 7 8 9 10 n 12 13 14 15 16 40 41 43 46 43 46 52 49 47 43 47 48 47 45 46 44 39 39 43 44 42 47 45 47 47 48 48 49 48 48 50 48 40 38 42 44 42 45 43 44 46 37 44 45 - - 38 40 43 44 38 45 41 41 43 31 " 32 33 35 36 35 38 37 41 40 37 40 40 40 41 42 40 34 34 37 39 38 40 41 40 40 42 43 42 41 44 39 38 31 34 35 37 36 38 36 40 39 30 40 3? 38 40 38 38 31 34 35 36 37 37 34 37 39 27 17 43 ` 40 18 Change 43 6 ` ' 39 10 " - - No more animals remaining in group. v / 17^' 33S O' / l l TABLE IV TEST MATERIAL.: Vinyl Chlovido (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rate. Albino Mice and Golden Hamster* Summary oJ Moan Body Weight* - Golden Hamsters Mean Body Weights (grams) VMonth Humbert Sex Group 0 12 1 4 5 6 7 3 10 H_____ U_____13_____H------- -------------------- 12-------- 1 . Ciang. Male UC T-l T-1I T-m 73 71 63 60 98 70 69 87 Female uc T-I T-ll T-IU 77 78 74 67 104 95 94 92 110 101 94 91 120 114 99 93 129 130 120 121 119 108 91 88 1331 122 120 112 130 120 118 11Q 138 126 122 116 141 129 126 110 115 no 117 115 115 115 115111114 125 131 115 121 121 126 no 123 120 124 13 120 125 122 129 124 126 125 130 129 133 132 133 130 130 132 134 127 108 102 99 100 118 112 108 106 120 121 118 118 107 106 106 104 124 122 114 110 125 130 112 lie 126 126 116 105 133 125 110 107 119 116 11B 110 112 112 103 99 117 no 109 101 115 115 114 105 122 117 1)6 109 119 121 117 112 215 122 122 96 120 125 126 - 118 124 122 - 65 61 71 67 41 46 48 - - s No more animals remaining in group. / L/l t see -0215 yna+iAVutu, d i v * i CD-I JlaMosiaityue^ ync. 15 V. Mortality Data The cumulative monthly mortality data are presented in Tables V through VH. y Marked increases in mortality were noted after the ninth month in both T-in male and female rats. The T-IV group which is composed, of only females, and the females in the T-II group showed increases in mortality after the tenth month. Effects in mortality rates were also observed in mice. Mortality in all three test groups of mice were significantly higher than that of the control group. This phenomenon became apparent among females following the seventh test month, and was noted among males during the ninth month. A significant increase in mortality was noted among T-III male and female hamsters during the twelfth month of testing. see 5-0216 Month Number 1 2 3 4 5' 6 7 8 9 10 11 12* 13 14 15 16 17 18 TABLE V TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary of Mortality Data - Albino Rats UC M 0 0 0 0 2 3 4 4 4 5 7 13 16 19 21 23 28 33 Cumulative Number of Mortalities at End of Month T-I T-II T-EI F M F M -F M F 0 00 0 0 00 0201000 1. 2 0 1 0 0 4 2 4 11 3 0 1 4 3 5 1 6 1 3 4_ 461 6154 4a 2 6 265 5 9 3 10 5 10 8 6 10 4 11 5 16 15 7 11 7 12 9 24 28 8 13 9 14 19 34 52 14 19 16 21 37 58 66 17 23 24 26 50 73 83 21 26 30 33 63 85 86 23 28 37 40 75 94 89 25 31 45 46 87 100 (4) 100 27 35 53 55 90 100 100 28 38 59 64 94 100 100 T-rv F 0 0 0 0 0 0 0 1 4 7 17 40 46 76 86 100 100 OO * Includes 5 males and 5 females from each group excluding T-IV sacrificed for cytogenic study. () Indicates moribund or sick animals sacrificed. see 5-0217 ^^44^^04 kJ 4 - t L* ^ ' C-. Month Number I 2 3 4 5 6 7 8 9 10 11 12 i3 14 15 16 17 18 TABLE VI TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary of Mortality Data - Albino Mice UC M Cumulative Number of Mortalities at End of Month tT-I T-n T-IH F MF MF MF 0 0 0 0 0 000 0 0030000 2 06430 10 5 1 19 5 4 1 4 7 8 2 26 6 4 2 8 712 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 34 16 57 66 98 95 100 100 44 23 70 80 99 97 100 100 54 28 79 91 100 100 100 100 67 . 39 88 97 100 100 100 100 82 46 100 100 100 100 100 100 82 54 100 100 100 100 100 100 82 58 100 100 100 100 100 100 see c_zl ~02l3 VttduA&uuil BIU - l I Xaiwu2l&u4.r ^nc. 1o Month Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 TABLE VII TEST MATERIAL: Vinyl Chloride (Ethylene D.erived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters Summary of Mortality Data - Golden Hamsters UC M 5 8 8 9 9 13 13 14 14 14 15 18 23 28 39 50 57 62 Cumulative Number of Mortalities at End of Month T-I T-II T-HI F MF MF MF 4447 5 2 5 11 10 12 9 16 10 11 13 12 14 12 18 14 13 15 16 16 15 19 15 13 18 16 16 16 20 15 16_ 18 16 16 20 21 16 16 28 24 19 22 33 18 26 28 24 19 23 35 19 28 29 24 20 25 36 20 28 30 26 20 26 37 23 29 31 28 21 26 " 38 28 36 36 34 33 37 46 40 45 40 43 49 46 49 49 58 46 49 58 54 53 61 69 61 53 72 66 55 71 84 78 58 83 74 59 84 100 (3) 81 61 85 76 66 86 100 85 62 86 77 75 88 100 O Indicates moribund or sick animals sacrificed. see 5-0219 jnauG^/i4Cu. uiw -- & j i ^_uocyu-i*s^u^(y, >. a7 VI. Hematologic Studies The results of hematologic studies done on male and female rats from the control group and from treatment groups I and II are presented in Tables VUI and IX. Mean values for total leukocyte and erythrocyte counts, hemoglobin concentration and hematocrit of male and female rats in treatment groups I and II were normal when these values were compared to those of their respective control groups after 18 months of treataient. Differential leukocyte counts were done on individual animals' that had high total leukocyte counts, as follows: 3 male control rats, 4 male rats in T-I, one female rat in T-I and one male rat in T-U. These data are presented in Table X. see 5-0220 TABLE VIII TEST MATERIAL; Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters 18-Month Hematologic Data - Male Albino Rats Group Animal Number Total Leukocyte Erythrocyte Count Count (thousands/mm^)________ (millions/mm^) Hemoglobin Concentration (g/100 ml) Hematocrit Value (%) Untreated Control 1 2 4 5 7 10 11 13 15 16 17 18 19 20 21 Mean 11.4 19.2* 9.6 9.3 9.4 88.2 10.7 11.8 8.5 7.8 8.9 11.6 24.6* 18.7* 8.4 11.9 8.78 8.25 8.55 9.30 9.01 7.36 7.73 6.29 8.12 f 8.95 8.91 8.93 7.84 8.13 8.12 8.28 14.8 15.6 15.0 15.4 14.8 13.7 14.6 11.4 15.9 15.6 17.0 15.5 13.8 13.2 14.4 14.7 47 50 48 50 48 46 47 38 50 52 54 51 45 44 50 48 IC./) ~ c ttt l Q - I ^ i Group T-I r_n I o in hj n to n r^\ TABLE VIII continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters 18-Month Hematologic Data - Male Albino Rats Animal Number 201 204 206 207 208 209 212 213 214 216 217 218 222 224 233 Mean Total Leukocyte Count (thousands/mm^) 11.9 23.3* 16.6* 11.7 28.2* 8.6 11.3 8.9 11.0 12.8 24.4* 13.5 9;0 13.2 9.414.2 Erythrocyte Count (millions/mm 8.20 8.11 8.86 7.52 6.73 8.51 8.31 8.52 8.12 t 8.27 8.38 7.83 7.99 9.62 8.29 8.22 Hemoglobin Concentration (E/100 ml) 14.2 14.4 14.6 13.9 12.6 15.0 16.1 14.6 14.2 14.7 14.6 14.7 14.6 15.7 15.0 14.6 Hematocrit Value (%) 47 48 48 46 40 49 52 49 46 48 48 49 46 `52 49 48 Croup T-II TABLE VIII continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters 18-Month Hematologic Data - Male Albino Rats Animal Number Total Leukocyte Count (thousands/mm^) Erythrocyte Count (millions/mm^) Hemoglobin Concentration (g/100 ml) Hematocrit Value (%) 403 408 412 413 416 418 419 421 425 428 429 430 434 435 436 Mean 14.0 10.6 10.9 12.9 14.4 12.9 12.2 11.4 15.0 9.3 30.4* 9.5 8.1 10.4 14.0 13.1 00 CO 7.23 5.30 7.87 8.30 5.86 7.52 7,84 7.22 9;56 8.90 7.98 8.82 9.10 7.87 rj <\j om 12.1 11.0 14.7 14.0 9.7 13.8 13.9 13.9 17.7 14.6 9.7 14.5 13.4 15.3 14.9 13.5 40 41 47 44 34 44 44 46 55 48 40 46 44 50 50 45 * Differential leukocyte counts were performed on these animals. see 5-0223 9* B IO -TE S T {rNoJ TABLE IX TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters 18-Month Hematologic Data - Female Albino Rats Group Animal Number Total Leukocyte Count (thousands/mm^) Erythrocyte Count (millions/mm^) Hemoglobin Concentration (g/100 ml) Hematocrit Value (%) Untreated Control . 102 103 104 105 107 ioa 110 111 112 113 114 115 117 118 119 Mean 9.1 8.0 9.1 9.4 7.8 14.6 6.0 5.8 6.5 6.3 9.8 5.2 4.2 5.3 6.5 7.6 7.26 7.02 5.90 7.71 7.59 7.05 6.58 6.36 7.04 , 7.26 6.80 6.72 7.35 6.68 7.27 6.97 14.7 13,4 11.5 14.2 14.2 14.7 13.0 13.0 14.0 14.1 14: o 14.0 14.6 13.8 14.6 ' 13,8 46 44 40 46 46 48 42 42 44 46 46 46 47 45 46 45 i see 5-0224 Group T-I see 5-0225 TABLE IX continued TEST MATERIAL: Vinyl Chloride (Ethylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters 18-Month Hematologic Data - Female Albino Rats Animal Number 304 305 309 310 312 315 317 322 323 324 326 327 329 331 332 Mean Total Leukocyte Count (thousands/mm 3.0 12.7 6.9 12.9 13.2 7.7 6.0 8.3 5.6 7.2 7.9 7.1 8.8 16.0* 7.4 8.7 Erythrocyte Count * (millions/mm3) 7.17 6.16 7.11 6.38 7.16 6.98 6.23 7.23 7.30 7.40 '' 6.79 7.08 7.12 4.50 5.89 6.70 Hemoglobin Concentration (g/100 ml) 13.4 13.6 14.4 12.4 13.6 13.3 11.9 13.7 14.3 13.3 13.2 13.2 12.6 9.0 11.2 12.9 Hematocrit Value (%) 44 44 48 42 48 44 38 45 46 43 44 44 43 33 36 43 \ \ Group T-II TABLE IX continued TEST MATERIAL: Vinyl Chloride CEthylene Derived) Chronic Vapor Inhalation Toxicity Study - Albino Rats, Albino Mice and Golden Hamsters 18-Month Hematologic Data - Female Albino Rats Animal Number Total Leukocyte Count (thousands/mm 3) Erythrocyte Count (millions/mm^) Hemoglobin Concentration (r/100 ml) Hematocrit Value (%) 511 514 522 557 566 580 Mean 7.6 7.8 4.8 5.3 7.5 11.1 7A 6.60 7.20 6.22 7.24 6.44 6.85 6.76 12.0 13.7 11.7 13.4 12.6 13.2 12.8 40 43 40 44 42 43 42 / S' 1 ^ ^ See ?~226 U