Document ExjJXZrVqeMybXx1ko2pOR6QR

APR-22-97 TUE 01:08 PH HUNT INGDON 11FE SC 1ENCES FAX NO, 908 873 3992 P. 01/22 TOTAL NUMBER OF PAGES INCLUDING THIS PAGE; If this transmission is unsatisfactory please contact us by telephone at (908) ATTENTION OF: Or. J. Knaak COMPANY: Occidental Chemical Corporation Dallas, TX 75244 CC: Dr. Hasmukh Shah <2s. Wendy Sherman^ Chemical Manufacturers Association Arlingon, VA 22209 FROM: DATE: Raymond E. Schroede-r 22 April 1997 MESSAGE; Study No. 96-4080 - Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats This fascimile includes the following summary data for the above referenced study for your review (Study Weeks -1 through 14); Tables 1. Summary of Cl ini cal'Observations 2. Mean 8ody Weights - Premating Period 3. Mean Body Weight Change during Premating Period (Weeks 0-10) 4. Mean Food Consumption - Premating Period 5. Mean Body Weights - Mating and Post-mating Periods (Males) 6. Mean Food Consumption - Post-mating Period (Males) Appendix A. Methodology and References Please contact me with any questions. Best; Regards, ^ . (_y Raymond E. Schfoeder Study Director CMA 118725 APR-22-97 TUE 01:08 PH HUNTINGDON LIFE SCIENCES FAX NO. 908 873 3992 ?. 02/22 STUDY NO. 96-4080 VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS Slam Resort Submitted to: Chemical Manufacturers Association Chemstar Department 1300 Wilson Blvd. Arlington, Virgiana 22209 Attn: Hasmukh c. Shah, Ph.0. Date: 22 April 1997 CMA 118726 APR-22`9? TUE 01:08 PH HUNTINGDON LIFE SCIENCES FAX NO. 908 873 3992 P. 03/22 * Of ANIMALS examined NORMAL WITHIN NORMAL LIMITS OSNL APPEARANCE EARS SWOLLEN/RED BILATERAL DERMAL -pENERAL ULCERATION - CERVICAL ALOPECIA SXTREM]T1ES/SNOUT ALOPECIA - GENERAL YELLOW ANO-GEN1TAL STAINING UNAUDITED DRAFT 7 1-t TABLE 1 VINYL CHLORIDE COMBINED INHALATION TWO*GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS 96-4080 WEK; I r 30 I! 30 in 30 IV 30 SUNMARY Of CLINICAL OBSERVATIONS - MALES 1 2 3 4 5 6 7 8 9 10 11 T2 13 U 30 30 SO 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 JO 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 SO 30 30 SO 30 30 30 30 30 30 30 30 30 30 30 30 30 30 1 30 II 30 III 30 IV 30 29 29 29 29 30 29 28 26 30 29 28 28 30 JO 29 28 29 27 27 25 26 27 27 26 2* 26 24 23 27 27 27 27 2? 23 23 23 23 23 26 26 26 26 26 25 26 24 23 24 24 23 29 28 2S 26 26 26 I0 ua in o IV 0 0 0 0 0 0 o a o ooo ooo 0 0 0 o 0 ooo ooo 0 0 0 0 a 00 oo 00 oo ooo ooo 0 0 1 ooo ooo ooo I0 11 0 III 0 IV o I0 It 0 in 0 IV 0 I0 na III 0 IV 0 I0 II 0 111 0 IV 0 01 1 1 1 1 T 1 1 1 T 1 1 1 00000000 00 0000 000 0 00000 0 0 00 0 0000000o00 0000 0a0000 1 1 000o00 0 T 1 2 2 1 1 1 111112 0 0 0 0 0 0 0 1 110 1)1 0000 0 000 0oooao ooo 0 0 0 000 0 o a o o 0 0 1 1 1 1 1 1 1 1 0 0 01 ooo OOO ooo ooo 00 0 ooo 0 0 0 0 0 0 00 00 0000000000 0000 00 00 0 000 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 o 0 o 0 1 0 0 0 0 0 0 CMA 118727 APR-22-97 TUE 01:08 PH HUNTINGDON LIFE SCIENCES FAX NO, 908 873 3992 P. 04/22 # OF ANIMALS EXAMINED UNAUDITED T 1-2 TABLE 1 Ceoot.J DRAFT VINYL CHLORIDE COMBINED INHALATION TUO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CO RATS 4080 SUMMARY OF CLINICAL OBSERVATIONS - MALES WEEK: -1 1 2 3 4 5 6 7 8 9 10 11 12 13 K I 30 II 30 III 30 IV 30 30 30 30 30 30 SO 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 SO 30 30 30 30 30 30 30 30 30 SO OCULAR LACK [MAT I ON UNILATERAL CHROMODACRYORRHEA - unilateral CHROMOOACRYORRHEA BILATERAL LACK I NATION - BILATERAL ORAL/BUCCAL INCISORS MALOCUUOED I0 ii a in o iv o io ao HI 0 IV 0 I0 II o III 0 IV 0 I0 uo III 0 IV 0 I0 II 0 in o IV 0 1 00 0 0 0 ao oo ooaoo oooio 10 0 0 0 110 0 000 0 .1 1 0 1 0 0 0 0 10 12 o u o o i 1113 0 00 0 0 0 Z 0 0 0 0 12 1 1111 0 00 0 00 a oa ooo 000 ooo 1 a oo oo oo 1 00 0 ooo 0 0 0 ooo ooo ooo ooo ooo ooo ooo ooo ooo ooo ooo ooo 110 0 0 0 0 111 1 00 0 0 0 00 0 1 00 32 00 12 0 01 2 22 0 00 112 0 0 ooo 0 0 ooo 0 0 ooo 0 0 ooo 0 0 ooo 0 0 U 00 0 0 a ao 0 0 0 01 0 0 0 00 22 3 3 5 5 5 4 4 0 0 0 1 1 1 0 1 113 3 3 2 0 1 2 2 2 4 3 3 12 3 3 3 3 0 0 1 23 33 3 0 0 2 2 2 2 CMA 118728 APR-22-97 TUE 01:08 PM HUNTINGDON LIFE SCIENCES FAX _NQ. 908 873 3992 P, 05/22 # OF MI HALS EXAMINED UNAUDITED DRAFT T 1-3 TASLE 1 (cont.) VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY StUOT IN CD RATS SUMMARY OF CLINICAL OBSERVATIONS - MALES WEEK: -1 l 30 11 30 III 30 IV 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 30 30 30 3D 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 10 30 SO 30 30 30 30 30 30 INCISORS SROKEN/MISS1NG I0 II 0 III 0 IV 0 000000 1 1 1 22233 0000 000001 0000 00000033 232233 00000000 1 Z2222 96-4080 CMA118729 APR-22-97 TUE 01:08 PH HUNTINGDON LIFE SCIENCES Fffl NO. 90.8 873 3992 P. 06/22 # OF animals examined UNAUDITED T 1-4 DRAFT TASLE 1 (cont.) VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CO RATS 96-4080 WEEK: -1 SUMMARY OF CLINICAL OBSERVATIONS - FEMALES 1 2 3 4 5 6 7 8 9 10 11 12 13 14 l 30 II 30 III 30 IV 30 30 30 30 30 30 30 30 30 30 SO 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 JO normal WITHIN NORMAL LIMITS 1 30 U 30 III 30 iv 30 GENL APPEARANCE EARS SWOLLEN/RED BILATERAL I JI HI IV DERMAL-GENERAL ALOPECIA EXTREMITIES/SNOUT ALOPECIA - GENERAL I It III IV i n m IV OCULAR LACRIMATION - UNILATERAL CKROMOOACRYORRHEA UNILATERAL i ii in IV I II 11! IV 30 30 30 30 30 30 30 30 30 30 29 29 29 29 30 30 29 29 28 27 28 28 28 26 30 30 30 30 2& 28 28 28 25 26 25 25 26 26 27 26 26 28 28 28 27 25 27 28 28 26 27 25 24 23 22 21 CMA118730 APR-22-97 TUE 01:09 PM HUNTINGDON LIFE SCIENCES FAX NO. 908 873 3992 P, 07/22 # OF ANIMALS EXAMINED unwuiliO draftT 1-5 TABLE 1 (cont.) Ul! VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS WEEK: -1 I 30 II 30 III 30 IV 30 SUMMARY OF CLINICAL OBSERVATIONS - FEMALES I2 3 30 JO 30 30 30 30 30 30 30 30 30 30 A5 6 7 8 9 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 TO II 12 13 14 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 98-4080 CHROMOOACRYORRHEA ` BILATERAL LACRIMATION - bilateral QRAL/BUCCAI, INCISORS MALOCCIUDED 10 II 0 III 0 iv 0 10 II 0 III 0 IV 0 0 0 0 o 00 00 00 ao 0 0 1 11 0 00 00 ooooo 0 00 00 111111 0000 00 00 00 0 0 0 0 1111 0 0 0 0 00 00 00 00 ooooo ooooo ooooo ooooo 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 ORAL SORE INCISORS SROKEN/MISSING MASS!31 CMA 118731 APR-22-97 TUE 01:09 PH HUNTINGDON LIFE SCIENCES___ FAX NO, 908 873 3992 P, 08/22 -- / 3 wy L CHLORIDE COMBINED INHALATION TUG-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS UNAUDITED L/IV Arl ' STat SYMBOL; WEEK BODY WEIGHT IN GRAMS MALES DOSE LEVEL: PPM 0.0000 10.0000 100.0000 1100.0000 A-L- -1 MEAN 161.0 S.D. 9.3 N 30 161.0 9.3 30 161.1 9.4 30 160.9 9.4 30 A-L - 0 MEAN 233.3 S.D. 11.6 N 30 237.7 IS.3 30 236.6 12.6 30 234.3 14.0 30 A-L- 1 MEAN 274.5 S.D. 13.4 N 30 279.6 19.0 JO 277.8 14.S 30 272.4 16.6 3o A-L* 2 MEAN 314.2 S.D. 16.5 H 30 322.1 23.5 30 321.7 17.9 30 318.3 20.5 30 A-L' 5 MEAN 348,8 S-D. 18.0 N 30 357.7 27.2 30 357,2 20.4 30 348.0 25.3 SO A-L 4 MEAN 375.3 S.O. 22.4 N 30 384.2 32.8 30 382.3 25,5 30 374.7 27.8 30 A-L- 5 MEAN 401.8 S.O, 25.1 N 30 412.1 36.2 30 409.2 28.0 30 405.5 30.1 30 A-L ' 6 MEAN 417.1 S.S. 32.7 N 30 432.4 38.8 30 426.1 29.2 30 424.5 33.3 30 CMA 118732 APR-22-97 TUE 01:09 PN HUNTINGDON LIFE SCIENCES FAX NO, 908 873 3992 P. 09/22 UNAUDITEDj 2-2 *6*4080 v,,,`" DRAFT ST AT STMSOl ; WEEK BOOr WE HINT IN oPams MALES OOSE LEVEL; PPM 0.0000 10.0000 4"L* 7 MEAN 435.9 S.D. 31.6 N 30 452.3 41.1 30 A-L- a MEAN 447. A S.D. 32.4 N JO 465.0 42.1 30 A-L- 9 mean 462.6 S.D. 36.6 N 30 482,0 46.4 30 A-l- 10 MEAN 478,9 S.D. IS.6 M 30 498.8 46,7 30 100.0000 1100.0000 447.3 31.0 30 447,6 37.0 30 460.8 32.9 30 477.6 34.8 30 463.5 37.0 30 477.8 38.9 30 492.5 35.7 30 490.6 39.2 SO CMA 118733 APR-22-97 M 01=09 PN HUNTINGDON LIFE SCIENCES FAX NO, 908 873 3992 P, 10/22 UNAUDITEDT 2-3 '6*4080 n"L draft S TAT SYH8QL: WEEK FEMALES DOSE LEVEL: PPM 0.0000 10.0000 A-l* *1 MEAN 116.5 S,D. 6.0 N 30 116.2 6.1 30 A-L* 0 MEAN 15S.0 S.D. 7.5 N 30 158.5 9,1 so A-L- l MEAN 177.1 S ,D, 6.7 N 30 173.8 9.5 30. a-l* 2 MEAN 106.4 S.D, 11.9 N 30 197.3 10.4 30 A-L- 2 MEAN 213.2 S.D. 12.3 H 30 209.8 10.J SO A-L- 4 MEAN 225.6 5.0. 15.3 N 30 222.0 10.7 30 K-J* 5 MEAN 241.6 S.O. 14.7 N 30 236.6 10.5 30 a-l* 6 MEAN 250.7 i.D. 15.5 N 30 247.8 U.8 30 100,0000 1100,0000 116.S 5.7 30 116.7 5.8 30 156.3 9.3 30 157.0 7.7 30 178.1 12.1 30 175.8 9.3 30 199.1 14.1 30 197,1 11.7 30 214.4 16.6 50 212.2 12.7 30 226.7 17.4 30 223.0 13.1 30 241.5 19.4 30 236.4 13.0 30 252. 1 20.7 30 247.5 13.8 30 CMA 118734 APR-22-97 TUE 01:09 PH HUNTINGDON LIFE SCIENCES FAX NO. 90B 873 3992 P, 11/22 T 2-4 96-4080 TABLE 2 (cont,) VINYL CHLORIDE COWTWO INNALATION TWO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CO RATS UNAUDITED DRAFT 5TAT SYMBOL: wEEK BODY WEIGHT IN GRAMS females DOS! LEVEL: PPM 0,0000 10.0000 100.0000 1100,0000 A-w 7 MEAN 258.5 S.O. 15.8 H 30 2S3.4 14.3 30 259.6 20.7 30 253.1 14.2 30 A-l- 3 MEAN 264.8 S.O. 16.4 N 30 259.5 14.0 30 265.4 21.4 30 258.2 15,9 30 A-LA 9 MEAN 274.3 S.O. 15.4 N 30 10 MEAN 280.6 S.O, 17.9 N 30 266.5 16.5 30 271.6 16.4 30 272.8 22.2 30 279.7 23.6 30 265.4 15.5 30 271.0 16.9 30 CMA 118735 APR-22-97 TUE 01:09 PH HUNTINGDON LIFE SCIENCES FAX NO. 908 873 3992 P, 12/22 V! STAr SYMBOL; T 3-1 TABLE 3 800Y WEIGHT CHANG! PROH WEEK MALES DOSE LEVEL 1 PPM 0 96-4030 UNAUDITED DRAFT WEEK 0.0000 igjaao loc.ccoo 1100.0000 A-!. 10 MEAN S.O. 245.6 34.4 261.t 37.5 255.9 31.8 256.3 31.6 N 30 30 JO 30 CMA118736 APR-22-97 TUE 01:09 PH HUNTINGDON LIFE SCIENCES 908 873 3992 P. 13/22 T ,.f TABZtE 3 (COST ) 1 "`SISSS,;^ 0 DRAFT STAT SYMBOL: 800V WEIGHT CHANGE FSOM WEEK FEMALES DOSE LEVEL! PPM 0 WggK 0.0000 10.0000 100.0000 1100.0000 AL-2 10 MEAN S.O. K 122.6 16.2 30 115-1 13-8 30 123.4 21.0 30 114.0 14.6 30 CMA 118737 APR-22-97 TUE 01:10 PH HUNTINGDON LIFE SCIENCES FAX NO. 908 873 3992 P. 14/22 r 4-i 96*4080 TABLE 4 v'tNYL chloride combined inhalation TWO-GINERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS UNAUDITED draft STAT SYH60L-. Al-0 FOOD CONSUMPTION G/KG/DAY MALES DOSE LEVEL; PPM WEEK 0.0000 0 MEAN 122.6 S.D. N 6.2 29 10.0000 125,1 4.4 30 100.0000 * 127.1 5.1 30 1100.0000 124.8 6.6 30 A-lA*L-U+ A*L-Ot I MEAN S.D. N 98,3 4.8 30 2 MEAN S.D. N 86.7 6.3 30 3 MEAN S.D. H 78.5 3.2 30 98,8 4,0 30 89.3 3.9 30 79.1 3.5 30 99.5 4.9 30 r* 91,2 4.3 30 00 82.1 3.8 30 97.0 4.8 30 89.1 4,7 30 80.3 3.8 30 A L ' u mean S.O. N 72.7 3.1 JO 72.J 3.9 30 73.3 3.2 30 73.2 3.5 30 AL* AL-0 AL i MEAN S.D. N 66.6 2.7 30 6 MEAN S.D. N 62.6 4.6 30 7 MEAN S.D, M 60.2 3.7 30 69.5 3.5 29 66.0 3.4 29 61.0 2.3 30 70.3 3.5 JO 65.0 6.0 30 9 62.4 3.5 30 71.4 3.8 30 45.6 3.9 30 * 62.3 3.5 30 CMA118738 APR-22-97 TUE 01:10 PM HUNTINGDON LIFE SCIENCES FftX NO, 908 873 3992 ''"'l STAT SVMBOL: a-l- K*v r A'L-0 y issTa" POOO consumption G/KG/OAT MALES DOSE LEVEL; PPik ^6"4080 UNAUDITED draft WEEK 0.0000 8 mean S.O. N sr.3 3.3 30 9 mean S.D. N 36.0 3.3 30 10 MEAN S.O. N 34.A 2.3 30 10.0000 100.0000 1100.0000 58.1 3.4 30 36.1 2.7 30 39.1 2.4 30 57.4 6,2 29 58.4 3.0 30 am 59.4 4,0 Jo 55.6 2.9 29 56.6 3.1 29 35.2 3.9 30 CMA 118739 APR-22-97 TUE 01:10 PM HUNTINGDON LIFE SCIENCES FAX NO. m 873 3992 P. 18/22 T 4*3 WNYL CHL^r0*^*0 'NH4lAno"?w^ENB(WTIQN REPRODUCTION AKO DEVELOPMENTAL TOXICITY STUDY IN CO RATS unaudited STAT SYMBOL: WEEK FOOD CONSUMPTION G/K8/DAY FEMALES OOSB LEVEL: PPM 0.0000 10.0000 100.0000 1100.0000 DRAFT A*l- 0 MEAN 131.8 S.O. 5.9 N 29 133.5 9.4 29 134.9 7.8 28 154.9 8.0 26 al- 1 MEAN 107.4 S.O. S.2 N 30 104.3 5.4 28 109.2 3.7 29 105.4 6.7 27 <. 2 MEAN S.O. N 103.6 10.3 50 103.9 5.5 30 105.9 9.5 30 103.9 8.6 30 a-l- 3 MEAN S.O. N 94.3 5.2 30 94.7 6.2 30 96.9 5.8 30 96,9 6.5 29 A*L* MEAN S.O, u 90.3 5.6 30 89.0 4.9 30 92.2 5.9 30 90.4 5.9 30 `0* 4 5 MEAN S.O. M 35,8 4,3 30 MEAN S.O, N 79.4 3.4 29 MEAN s.o, N 77.4 5.9 30 87.6 5.6 30 ** 84.9 5.7 30 76,5 5.7 30 87.6 7,0 30 84.7 9,0 30 76.5 5.0 30 87.1 r.s 30 * 85.0 3.9 30 77,7 6.1 30 CMA 118740 APR-22-97 TUE 01:10 PM HUNTINGDON LIFE SCIENCES FAN NO, 908 873 3992 P. 17/22 Wnh Chloride combined ^AUDITEDm wtiommi toxrcm ^Tf"2* "PROOUeT,OM STM SVM30L : A-L* A-L- a+l* FOOO CONSUMPTION $/Ka/0Ay FEMALES OOSS LEVEL: PPM MEEK 0.0000 S MEAN S.D. N 74.9 5.3 30 9 MEAN S.D. N 71.9 5,7 30 10 MEAN S.D. H 47.1 6.3 39 10.0000 100.0000 74.3 5.0 30 75.3 5.3 30 70.9 3.3 30 73.1 7.0 30 43.5 6.5 30 70.1 5.0 30 ` 1100.0000 76.5 5.9 SO 74.4 6.1 28 ** 72.2 5.1 29 Dm CMA 118741 APR-; >2-97 TUE OHIO PH HUNTINGDON LIFE SCIENCES FAX NO. 908 873 3992 P. 18/22 VWL STAT SYMBOL: MEEK r j.t tcor WEIGHT IN GRAMS MALES OQSg LEVEL: PPM 96-4080 UNAUDITED draft 0.0000 10.0000 100.0000 HOO.OOOO L' L1-LL- ii MEAN 479.3 S.O. 36.6 N 30 12 MEAH 488.2 S.D. 37,2 N 30 U MEAN S00.6 S.O. 39.6 N 30 14 MEAN 508.0 S.O. 43.0 N 30 499.7 49.8 30 512.0 51.0 30 523.7 51.3 30 523.1 33.7 30 493.6 34.4 30 502.1 36.8 30 511.5 45.6 30 520.3 41.9 30 493.7 38.1 30 505.8 38.7 30 518.2 39.4 30 520.3 42.9 30 CMA 118742 APR-22-97 TUE 01:10 PM HUNTINGDON LIFE SCIENCES FAX NO. 908 873 3992 P. 19/22 r 6-i 96'4080 VINYL CHL^Dl!.F?'8,Ne> INHALATION TWO'GENERATION AEPRODL/Crmu ANP DEVELOPMENTAL TOXICITY STUDY ,n CB^A?| rW UNAUDITED DRAFT FOOD CONSUMPTION Q/K&/DAY MALES DOSE LIVELi PPM STAT SYMBOL; weiK a. oooo 10.0000 100.0000 1100.0000 K-JA+L-0+ 13 MEAN S.B. N AS.A 9.S 30 H MEAN S.O. N SO.8 3.1 29 50.2 7.5 30 49.9 3.8 30 51-1 3.8 30 * 53.0 3.9 29 51.0 3.6 30 51.2 3.0 30 CMA 118743 APR-22-97 TUE 01:10 PM HUNTINGDON LIFE SCIENCES FAX NO, 908 873 3992 P. 20/22 UNAUDITED Vinyl DRAFT A-l 96-4080 Appendix A Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats Methodology and References - Statistical Analysis Parameters analyzed statistically for this status report: body weights and food consumption MULTIPLE GROUP ANALYSIS STAT SYMBOL No Sio D3Q.Q5 paQ.Ql Parametric A- A A* L- L L+ Q Q+ * ** STATISTICAL STATEMENT No statistical differences among the means (parametric ANOVA). The means differ significantly (parametric ANOVA). The response is not linearly related to the dose levels. The response is linearly related to the dose levels. The response shows a lack of fit. Significantly different from control (Dunnett 's). CMA 118744 APR-22-97 TUE 01:10 PM HUNTINGDON LIFE SCIENCES FAX NO, 908 873 3992 P. 21/22 UNAUDITED draftA-2 Appendix A (cant.) 96-4080 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats Methodology and References - Statistical Analysis MULTIPLE GROUP ANALYSIS STAT SYMBOL Ne_lia pj-kjQ.5 p*oj)i Nonparametric K- K K+ JJ J+ NT STATISTICAL STATEMENT No statistical differences among the means (Kruskal-Wallis, nonparametric). The means differ significantly (Kruskal-Wallis nonparametric). There is not an ordered response to dosage. There is an ordered response to dosage. Significantly different from control (Dunn's Rank 5um). Not tested due to lack of variance. Statistical evaluation of equality of means was made by the appropriate one way analysis of variance technique, followed by a multiple comparison procedure if needed. First, Bartlett's test was performed to determine if groups had equal variance. If the variances were equal, parametric procedures were used; if not, nonparametric procedures were used. The parametric procedures were the standard one way ANOVA using the F distribution to assess significance. If significant differences among the means were indicated, Qunnett's test was used to determine which means were significantly different from the control. If a nonparametric procedure for testing equality of means was needed, the Kruskal-Wallis test was used, and if differences were indicated a summed rank test (Dunn) was used to determine which treatments differed from control. CMA 118745 APR-22-97 TUE 01 HI PM HUNTINGDON LIFE SCIENCES FAX NO, 908 873 3992 __ P, 22/22 r UNAUDITED Vinyl DRAFT A-3 96-4080 Appendix A (cont.) Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats Methodology and References - Statistical Analysis A statistical test for trend in the dose levels was also performed. the parametric case (i.e., equal variance) standard regression techniques with a test for trend and lack of fit were used. In the nonparametric case Jonckheere's test for monotonic trend was used. In The test for equal variance (Bartlett's) was conducted at the 1%, two-sided risk level. All other statistical tests were conducted at the 5% and 1%, two-sided risk level. References for these techniques are Snedecor, G.W., and Cochran, W.G., Statistical Methods, 6th edition, Iowa State University Press (1967); Hollander, M. and Wolfe, O.A., Nonparametric Statistical Methods. John Wiley and Sons, New York (1973); Dunnett, C.W., J. Am. Sto. Assn. Vol. 50 (1955) and Biometrics. Vol. 20 (1964). $&C S&C D Bio H&W H&W S&C S&C H&W CMA 118746