Document 600kXN7OQB69gXoy6ZVO8pB4

KECEIVED DEC 15 B.U K I Bio/clynamics Inc. M Division of Biology and Safety Evaluation PROJECT NO. 79-2425 * AN INHALATION FEMALE FERTILITY STUOY WITH BENZENE IN RATS Final Reoort Submitted To: Chemical Manufacturers Association Washington, D.C. 20009 Date; Decanter 1, 1980 ;;4\ i;i; ' rf 5, '-I \ i '| it l*- -6|. 'M .. i ` r?t * ty> !P i A i DO 067673 OONFTDFNT1 Al -- 02217 rtj 4E 3 YZ0014328 Bio/dynamics Inc. PROJECT NO. 79-2425 AN INHALATION FEMALE FERTILITY STUDY WITH BENZENE IN RATS ABSTRACT This study was conducted for the Chemical Manufacturers Association and;* American Petroleum Institute to assess the effects of benzene on fertility of female rats. Benzene was administered by the Inhalat on route at dose level!-of 1, 10, 30 and 300 ppm. Female Charles River CD rats 26/group) were treated,T 6 hours/day, five days/week during a ten-week pre-mat ng treatment period ana! ensuing mating period. Mated females were exposed dal ly,, (.6 hours./d.a.y) during, gestation to Day 20 and dally exposures resulted on Day 5 of lactation until weaning (Day 21 of lactation). Included In the study was a chamber-exposed control group. Pups were sacrificed on Day 21 and given a gross postmortem < examination. Additionally, the weight of the testes, liver and kidneys were:! recorded for each male pup; the weight of the liver and kidneys was recorded for each female pup. Parameters evaluated Include: maternal mortality, body weight data, Irw.. life physical observation data, pregnancy rates and parturition data (gestation . length, minber of live and dead pups at birth, sex distribution data). Pupsj j were evaluated for survival, growth, organ weight data (absolute and relatives , Day 21 body weight) and gross postmortem observations. No treatment effect was evident In maternal mortality, bbdy weight date#, In-llfe observations or pregnancy rates. At parturition, a slight Increase In the mean number of dead pups was sfin at the high-dose level; however, this difference was not statistically slgnl-l flcant. A slight, although statistically significant, decrease In pup survive) Index for the Day 4-21 lactation Interval was seen In the 10 ppm group. This, was attributed to high pup mortality In two litters and since pup survival ^ Indices were not effected at the higher dose levels, no treatment-related effect was Indicated. Mean pup weights during lactation were comparable to control at the 1 ejjf 10 ppm levels. At 30 ppm, mean pup weights (both sexes) were slightly lower than control at Day 21 and, In the 300 ppm level, mean pup weights were lower, than control at Days 14 and 21 of lactation. DO 067674 CONFIDFNT TAl, P. .Box 43 Mettftrt Road East Millstone, New Jersey 06873 (201)873-2860 Tel** 844897 Cable: BKWDYN YZOO14329 79-2425 Mean liver weights for the male pups (absolute and relative to boty weights)i were comparable to control at the 1 and 10 ppm levels and slight! lower than control at the 30 and 300 ppm levels', however, these latter 41ff ces were not statistically significant. Mean liver weights for the fewam were comparable to the control at the 1, 10 and 30 ppm levels and lower tti. control at the 300 ppn level. Mean liver/body weight ratios for the fenyjili pups were comparable between the control and treated groups. Mean kidney weights and kidney to body weight ratios for the treated female jpups Were C sldered comparable to controls, although kidney to body weight ratios wf#] statistically higher for Groups III, IV and V (10, 30 and 300 ppm), respecj 1y. No treatment effect was evident In the gross postmortem examinations adult females or their offspring (Day 21). ! Thus, benzene administered by Inhalation at dose levels of 1, 10,,;?p< 300 ppm to female rats during a pre-mating and mating period and th# ensul gestation and lactation periods was without adverse effects on repppdjidtl: A trend toward reduced mean body weights and certain mean organ weights ftifi observed In the Day 21 pups at the 30 and 300 ppm dose levels. $xcdpt fOI single data point (reduced liver weight In the female pups at 300 pftnjJtl differences were not statistically significant. No treatment effects )Njr In pup survival data during lactation and gross postmortem evaluations of pups on Day 21. I' -m DO 067675 CONFTDFNTTA1 it ' . h !U 1 i iM,i ' -1. - .&Mr YZ0014330 -7TO4"2S*/dynamic** Ino. Table of Contents I. Introduction.................................................................. .................................. 1 II. Materials and Methods........................................... ........................................ 1 A. Test Substance.................................................. 1 B. Test Animals...................................................... 1 C. Experimental Design................................................................................. 2 D. Assignment to Group................................................................................ 3 E. Animal Identification....................................................................... 3 F. Husbandry....................................... 3 G. Test Substance Administration.............................................................. 4 H. Estrous Cycle Determination.................. 5 I. In-Life Observations and Measurements................................... 5 0. Postmortem............................... 6 K. Statistical Analysis....................................................................... 6 III. Results and Discussion......... .................................................... . 9 A. Maternal Data............................... 9 1. Mortality.................................................... 9 2. Body Weight Data - Pre-mating Treatment Period............... . 9 3. Physical In-Life Observation Data............................................... 9 4. Pregnancy Rate Data.................................................................... . 10 5. Gestation and Lactation Body Weight Data.................................. 10 B. Litter Examination Data................................................................. 10 1. Gestation Length............................................................................... 10 2. Parturition Data......................................................................... 11 3. Pup Survival Indices................................ ................................ .. 12 4. Pup Sex Distribution Data........................................................ 12 5. Pup Body Weight Data................................................................... . 13 6. Pup Organ Weight Data - Absolute and Relative to Day 21 Body Weights........................................................ 13 C. Postmortem Observations....................................................................... 14 1. Females.................................................. 14 2. Pups...................................................................................................... 14 TABLES 1. Mean Body Weights and Weight Gains - Pre-Mating Treatment Period....................................... 16 2. Pregnancy Rate Data................................................................................ 17 3. Maternal Body Weights and Body Weight Gain.................. 18 4. Parturition Data....................................................................................... 19 5. Pup Survival Indices............................. 20 6. Pup Sex Distribution Data...................................................................... 21 7. Mean Pup Weights Distinguished by Sex.22 8. Kean Pup Organ Weights. Day 21 Body Weights and Organ/Day 21 Body Weight Ratios Males and Females............. 23 DO 067676 CONFIDFNTTAl YZ0014331 -rr-ziz Table of Contents (cont.) APPENDICES A. Inhalation Report..................................... ...............................................A-l 8. Individual and Mean Body Weight Data Pre-Mating Treatment Period..................... ......................................... 8-1 C. Individual and Mean Maternal Body Weights Gestation and Lactation............................................... ..........................................C-l D. Litter Information....................................... ..........................................D-l E. Implantation Scar and Unaccounted-for-Conceptl Data......E-l F. Gross Postmortem Observations - Females.....................F-l G. Pup Organ and Body Weights and Organ/Body Weight Ratios........ 6-1 H. Gross Postmortem Observations - Day 21 Weanlings (Unselected).. H-1 I. Gross Postmortem Observations - Day 21 Weanlings (Selected).... I-l J. Mating Performance............................................................................... J-1 K. Postmortem Observations for Pups Culled from LI Iters on Day 4 of Lactation........ ................................................................... K-l L. Dead Pup Observations............................................................................ L-l M. Certified Feed Information................... ... M-1 N. Analysis of Benzene.................................................................................H-1 O. Mean Pup Weights........................................... .............................. . 0-1 P. Water Analysis.......................................................................... P-1 Q. Methodology and References............................................................. Q-l R. Personnel....................................... ............................. ...............................R-l o. 067677 OONFTDFNT IAI 1 YZOO14332 I. INTRODUCTION This study, conducted for the Chemical Manufacturers Association and the American Petroleum Institute, was designed to evaluate the fertility and reproductive performance of female rats when administered benzene by Inhalation at dose levels of 1, 10, 30 and 300 ppm. Test substance was administered 6 hours per day, 5 days a week for 10 consecutive weeks prior to mating. Treatment of females continued for 6 hours per day, 7 days a week during the ensuing gestation (Day 0*20) and lactation periods (Days 5-21). Species and strain of test animal, dose levels and route of test substance administration were established by the sponsors. Testing was conducted at Blo/dynamlcs, Inc., Mettlers Road, East Millstone, New Jersey 08873. Raw data will be stored In the archives of Blo/dynamlcs, Inc. II. MATERIALS AND METHODS A. Test Substance: Supplier: Benzene Chemical Manufacturers Association Description: Clear, colorless liquid with characteristic odor. Lot No.: API-CMA Benzene Lot No. 1 (Sample withdrawal date 11/13/79). Stability: Benzene was analyzed for purity at four Intervals during the study; l.e Pre-test, prior to Initiation of Treatment, Week 6 of the Treatment Period and at Termination of treat ment. (Appendix N). Date Received: 13 November 1979 Storage: Amber glass 1 gallon bottles at room temperature. B. Test Animals; Species: Rat Strain: Justification of Animal Selection: CD* (Sprague-Oawley derived) Generally recognized standard laboratory rat. DO 067678 CONFTDFNTIAL YZOO14333 -2- 79-2425 Bto/d/yn_ tmlM B. Test Animals (cont'd): Number of Animals Received: 153 females Placed on Test: 130 females (26/group) Age: Males: In-house breeding colony - males were proven fertile and less than one year In age at Initiation of mating. Females: Virgin; 7 weeks at Initiation of pre mating treatment period. Supplier: Charles River Breeding Laboratories Wilmington, Massachusetts 01887 Date Received: 13 December 1979 C. Experimental Design: Group Dose ppm Pre-Mating Treatment Period (days)* Male Female No. of Rats Females Sacrificed Mated Post Weaning" Male0 Female I Chamber- N.T.C 70 Exposed 13 26 All 11 1 N.T. 70 13 26 All III 10 IV 30 N.T. 70 N.T. 70 13 26 13 26 All All V 300 N.T. 70 13 26 All treatment Schedule: Six hours/day, five days/week for the 10 consecutive weeks pre-mating treatment period and ensuing mating period. Six hours dally seven days a week during gestation (Days 0-20) and dally seven days a week from lactation Days 5-21. "Males from the In-house breeding colony were used for mating. <-N.T,Not treated. "The first females to wean litters were retained until sponsor decision was made to sacrifice. The last females to wean litters were sacrificed at weaning (Day 21 of Lactation). DO OONF 067679 -rOFNTTAl YZOO14334 0. Assignment to Group: E. Animal Identification F. Husbandry: Housing: Food: Water: -3nmle Ino. Prior to Initiation of the pre-mating treatment period, females were assigned to groups so as .to equalize mean body weights at Initiation of treatment', A sufficient nunber of females were received so as to discard unhealthy females prior to distributing Into groups. Each female rat was identified with e metal ear tag bearing Its animal number. The Individual animal nunber plus the Bio/dynamics project number comprised a unique Identification nunber. Females: Acclimation two/cage during the first week and Individually for Week 2; Pre-mating Treatment period - Indi vidually during exposure and non exposure periods; Mating - one male and two females; Gestation and Lactation - females were housed Individually during gestation and with litter during lactation. Caging: Animals were housed In stainless steel wire mesh cages (exposure and non-exposure Intervals). Purina Laboratory Choir-5002 (Certified Diets); mash; females were without food during the exposure period, (luring the first week of acclimation, females were given Purina Laboratory Chow - 5001 pellets (certi fied diets used during study. See Appendix M). ad Vlb1tun. By automated water system rTlzabethtown Water Company (none dur ing exposed period). Special water analyses were performed at two Intervals during the study; during the pre-mating treatment period and near termination of the study (Appendix P). ^Monroe 1860 calculator - In-house sorting program. DO 067680 OONFTDFNTTAl YZ0014335 F. Husbandry (cont.): Water (cont.): -4- 79T2425 1 /dyn*mo* Ino, Included In these water analyses were: Heavy metals: Cd As, Pb, Hg, Se, Be and Sb PCD11 Organic Phosphate Pesticides - Mel- athlon Chlorinated hydrocarbons Including lindane, heptachlor, DDT and dleldrtn Benzene Carbamate pesticide screen Environmental Conditions: 12 hour llght/dark cycle Temperature: Humidity: Monitored twice dally. In the animal room: recorded twice dally morning and afternoon (during non-exposure period); acceptable range 40-60%. Humidity was recorded for the duration of the study (164 days). It was found to be out of range approx imately 7% of the time. In the chambers: recorded routinely during the exposure Intervals (at least three distinct Intervals dally). It was found to be out of range approximately 18%-25% of the time. G. Test Substance Administration: Route: Inhalation Chamber Operation: See Appendix A Frequency: 6 hours/day, 5 days/week (Monday Friday) during 10 week pre-mating treatment period and mating period; dally from Days 0 to 20 gestation and Days 5 to 20 of lactation. Duration (Dates of Treatment): Atmospheric Sampling: Pre-mating Treatment Period: 7 Januar .1980 - 14 March I960 Mating Period: 16 March 1980 - $ Aprl 1980 Gestation Interval (First Day 0 - last Delivery): 17 March 1980 - 23 April 1980 lactation Interval (First Day 0 last weaning): 7 April - 14 May 1980 , See Appendix A DO 0676R1 CONFTOFNTTAl YZ0014336 -5- 79-2425 I n*mlc* Ino. H, Estrous Cycle Determination: To determine If estrous cycling was being affected by treatment, dally vaginal smears were made and evaluated for each female beginning two weeks {14 days) prior to Initiation of mating. Mating: Two females were caged with a male nightly. Females were then examined each morning for evidence of mating (vaginal plug and/or sperm in the vaginal smear). The day on which such evidence was observed was defined as Day 0 of gestation. Once mated, females were housed Individually for the duration of gestation. The same male was caged with the same females nightly until both females were mated or for seven days (due to a scheduling error, males and females mated for eight days during the Initial Interval). If, following this Interval, a female did not mate, she was placed with a different male for an additional seven day Interval to be followed If necessary, with yet another seven day interval with a third male. I. In-Life Observations and Measurements; For Mortality and Gross Signs of Toxicologic or Pharmacologic Effects: Females - Twice dally (morning and afternoon); pre- and post-exposure. Detailed Physical Examination: Weekly throughout the study. During the treatment period these examina tions were performed In the afternoon following the exposure Interval. Body Weights: Females: Once weekly through completion of the mating period. Mated females were weighed on Days 0, 7, 14 and 21 of gestation and Days 0, 4, 14 and 21 of lactation. 0 06768? I'ONFroFNrrfl,. YZ0014337 -6- 79-2425 I. In-Life Observations and Measurements (cont.): Body Weights (cont.): B,y<'dyntmie* Utters: Pups were counted on Day 0, 4 (pre-cull and post-cull), 14 and 21 of lactation. Litters were observed twice dally; (mornlngtafternoon) presence of dead pups were recorded. On Day 4 of lactation, litters with greater than 10 pups were culled to 10 with an equal number per sex when possible (random culling procedure was employed). Body weights were measured and sex determination made for each pup on Days 0, 4 (pre-cull and postcull), 14 and 21 of lactation. As found, dead pups were weighed and sexed Internally. 0. Postmortem: Sacrifice Method: Evaluation: Overdose of ether. All females were given a gross post mortem examination. Abnormal tissues noted during these evaluations were saved In 10% neutral buffered formalin. For females that were exposed to males the uteri were evaluated for the presence and number of Implantation sites or scars. Unmated Females: Females that did not show evidence of mating were sacrificed at completion of the 21-day mating period (9 April 1980). Mated Females That Did Not Deliver a Utter: Mated females that did not deliver a litter were retained and sacrificed after all litters were weaned. These females were subsequently sacrificed with those females that did wean litters, uteri and ovaries for each of these females were saved In 10% neutral buffered formalin solution. DO 067683 CONFTDFNTTAl YZ0014338 -7- rdynmlN Ins. 0. Postmortem (cont.): Females That Delivered Litters: Pups: The first females to wean litters were retained until sponsor decision was made to sacrifice. The last female to wean litters were sacrificed at weaning (Day 21 of lactation) These females were sacrificed over a three day Interval (May 12-14, 1980). The uterus and ovaries of each female were saved In a 10% neutral buffered formalin solution. Gross postmortem examinations. Includ ing Internal sex determination, per* formed on all pups sacrificed on Day 21 (weaning) and pups found dead during lactation. The latter were also checked for the presence or absence of milk In the stomach. Pups found dead prior to Day 4 of lactation were preserved In 70% ethanol; those found dead after Day 4 of lactation were discarded. Only abnormal tissues were saved (10% neutral buffered formalin). DO 067684 CONF T DFNT I Al YZ0014339 -8- 79-2425 0. Postmortem (cont.): Sacrifice (cont.): Sacrifice Method for pups: Lethal exposure to ether* The following organs were weighed for each pup (control and each treated group) sacrificed at weaning (Day 21 lactation)* liver kidneys (2) testes (2) Additionally, the following tissues were taken from two pups/sex/ litter (control and each treated group) and preserved In 10% neutral buffered formalin' (eyes and testes placed Initially In Bouln's solution prior to permanent storage In formalin): adrenals (2) bone marrow (sternal) brain (2 sections) epididymides eyes (2) gonads heart intestine colon duodemm Ileum kidneys (2) liver (2 sections) lung lynph nodes (mesenteric) mammary gland (right Inguinal) pancreas salivary glands seminal vesicles skeletal muscle (biceps femorls with sciatic nerve attached - right side) skin (with mammary gland) spinal cord (cervical) spleen stomach thyroid (attached to trachea) urinary bladder uterus/prostate gross lesions tissue masses thymus pituitary No hlstopathologlcal evaluations were performed (maternal and offspring). K. Statistical Analysis: (See Appendix Q). Ityote that during the procedure of preserving tissues In formalin the tissues of some pups were inadvertently placed In containers filled with saline* These tissues were subsequently lost from the study. The pups whose tissues were lost from study are Indicated In Appendix I (see footnote "b"). 00 067685 CONFTDFNTTAI YZ0014340 m -9- 79-2425 W ... - ............ -... .... Inc, III. RESULTS AND DISCUSSION A. Maternal Data m 1. Mortality: No mortality occurred In the control or treated Groups III (10 ppm) or M V (300 ppm). In Group II (1 ppm) female No. 448 was killed In a moribund condition during the post-weaning Interval. This female had weaned a litter and at time of sacrifice was extremely emaciated having malocclusion and ocular Irregularities. In Group IV (30 ppm) one female (No. 829) died during Week 5 9 of the pre-mating treatment period. Death was accidental due to a handling am problem. No treatment effect on mortality was Indicated, ft 2. Body Weight Data - Pre-mating Treatment Period: Individual female body weight data during the pre-mating treatment p P' period are presented In Appendix B, and are summarized In Table 1 (page 16). Mean weekly body weight data during the pre-mating treatment period were comparable between the control and treated groups. Likewise, mean body p weight gain during this same Interval was comparable between these same groups. 3. Physical In-Life Observation Data: The type and Incidence of observations noted during the weekly P physical evaluations were generally comparable between the control and treated m groups throughout the study. * During one week of study (lactation period) several treated females fl were noted to have swelling In the cervical area. This observation was noted In three Group II (1 ppm) females, four Group III (10 ppm) females, seven Group IV i P (30 ppm) females and three Group V (300 ppm) females; this observation was _ not noted in the control group. Swelling In the cervical region Is 067686 CONFTDFNTTAI YZ0014341 -10- 79-2425 consistent with sialodacryoadenltls (SDA) Infection In rats. Due to the transient nature of the observation In this study, no treatment effect was Indicated. 4. Pregnancy Rate Data: Pregnancy rates derived from data In Appendices D and 0 are presented In Table 2 (page 17). Pregnancy rates were comparable between the control and treated groups. One control and two low-dose females failed to show evidence of mating during the 21-day mating period. These females were sacrificed at completion of the mating period and uterine Implantation sites were noted for each of the low-dose females (Nos: 437 and 446). The control female (No. 241) was not pregnant. No treatment effect on pregnancy rate data was Indicated. 5, Gestation and Lactation Body Weight Data: Individual female body weight data during the gestation and lactation Intervals are presented In Appendix C. Mean body weight data during these same Intervals are summarized In Table 3 (page 18). Mean body weights during the gestation and lactation intervals were comparable between the control and treated groups. Likewise, mean body weight changes during these same Intervals were comparable between these same groups. No treatment effect was Indicated In gestation-lactation weight data. B. Litter Examination Data: 1. Gestation Length (Appendix D): Mean gestation lengths (Table 4, page 19) were comparable between the control and treated groups. DO oohf YZ0014342 -n- 79-2425 i L /dyn mio Inci. No problems In delivery were noted In the treated females. In the control group, one female (No. 232) Initiated delivery on Day 24 of gestation* At this time, the hlndllmbs of one pup were noted In the vaginal canal. At subsequent evaluations no evidence of a delivered pup was noted. Terminal sacrifice of this female revealed one Implantation scar. 2. Parturition Data: The mean number of live and dead pups at birth (Day 0) are presented in Table 4 (page 19). These data are summarized from Individual female litter data presented In Appendix D, The mean number of live pups at birth was comparable between the control and treated groups. The mean number of dead pups at birth was compar able between the control and treated Groups II to IV (1, 10 and 30 ppm). In Group V (300 ppm) the mean nunber of dead pups at birth was slightly higher than control; however, this difference was not statistically significant. The increase In mean nunber of dead pups in the high-dose group was. In part, attributed to two litters. High-dose female No. 1025 delivered a litter of five viable pups and four dead pups. Klgh-dose female No. 1031 had initiated delivery during the afternoon litter evaluations. At that time four dead pups were noted and removed, delivery was not considered complete but four viable pups were observed. When evaluated the next morning only two viable pups were noted. The mean total litter size at birth (Including live and dead pups) was comparable between the control and treated groups (Table 4). Mean numbers of Implantation scars and unaccounted-for-conceptl (UFC) are presented in Table 4 (page 19); Implantation scar data and UFC data for Individual females are tabulated In Appendix E. The mean numbers of Implantation scars and UFC were comparable between the control and treated groups. Do T^6F7N,6rFsMs /, YZOO14343 -12- 79-2425 "'/<dynamic* p. 3. Pup Survival Indices: Pup survival Indices for Days 0-4 and 4-21 of lactation are presented In Table 5 (page 20). These Indices are derived from data In Appendix D. Pup survival Indices for the Oay 0-4 Interval were considered comparable between the control and treated groups. The Oay 0-4 survival Index for Group IV was significantly higher than control; however, this was not considered Indicative of an adverse effect of treatment. Pup survival Indices for Days 4-21 were comparable between the control and treated Groups II, IV and V (1, 30, 300 ppm). In Group III (10 ppm) the pup survival Index for Days 4-21 was significantly lower than control. This decrease In pup survival was attributed to Increased pup mortality in two litters. In the absence of Increased pup mortality at higher dose levels, this decrease In pup survival in Group III was considered spurious and not related to ' treatment. 4. Pup Sex Distribution Data: Mean nunber of male and female pups at birth and sex ratios for Days 0, 4 (post-cull) and 21 are presented in Table 6 (page 21). These data are summarized from Individual litter data (Appendix D). The mean nunber of male and female pups at birth (Day 0) was con sidered comparable between the control and treated groups. Sex ratios at birth (Day 0) Indicated an Increase In total number of male pups In Groups II (1 ppm) and V (300 ppm) and Increase In total number of female pups In Group IV (30 ppm). These differences were attributed to normal biological variability within this parameter and not related to treatment. Sex ratios at Day 21 were similar to sex ratios at Day 4 post-cull In the control and each treated group. No treatment effect on sex ratio data was Indicated. DO 067689 C.ONFTDFNTT Al ______________________ ___________________ YZ0014344 -13- 79-2425 mo/d/,ynamic* ino. 5. Pup Body Weight Data (Appendix 0): Mean pup body weight data distinguished by sex are presented In Table 7 (page 22). Mean body weight data for both male and female pups were comparable between the control and Groups II and III (1 and 10 ppm) throughout lactation. In Group IV (30 ppm) mean pup weight data (both sexes) were comparable to control on Days 0. 4 and 14 of lactation and slightly lower than control on Day 21. This latter difference was not statistically significant. In the high-dose group (300 ppm) mean pup body weights (both sexes) were comparable to control on Days 0 and 4 of lactation. On Days 14 and 21 mean pup weights for the high-dose group were slightly lower than control; however, these differences were not statistically significant. 6. Pup Organ Weight Data - Absolute and Relative to Day 21 Body Weights: Individual pup organ weights, Day 21 body weights and organ/body weight ratios are presented In Appendix G. Mean pup organ weight data (absolute and relative to body weight) for both males and females are summarized In Table 8 (page 23). Mean testes weights (absolute and relative to Day 21 body weights) were considered comparable between the control and treated groups. Mean liver weights (absolute and relative to body weight) for the male pups were comparable to control In Groups II and III (1 and 10 ppm, respectively) and slightly lower than control at the higher dose levels (30 and 300 ppm); however, these latter differences were not statistically significant. Mean kidney weights and mean kidney to body weight ratios for the treated male pups were considered compara ble to the controls. DO 067690 CONFTDFNTIAL YZOO14345 -14- 79-2425 Bio/ /4yntmlo* In the females, mean liver weights were considered comparable between the control and Groups II, III and IV (1, 10 and 30 ppm, respectively) and significantly lower than control at the high-dose level {300 ppm). However, when liver weights were analyzed relative to body weight data (mean liver/ body weight ratios) these data were comparable between the control and treated groups. Mean kidney weights and kidney to body weight ratios for the treated female pups were considered comparable to controls, although kidney to body weight ratios were statistically higher for Groups III, IV, and V (10, 30 and 300 ppm, respectively). C. Postmortem Observations: 1. Adult Females: Gross postmortem observations for the females are presented In Appendix F. No treatment-related effects were Indicated. 2. Pups: Gross postmortem observations for the pups sacrificed on Day 21 are presented In Appendices H (pups for which tissues were not retained) and I (pups with selected tissues taken and saved In 10X formalin). Postmortem observations for dead pups recovered during the lactation Interval and pups culled on Day 4 are presented In Appendices L and K, respectively. 00 067691 CONFTDFNTTAl YZOO14346 -15- 79-2425 Ht /flyn. mloa lno. Evaluation of gross postmortem observations of pups sacrificed at weaning did not reveal a treatment-related effect. Likewise, evaluation of observations for dead pups recovered during the study or pups culled from litters at Day 4 did not reveal effects attributed to treatment. DO 067692 00NFTDFN1 IAI YZ0014347 Table 1 An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Mean Female Body Heights and Height Gains - (grams) Pre-Mating Treatment Period Group ppm Change in Height Week: 0 1 2 3 4 5 6 7 8 9 10 1-10 I Mean 0 S.D. N 159 179 191 202 217 225 234 239 245 250 255 10 12 15 15 16 18 17 20 22 22 22 26 25a 26 26 26 26 26 26 26 26 26 76 14 25a II Mean 1 S.O. N 160 179 193 205 219 229 236 239 244 252 255 11 12 14 15 16 17 16 16 18 20 18 26 26 26 26 26 26 26 26 26 26 26 75 11 26 III Mean 10 S.D. N 160 179 192 204 218 228 235 238 243 252 254 9 12 12 13 13 17 17 16 17 20 19 26 26 26 26 26 26 26 26 26 26 26 75 10 26 IV Mean 30 S.D. N 160 177 193 205 217 227 234 241 246 253 257 10 12 13 13 14 16 17 17 19 22 21 26 26 26 26 26 25**> 25 25 25 25 25 79 U 25 V Mean 300 S.D. N 161 180 194 205 219 227 234 238 245 251 253 12 14 16 19 20 21 22 24 24 24 24 26 26 26 26 26 26 26 26 26 26 26 72 14 26 No statistically significant differences from control group. *N equals 25 due to the Incorrect recording of one animal's body weight (weight excluded from calculations) bN equals 25 due to death of an animal. Key: S-D. Standard deviation N " Kanber of observations -16- a O ly iIN j a i j N0J 69^90 00 'd yn m io i In -17Table 2 An Inhalation Female Fertility Study -------------with Penzene tn-Rats------------- 79-2425 io/ /clyntmlM Ins, Pregnancy Rate Data Group ppm I 0 II 1 III 10 IV 30 V 300 Exposed to Males Number of Females Pregnant" Tmplaiv Implant tatIon Scars Sites Parturition Onlyc Only* Total 26 21 2 0 23 26 22 1 2 25 26 24 0 0 24 25 19 2 0 21 26 23 0 o 23 Pregnancy Rateb NO. % 23/26 88.5 25/26 96.2 24/26 92.3 21/25 84.0 23/26 88.5 No statistically significant differences from control group. aFemales with no evidence of mating were sacrificed at completion of the mating period. Several of these females did have uterine Implantation sites. "Total number of females pregnant/total nunber females exposed to males X 100. Pregnancy defined as parturition and/or Implantation scars or Implantation sites. cFemale did not deliver a litter but at terminal sacrifice Implantation scars were noted along the uterine horn. 00 067694 conftofnttai YZ0014349 YZ0014350 Tabic 3 79-2425 An Inhalation Female Fertility Study i with benzene In Rats Mean Katernal Body Weights and Body Height Gain - (grans) Group PI" I 0 II 1 III 10 IV 30 V 300 Mean SJ). H* Mean S.D. N* Mean S.O. N* Bean SJ). Mean S.D. N* Pays: 0 253 20 22 255 21 22 251 19 24 254 21 19 254 28 23 Gerstation 14 273 300 22 23 22 22 273 301 24 26 22 22 282 311 20 23 24 24 273 301 23 25 19 19 273 301 28 29 23 23 JL 375 32 22 376 32 22 3B8 30 24 384 30 19 377 39 23 Change in Body Height 0-21 IS 23 22 121 20 22 126 21 24 130 18 N 126 22 23 S Lactation "4 14 284 289 25 23 21 21 311 24 21 282 291 24 22 22 22 319 23 22 288 298 24 26 24 24 325 23 24 289 294 23 25 19 19 318 26 19 289 296 34 31 23 22 316 28 22 JL. 322 23 21 320 22 22 325 24 24 328 25 19 330 35 22 Change In --BodIyvWveirgh-t TT 13 21 38 15 22 37 19 24 39 12 19 41 18 22 oO o No statistically significant differences fron control group. .... .. *11 wur be less than 26 due to exclusion of nonpregnant anInals, death of an anlnal or because no evidence of eating was observed (Boy 0 Indeterminable). Kay: SJ). - Standard deviation N - tader of observations -18- 5 sj H v) Cn X> i -1 s79-2425 Table 4 An inhalation Female. Fertility St^y_________ with Benzene In Rats ino. Parturition Data Group ppn I 0 11 1 III 10 IV 30 V 300 No. of Litters 21 22 24 19 23 Mean Gestation Length (Days) 21.7 21.8 21.9 21.7 21.5 Mean No Pups at Birth Live Dead Total 11.6 0.1 11.7 11.5 0.3 11.8 12.2 0.4 12.6 11.7 0.1 11.8 11.3 0.7 12.0 Mean No. of Implant Scars 12.5 12.8 13.4 12.9 13.5 Mean No UFC 1.3 1.0 0.8 1.1 1.5 No statistically significant differences from control group. aUFC unaccounted-for-concept1 - derived for each female by subtracting total number of pups at birth (live and dead) from number of Implant scars. 00 c-ONF 06?696 Tdfnttai YZ0014351 -20- Table 5 An Inhalation Female Fertility Study with Benzene In Rats nio/-'dynamic* 79-2425 Pup Survival Indices Group ppm I 0 11 1 III 10 IV 30 V 300 Survival Indices8 Days 0-4b Days 4C-ZI No. i No. % 236/243 97.1 195/197 99.0 251/254 98.8 206/206 100.0 290/293 99.0 216/229 94.3# 217/218 99.5# 177/178 99.4 253/261 96.9 198/202 98.0 Significantly different from control group: #p<0.05 (Fisher-Exact Test); for explanation of statistical procedure, see Appendix Q. Survival Indices are derived by dividing the total number of pups alive at the end of a time Interval by the total number alive at the beginning Of the Interval. bPre-cull. cPost-cull. DO 067697 CONFIDENT! Al YZ0014352 -21- Table 6 An Inhalation Female Fertility Study with Benzene In Rats BleZ9-2425 /dynmmioi Inn. Pup Sex Distribution Data Group ppm I 0 II 1 III 10 IV 30 V 300 Day 0 Mean No. Pups TteTe Female Sex Ratio W No. 4 5.9 5.7 123/120 102.5 6.2 5.3 137/117 117.1 6.2 6.0 148/145 102.1 5.3 6.4 101/122 82.8 6.3 5.1 144/117 123.1 Day 4 (Post-Cull) Sex Ratio WF) No. t 102/95 107.4 Day 21 (Weaning) Sex Ratio (M/F) No. % 101/94 107.4 111/95 116.8 111/95 116.8 112/117 95.7 108/108 100.0 80/98 81.6 79/98 80.6 103/99 104.0 101/97 104.1 Ratios not analyzed statistically. Key: M/F * Total No. Male Pups/Total No. of Female Pups. DO 0676.98 OONFTDFNTTAl YZOO14353 -22 Table 7 An Inhalation Female Fertility Study with Benzene In Rats Mean Pup Weights (grams) - Distinguished by Sex loWynmle 79-2425 Group ppm I 0 II 1 III 10 IV 30 V 300 MF 6.3 6.1 6.4 5.9 6.5 6.2 6.4 6.1 6.1 5.9 Pre-Cull "TosT-CuTT "H--r M 9.6 9.3 9.6 9.3 10.1 9.2 10.1 9.2 10.3 9.8 10.3 9.9 10.0 9.6 10.0 9.6 9.7 9.3 9.7 9.4 Dav 14 h ~ "r 23.0 22.1 Dav 21 T""f 37.3 36.6 23.3 22.1 37.4 35.6 23.5 23.0 38.1 37.1 22.3 22.1 34.7 34.2 21.8 21.1 34,3 33.2 No statistically significant differences from control group. Key: M Male F * Female DO 067699 CONFTDFNTTAl YZ0014354 Table 8 An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Mean Pup Organ Heights, Day 21 Body Heights and Organ/Day 21 Body Weight Ratios - Males Group ppm I Mean: 0 S.D.: H II Mean: 1 S.D.: N III Mean: 10 S.D.: N IV Mean: 30 S.D.: N V Mean: 300 S.O.: N Day 21 Body Wt.a (g) 37.6 5.7 101 38.2 7.2 111 38.0 7.7 108 34.0 6.2 79 34.1 5.7 101 Organ Weight (?) Testes Li ver Kidneys (g) (<j) (g) 0.162 1.705 0.443 0.037 0.390 0.080 101 101 101 0.178 1.711 0.467 0.051 0.435 0.101 111 no 111 0.169 1.693 0.043 0.465 108 108 0.469 0.099 108 0.151 1.510 0.042 0.408 79 79 0.424 0.088 78 0.151 1.453 0.419 0.031 0.347 0.086 101 101 101 Organ/Day 21 Height Ratios x IO-2 Testes Liver Kidneys (g) "nr 0.426 4.493 0.068 0.513 101 101 1.177 0.108 101 0.470 4.438 1.226 0.145 0.479 0.145 111 no 111 0.443 4.435 0.059 0.665 108 108 1.241 0.125 108 0.442 4.380 0.078 0.536 79 79 1.239 0.093 78 0.446 4.216 1.229 0.060 0.470 0.142 101 101 101 YZ0014355 n g ^ oS J \j ho -o No statistically significant difference from the control group. Key: S.D. - Standard deviation N * Number of observations aData not evaluated statistically - mean pup body weight data during lactation are presented in Table 7 and sumarized in Appendix 0. Differences in mean pup body weight data between Tables 7 and 8 are due to analysis of Individual pup data (Table 8) versus mean litter data (Table 7). -23- r Table 8 (cent.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Mean Pup Organ Weights, Day 21 Body Weights and Organ/Day 21 Body Weight Ratios - Females Group ppm Day 21 Body Wt.a 19) 1 Mean: 36.3 0 S.O.: 5.2 N 94 II Mean: 35.5 1 S.D.: 5.9 N 95 III Mean: 37.7 10 S .0 t 7.1 H 108 IV Mean: 33.8 30 S JO.: 5.3 N 98 V Mean: 32.6 300 S D * i 5.1 n 97 1- *>^i Organ Weight (grams) Kidneys 19) 1.690 0.355 94 0.444 0.075 94 1.587 0.408 95 0.444 0.075 94 1.783 0.431 108 0.488 0.102 108 1.560 0.326 98 0.450 0.084 98 1.462t 0.339 97 0.436 0.079 96 Orqan/Day 21 Body Weight Ratio x 10"2 Li ver Kidney s (9) (g) 4.626 0.546 94 1.223 0.103 94 4.438 0.674 95 1.256 0.095 94 4.700 0.492 108 1.295tt 0.103 108 4.601 0.507 98 1.330tt 0.115 98 4.442 0.469 97 1.333tt 0.136 96 n oo 2n o -i o Oo' Significantly different from control group: t{K0.05, tt p<0.01 see Appendix Q for explanation of statistical procedure. Key: S.D. Standard deviation N * Number of observations tN --22H>I si ^Osj Data not evaluated statistically - mean pup body weight data during lactation are presented In Table 7 and summarized In Appendix 0. Differences In mean pup body weight data between Tables 7 and 8 are due t analysis of Individual pup data (Table 8) versus mean litter^^rta U> 71 \ ___ A-1 Appendix 79-243&0ArdynmlM In. A Female FertllIty Study In Rats with Benzene Inhalatlon Report SUMMARY Four groups of 26 female Sprague-Oawley (CD*) rats were exposed to benzene vapors for six hours per day. five days per week for ten consecutive weeks and were then blgamously paired with untreated males. During the mating phase the females only were exposed as before. Animals that successfully mated were exposed throughout the gestation and lactation periods for 6 hours per day, seven days per week. Following the 21-day lactation period the exposure regime reverted to 5 days per week for two weeks to assess the need for further matings. A similarly constituted group was exposed to air alone according to the same regime, and served as a control. Air samples fron each chamber were analyzed by either Infra-red spectroscopy or gas liquid chromatography six times during each exposure. The variable background Interference of the Infra-red technique, due to the presence of animals In the exposure chamber, was significant at the two lower levels and in part accounts for the greater fluctuations In chamber concentration at these levels. Mean levels and ranges (as determined analytically) on samples of chamber atmospheres (expressed In PPM) were as follows: Reproductive Phase it til Group iv V Premating Mating Gestation Lactation 1.0 (0.3-3.5) 9.8 (7.4-12.7) 0.7 (0.0-1.4) 9.8 (8.0-12.1) 0.8 (0.0-1.4) 10.9 (8.0-14.1) 1.2 (0.2-1.4) 12.7 (9.5-15.2) 30.3 (26.3-35.4) 299 (273-334) 30.9 (29.6-33.0) 300 (287-319) 30.9 (29.6-33.0) 296 (260-319) 30.7 (29.0-32.4) 296 (260-337) _ Biol. Director, Inhalatlon'ToxIcology for George M. Rusch, Ph.D. Report Preparation: Cecelia A. Bozak, B.A. Study Monitor, Inhalation DO 06770? OONFTDFNTTAI YZ0014357 JU2- Itt J42S'"/'dyiumltt Ino Appendix A (Cont.) A Female Fertility Study In Rats with Benzene INTRODUCTION This study was designed to evaluate the fertility and reproductive performance of female rats treated with benzene for ten consecutive weeks prior to mating. Treatment of the females continued during the ensuing gestation and lactation periods. In this report, nominal and actual concentrations are presented from Pay 1 (January 7, 1980) through termination (May 14, 1980) of the study. EXPERIMENTAL DESIGN Group Pre-Mating Treatment Schedule (days) Exposure Treatment M Number of Rats Females Sacrificed Mated at Weaning M '1 F I Control-chamber exposed II Benzene - 1 ppm III Benzene - 10 ppm IV Benzene - 30 ppm V Benzene - 300 ppm N.T. 70 N.T. 70 N.T. 70 N.T. 70 N.T. 70 13 26 13 26 13 26 13 26 13 26 All All All All All ^Treatment schedule: Six hours/day, five days/week for the 10 consecutive week pre-mating treatment period and ensuing mating period. Six hours dally seven days per week durlnq gestation (Day 0-20) and Days 5-21 of lactation. ^Males from the In-house breeding colony were used for mating. N.T. Not treated. YZ0014358 A-3 - 79-2425 - /dymmi ine. Appendix A (Cont.) A Female Fertility Study In Rats with Benzene Test Material Administration Benzene vapor concentrations were generated Into one cubic meter stainless steel and glass chambers using a flash-evaporation generating system. Liquid benzene was pimped Into a heated 3-neck flask through a 3-1nch length of l/8-1nch diameter teflon tubing from a glass syringe fitted with a 16 gauge stainless steel needle. Flask temperature was maintained at 50C In Groups II, III, and IV and 80C In Group V. These temperatures were selected as the minimum required to achieve complete volltallzatlon of the test material. The 3-neck flask was heated using a Glas-Col heating mantle and temperature was measured using a Glas-Col laboratory pyrometer. The benzene was pimped using Sage Instrunents Model 220 and 341 syringe pimps. Adjustments In chamber concentration were made by adjusting pump flow rates (ml/hr) or chamber air flow (1pm). Air flow was determined by measuring the change In pressure (AP, cm H2O) over a one inch orifice plate using a Dwyer magnehellc pressure gauge. Airflows were maintained between 150 and 250 Ipn for the duration of the six hour exposures. Oo ^OMp Tn^Nr tai YZ0014359 A-4 79-2425 Appendix A (Cont.) A'Female reUHlly Study In Rata with Benecno Chamber Operation The stainless steel and glass exposure chambers In which the animals were exposed had a total volune of one cubic meter with an effective volune of 760 liters. They were operated dynamically at an air flow between 155 and 245 liters per minute, providing one air change In from 6.5 to 4.1 minutes and a 991 equilibration time (tgg) from 29,9 to 18.9 minutes. Dally Nominal Concentration Nominal exposure concentrations were calculated dally using the fol lowing equation: where 307.78 mg/ul Is the factor of conversion of mg/1 to ul/1 (ppm) for benzene based on gas constant laws. Dally nominal concentrations are presented for Groups II-V In Table 23. Chamber Atmospheric Concentration One sample per hour (at about 0,5, 1.5, 2.5, 3.5, 4.5 and 5.5 hours) was drawn from each exposure chamber using either a Wilks Instrument Company, Ml ran Long Pathlength Infrared Analyzer Model IA (In-house Iden tification numbers "L" and M4") or an on-line TTacor Gas Chromatograph Model 550,1 The exposure levels were determined by comparing the observed absorbance of these samples to a previously determined standard curve generated using the test material under the same Instrumental settings. The calibration curves for this test material are presented on pages 10-18 of this appendix. iMIran L was used from Day 1 (1/7/80) through Day 66 (3/12/80) of the study. Ml ran 4 replaced Ml ran L on Day 67 (3/13/80) and was used through termination of the study (Day 130 - 5/14/80). Therefore, calibration curves were generated for each phase of the study, the first set corresponding to Mlran l (1/7/80 - 3/12/80) and the second set corresponding to Mlran 4 (3/13/80 - 5/14/80). Measurements were taken using the on-line Tlracor gas chromatograph In Groups II and III from Day 94 (4/9//80) through termination of the study. These values were used for measuring chamber concentration through termination of the study. Infrared measurements were taken during this period for comparative purposes only. DO 067705 OONFTDFNTTAl, YZOO14360 ntmiot in. Appendix A (Cont.) A Female Fertility Study In Rats with ftenzene Calculation of Chamber Concentrations Upon Initiation of the study. It was observed that the presence of the animals In the chamber created a background Interference In the Infrared monitoring procedure used to analyze the benzene exposure concentration. This Interference was negligible for the Group IV (30 ppm) and Group V (300 ppn) exposure groups but If uncorrected, could have resulted in a signifi cant overstatement of the concentration In the Group II (1.0 ppm) and Group III (10 ppm) exposure groups. Using the first few weeks of data a correc tion factor was calculated, based on measurements of the background Infrared absorption In the control chamber. An attempt was made to adjust the measurements using the control chamber data on a point-for-point basis. However, since the animals were exposed In a separate room, this approach did not produce a good correla tion; therefore, a correction procedure was developed using the average measured absorbance In the control chamber. This procedure Involved the calculation of the average measured Interference In the control chamber and then correcting each Individual measurement In the Group II and Group III chambers by subtracting this average background reading from the observed exposure chamber absorbance measurement. During the first week of the study, when only the reproduction animals were exposed, the correction factor was estimated at 0.003 absorb ance units. During the period of the study when the animals from the re production study were receiving simultaneous exposure with the animals from the dominant-lethal study (79-7342) the correction factor was estimated at 0.007 absorbance units based on the first three weeks of data. It was also DO 067706 OONF TDFNT T Al YZ0014361 A-6- Appendix A (Cont.) A Female Fertility Study In Rats with Benzene ^yntmloi Ino. m Calculation of Chamber Concentrations (cont.) TM observed during this period that the first one or two samples of the day had higher absorbances than the remaining samples In both the control and low level exposure groups. This was attributed to the Increased activity of the animals following loading of the chamber. During the last part of the study, exposure concentrations were monitored using the on-line gas chroma- | tography procedure described above. Measurements were still taken by | Infrared to allow for comparison. TM At the conclusion of the study, samples collected at each sampling H Interval (1e. 1/2 hr, 1-1/2 hr, 2-1/2 hr, 3-1/2 hr, 4-1/2 hr and 5-1/2 hr) were separately averaged and then statistically compared to one another.2 Where possible, separate calculations were performed for each phase of the study and following replacement of the original Infrared monitor. When It was found that a particular Interval possessed a unique correction factor, A either by being statistically different, or In the case of the smaller sample groups, by appearing to be unique, this factor was applied to all absorbance measurements taken at that sample Interval, for that period. These values have been used to calculate the corrected Individual exposure | concentrations. The statistical comparison Is presented In Table 1 and the m actual correction factors are presented In Table 2. TM 2F-test and Student's t-test (modified using Cochrans approximation Ctl when variances differ). Snedecor G.S., and W.G. Cochran, Statistical Methods. 6th ed., Iowa State University Press, flmes, 1967, pp 104-106, 114-119. fto ftO/v/r rF/vr TAl YZOO14362 A-7 79-242| "Adynamic* Ino. Appendix A (eont.) A Female Fertility Study In Rats with Benzene Nominal vs. Analytical Concentrations (Table 25)--------- ------------------------- A comparison of mean dally nominal concentrations and mean dally analytical concentrations was performed for Groups II through V for the entire study. In addition, In Groups II and III mean dally nominal and analytical concentrations were compared separately for the periods when Infrared measurements of concentration were taken (1/7/80 - 4/8/ftO) and when gas chronatgqraphlc measurements of concentrations were taken (4/9/80 - 5/12/80). Differences between mean nominal and analytical measurements ranged from 6 to 16% during the entire study. For Group II the difference In mean nominal and analytical concentrations was 24% when Infrared analysis was used and R% when gas chromatoqraphlc analysis was used. For Group III the difference In mean nominal and analytical concentrations was 1% when Infrared analysis was used and 9% when qas chromatographic analysis was used. The close agreement between mean nominal and analytical concentra tions for all phases of this study Is considered to be confirmation of the mean analytical values. 067708 DO tdfnttai gonf YZOO14363 Appendix A (Cont.) Table 1 A Female Fertility Study in Rats with Benzene Statistical Calculation of Correction Factors Used for Determination of Exposure Concentrations for Groups II and III 79-2425 Time Interval Exposure Hos. 1/7/80 - 1/11/80 1/14/80 - 3/12/80 3/13/80 - 3/21/80 3/22/80 - 5/14/80 1-5* 6-4R 49-55 56-109 Mean S.D. N Mean S.D. N Kean S.O. N Mean background Absorbances (Group I) _________________________Sample Intervals: 1/2 hr----- 1-1/2' Kr ' 2-172' h~ 3-1/2 hr 4-1/2 hr ' 5-1/2 hr 0.003 0.003 0.003 0.003 0.003 0.003 0.0128* 0.0030 43 0.0081* 0.0027 43 0.0068 0.0022 43 0.0066 0.0021 43 0.0061 0.0015 42 0.0061 0.0021 43 0.0115tf 0.0090 0.0042 0.0048 77 0.0088 0.0044 7 0.0087 0.0034 7 0.0084 0.0035 7 0.0085 0.0034 7 0.0071+ 0.0027 45 0.0060 0.0023 46 0.0056 0.0023 46 0.0053 0.0026 46 0.0052 0.0026 46 0.0049 0.0025 46 n oo tSignificwtly different from succeeding values (p<0.05). 2T1 O morn ocV*j '*Different from succeeding values (pX1.05). The limited amount of data available did not allow for specific Interval correction 2 vi HO `J->t o A-8 Appendix A (Cent.) Table 2 A Female Fertility Study in Rats with Benzene Correction Factors Applied to Measured Absorbance for Groups II and III 79-2425 Time Interval Exposure NOS. 1/7/80 - 1/11/80 1-5 1/14/80 - 3/12/80 6-48 3/13/80 - 3/21/80 49-55 3/22/80 - 5/14/80 56-109 1/2 hr 0.003 0.013 0.012 0.007 1-1/2 hr 0.003 0.008 0.009 0.005 Correcti on Factors Sample Intervals: 2-1/2 fir 3-1/2 hr 4-1/2 hr 0.003 0.003 0.003 0.006 0.006 0.006 0.009 0.009 0.009 0.005 0.005 0.005 5-1/2 hr 0.003 0.006 0.009 0.005 n oo zo ^o O O' N 2 NJ .u u> UOsl r A-9 A-10 79-2425 Appendix A (Cont.) A Female Fertility Study in Rats with Benzene Infrared Analysis of Benzene CALIBRATION FOR: Molecular Wfelght: Density: Renzene 78.11 amu 0.878 g/ml MIRAN SETTINGS: Wavelength: Pathlength: Range: Slit Width: Meter Response Time: Coarse Zero: 3.3 u - optimized to 3.28 u 21.75 m (14.0 dial reading) 0.1 l (Groups I. II, III) 1.0 X (Groups IV, V) 1 mm 1 second x1 STANDARD: Measured volumes of benzene were Injected Into a closed loop circulation system In order to generate atmospheres Inside the Mlran of known concentration levels. The closed loop system, Including the Mlran, measures 5.64 liters In volune. DO 067711 OONFTDFNTTAL YZ0014366 i A-n 79-2425 Appendix A (Cont*) A Female Fertility Study In Rats with Benzene Mlran Ambient Air Analyzer Closed Loop Calibrations Mlran L (1/14/80 - 3/12/80) Injection Ranqe Volume Concentration OjI) (ppm) Al Absorbance A? A3 "XT 0.1 * 0.01 0.02 0.03 0.05 0.10 0.15 0.19 0.21 0.23 0.30 0.50 0.60 0.5 1.0 1.4 2.4 4.8 7.2 9.1 10.1 11.0 14.4 24,0 28.6 0.001 0.003 0.004 0.007 0.015 0.023 0.029 0.032 0.034 0.045 0.075 0.091 0.001 0.002 0.003 0.006 0.014 0.022 0.029 0.032 0.035 0.046 0.077 0.092 0.001 0.003 0.005 0.007 0.012 0.019 0.024 0.026 0.028 0.038 0.065 0.079 0.001 0.002 0.003 0.006 0.014 0.021 0.027 0.030 0.033 0.043 0.074 0.088 1.0 % 0.50 0.60 0.63 0.65 0.70 1.00 2.00 3.00 4.00 5.00 6.00 6.20 6.30 6.50 7.00 7.50 8.00 24.0 28.8 30.2 31.1 33.5 47,9 95,8 143.7 191.6 239.6 287.5 297.0 301.8 311.4 335.4 359.3 363.3 0.075 0.09 0.10 0.10 0.11 0.15 0.30 0.44 0.56 0.68 0.79 0.81 0.82 0.B4 0.89 0.94 0.99 0.070 0.090 0.095 0.10 0.11 0.15 0.30 0.43 0.56 0.68 0.79 0.81 0.82 0.84 0.89 0.94 0.99 0.070 0.080 0.090 0.090 0.10 0.14 0.28 0.41 0.53 0.64 0.74 0.76 0.77 0.79 0.83 0.87 0.91 0.075 0.090 0.095 0.095 0.10 0.15 0.29 0.43 0.55 0.66 0.76 0.78 0.79 0.81 0.85 0.89 0.94 DO 06771? c ONFTDFNTTAI. YZ0014367 s iI N W O' VO J c.* - 0.2 0.7 : o.o !s i cy* s ^ o.v 0.3- oo o 3 -255^( -SJ\^.Jf ^ Cn w-4 O 0.a-| ai:r Appendix A (Coot,) A Female Fertility Study in Rats with Benzene Infrared Calibration Curve Range: 6-400 ppm (1/7/80-3/12/80) 79-2425 a tfi lv m-ts 7+-2*25,73+2 PUAfit* CAU&tlffTiOrt CVGV5 imwrtovifrw fo^ntmzeo to *>*THLe*GTH * ai.7y /bt nwj Awwjf s ^54 sur: fnn .m e*.r,ff(ac i n **. nr jr ?u 79-2425 Appendix A (Cont.) A Female Fertility Study In Rats with Oenzene Mlran Ambient Air Analyzer Closed Loop Calibrations Mlran 04 (3/13/80 - 5/14/80) Injection Range Volume Concentration (iil) <PP*n) ir Absorbance "ST W 0.1 % 0.01 0.02 0.03 0.05 0.10 0.15 0.19 0.21 0.23 0.30 0.50 0.60 0.5 1.0 1.4 2.4 4.8 7.2 9.1 10.1 11.0 14.4 24.0 28.8 0.001 0.002 0.002 0.005 0.012 0.018 0.024 0.026 0.029 0.039 0.068 0.081 0.001 0.002 0.004 0.007 0.014 0.022 0.027 0.030 0.034 0.044 0.072 0.086 0.002 0.003 0.005 0.008 0.016 0.023 0.029 0.032 0.036 0.046 0.074 0.088 1.0 % 0.50 0.60 0.63 0.65 0.70 1.00 2.00 3.00 4.00 5.00 6.00 6.20 6.30 6.50 7.00 7.50 8.00 24.0 28.8 30.2 31.1 33.5 47.9 95.8 143.7 191.6 239.6 287.5 297.0 301.8 311.4 335.4 359.3 383.3 0.07 0.09 0.09 0.10 0.10 0.14 0.27 0.38 0.48 0.57 0.65 0.66 0.67 0.68 0.71 0.75 0.77 0.07 0.08 0.09 0.09 0.10 0.14 0.26 0.38 0.48 0.58 0.66 0.68 0.68 0.70 0.73 0.76 0.79 0.07 0.08 0.09 0.09 0.10 0.14 0.26 0.37 0.46 0.55 0.62 0.63 0.64 0.65 0.68 0.71 0.75 0.000 0.001 0.002 0.003 0.009 0.015 0.020 0.022 0.025 0.033 0.062 0.074 0.07 0.08 0.09 0.09 0.10 0.14 0.25 0.37 0.46 0.55 0.62 0.63 0.64 0.65 0.69 0.72 0.75 DO 067716 CONFTDFNT TA1 YZ0014371 Appendix A (Cont.) A Female Fertility Study in Rats 79-2425 YZOO14373 Appendix A (Cont.) 79-2425 tfeSOVHArJCt Appendix A (Cont.) 79-2425 r> oO f T g \) o 2> o W Ol 1 Animal Number 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241* 242 243 244 245 246 247 248 249 250 Appendix A (cont.) Table 3 A Female Fertility Study in Rats with Benzene Individual Exposure Record for Group I Pre-Kat1rq Number of Exposures Mating Test Days Number of of Exposure Exposures 50 71-72 2 50 _ 50 71-72 2 50 71 1 50 * 50 71-73 3 50 50 71 1 50 - 50 71-75 5 50 71-75 5 50 71-75 5 50 50 71-76 5 50 71-72 2 50 71-73 3 50 71-93 17 50 _ - 50 71-84 10 50 71 1 50 50 - - 50 71 1 50 71-73 3 50 71-73 3 50 - - Gestation Test (lays Number of of Exposure Exposures 73-93 71-91 73-93 72-92 71-91 74-94 71-91 72-9e 71-91 76-96 76-96 76-96 71-91 77-97 73-93 74-94 71-91 85-105 72-92 71-91 71-91 72-92 74-94 74-94 71-91 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 Lactation Test Days Number of of Exposure Exposures 100-116 97-113 100-116 99-115 97-113 101-117 98-114 b 98-114 b 103-119 102-118 98-114 103-119 100-116 101-117 97-113 111-127 99-115 b 98-114 98-114 b 101-117 96-114 17 17 17 17 17 17 17 - 17 - 17 17 17 17 17 17 * 17 17 17 17 17 17 17 79-2425 PostLactation Number of Exposures 6 9 6 7 9 5 8 - 8 - 5 5 8 6 7 6 10 - 8 9 9 - 6 9 Cumulative Total total Number of Exposures 96 97 96 96 97 96 96 72 96 76 98 98 96 99 97 97 67 96 98 97 71 97 96 74 97 97 MntMl not mated. sacrificed 4/9/80. ^Animal did not deliver pups. no exposures received during lactation or post-lactation period. A-19 ' * A-20 79-2425 Appendix A (cont.) Table 4 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Pre-Mating Treatment Period Group II - 1 ppm Date Mean Dally Dally Total Exposure Dally Concen- Total Concen- Test Exposure Concen- Exposure tration Exposure tratlon Day Number tratlon SD Hours Hours Hours Hours Integrated Mean Concentratlon Ml ran L 1/7/80 1/8/80 1/9/80 1/10/80 1/11/80 1/14/80 1/15/80 1/16/80 1/17/80 1/18/80 1/21/80 1/22/80 1/23/80 1/24/80 1 /25/80 1 /28/SO 1/29/80 1/30/80 1/31/80 2/1/80 2/4/80 2/5/80 2/6/80 2/7/80 2/8/80 2/11/80 2/12/80 2/13/80 2/14/80 2/15/80 2/18/80 2/19/80 2/20/80 1 2 3 4 5 8 9 10 11 12 15 16 17 18 19 22 23 24 25 26 29 30 31 32 33 36 37 38 39 40 43 44 45 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 0.6 0.8 6 3.6 6 3.6 0.7 0.7 6 4.2 12 7.8 0.5 0.5 6 3.0 18 10.8 1.4 0.4 6 8.4 24 19.2 0.8 0.5 6 4.8 30 24.0 0.5 0.4 6 3.0 36 27.0 0.3 0.4 6 1.8 42 28.8 0.8 0.6 6 4.8 48 33.6 0.5 0.5 6 3.0 54 36.6 0,5 0.3 6 3.0 60 39.6 1.1 0.7 6 6.6 66 46.2 1.0 0.6 6 6.0 72 52.2 0.9 0.6 6 5.4 78 57.6 1.6 0.5 6 9.6 84 67.2 1.2 0.6 6 7.2 90 74.4 1.2 0.6 6 7.2 96 81.6 1.4 0.4 6 8.4 102 90.0 0.9 0.5 6 5.4 108 95.5 1.3 0.4 6 7.8 114 103.2 1.1 0.4 6 6.6 120 109.8 1.5 0.9 6 9.0 126 118.8 1.2 0.4 6 7.2 132 126.0 0.7 0.5 6 4.2 138 130.2 1.5 0.7 6 9.0 144 139.2 0.7 0.3 6 4.2 150 143.4 0.4 0.4 6 2.4 156 145.8 0.8 0.3 6 4.8 162 150.6 0.9 0.6 6 5.4 168 156.0 0.7 0.9 6 4.2 174 160.2 1.1 1.2 6 6.6 180 166.8 1.5 0.4 6 9,0 186 175.8 0.5 0.6 6 3.0 192 178.8 1.2 0.5 6 7.2 198 186.0 0.6 0.7 0.6 0.8 0.8 0.8 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.8 0.8 0.9 0.9 0.9 0.9 0.9 0.9 1.0 0.9 1.0 1.0 0.9 0.9 0.9 0.9 0.9 0.9 0.9 0.9 no oe.77;'] CONFIDENTTAl YZ0014376 / A-21 79-2425 Appendix A (cont.) Table 4 (cont.) A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Pre-Mating Treatment Period Group II - 1 ppm (cont.) Date Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Day Number tratlon SD Hours Hours Hours Hours tratlon 2/21/80 2/22/80 2/25/80 2/26/80 2/27/80 2/28/80 2/29/80 3/3/80 3/4/80 3/5/80 3/6/80 3/7/RO 3/10/80 3/11/80 3/12/80 46 47 50 51 52 53 54 57 58 59 60 61 64 65 66 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 1.2 0.3 6 0.9 0.3 6 1.0 0.4 6 0.8 0.6 6 0.8 0.7 6 1.1 0.4 6 3.5 4.9 6 1.3 0.7 6 1.0 0.4 6 0.8 0.3 6 1.4 0.3 6 0.9 0.8 6 1.1 0.7 6 1.2 0.5 6 1.0 0.4 6 7.2 204 193.2 5.4 210 198.6 6.0 216 204.6 4.8 222 209.4 4.8 228 214.2 6.6 234 220.8 21.0 240 241.8 7.8 246 249.6 6.0 252 255.6 4.8 258 260.4 8.4 264 268.8 5.4 270 274.2 6.6 276 280.8 7.2 282 288.0 6.0 288 294.0 0.9 0.9 0.9 0.9 0.9 0.9 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Ml ran 04 3/13/80 67 49 3/14/80 68 50 0.8 1.1 6 0.3 0.4 6 4.8 294 298. R 1.8 300 300.6 1.0 1.0 Dn 0677?? C0Nf7TDFNTTAt. YZ0014377 A-22 79-2426 Appendix A (cont.) Table 5 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Hating Period Group II - 1 ppm ----------- -------- ---------------------------------------------- CumuTaftve Mean Inte- Oally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Goncen- Date Dav Number tratlon 5D Hours Hours Hours_ Hours tratlon Ml ran 04 3/17/80 71 51 0.3 0.4 6 3/18/80 72 52 1.4 0.6 6 3/19/80 73 53 0.4 0,4 6 3/20/80 74 54 0.4 0.6 6 3/21/80 75 55 0.0 0.0 6 3/24/80 78 58 0.8 0.5 6 3/25/80 79 59 1.0 0.4 6 3/26/80 80 60 1.3 0,3 6 3/27/80 81 61 0.7 0.5 6 3/28/80 82 62* 1.1 0.5 6 3/31/80 85 65 0.8 0.3 6 4/1/80 86 66 1.0 0.6 6 4/2/80 87 67 0.7 0.3 6 4/3/80 88 68 0.9 0.6 6 4/4/80 89 69* 0.6 0.2 6 4/7/80 92 72 0.6 0.5 6 4/8/80 93 73 0.2 0.4 6 1.8 8.4 2.4 2.4 0.0 4.8 6.0 7.8 4.2 6.6 4.8 6.0 4.2 5.4 3.6 3.6 1.2 6 1.8 0.3 12 10.2 0.9 18 12.6 0.7 24 15.0 0.6 30 15.0 0.5 36 19.8 0.6 42 25.8 0.6 48 33.6 0.7 54 37.8 0.7 60 44.4 0.7 66 49.2 0.7 72 55.2 0.8 78 59.4 0.8 84 64.8 0.8 90 68.4 0.8 96 72.0 0.8 102 73.2 0.7 ^Exposure mmbers 56, 57, 63, 64, 70, and 71 for animals receiving exposure during the gestation period. DO 067773 CONFIDFNTTAt YZ0014378 A-23 79-2425 Appendix A (eont.) Table 6 A Female Fertility Study In Rats with Benzene emulative Exposure Record Gestation Period Group II - 1 ppm ...................... ... Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Goncen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Date Pay Number tratlon SO Hours Hours Hours Hours, tratlon Ml ran 04 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/22/80 3/23/80 3/24/80 3/25/80 3/26/80 3/27/80 3/28/80 3/29/80 3/30/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 4/5/80 4/6/80 4/7/80 4/8/80 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 GC 4/9/80 94 4/10/80 95 4/11/80 96 4/12/80 97 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 0.3 0.4 6 1.8 6 1.8 0.3 1.4 0.6 6 8.4 12 10.2 0.9 0.4 0.4 6 2.4 18 12.6 0.7 0.4 0.6 6 2.4 24 15.0 0.6 0.0 0.0 6 0.0 30 15.0 0.5 1.1 0.1 6 6.6 36 21.6 0.6 0.6 0.4 6 3.6 42 25.2 0.6 0.8 0.5 6 4.8 48 30.0 0.6 1.0 0.4 6 6.0 54 36.0 0.7 1.3 0.3 6 7.8 60 43.8 0.7 0.7 0.5 6 4.2 66 48.0 0.7 1.1 0.5 6 6.6 72 54.6 0.8 0.9 0.2 6 5.4 78 60.0 0.8 1.2 0.2 6 7.2 84 67.2 0.8 0.8 0.3 6 4.8 90 72.0 0.8 1.0 0.6 6 6.0 96 78.0 0.8 0.7 0.3 6 4.2 102 82.2 0.8 0.9 0.6 6 5.4 108 87.6 0.8 0.6 0.2 6 3.6 114 91.2 0.8 0.3 0.3 6 1.8 120 93.0 0.8 0.8 0.3 6 4.8 126 97.8 0.8 0.6 0.5 6 3.6 132 101.4 0*8 0.2 0.4 6 1.2 138 102.6 0.7 1.0 0.1 6 6.0 144 108.6 0.8 1.3 0,1 6 7.8 150 116.4 0.8 1.1 0.1 6 6.6 156 123.0 0.8 1.3 0.1 6 7.8 162 130.8 0.8 0677?4 CONFrDFNTTAl YZOO14379 J A-24 79-2425 Appendix A (cont.) Table 7 A Female Fertility Study In Rats with Benzene Cunulatlve Exposure Record Lactation Period Group 11-1 ppm Date Cumulative Mean Into nally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Day Number tratlon SD Hours Hours Hours Hours tratlon Ml ran 04 4/7/80 92 72 0.6 0.5 6 3.6 6 3.6 0.6 4/8/80 93 73 0.2 0.4 6 1.2 12 4.8 0.4 GC 4/9/80 94 74 1.0 0.1 6 6.0 18 10.8 0.6 4/10/80 95 75 1.3 0.1 6 7.8 24 18.6 0.8 4/11/80 96 76 1.1 0.1 6 6.6 30 25.2 0.8 4/12/80 97 77 1.3 0.1 6 7.8 36 33.0 0.9 4/13/80 98 78 1.1 0.1 6 6.6 42 39.6 0.9 4/14/80 99 79 1.2 0.1 6 7.2 48 46.8 1.0 4/15/80 100 80 1.1 0.1 6 6.6 54 53.4 1.0 4/16/80 101 81 1.2 0.1 6 7.2 60 60.6 1.0 4/17/80 102 82 1.2 0.2 6 7.2 66 67.8 1.0 4/18/80 103 83 1.3 0.1 6 7.8 72 75.6 1.0 4/19/80 104 84 1.1 0.2 6 6.6 78 82.2 1.1 4/20/80 105 85 1.4 0.2 6 8.4 84 90.6 1.1 4/21/80 106 86 1.2 0.2 6 7.2 90 97.6 1.1 4/22/80 107 87 1.2 0.1 6 7.2 96 105.0 1.1 4/23/80 108 88 1.3 0.3 6 7.8 102 112.8 1.1 4/24/80 109 89 1.2 0.2 6 7.2 108 120.0 1.1 4/25/80 no 90 1.2 0.1 6 7.2 114 127.2 1,1 4/26/80 111 91 1.1 0.1 6 6.6 120 133.8 1.1 4/27/80 112 92 1.2 0.2 6 7.2 126 141.0 1.1 4/28/80 113 93 1.2 0.2 6 7.2 132 148.2 1.1 4/29/80 114 94 1.2 0.2 6 7.2 138 155.4 1.1 4/30/80 115 95 1.2 0.1 6 7.2 144 162.6 1.1 5/1/80 116 96 1.2 0.2 6 7.2 150 169.8 1.1 5/2/80 117 97 1.2 0.2 6 7.2 156 177.0 1.1 5/3/80 118 98 1.3 0.3 6 7.8 162 184.8 1.1 5/4/80 119 99 1.2 0.2 6 7.2 168 192.0 1.1 5/5/80 120 100 1.3 0.3 6 7.8 174 199.8 1.1 5/6/80 121 101 1.3 0.2 6 7.8 180 207.6 1.2 5/7/80 122 102 1.3 0.1 6 7.8 186 215.4 1.2 5/8/80 123 103 1.3 0.2 6 7.8 192 223.2 1.2 5/9/80 124 104 1.3 0.1 6 7.8 198 231.0 1.2 5/12/80 127 105 1.2 0.1 6 7.2 204 238.2 1.2 00 067725 OONFTDFNTTAI. YZOO14380 Appendix A (cunt.) Table 8 A Female Fertility Study In Rats with Benzene 79-2425 Individual Exposure Record for Group II* 2 Pre-Hatlnd' Hating I--------------- -------------------------------- a------Gestation* lactation3 ................... ......T-- Post-Lactation' Cuoul atlve Total^ Ctmil at1* Cumulative Omul atlve Cuaulatlve Cumulative Cumul atlve Hean Test Hean Test Hean Test Hean Hean Hean Nwtwr Exposure Days Umber Exposure Days Number Exposure Days Umber Exposure Nwber Exposure timber Exposure An. of Concern- of of Concern- Ho. Exposures tratIon Exposure Exposures tratIon tpi) (PP) of of ConcernExposure Exposures tratlon (Pi") (PP*) of of GoncenExposure Exposures tration (ppm) of ConceitExposures tration tPF} of ConcernExposures tration (PP") 425 426 427 42B 429 430 431 432 433 434 435 436 437* 438 439 440 441 442 443 444 445 446* 447 448 449 450 50 50 50 SO 50 50 50 50 SO so 50 50 50 50 50 SO 50 SO 50 50 SO 50 50 50 50 50 1.0 1.0 1.0 1.0 . 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 71-73 .. 71-73 71-72 71 71-76 71-72 71 71-74 71 71-73 71-73 71-93 71-72 71-73 71-72 71-72 71-73 _ 71-93 71-74 71 71-75 - 3 3 2 1 5 2 I 4 1 3 3 17 2 3 2 2 3 - 17 4 l 5 - 0.7 74-94 21 - 71-91 21 0.8 101-117 17 0.8 98-114 17 0.7 74-94 21 0.8 b 0.9 73-93 21 0.7 100-116 17 0.3 72-92 21 O.fl 99-115 17 0.5 77-97 2! 0.9 b 0.9 73-93 21 0.7 99-115 17 0.3 72-3? 21 0.8 98-114 17 0.6 75-95 21 O.B 102-118 17 0.3 72-92 21 0.8 98-114 17 0.7 74-94 21 0.8 101-117 17 0.7 74-94 21 0.8 101-117 17 0.7 -. 0.9 73-93 21 0.7 100-116 17 0.7 74-9* 21 0.8 100-116 17 0.9 73-93 21 0.7 100-116 17 0,9 73-93 21 0.7 100-116 17 . 71-91 21 0.8 98-114 17 0.7 74-9* 21 0.8 101-117 17 71-91 21 0.8 98-114 17 . 71-91 21 0.7 - . 0.8 98-114 17 . 0.6 75-95 21 0.8 102-118 17 0.3 72-92 21 0.8 98-114 17 0.5 76-96 21 0.9 104-120 17 - 71-91 21 0.8 98-114 17 1.2 1.2 1.2 1.2 - 1.2 1.2 1.2 1.2 1.2 1.2 . 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 - 1.2 1.2 1.2 1.2 5 1.3 96 1.0 8 1.3 96 1.0 - 74 0.9 6 1.3 96 1.0 7 1.3 96 1.0 - 76 0.9 7 1.3 97 1.0 8 1.3 97 1.0 5 1.3 97 1.0 8 1.3 97 1.0 5 1.3 96 1.0 S 1.3 96 1.0 - 67 0.9 6 1.3 96 1.0 7 1.3 9B 1.0 7 1.3 97 1.0 7 1.3 97 1.0 9 1.3 97 1.0 6 1.3 97 1.0 9 1.3 97 1.0 9 1.3 97 1.0 . m 67 0.9 6 1.3 SB 1.0 7 1.3 96 1.0 5 1.3 98 1.0 9 1.3 97 1.0 ^Individual crneul atlve exposure concentrations taken directly fraa Tables 4 and 5 for the prematlng and mating period, respectively. q ~j `Individual cuavlative exposure concentrations Mere calculated using Table 6 for the gestation period. Using anInal raaber 425 as an exaaple, a total -z o of 21 exposures Mere received during the oestatlon period (Days 74-94, Inclusive). Bering this period, a total of 126 exposure hours (144 - 18 126) ~ri and a total of 136.2 concentration hours (146-8 - 12.6 136.2) uere aceiamlated. Ihe cuaulatlve exposure concentration for this period was 1.1 ppm ^ (136.2 * 126 - 1.1). 2 J ^individual CHMlatlve exposure concentrations mere calculated using Table 7 for the lactation period using the procedure described for the gestation 2 ^ nerlod. _i \> *20st-lactation concentrations uere obtained by averaging the dally exposure concentrations that uere obtained post-lactation for each animal. h O' 5lbe total emaelatlve exposure concentration was calculated by dividing the total cuaulatlve exposure concentration of the pre-mating, mating, gesta- 1> tlem, lactation, and post-lactation periods by the total nmfter of exposures. *< BRetaal not mated, sacrificed 4/9/80. N Ax Inal did not deliver pops, no expnswci received daring lactation or post-lactation period. A-2S Jb. W 00 A-26 79-2425 Appendix A (cont.) Table 9 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Pre-mating Treatment Period Group III - 10 ppm 1 --- - Cumulative Date Mean Dally Dally Total Exposure Dally Concen- Total Concen- Test Exposure Concen- Exposure tratlon Exposure tratlon Day Number tratlon SD Hours Hours Hours Hours Integrated Mean Concen- tratlon Ml ran L 1/7/80 1/8/80 1/9/80 1/10/80 1/11/80 1/14/80 1/15/80 1 /16/Bn 1/17/80 1/18/80 1/21/80 1 /22/80 1 /23/80 1 /24/80 1/25/80 1/28/80 1 /29/80 1/30/80 1/31/80 2/1/80 2/4/80 2/5/80 2/6/80 2/7/80 2/8/80 2/11/80 2/12/80 2/13/80 2/14/80 2/15/80 2/18/80 2/19/80 2/20/80 2/21/80 2/22/80 1 2 3 4 5 8 9 10 11 12 15 16 17 18 19 22 23 24 25 26 29 30 31 32 33 36 37 38 39 40 43 44 45 46 47 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 9.4 0.8 6 8.6 2.7 6 8.7 1.0 6 9.7 0.4 6 7.8 2.1 6 8.6 0.8 6 8.7 0.7 6 9.2 0.6 6 7.4 0.4 6 8.6 0.5 6 9.6 0.3 6 8.9 0.4 6 8.5 0.7 6 9.7 0.4 6 11.5 0.7 6 12.4 1.6 6 10.4 1.4 6 10.1 1.1 6 9.8 2.1 6 9.3 1.6 6 10.2 3.4 6 12.7 2.6 6 8.6 0.9 6 9.5 0.8 6 10.0 1.4 6 9.4 1.0 6 8.5 2.9 6 11.3 2.3 6 9.6 1.1 6 10.4 1.6 6 10.6 1.3 6 8.9 0.6 6 10.5 1.3 6 11.2 1.2 6 9.7 1.3 6 56.4 6 56.4 9.4 51.6 12 108.0 9.0 52.2 18 160.2 8.9 58.2 24 218.4 9.1 46.8 30 265.2 8.8 51.6 36 316.8 8.8 52.2 42 369.0 8.8 55.2 48 424.2 8.8 44.4 54 468.6 8.7 51.6 60 520.2 8.7 57.6 66 577.8 8.8 53.4 72 631.2 8.8 51.0 78 682.2 8.7 58.2 84 740.4 8.8 69.0 90 809.4 9.0 74.4 96 62.4 102 883.8 946.2 9.2 9.3 60.6 108 1006.8 9.3 58.8 114 1065.6 9.3 55.8 120 1121.4 9.3 61.2 126 1182.6 9.4 76.2 132 1258.8 9.5 51.6 138 1310.4 9.5 57.0 144 1367.4 9.5 60.0 150 1427.4 9.5 56.4 156 1483.8 9.5 51.0 162 1534.8 9.5 67.8 168 1602.6 9.5 57.6 174 1660.2 9.5 62.4 180 1722.6 9.6 63.6 186 1786.2 9.6 53.4 192 1839.6 9.6 63.0 198 1902.6 9.6 67.2 204 1969.8 9.7 58.2 210 2028.0 9.7 no Co mf 6?7o7 JfNT tai YZOO14382 A-27 79-2425 Appendix A (cont.) Table 9 (cont*) A Female Fertility Study In Rats with Benzene Cunulatlve Exposure Record Pre-mating Treatment Period Group 111 10 ppm (cont*) Date 1 tumulatlve Mean Inte- Dally Dally Total grated Exposure DallyConcen- Total Concen* Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Day Number tratlon SD Hours Hours Hours Hours tratlon 2/25/80 2/26/80 2/27/80 2/28/80 2/29/80 3/3/80 3/4/80 3/5/80 3/6/80 3/7/80 3/10/80 3/11/80 3/12/80 50 51 52 53 54 57 58 59 60 61 64 65 66 36 37 38 39 40 41 42 43 44 45 46 47 48 10.1 0.7 6 10.2 1.6 6 10.3 0.7 6 10.4 0.8 6 8.1 4.0 6 10.2 1.2 6 10.4 0.6 6 10.6 0.5 6 10.6 0.7 6 10.4 1.0 6 9.4 0.7 6 11.4 1.4 6 9.6 0.6 6 60.6 216 61.2 222 61.8 . 228 62.4 234 48.6 240 61.2 246 62.4 252 63.6 258 63.6 264 62.4 270 56.4 276 68.4 282 57.6 288 2088.6 2149.8 2211.6 2274.0 2322.6 2383.8 2446.2 2509.8 257 3.4 2635.8 2692.2 276 0.6 2818.2 9.7 9.7 9,7 9.7 9.7 9.7 9.7 9.7 9.7 9.8 9.8 9.R 9.8 HI ran 04 3/13/80 67 49 3/14/80 68 50 10.3 1.0 6 9.3 0.9 6 61.8 294 2880.0 9.8 55.8 300 2935.8 9.8 ^>0 0677,^8 CONFIDFNT TAl YZ0014383 A-2 8 79-2425 Appendix A (cont.) Table 10 A Female Fertility Study In Rats with Benzene Cunulatlve Exposure Record Mating Period Group III - 10 ppm -- Mean Dally Exposure Test Exposure ConcenDate Day Humber tration Cumulative Dally InteTotal grated Dally Concen- Total Concen- Mean Exposure tratlon Exposure tratlon Concen- SP Hours Hours Hours Hours. tra.t1o_n_ Ml ran 04 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/24/80 3/25/80 3/26/80 3/2 7/80 3/28/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 71 72 73 74 75 78 79 80 81 82 85 86 87 88 89 51 52 53 54 55* 58 59 60 61 62* 65 66 67 68 69 9.1 9.5 9.3 9.3 8.9 9.8 10.2 11.0 10.0 12.1 8.0 10.2 9.9 9.5 9.7 0.6 6 0.8 6 1.2 6 2.1 6 1.6 6 0.5 6 0.4 6 0.7 6 0.7 6 1.4 6 2.7 6 1.3 6 0.8 6 1.0 6 0.9 6 54.6 57.0 55.8 55.8 53.4 58.8 61.2 66.0 60.0 72.6 48.0 61.2 59.4 57.0 58.2 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 54.6 111.6 167.4 223.2 276.6 335.4 396.6 462,6 522.6. 595.2 643.2 704.4 763.8 820.8 879.0 9.1 9.3 9.3 9.3 9.2 9.3 9.4 9.6 9.7 9.9 9.7 9.8 9.8 9.8 9.8 ^Exposure ntmbers 56, 57, 63, and 64 for animals receiving exposure during the gestation period. oo o^7 10? c YZ0014384 A-29 79-2425 Appendix A (cont.) Table 11 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Gestation Period Group III - 10 ppm Date Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Day Number tratlon SD Hours Hours Hours Hours tratlon Ml ran 04 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/22/80 3/23/80 3/24/80 3/25/80 3/26/80 3/27/80 3/28/80 3/29/80 3/30/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 4/5/80 4/6/80 4/7/80 4/8/80 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 9.1 0.6 6 9.5 O.R 6 9.3 1.2 6 9.3 2.1 6 8.9 T.6 6 10.0 0.8 6 8.8 0.8 6 9.8 0.5 6 10.2 0.4 6 11.0 0.7 6 10.0 0.7 6 12.1 1.4 6 9.7 0.7 6 9.9 1.0 6 8.0 2.7 6 10.2 1.3 6 9.9 0.8 6 9.5 1.0 6 9.7 0.9 6 8.9 1.2 6 9.7 0.5 6 9.7 1.0 6 8.8 0.7 6 54.6 6 54.6 57.0 12 111.6 55.8 18 167.4 55.8 24 223.2 53.4 30 276.6 60.0 36 336.6 52.8 42 389.4 58.8 48 448.2 61.2 54 509.4 66.0 60 575.4 60.0 66 635.4 72.6 72 708.0 58.2 78 766.2 59.4 84 825.6 48.0 90 873.6 61.2 96 934.8 59.4 102 994.2 57.0 108 1051.2 58.2 114 1109.4 53.4 120 1162.8 58.2 126 1221.0 58.2 132 1279.2 52.8 138 1332.0 9.1 9.3 9.3 9.3 9.2 9.3 9.3 9.3 9.4 9.6 9.6 9.8 9.8 9.8 9.7 9.7 9.7 9.7 9.7 9.7 9.7 9.7 9.7 GC 4/9/80 94 4/10/80 95 4/11/80 96 4/12/80 97 4/13/80 98 4/14/80 99 4/15/80 100 4/16/80 101 4/17/80 102 4/18/80 103 4/19/80 104 4/20/80 105 4/21/80 106 4/22/80 107 74 75 76 77 78 79 80 81 82 83 84 85 86 87 11.9 0.8 6 13.3 0.4 6 12.9 0.7 6 12.9 1.7 6 12.8 0.8 6 14.1 1.7 6 12.5 1.0 6 12.8 1.3 6 13.8 0.9 6 12.3 1.3 6 12.2 1.3 6 12.6 0.7 6 12.7 0.6 6 13.1 1.9 6 71.4 144 1403.4 9.7 79.8 150 1483.2 9.9 77.4 156 1560.6 10.0 77.4 162 1638.0 10.1 76.8 168 1714.8 10.2 84.6 174 1799.4 10.3 75.0 180 1874.4 10.4 76.8 186 1951.2 10.5 82.8 192 2034.0 10.6 73.8 198 2107.8 10.6 73.2 204 2181.0 10.7 75.6 210 2256.6 10.7 76.2 216 2332.8 10.8 78.6 222 2411.4 10.9 YZ0014385 A-30 Appendix A (cont.) Table 12 A Female Fertility Study In Rats with Benzene 79-2425 emulative Exposure Record Lactation Period Group 111 - 10 ppm Oate Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Day Number tratlon SD Hours Hours Hours Hours tratlon Mlran 04 4/7/80 92 4/8/80 93 GC 4/9/80 4/10/80 4/11/80 4/12/80 4/13/80 4/14/80 4/15/80 4/16/80 4/17/80 4/18/80 4/19/80 4/20/80 4/21/80 4/22/80 4/23/80 4/24/80 4/25/80 4/26/80 4/2 7/80 4/28/80 4/29/80 4/30/80 5/1/80 5/2/80 5/3/80 5/4/80 5/5/80 5/6/80 5/7/80 5/8/80 5/9/80 5/10/80 5/11/80 5/12/80 5/13/80 5/14/80 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 no in 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 72 73 74 75 76 77 78 79 80 81 62 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 9.7 1.0 6 8.8 0.7 6 11.9 13.3 12.9 12.9 12.8 14.1 12.5 12.8 13.8 12.3 12.2 12.6 12.7 13.1 13.9 12.8 12.4 12.3 13.1 12.9 11.9 14.0 15.2 13.1 13.1 10.9 14.5 13.0 13.8 14.7 14.1 10.7 9.5 13.0 14.2 12.7 0.8 6 0.4 6 0.7 6 1.7 6 0.8 6 1.7 6 1.0 6 1.3 6 0.9 6 1.3 6 1.3 6 0.7 6 0.6 6 1.9 6 1.4 6 1.0 6 0.5 6 0.6 6 1.8 6 1.0 6 2.7 6 0.7 6 2.7 6 1.0 6 1.5 6 4.3 6 1.0 6 1.5 6 0.8 6 1.3 6 1.4 6 1.5 6 1.4 6 0.8 6 1.3 6 2.9 6 58.2 6 58.2 9.7 52.8 12 111.0 9.3 71.4 18 182.4 10.1 79.8 24 262.2 10.9 77.4 30 339.6 11.3 77.4 36 417.0 11.6 76.8 42 493.8 11.8 84.6 48 578.4 12.1 75.0 54 653.4 12,1 76.8 60 730.2 12.2 82.8 66 813.0 12.3 73.8 72 886.8 12.3 73.2 78 960.0 12.3 75.6 84 1035.6 12.3 76.2 90 1111.8 12.4 78.6 96 1190.4 12.4 83.4 102 1273.8 12.5 76.8 108 1350.6 12.5 74.4 114 1425.0 12.5 73.8 120 1498.8 12.5 78.6 126 1577.4 12.5 77.4 132 1654.8 12.5 71.4 138 1726.2 12.5 84.0 144 1810.2 12.6 91.2 150 1901.4 12.7 78.6 156 1980.0 12.7 78.6 162 2058.6 12.7 65.4 168 2124.0 12.6 87.0 174 2211.0 12.7 78.0 180 2289.0 12.7 82.8 186 2371.8 12.8 88.2 192 2460.0 12.8 84.6 198 2544.6 12.9 64.2 204 2608.8 12.8 57.0 210 2665.8 12.7 78.0 216 2743.8 12.7 85.2 222 2829.0 12.7 76.2 228 2905.2 12.7 n 067731 CONFrDFNT TAI. YZ0014386 I oo o zn o -o< o O' "ft Si z vj --4 CO ^ 3> hppendli * (cant.) Table 13 I Fenele Fertility ftedr In btt tth hemeno TMS MIMhI Eiieurr Record for Croup III Fre-Hattad* htina E destotfon* lactation 1 Pott-Leetatloe* Qaelatfoe Total*0 An* hb. Usher f taootarot Matin Men Eaponre ConceittretInn sett Dayt *f tipnswe IlMftr txKurM Caaalatlvc Mean (aposere Concentrotfan Tort Opyt of Eaoooaro CMlJttve Man ( Exposure 9* COncen- Eipoaorot trptlon Tott Ibjn hater of of Fapotore Eantero* emulative Ifca* Expotaro C&fKCTK trotIon Ihi^wr Uwww CiMlatfva Mem Exposure Coaceotrattan Btear of Exposures Canalattve ban Exposure Conceittrettna (non) " (*Pn) (*) (nan) iPPnJ (non) (opn) i SO 121 so Cl so 08 so in so 830 so 31 so (37 so (33 so (34 so (35 so CM so at 50 ns so 131 so (40 so Ml so HI so (43 so (44 so MS so 64* so M7 so (40 so MS so 650 so S.8 71-7* S.8 71-85 hi 71 S.B 71 S.8 71-73 S.8 71 t.e 71-77 S.8 71 8.8 71-75 S.1 71-81 SlO 71 M 71-73 S.8 71-73 S.8 71-88 S.8 71-78 S.8 71 0.8 71-7* S.8 71-73 S.8 71 S.8 71-77 S.8 71 S.8 71-7* S.8 71-7* S.8 71-7* S.8 71 S.8 71-78 * w a. 3 S 1 s s 1 3 3 13 S 1 2 3 1 1 t I I 1 5 S.3 73-SI It S.7 100-1M 17 13.0 S.7 86-106 *1 ll.t 113-US 17 13.0 S.1 R-S* *1 S.7 SO-1)4 17 11.8 * H-K *1 S.7 S8-114 17 12.8 S.3 74-SI *1 S.8 f _ 7*-S* *1 S.7 S8-114 17 H. S.* 78-SO *1 m.s 305-1*1 17 13.0 S.1 R-se *1 S-7 99-115 17 H.S x* 76-96 II M.I 103-119 17 12.9 9.7 82-10* *1 lt.1 10S-12S 17 1X1 S.1 R-K *t S.7 SS-115 17 H.S S.1 74-St *1 S.8 107-118 17 13.0 S.1 71-SI *1 S.8 101-117 17 1X0 S.8 87-W7 II 11.7 a * S.Z 77-S7 *1 10.3 104-1*0 17 1X0 S.1 R-S* *1 S.7 ss-m 17 H.S S.3 73-93 *1 S.7 100-116 17 13.0 S.1 74-94 *1 S.8 16Z-110 17 13.0 S.1 77-9* 21 S.7 SS-115 17 H.S x* 78-98 *i W.5 1M-120 17 13.0 R-S* *i S.7 98-1)4 . 17 12.0 S.1 73-S3 S.7 SS-115 17 H.S S.3 73-93 zt S.7 100-1K 17 13.0 S.3 73-SJ *1 t.7 100-116 17 13.0 8.1 R-S* *1 S.7 9S-I1S 17 H.S S.* 77-S7 *1 W.3 103-1 IS 17 H.S 1 13.9 8 M.1 8 H.1 8 M.1 3 H.Z 7 M.1 S M.O 8 M.1 5 M.O S M.O S n.7 8 n.s 7 13.7 S M.O 8 .s 5 1X7 S 13. S 8 1X1 7 1X7 7 13.7 8 13.9 S 13.7 SS 10.8 1C 10-7 ft 10.7 ft 10.7 74 X8 ft M.7 ft 10.6 96 M.1 98 10.6 97 10.7 97 10.0 96 10.6 96 W.f 84 . 3 98 10.6 97 10.7 ft H7. 9t 10.6 ft 10.5 98 10.7 97 10,7 SS 10.8 97 W.S 97 10.8 97 10.7 98 n.d iftdfvtonl coeolatlre aeonorm concmtrattoo* UUn directly fr<m Trtlet * and 10 for the rK*w aid natto* pertod, respectively. 'ladtvMai Mriitlw amri (ancMttlttMi arc calculated ala tibia 11 for tbe dotation pertad. Mins aitait i--tiw 625 n an eaao4e total - Of *1 HMWH aero racafrad dartnd tfca antatton period (8ey 73-tt. Inctolve). Ihrfop tbit period. a total or Hi eqinirt boon (138-17-U4) end .*(n**j*i*t*in*fwIt*,7.t*. cooceatrottoa hoar* (DK,t>ljl>t!At) art accaotlatad. *a cw>l ottvo Oman concentration *ar thlt nortod <* *.7 ppo *in01v(dMl CamaIlaa tloo < i concentrations utro catcalatad to labl* 17 for the lactattoa prtd otlof Do procadore desertbed 0r the oeototton t*Po*.1actotleo cancontrat torn aero eHalnod by aoeroflad the dally oepoaare coocentratteoa that aero obtained port-lactattea for each anhul. **' BOl*t1oo oapopare caacoatrattaa aei catcalatad by dlvldlne tbe total caaailottvo apran concentration or tbe pro notlne. nettop, fntattea, 1 octetlea, and pa*t-lacUtlon parted* by the total neebor ef oepatarei. ***< dM eat doltvor paps, ee aaooaeree rocatred darted lectatlea or pott-lecutlaa period. *-Jt YZ0014387 A- 32 79-2425 Appendix A (cont.) Table 14 A Female Fertility Study In Rats with Benzene emulative Exposure Record Pre-Mating Treatment Period Group IV - 30 ppm Date Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Ooncen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen Day Number tratlon SO Hours Hours Hours Hours tration Ml ran l 1/7/80 1 1/8/80 2 1/9/80 3 1/10/80 4 1/11/80 5 1/14/80 8 1/15/80 9 1/16/80 10 1/17/80 11 1/18/80 12 1/21/80 15 1/22/80 16 1/23/80 17 1/24/80 18 1 /25/80 19 1/28/80 22 1 /29/80 23 1/30/80 24 1/31/80 25 2/1/80 26 2/4/80 29 2/5/80 30 2/6/80 31 2/7/80 ,32 2/8/80 33 2/11/80 36 2/12/80 37 2/13/80 38 2/14/80 39 2/15/80 40 2/18/80 43 2/19/80 44 2/20/80 45 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 26.3 8.5 6 157.8 6 157.8 26.3 35.4 7.6 6 212.4 12 370.2 30.9 32.7 1.3 6 196.2 18 566.4 31.5 32.2 2.0 6 193.2 24 759.6 31.7 28.5 5.5 6 171.0 30 930.6 31.0 32.7 2.4 6 196.2 36 1126.8 31.3 32.2 2.0 6 193.2 42 1320.0 31.4 28.5 6.8 6 171.0 48 1491.0 31.1 30.6 2.7 6 183.6 54 1674.6 31.0 30.1 2.6 6 180.6 60 1855.2 30.9 29.0 6.7 6 174.0 66 2029.2 30.7 29,3 2.2 6 175.8 72 2205.0 30.6 29,5 2.4 6 177.0 78 2362.0 30.5 29.5 1.3 6 177.0 84 2559.0 30.5 29.5 1.3 6 177.0 90 2736.0 30.4 32.2 2.0 6 193.2 96 2929.2 30.5 32.8 3.2 6 196.8 102 3126.0 30.6 29.0 2.9 6 174.0 108 3300.0 30.6 30.6 4.0 6 183.6 114 3483.6 30.6 32.2 2.0 6 193.2 120 3676.8 30.6 33.3 4.8 6 199.8 126 3876.6 30.7 32.2 0.0 6 193.2 132 4069.8 30.8 31.7 1.3 6 190.2 138 4260.0 30.9 30.1 1.7 6 180.6 144 4440.6 30.8 30.6 1.8 6 183.6 150 4624.2 30.8 29.5 1.3 6 177.0 156 4801.2 30.8 31.1 2.6 6 186.6 162 4987.8 30.8 30.6 3.4 6 183.6 168 5171.4 30.8 29.0 2,1 6 174.0 174 5345.4 30.7 29.5 1.3 6 177.0 180 5522.4 30.7 29.5 1.3 6 177.0 186 5699.4 30.6 29.5 1.3 6 177.0 192 5876.4 30.6 29.5 1.3 6 177.0 198 6053.4 30.6 DO 067733 CONFIDENT I A[ YZ0014388 A-33 79-2425 Appendix A (cont.) Table 14 (cont.) A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Pre-Mating Treatment Period Group IV - 30 ppm (cont.) Date " ~ Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concert- Day Number tratlon SD Hours Hours Hours Hours tratlon 2/21/80 46 34 30.1 2.6 6 2/22/80 47 35 29.5 1.3 6 2/25/80 50 36 29.5 1.3 6 2/26/80 51 37 29.5 2.4 6 2/27/80 52 38 29.0 2.1 6 2/28/80 53 39 30.1 1.7 6 2/29/80 54 40 28.5 1.3 6 3/3/80 57 41 30.6 2.7 6 3/4/80 58 42 30.1 1.7 6 3/5/80 59 43 29.5 1.3 6 3/6/80 60 44 30.1 1.7 6 3/7/80 61 45 29.5 1.3 6 3/10/80 64 46 29.0 2.1 6 3/11/80 65 47 29.5 1.3 6 3/12/80 66 48 30.1 3.3 6 Mi ran 04 3/13/80 67 49 30.1 1.4 6 3/14/80 68 50 30.7 2.2 6 180.6 177.0 177.0 177.0 174.0 1R0.6 171.0 183,6 180.6 177.0 180.6 177.0 174.0 177.0 180.6 204 210 . 216 222 228 234 240 246 252 258 264 270 276 282 288 6234.0 6411.0 6588.0 6765.0 6939.0 7119.6 7290.6 7474.2 7654.8 7831.8 8012.4 8189.4 8363.4 8540.4 8721.0 30.6 30.5 30.5 30.5 30.4 30.4 30.4 30.4 30.4 30.4 30.4 30.3 30.3 30.3 30.3 180.6 294 8901.6 184.2 300 9085.8 30.3 30.3 " I I __________ DO 067734 CONFTDFNT IAl YZ0014389 A-34 79-2425 Appendix A (cont.) Table 15 A Female Fertility Study In Rats with Benzene Cunulatlve Exposure Record Mating Period Group IV - 30 ppm Date Mean Dally Exposure Test Exposure Concen- Day Number tratlon Cumulative Inte- Dally Total grated Dally Concen- Total Concen- Mean Exposure tratlon Exposure tratlon Concen- SD Hours Hours Hours Hours tratlon Ml ran 04 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/24/80 3/25/80 3/26/80 3/27/80 3/28/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 71 72 73 74 75 78 79 80 81 82 85 86 87 88 89 51 52 53 54 55 58 59 60 61 62 65 66 67 68 69 33.0 30.7 30.7 `31.9 30.2 30.7 31.3 32.4 29.6 30.2 29.6 31.3 31.3 30.1 30.7 1.8 6 3.1 6 2.2 6 2.8 6 2.6 6 0.0 6 1.4 6 2.9 6 1.8 6 2.6 6 1.8 6 3.4 6 1.4 6 1.4 6 2.2 6 198.0 6 198.0 33.0 184.2 12 382.2 31.9 184.2 18 566.4 31.5 191.4 24 757.8 31.6 181.2 30 939.0 33.0 184.2 36 1123.2 31.2 187.8 42 1311.0 31.2 194.4 48 1505.4 31.4 177.6 54 1683.0 31.2 181.2 60 1864.2 31.1 177.6 66 2041.8 30.9 187.8 72 2229.6 31.0 187.8 78 2417.4 31.0 180.6 84 2598.0 30.9 184.2 90 2782.2 30.9 Exposure numbers 56, 57, 63, and 64 for animals receiving exposure during the gestation period. DO 067735 OONFTDFNTT At YZOO14390 A-35 79-2425 Appendix A (cont.) Table 16 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Gestation Period Group IV - 30 ppm Cumulative Mean Inte- Pally Dally Total grated Exposure DallyConcen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Pate Day Number tratlon SO HoursHours Hours Hours tratlon Mi ran 04 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/22/80 3/23/80 3/24/80 3/25/80 3/26/80 3/27/80 3/28/80 3/29/80 3/30/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 4/5/80 4/6/80 4/7/80 4/8/80 4/9/80 4/10/80 4/11/80 4/12/80 4/13/80 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 33.0 30.7 30.7 31.9 30.2 32.4 30.1 30.7 31.3 32.4 29.6 30.2 30.2 31.3 29.6 31.3 31.3 30.1 30.7 31.3 31.3 30.7 29.6 31.9 30.7 31.3 29.6 30.2 1.8 6 3.1 6 2.2 6 2.8 6 2.6 6 4.2 6 1.4 6 0.0 6 1.4 6 2.9 6 1.8 6 2.6 6 2.6 6 1.4 6 1.8 6 3.4 6 1.4 6 1.4 6 2.2 6 5.0 6 1.4 6 2.2 6 1.8 6 2.8 6 2.2 6 3.4 6 1.8 6 2.6 6 198.0 184.2 184.2 191.4 181.2 194.4 180.6 184.2 187.8 194.4 177.6 181.2 181.2 187.8 177.6 187.8 187.8 180.6 184.2 187.8 187.8 184.2 177.6 191.4 184.2 187.8 177.6 181.2 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 114 120 126 132 138 144 150 156 162 168 198.0 382.2 566.4 757.8 939.0 1133.4 1314.0 1498.2 1686.0 1880.4 2058.0 2239.2 2420.4 2608.2 2785.8 2973.6 3161.4 3342.0 3526.2 3714.0 3901.8 4086.0 4263.6 4455.0 4639.2 4827.0 5004.6 5185.8 33.0 31.9 31.5 31.6 31.3 31.5 31.3 31.2 31.2 31.3 31.2 31.1 31.0 31.1 31.0 31.0 31.0 30.9 30.9 31.0 31.0 31.0 31.0 30.9 30.9 30.9 31.0 30.9 DO 067736 CONFTDFNTT Al YZ0014391 A-36 79-2425 Appendix A (cont.) Table 17 A Female Fertility Study In Rats with Benzene emulative Exposure Record lactation Period Group IV - 30 ppn tumul atlve Mean Inte- % Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon ConcenDate Day Number tratlon SO Hours Hours Hours Hours tratlon Ml ran 04 4/7/80 4/8/80 4/9/80 4/10/80 4/11/80 4/12/80 4/13/80 4/14/80 4/15/80 4/16/80 4/17/80 4/18/80 4/19/80 4/20/80 4/21/80 4/22/80 4/23/80 4/24/80 4/25/80 4/26/80 4/27/80 4/28/80 4/29/80 4/30/80 5/1/80 5/2/80 5/3/80 5/4/80 5/5/80 5/6/80 5/7/80 5/8/80 5/9/80 5/12/80 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 10 9 no m 112 113 114 115 116 117 118 119 120 121 122 123 124 12 7 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 30.7 29.6 31.9 30.7 31.3 29.6 30.2 31.9 29.0 31.3 31.9 29.6 31.9 30.7 30.1 32.4 30.1 30.2 31.9 31.3 30.7 31.3 29.6 30.1 30.7 29.6 30.7 30.1 32.4 30.2 30.7 31.9 30.1 30.2 2.2 6 1.8 6 2.8 6 2.2 6 3.4 6 1.8 6 2.6 6 4.7 6 1.9 6 3.4 6 2.8 6 1.8 6 5.2 6 2.2 6 1.4 6 4.2 6 1.4 6 2.6 6 2.8 6 1.4 6 3.8 6 1.4 6 1.8 6 1.4 6 2.2 6 1.8 6 2.2 6 1.4 6 4.2 6 2.6 6 2.2 6 2.8 6 1.4 6 2.6 6 184.2 177.6 191.4 184.2 187.8 177.6 181.2 191.4 174.0 187.8 191.4 177.6 191.4 184.2 180.6 194.4 180.6 181.2 191.4 187.8 184.2 187.8 177.6 180.6 184.2 177.6 184.2 180.6 194.4 181.2 184.2 191.4 180.6 181.2 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 114 120 126 132 138 144 150 156 162 168 174 180 186 192 198 204 184.2 361.8 553.2 737.4 925.2 1102.8 1284.0 14 75.4 1649.4 1837.2 2028.6 2206.2 2397.6 2581.8 2762.4 2966.8 3137.4 3318.6 3510.0 3697.8 3882.0 4069.8 4247.4 4428.0 4612.2 4789.8 4974.0 5154.6 5349.0 5530.2 5714.4 5905.8 6086.4 6267.6 30.7 30.2 30.7 30.7 30.8 30.6 30.6 30.7 30.5 30.6 30.7 30.6 30.7 30.7 30.7 30.8 30.8 30.7 30.8 30.8 30.8 30.8 30.8 30.8 30.7 30.7 30.7 30.7 30.7 30.7 30.7 30.8 30.7 30.7 DO 067737 CONFIDENTIAL YZOO14392 A-38 79-2425 Appendix A (cont.) Table 19 A Female Fertility Study In Rats with Benzene emulative Exposure Record Pre-Mating Treatment Period Group V - 300 ppm Date Mean Oally Dally Exposure Dally Concen- Total Test Exposure Concen- Exposure tratlon Exposure Dav Number tratlon SO Hours Hours Hours Cumulative InteTotal grated Concert- Mean tratlon ConcenHours tratlon HI ran L 1/7/80 1/8/80 1/9/80 1/10/80 1/11/80 1/14/30 1/15/80 1/16/80 1/17/80 1/18/80 1/21/80 1/22/80 1/23/80 1 /24/80 1/25/80 1/28/80 1/29/80 1/30/80 1/31/80 2/1/80 2/4/80 2/5/80 2/6/80 2/7/80 2/8/80 2/11/80 2/12/80 2/13/80 2/14/80 2/15/80 2/18/80 2/19/80 2/20/80 2/21/80 2/22/80 2/25/80 2/26/80 2/27/80 2/28/80 2/29/80 1 .2 3 4 5 8 9 10 n 12 15 16 17 18 19 22 23 24 25 26 29 30 31 32 33 36 37 38 39 40 43 44 45 46 47 50 51 52 53 54 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 334 45 6 273 41 6 277 26 6 306 52 6 287 24 6 292 25 6 275 3 6 300 22 6 294 22 6 293 15 6 296 8 6 296 14 6 284 12 6 285 12 6 305 3 6 295 7 6 303 6 6 303 16 6 304 19 6 306 5 6 303 29 6 302 3 6 299 13 6 303 4 6 304 6 6 299 11 6 300 5 6 300 12 6 300 3 6 301 12 6 301 6 6 299 5 6 301 8 6 298 7 6 301 8 6 299 4 6 299 17 6 302 12 6 303 4 6 294 11 6 2004 6 2,004 334 1638 12 3,642 304 1662 18 5,304 295 1836 24 7,140 298 1722 30 8,862 295 1752 36 10,614 295 1650 42 12,264 292 1800 48 14,064 293 1764 54 15,828 293 1758 60 17,586 293 1776 66 19,362 293 1776 72 21,138 294 1704 78 22,842 293 1710 84 24,552 292 1830 90 26,382 293 1770 96 28,152 293 1818 102 29,970 294 1818 108 31,788 294 1824 114 33,612 295 1836 120 35,448 295 1818 126 37,266 296 1812 132 39,078 296 1794 138 40,872 296 1818 144 42,690 296 1824 150 44,514 297 1794 156 46,308 297 1800 162 48,108 297 1800 168 49,908 297 1800 174 51,708 297 1806 180 53,514 297 1806 186 55,320 297 1794 192 57,114 297 1806 198 58,920 298 1788 204 60,708 298 1806 210 62,514 298 1794 216 64,308 298 1794 222 66,102 298 1812 228 67,914 298 1818 234 69,732 298 1764 240 71,496 298 no 067709 CONF TDFNT T Al YZOO14394 A-39 79-2425 Appendix A (cont.) Table 19 (cont.) A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Pre-Mating Treatment Period Group V - 300 ppm (cont.) Oate Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Day Number tratlon SD Hours Hours Hours Hours tratlon 3/3/80 3/4/80 3/5/80 3/6/80 3/7/80 3/10/80 3/11/80 3/12/80 57 58 59 60 61 64 65 66 Mlran 04 3/13/80 67 3/14/80 68 41 42 43 44 45 46 47 48 49 50 311 42 6 301 5 6 299 11 6 300 14 6 300 5 6 303 20 6 310 22 6 297 25 6 291 18 6 300 32 6 1866 246 73.362 298 1806 252 75,168 298 1794 258 76,962 298 1800 264 78,762 298 1800 270 80,562 298 1818 276 82,380 298 1860 282 84,240 299 1782 288 86,022 299 1746 294 87,768 299 1800 300 89,568 299 no nO7740 n onf rnFNTTAI YZ0014395 A-40 79-2425 Appendix A (cont.) Table 20 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Hating Period Group V 300 ppm Date Mean Dally Dally Exposure DallyConcen- Total Test Exposure Concen- Exposure tratlon Exposure Day Number tratlon SD HoursHours Hours Cumulatlve InteTotal grated Concen- Mean tratlon ConcenHours tratlon Ml ran 04 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/24/80 3/25/80 3/26/80 3/27/80 3/28/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 71 72 73 74 75 78 79 80 81 82 85 86 87 88 89 51 52 53 54 55 58 59 60 61 62a 65 66 67 68 69 293 18 6 302 32 6 303 31 6 319 51 6 302 23 6 306 25 6 304 20 6 302 15 6 300 32 6 291 44 6 293 24 6 294 21 6 298 24 6 287 11 6 299 13 6 1758 1812 1818 1914 1812 1836 1824 1812 1800 1764 1758 1764 1788 1722 1794 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 1,758 3,570 5,388 7,302 9,114 10,950 12,774 14,586 16,386 18,150 19,908 21,672 23,460 25,182 26,976 293 298 299 304 304 304 304 304 303 303 302 301 301 300 300 Exposure nimbers 56, 57, 63, and 64 for animals receiving exposure during the gestation period. DO 067741 OONFTDFNTTAl YZOO14396 Appendix A (cont.) Table 21 A Female Fertility Study in Rats with Benzene 79-2425 Cumulative Exposure Record Gestation Period Group V - 300 ppm -- Oate Cumulative Mean Inte- Dally Dally Total grated Exposure Daily Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Day Number tratlon SD Hours Hours Hours Hours tratlon Ml ran 04 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/22/80 3/23/80 3/24/80 3/26/80 3/26/80 3/27/80 3/28/80 3/29/80 3/30/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 4/5/80 4/6/80 4/7/80 4/8/80 4/9/80 4/10/80 4/11/80 4/12/80 4/13/80 4/14/80 4/15/80 4/16/80 4/17/80 4/18/80 4/19/80 4/20/80 4/21/80 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 65 86 293 18 6 302 32 6 303 31 6 319 51 6 302 23 6 309 29 6 307 64 6 306 25 6 304 20 6 302 15 6 300 32 6 291 44 6 296 23 6 300 14 6 293 24 6 2M 21 6 298 24 6 287 11 6 299 13 6 295 55 6 289 29 6 303 23 6 288 40 6 296 16 6 285 25 6 293 23 6 291 18 6 280 27 6 268 16 6 260 60 6 303 39 6 293 50 6 303 29 6 294 40 6 304 15 6 289 45 6 1758 6 1,758 293 1812 12 3,570 298 1818 18 5.388 299 1914 24 7,302 304 1812 30 9,114 304 1854 36 10,968 305 1842 42 12,810 305 1836 48 14,646 305 1824 54 16,470 305 1812 60 18,282 305 1800 66 20,082 304 1764 72 21,846 303 1776 78 23,622 303 1800 84 25,422 303 1758 90 27,180 302 1764 96 28,944 302 1788 102 30.732 301 1722 108 32,454 301 1794 114 34,248 300 1770 120 36,018 300 1734 126 37,752 300 1818 132 39,570 300 1728 138 41,298 299 1776 144 43,074 299 1710 150 44,764 299 1758 156 46,542 298 1746 162 48,288 298 1680 168 49,968 297 1608 174 51.576 296 1560 180 53,136 296 1818 186 54,954 295 1758 192 56,712 295 1818 198 58,530 296 1764 204 60,294 296 1824 210 62,118 296 1734 216 $3,864 296 Do 06774? YZ0014397 A-42 Appendix A (cont.) Table 22 A Female Fertility Study In Rats with Benzene 79-2425 Cumulative Exposure Record Lactation Period Group V - 300 ppm Date "" Curiu'l atlve Mean Dally Exposure Dally Dally Goncen- Total Total Concen- Integrated Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen Day Number tratlon SD Hours Hours Hours Hours tration Ml ran 04 4/7/80 92 4/8/80 93 4/9/80 94 4/10/80 95 4/11/80 96 4/12/80 97 4/13/80 98 4/14/80 99 4/15/80 100 4/16/80 101 4/17/80 102 4/18/80 103 4/19/80 104 4/20/80 105 4/21/80 106 4/22/80 107 4/23/80 108 4/24/80 109 4/25/80 110 4/26/80 111 4/27/80 112 4/28/80 113 4/29/80 114 4/30/80 115 5/1/80 116 5/2/80 117 5/3/80 118 5/4/80 119 5/5/80 120 5/6/80 121 5/7/80 122 5/8/80 123 5/9/80 .124 5/10/80 125 5/11/80 126 5/12/80 127 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 303 23 6 288 40 6 296 16 6 285 25 6 293 23 6 291 18 6 280 27 6 268 16 6 260 60 6 303 39 6 293 50 6 303 29 6 294 40 6 304 15 6 289 45 6 300 23 6 296 41 6 283 37 6 300 14 6 305 18 6 296 16 6 337 42 6 302 33 6 293 24 6 315 42 6 289 34 6 316 32 6 293 11 6 319 30 6 292 15 6 292 21 6 309 20 6 309 20 6 315 21 6 311 29 6 301 39 6 1818 6 1,818 303 1728 12 3,546 296 1776 18 5,322 296 1710 24 7,032 293 1758 30 8,790 293 1746 36 10,536 293 1680 42 12,216 291 1608 48 13,824 288 1560 54 15,384 285 1818 60 17,202 287 1758 66 18,960 287 1818 72 20,778 289 1764 78 22,542 289 1824 84 24,366 290 1734 90 26,100 290 1800 96 27,900 291 1776 102 29,676 291 1698 108 31,374 291 1800 114 33,174 291 1830 120 35,004 292 1776 126 36,780 292 2022 132 38,802 294 1812 138 40,614 294 1758 144 42,372 294 1890 150 44,262 295 1734 156 45,996 295 1896 162 47,892 296 1768 168 49,650 296 1914 174 51,664 296 1752 180 53,316 296 1752 186 55,068 296 1854 192 56,922 296 1854 198 58,776 297 1890 204 60,665 297 1866 210 62,532 298 1806 216 64,338 298 DO 067743 OONFTOFNTTAl YZOO14398 ro> z oo n n O'll z soSvjj' -i >P U4*>. 'O Appendix A (coot.) Table 23 A Female Fertility Study in Rat* with benzene 79-Z425 Individual Exposure Record for Group V Pre-Mating16 * * mtinq 16 GestationT7---------------- Lactation 1b Post-Lactation19 Simulative TotalZt> Cunulatlve Cumulative Cumulative Cumulative Cumulative Cumulative Number Naan Exposure Test Days Kfiber Hhan Exposure Test Days Hean Test (timber Exposure Days Umber dean Exposure Number Mean Exposure (limber Nean Exposure An. of Concern- of of Concen- of of Concen- of of Concen- of Concen- of Concen- Ho. Exposures tretlon Exposure Exposures tration Exposure Ex posures tration Exposure Exposures tration Exposures tration Exposures tration Tom) loom) [ppm] (pm) (PP) (PP") (ppm) 1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1046 1049 1050 50 so 50 so 50 so 50 so 50 50 50 50 so so 50 50 so 50 SO so 50 50 50 50 50 50 299 71-84 299 71 299 71-73 299 71-83 299 71-72 299 _ 299 71-74 299 299 71-73 299 71 299 71-73 299 299 299 299 71 299 71-7* 299 299 71-73 299 71-74 299 71-72 299 71-75 299 299 299 299 71-75 299 - 10 l 3 10 2 4 _ 3 1 3 * . 1 4 3 4 2 6 - 5 - 303 85-105 21 293 72-92 21 299 74-94 21 303 84-104 21 298 73-93 21 _ 71-91 21 304 75-95 21 71-91 21 299 74-94 21 293 72-92 21 299 74-94 21 _ 71-91 21 . 71-91 21 _ 71-91 21 293 72-92 21 304 75-95 21 71-91 21 299 74-94 21 304 75-95 21 298 73-93 21 304 76-96 21 71-91 2! 71-91 21 71-91 21 304 77-97 21 - 71-91 21 291 300 99-115 17 299 101-117 17 291 111-127 17 299 99-115 17 300 a - 297 103-119 17 300 97-113 17 299 100-116 17 300 99-115 17 299 TOO-116 17 300 97-113 17 300 98-114 17 300 97-113 17 300 99-115 17 297 103-119 17 300 a _ 299 100-116 17 297 101-117 17 299 99-115 17 297 103-119 17 300 97-113 17 300 a . 300 99-115 17 296 104-120 17 300 98-114 17 8 296 7 300 5 306 296 7 - 301 5 294 9 298 6 296 7 298 6 294 9 295 8 294 9 296 . 8 301 6 .- 298 7 300 6 296 8 301 6 291 10 - 296 a 302 s 295 9 296 296 296 296 - 296 296 296 296 296 296 296 296 296 297 - 296 297 296 297 296 - 296 297 296 88 297 96 298 96 299 98 299 97 298 71 299 97 299 97 298 97 299 96 298 97 299 97 298 96 298 97 298 97 298 98 299 71 299 98 299 98 299 98 298 99 299 98 298 71 299 96 298 98 299 97 298 Individual cuuulative exposure concentration* taken directly from Table* 19 and 20 for the prnaiting and meting period, respectively. ''individual canulative exposure concentrations were calculated ntm Table 21 Aar the ye*tation period. Using animal nuaber 1025 as an cxuplt a total of 21 expotore* uern rncntvnd daring 9esut1on (Days 56-105, inclusive). During this period, a total of 126 exposure hours (210-04-126) and a total or KOI concontratton hoars (62110*25422-36696) were accnaulatod. Thu cwmlatlve exposure concentration for this period was 291 ppn (36696*126-291). '"Individual aaariatlva exposure concentrations ware calculated using Table 22 dor the lactation period using the procedure described for the gestation , iwM. 'Pest-lactation wncnutratlons wart obtained hy averaging the dally exposure concentrations that were obtained post-lactation For each anInal. *The total canal atfvn ntpaiari concentration was calculated hy dividing the total oanilatlve exposure concentration of the pro mating, meting, gestation, lactation, and post-lactation periods by Me total amber of exposures. *Jt*haal did not deliver pups, no exposures received during lactation or post-lactation period. Ml !i I Date Ml ran L 1/7/80 1/8/80 1/9/80 1/10/80 1/11/80 1/14/80 1/15/80 1/16/80 1/17/80 1/18/80 1/21/80 1/22/80 1/23/80 1/24/80 1/25/80 1/28/80 1/29/80 1/30/80 1/31/80 2/1/80 2/4/80 2/5/80 2/6/80 2/7/80 2/8/80 2/11/80 2/12/80 2/13/80 2/14/80 2/15/80 2/18/80 2/19/80 2/20/80 2/21/80 2/22/80 A-44 79-2425 Appendix A (Cont.) Table 24 A Female Fertility Study In Rats with Benzene Dally Nominal Concentrations Test Exposure Day Number Nominal Concentration iPpnJ Group Group Group Group 11 III IV V 11 0.6 7.8 26.5 329 22 0.2 6.1 25.7 276 33 0.8 8.2 30.1 304 44 2.2 8.3 31.6 287 55 0.9 9.1 28.3 328 86 0.7 8.1 29.8 316 97 0.7 8.1 30.7 305 10 8 . 1.0 8.5 29.0 337 n9 0.9 8.4 28.5 302 12 10 1.3 8.2 30.6 307 15 11 1.3 8.2 28.9 321 16 12 1.4 8.2 27.9 310 17 13 1.4 8.0 28.2 290 18 14 1.5 8.8 30.7 300 19 15 1.4 10.9 31.4 300 22 16 1.5 6.1 25.9 299 23 17 1.3 10.6 32.7 290 24 18 0.7 10.7 31.3 317 25 19 1.6 10.4 31.3 312 26 20 1.4 10.2 29.5 317 29 21 1.4 6.1 25.2 302 30 22 1.3 9.9 30.2 312 31 23 1.5 8.5 29.8 320 32 24 1.8 9.0 30.2 324 33 25 2.0 11.5 30.6 319 36 26 a a 23.5 308 37 27 1.0 9.1 30.3 319 38 28 0.8 9.1 31.1 314 39 29 1.9 12.7 30.9 329 40 30 0.8 10.4 28.6 321 43 31 1.2 11.3 30.0 325 44 32 1.3 10.3 29.7 317 45 33 1.1 10.1 28.7 326 46 34 1.1 9.5 28.3 315 47 35 1.1 10.6 29.1 320 ^Nominal concentration suspect due to possible weighing error, not Included In mean calculation. DO 067745 OONFrDFNTTAI.. YZOO14400 A-45 79-2425 Appendix A (Cont.) Table 24 (cont.) A Female Fertility Study In Rats with Benzene Dally Nominal Concentrations (cont.) Date Test Exposure Day Number Nominal Concentration Group Group Group II JUL. IV Group Hi ran L (cont.) 2/25/80 2/26/80 2/27/80 2/28/80 2/29/80 3/3/80 3/4/80 3/5/80 3/6/80 3/7/80 3/10/80 3/11/80 3/12/80 50 51 52 53 54 57 58 59 60 61 64 65 66 36 37 38 39 40 41 42 43 44 45 46 47 48 1.0 10.5 a 10.0 1.1 12.1 1.9 10.4 1.3 8.3 1.4 10.3 1.2 10.8 1.2 10.2 1.4 10.9 1.2 10.4 1.3 11.3 1.0 10.5 1.3 10.7 29.3 30.1 30.5 30.3 29.4 32.5 31.0 30.4 30.3 30.4 30.6 32.4 31.3 318 324 325 319 314 318 321 337 338 343 344 361 338 Ml ran 04 3/13/80 3/14/80 3/17/80 3/18/80 3/19/80 3/20/80 3/21/80 3/22/80 3/23/80 3/24/80 3/25/80 3/26/80 3/27/80 3/28/80 3/2 9/80 3/30/80 3/31/80 4/1/80 4/2/80 4/3/80 4/4/80 4/5/80 67 68 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 66 87 88 69 90 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 1.2 11.9 1.5 11.0 1.9 6.9 0.8 9.9 0.9 10.3 1.0 11.3 1.0 10.4 1.1 10.6 0.8 9.6 1,3 10.9 1.3 10.4 1.1 10.4 0.8 10.1 1.1 10.5 1.2 10.4 1.3 11.2 1.6 9.7 1.2 11.1 1,1 10.3 1.5 10.3 1.1 10.5 1.2 9.8 35.9 32.9 32.0 34.5 34.7 32.4 34.4 36.6 36.9 37.8 34.4 33.4 32.9 32.5 34.5 34.6 35.4 36.1 34.3 35.9 34.8 35.5 352 362 321 375 355 343 363 348 367 367 375 357 378 355 398 419 384 381 390 406 421 347 *Nom1nal concentration suspect due to possible weighing error* not Included In mean calculation. DO 067740 OONFIDFNTTAI YZ0014401 A-46 79-2425 Appendix A (Cont.) Table 24 (cont.) A Female Fertility Study In Rats with Benzene Dally Nominal Concentrations (cont.) Horn fna1 (jonceniraTforT Test Exposure Group Group Group Group Date Dav Number II III IV V 4/6/BO 91 71 4/7/80 92 72 4/8/80 93 73 1.1 11.0 1.2 10.3 1.2 10.7 36.1 34.2 35.9 375 381 376 GC (Groups II and III, Ml ran 04 (Groups IV and V) . 4/9/80 4/10/80 4/11/80 4/12/80 4/13/80 4/14/80 4/15/80 4/16/80 4/17/80 4/18/80 4/19/80 4/20/80 4/21/80 4/22/80 4/23/80 4/24/80 4/25/80 4/26/80 4/27/80 4/28/80 4/29/80 4/30/80 5/1/80 5/2/80 5/3/80 5/4/80 5/5/80 5/6/80 5/7/80 5/8/80 5/9/80 5/10/80 5/11/80 5/12/80 5/13/80 5/14/80 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 no 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 1.3 11.6 1.5 11.0 1.1 11.5 1.2 11.1 2.2 16.1 1.1 11.1 1.8 12.1 1.2 11.6 1.0 11.2 1.3 11.4 1.2 11.7 1.3 13.0 1.4 10.9 1.2 12.6 1.8 12.6 1.3 13.4 1.3 11.3 1.3 11.1 1.7 12.1 1.1 11.0 1.3 11.0 1.2 11.5 1.2 11.5 1.3 11.3 1.2 11.1 1.3 10.3 1.2 11.7 1.2 12.2 1.0 11.1 1.2 12.7 1.2 11.2 b 10.9 b 11.3 1.4 11.7 c 11.0 c 11.1 35.2 32.8 33.7 35.9 39.7 34.8 38.1 40.4 34.8 40.1 34.3 36.9 38.3 35.2 36.5 36.0 33.4 31.6 32.3 31.6 33.1 32.4 33.8 39.6 37.4 39.6 35.3 35.1 38.5 34.0 36.1 b b 39.9 C c 409 405 402 418 408 412 403 397 390 404 395 420 379 408 420 390 407 399 362 340 296 309 333 322 345 316 351 320 296 345 365 356 313 272 c c Mean S.O. N 1.2 0.3 103 10.4 1.6 108 32.7 3.5 105 346 39 107 ^Non-exposure day. cExposures terminated DO 067747 CONFTDFNTTAl I YZOO14402 A-47 79-2425 Appendix A (cont.) Table 25 A Female Fertility Study In Rats with Benzene Mean Dally Nominal Concentration vs. Mean Dally Analytical Concentrations Group Date II 1/7/80 - 4/8/80 4/9/80 - 5/12/80b 1/7/80 - 5/12/80 III 1/7/80 - 4/8/80 Nominal Cone. |ppnr Analytical Cone. (ppm) % Difference Mean 1.2 S.D. .3 N 71 .92 .5 73 24 Mean 1.3 S.D. .2 N 32 1.2 .9 32 8 Mean 1.2 S.D. .3 N 104 1.1 .4 105 9 Mean 9.8 S.D. 1.4 N 72 9.7 1.0 73 1 4/9/80 - 5/14/80h 1/7/80 - 5/14/80 IV 1/7/80 - 5/12/80 V 1/7/80 - 5/12/80 Mean S.D. N Mean S.D. N Mean S.D. N Mean S.D. N 11.7 1.0 36 10.4 1.6 108 32.7 3.5 105 346 39 107 12.9 1.0 36 11.1 1.9 109 30.6 1.3 105 299 11 107 9 6 7 16 Analytical concentrations measured using Ml ran Infrared Analyzer. "Analytical concentrations measured using on-line Tracor gas chromatograph. DO 067748 OONFIDFNTTAl YZOO14403 o Z^O oo W*} p. ^A is Appendix 8 An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Mean Body Weight Data - (grams) Pre-Mating Treatment Period Animal Change fn Group Number Meek: 0 1 2 3 4 5 6 7 8 9 10 Wt. 1-10 ppa I 225 0 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 A" A" A~ A" A" A" A" A" A" A" A" 169 188 199 210 228 236 244 245 255 258 258 176 197 210 226 241 253 266 275 280 279 288 157 175 183 198 207 221 232 232 250 265 245 155 176 203 196 208 214 221 215 218 222 225 160 028} 187 197 209 215 225 231 238 237 247 164 179 191 205 219 227 230 242 245 249 251 158 164 188 195 209 212 226 237 245 244 257 161 182 200 210 218 225 238 249 240 254 266 151 161 163 182 196 200 212 217 220 221 229 171 193 205 211 221 229 242 244 251 255 263 174 188 203 214 228 236 249 244 257 257 263 139 163 167 174 190 196 209 213 212 219 228 158 180 188 195 209 221 231 231 239 240 241 140 186 194 202 224 233 237 238 244 249 249 150 168 177 184 201 207 216 218 226 232 237 161 185 189 202 222 229 237 247 246 257 265 153 165 180 194 211 218 232 242 244 248 257 162 186 202 216 229 242 243 249 256 260 271 158 181 200 211 222 232 239 242 249 258 264 168 187 202 212 228 237 244 262 281 276 280 166 181 180 204 220 226 232 235 235 241 246 162 179 208 215 233 239 245 250 257 261 265 147 162 169 174 193 191 206 209 205 213 215 172 205 219 234 259 267 279 291 300 306 312 145 159 167 181 196 201 203 208 214 216 218 159 180 197 214 232 250 251 257 271 279 278 A" 70 91 70 49 (72) 72 93 84 68 70 75 65 61 63 69 80 92 85 83 93 65 86 53 107 59 98 Mean 159 179 191 202 217 225 234 S.O. 10 12 15 15 16 18 17 N 26 25 26 26 26 26 26 For explanation of statistical symbol: A-; see Appendix 0. Body weight Meek 1 aooears Incorrectly recorded. UMntit dart* fin 239 245 20 22 26 26 250 22 26 pltdail 255 76 22 14 26 25 mi(l 4 nee Appendix B (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Hean Body Height Bata - (grams) Pre-Hating Treatment Period Animal Change in Group Number Week: 0 1 2 3 4 5 6 7 8 9 10 Wt. 1-10 PP II 425 1 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 153 172 182 199 213 225 229 233 241 244 245 160 172 191 198 213 228 229 234 237 240 251 159 194 192 208 219 229 240 236 248 247 248 181 202 214 227 244 253 261 257 267 273 279 158 176 188 198 206 213 221 226 228 233 239 147 169 185 195 215 226 235 231 244 248 256 190 208 223 240 256 263 271 274 284 309 293 168 191 206 224 236 248 258 264 266 280 289 167 187 210 227 239 250 249 262 273 278 280 149 166 184 195 196 213 222 225 222 233 242 155 169 174 185 206 209 212 218 224 224 221 167 187 201 207 221 232 233 238 237 241 243 172 190 210 222 235 236 251 252 257 263 261 156 174 193 214 218 225 239 245 239 253 255 157 170 172 184 196 200 207 213 219 222 226 160 177 195 196 232 261 241 234 244 259 261 151 171 184 195 211 219 225 226 234 241 246 163 187 197 205 222 237 257 253 257 255 264 164 172 190 204 216 224 231 242 241 256 249 140 156 170 179 194 200 209 214 218 222 231 165 192 208 215 230 243 248 248 275 273 273 155 177 191 205 216 229 232 240 241 252 258 166 183 201 207 226 235 245 247 253 261 264 144 162 167 181 196 214 217 218 223 231 232 161 187 198 208 220 230 236 247 243 260 257 154 173 187 200 211 223 233 235 239 244 254 73 79 54 77 63 87 85 98 93 76 52 56 71 81 56 84 75 77 77 75 81 81 81 70 70 81 DO 0 6 7 7 5 0 C O N F ID E N T IA L Mean 160 179 193 205 219 229 236 239 244 252 255 75 S.O. 11 12 14 15 16 17 16 16 18 20 18 11 N 26 26 26 26 26 26 26 26 26 26 26 26 Appendix 6 (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Mean Body Weight Data - (grans) Pre-Mating Treatment Period Animal Change in Group Number Week: 0 1 2 3 4 5 6 7 8 9 10 Wt. 1-10 ppn III 625 10 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 648 649 650 174 194 202 215 233 239 249 249 259 265 267 162 180 192 210 218 231 241 241 250 259 263 160 175 188 196 219 216 224 224 223 237 244 159 165 185 185 209 207 224 221 220 230 238 14! 159 166 179 194 201 205 213 217 221 221 148 170 180 192 201 206 214 219 220 224 236 152 166 183 194 206 213 219 229 228 240 237 153 175 186 198 211 215 229 237 235 242 249 157 174 190 207 218 231 242 243 244 257 258 158 184 194 210 222 238 240 250 250 264 268 167 180 194 210 223 235 241 237 244 253 251 173 191 209 218 238 250 257 258 263 267 269 156 164 177 190 205 210 209 220 225 229 229 158 176 185 194 209 212 221 218 232 236 237 152 166 181 189 200 208 211 216 223 227 227 165 178 190 208 215 227 235 239 242 252 255 165 186 192 202 222 231 235 240 251 265 267 161 183 190 213 223 228 236 243 250 254 251 161 188 203 213 220 236 244 246 252 263 271 153 187 209 225 235 257 259 271 274 284 281 156 169 178 196 207 213 220 225 228 228 232 161 177 189 197 211 223 228 230 237 249 247 170 190 201 214 228 242 245 246 252 261 263 176 201 215 226 245 260 267 269 279 293 295 177 207 220 231 233 256 261 264 264 284 285 152 175 190 204 224 237 244 244 251 268 266 73 83 69 73 62 66 71 74 84 84 71 78 65 61 61 77 81 68 83 94 63 70 73 94 78 91 Mean S.D. N 160 179 192 204 218 228 235 238 243 252 254 9 12 12 13 13 17 17 16 17 20 19 26 26 26 26 26 26 26 26 26 26 26 75 10 26 No statistically significant differences froa control 8-3 ! Appendix B (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Mean Body Weight Data - grams Pre-Kating Treatment Period Animal Change in Group Number Week: 0 1 2 3 4 5 6 7 8 9 10 Wt. 1-10 ppm IV 825 30 826 827 828 829*> 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 o o 846 2 o 847 >-< o o^ -T| SJ Z SI -t CP -< \) I> 848 849 850 Mean S.0. OH 166 191 205 216 223 237 250 252 256 272 272 174 191 203 215 230 242 251 248 255 268 270 161 184 197 208 225 227 250 251 268 278 279 142 161 173 183 198 203 213 218 221 224 232 150 165 173 190 197 - - -- - - 166 183 204 207 220 231 234 240 249 254 256 163 184 199 214 221 226 236 244 247 256 254 170 188 210 225 236 255 261 268 273 289 290 ICS 182 192 207 220 232 235 240 245 249 249 172 193 204 224 241 253 256 265 274 288 292 175 193 215 219 234 243 250 255 258 267 270 157 178 198 214 226 237 241 248 253 258 259 153 171 194 215 228 237 253 266 268 278 282 178 197 211 223 241 249 254 264 275 285 286 165 178 188 199 212 218 224 233 241 240 247 134 146 160 175 186 192 194 200 199 203 206 156 168 187 195 203 217 227 226 235 236 245 152 174 184 191 202 212 214 223 227 233 232 166 186 197 204 219 221 231 237 244 248 253 155 172 193 202 218 230 241 242 246 252 260 159 176 195 210 216 232 236 247 256 254 266 161 171 200 207 222 233 233 247 249 262 265 147 162 176 186 199 201 207 217 223 224 233 151 164 179 193 202 205 211 220 228 230 228 158 184 200 208 225 236 241 242 241 252 257 157 171 188 197 206 218 217 229 229 235 240 160 177 193 205 217 227 234 241 246 253 257 10 12 13 13 14 16 17 17 19 22 21 26 26 26 26 26 25 25 25 25 25 25 81 79 95 71 - 73 70 102 67 99 77 81 111 89 69 60 77 58 67 68 90 94 71 64 73 69 79 14 25 mm mm 1 1 i - 1 f Appendix B (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Body Weight Data - (grams) Pre-Mating Treatment Period Animal Change in Group Number Week: 0 1 2 3 4 5 6 7 8 9 10 Wt. 1-10 PP" V 1025 300 1026 1027 165 187 206 221 233 242 254 256 256 271 270 148 165 178 187 201 213 220 222 227 229 238. 158 169 183 193 211 218 223 224 232 237 234 83 73 65 1028 148 166 169 172 181 184 186 188 189 190 193 27 1029 157 176 186 191 204 215 215 217 227 229 227 51 1030 164 185 196 196 202 209 221 229 242 253 258 73 1031 156 174 183 195 210 222 226 222 232 236 240 66 1032 189 217 237 257 273 280 293 303 309 305 313 96 1033 140 152 167 175 190 203 212 213 223 226 229 77 1034 169 195 212 224 239 245 260 263 268 274 281 86 1035 171 197 205 217 238 257 243 249 260 270 267 70 1036 156 179 187 200 216 220 238 242 246 247 257 78 1037 1038 139 165 180 187 201 206 214 215 218 230 227 149 169 178 189 206 212 216 221 231 232 237 62 68 1039 162 182 197 211 221 231 238 246 250 251 252 70 1040 166 178 194 215 223 231 233 239 246 250 249 71 1041 165 188 202 217 234 236 247 251 260 265 265 77 1042 181 209 215 228 244 250 251 261 270 278 274 65 1043 155 168 183 191 198 207 209 213 226 231 229 61 1044 156 180 190 199 216 228 236 233 247 257 255 75 1045 161 178 197 213 225 238 244 246 240 257 255 77 1046 170 191 211 228 246 245 264 274 282 283 291 100 oz zo> 1047 153 167 ' 182 194 206 215 226 230 235 242 244 77 1048 169 181 201 214 223 233 246 250 253. 264 265 84 Ma O m sj 1049 1050 174 193 207 213 237 248 256 255 268 280 274 157 175 187 196 211 212 220 226 235 232 241 81 66 Z Nt H 'jn I> jJ Mean 161 180 194 205 219 227 234 238 245 251 253 72 N S.O. N 12 14 16 19 20 21 22 24 24 24 24 26 26 26 26 26 26 26 26 26 26 26 14 26 Oh- No statistically significant differences fren control. B-5 00 C-l Appendix C An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights - Gestation and Lactation Preface This female Initiated delivery. The hlndllmbs of the pups were noted In the vaginal canal. At later evaluation, pup was not observed. No other pups were delivered. "Not pregnant; values In parentheses excluded from calculations. Mating not confirmed; sacrificed at completion of the mating period. Mating confirmed; no evidence of parturition. Implantation scars observed at sacrifice; data In parentheses excluded from calculations. Animal was killed accidentally (l.e., dropped during handling) during Week 5 of the pre-mating treatment period. 'No pups remaining on Day 1 of lactation. 9Body weight taken after 6 hours of no food or water. 00 067754 CONFTDFNTTAi YZOO14409 C-2 Appendix C (cent.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Gestation - grains Group I - (0 ppm) An. No. Day: 225 226 227 228 229 230 231 232 233 234b 235 236 237 238 239 240 241c 242 243 244 245 b 246 247 248<1 249 250 0 A" 262 286 248 225 249 252 257 262 229 (266) 270 232 232 262 236 256 - 272 275 281 (244) 259 216 (322) 227 278 7 A" 274 300 267 232 266 276 284 292 252 (277) 284 243 257 277 257 284 - 287 297 297 (264) 282 238 (336) 241 311 14 A" 308 327 305 259 293 303 315 302 276 (293) 306 268 291 306 283 322 316 320 323 (278) 306 260 (360) 267 347 21 A" 354 418 394 335 380 393 392 315 369 (287) 385 325 362 389 356 403 - 412 403 417 (269) 356 334 (351) 342 423 Change In Body Weight 0-21 A' 92 132 146 no 131 141 135 63 140 (21) 115 93 130 127 120 147 - 140 128 136 (25) 97 118 (29) 115 145 Mean $.0. N 253 273 300 375 20 22 23 32 22 22 22 22 122 23 22 For explanation of statistical symbol: A-, see Appendix Q. DO 067755 CON FTDFNTIAl YZ0014410 C-3 Appendix C (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Gestation - grams Group II - (1 ppm) An. No. Day: 425 426 427 b 428 429. 430d 431 432 433 434 435 436 437c 438 439 440 441 442 443 444 445 446c 447 448 449 450 0 252 255 (252) 281 237 (263) 293 285 290 235 233 242 - 259 220 267 248 262 257 226 268 - 265 231 250 256 7 266 268 (258) 303 253 (286) 314 303 302 267 241 253 * 264 227 292 271 282 284 254 303 - 285 231 261 282 14 307 295 (263) 335 281 (302) 341 329 325 291 272 287 - 304 266 331 295 298 313 286 325 314 232 292 308 21 397 372 (254) 414 370 (285) 418 406 400 376 334 352 - 382 331 422 380 370 388 344 416 m 387 316 316 390 Change In Body Weight 0-21 145 117 (2) 133 133 (22) 125 121 no 141 101 no m 123 111 155 132 108 131 118 148 m 122 85 66 134 Mean 255 273 301 376 121 S.D. 21 24 26 32 20 N 22 22 22 22 22 No statistically significant differences from control. DO 067756 CONFTDFNTT Al YZ0014411 C-4 Appendix C (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Gestation - grams Group III - (10 ppm) Change In An. Body Weight No. Day: 0 7 14 21 0-21 625 626 627 628 629b 630 631 632 633 634 635 636 637, 638b 639 640 641 642 643 644 645 646 647 648 649 650 270 262 243 247 (230) 232 257 245 268 281 256 272 232 (256) 232 252 275 260 272 286 239 256 265 304 286 275 289 294 262 265 (236) 256 264 268 285 315 259 291 266 (264) 261 271 295 287 276 310 254 278 287 315 321 300 320 322 289 290 (235) 272 283 295 315 343 299 320 296 (258) 279 306 333 309 317 341 285 308 309 347 358 326 352 406 356 376 (231) 348 330 383 388 431 389 362 370 (257) 358 399 393 395 417 423 368 382 381 430 451 413 82 144 113 129 (1) 116 73 138 120 150 133 90 138 (1) 126 147 118 135 145 137 129 126 116 126 165 138 Mean 261 282 311 388 126 S.D. 19 20 23 30 21 N 24 24 24 24 24 No statistically significant differences from control. DO 067757 CONFTDFNTTAL YZ0014412 C-5 Appendix C (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Gestation - grams Group IV - (30 ppm) An. No. Day: 0 825 826 827 828 829e 830 831 832d 833b 834b 835 836d 837 838 839 840 841 842 843 844 845b' 846 847 848 849 850b 268 260 272 232 - 251 274 (286) (243) (288) 270 (257) 283 287 251 203 246 228 251 258 (260) 261 227 236 263 (229) 7 294 279 298 255 263 279 (275) (265) (301) 294 (275) 304 298 270 212 270 244 276 276 (272) 288 252 252 286 (245) 14 315 313 326 278 281 304 [3261 267) 303) 315 (299) 331 341 299 237 299 280 295 305 (282) 323 277 279 314 (252) 21 404 409 404 348 359 403 (361) 267) (301) 407 (287) 383 445 397 320 390 376 350 393 (269) 416 362 362 369 (255) Change In Body Weight 0-21 136 149 132 116 w 108 129 75' 24; (13 137 (30) 100 158 146 117 144 148 99 135 (9) 155 135 126 106 (26) Mean S.D. N 254 273 301 384 21 23 25 30 19 19 19 19 130 18 19 No statistically significant differences from control. no 067750 XOFNT T Al conf YZ0014413 C-6 Appendix C (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Sains During Gestation - grams Group V - (300 ppm) An. No. Day: 0 1025 1026 1027 1028 1029 1030b 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041b 1042 1043 1044 1045 1046 1047b 1048 1049 1050 288 238 230 200 227 (246) 231 321 231 268 275 238 238 230 253 246 (272) 285 230 263 270 296 (247) 256 280 244 7 301 257 254 216 243 (267) 264 337 253 280 294 269 256 246 262 271 (279) 304 247 285 274 324 (261) 267 303 261 14 321 291 284 246 270 (276) 293 365 277 316 337 300 276 268 289 307 (280) 333 266 315 307 353 (261) 300 330 288 Change In Body Weight 21 0-21 374 379 365 312 342 (258) 353 458 352 391 438 390 364 371 367 394 (271) 403 316 394 373 " 454 (260) 343 434 371 86 141 135 112 115 (12) 122 137 121 123 163 152 126 141 114 148 (1) 118 86 131 103 158 03) 87 154 127 Mean S.D. N 254 273 301 377 28 28 29 39 23 23 23 23 126 22 23 No statistically significant differences from control. 00 067759 OONFTDFNTTAL _________ I YZ0014414 C-7 Appendix C (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Lactation - grams Group I - (0 ppm) Change In An. Body Weight No. Day: 0 4 14 21 0-21 225 226 227 228 229 230 231 232a 233 234b 235 236 237 238 239 240 241c 242 243 244 245b 246 247 248<l 249 250 A" A' A" A* 293 292 342 343 318 310 3029 354 278 290 306 308 251 263 283 289 282 289 2839 320 286 301 320 321 298 295 315 316 m m -- 257 285 307 320 - -- 291 321 336 330 258 251 275 303 285 286 312 306 289 291 329 347 253 280 296 300 298 315 346 346 *** 312 297 3019 330 284 296 343 340 305 282 326 346 V p* - - 304 293 311 320 250 248 273 296 ---- 232 249 283 276 331 336 350 361 A' 50 36 30 38 38 35 18 - 63 * 39 45 21 58 47 48 - 18 56 41 4* 16 46 - 44 30 Mean S.D. N 284 289 311 322 25 23 24 23 21 21 21 21 39 13 21 For explanation of statistical symbol: A-; see Appendix Q. DO 067760 CONFTDFNTTAI YZ0014415 C-8 Appendix C (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Lactation - grams Group II - (1 ppm) Change In An. Body Weight No. Day: 0 4 14 21 0-21 425 426 427b 428 429 430^ 431 432 433 434 435 436 437C 438 439 440 441 442 443 444 445 446c 447 448 449 450 275 296 327 323 279 282 292 310 -- 313 318 330 328 269 295 316 298 ---- 333 329 350 374 325 317 345 345 303 296 334 343 286 267 310 311 242 264 298 300 257 278 305 323 m- - 286 310 327 318 255 260 287 295 300 305 341 325 262 283 310 311 265 277 326 321 296 300 333 344 267 283 308 296 292 324 357 356 -.-- 295 297 338 334 243 244 256 283 285 280 304 298 279 300 322 311 48 31 - 15 29 # 41 20 40 25 58 66 a* 32 40 25 49 56 48 29 64 39 40 13 32 Mean S.D. N 282 291 319 320 24 22 23 22 22 22 22 22 38 15 22 No statistically significant differences from control. 00 067761 OONFTOFNTTAl YZ0014416 C-9 Appendix C (cont) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Lactation - grams Group III - (10 ppm) Change In An. Body Weight No. Day: 0 4 14 21 0-21 625 626 627 628 629b 630 631 632 633 634 635 636 637 638b 639 640 641 642 643 644 645 646 647 648 649 650 294 292 342 334 286 314 325 327 281 280 316 , 316 275 262 296 273 - - a* - 257 256 282 286 274 272 277 272 261 286 323 319 302 306 334 321 324 347 343 355 262 299 323 314 298 306 332 324 252 282 337 333 * - -- 254 254 291 309 291 282 310 329 296 305 327 334 272 290 349 323 293 304 329 348 325 336 343 355 273 285 302 313 282 307 322 324 284 287 318 330 341 342 365 354 314 337 367 364 325 320 341 345 40 41 35 -2 - 29 -2 58 19 31 52 26 81 - 55 38 38 51 55 30 40 42 46 13 50 20 Mean S.D. N 288 298 325 325 24 26 23 24 24 24 24 24 37 19 24 No statistically significant differences from control* HO 06776? C0NFTDFNTIA1 YZ0014417 C-10 Appendix C (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Lactation - grams Group IV- (30 ppm) Change In An. Body Weight No. Day: 0 4 14 21 0-21 825 826 . 827 828 829e 830 831 832? 833b 834b 835 836d 837 838 839 840 841 842 843 844L 845b 846 847 848 849 850b 299 306 332 351 292 313 348 328 306 324 332 332 269 265 282 308 # - to - 277 285 302 302 299 314 332 340 m-- - to - - - to 293 315 336 356 to - - 320 313 333 359 330 334 371 368 297 295 330 348 245 238 260 268 299 291 321 327 263 273 311 316 284 284 320 329 303 308 2809 335 -**302 296 333 344 255 260 296 309 250 261 299 289 305 311 318 325 -- 52 36 26 39 to 25 41 to to - 63 - 39 38 61 23 28 53 45 32 to 42 54 39 20 Mean 289 294 318 328 39 S.O. 23 25 26 25 12 N 19 19 19 19 19 No statistically significant differences from control* on OnNf rop^7-.r^, YZ0014418 C-ll Appendix C (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Lactation - grams Group V - (300 ppm) Change In An. Body Weight No. Day: 0 4 14 21 0-21 1025f 1026 1027 1028 1029 1030b 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041b 1042 1043 1044 1045 1046 1047b 1048 1049 1050 292 262 282 316 312 274 290 306 306 220 234 245 266 261 271 295 285 . - - 273 281 298 290 363 362 3489 386 276 277 303 308 314 303 340 362 346 348 350 359 289 294 2969 336 262 280 315 328 276 272 2709 302 277 297 323 349 261 295 329 337 -- 331 311 350 381 256 254 291 301 295 297 336 347 309 289 326 339 342 353 3479 389 -* 287 314 310 306 313 335 358 370 274 282 310 311 50 32 46 24 m 17 23 32 48 13 47 66 26 72 76 50 45 52 30 47 m 19 57 37 Mean S.D. N 289 296 316 330 34 31 28 35 23 22 22 22 41 18 22 No statistically significant differences from control. 00 067764 confident tai YZ0014419 0-1 Appendix 0 An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Litter Information Preface Footnotes: aMales drawn from proven fertile In-house breeder colony. bDam had not finished delivery at time of afternoon evaluation but at this time 13 viable pups were noted; on the next day only 12 pups were present. The one missing pup Is presented In brackets In the No. Dead colunn (Day 0) and Included In calculation of mean number of dead pups. cFour dead pups were removed from the litter prior to the completion of parturition. At that same time four live pups were noted. On the next day (Day 0 of Lactation), only two viable pups were noted. The two missing pups are Identified In brackets In the No. Dead column and these pups are included In calculation of mean number of dead pups. dAn1ma1 was killed accidentally (l.e., dropped during handling) during Week 5 of the pre-mating treatment period. eFema1e considered pregnant for purposes of calculating pregnancy rates (Table 2). fNo evidence of mating; however. Implantation sites were noted at post-mating sacrifice; female considered mated and pregnant for purpose of calculating pregnancy rates (Table 2). 90n Day 2 of lactation, litter found to contain one additional pup; data for this litter were excluded from calculation of Day 0-4 pup survival Index (Table 5). **0n gestation Day 24, this female Initiated delivery. The hlndllmbs of one pup were noted protruding from the vaginal canal. At later evaluation, pup was not observed; apparently the female had cannaballzed this pup. No other pups were delivered. ^Numbers In brackets designate pups recovered from litter prior to actual Day 0 of lactation. ^Female Initiated delivery late afternoon - 15 pups were noted; however, fsnale did not appear to have completed delivery. During the Day 0 litter check the next morning only 13 live pups were noted; the two missing pups are designated In brackets In the No. Dead column and Included In calcula tions for number dead pups. DO CO/S/P 067765 rDfrNTTA( YZ0014420 ! Appendix 0 (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Litter Information - Group I (G ppm) Dam Sire No. No.4 225 4 226 4 227 S 228 $ 229 6 230 6 23! .7 232*,"7 233 a 234 i 235 9 236 9 237 10 238 10 239 11 240 11 241 242 12 243 S 244 13 245 15 246 15 247 16 248 16 249 17 >50 17 Day 0 Best. Total No. Naan Lengthi Pups 1la. Alive Dead Pup Wt. Days "H F Total 9 --Bay 4 Pre-Cull Post-Cull Mean Mean No. Alive Pup Wt. No. Alive Pup Wt. K F Total 9 M Total 9 A' A" A" A* A' r A" A" A" A" A' A' 22 6 2 4 6 0 6.B 2 4 6 8.7 246 21 15 8 7 15 0 5.5 8 7 15 8.0 5 5 10 22 13 5 8 13 0 6.0 5 8 13 9.8 5 5 10 22 10 4 6 10 0 6.1 4 6 10 9.7 4 6 10 21 14 6 8 14 0 5.7 6 8 14 8.3 5 5 10 22 11 6 4 10 1 6.9 6 4 10 11.4 6 4 10 22 11 6 5 11 0 6.9 6 5 11 9.9 5 5 10 Mating confirmed; evidence of parturition; one Implantation scar noted at term sacrifice. 22 14 6 8 14 0 5.9 6 8 14 9.1 5 5 10 Mating confirmed; no evidence of parturition; no Inplant scars at term sacrifice- not pregnant. 22 11 7 4 11 0 6.6 7 4 11 10.8 6 4 10 21 10 5 5 10 0 5.8 5 5 ID 8.8 5 5 10 22 10 5 4 9 1 7.1 5 4 9 10.4 549 21 13 9 4 13 0 6.0 9 4 13 9.0 6 4 10 22 12 7 5 12 0 6.0 7 4 11 10.8 6 4 10 22 12 7 5 12 0 6.5 7 5 12 10.4 5 5 10 Mating not confirmed; female sacrificed post-mating- no lamlant scars not pregnant. 21 13 7 6 13 0 6.2 7 6 13 9.4 5 5 10 21 17 7 10 17 0 5.3 6 10 16 7.7 5 5 10 22 13 6 6 12 l 5.9 4 3 7 6.5 437 Mating confirmed; no evidence of parturition; no Implant scars at term sacrifice- not pregnant. 22 5 4 1 S 0 7.1 4 1 5 12.4 4 1 5 21 11 4 7 11 0 5.7 4 7 11 8.6 4 6 10 Mating confirmed; ao evidence of parturition; however. 17 lanlantatlon scars noted at term sacrifice. 22 13 7 6 13 0 5.9 7 6 13 8.2 5 5 10 22 12 5 7 12 0 6.6 5 7 12 11.0 5 5 10 8.7 8.1 9.8 9.7 8.3 11.4 9.8 9.3 10.8 8.8 10.4 8.9 10.8 10.3 9.4 7.8 6.5 12.4 8.5 8.2 11.1 Ho. Alive A" 6 10 10 K) 10 10 10 10 10 8 9 10 10 10 10 10 7 5 10 10 10 tfean Pup Wt. No. Alive 9 "if------- F Total 21.6 22.4 21.4 22.2 21.8 25.1 23.3 A" A' A* 246 5 5 10 5 5 10 4 6 10 5 5 10 6 4 10 5 5 10 22.6 5 5 10 26.4 6 4 10 19.9 4 4 8 24.1 5 4 9 21.7 6 4 10 23.8 6 4 10 24.3 5 5 10 23.9 5 5 10 22.6 5 5 10 11.4 4 3 7 27.2 4 1 5 21.6 4 6 10 21.5 5 5 10 26.5 5 5 10 Mean Pup Wt 9 38.3 35.2 38.3 36.4 31.7 39.1 38.5 38.7 44.9 33.7 40.3 33.0 42.0 35.9 36.1 36.1 21.5 45.5 32.3 34.7 44.5 CO NFTO FNTIAL otal 455 246 123 120 243 3 130.5 120 116 236 198.9 102 95 197 199.0 195 475.3 101 94 195 775.8 lf) 21.7 11.7 6.9 5.7 11.6 0.1 6.2 5.7 5.5 11.2 9.5 4.9 4.5 9.4 9.5 9.3 22.6 4.8 4.5 9.3 36.9 .0. 0.5 2.7 1.6 2.0 2.7 0.4 0.5 1.6 2.1 2.8 1.4 0.9 1.1 1.5 1.4 1.5 3.2 0.9 1.1 1.5 5.3 .E. 0.1 0.6 0.3 0.4 0.6 0.1 0.1 0.4 0.5 0.6 0.3 0.2 0.2 0.3 0.3 0.3 0.7 0.2 0.2 0.3 1.1 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 For explanation of statistical tjabtl: A". K~; see Appendix q. (tey; N - male; F - female. < N D-2 f i K ft MHMMI Appendfx D (cont.) An Inhalation Female Fertility Study with tenzene In Rats 79-2425 Litter Informatton - Group II (1 ppm) Dan Sire NO. No." 425 18 426 18 427 19 428 19 429 21 430* 21 431 22 432 22 433 23 434 23 435 24 436 24 437* 438 25 439 27 440 27 441 29 442 29 443 30 444 30 MS, 31 446* 447 32 448 32 o o :? 449 33 4501 33 z3 U O Total 'TOl Nj Mean z NJ SJ. -t O' S.E. 11 Gest. Total Length Pups Days Day 0 Pre-Cull M7!. lb. Mean Mean No . Alive Dead* Pup Vt. No. Alive Pup Vt. tt ^StaT 9 H --j-- Total 9 M Post-Cu!1 No. Alive Total 22 14 a 6 14 0 6.3 8 6 14 9.0 5 5 10 22 13 3 9 12 1 6.2 3 8 11 10.4 3 7 to Hating confirmed; no evidence of parturition; no Ismlant scars at term sacrifice- not pregnant. 22 13 5 0 13 0 6.4 5 8 13 10.4 $ 5 10 22 14 6 8 14 0 6.0 6 8 14 9.1 5 5 10 feting confirmed; no evidence of parturition; two laplant scars noted at term sacrifice. 21 14 6 8 14 0 5.6 6 8 14 8.4 5 5 10 21 12 5 7 12 0 5.6 5 7 12 8.3 5 5 10 22 13 8 5 13 0 6.5 8 5 13 8.6 5 5 10 21 13 8 4 12 1 6.1 a 4 12 8.8 6 4 10 22 11 3 8 11 0 6.0 3 8 11 8.8 3 7 10 22 10 4 5 9 1 6.1 4 5 9 11.4 45 9 feting not confirmed; fenales sacrificed post-mating- 13 Imputation sites observed. 22 13 10 3 13 0 5.9 10 3 13 10.0 7 3 10 21 10 5 5 10 0 5.8 5 4 9 10.0 549 22 16 9 7 16 0 5.9 8 7 IS 9.1 5 5 10 22 14 8 6 14 0 6.5 8 6 14 7.6 5 5 10 22 12 9 3 12 0 6.8 9 3 12 9.5 7 3 10 22 10 4 6 10 0 6.8 4 6 10 11.1 4 6 10 22 7 6 1 7 0 6.6 6 1 7 11.9 61 7 22 13 5 8 13 0 6.6 5 8 13 10.5 5 5 10 feting not confirmed; fenales sacrificed post-mating- 15 laplantatlon sites observed. 22 11 7 4 11 0 6.6 7 4 11 W.1 6 4 10 21 10 7 2 9 1 5.2 7 2 9 9.6 729 23 2 2 0 2 0 7.3 2 0 2 12.4 2 0 2 22 IS 9 4 13 [2] 6.6 9 4 1 11.0 6 4 10 400 21.0 0.5 0.1 22 260 1M 3.0 0.6 22 137 6.2 2.2 0.5 22 117 5.3 2.5 0.5 22 254 11.5 3.0 0.6 22 6 137.4 0.3 6.2 0.5 0.5 0.6 0.1 22 22 136 6.2 2.2 0.5 22 115 5.2 2.4 0.5 22 251 11.4 2.9 0.6 22 216.0 9.8 1.2 0.3 22 111 5.0 1.3 0.3 22 95 4.3 1.7 0.4 22 206 9.4 1.8 0.4 22 Mean Pup Vt. 9 Day 14 Oav 21 Mean Alive Pup Vt. Ns. Alive 9 1 H... F Total fean *P W? 9 9.0 10 23.5 5 5 10 35.1 10.4 10 24.1 3 7 10 39.3 10.5 10 22.9 5 5 10 43.2 9.1 10 23.5 5 S 10 40.7 0.4 10 21.8 5 5 10 33.3 8.4 10 20.5 5 5 10 30.9 8.8 10 20.2 5 5 10 33.9 8.8 10 22.2 6 4 10 35.3 8.8 10 20.9 3 7 10 32.7 11.4 9 25.4 4 5 9 40.5 9.9 10 26.1 7 3 10 45.1 10.0 9 20.4 5 4 9 32.2 9.1 10 21.0 5 5 10 35.5 7.2 10 19.4 5 5 10 33.0 9.4 10 24.8 7 3 w 37.8 11.1 10 19.9 4 6 10 26.2 11.9 7 25.9 6 1 7 45.3 10.6 10 25.4 5 5 10 41.7 10.1 10 24.0 6 4 10 40.8 9.6 9 20.7 7 2 9 30.2 12.4 2 16.3 2 0 2 16.3 11.0 10 29.1 6 4 10 - 49.1 215.9 9.8 1.3 0.3 22 206 9.4 1.8 0.4 22 498.0 22.6 2.9 0.6 22 111 5.0 1.3 0.3 22 95 4.3 1.7 0.4 22 206 9.4 1.6 0.4 22 798.1 36.3 7.2 1.5 22 No statistically slpilficaat differences fron the control Group. Key: N - male; F - ramie. 0-3 YZOO14422 Appendix 0 (coot.) An Inhalation Female Fertility Study with Benzene In Rats Litter Information - Groap HI (10 ppm) Dam Sire No. No.* 62S 34 (26 a (27 35 (28 35 (29 36 (30 36 (11 37 (32 37 (33 39 (3* 35 (35 40 (36 40 (37 41 (38 44 (39 44 (40 44 (41 45 (42 45 643 46 (44 46 (45 47 (46 47 (47 48 (48 48 (49 SO (SO 50 Gest. Length Days Day 0 Total PP(- *I. Alive "1---- F Total Ho. Dead Mean Pud tit. 9 -------- DS7T Pre-Cull Post-Cui 1 Day 14 Mean Mean NO. Mean No. Alive Pud Ht. M F Trial 9 No. Alive Pud Ut. Alive Pud Ut. n F Total 9 9 22 11 4 6 10 i 6.6 4 6 10 10.3 4 6 10 22 13 8 5 13 0 6.4 8 5 13 11.0 5 5 10 21 11 7 4 11 0 5.5 7 4 11 8.1 6 4 10 22 14 9 5 14 0 5.5 8 5 13 8.8 5 5 10 Katina confirmed; no evidence of parturition: no Implant scars at term sacrifice- not pregnant. 22 13 7 6 13 0 6.1 7 6 13 8.3 5 5 10 22 5 3 2 5 0 7.1 3 2 5 13.0 3 2 5 22 15 6 9 15 0 6.3 6 9 15 9.0 5 5 10 22 10 4 6 10 0 6.5 4 6 10 11.5 4 6 10 22 13 7 6 13 0 5.8 7 6 13 10.4 5 5 10 22 14 7 7 14 0 6.5 7 7 14 9.7 5 5 10 23 5 3 2 S 0 7.8 3 Z 5 15.8 3 2 5 22 15 9 5 14 1 6.1 8 5 13 9.1 5 5 10 Nrtlna confined: no evidence of parturition; no Inplant scars at term sacrifice- not pregnant, 22 13 6 7 13 0 6.6 6 6 12 10.5 5 5 to 22 13 5 8 13 0 6.4 5 8 13 8.7 5 5 10 22 13 8 4 12 1 6.4 8 4 12 9.2 6 4 10 23 14 3 6 9 5 7.0 3 6 9 12.0 369 22 15 6 9 IS 0 6.4 6 9 IS 9.6 5 5 10 21 16 7 9 16 0 5.3 7 9 16 7.7 5 5 10 22 13 4 8 12 [llb 6.1 4 a 12 9.0 4 6 10 21 15 8 7 15 0 5.3 6 7 15 8.3 5 5 10 22 11 5 6 11 0 7.0 5 6 11 HU 5 5 HI 22 11 3 8 11 0 7.0 3 8 11 12.0 3 7 10 22 16 12 4 16 0 6.4 12 4 16 9.7 6 4 10 21 13 7 6 13 0 5.8 7 6 13 9.4 5 5 10 10.3 10 14.2 10.8 10 24.5 8.0 10 18.3 8.7 10 18.8 8.3 s 12.3 13.0 5 30.6 9.0 10 22.5 11.5 10 25.1 10.3 10 25.9 9.7 10 25.1 15.8 5 32.4 9.0 10 24.0 10.4 10 24.3 8.9 10 22.9 9.2 10 20.1 12.0 9 24.5 9.7 10 24.0 7.8 9 23.0 9.1 10 22.6 8.4 10 23.6 10.2 21.2 12.0 9 29.1 9.8 10 24.1 9.S 10 24.3 79-2425 Day 21 No . Alive _____ F. Tof1 Mean Pub Ut. 9 2 2 4 15.2 5 5 10 40.5 6 4 10 27.6 5 5 TO 28.0 3 2 5 24.7 3 2 5 50.8 5 5 10 37.1 4 10 41.1 5 5 10 40.5 5 5 10 42.9 3 2 5 54.7 5 5 10 38.5 S 5 10 41.5 5 5 10 38.6 6 4 10 29.7 3 .( 9 43.3 5 S 10 40.2 5 4 9 33.8 4 6 W 36.4 5 5 10 36.4 5 5 10 36.5 3 ( 9 47.6 6 4 10 39.5 5 5 10 38.5 Total Kean\ S.O. S.E. N (26 21.9 0.5 0.1 24 302 12.6 2.8 0.6 24 148 (.2 2.3 0.S 24 145 6.0 2.0 0.4 24 293 12.2 2.9 0.6 24 9 0.4 1.0 0.2 21 151.9 6.3 0.6 0.1 24 146 6.1 2.2 0.5 24 144 6.0 2.0 0.4 24 290 12.1 2.9 0.6 24 241.2 10.1 1.8 0.4 24 112 4.7 0.9 0.2 24 117 4.9 1.1 0.2 24 229 9.5 1.4 0.3 24 241.4 10.1 1.8 0.4 24 222 9.3 1.7 0.3 24 557.4 23.2 4.4 0.9 24 108 4.5 1.1 0.2 24 108 4.5 1.3 0.3 24 216 9.0 2.0 0.4 24 903.7 37.7 8.4 1.7 24 Ha statistically significant 41fftranceI fnaa the control gr Key: 11 - male; F * fwlc. 0-4 ta Sir* >to. tej* 825 SI 826 SI 627 $2 B28, 52 829* - 830 53 831 54 832* 54 833 55 834 55 835 55 835 56 8378 57 838 57 839 58 840 58 841 59 842 59 843 50 844 50 845 61 645 61 847 62 848 62 849 $3 850 63 Appendix D (cont.) An Inhalation Fenale Fertility Study with Benzene In Rats Litter Information - Group If (30 ppu} Gest. Total length ES_ Days Pay 0 Prc-iuil' Pay 5 Post-dull 22 13 22 13 9 13 10 13 6.9 6.2 9 13 10 13 9.1 9.8 22 14 22 10 6 14 7 10 6.2 6.6 6 14 7 10 n.5 10.2 22 22 Hating 93 11 7 confirmed; no 69 4 11 evidence of 0 6.1 369 0 6.2 7 4 11 parturition; however, 23 i^lantettoe 11.3 9.5 scars noted 3 6 at $9 4 10 term stcrlflce. ffatlng confirmed; Kiting confirmed; 22 15 8 no evidence of parturition; no no evidence of 7 15 parturition; no 5.9 1mil ant Inplant - scars scars - at term sacrifice* at term sacrifice- ~ 8.5 net pregnant, not pregnant. 55 10 Hating 22 confirmed; 52 no evidence of parturition; however, 6.9 14 Implantation scars noted 11.7 at term sacrifice. 21 21 21 21 22 22 21 15 7 8 1$ 0 5.9 7 8 15 9.1 5 5 10 14 6 8 14 0 5.5 6 8 14 11 6 5 11 0 5.7 6 5 11 8.7 5 s 10 8.9 5 5 10 13 8 5 13 0 6.4 8 5 13 8.1 5 $ 10 15 4 11 15 0 5.7 3 11 14 8.3 3 7 10 63 3 60 13 3 W 13 0 7.1 5.5 3 36 3 10 13 13.1 8.4 3 3 36 7 10 Hating confirmed; 22 15 6 no evidence of parturition; no 5 13 2 5.7 Inplant 8 scars at term sacrifice- 5 13 7.8 not 5 pregnant. 5 w 22 22 22 13 S 13 9 74 8 13 0 4 13 0 3 70 6.6 6.1 7.8 5 9 4 B 13 4 13 37 9.5 9.3 13.8 5 6 4 5 10 4 10 37 Hating confirmed; no evidence of parterltlon; no loplaat scars at term sacrifice- not peasant. 79-2425 9.1 10.0 10.6 10.2 11.3 9.5 inIT W Ho. Hean Alive Pup Wt. 9 ______5Z-&I-- NO. Alive f__M__________ Total Hean Pupht. 9 10 21.0 4 6 10 34.0 10 24,4 3 7 10 37.7 10 25.2 5 5 K> 38.2 10 19.6 3 7 10 32.1 9 26.5 3 6 9 .40.3 10 19.3 6 4 10 30.3 8.4 10 21.3 5 5 10 32.5 11.7 6 26.5 2 4 6 41.3 9.4 10 24.2 5 5 10 38.0 8.6 10 20.7 5 5 10 31.0 8.8 10 18.4 5 5 10 26.9 8.1 10 20.2 5 5 10 30.3 8.4 10 20.0 3 7 10 30.6 13.1 6 27.7 3 3 6 43.9 8.4 10 20.6 3 7 10 29.8 7.9 9 10.7 4 5 9 30.5 9.5 10 18.8 5 5 10 31.1 9.3 10 20.0 6 4 10 31.6 13.8 7 29.3 4 3 7 44.9 Total ItM S.0. S.C. 11 413 21.7 9.5 0.1 19 225 1 122 223 2 m.o 11.8 5.3 6.4 11.7 0.1 6.2 3.1 2.3 2.5 3.0 0.5 0.6 0.7 M 0.6 0.7 0.1 0.2 19 19 19 19 19 19 100 5.3 2.3 0.S 19 123 6.5 2.5 0.6 19 223 11.7 2.9 0.7 19 185.6 9.8 1.7 0.4 19 80 98 178 186.1 4.2 5.2 9.4 9.8 1.2 1.3 1.4 1.7 0.3 0.3 0.3 0.4 19 19 19 19 177 9.3 1.4 0.3 422.4 22.2 3.4 0.8 19 79 90 177 655.0 4.2 5.2 9.3 34.5 1.2 1.3 1.4 5.3 0.3 0.3 0.3 1.2 19 19 19 19 No statistically significant dlffi Reg: R * mle; F - fenale. from the control group. *< g 8-5 K> -U Appendix 0 (cent.) An Inhalation Female Fertility Study with Oenzene In Rats titter Information - Group V (MO pp) Dan Sire Ho. Mo.* 1025 68 1026 66 1027 65 1028 70 1029 66 1030 66 1031 67 1032 67 1033 68 1036 68 1035 69 1036 69 1037 70 1038 70 1039 71 1060 71 1061 72 1062 72 1063 73 1066 73 1065 76 1066 76 1067 75 1068 75 1069 77 1050 77 ----- 6est. ToGT kst~ Naan Length Pups Noi. Alive Doad Pup wt. bays T'~ F ~TotaT 9 n Mo. Alive F Total Par 4 Post-Cult Mean Pud Wt. No. Alive 9 _5_ F Total Mean Pup Wt. 9 Hoi-- Mean Alive Pud Wt. 9 22 9 1 4 5 4 6.1 0 0 22 15 9 6 15 0 5.6 9 6 15 9.2 5 5 10 22 11 3 6 9 2 6.6 3 6 9 10.7 3 6 9 22 12 7 S 12 0 5.9 6 4 10 6.1 6 4 10 21 11 6 5 11 0 5.6 6 $ 11 9.3 5 5 10 IUt<M confirmed; no evidence of parturition; no Inplant scars at tern sacrifice- not pregnant. 22 8 0 2 2 L6JC 7.0 0 2 2 13.1 0 2 2 21 IS 10 5 15 0 5.4 10 5 15 8.2 5 5 10 21 t? 5 6 11 0 5.4 5 6 11 9.4 5 5 w 22 11 6 5 11 0 5.9 6 5 11 8.8 5 5 10 21 13 8 5 13 0 6.0 8 5 13 9.8 5 S 10 21 14 9 5 H 0 5.6 9 5 14 8.4 5 5 10 22 13 6 7 13 0 6.2 6 7 13 9.4 5 5 w 21 15 5 10 15 0 5.5 5 10 15 8.3 5 5 10 22 11 4 6 10 1 5.6 4 6 10 9.8 4 6 10 22 15 8 7 15 0 6.6 8 7 15 9.5 5 5 n Mating confirmed: no evidence of parturition; no iMptmt scars at tern sacrifice- not pregnant, 21 10 3 7 10 0 5.8 3 7 10 10.3 3 7 10 21 8 5 3 8 0 5.6 5 3 8 9.8 5 3 8 21 15 11 4 15 0 5.5 11 3 14 8.S 7 3 10 22 10 5 3 82 6.5 5 3 8 10.0 5 3 8 21 16 10 6 16 0 5.8 10 6 16 8.6 5 5 10 Mating confirmed; no evidence of parturition; no Inplant scars at term sacrifice* not pregnant, 23 5 3 2 50 7.4 3 2 5 13.9 3 2 5 22 15 11 4 15 0 6.1 11 4 IS 10.3 6 4 W 22 13 * 4 13 0 6.4 9 4 13 9.9 6 4 w 9.1 10.7 6.1 9.2 13.1 8.1 9.5 8.8 9.9 8.3 9.6 8.3 9.8 9.6 10.3 9.8 8.5 10.0 8.5 13.9 10.2 9.8 9 9 8 HI 2 10 10 9 10 10 10 10 10 TO 10 8 10 8 M 5 10 10 15.0 22.2 16.2 20.7 28.0 22.5 22.0 21.9 22.1 21.0 21.6 20.7 21.6 24.2 21.0 19.3 21.6 21.2 19.7 26.5 25.3 21.0 79-2425 netn No. Alive Pup Wt N T Total 9 4 5 9 24.5 3 6 9 36.8 6 3 9 23.8 5 5 10 28.1 0 2 2 46*0 5 5 to 33.2 5 5 10 37.0 4 5 9 31.7 5 5 10 34.6 5 S 10 30.9 5 5 10 34*5 5 5 10 31.8 4 6 10 32.5 5 5 10 40.6 3 7 10 34.0 5 3 8 30.4 7 3 34.4 5 2 7 37.0 5 5 10 28.7 3 2 s 42.1 6 4 10 40.9 6 4 10 34.0 Tetat Mean SJ0. S.E. i 497 21.6 0.6 0.1 23 276 12.0 2.9 0.6 23 144 6.3 3.1 0.6 23 117 5.1 1.8 0.4 23 261 11.3 3.8 0.8 23 15 0.7 1.5 0.3 23 138.1 6.0 0.5 0.1 23 142 6.2 3.0 0.6 23 111 4.8 1.9 0.4 23 253 11.5 3.6 0.8 22 211.3 9.6 1.6 0.3 22 103 4.7 1.4 0.3 22 99 4.5 1.3 0.3 22 202 9.2 2.0 0.4 22 211.1 9.6 1.6 0.3 22 198 9.0 2.0 0.4 22 475.3 21.6 2,9 0.6 22 101 4.6 1.4 ' 0.3 22 97 4.4 1.4 0.3 22 198 9.0 2.0 0.4 22 748.3 34.0 5*5 1.2 22 do statistically significant differences frcai the control group. Kay: H aria; F fenale. -* YZ0014425 ^oo Appendix 0 (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Dm Sire no. No.* B2S 51 826 51 827 52 828 52 82911 830 53 831 54 832* 54 833 65 834 55 835 56 836 56 8379 57 838 57 839 58 840 58 841 59 842 59 843 60 844 60 845 61 846 61 847 62 848 62 849 63 850 63 titter Information - Group IV (30 ppm) Cost. Total Length Tups Says ---------------------------- forT""-- - -- --------- ---------------------------------- Par 0 Ere-Cul! Post-Cull Pay 14Pay 21 No. Hean No. Alive Dead Pud Wt. H " T~ ' Total 9 Hean Ho. Alive Pup tit. H F Total 9 Kean No. Hean Ho. Alive Pud tit. Alive Pud tit. )( F Total 9 9 Hean No. Alive Pujlt_. F Total 9 22 22 22 22 13 4 9 13 0 6.9 4 9 13 13 3 10 13 0 6.2 3 10 13 9.1 4 6 10 9.1 10 21.0 4 6 10 34.0 9.B 3 7 10 10.0 10 24.4 3 7 10 i/i 14 8 6 14 0 6.2 8 6 14 10 3 7 10 0 6.6 3 7 10 10.5 10.2 5 3 5 10 7 10 10. s 10 25.2 10.2 10 19.6 5 3 5 10 7 10 38.2 32.1 - 22 22 93 11 7 6 90 4 11 0 6.1 6.2 3 7 69 4U 11.3 9.5 3 6 69 4 10 11.3 9 26.5 9.5 10 19.3 3 6 9 4 TO 40.3 30.3 Hating confirmed: no evidence of parturition; however, 23 implantation scars noted at term sacrifice. Hating confirmed*, no evidence of parturition; no Implant scars at tens sacrifice- not pregnant. Katina confirmed: no evidence of parturition; no Implant scars at term sacrifice- not pregnant. 22 15 8 7 15 0 5.9 8 7 15 8.5 5 5 10 8.4 K) 21.3 5 5 10 3ZaS Hating confirmed: no evidence of parterltlon; however. 14 Implantation scars noted at term sacrifice. 22 5 2 3 5 0 6.9 2 4 6 11.7 2 4 6 21 IS 7 8 15 0 5.9 7 8 15 9.1 5 5 10 11.7 9.4 S 10 26mS 24.2 21 21 21 22 22 21 14 6 8 14 0 5.5 6 8 14 11 6 5 11 0 5.7 6 5 11 13 8 5 13 0 5.4 8 5 13 8.7 5 5 10 8.9 5 5 10 8.1 5 5 10 8.6 10 20.7 8.8 10 18.4 8.1 TO 20.2 15 4 11 15 0 6 3 3 60 13 3 10 13 0 5.7 7.1 5.5 3 11 14 336 3 10 13 8.3 13.1 8.4 3 3 3 7 10 16 7 10 B.4 10 20.0 13,1 6 27.7 8.4 TO 20.6 2 5 5 5 5 3 3 3 4 5 10 5 to 5 10 5 10 7 10 36 7 10 41.3 38.0 31.0 26.9 30.3 30.6 43.9 29.6 Hating confirmed; no evidence of parturition; no Inplant scars 22 15 8 5 13 2 5.7 a 5 at term 13 sacrifice7.8 not 5 pregnant. 5 TO 22 13 5 8 13 0 6.6 5 8 13 9.5 5 5 10 22 13 9 4 13 0 6.1 9 4 13 9.3 6 4 10 22 7 4 3 7 0 7.8 4 3 7 13.8 4 3 7 7.9 9 T8*7 9.5 10 18.8 9.3 10 20.0 13.8 7 29.3 4 5 6 4 sD 5 10 4 10 37 30.5 31.1 31.* 44.9 Hating confirmed} no evidence of parturition; no hplnt scars at term sacrifice- not pregnant. Total Moan S.P. S.E. R 413 21.7 0.5 0.1 19 225 Wl 122 223 2 m.o 11.8 5.3 6.4 11.7 0.1 6.2 3.1 2.3 2.5 3.0 0.5 0.6 0.7 0.5 0.6 0.7 0.1 0.2 19 19 19 19 T9 19 ,100 ' 5.3 2.3 0.5 19 123 6.5 2.5 0.6 19 223 11.7 2.9 0.7 19 185.6 9.8 1.7 0.4 19 80 4.2 1.2 0.3 19 98 5.2 1.3 0.3 19 17B 9.4 1.4 0.3 19 186.1 177 422.4 9.8 9.3 22.2 1.7 1.4 3.4 0.4 * 0.3 0.8 19 19 19 79 98 177 655.0 4.2 5.2 9.3 34.5 1.2 1.3 1.4 *3 0.3 0*3 0.3 1.2 19 19 19 19 Ho Artistically *l9if1ca(it differences from the control Key: H male; F * faMle. P-S Appendix 0 (cont.) An Inhalation Fenale Fertility Study with Benzene In Rats litter Information - Croup {300 ppn) Dam Sire No. Mu.* 1025 60 1026 64 1027 65 1020 70 1029 66 1030 66 1031 67 1032 67 1033 60 1034 60 1035 69 1036 69 1037 70 1030 70 1039 71 1040 71 1041 72 1042 72 1043 73 1044 73 1045 74 1046 74 1047 75 1040 75 1049 77 1050 77 Par 0____________ Gestm Total length ftiw No. Alive No. Hean Dead Pud Ut. Days ~1T~ f Tota) 9 Pax * Pre-Cull Port-CulI ~ Oar 11 Hean hean Mo. Mean Ho. Alive Pun Ut. No. Alive Pun Ht. Alive Pun Ut. H F Total 9 H F Total 9 9 22 9 1 4 54 6.1 0 0 22 15 9 6 15 0 5.6 9 6 IS 9.2 5 5 10 22 11 3 6 9 2 6.6 3 6 9 10.7 3 6 9 22 12 7 5 12 0 5.9 6 4 10 6.1 6 4 10 21 11 6 5 11 0 5.6 6 5 11 9.3 5 5 10 Hating confirmed; not evidence of parturition; no Inplant scan at tana sacrifice- not pregnant. 22 0 0 2 2 C6F 7.0 0 2 2 13.1 0 2 2 21 15 10 5 1$ 0 5.4 10 5 IS 0.2 5 5 W 21 11 s 6 11 0 S.4 5 6 11 9.4 5 5 10 22 11 6 5 11 0 5.9 6 5 11 8.8 5 S 10 21 13 0 5 13 0 6.0 6 5 13 9.0 5 5 10 21 14 9 5 14 0 5.6 9 5 14 22 13 6 7 13 0 6.2 6 7 13 8.4 5 5 10 9.4 5 5 10 21 15 5 10 15 0 5.5 5 10 15 8.3 5 S 10 22 II 4 6 10 1 5.6 4 6 10 9.0 4 6 10 22 15 B 7 15 0 6.6 8 7 15 9.5 5 5 10 Katina confirmed; no evidence of parturition; no Inplant scars at term sacrifice- not pregnant. 21 10 3 7 10 0 5.0 3 7 10 10.3 3 7 10 21 0 5 3 0 0 5.6 5 3 8 9.8 5 3 8 21 15 11 4 15 0 5.5 11 3 H 8.5 7 3 10 22 10 5 3 0 2 6.5 5 3 0 10.0 5 3 0 21 16 10 6 M 0 5.0 10 6 16 8.6 5 5 10 Hating confirmed: no evidence of parturition; no Ini ant scan at term sacrifice- not pregnant. 23 5 3 2 5 0 7.4 3 2 5 13.9 3 2 5 22 15 11 4 15 0 6.1 11 4 IS 10.3 6 4 10 22 13 9 4 13 0 6.4 9 4 13 9.9 6 4 10 9.1 10.7 6.1 9,2 13.1 8.1 9.5 8.8 9.9 8.3 9.6 8.3 9.8 9.6 10.3 9.8 8.5 10.0 B.5 13.9 10.2 9.8 9 9 8 10 2 10 10 9 10 10 10 10 10 10 10 8 10 8 10 5 10 10 15.0 22.2 16.2 20.7 28.0 22.5 22.0 21.9 22.1 21.0 21.6 20.7 21.6 24.2 21.0 19.3 21.6 21.2 19.7 26.5 25.3 21.0 79-2425 Piy 21 Hean No. Alive Pup Ut M F TotaT 9 4 5 9 24.5 3 6 9 36.8 6 3 9 23.8 5 5 10 28.1 0 2 2 46*6 5 5 10 33.2 5 5 10 37.0 4 5 9 31.7 5 5 10 34.6 S 5 10 30.9 5 5 K) Ha5 5 5 10 31.8 4 6 10 32.5 5 5 H> 40.6 3 7 10 34.0 5 3 8 30.4 7 3 10 34.4 5 2 7 37.0 5 S 28.7 3 2 5 42.1 6 4 10 40.9 6 4 10 34.0 Total Hean SJB. S.E. N 497 21.6 0.6 0.1 23 276 12.0 2.9 0.6 23 144 6.3 3.1 0.6 23 117 5.1 1.8 0.4 23 261 11.3 3.8 0.8 23 15 0.7 1.5 0.3 23 138.1 6.0 0.5 0.1 23 142 6.2 3.0 0.6 23 111 4.8 1.9 0.4 23 253 11.5 3.6 0.8 22 211.3 9.6 1.6 0.3 22 103 4.7 1.4 0.3 22 99 202 4.5 9.2 1.3 2.0 0.3 0.4 22 22 211.1 9.6 .1.6 0.3 22 198 9.0 2.0 0.4 22 475.3 21.6 2.9 0.6 22 wi 4.6 1.4 0.3 22 97 198 4.4 9.0 1.4 2.0 0.3 0.4 22 22 748.3 34.0 5.5 1.2 22 No statistically significant differences Ira the control Key: H Hie; F - female. E-l Appendix E An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Implantation Scar and Unaccounted-for-Conceptl Data Group I (Control) - 0 ppm Female NO. 225 226 227 228 229 230 231 232c 233 234b 235 236 237 238 239 240. 241b 242 243 244 245b 246 247 2484 249 250 No. of Implantation nr Scars L Total 43 79 77 28 95 56 66 10 4 11 (0) (0} 78 56 75 59 97 84 (0) (0) 86 14 5 10 5 (0) (0) 42 57 (4) (13) 59 2 13 7 16 14 10 14 11 12 1 15 (0) 15 11 12 14 16 12 (0) 14 19 15 (0) 6 12 (17) 14 15 Total No. Puds at Birth 6 15 13 10 14 11 11 1 14 (0) 11 10 10 13 12 12 (0) 13 17 13 (0) 5 11 (0) 13 12 Unaccountedfor - Conceotl K- ' 1 1 1 0 0 0 1 0 1 - 4 1 2 1 4 0 - 1 2 2 1 1 (17) 1 3 Total: Mean: N: 275 12.5 22 247 11.2 22 28 1.3 22 Key: R right uterine horn; L left uterine horn. aFema1e did not deliver a litter; however. Implantation scar(s) was ob served at term sacrifice; data In parentheses excluded from calculations* "Female did not deliver a litter; data In parentheses excluded from calculatIons. CFemale Initiated delivery; one pup noted In vaginal canal. This pup was apparently cannablllzed prior to Day 0 litter examination. DO 067773 CONFIDFNTTAl YZ0014428 E-2 Appendix E (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Implantation Scar and Unaccounted-for-Conceptl Data Group II - (1 ppm) Femal e No. 425 426 427b 428 429 430" 431 432 433 434 435 436 437d 438 439 440 441 442 443 444 445. 446d 447 448 449 450 No. of Implantation Scars R _L_ Total 7 7 14 6 8 14 (0) (0) 58 (0) 13 8 6 14 (Z) (0) 76 (2) 15 5 7 12 5 9 14 5 8 13 7 4 11 8 2 10 (8) (5) 03) 7 6 13 64 12 9 8 17 8 7 15 8 5 13 5 5 10 6 10 16 4 10 14 (8) (7) (15) 5 8 13 5 6 11 20 2 6 9 15 Total No. Pups at Birth 14 13 (0) 13 14 (0) 14 12 13 13 11 10 (0) 13 10 16 14 12 10 7 13 (0) 11 10 2 15 Unaccountedfor - Concept1 0 1 - 0 0 (2) 1 0 1 0 0 0 0 2 1 1 1 0 9 1 - 2 1 0 0 Total: Mean: N: 281 12.8 22 260 11.7 22 20 1.0 22 No statistically significant differences from control. Key: R * right uterine horn; L * left uterine horn. "Female did not deliver a litter; however. Implantation scars were observed at term sacrifice; data In parentheses excluded from calcula tions. bFema1e did not deliver a litter; data In parentheses excluded from cal culations. (Female had no evidence of mating; sacrificed at completion of mating period and Implantation sites were evident; data In parentheses excluded from calculations. DO 067774 CONFtDFNTT Al YZ0014429 E-3 Appendix E (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Implantation Scar and Unaccounted-for-Concepti Data Group III - (10 ppm) Female No. 625 626 627. 628 629b 630 631 632 633 634 635 636 637 638^ 639 640 641 642 643 644 645 646 647 648 649 650 No. of Implantation Scars R L Total 10 5 77 56 79 (0) (0) 94 50 89 92 87 87 23 96 (0) (0) 76 59 77 87 79 10 6 85 96 66 66 6 10 58 15 14 11 16 (0) 13 5 17 11 15 15 5 15 (0) 13 14 14 15 16 16 13 15 12 12 16 13 Total No. Puds at Birth 11 13 11 14 (0) 13 5 15 10 13 14 5 15 (0) 13 13 13 14 15 16 13 15 11 11 16 13 Unaccountedfor - Conceotl 4 1 0 2 - 0 0 2 1 2 1 0 0 - 0 1 1 1 1 0 0 0 1 1 0 0 Total: Mean: N: 321 13.4 24 302 12.6 24 19 0.8 24 No statistically significant differences from control. Key: R right uterine horn; L left uterine horn. 'Female did not deliver a litter; data In parentheses excluded from cal- culatlons. DO 067775 CONFTDfTNT T At YZ0014430 E-4 Appendix E (cont.) An Inhalation Female Fertility Study with Benzene in flats 79-2425 Implantation Scar and Unaccounted for-Conceptl Data Group IV - (30 ppm) Female No. 825 826 827 828 829e 830 831 832a 833b 834b 835 836a 837 838 839 840 841 842 843 844 845b 846 847 848 849 850b No. of Implantation Scars R L Total 76 11 3 97 38 -- 65 85 01] (12) W0 0 (0) 87 (9) (5) 71 79 77 66 87 6 11 60 77 (0) (0) 88 58 86 26 (0) (0) 13 14 16 11 * 11 13 (23 (0 (0 15 04) 8 16 14 12 15 17 6 14 (0) 16 13 14 8 (0) Total No. Puds at Birth 13 13 14 10 - 9 11 0 io0: 15 (0) 5 15 14 11 13 15 6 13 (0) 15 13 13 7 (0) Unaccountedfor - Concent1 0 \ 2 1 - 2 2 (23) 0 (14) 3 1 0 1 2 2 0 1 m 1 0 1 1 * Total: Mean: N: 246 12.9 19 225 11.8 19 21 1.1 19 Key: R - right uterine horn; L left uterine horn. aFema1e did not deliver a litter; however. Implantation scar(i) was ob served at term sacrifice; data In parentheses excluded from calculations. bFemale did not deliver a litter; data In parentheses excluded from cal culations. ^Female was killed accidentally during Week 5 of the pre-mating treatment period. DO 067776 CONFTDFNTTAI YZ0014431 E-5 Appendix E (cont.) An Inhalation Female Fertility.Study with Benzene In Rats 79-2425 Implantation Scar and Unaccounted-for-Conceptl Data Group V - (300 ppm) Female No. 1025 1026 1027 1028 1029 1030b 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041** 1042 1043 1044 1045 1046 1047b 1048 1049 1050 No. of Implantation Scars ft L Total 11 0 87 11 6 84 75 (0) (0) 11 5 96 94 76 67 69 4 11 96 48 79 (0) (0) 55 84 79 73 7 10 (0) (0) 60 96 5 10 11 15 17 12 12 (0) 16 15 13 13 13 15 15 15 12 16 (0) 10 12 16 10 17 (0) 6 15 15 Total No. Pups at Birth 9 15 11 ' 12 n (0) 8 15 11 11 13 14 13 15 11 15 . (0) 10 8 15 10 16 (0) 5 15 13 Unaccountedfor - Concent1 2 0 6 0 1 8 0 2 2 0 1 2 0 1 1 0 4 1 0 1 w 1 0 2 Total: Mean: N: 301 13.5 23 276 12.0 23 35 1.5 23 No statistically significant differences from control. "Female did not deliver a litter; data In parentheses excluded from cal culations. DO 067777 CONFTDFNTTAl YZOO14432 F-l Appendix F An Inhalation Female Fertility Study With Benzene In Rats Gross Postmortem Observations - Females 79-2425 PREFACE Morphologic abnormalities observed grossly In the animals from this study occurred sporadically and do not appear to be compound-related. DO 067778 rONFTDFNTTAl YZOO14433 F-2 Appendix F (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Females Group ppm I 0 An. No. 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 Type of Death3 T T T T T T T T T T T T T T T T P-M T T T T T T T 249 T 250 T II 425 1 426 427 428 429 430 431 432 433 434 T T T T T T T T T T *T Terminal; P-N post-mating period. "N.O.A. No observable abnormalities. Observation!s)b N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Uterus: moderately distended area (6.4 X 0.3 cm.) filled with yel lowish fluid on distal end of left horn. Distal end of right horn extremely distended (1.2 X 0.3 cm.); filled with clear fluid. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. DO 067779 CONFIDENT TAt. YZOO14434 F-3 Appendix F (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Females Group ppm II 1 (cont.) An. No. 435 436 437 438 439 440 441 442 443 444 445 446 447 448 Type of Death! T T P-M T T T T T T T T P-M T M 449 450 III 625 10 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 T T T T T T T T T T T T T T T T T T T Observation s)b N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Kidneys (Both): slight red renal papilla. Lungs; all lobes slightly red. FvetRight): 20X opacities. Eve (left): slight alopecia and red crusty material around the eye; cyst on surface (.1 cm. dm,); lens moderately protruding. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Ovary (left): paraovarian cyst (0.3 cm. In dlam.). N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. ai Terminal; M Moribund; P-M - post-mating. bN.O.A. - No observable abnormalities. DO 067780 CONFTDFNTTAl -- YZOO14435 F-4 Appendix F (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Females Group ppm III 10 (cont.) IV 30 An. No, 642 643 644 645 646 647 648 649 650 825 826 827 828 829 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849 850 Type of Deaths T T T T T T T T T T T T T A T T T T T T T T T T T T T T T T T T T T T Observation s) b N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Uterus: distal end of left horn extremely distended with clear fluid. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. aT Terminal; A - Accidental, bN.0.A. No observable abnormalities. no 067781 CONF TOFNT T A( YZOO14436 F-5 Appendix F (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Gross Postmortem Observations - Females Group ppm V 300 An. No. 1025 1026 1027 1028 1029 TvDe of Death3 T T T T T 1030 T 1031 T 1032 T 1033 T 1034 T 1035 T 1036 T 1037 T 1038 T 1039 T 1040 T 1041 T 1042 T 1043 T 1044 T 1045 T 1046 T 1047 T 1048 T 1049 T 1050 T 3Y - terminal. bN.0.A. * No observable abnormalities. 0bservat1on(s)b N.O.A. N.O.A. N.O.A. N.O.A. Lungs: greenish-tan round nodule (approx. 0.6 cm. In dlam.) on superior lobe of right lung; two greenish-tan round nodules On middle lobe of right lung (approx. 1.1 cm. and 1.0 cm. In dlam.); greenish-tan round nod ule on Inferior lobe of right lung (approx. 0.5 cm. In dlam.); greenish-tan round nodule (ap prox. 1.2 cm. in dlam.) on left lobe. Right Lung: Masses on lobes; adhered to thoracic cavity; filled with a green caseous material. N.O.A. N.O.A. N.O.A. N.O.A. Axlllarv Area (Left): tan mass subcutaneous (l.l cm.). N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. DO 06778? CONFIDFNTTAl YZ0014437 F-6 Appendix F (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Females (cont.) Group ppm V 300 An. No. 1025 1026 1027 1028 1029 Tvoe of Death T T T T T 1030 T 1031 T 1032 T 1033 T 1034 T 1035 T 1036 T 1037 T 1038 T 1039 T 1040 T 1041 T 1042 T 1043 T 1044 T 1045 T 1046 T 1047 T 1048 T 1049 T 1050 T ^"Terminal. bN.0.A. - No observable abnormalities* Observation slb N.O.A. N.O.A. N.O.A. N.O.A. Lungs: greenish-tan round nodule (approx. 0.6 cm. In dlam.) on superior lobe of right lung; greenish-tan round nodules on middle lobe of right lung (approx. 1.1 cm. and 1.0 cm. In dlam.); greenish-tan round nodule on inferior lobe of right lung (approx. 0.5 cm. In dlam.; greenish-tan round nodule (approx. 1.2 cm. In dlam.) on left lobe. Right lung: Hasses on lobes; ad hered to thoracic cavity; filled with a green caseous material* N.O.A. N.O.A. N.O.A. N.O.A. Axillary Area (Leftl: tan mass li.i cm.}. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. DO 067783 CONFTDFNTTAl YZOO14438 G-l Appendix G An Inhalation Female Fertility Study With Benzene In Rats Pup Organ Weight Data Preface L/BW ratio of liver weight to boc|y weight (Day 21). K/BW * ratio of kidney weight to bocly weight (Day 21). T/BW ratio of testes weight to bocty weight (Day 21). 79-2425 DO 0R77R4 CONFTDFNITI Al. YZ0014439 G-1 Appendix G (cent.) An Inliilitlw Futile Fertility Study with kune 1* fats T9-2425 GROUT 30 UTTER r> oo V2 O ~o 5m J-->* aJ (J\ i i .t i 7 I 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I t 1 1 1 1 1 1 1 I 1 1 1 1 1 l 1 1 1 * 225 9 225 s 226 M 226 M 226 *t 226 M 226 H 227 1 227 N 227 * 227 K 227 1 223 M 223 S 223 *1 223 n 229 M 229 N 229 ? 229 *1 229 1 2;C 'I n 233 2:3 i 2:0 H 230 i 233 f 231 1 2*1 H 2;1 * 2:1 1 221 * 2:: *1 222 * 23; H 233 * 223 H >.*5 * 2)5 ! 2y ..5s S . r. ; % w TESTES "rar i r.i is 2 r.-.ti 1 r.i?i 2 i* m fCC > 1M*4 4 0.222 5 2.1 19 i 0.112 2 2.211 3 0.1S1 4 1.153 5 0.156 i 6*. 152 2" C. 145 0.129 4 2. 160 1 C. 151 2* 0.1;3 C.lt4 i If. 104 C 0.1 ;5 \ C. 159 2 2.153 0.137 1. 0.179 5 0.131 6 C.'3: 1 0.162 2" 0.141 C. It? 4 0.171 0.177 1 0.222 2 r. 169 4 0.163 4 0.192 5 2.176 11 PI # *** | * ll! M i-.l-jt 5 0.226 LITER Tir i.3>1.739 ' ~ri; 1.5'i 1 .4):' 1.236 1.254 1.324 2.043 1.611 1.53: 1.551 1.753 1.450 1.359 2.272 1.113 1.222 1.071 0.900 C.975 1.727 2.022 1.920 1.912 2.149 2.205 1.743 1.530 1 .*>05 2.212 1.555 1.771 1.309 1.J54 1 * 771 1.339 1.f-51 fc.i*97 2. 17.2 2.5 .6 2m '^i1 KtONETS "T5T" 2. ** 0.474 0.443 0. -?3 0.4C4 3 0.:24 2,4:2 2.? 39 2. = 61 2.;?1 0. 334 0.:-6 C. 345 3.-.27 2. =4 3 i.". ; V t 2.53: !!. 509 2. >31 0.4=6 2.436 2.49; 2.431 0.310 2.556 0.520 o.trc 0.470 2.47: 2.494 0.446 a. *22 2. >92 0.4:9 0.425 !.517 4.5SJ 0.S15 ' V4 .'.'51 T Iff. Til-- 41.4 * |1 **>.3 36. 3 35.3 5*i i 2.6 42.2 42.3 55.3 j7* ;*.G :2.5 32.2 36.2 41.9 2.9 iC. 1 29-7 30.1 30.4 4C.0 39-6 39.5* 41.1 42.6 4-.2 :.5 37. 4 39.? 3*1.3 IrC.2 4;.o 3.7 '5.6 40.0 it. 9 39.3 *5.o *>.* S3.5 it.i' T/BH L/BW K/BW 0.00448360 r.ortrnooo r..'04 >34 62 0.00434737 C.204r22>5 C.0055296'* 0.00426*30 2.22455224 0.00455526 0.02421733 0.2042021; 0.20647977 C.00557592 O.C2453125 0.00 3533?; C.CC531362 0.00453967 0.00453472 2.22434343 0.00=45515 C.00644279 C.OC397500 C.CC393990 0.02463672 0.00635523 0.00626333 0.00423611 0.0062077 2.00377025 C.ro?7739;> t.00*29663 0.20462299 c.rc926i? 0.004:6693 0.2C457355 0.20430000 C.C047*965 2.crt*K7.!>: o. 02*60:: oo r.;:;:t6a-*29 C.r-it-lf-iTG t .r;:5iiP*i 0,0453696 0.0467297 r.n6>/,32; 0.04007?3 0.0415403 r.03732:5 0.0334663 0.0443755 0.0473525 0.0450000 0.0621011 0.2442436 C.05*0923 0.0453125 C.C516319 2.0541766 0.0333293 0.2405930 c. 0360606 0.2299203 0.0320724 0.2431730 0.0555556 0.2476190 C.C465207 O.C50446G 0.0510417 3.0454026 0.0449193 0.r439717 0.0505025 0.2436*13 C.C431951 O.C667642 0.0374719 C.C444500 2.0493103 0.0490201 0.0510444 3.0*33?4r 0.0557163 0.05091:0 0.0115700 0.0123103 0.0114372 C.0103152 0.0112349 0.0099412 0.0099:37 0.0122335 0.0112617 0.C1C3659 0.0396011 0.01121;? O.P1131E4 0.0105CCC C.0095353 C.C1C1939 0.C1C5775 0.212526? O.C12395& C.01691O3 C.0125329 C.Clitcco 0. Cl22727 O.r12:559 P.0117032 0.012441; 2.012370* 0.01;5065 0.0112299 0.012032* C.C113345 O.C122336 C.0103730 0.010906* 0.C11C112 C.C1O9750 0.0115(76 C.0129399 C.0122339 3.011366* 2.21:27*7 C.012L ?Ct G-2 Appendix 6 (coot.) An Inhalation fewle Fertility Study with tenant I* Rats 79-2425 o ~7 r> T) MC? oO' "Tj SJ Z Nl M> i i i X X I X z I X I I I 1 X X X X X X I I X X I XI I I X X z X X X X X XI XI I SM LITTER M 235 M 234 M 234 M 234 N 235 M 237 M 237 N 237 N 237 M 237 H 238 M 238 n 238 H M 723JJ8 N 238 N 239 N 239 N 239 M 239 II 239 H H 223*09 N 240 N 240 H 240 H 240 N 242 N 242 M 242 H 242 H M 224423 H M nM 2*3 243 243 243 M 244 H 244 R 244 n 244 n 245 W ItSTtS T?1-- 6 0.234 t 0.069 2 0.164 3 0.422 4 0.146 1 0.478 2 0.188 3 C.497 4 0.204 5 0.478 1 2 0.152 0.456 3 0.159 4 0.148 5 0.442 6 0.452 4 0.491 2 0.192 3 0.476 4 0.204 5 0.499 8 0.184 4 0.467 2 0.485 3 0.441 4 5 00..117302 4 0.445 2 0.446 3 0.4T2 4 0.452 51 0.167 0.466 2 0.430 3 0.139 4 0.438 54 2 0.453 0-058 0.049 53 0.012 0.054 4 0.195 LIVER TiT 2.434 0.932 4.564 1.359 4-515 1.824 2.4 ?4 1.844 1.991 2.041 1.360 1.664 1.699 4.398 4.539 1.571 2.435 1.914 1.818 2.002 2.307 2.248 4.452 4.648 4.728 4.522 1.534 4.234 1.668 1.603 1.592 1.939 1.749 1-599 1.333 4.691 1.455 0.834 0.810 0.807 0.844 2.289 K10NEVS MOT vr. (9) " W 0.617 0.258 47.0 23-7 0.4C7 0.397 0.428 0.494 39.5 34.4 36.7 40.0 0.554 45.8 0.505 C.486 0.494 40.5 42.1 39.0 C.387 0.441 31-9 33.0 d.*P3 35.7 0.396 0.422 0.381 0.516 0.523 0.452 0.482 32-0 33.2 34.6 *2.9 41.8 40.9 42.6 0.545 45.0 0.496 0.414 49.7 35.6 0.452 37.3 0.429 0.447 34.9 36.0 0.433 38.0 0.400 0.502 0.439 0.468 0.444 34.1 3367..69 36.9 37.0 0.440 39-7 0.396 0.356 3**4 31.0 0.425 34.7 0.394 0.210 33*3 20.9 0.246 23.2 0.234 22.5 0.264 24.6 0.598 46.3 T/BW 0.00*91*89 0.00291139 0.00407595 0.00357771 0.00403270 0.00445000 0.00*10480 0.00486420 O.OC484561 0.00*56410 0.00*76489 C.C0472727 0.004*5378 0.00*62500 0.00427744 0.00*39306 0.00**5224 0.00*59330 0.00*30348 0.00*78873 0.00442222 0.00370221 0.00*69104 0.00*95979 0.00*0*014 0.00366667 0.00*47368 0.00425220 0.00390501 0.004699*5 0.00414924 0.00454351 0.00418436 0.00377907 0.00448387 0.00397695 0.00*59*59 0.00277542 0.00214207 0.00053333 0.00250000 0.00421166 L/BW 0.0517872 0.03932*9 0.03959*9 0.039853* 0.0412607 0.0*56000 C.0465939 0.0*55309 C. 04 729 22 0.0523333 0.042633? 0.0504242 0.0475910 0.0*36875 0.046355* 0.0*5*046 0.0567599 0.0457895 0.0*44*99 0.0469953 0.0512667 0.0452314 0.0407665 0.0444823 0.0*95129 0.0*22778 0.0*03684 0.0361877 0.0440106 0.0437978 0.0434436 0.052405* 0.0440554 0.0464826 0.0430000 0.0487320 0.0436937 0.0399043 0.0349138 0.0358667 0.0390741 0.0494384 IV BU 0.0131277 0.0108861 0.0103038 0.0116*22 C.0116621 0.0123500 0.0120961 0.0124691 0.0115*39 0.0426667 0.0121317 0.0133636 0.0112685 0.0423750 0.0127408 0.0110116 0.0120280 0.0125120 0.0110513 0.01131*6 0.0124114 0.0099799 00..00114215148409 0.0122923 0.0124167 0.0113947 0.0417302 0.0132454 0.0419945 0.0426829 0.0119489 0.0440831 0.0115116 0.0415484 0.0122478 0.0118318 0.0104306 0.0106897 0.0104000 0.0422222 0.0129158 -U U mm my i zz I X XI rX i i XI XI I I MEAN S.D. N su N H M M H N H H N H M Hti H N M H UT1CT 2*6 2*6 2*6 2*T 2*7 2*7 2*7 2*9 2*9 2*9 2*9 2*9 250 250 250 250 250 6-3 Appendix 6 (cant.) An Inhalation Fmle Fertility Study with fciiifia in Rats 79-2*25 MP TCS1ES 1?r 2 0.179 3( 0.194 0.472 1 0.4*6 2 0.139 3 0.152 * 0.4*2 4 0.13* 2 0.4*0 3 0.17* * 0.1*7 5 0.152 4 0.243 2 0.193 3 0.260 * 0.1*5 5 0.487 tmo T5T 1.913 2.357 2.000 1.321 1.339 4.<39 4. *58 1.267 1.57* 1.771 1.61? 1.812 2.065 2.117 2.122 4.916 2.060 KIDNEYS Tar 0. *95 0.576 0.5*0 0.359 0. 371 0.M3 0. ?79 0.3** 0. *02 0.459 0.520 C.*?8 0.550 O.*90 0.*91 0.502 0.502 BODY WT. TT <9.0 *6.0 **.3 32.7 31.9 35.9 3*.5 33.7 36.9 39.3 3*.6 37.0 *5.9 *3*0 **.9 *1.3 *3.5 T/BW 0.00365306 0.00*15217 0.00368262 0.00**6*03 0.00*35737 0.00*23396 0.00*1459* 0.00397626 0.00379*0* 0.00**27*0 0.00*2*855 0.00*10841 0.00*6*052 0.00**8837 0.00596882 C.0C3S1090 0.00*29885 L/BW 0.0390*08 0.0512391 0.0*69526 0.0*03976 0.0*197*9 0.0*00836 0.0*22609 0.037596* 0.0*26558 0.0*50636 0.0*673*1 0.0*09730 0.0**9891 0.0*92326 0.0*72606 0.0*6*407 0.0473563 K/BW 0.0101020 0.0125217 0.0124896 0.0109786 0.0116304 0.01150*2 0.0109055 0.0102077 0.01089*3 0.011679* 0.0150289 0.0129189 0.0149626 0.0*1501* 0.010935* 0.0121550 0.0115*02 0.162 1.705 0.443 0.037 0.390 0.060 101 101 101 37.6 0.00426 5.7 0.00068 101 101 0.04493 0.01177 0.00513 0.00108 101 101 oo o zo -H O "nO Osj' z SI N ---iI 0s0i x> fe. K) 6-4 Appendix 6 (cent.) An Inbnletlen Fault Fertility Study wttfi Imtene in bti 79-2425 POf sa tina HP HSTES Is) IIVEX (9) Kionm soot WT. Is) Ill T/BW L/BH K/BW II II II II II II II II II II II II II II II II II II II II II 11 II II ZI II II o oo 2a II II II XI II n Tz7> ^ iiii zi Z M zi 3 |-->*1 00 30 ii ii zi ii IZ H K 425 425 H K 425 42S (t 425 Ft 426 Ft 426 M 426 M 426 FHI 428 428 FI 428 n 428 H 429 H 429 H K 429 429 H 429 FI 434 HH 434 434 It H 434 434 Ft 432 It N 432 432 H M N H N H 432 432 433 433 433 433 H 433 H 4|4 H 4|4 Ft 434 H 434 H 434 H 434 H 435 H 435 Ft 435 1 0.157 1.751 0.457 2 0.462 1.581 0.452 3 C.U6 4.537 0.385 4 0.172 4.630 0.478 5 C. 162 1.433 0.438 1 0.190 1.940 0.446 2 0.199 1.938 0.479 3 0.209 1.878 0.457 1 0.159 1.561 0.398 2 0.204 2.210 0.504 3 0.478 2.216 0.513 4 0.165 4.775 0.435 5 0.470 2.081 0.437 4 0.254 2.011 0.500 2 0.233 2.457 0.579 3 0.181 4.830 C.50B 4 0.469 4.564 0.534 5 0.187 2.430 0.495 1 0.452 4.350 0.456 2 0.174 4.643 0.510 3 0.419 1.229 0.372 4 0.410 4.161 0.385 5 0.455 1.363 0.481 4 2 0.185 0.496 4.249 1.349 0.391 0.406 3 0.432 1.189 0.359 4 0.483 4.455 0.428 5 0.242 4.153 0.331 4 0.459 4.335 0.362 2 0.158 4.249 0.387 3 0.457 4.281 0.367 4 0.445 4.207 0.359 5 0.462 1.619 0.404 4 2 0.479 0.446 4.562 1.483 0.374 0.399 3 0.198 4.267 0.394 4 0.474 4.6T4 0.400 5 0.167 4.474 0.412 6 0.486 1.690 0.438 42 0.167 0.444 4.562 4.418 0.414 0.368 3 0.454 1.3T3 0.362 37.0 35.9 36.3 37.5 34.8 39.6 40,0 39.8 1G. 3 46.0 46.9 37.3 43.2 43.5 46.5 44.8 38.6 43.0 33.0 39. T 29.6 30.3 35.7 33-3 33.9 29-9 33.3 30.7 33.2 36.5 33.0 34.0 35.6 34.8 34.0 35.4 36.7 35.6 37.5 38.0 35.2 32.9 C.00424324 0.00451253 O.OP464848 0.00458667 0.00465517 0.00479798 C.CC497500 0.00525126 0.00438047 0.00443478 0.00379531 0.00442359 0.00393519 0.005T7011 0.00501075 0.00433014 0.00437824 0.00434884 0.00460606 0.00438287 0.00399329 0.00363036 0.00434474 0.00555556 0.00578171 0.00441472 0.00549550 0.00690554 0.00478916 0.00432877 0.00475758 0.00467742 0.00455056 0.00514368 0.00429412 0.00559322 0.00474144 0.00466480 0.00496000 0.00439474 0.00409091 0.00458967 0.04732*3 0.0440390 0.0423*16 0.043*667 0.0411782 0.0489899 0.0464500 0.0471859 0.0410028 0.0460435 0.0472495 0.0475874 0.048*713 0.0462299 0.0463871 0.0437799 0.0405481 0.0495349 0.0409091 0.0443654 0.0412416 0.0383168 0.0381793 0.0375075 0.0397935 0.0397659 0.0436937 0.0375570 0.0402408 0.0342192 0.0388182 0.0389355 0.0454775 0.0448851 0.0436176 0.0357910 0.0456131 0.0444732 0.0450667 0.0411053 0.0402844 0.0417325 D.C123514 0.0125905 0.0106061 0.0127467 0.0125862 0.0112626 D.0119750 0.0114824 0.0109642 0.0109565 0.0113646 0.0116622 0.0101157 0.04149*3 0.0124516 0.0121531 0.0138342 0.0115116 0.0138182 0.0428463 0.0424832 0.0427063 0.013*734 0.0117417 0.0119764 0.0120067 0.0128529 0.0107818 0.0109036 0.0106027 0.0444242 0.0415806 . 0.0443*83 0.0107471 0.0147353 0.0444299 0.0108992 0.0415064 0.0116800 0.0108947 0.0104545 0.0410030 U> f 00 067789 CONFTOFNT T SEX LITTEt XX XX IX XX XX II XX XX XI XI IX II XI XI II II II II II II II II IX II XI XI XX XI 11 XX XX II II XX XI XX XI XI XX XX II XX 3> N 436 H 436 H 436 H 436 N 438 N 436 H A 38 K *36 H *38 R *38 H *38 H *39 R *39 H *39 H *39 H H *39 *fco H MO H **0 h **0 R *0 H 444 M Ml n Ml R ** M Ml M 442 R M2 H M2 R M2 M 4*2 H M2 K M2 H M3 N 4*3 R **3 H R 54542* R *** H *** H *** H M* G-5 Appendix 6 (cent.) An Inhelntton Ftmle Fertility Study with Aemene In bts 79-2425 W TESTES 1?T 4 0. <75 2 0.196 3 0.205 * 0.1T5 1 0.209 2 0.218 3 0.203 * 0.197 5 0.496 6 0.223 7 0.214 4 0.1*2 2 0.136 * 0.155 * 0.120 5 0.1** 1 0.153 2 0.1 2 9 0.150 * 0.160 5 0.167 1 0.260 2 0.1*9 3 0.225 * 0.223 5 0.139 1 0.076 2 0.23* 3 0.17* * 0.217 5 0.189 ( 0.159 7 0.198 * 0.096' 2 0.416 3 0.113 * 0.095 4 0.497 2 0.22T 3 0.23* * 0.233 5 0.225 LIVER -fir 4.6*1 1.856 1.986 1.89* 2.0*6 2.280 2.1*6 2.327 2.216 2-315 2.2T* 1.312 !.*12 4.6*3 1.276 1.298 1.523 4.691 I.695 1.797 1.689 1.835 4. *89 2.470 2.172 1.361 1.856 4.3*5 1. *18 1.0*0 1.592 4.709 4.01* 4.442 1.431 0.995 2.429 2.410 2.533 2.26* 2.337 MONETS "7iT 0.435 0,501 0.519 0.*88 0.552 0.523 0.553 0.575 0.762 0.626 0.578 0.361 0.*17 0.*?3 0.357 0.361 0.376 C.**6 C.*'1 c.*se 0.**7 C.5C* 0.401 0.556 0.583 0.362 0.556 0.4*5 0.362 0.436 0.503 0.427 0.493 0.330 0.240 0.369 0.3*8 0.584 0.686 0.802 0.670 0.677 MOT or. "Til *0.9 *3.6 45.0 *1.9 46.* *8.6 **.9 *7.3 *5.7 5C.0 *6.8 31.8 33.0 36.2 28.9 29.1 3*.8 37.9 36.6 38.2 37.0 39.9 *6.8 46.9 32.0 29.0 39.1 39.0 32.5 37.8 *2.0 37.0 39.8 25.6 27.4 27.6 26.2 42.4 49.0 50.9 47.5 49.0 T/BH` L/BW K/BW 0.00*27673 0.00**95*4 0.00*55556 0.00*17661 0.00*50*31 0.00**8560 0.00*52116 0.00*16*90 0.00*33260 0.00**6000 0.00*50855 0.00**65*1 0.00*12124 0.00*28177 0.00*15225 0.00*9*8*5 0.00*39655 0.00*80211 0.00*09836 C.00*188*8 0.00*51351 0.0'C51629 0.0031838 0.00*797* ' 0.0069687 0.00*7931 0.0019*37 0.0059234 0.0053538 0.0057407 0.0045000 0.0042973 0.0049749 0.0037209 0.0042336 0.0040942 0.0036260 0.0046462 0.00*6327 9.00*5972 0.00*9053 0.0045948 0.0401222 0.04256BB 0.0441333 0.0452029 0.04*09*8 0.0*69136 0.0*77951 0.0*91966 0.0*85339 0.0*63000 0.0*85897 0.0*42579 0.0*27679 0.0*53867 0.0**1522 0.0**60*6 0.0*376** 0.0M617* 0.0*63115 0.0*70*19 0.0*56*86 C.0*59900 0.0318162 0.0*62687 0.0678750 0.0*693*0 0.0*75897 0.0*138*6 0.0375132 0.0*61905 0.0*30270 0.0*29397 0.0393023 ' 0.0*05639 0.0*09763 0.0379774 0.0502423 0.0*91837 0.0*976*2 0.0476632 0.0478939 0.0466357 0.044*908 0.0145333 0.0416*68 0.0118966 0.0107613 0.0123163 0.042156* 0.01667*0 0.0125200 0.012350* 0.0113522 0.012636* 0.0116851 0.0123529 0.012*055 0.01080*6 0.0117678 0.0117760 0.0119695 D.0120811 0.0126316 0.006568* 0.0148550 0.0462187 0.012*828 0.01*2199 0.041*103 0.0147538 0.01453** 0.0419762 0.0445*05 0.0123669 0.0427907 0.0087594 0.0433696 0.0432824 0.0437736 0.01*0000 0.045756* 0.0441053 0.0438463 r> OD 2O O 25a sVJj H vO i S'0 CMW II II II II II II II II II XI II XI II XI XI It II II XX II II XX XX II XI II II NEAH S.D. N SEX N N H N K N N H N M K M M H K H M H H K M H M H M B M LITTEt AM MS M5 MS M5 MS mt mt M7 **7 mt **7 MS MS MS MB MB MB MS MJ **9 A 50 *50 A50 ASO ASO ASO G-6 Append!* 6 {coni.) An Militln feaile Fertility Stutf nltk Oewene In lUtt 79-2425 w TCSTES (a) 6 0.199 A 0.A79 2 0.1 T1 3 0.2A8 A . 0.178 5 0.202 A 0.177 2 0.172 3 0.195 A 0.492 S 0.188 6 D.A73 1 0.135 2 0.119 3 0.135 A 0.465 5 0.A 37 6 0.532 7 0.129 I 0.071 2 0.065 1 0.2A6 2 0.209 3 0.2A2 A 0.217 5 0.208 6 0.213 unit "TiT 2.136 1.863 A.8A6 2.A32 1.732 2. A 37 2.206 1.73A 2.210 A.925 A.996 1.765 A.28A 1.168 A.173 1.101 A. 321 A. 239 A.1A1 0.71 A 0.789 2.276 2. A 38 2.106 2.388 2.539 2.8AA 0.178 1.711 0.051 0.435 111 110 ~KIDaKTrS 0.565 0.513 0.AS9 0.536 0.507 0.513 0.568 0.559 0.637 0.52A 0.A89 O.A88 0.A29 0.367 0.390 0.385 O.A31 0.395 0.376 0.272 0.250 0.596 0.608 0.5A6 0.525 0.598 0.702 0.867 0.101 111 8001 VT. (si A2.T A3.0 39.9 A7.0 AC. 3 AA.A A1.5 37-7 A 3-7 AO.9 A5.0 38.6 30.9 30.0 28.9 32. A 3A.1 29.0 29-7 46.5 16.0 50.5 51.2 A8.A 50.0 A6.9 53.2 T/BW O.COA660A 0.00*1628 O.OOA2857 O.OOA6383 0.00**169 O.00A5805 0.00A265A O.OOA5623 0.D0AA622 0.00A69AA 0.00A1778 0.00**819 O.OOA3689 0.0039667 O.OOA67A3 0.0051A02 0.00**051 0.0483**6 O.OOA3A3A 0.00A303O 0.00A0625 O.OOA6713 0.00*0620 0.00500c0 O.OOA3AOO 0.00**350 O.OOAOC38 L/BW- 0.050023A 0.0A33256 0.0A62657 0.05A7AA7 0.0A2977T O.0A8A5S0 0.0531566 0.0*59151 0.0505T21 O.OA70660 O.OAA3556 0.OA5725A 0.0A1553A 0.0389333 O.0A05882 0.03A299A 0.0*2*759 0.0*272*1 0.038*175 0.0*32727 0.0*93125 0.0*50693 0.0*76172 0.0*3512* 0.0*77600 0.05*1365 0.053*586 K/BW 0.0132319 0.01A9302 0.0115038 0.01AAOA3 0.0125606 0.01A6327 0.0136867 0.01*8276 0.01*5767 0.0128117 0.0108667 O.OA26*25 O.OA38835 0.0122333 0.013*9*6 0.0119936 0.0136585 0.0136207 0.0126599 0.016*8*6 0.0156250 0.0116020 0.0AA875B 0.0AA2810 0.0105000 0.0127505 O.OA31955 38.2 0.00470 0.M438 0.01226 7.2 0.00145 0.00479 0.00145 111 111 no 111 G-7 Appmlli G (cont.) An MiUUm Fcailt Fcrttlttf Study with Ihikm In Itots 79-212S (MUP sei UTTER PUT TESTES LIVER MONETS MOT vr. T/BW L/BW K/BW (9) "RT "TiT* (9) w* III ?i 655 f 6.033 0.788 0.253 16.0 0.0023750 0.0*65000 0.0453125 111 H 625 2 0.055 0.323 0.235 13.5 0.0029730 . 0.0487563 0.0158054 111 * 626 1 C. 131 1.968 0.585 38.0 0.0053235 0.0577687 0.0160294 111 N 626 2 0.175 2.336 C.58; 83.O 0.0040693 C.0435116 0.0126279 111 Ft 626 3 C.203 0.258 0.676 46.3 O.C043376 0.CO50C00 0.0144444 111 n 626 t 0.172 2.013 0.567 32.6 0.0052761 0.0616568 0.0173925 111 FI 626 5 0.162 1.367 0.522 56.6 0.0084262 0.C51C1C9 0.0142623 111 M 627 1 0.122 1.260 0.385 30.3 0.0080264 C.0415382 0.0113361 N r> oo 2o "n n^ roK m vi 2 SJ in III III IZI III IZI IZI III III III III III III III HI ZII HI III III III III IZI IZI III III III III III III III III III HI III Ft K H K M M N M M K H H M H K H H R H K M N R N N K H M H M R M H K 627 2 627 3 627 * 627 5 627 6 626 1 628 2 626 3 628 1 626 5 630 1 630 2 630 3 631 1 631 2 631 3 632 1 632 . 2 632 3 632 8 632 5 633 1 633 2 633 3 633 8 638 1 2 638 3 638 8 638 5 615 1 635 2 635 3 635 8 0.123 0.328 0.127 0.122 0.137 0.128 0.150 0.168 0.129 0.139 0.142 0.072 0.071 0.205 0.229 0.229 0.161 0.117 0.111 0.18B 0.216 0.187 0.196 0.198 0.182 0.20T 0.167 0.153 0.165 0.177 0.221 0.199 0.200 0.218 1.167 1.093 1.276 1.010 1.138 0.922 4.146 1.199 1.097 1.287 1.160 0.816 0.693 2.868 2.336 2.569 1.538 1.182 1.182 1.781 1.813 1.982 2.322 2.105 2.116 1.623 1.661 1.875 1.7T0 1.672 2.281 1.632 2.185 2.006 0.310 0.305 0.356 0.*26 0.386 0.297 0.232 0.339 0.337 0.366 0.362 0.288 0.298 0.586 0.636 0 656 0.892 0.556 0.357 0.505 0.882 0.507 0.536 0.515 0.526 0.825 0.889 0.805 0.899 0.513 0.590 0.850 0.528 0.523 27.2 27.8 29.3 27.1 28.6 26.0 30.8 31.8 29.0 30.8 29.5 24.8 22.8 51.1 53.1 50.0 37-9 36.7 28.9 38.3 39.0 81.0 *0.1 85.0 81.0 82.0 39.8 31.0 82.7 81.0 89-8 83.3 85*8 84.8 0.00452206 0.00846083 0.00833*87 0.00850165 C.00879021 0.00892308 0.00887013 0.00598726 0.00888828 0.00851299 0.00379661 0.00330275 0.00311808 0.00801178 0.00831262 0.00858000 0.00828802 0.0031B801 0.00388083 0.00386823 0.00553686 0.00856098 0.00888778 0.00880000 0.00883902 0.00892657 0.00869849 0.00893566 0.00833255 0.0083170T 0.00887368 0.00859588 C.00880529 0.00881982 0.0829088 0.0393165 0.0835895 0.0383768 0.0396503 0.0358615 0.0372078 0.0384887 0.0378276 0.0808870 0.0393220 0.0378312 0.0391667 0.0862192 0.0439925 0.0513500 0.0805805 0.0311172 0.0806997 0.0465013 0.0864872 0.0463415 0.0579052 0.0467T76 0.0516096 0.0386429 0.0417337 0.0475606 0.0414520 0.0456585 0.0461741 0.0423095 0.0472467 0.0451802 0.0413971 0.0109712 0.0121502 0.0120295 0.0120979 0.0114231 0.0075325 0.0107962 0.0116207 0.0118831 0.0122712 0.0432410 0.0128947 0.0144677 0.0119774 0.0131600 0.0129815 0.0151499 0.0123529 0.0431854 0.0123590 0.0123659 0.0133664 0.0114444 0.0128293 0.0104190 0.0412814 0.0130645 0.0416862 0.0425122 0.0419433 0.0103926 0.0415419 0.011T793 --H i--i i> * bo zo "!HH O a& *< m Ni N H-t 'O fO Q x> h- 6* <1 croup sa unn hi K 635 hi N 636 hi hi K H 636 636 ZII M 63? III M 637 IZI III H- n 637 637 III H 637 III N 639 ZIZ H 639 IZI N 639 III N 639 III H 839 III M 660 ZIZ H 660 III III K M 666600 III * 660 Eli H 661 III N 66* III III M M 661 661 ZII H 661 ZII N 661 III n 662 III H 662 IZI H 662 ZIZ K 663 III H 663 IZI H 663 ZIZ M 663 ZII n 663 XII ZZZ H K 666 666 ZZI N 666 IZI H 666 ZZZ n 666 III H 665 ZII H 165 III H 665 ZZZ H 665 G-8 Mfiptndlx 0 (coot.) An lKMIitton F mile Fertility Study with ItMMt lit )UtS 79.-242S PUP TESTES (9) 51 0.196 0.267 2 3 00..331086 1 0.172 2 0.167 63 0.156 0.153 51 0.162 0.188 2 0.215 36 0.161 0.173 5 0.166 1 0.166 2 0.160 3i 00..129009 5 0.175 1 2 0.133 0.137 63 0.160 0.13* 5 0.126 6 0.111 1 0.230 2 0.212 31 00..220315 2 0.170 3 0.173 6 0.170 5 0.677 1 0.160 2 0.165 36 0.162 0.160 5 0.165 1 0.161 2 0.209 63 0.153 0.1*9 LIVER TST 1-909 1.966 2.T06 2.697 1.730 1.667 1.832 1.825 21..171713 2.350 1.926 1.189 2.009 1.781 1.7*7 1.726 1.859 1.736 4.185 1.157 4.502 4.260 11..105892 2.307 1.812 2.183 1.850 2.102 2.126 1.965 1.9*5 1.9*5 1.525 1.062 1.3*0 1.636 1.628 1.598 1.272 1.175 KIDNETS (,J 0.5*0 0.5*0 0.692 0.690 0.676 0.6*1 0.681 0.698 o.*?* 0.5*8 0.5T* 0.518 0.5*8 0.521 0.657 0.656 0.689 0.50* 0.660 0.371 0.381 0.606 0.377 0.350 0.3*1 0.576 0.692 0.598 0.561 0.597 0.508 0.526 0.557 0.529 0.633 0.365 0.619 0.652 0.512 0.648 0.693 0.378 BOOT WT. (9) *1.9 68.8 59.6 56.6 39.1 37.7 39.9 61.9 60.9 61.6 67.8 60.2 *6.7 6600..09 38.0 *21J.*9 39.9 29.6 28.0 36.2 31.6 29.6 26.8 67.6 60.2 68.2 *1.9 66.0 62.6 61.6 60.9 62.1 36.8 26.0 30.2 34-5 36.7 36.0 61.2 26.8 T/BW 0.00*72556 0.005061*8 0.00533557 0.00539007 0.00*39890 0.00369920 0.00390977 0.00365155 0.00396088 0.00*51923 0.00*69791 0.00600498 0.00387025 0.00*05866 0.00365000 0.00421053 0.0056*865 0.00*53*61 0.00*38596 0.00*52381 0.00*7569* C.00609357 0.00626752 0.00625676 0.00616179 0.00*81172 0.00527363 0.00667552 0.0067971* 0.0038636* 0.00606103 0.00*10626 0.00632763 0.00627553 0.0039*022 0.00600000 Q.006635T6 0.00523810 0.00*38692 0.00616706 0.00371359 0.0061319* L/BVJ 0.0655609 0.0*02*59 0.0653691 0.0662730 0.0662*55 0.06*2175 0.06591*8 0.0635561 0.0*33*96 0.0507*52 0.0691632 0.067910* 0.0265996 0.0*91198 0.0665250 0.0*51662 0.0667027 0.06*3675 0.063*566 0.0403061 0.0601736 0.0*39181 0.039*906 0.039155* 0.0*03734 0.0682636 0.0*507*6 0.0*52905 0.0664527 0.0*77727 0.0*99061 0.0669807 0.0*75550 0.0661995 0.0616602 0.0379286 0.0643709 0.0519365 0.0443597 0.0470000 0.0300738 0.0407986 K/BW 0.0126878 0.0110656 0.0116107 0.0122340 0.0422251 0.0116976 0.0120551 0.0148854 0.0120762 0.0131731 0.0120084 0.0120656 0.0122595 0.0127384 0.0414250 0.0120000 0.0132162 0.0120286 0.0120301 0.0126190 0.0132292 0.0118429 0.0120064 0.0118243 0.0127239 0.0420086 0.0122386 0.0124066 0.0133690 0.0435682 0.04492*9 0.0427536 0.0136486 0.0425653 0.0447663 O.Q1303ST 0.0438742 0.0443*92 0.0139540 0.04229*4 9.0449660 0.043*250 * ; CHOtlf SEX LITTER III 111 III III III III III III III III III III III III III III III III III III III III III III HOW S.D. II K H N N K Hn H H M K n H N M H H K M N N M 'N H 6*6 6*6 6*6 6*6 6*6 6*7 6*7 6*7 6*7 6*7 6*8 6*8 6*8 6*9 6*9 6*9 6*9 6*9 6*9 659 650 650 650 650 6-9 Appendix 6 (cont.) An InfitUtfon Fcvlc Fertility Study with Bemene In Hits n-n& W TESTES toi 1 0.480 2 0.160 3 0.465 * 0.184 5 0.4*1 1 0.455 2 0.467 3 0.469 * 0.46* 5 0.4*3 1 0.490 2 0.2*7 3 0.233 1 0.186 2 0.472 3 0.185 * 0.472 5 0.179 6 0.200 4 0.174 2 0.468 3 0.176 * 0.427 5 0.204 0.169 0.043 108 LIVER *isT 4.77S 4.692 4.492 4.288 4.465 4.739 4.920 4.965 2.457 4.819 2. *9* 2.*7? 2. 3*7 4.769 4.862 4.719 4.806 4.8*1 2.158 1.599 2.033 4.819 2.120 1.769 MONETS (9) 0.*97 0.*59 0.3*6 0.383 0.356 0.127 0.463 C.*95 0.529 0.415 0.676 0.570 0.63* C.A83 0.46? 0.417 0.466 0.446 0.565 0.432 0.481 0.462 0.510 0.475 1.693 0.469 0.465 0.099 108 106 BODY NT. (9) *2.7 37.* 33.6 33.9 2B.9 35.5 *0.2 37-5 *0.5 35.1 *7.6 *9.* 48.8 38.2 38.9 37-9 39.9 38.9 *2.0 36.0 *1.0 38.9 *0.2 *0.0 T/BW 0.00*245*6 0.00*27807 0.00*91074 0.00533923 0.00*87669 0.00*36620 0.00*15*23 0.00*50667 0.00*0*938 0.00*07*07 0.00399160 0.00500000 0.00*77*59 0.00*86911 0.00**2159 0.00*86127 0.00*31078 0.0046015* 0.00*76190 0.00*75000 0.00*09756 0.00*52**2 0.00315920 0.00502500 L/BH 0.0*1569* 0.0*52*06 0.035*762 0.03799*1 0.0*0341* 0.0*89659 0.0*77612 0.052*000 0.0532593 0.051823* 0.0523950 0.0501*17 0.0*809*3 0.0*63089 0.0*78663 0.0*53562 0.0*52632 0.0473265 0.0513810 0.0*44167 0.0*95854 0.0*67609 0.0527363 0.0**2250 a/uh 0.0146393 0.0422727 0.0402976 0.0442979 0.0123163 0.0120282 0.01201*9 0.0132000 0.0130647 0.041823* 0.04*2*37 0.0415385 0.0129948 0.0126**0 0.0420054 0.0410026 0.0147293 0.041*653 0.013*52* 0.0420000 0.0147317 0.0116766 0.0126866 0.0418T50 38.0 7.7 108 0.00443 0.00059 108 0.04435 0.00665 108 0.01241 0.00125 108 r> oo 2n O N mO^ XoOj' u 2 -< OvSOJJ 44kk. 00 tmr o i ~f o O (j\ 2 SJ H vO it IT ZT IT IT IT IT IT IT IT IT IT IT IT IT IV IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT ZT ZT ZT IT IT IT IT ZT SEI H M K N H N M H M N M M K M K M M H N H H M H H M H K N H H n n n N M M K H M M H M UTTER 825 825 825 825 826 826 826 827 827 827 827 827 828 828 828 830 830 830 83* 838 83< 838 838 838 835 835 835 835 835 837 837 838 838 838 m 839 839 839 839 S3 G-10 Appendix G (cont.) Aft Inhalation Female Fertility Rudy with Semene In Rats T9-242S MR TESTES (9) 8 0.863 2 0.188 3 0.842 4 0.878 1 0.874 2 0.152 3 0.885 1 0.282 2 0.891 3 0.183 4 0.203 5 0.890 1 0.126 2 0.854 3 0.842 1 0.885 2 0.195 3 0.285 8 0.12T 2 0.886 3 0.887 4 0.155 5 0.830 6 0.801 8 0.842 2 0.849 3 0.138 4 0.844 5 0.857 8 0.982 2 0.202 1 0.849 2 0.167 3 0.833 4 0.154 5 0.849 8 0.133 2 0.835 3 0.888 4 0.888 5 0.108 9 0.856 LITER TfT 8.559 8.379 8.639 8.817 8.476 8.713 1.934 2.132 8.604 8.667 2.067 1.819 8.415 8.773 1.071 1.822 1.445 8.361 8.236 8.096 8.347 9.732 4.607 9.817 8.637 9.903 8.387 1.698 8.800 2.495 2.127 1.845 8.987 1.761 1.763 1.893 9.303 1.469 1.053 8.882 1.24T 8.978 KHMETS (9) 0.474 0.419 0.466 0.453 0.409 0.44$ 0.499 0.509 0.422 0.461 0.492 0.475 0.389 0.444 0.333 0.503 0.534 0.449 0.342 0.295 0.353 0.429 0.395 0.455 0.462 0.402 0.407 0.426 0.555 0.581 0.528 0.558 0.469 0.468 0.579 0.345 0.412 0.393 0.328 0.353 0.367 SOOT NT. It) 36.9 33.0 35.3 36.4 35.8 36.7 42.5 48.7 36.7 37.5 41.5 39.9 30.8 36.9 25.9 39.6 38.0 35.8 2B.1 26.1 30.0 34.0 32.1 25.0 35.0 34.0 30.8 33.5 35.1 41.8 43.0 38.0 42.0 39.0 38.1 43.2 33.0 33.4 39.9 28.9 29.9 28.0 T/BW- 0.00451524 0.00569697 0.00402266 0.00469760 0.00486034 0.00414169 0.00435294 0.00508393 0.00520436 0.00488000 0.00489157 0.00476490 0.00409094 0.00417344 0.00548263 0.00467172 0.00513158 0.00796089 0.00451957 0.00444444 0.00390000 0.00455882 0.00404984 0.00404000 0.00405714 0.00438235 0.00448052 0.00429851 0.00447293 0.00435407 0.00469767 0.00392105 0.00397619 0.00341026 0.00404199 0.00344907 0.00403030 0.00404192 0.00347962 0.00364083 0.00361204 0.00557143 L/BW 0.0431856 0.0417879 0.0464306 0.0499176 0.0412291 0.0466757 0.0455059 0.0511271 0.0437057 0.0444533 0.0498072 0.0455890 0.0459416 0.0480488 0.0413514 0.0460101 0.0380263 0.0360168 0.0439858 0.0419923 0.0449000 0.0509412 0.0500623 0.0446800 0.0467774 0.0559706 .0.0450325 0.0506866 0.0542821 0.0596690 0.0494651 0.0485526 0.0473095 0.0451538 0.0462730 0.0436194 0.0394646 0.0439820 0.0330094 0.0408997 0.0417057 0.0420714 K/BU 0.013*302 0.0126970 0.0132011 0.0124451 0.0114246 0.0121253 0.0117412 0.0122062 0.0114986 0.0122933 0.0118554 0.0119046 0.0126299 0.0120325 0.0128571 0.0127020 0.0140526 0.0125419 0.0121708 0.0113027 0.0117667 0.0126176 0.0123053 0.0130000 0.0135682 0.0130519 0.0121493 0.0121368 0.0132775 0.0135116 0.^0138947 0.0132857 0.0120256 0.0120997 0.0134028 0.0104545 0.0123353 0.0123197 0.0143495 0.0418060 0.0131071 OMUF sot LI TIE* IT K 840 IT N 840 IT h 840 IT M 840 IT K 844 IT H 841 IT n 841 IT N 844 IT K 841 IT H 842 IT H 842 IT H 842 IT N 843 IT H 843 IT M 841 IT M 844 IT n 844 IT K 844 IT M 846 IT M 846 IT N 846 IT N 846 IT n 847 IT n 847 IT 8 84T IT 8 B47 IT M 847 IT 8 848 XT 8 848 IT 8 848 IT n 848 IT K 648 IT M 848 IT n 849 IT XT ZVO O O IT O HEM *< N 3 \&j 2 SJ 0 S.D. H N it M 849 849 849 1--L C/l G-ll AppcnOt* 6 (rant.) An Inflation Fault Fertility Sti^r with Otntene In Fats 19-2425 no THUS (9) 2 0.113 3 0.139 4 0.120 5 0.129 1 0.138 2 0.143 3 0.135 4 0.152 5 0.080 4 0.161 2 0.094 3 0.130 1 0.215 2 0.481 3 0.176 1 0.436 2 0.168 3 0.131 1 0.063 2 0.094 3 0.127 4 0.095 1 0.125 2 0.159 3 0.159 4 0.128 5 0.133 1 C.15B 2 0.106 3 0.109 4 0.094 5 0.103 6 0.424 1 0.207 2 0.268 I3 0.276 0.266 W 1.082 1.131 4.101 1.407 1.086 1.280 1.266 1.245 1.020 1.470 0.969 4.069 2-377 2.423 2.173 1.435 4.127 4.037 1.000 1.357 1.399 1.161 1.413 4.144 1.192 1.662 1.657 1.639 1.144 0.745 1.125 i:S 4.988 2.494 2.366 2.387 0.151 0.042 79 1.510 0.406 79 KIDNETS (9) 0.357 0.?94 0.330 0.248 0.556 0.407 0.396 0.361 0.345 0.427 0.368 0.359 0.607 0.517 0.557 0.307 0.361 0.335 0.3*6 0.419 0.433 0.376 0.355 0.32* 0.328 0.393 0.406 0.608 0.326 0.299 0.333 0.323 0.3*6 0.557 0.588 0.632 0.593 BOOT WT. 27.0 27.7 26.8 27.1 28.9 32.5 32.9 32.0 28.8 34.5 25.0 31.7 47.7 45.0 45.0 29.3 29.5 28.2 26.0 30.4 31.9 29.4 30.7 27.9 30.0 33.7 30.9 43.4 28.3 24.6 28.8 25.1 31.4 42.7 45.3 48.5 46.9 T/BW 0.00418519 0.00501805 0.00447761 0.00476015 0.00477509 0.00440000 0.00410334 0.00475000 0.00277778 0.00466667 0.00376000 0.00410095 0.0045073* 0.00402222 0.00391111 0.00470990 0.00569*92 0.00464539 0.00319234 0.00309214 0.00398419 0.C0323129 0.00407166 0.00569892 0.00530000 0.00379822 0.00430*21 0.0036*055 0.0037*558 0.00439546 0.00326389 0.00410359 O.OO394904 0.00484776 0.0059U11 0.00573196 0.00567164 L/BW 0.04007*1 0.0408303 0.0410821 0.0406487 0.0375779 0.0393646 0.0384802 0.0389062 0.035*167 0.0426087 0.0387600 0.0337224 0.0498323 0.0471776 0.0482689 0.0387372 0.038203* 0.0367730 0.0364615 0.0446382 0.0438558 0.039*898 0.0460261 0.0410036 0.0397333 0.0493175 0.0536246 0.0423733 0.0404240 0.0300*03 0.0390625 0.04139*4 0.03*6*97 0.0*6557* 0.0484327 0.0487835 0.0506955 K/BW 0.0132222 0.0101455 0.0423430 0.0091543 0.0123183 0.0425234 0.01203&5 0.0149062 0.0419792 0.0123768 0.0147200 0.0113249 0.0127254 0.0444889 0.0423778 0.0104778 0.0422373 0.0148794 0.0133077 0.0437829 0.0135737 0.0128571 0.0115635 0.0116129 0.0109333 0.0416617 0.0431392 0.0140092 0.0145194 0.0420565 0.0415625 0.0128685 0.0410191 0.0430445 0.0129801 0.0130309 0.0426439 0.424 0.068 78 34.0 6.2 79 0.00442 0.00078 79 0.04380 0.00536 79 0.01239 0.00093 78 n r> zo ~n nD o T' T1 Nl --i ,n -i jI> SEX UTTER M 1026 * 1026 H 1026 H 1026 H 1027 M 1027 M 1027 M 1026 N 1026 H 1026 K 1026 M 1028 K 1026 M 1029 M 1029 N 1029 M 1029 N 1029 K 1032 H 1032 K 1032 M 1032 K 1032 M 1033 K 1033 N 1033 N 1033 H 1033 N 1031 H 103* K 1031 H 1031 * M 1035 T H 1035 T H 1035 V n 1035 y y N 1035 H 1036 J ft 1036 t T H 1036 ft 1036 G-12 Appendix S (coot.) An lnhilitloi Femle Fertility Study with Beeitem In lets 79-2425 TESTES (91 1 0.133 2 0.097 3 0.096 1 0.103 1 0.119 2 0.150 3 0.119 1 0.122 2 0.100 3 0.118 1 0.138 5 0.138 6 0.106 1 0.132 2 0.113 3 0.123 1 0.115 5 0.119 1 0.111 2 0.122 3 0.151 1 0.112 5 0.126 1 0.111 2 0.098 3 0.111 1 0.118 5 0.129 1 0.121 2 0.156 3 0.129 1 0.120 1 0.123 2 0.116 3 0.126 1 0.121 5 0.115 1 0.136 2 0.131 3 0.165 1 0.131 LIVER "BT 0.999 0.811 0.912 0.736 2.001 1.999 1.667 0.975 0.855 0.732 0.855 1.107 0.755 1.117 9.179 0.957 1.217 1.253 1.276 1.226 1.539 1.337 1.288 1.791 1.766 1.619 9.715 1.610 81..60156J 1.560 1.268 1.261 1.733 1.626 1.158 1.661 1.236 1.302 1.206 1.315 KIDNEV5 (l> 0.269 0.279 0.331 0.285 0.510 0.536 0.160 0.287 0.268 0.275 0.328 0.351 0.217 0.317 O.316 0.318 0.373 0.310 0.357 0.350 0.135 0.392 6.353 0.1*9 0.505 O.I31 0.116 0.120 .3>8 0.136 0.1M 0.387 0.115 0.153 0.M6 0.381 0.1*7 0.102 C.1*5 0.?71 0.110 BOOT UT. (9) 26.9 23.0 25.1 23.0 11.6 39.9 37-9 25.6 22.9 21.7 28.3 23.0 20.0 27.7 27.9 25.0 28.0 30.9 32.9 30.9 36.7 31-0 31.5 10.9 36.2 36.7 39.9 33.6 31.1 35.0 36.7 31-7 32.6 37.7 35.7 29.7 17.2 32.0 31.9 29-9 29.6 T/BW 0.00191121 0.00121739 0.00382170 0.00117626 0.00356159 0.00375910 0.00393110 0.00176562 0.00136661 0.00177733 0.00167633 0.00600000 0.00530000 0.00176531 0.00512515 0.00192000 0.00517857 0.001B2201 0.0012857* 0.00391622 0.001*1111 0.00117617 0.00100000 0.00352078 0.0027071a 0.00381*96 0.00370927 0.00383929 c.00391901 0.00115711 0.00351199 0.00378519 0.00377301 0.00392573 0.00358513 0.00107107 0.00307203 0.C013125O 0.00120063 0.00551639 C.00139597 L/BW 0.0371375 0.0353913 0.0375299 0.0320000 0.0178706 0.0501003 0.0139612 0.0380659 0.0373362 0.0296356 0.0302120 0.0181301 0.0377500 0.0111079 0.0122581 0.0382800 0.0115357 0.0105502 0.0366159 0.03971*4 0.0119316 0.0393235 0.0106669 0.013863* 0.0187815 0.0195610 0.0137313 0.0179167 0.0335350 0.0162266 0.0130516 0.0106309 0.0392915 0.0159682 0.015(022 0.0369699 0.0352512 0.0386675 0.0106150 0.0103311 0.0111275 K/BW 0.0100000 0.0*2*301 0.0131873 0.0*23913 0.0*22010 0.0*31336 0.0*26619 0.01*2*09 0.0*1703* 0.01**336 0.0*15901 0.0*52609 0.0423500 0.0*25274 0.0**3262 0.0*27200 0.0*332*1 0.01*0032 P.01065** 0.0**3269 0.0416529 0.0*1529* 0.0112063 0.0109760 0.0139503 0.0117*39 0.0**1779 0.0125000 0.0107613 0.0*2157* 0.0*2098* 0.0122082 0.012736* 0.0120159 0.0*21930 0.0128263 0.009*703 0.0125625 0.0139*96 0.0125061 0.0016960 4*. (/I 6-13 Append!( 6 (cant.) An Inhalation Femle Fertility Study with Benzene In Rats 79-2425 SET LITTER K 1036 H 1037 M 1037 H M K 1037 1037 1037 n 1036 n 1036 M 1038 H 1036 M M HM 1038 1039 1039 1039 H H 1019 1010 M 1040 N 1040 H N 1040 1040 N H 1042 1042 H 1042 H 1043 M 1043 H 4043 NN 1043 1043 M 1044 n 4044 HK 4044 4044 HH 4044 4044 K M H 1044 4045 1045 H 4045 HK n K 1045 4045 4046 4046 W TESTES "Tii- 5 0.115 1 0.441 2 0.170 3 0.174 4 0.161 5 0.465 1 0.165 2 0.167 3. 0.136 4 0.159 5 0.166 1 0.196 2 0.156 3 0.431 4 0.439 4 0.220 2 0.202 3 0.203 4 0.462 5 0.235 1 0.157 2 0.157 3 0.159 1 0.122 2 0.129 3 0.422 4 0.127 5 0.441 1 0.469 2 0.474 4) 0.139 0.45T 5 0.176 6 O.W 7 0.153 1 0.473 2 0.166 3 0.462 4 0.470 5 0.461 4 0.146 2 0.454 LITER "fir 1.132 1.632 2.059 1.614 4.444 1.631 4.420 1.360 1.322 4.693 1.536 1.399 4.543 4.07* 4.252 1.854 4.905 1.815 4.674 2.026 1.705 4.571 1.313 1.227 4.261 4.446 4.262 4.486 1.595 1.779 1.313 1.650 1.666 4.626 1.138 1.644 1.744 4.637 1.653 4.542 4.087 4.446 R10RETS ~i%r 0.407 0.412 0.496 0.451 0.398 0.735 0.426 0.418 0.396 0.451 0.439 0.317 0.431 0.363 0.364 0.503 0.542 0.505 0.485 0.511 0.470 0.434 0.397 0.367 0.347 0.365 0.399 0.339 0.409 0.497 0.398 0.432 0.466 0.441 0.393 0.448 0.475 0.507 0.476 0.467 0.366 0.393 SOOT VT. 28.9 32.2 39.3 36.0 34.7 37.5 31.9 31.9 30.2 34.5 36.1 36.0 37-9 33.2 31.3 43.0 44.6 41.9 37.1 42.9 36.2 34.6 33-8 30.6 30.4 28.0 30.6 29.9 35.6 38.7 30.3 35.3 36.9 34.0 31.6 37.4 37.8 36.0 37.0 36.4 27.9 29.9 T/BM 0.00397924 0.00437688 0.004 325 70 0.00483333 0.00521614 0.00440000 0.00517241 0.00523511 0.00450331 0.00460870 0.00515235 0.00544444 0.00411609 0.00394578 0.00444089 0.00511628 0.00485577 0.00484487 0.00490566 0.00547786 0.00410995 0.00453757 0.00470414 0.00396104 0.00424342 0.00435714 0.00442336 0.00371237 0.00474719 0.00449612 0.00458746 0.00444759 0.00482385 0.00541476 0.00464177 0.00466307 0.00439153 0.00478947 0.00459459 0.00445983 0.00530466 0.00505047 L/BW 0.0391696 0.0506832 0.0523919 0.0447500 0.0416138 0.0486267 0.0445141 0.0426332 0.0437748 0.0490725 0.0425465 0.0388611 0.0407124 0.0323494 0.0400000 0.0431463 0.0457933 0.0433174 0.0451243 0.0472261 0.0446335 0.0454046 0.0368462 0.0398377 0.0424382 0.0398574 0.0409740 0.0396656 0.0448034 0.0459690 0.0433333 0.0467422 0.0454491 0.0478824 0.0360127 0.0443127 0.0461376 0.0430789 0.0446757 0.0427447 0.0389606 0.0363278 K/BH 0.0140630 0.0127950 0.0126209 0.0125278 0.0114697 0.0196000 0.0133542 0.0134034 0.0131768 0.0130725 0.0121607 0.0088056 0.0113729 0.0109337 0.0116294 0.0116977 0.0123077 0.0120525 0.0130726 0.0119114 0.0123037 0.0425434 0.0417456 0.0149156 0.0444145 0.0130357 0.0129545 0.0143376 0.0414868 0.0128424 0.0131353 0.0122380 0.0426287 0.0129706 0.0124367 0.0120755 0.0125661 0.0133424 0.0128649 0.0429363 0.0431163 0.0131438 067797 C O N F TDFNT TAI 4a. 4a. sn LITTER H K lOt 6 1016 N lots M tots H tots N tots MK 19 tots NH tots tots H 10t9 K tots M 1050 K 1050 M 1050 n 1050 N 1050 H 1050 G-14 Appendix C (cont.J A* lakilitfw Fcvlt Fertility Study with lenxene In Rats 79-242S W TESTES (l) 3 O.ltt t 0.113 5t 0.136 0.25T 2 0.155 3t 0.221 0.222 2 0.202 i3 0.194 0.1ST 56 0.197 0.173 1 0.151 2 0.156 3 0.419 t O.ltt 5 0.106 6 0.155 ItVER (l) 1.429 1.066 0.953 1.902 1.660 1.625 2.071 2.059 22..111022 1.902 2.039 1.105 4.195 1.291 1.642 1.367 1.542 KIDNETS (9) 0.391 0.366 0.328 0.570 0.518 0.536 0.557 0.516 0.59 0.555 0.533 0.529 0.113 0.136 0.391 0.152 0.116 0.153 Ban ht. (9) 30.9 29.3 29.6 12.0 12.7 15.5 15.9 11.1 13-0 12.8 15.2 12.6 35.6 37.0 31.7 37.0 32.5 35.1 T/BW 0.00166019 0.00186055 0.00166216 0.00611905 0.00362996 0.00165711 0.00163660 0.00191181 0.00111186 0.00136916 0.00135611 0.00101206 0.0012115? 0.0012702? 0.00170032 0.00389189 0.00326151 0.00137853 L/BW 0.0365372 0.0363623 0.0321959 0.0152857 0.0110281 0.0357113 0.0151652 0.0500973 0.0166837 0.0500167 0.0120796 0.0176102 C. 0391663 0.0101051 0.0108202 0.0135676 0.0120615 0.0127419 K/BW 0.0127508 0.0132123 0.0110811 0.0135T11 0.0128337 0.0147802 0.0121351 0.013281? 0.0439070 0.0129673 0.0417920 0.0123596 0.0121136 0.0117638 0.0123311 0.0122162 0.0126000 0.0427966 0.151 1.453 0.419 0.031 0.347 0.086 101 101 101 34.1 0.00446 0.04216 0.01229 5.7 0.00060 0.00470 0.00142 101 101 101 101 DO 0 6 7 7 9 8 CONFTDFNTT, X> G-1S Appendix G (cont-) An InhilitlM Female Fertility Study with Benzene In Rett 79-2425 GROUP SEX LITTER PUP W RICHEYS BODY Iff. is) L/BW K/BW I l t t 1 l 1 l t l 1 I l l t t .....r i i Z i i i i i l i t i 1 i E 1 t i t z I 1 l 1 t 1 1 1 I I 1 1 1 t 1 t 1 t its f Ate l tee F Ilf {> r tee F tee tee F tee r tlf F lit F ur f lif F It 7 F III F ill "` III F 131 r 2i F III F 19 t i*v ~T~` I2e F tee F tee f 130 F 130 F 130 / J58 r i)l F 131 F 111 F 131 F 111 F *21 F 133 F til f 133 F jyj F 13! F ni F 13! F "lie "" r 13! t lie t lie t idC f 1ST ' ill "" t 131 t 137 F 130 131 36 * 3 I.OIC e.soi 3C.0 1.0413404 o.oi out 4 4 MU "1---- 1.77! *4*7 C.TT8 37.1 ii .e 0.041*131 0.0441110 .eiiieif .oi toiii e i.o ee o.ei*. 37.1 0,0141410 0.0131(10 < --I74T7 tlVSi 3C.I "TTiTilHI 5.0114705 7 1 .103 0.401 te.i 0.03(4111 "0.0113(05 1 MH e.iec 31.4 0.0410ISI 0.01100(7 0 Mil 0.4*1 34.1 0.04(0011 0.01101*5 10 1.430 0.374 34.0 *.0410*0* 5.0111471 e 1.707 0.431 17.1 0.04*0100 "0.0111330 -- ~ran*-- IdKO fill 1 .0411434 --5.5111555 " c 1.0 14 c .4ie 0.4*1 5.40* 37.1 3C.7 O.OfOlOl'3 0.0407*43 MH 0113441 10 1.00! 0.441 37*1 0.0(010*1 0.0130011 c i.ii? i.T" 34.1 0.1470401 (TeiiiiTi e 3 1J.-3J1-j1jl o.toi 0 *414 41.1 5171 1.0143(00 V.1(15145" 0.0110415 1.4111555-------- t 1.3*1 0.4*7 *0.< 0.0111773 5.0110035 V 1.030 *.3<i 3t.e 0.04(1714 --Ti7eil*vi IB 1.004 0.440 1C.1 o.tociooi 0.0131047 e 1.4*0 C.44! 31.t t.*43*1*1 i.(fjiul T 1.517 ( 8.70 0.4*3 5.3(1 31.4 l*.l 0.04(1337 OtOIC1911 .0141035 # dl tlUl... ( i.eoi 10 1.30* 0.11* 0.371 31.1 l.t 0.14(4400 *.(4141*1 0. 01 41035 .dfiioii 7 l.71 f i.eto 0.477 0.471 3C.4 34.1 04771*0 0.14*3(14 0.0133050 i. ii f 1.471 0.411 34.* .41(14! "0.0130 017 15 1 liil 0.417 If 1 0.0(01107 --17BTI5III--------- 1.617 0.431 K.t 0.04t(414 0.0110I03 7 1 7C 0.470 3C.3 (.(ill 0.5111 *n-- 1 1.700 0.31* 11.1 0*044(714 O.OI00705 1.1*3 --i.tfi------ .....ii;< " 0.5(4(145 5145441 10 1.031 0.4C* 30.4 0.04770*3 0.0110753 4 'i .047 5TJTI------ 40.0 5.54ec7>d 5.5115914-------- 1 1.70! 0.441 3*. 0.541(141 011(037 e TSil r.u 30.1 5 .ilfflll--------k'HilYH--------- f i.eii 0.4*4 37.0 o.ototeic 0. 0115405 10 1.174 --i.{|1----st;*-- i.ii rim iTrniiTi-- 7 *.3*C 0.404 44.0 4.4t!0llt 5.0130004 1 1.K4 0 .*47 il.l ------ c.ttiioii 0.0140100 C C.lto 0.C43 id i.oel"' d.*do 41.0 44.3 0.Otltd* e.ooiiiie 0.0133410 *. dll iff? e 1.437 0.437 34.7 0.0414131 5.0135037 i .i3T'' i.ili----Se.T* i.ihffll---------Urttili--------- 7 1.3*1 0.431 eo.i o.oilive? 5.5110041 l"" i.eid 1.341 If *4 "4.4111415" 4.4119111--------- 1 1.754 V"" "HOT 1.570 0.47* r.n<-- 0.410 3* .7 o.4Tivei "4171-------- i.mnn- 30.0 0.044(511 0.01 *0750 5.irmtr-- 4. M 30000 t ' ~ra<fi 7 1 .555 "| 1.71V --e.nnfi 0.41* 0*431 1T71---------"i .'form r- T.onim 31 .* C .04(1701 0.0133(10 ------5T71--------- i.timn--"cimur 1.504 0.37* '31.0 id 1.4*4 --d.i>i-- >1.5 0.(41*001 o.idieoi 0.011(130 ". ell4407 DO 067799 CONFTDFNTTAl YZOO14454 G-ie Appendix G (cent.) An inflation Fetaalt Fertility Study with Gtnnno In Rats 79-2425 GROUP SEX LITTER PUP w II 1 | ------1j------I 9 r t I 1 9 9 ------t1---------jf-- t IN iia t IN 140 *40 <40 <40 140 <4* <4< <42 7 < 0 10 e 7 e 0 to 0 --r" < 1*00< !<< l.OIC 1.033 1*677 I.43C 1.400 1.787 1.077 <007 1*0 18 1 .<01 t <4i 0 3 .OH I * <4< 10 1.4(4 t r X4J e 1 .4*3 l ------1----------- --ff-------- <43 1*5--------- I i 1.(43 1.0 II t <43 0 1.907 t 9 <43 to | .440 I l4 0 1.034 I 9 <44 i 0.044 1 ------ 9f----------- 1----------- <44 <44 7 0.000 t --HoTi 1 9 (47 1 .4(7 I 9 <47 0 1.144 l <4? T 1.107 K <4? < 1.68* F <47 0 t.MJ --i---------- f ------ 177--------- "'to 1.348 i 9 <40 < I .400 i 9 <40 1 1.347 1 <40 * 0.016 i <40 0 1.317 i <40 10 1.961 i 9 HO 1.1(1 i <00 7 l*TI t 9 <80 0 1.9(8 i <00 0 (.138 9 180 10 1.6(7 MEAN 1.690 S.O. 0.355 N 94 KIDNEYS nf9l" 0.848 o.to O.HC 0.H3 4*412 0.387 0.414 0.419 0.8(0 0.480 0.1*6 (.180 0.810 0.4(8 0.*H 0.480 1.44$ 4.444 0.431 0.188 0.164 0.<4| 0.48* 0.387 8.347 C .336 0.430 0.387 .4*6 <!< 0.138 0.478 0.388 0.480 0.60 < 0.4(0 0.476 (.886 0.866 m1t9a) -. L/8W 41.6 40,1 _ 36.7 27.6 ti.i W33.7'l33,6 _ 41.6 30.1 38.6 31.0 37.1 34 .3 30.6 36.6 '!*.* 37.7 36.8 (4.4 14.4 11.8 " '41.0 ~ *.< 31.1 30.8 24.1 <7.6 ioTS ll.o (0.7 37.4 31 .< 27.0 48.0 38.0 48.0 40.7 44.7 0.4404773 0.64(8(63 0.081(071 a.<(10(l o.ittotit t.0441017 ' 0.0436146 00..0848711(0305_ 0.0(80773 0.04*107* 0.01(0066 0.0648(11 0.0433607 (.8417(06 0.8(03(79 cTWirn (.0(08038 0.04(44(6 0.4*13770 0.034360t 0.03 7<00< (.OtUiM 0.0486748 0.83(7830 0.8176344 0,04(1700 0.643(301 0.0441i1T ((4(0000 0.0424408 0.0(36037 0.0434634 0.0(113(1 0.04(0430 0.(4677(7 0.04HI46 0.(4(7177 4.0404000 K/BW .t0t.0t1m430w40 , 0.411(071 __ 0.(1*1111 0*0111049 `09*.0011(16308011*__ 0.0110134 |||4I|4l <> 0.01374*4 0.0128040____ 0* 411*01* 6. 01 *34*1 f-H 771____ '4.01190*1 4.0110443 4.01(4000 0.0111*03 0. (1170(7 ;0.011I317 0.01*0140 0.0110H_4_ 0.0114711 0.0117017 lillltill 1.1101(11 0.1110470 0.0117007_____ 0.0114403 (.0111(73 0. 0114(01 0,01 IlfIt 0.01043(1 4. 01 OHIO Miiirn 0.444 0.075 94 36.3 0.04626 5.2 0.00546 94 94 0.01223 0.00103 94 00 0&7B00 -(OfNlTW C.OHF YZ0014455 G-17 Appendix G (cont.) An Inheletlon Female Fertility Study Nltti Beniene In lute 79-2425 GROUP SEX UTTER PUP LIVER <sir KIOHEYS fODYUL. tfll L/BH K/BW --- InI------- P t If! ape C 1 *310 --------1--oran It t as 2 i*pi II F *st ip | | F 419 10 i*xao U f ace ""4~ " iit II F ------IT----------- # ate e 1 >TI1 --m-----------------1-- l.l IS II F 4f* 7 ipa --rr Fm i.eoa tt r n-- ----------- t ait 4<e f i.tt 10 l.ial ti F 430 * i.vaf n-- -------------t--------J7I-----------i-- 1.311' 11 t ate P.374 iv t ait i 1*403 0.000 d.aii o.aae 4.4(3 0.300 0.001 O.aie 4.470 C.4II 4 *41C o.cte e.aoo e.api 4 * 444 0.C07 o.aoo 30.1 0.0400410 *014010* 34.1 4.0473019 0*01 >0000 31.0 o*omi. IC.I c.cifieil 0* 0137(07 31.0 4.4101000 '0.01104*7 10.4 --------4 .`oiiTfoi-- 0.011*0*4------ --1n7..7r 0.ea407 I.OIltlll 0*011034* iolmccl 11.7 C.0417710 *100100 iT.r iiltinsi -MIlTltl at .4 0.0014100 0*0130000 30.4 43.0 0.0(01700 0.P4I170I "S. Si ifVA9 0. 4111040 "4.l --------I.lilllll 0(01 00770 47.3 (.0(01003 0.41(71*4 'tl.'f T .4(0till ~r0. 4110311 ii it tt it Ti........ ii ii 11 ii ii II ...... ii it ii ii it (( ti ti ii it n M ii ti ii It it II ii ii ii ti tt II ti TI it F pF f A F F f F F F p F F p p p F F p p F F F p p F 1 F p F F F "i1 p p til ate 419 a aiv 419 411 asi 431 431 all 431 aa* til 431 all ti i in 433 an asi 4J4 434 aft 424 432 43t 439 439 430 "All.. ait aae aja 4jc 434 430 439 t I.PII o.eie 40*9 0.4f0l4l (iiuISi e 1.707 o.aoa 30.0 0*0410101 0.01 to 300 7 lToTi f.atl 41*4 0.44400*1 htiiilll c 1 *340 0.470 14.7 ' 4.4(411*1 0.0100700 c - -Tins S.003 37.4 4.4447*17 i.TlSitil te 1 .371 0.004 t 1.400 0.441 30.7 14.4 0.4471*37 0.04144I3 0.014* MO o.oiifoai l.ltt 0.437 34.0 ... _ 0*0170700 . . .OlOfUO e l.llo 0.377 30.0 0*0300007 "4. 4100447 f 400 4.411 34*0 ' 0.043013* HOMO "IS 1 '1.311 b.aos 31*4 CtVCillCC 0. 9137100 ----ef----- 1 .303 1.100 C.aoi r.iti JC.4 0*0400314 --------*7*11*1*1 0. 0131000 "wnroi" t I .OOP 0.374 31.3 *301140 4111104 T7o* i.iit it.r 041(041 0*01304*0 10 c 1l..0l0t0t 0.340 t.aoo 1 1 .007 C.34C >4*0 ll.l 30.0 0*0404341 i.iiirm" s0.n01i3n4s33i0i 0101404 0.00014*3 e I.IU r.iae 30.0 0.4373700 0.4111*74 t 1.001 0.347 31*0 ' C.01(4401 '.outfit ip i 1' i .pal 1.407 1 *379 0.414 0.3CI 0.400 30.3 31.0 .....11.1 0*04(0117 0*0431300 0*0400000 4.41 It 003 .OtOtOPO i; truin' o i oie 0.430 10 1 .713 I.ail 30.4 IC.C 0.04M037 c.taeTSJl *111400 4. 411 ti4 4 0.000 0.311 < 0.300 0.343 <7.0 10.1 0*0147101 o.OTcoSn 0*0110)04 r.TITolil C 1.377 0*347 11 .0 0*4410041 0*0117410 7 1 .111---- Collf ll.t 4.14(1011 ' onnxfi-- t.aac * l.lii 0.413 ' I1T1..l" *0411443 ijiiiiwr- 0*01)0077 IP 1.440 0.404 34*3 0.441I0II *0110110 e" i**o--"4 .til----nx--iniTTOT-i.irnm-- < i.oao 7 "l.0 O.CIO 4.411 30.3 mi" *400103 e.sinrouinll -1 0 !* 0.444 ~r.vi7-- i.tit 34*3 --;r o*.*(4*0o0s4o4n0 *110171 4*ftltll ~ - m a 4 .1 . too _ 00.0, 0*0404100 0.011(710 00 CoNF 67Soi rF`NTTAl YZ0014456 G-18 Appendix G (cont.) An Inholitlon Fenele Fertility Study with Benzene In Ru067 79.2425 GROUP SEX " 11 f... ti F If r vv F ' it ..... t it F !l 1 II II it t II """ it t ~TC li II t "" ' 1 II F ti li II II it ki ii u ii ii ii II It it ti " 1 li II II---- it ti II it ti II" li F F F F F f- F F F f F F F F F 1 F F F F F F F UTTER HI eaa ISi' M 1 'eat 41* eee eee ae#'"" eei - eei 44! eei 44 4 eet Ml e44e3z 443 Ml eez eez 444 eee **# eee eee eee eel eez '"Til eei 44ft eea eee eee eee eee PUP W KIDNEYS (9) BOOT WT. It) L/BW k/bh e i.aee e.ete le i.*i e.eez e M7I e.eit ee.e 36.6 3771 0.0130700 0.0411031 0*0120600 --17)411111-- 0.01fi062 --7 1.377 e.eit 31.2 0.0441346 0*0130210 4 T.534 t.ell ------ 337f V.liUlH-------- 17)111(11 c I.6CC e.eti 36.0 6.0473143 0.0120000 t iee ~e*si ------ 14.1-- e.eeirm------- nrniii-- "7 "T 1 .eez 1 *0 13 c.eze Zt. 3lT e.eeeejti VtVli1414 0* 0122101 i* 11 inat-- e 1.71* e.eit 22.1 H--"'"l.T*0 7 -- I.ZIB '~B".e*7' * 'f i.eu i.oee '1.411 0.J31 6.247 e.ze? B;36l " --i;r~ 27.2 31 .2 ze.e ee.e ie I.SK e.eei --i.ee* " ' t.en ' 20.1 ze'.t'- *6116426 0.012I3T0 i.timn-- o..eCeeKie4iMe -"0.,0(112|0|3*64| .*40600 0.01IIC67 V efllilwi i.mnn-- 6. (466616 0.01 26773 0.0472921 0.0122136 4 1 .741 e.eif le .2 e.oeoi6( 0* 0124(12 ie i.eti e.ete 3. .#432633 0121270 t i.eie e.zze < 7 i1..o6t*e1 *.zte T3n C 1 .oee e.Zei * e.eei e.zee 10 i.iex e.zee 1 i.*c? e.eii 22.6 (t.l ee.e ii.i e.e Mil__ 31.e O.III30IO 0.0127413 2.0416620 0.0366604 T0D*0T1J4T11e3V3l---- 0.0413134 --o* otl.tiie 0.0362466 0130000 .oejieii_____ Ilium* - 0.0470064 0.0144033 e 7' et ie ? < " 4'" i.eei I.iee 1*630 *.oei 1 .67* i.ooe 11..767673 e.ete 0.6/i e.ezt e.eii e.ete e.tie e.ete 6.471 62.7 4177 ze.e 61*6 It *2 41 .6 ee.e zt.e 317206 niiiiifi 6.6416363 *0>663 0.0463310 0*0410200 --I.MflHI 0*0130*24 i.tiimr __*! 10)20 ' e. ei *400* e.omtei e* ei*7oi 0.0121*00 " f.'IUlfll-- cie 2 .eee 1.277 e 1.260 7 1.36* e.ete 0.370 e.zee e.fn 43 .6 36.4 if.c ee.e 0*040020? 0.0400C10 0.0411*16 t .24 76302 0.0130110 0.01*171 i 0*0120020 .oiiotil e 2.12* e.tee c --mn-- e.eee ee.e el.I 0*0432001 aMIVIOI 0*0120400 0.0114*00 ie 1.6*1 0.637 46.2 0.0*10760 0.012(106 MEAN 1587 0.444 35.5 0.04430 0.01256 S.D N 0,403 0.075 95 94 5.9 95 0.00674 95 0.00095 94 Do COhip 06780z TnFNTTAl YZOO14457 6-19 Append* G (cont.) An Inhilitlon F(m1e Fertility Study with Benzene In Rti 79-2425 GROUP SEX UTTER PUP i|W|R KIDNEYS ` IflJ L/BW K/BW III f CIO 3 0.(89 0.110 13.0 0.081(018 ' 0.0100403 ttf F III r --------ImII--------- Fj 111 in tat (id 4 0.(71 ( t itll 7 1.301 1 1.001 0.113 Mil 0.(43 a.tio IJ.l (0.1 43.0 --rra 0.1494030 0.8148034 (.1104(14 * (.(137113 0.0147(77 (.013(4Y( in F etc in f lit 4 1.070 10 1*3(4 0.(03 0.(71 41.0 eo.i 0.141(401 0.047091 (.0143100 0.0133000 HI F (IT 7 1.0(3 0.334 ie.9 0.019(101 ' 0.0130(01 tit t IT ~~t i.iid o.tti 10.1 0*84(7433 TViiticot --m111----rF ~ (IT ei* 0 1.0(8 10 1.141 0.134 (.if t 15.4 "*7T^1 (.41(314 1 04(9410 0. 0090513 o.ciiiii i hi f (1C ( (.(11 (t(* 11.1 8.(1(9814 0117100 in * 111-------------- 7 (.000 o.5i3 18.0 e.iiilbtr rtiii'm in tit 1.104 0.394 31.8 *418794 0. 010007 in * in --Fr --m-- (11 cm (It --rati* --------f.Tl-------- 10 1.001 0.317 4 FtflfS ran 10. ' *(.( iuiiirir 0.040(494 Tiniur 1.T1aoioo 5. 0130305 t.oflivio It 1 F cae ( 1.014 0.318 It .4 (.(1(4(01 5*5133100 --nr-' F (31 " 4 1.I4< 0.710 *" tt.r` ~ (.(4fr^ iiii 4iio in * (31 F " * (31 I 1.0(7 0.(00 i i.rii '0.4M .. ^88.0 413400 .0411535' 0.01 >0(00 in F (31 7 !.*( 1*498 37.0 0.04(8070 0.0133704 "HI i ASA ~~t r.tti 0.131 It.T 9iv tviav ( 01 Jill* in F (31 5 1.015 (.CIO 39.3 0.Of 11107 0.0134100 ------- tfTi-- F 10 1.500 ------f.Ifl.............' 38.d' 4.1413300 --ramie r III f (33 C 1.003 0.4(0 41.9 0.(47(043 0.0110703 III'"' f u! 1 i.07( 4ll iiTI (.0447141 1.010(111 in .... ' III (11 03 7 f.OOt 1.037 0.(31 ran 41.0 (.(109013 0.01(9700 40. l' ' " 'wmur O.WIC140I hi F (33 0 I.114 0.491 41.0 0.(81(048 0. 011(144 11 1 f cii le i.Poo' ' 0.4(1 fill t.miTii 4.0133(31 im ' F (34' C 1.074 o.iffi' ' 40.9 0.04(|((1 .oi iiifi ' ' in F (34 7 1.000 O.Clt 44.4 C.(4(171 (.(11(401 tit F ' (34 ( "1.7(0 0.403 4i.t-- 0.414%4( 4. 0114301 in F (34 9 1.075 o.toc 41.0 (407117 011350* III --r~ it i F (14 (38 "TO 1.015 ( 1.708 o.4t( c.eoc 41.4 40.0 iMJUtlt 415801 raumi 0.0103730 ~ i" (39 "'7 1.0(4" c.t'ot 41.7 i.Mlllir (.0113013 in F C3C 1.071 0.CI7 44.0 (410008 131(40 HI f (31 ( 1411 0.4(0 io.d O.C4SC70 * 0.0113700' III # (3! If l57( 0.411 37.0 0.0418(31 0.0110007 --m-- HI III r ---------m-------------- 4 F (1C C F C3T ( ' l.U --ran-- 1.701 1.0(1 0.719 (04 3.1 ( .7 30.1 0.0418910 (.047(043 i.ioiiili ramnx-- 100(00 ft 011(4(6 111 F (37 7 1.517 0.441 30.0 0.041404C 0.0110(17 til F (31 o r.f*o" 4.4TC tt.l *i.((Uir--uiimi-- nrIII r ' 'I" (37 Hr 0 1.0(1 0.4C( n nnr o.lci 39.1 J6 V 4(0100 0.0104307 O.MMttt --rarvmi-- hi r (3 HI P (! r( 1.001 t.ui (030 0.111 31.9 41.1 O.OIIIOOI 0.0134MI o.otioifT^--ftMftffr~ III F (3V 1.7(4 0*510 (0.7 0413(10 0.0100307 HI f cic 0 1 .(45 1.131 u.r 1 t.liifiir"Tinnii-- HI F (1C 10 I.HI 0.(93 (0.0 0.0(17431 (.014(005 1I1 (48 "i--------- romr 814 IQ 5T.I 0.04(4105 e.0111811 HI F (48 7 1.700 0.(91 39.0 0.04IIHO 0.013(004 ^0 06780? conf t of/vt t ai YZ0014458 6-20 Appendix G (cant.) An InhiltMon Femtle Fertility Study with Denzene In Rite 79-E5 GROUP SEX LITTER PUP W -KIIDNTEY4S ID) 17 BW IV BW III f a III P to 9 III P til I* --ImII------ Pp---- 41 41 ? 1 Ml P <41 in f 41 in f 41 10 4 in ---- 1---- <4( * --imn----pt------C^4J------ c 1 Mi ii i F r <<4441 I i ii i t 43 < nt F Ii3 * --hmi----rf-- 43 S c 1 in r 43 10 " tir P 44 " " ( in i> --m-- t 6<444 7 t in f ---m-- r t4 4 lift --tj. --hmi-- t ~ <41 < '(4l------ 1 i ' hi 1 IT --- yP -- <49 i*% --<< --mIII------ fF---- f 4C ----EH------ . 10 ihi ir iF--- C4C tit 7 E !1*<( ~ I.*10 I1..146f<0 0.4(0 0.0*0 T7i?l 0*310 o.4ir If .0 0.9470443 0.0113071 10.1 0.0401130 0.0139100 33 O.oiSoSjo o. iiftiM If .0 0.03(1044 0131101 l.llltlll . IIJII01 * 1 .4(0 1 .TTl <*39 J *144 1.0(1 1.0(1 1.7(9 no I.OfC i.90 0.3ft *.!< o.oie O.Tio o.eei ~ 0.(74 oo..eteiti 0.4(4 eO..ttieei --mm 10.0 19.f 43.0 41.i 41.( 44.C 41. JT.f 11.( ST. 4 40.1 ki.i C.94004*! 0.040(444 0.04(0110 4i.*i9o4(i4t1a74ii11 i.iiiiiir (.44(1(41 iiiil1i4r 0.04(1344 k.iiinir 0.0413311 l9Ctill! 0*0130933 i* ofiiiiT 0.0131379 o.oiffilt 0*0131300 (.(iidii .01(9(00 Ii0111II0 0.0130 043 I.Till 4*0 0143(41 13(147 1,110 0.470 .f 0.041(100 0.0130(10 1.444 ' *.40d' 1 .013 0.4(0 lilil 4*471 I.34C (.1(1 14.1" 17.1 --If.4~ 31.f i.tiihin kli 00(70 0.0.4m(00n43ir 0.01313*4 i.ititur 0.(431944 0131(30 1.7(4 --r.iTJ-- 30.1 1.4 It (,401 30.f 9*1)4194*9 ....1.1111194 0.04(1409 0131047 iak 1 .943 4 f 44 ""vr.T 0.(43 3f .0 d.(iifir 04(0191 i0i.0ll1l3l0t4l0l0l i'.les'" ' * t.iil ' ' !U _ -- (.tilikir 9.01 lifts 1.1(3 i *4 04 c.iet 0.4*4 31 .3 (.01119(0 0.011(101 ki.t 0.04(1(31 0.0114437 t.rci C.40C 0,494" If .0 >i.i ((44(04(110(00 0.0114931 (.OtlCtK in in nt" --mn-- in hi hi in in ITT in tit ill ik i HI IN in in imn tit F P P P F P P P P P f p t P r p F P P P F mb <4< cu 447 <4T <41 41 <49 eta A4 Mi 4 in in 49 OtO "' HI < eoi se 10 "< 1 * 9 10 4 c < t 4 1 c 9 10 " ? c c 10 1 ,614 I.ICi 1.004 l.f9 1.14B 1.014 l.*4t (.710 1.4 It 1.704 liiif I .00 r.iii 11..040107 1.030 1.6 tO 1*001 1*040 1.041 1.040 I.070 0.401 0.401 31.f 30 .( 0.0419010 .414(10 0.0114301 0.0133063 0.30C 0.4(4 0.4*1 33*1 30.0 34.4 0.0491401 0.0133000 0,.0(((3ll403910 ..0.413(340 4.01 lUil .(4i _ 1.7_ 3,0(14013 0.0144033 0.4(0 0.<0I 33.( 01.1 ' 00..00((4100010110 0.0134334 _3.3133107 0*101 .<(! 44.0 (.0(41704 0.0130491 41.1 0.0014030 0.0144304 --ntmnr o. (i iiiii 0.(10 0.(14 00..0(3407 0.4(4 44.0 30.0 43.1 30*1 o.(aio (031040 ((Hij (.041o01t0ii4i 0*0143000 0.0130400 -4. 0130101 4.0140000 0.0117313 o.tld 30.4 O.MlitOO " 0.4(1 0.441 O.flt 0.400 0.0 3400.1 14. ,t4f044l ; 0.(10(033 0.0110304 ' 0.0131400 ... ((O44I.3U(0fl1L 0,0109(71 j. outfit 0.401 10 0.0039091 0.0130703 MEAN S.D. N 1.783 0.488 0.431 0.102 108 108 37.7 0.04700 0.01295tt 7.1 0.00492 0.00103 108 108 108 Do 067804 CONFTDFNTTAJ YZ0014459 G-21 Appendix G (cent.) An Inhalation Female Fertility Stmty with Benzene in Rats 79.2425 GROUP SEX LITTER v IV IV IV 1% IV "TV" IV IV El IV IV iv IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV 1v IV IV _ 1v IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV f a f a F f 1 p F a p p a a a P P a a F a' a F a / F F F F ... P | P r r F r F F F r K F F r r F r F F F F F F F 111 tit m 15 esc ett in at etc tic esc lit lie " in tti 27 eat 27 CSC 20 tie ZB is tit 30 30 30 30 20 aid 3 1 ' 331 331 S83355 835 835 835 . 823377 837 Hi 333 833 833 333 339 539 283"9 III PUP I-' c ? t 10 4" c e e t id e T e s 10 4 e T 4 "Iff" 4 t e f 1" ___ ? 1 041 sot leMI 1.241 1 .TOO i.ets i.ii I.IK 2.ai i * i.soe i.bit 1.911 1.914 1.4*1 llllf 1.4(7 i,.<a1n{) 1.242 1.910 1 .372 1.1 It I.94C 1.447 1.949 t.eif 1.121 2.094 1.444 1 .904 1.444 9 4.727 40 6 ' 1-333 1.582 7 1.536 3 1.790 9 1.626 40 1.32* i 2.233 2.29* 5 1.333 8 2.153 6 1.499 7 1.313 3 1.964 9 1.451 10 1.932 6 1.416 7 1.350 3 1.270 9 1.301 10 1.169 6 1.203 K1DKETS 9.419 9.412 o.ma 0.441 0.C4I 0.479 0 i 14 0*942 e.tii 0.412 0.404 O.eu O.tll 0.2*0 0.4*0 9*412 C.44I 6*4(2 9.401 4.447 e.ste 4.3(0 0.714 am* C.tOf r.iii 0.9(0 o.cce C.I17 C.4C1 0.406 0.324 0.460 0.450 0.425 0.430 0.369 0.570 0.533 0.512 0.583 0.*3l 0.509 0.575 0.395 0.536 0.443 0.377 0.331 0.412 0.337 0.371 BOOYU^ 10) L/BW K/BW KVf 9.0141961"--nrmn' 3.e 39.9 9.9491993 C4949I4 - 0*0107(01 0.013941* 2.l C.4497919 * 0.914049* 32.1 C.9119319 ' 9.9119(4* 39. t 9.9494090 ` 9.014991* it.S 9.0491944 ITSTTlTtl-- 42.t . 4.9413407 t.tiacti* 41.2 0.19*0193 0. 01304** 21.0 0.04170*7 *01*1*97 31.2 0*04114(2 0.013*0*1 34.9 49.7 (13490 'Ml**? oTiottSV l.oiJjUJ 31.f ___ 0.041717* _ Q. QI1393I ll.C 0.9490)14 0.01 IONS 49.3 0.044090* O.OI 14144 34*9 *.#41*111 6.611171* 39.4 32.I-- 0.04(1437 o.oiii in 0.0111*** O.OI 34*0) 30*9 0.04(410* *013*0*7 31.4 ((4(4C*I~ 31.t 0.04104*1 MltlUl 19.9 o*eiiii<n~ K *11(444 ifil 0.0411410 0. 01*0401 33.1 " 6.64(1166 " *.01 34471 42.1 0.04(1031 #*131(90 at.l f. (44(4*3 ------ 3S .9 0.041fl2( 0.0144 091 44.1 "* S'. (414(4* *.*11*4*1------- 49.9 0.0401441 0.(13114* AJ *4 6.IA3196I " 0.0131(3* 21. 1 .((*0304 0. OI401(t_ 26.1 33.1 3313..32 . 34.0 31.7 23.7 *1.6 41.0 33.7 41.7 32.1 31.0 41.0 36.2 33.9 31.9 31.5 31.2 30.7 27.9 27.5 0.0(61(96 0.0155556 0.0*02719 0.009TB35 0.0476506 0.0138554 0.0*33019 0.0141509 9.0577419 0.0137097 0.0512934 , 0.013564T 0.0*6(324 0.0128571 0,0536779. 0.0137019 0.0559512 . 0.0142195 0.0497855 0.0132300 0.0517506 0.0141007 0.0466973 0.013*263 0.0584339 0.016419* 0.0479024 0.0140244 0.0400329 . . 0.0109116 0.0496(59 0,0137789 0.0443937 0.0133371 0.0*29571 0.0119633 0.0*07051 0.0122115 0.0*23779 0.013*202 0.0413996 0.01)3710 0.0439273 0.0134909 DO 067805 CONFIDENTIAL YZ0014460 G-22 Appendix G (cant.) An Inhibition female Fertility Study with Benzene In Rett 79*2425 GROUP SX UTTER IV IV it tv IV tv lv ft IV IV IV vv IV IV Tv IV lv IV IV " IV IV IV 1V IV iv.. .. IV ----- Tv-------------- IV ' rv*" - IV IV ' ' '" ' IV rv ~ IV IV IV IV Iv IV tv IV IV IV MEAN S.D. N V40 eee eo co tl eel ' '141... C4I let 142 ee> ' ' 42 Hi eet lei ei e*a ees *41 '' 044 HT ee fee' " eee 144 044 tet" eee ee eee 04 44 7 44 V **1 47 ee? 044 eee eee eee eee eee ee PUP K1DKEY5 BODY WT. L/BW K/BW (9) 9 1 *300 c 0*0 e l.l ! J7JTI e.xii in ta.e If.* C00IV *.**01*1* * i.iiiiTiT ei mi* 9e..9o1iT4(T1A3I9i 10 1*3(1 3*0 37.3 *444317 *114*131 .. < i .iiF 0.30 1 se.t I.4113*9 01 IllIF V 1.33C ( --rmrr 0.07* 30.3 *407031 ' **099 NO 57JT7-------- --in-- A* .n*ur.... c 1.131 0.34* 33.4 0.0100030 0131479 10 1.103 0.373 *0.7' oneiii--r.tf**di~' 4 l.eez 1.(30 40.1 i.ilS ------- l. li-------- 31 0 o.*4*fe 9*0133179 i.Tiinn-- I.Tlli'lir CV i.ee* 1.000 4 i.oes 4 l.iii to i.3eo 4 B.oee O.ect 0.34 T 0.4*4 QoII4 0.401 O.eTe 33.* le.l 34. Tt.f 30.* *171 I.MIIIll I.HTHiT *4*0*13 C0*.0*4I]S**0400I 2. *40*119 01 30103 e. eioeoei 9.01 S3491 Vb 01 03 000 17(*1141(1710414 ' ' e i .eei 1 i .o ie o97.cTtSoI----- *3.C 41.* *04*0107 0.1*43774 0.0I3I40B *01414X7 4 1 .303 -"i;i'e4 e .a?* A iVif 11.f at.c *.*4(4479 tiUiiiri 9. (14(449 "irwidiic < i .sea C.H* H.C .*4(47*1 9139104 7 t 4 T:*cr~ {.eJe li .r O.MiTWH ' niiwiir --ran lie 0.341 se.3 (.0407*09 0*0117009 ------- 0.433-------- --VT*1---------nrrmn--'7.TITIUI------- 10 i.eoi 0.430 31.1 (*(41*030 913CC09 ' ' 1>030 t;eec' 33.1 0 .*4*7499 --*.tn*t*4 t 1.107 0.374 33.C 0499347 0.0139001 i .tie c.aeo 1C o9 ` 0.(4(0*4* "9*0140104 1 i.seo nm O.ff 1 0.441 34.3 40 * 1 --eB..e*4e1c9ie*o3o1-- 0. *101**9 T. HTVH C 1.411 0.430 Hot (.((4070 *.011(4*1 7 i.eoc 0.434 31. ((4(C4fC "`(. *130119 0 i.aoe ~*.3ll (0.1 4.044)033 9. 0130034 e 1 .973 0.34* 33.7 <(4(0734 * oi > not 1C i.etT 1 1.300 I 1.41? *.430 0.4*3 0.4*1 30*7 37.3 31 J 0*10199 9 *93 70*14 i.iiiiii* 0130434 9*0131409 *013(009 e 1.3*1 10 1.3I0 e.sta o.lie It.C at.* 1.(4(101? 9.04)493* 9117370 0.0117703 1 1.1*0 c 1 .0*4 3.107 O.tll c.et* e.ec* 43.( **.7 44.8 *.479*34 *.(41*477 9*4I*9C 0143391 0130304 *0149*03 1.560 0.450 0.326 0.034 96 98 33.8 0.04601 5.3 0.00507 96 98 0.01330 ft 0.00115 98 DO 067806 CONFIDENTIAL YZ0014461 GROUP 5 a fc V % V V' V a a V a V \ \ V \ * % a \ V V a a V a V * t V % V V a a V V V \ a V * \ % V a % V a a % G-23 Appendix G (cent.) An Inhalation Fmalt Fertility Study tilth Benzene In Rata 79-242$ X LITTER PUP ICI^RETS W19.JVi L/BW K/BN /. ~iw*-- itit iota loan idle ioit 1 Of 7 1017 r tmr e 0.047 7 1 .203 t 1.133 4 0(f 4 t.trc e 1 .434 C 1.721 0.172" 9.391 9.199 9.312 0.(39 9*904 1.111 0.C47 22.4 23.9 31.4 24.9 14.9 34.4 " 11.1 34.1 ranror 9.*39*429 ' 377119 (*9499(04 0.9337979 (99(491 0.444*130 .94491(3 ; raitiMi ~ 9. 01 21099 9.91 34791 9.911(139 2.913*797 9.911999V B.irilTST" 9* 9194499 1017 7 1.0*4 4.499 31.7 *(14999 9.9149(99 1017 1017 lots irn iota 1019 1019 10*9 iei ITT5 1031 toil 1011 1012 103* 1032 2 t 1.719 1.022 ' 0.4ft 0.491 34.7 37.0 T 0.977 0.222 21.3 i 9.909 --ran-- 4. i **29 13*7 < 1.30* t lt*9 9.lie 9.409 30.1 24.1 c 1.233 1.234 0.104 9.301 39.4 2*.9 W I #lf f 0.407 11.4 i 2.399 e.(7e 47.9 * 2.924 0.900 44.9 e I.4C1 0.419 39.4 7 1.442 9.471 3*.l ( 1.4 13 0.493 32.7 '* 1.233 9.140 31.0 9.9447119 9.9441433 9*9411737 o.osialft .9349791 9.94(1311 9.941(971 9 .9493(34 9.04(1734 0.0417401 9.9I93I99 9.0(44444 9.94(1173 9.94(1041 430119 9.0147742 9.9123343 9.9132*73 2.2132394 4.91l*l44 Miirar* 9.9149999 9.90 94321 9.9134201 9.dl43jil 9.9031(04 9* 9111431 9.9117(39 9. 4l 14799 9(.. 9dI3ll9ii1F2TX 1032 1033 1033 1033 10 1.313 ( 1.790 7 1.932 e 1.929 0*390 0.4(4 0.291 0.1*4 31.2 32.0 39.( 39.0 4.409233 403119 9.943I94C 9.940(143 9. 90 99 9 9 9 .9114474 9. 9197404 9.9102971 1033 1033 1024 1034 1034 1094 1034 rort 1039 toSi 1039 ins 103* |63( 103C 1030 1037 1037 1037 1037 1027 1030 1039 lose 1030 1.739 it 1.9(2 e i.oeo t 1.279* i i.o te 1.444 1.33C "i 1 1.211 7 0.900 C l.9ii 9 1.941 io < 1.004 7 l.aoc c 1.124 I.47C it 1 .949 < 1.992 7 c t " 1.992 1.704 1C 1.4 <7 c Mil 7 1.949 f 1.449 1.297 0*4(4 1.411 37.1 34.4 9.94(9914 i.iiiiiiT 9.9113191 9.411*794 0*340 '" 0.379 4.4 " ~'3i.r-' .411314 iitoiin"- 9. 9124399 9.i'i4i 0.319 19.3 (1*970 43 . 9*9139994 0.4(0' ~ 14.0 C.C4I0222 7*9i ii?9 9.344 12.2 9.9414997 <.3*1 IT'.I v*ftoikvi e.iot 17.4 9.9141(11 9.4IS---- "21.1 9.i4iiii-- 9139199 I. ft 13011 9.9110997 4. <1*4444 9.493 9.409 0.4(7 9 4d4 11.3 9.94(9I9( .129939 --ira-- .(*((*(( . errorr 32 ( 30.1 9i..9t(m121n(9 r--i9..n9I*nCi(uI9.. 9.370 0.491 31.1 21.9 9.92(|41( 9.C4C900C 9.9119471 9.9141(71 9.440 9.499 mi----- 9.941 i.i*4 24 .7 34 .9 1774 33.4 !* ((3114 9934709 9(it420 9.9(99291 9. 90 49499 9.9144939 9. 911(719 9i..9if1n41h31T9 9.49* 9.424 9.414 4.419 2.1(1 31.1 33.9 32.9 31.4 . (7.4 C.MM994 *9434**1 " 94(4991 9.9410793 449910 9.91 HIM 9.9143M9 9.9139999 9.913(494 '9.9139192 ' OO 0>7B07 conf^ta* YZ0014462 G-Z4 Appendix G (coot.) An Inhalation Female Fertility Study with Benzene In Rett 79-2429 GROUP SEX UTTER WPUP ------~ V ----- p--------- 1030 F lose 18 --ITBI7 i.zeo V F 1030 * f------- V ------F---------- V V6-------------F--------- -lilnodoraasrecee------ I1jI--. fe4 !.*( DJJi 1.300 l*3( V 7 F 1040 e 1*163 F 1040 1.010 % F 1040 ------?e-- *.031 % F l$40 I.FTO ----- \5--------- Fp---- 1040 "TUI-- 10 4 1.700 1 oBVl 1 8 F F 1043 ided t 1.741 4 l.TSS V V F 104* ---- 17---- 1.001 F 104* 1.007 V F 104* 0 1.(3* V 1 1641--- n met * t F 1043 F -Ril e 1 I.J3C UiT* ' % * f F 1043 ---- {-- 1.370 iS4 iVfii `--- 5V"-- --Ff------ 1044 Ui*----n-- t.aio i .Bel V F 1048 e 1.47* % F 104* 3 i.Fii" V F 1040 c I .04 T V F 1040 *' ClSi V F 1046 e 1.144 V F 1046 1 rrm V F 1040 10 1.01* V F 1040 4 i.eii 1V F t04ft t I.T37 * F 1040 1*84 1 V F 1040 * 1.710 V V FF load c 1 *6<i 1040 10 1.007 " 1------- "IM* " T----- --iuir' \ v --Fp-------- 10*0 ms ---- 11--- 1.000 I.T41 ' V F toco 10 1.3*1 KIJJP 0.414 0.30* o.iSi 0.300 0.1*7 0.400 C .344 0.003 0.000 0.130 i'iaT? O.tl* 4 *808 0.0*0 Yiioi 0.40* 0.(07 0*400 0.300 0.410 1.47* 0.41* 0.430 0*410 0.440 o.all 0.340 fiTii 0.37* 0.3(0 d.fii 0.(17 "i.fla 0 *403 0*413 0.044 o.fii 0.317 4.114 C.41C BODY VT. nrar" L/BW K/BVJ J8 *7 0.0410031 0. 0130(7* 30.0 0.(414000 .013(100 *o.l 0.(111041 kYiiwi 31.0 11 ( 0.040M37 0.0110313 l.lilTOf Y.OlllOlS 14.* *040*011 0.0117030 13.( (.141*00* 1 (1 1*104 41.1 30.3 (.0(41*14 l.Milill O.OilJlfY 0.0130041 41.0 *04(4*40 0.0110133 17.1 iTKailoi? EYTiHlf 30 .0 31.1 *(41(100 .14*1731~ i..i1i3t0n03u3 " 30.0 (04(11*7 0.0144(47 Jl.t r.i474fil KH4t|il 33.0 0.040*4*4 0.014(001 30.3 *TJ77U4 iToiTiTi* 17.0 0.0*44377 0.017(130 31 8V401||f o. oiidiiO 31.0 So.t 0.0430001 --SsfJLUi** 90484818 IVfIM *1.3 1171 (.0414140 0.0404100 0.0131(01 0.0I31001 33.0 ir;t *(30*33* 0.(433700 0.0111310 fc.Olio437 10.0 ir.i *( i.iifivn (3*1304 !iti!T?!i!t?u!!i 0.0110701 i.oiiifil EHiifia 10.1 (.1407117 0.0133401 ( --ortHir" 0.013*04*---- *4.0 **1*110 0.0I4I1K j4o0..e0 84<18V0 0.04K03C |l87488 0. 0130(00 i*.r .c<ii47i Y. ft 3i*i* 30 ,? 0.04(1(40 (.0111(60 3471 " 0.041 71X6 1.91 IIUI " 30.1 .C4C03K 0. 0141401 IT7T 10.0 .. ~n.* 30.( l.flttflT- VYirnwi 4.040I4O7 0.0131*14 i.inniT--tinmi 0.0417(00 (.0114304 MEAN S.D. N 1. *'t>Z t 0.436 0.339 0.079 97 96 37.6 5.1 97 0.04442 0.004C9 97 O.^l333 ft 0.03136 96 DO 067808 OONFTDFNTTAl m I 1 YZOOI4463 H-l Appendix H An Inhalation Female Fertility Study With Benzene In Rats 79-2425 Gross Postmortem Observations Day 21 Weanlings {Unselected) PREFACE Morphologic abnormalities observed grossly In the animals from this study 00 067809 cnftdfnttai YZ0014464 K-2 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. Pup No* Sex _____________ Observation^)* 225 3 F N.O.A. 4 F N.O.A. 226 1 M N.O.A. 2 M N.O.A. 3 M N.O.A. 6 F N.O.A. 8 F N.O.A. 9 F N.O.A. 227 2 M N.O.A. 3 M N.O.A. 5 M N.O.A. 6 F N.O.A. 8 F N.O.A. 10 F N.O.A. 228 3 H N.O.A. 4 M N.O.A. 5 F N.O.A. 6 F N.O.A. 7 F N.O.A. 10 F N.O.A. 229 2 H N.O.A. 3 M N.O.A. 4 M N.O.A. 6 F N.O.A. 7 F N.O.A. 9 F N.O.A. *N.0.A. No Observable Abnormalities. Key: M male; F female. DO 067810 OONFIOFNTT Al YZ0014465 H-3 79-Z425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected} GroupLitter No. ppm I(cont.) 230 0 231 233 Pup No. 1 3 5 6 7 8 1 4 5 6 7 9 235 Sex M N.O.A. M N.O.A. M N.O.A. M N.O.A. F N.O.A. F N.O.A. M N.O.A. M N.O.A. M N.O.A F N.O.A. F N.O.A. F N.O.A. N.O.A. N.O.A. N.O.A N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observations)8 aN.O.A.> No Observable Abnormalities. Key: M male, F female. DO Oo/\/fr TD^TTAi YZ0014466 H-4 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm I(cont.) 236 0 237 238 239 240 Pup No. 3 4 6 8 2 3 4 6 9 1 2 4 5 8 10 1 2 5 6 7 8 1 2 5 6 9 10 Sex M M F F M M M F F M M M M F F M M M M F F M H M F F F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observation s)a "N.O.A.- No Observable Abnormalities. Key: M - male; F - female. 00 06781? C0NFT08NTIAI,. YZ0014467 H-5 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group ppm Utter No. 242 243 244 246 247 249 Pup No. 1 2 4 6 7 9 3 4 5 7 9 10 3 4 5 2 4 2 3 5 8 9 10 2 4 5 6 8 10 Sex M M M F F F M M M F F F M M F M M M M F F F F M M M F F F N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A. N.O.A. N.O.A N.O.A N.O.A. N.O.A. N.O.A. N.O.A N.O.A. N.O.A Observations)8 aN.0.A.- No Observable Abnormalities* Key: H male; F female. DO 067818 OONFJDFNTTAI YZOO14468 H-6 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm I(cont.) 250 0 II 425 1 426 428 Pup No. 1 4 5 6 7 9 2 4 5 7 8 9 3 4 6 8 9 10 2 3 5 8 9 10 Sex M M M F F F H M M F F F M F F F F F K M M F F F Observatlon(s)* N.O.A. H.O.A. N.O.A N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Hlndllmb (Right): Compound fracture of "femur. N.O.A. N.O.A. N.O.A. N.O.A. .J Kidney (Rloht): pelvis moderately dilated} filled wftfi cl ear fluid. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. aN.O.A._ No Observable Abnormalities. Key: M * malej F - female. D 067814 CONFTDFNTTA! VZOO14469 H-7 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group litter No. ppm II(cont.) 429 1 431 432 433 434 Pup No. 3 4 5 8 9 10 1 2 3 6 9 10 1 2 4 6 9 10 1 2 5 6 7 10 2 3 5 6 8 9 Sex H H H F F F M M M F F F M M M F F F M M M F F F M M M M F F Observations)* N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A N.O.A. Tall: blunt N7U7A. N.O.A. N.O.A. aN.0.A. No Observable Abnormalities. Key: M male; F female. DO 0678 ]5 confidential YZOO14470 H-8 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm II(cont.) 435 1 436 438 439 440 Pup No. 1 4 5 6 8 9 2 3 6 8 9 1 4 5 6 7 10 2 3 5 6 9 1 3 4 7 9 10 Sex M F F F F F M M F F F N M M M M F M M M F F M M M F F F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observations)8 aN.0.A.- No Observable Abnormalities. Key: M male; F female. D0 067816 CONFTDFNTTAI I I YZ0014471 H-9 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene in Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm II(cont.) 441 1 442 443 444 445 Pup No. 2 4 5 7 9 10 1 3 4 6 7 10 2 4 6 8 9 10 1 2 3 4 1 2 3 6 8 9 Sex H M M F F F M M M M M F M M F F F F M M M M M M M F F F Observation s) * N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Eye j^Le-ft): 50% opacity. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. aN.0.A.- No Observable Abnormalities. Key: H male; F female. DO 067817 CONFIDENTIAL YZOO14472 H-10 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings {Unselected) Group Litter No. ppm II(cont.) 447 1 448 450 III 626 10 627 Pup No. 1 2 3 4 9 10 1 2 3 5 6 2 4 5 6 7 10 2 3 5 6 7 8 1 2 4 6 8 9 Sex M M M M F F M M M M M M M M M F F M M H F F F M H M M F F N.O.Ai N.O.A. N.O.A N.O.A, N.O.A, N.O.A. N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A N.O.A N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A N.O.A Observations)8 aN,0.A.* No Observable Abnormalities. Key: M male; F female. 067818 ^I^NTTA, YZOO14473 H-ll 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings {Unselected) Group Litter No. ppm lII(cont.) 528 10 630 631 632 633 634 Pup No. 1 4 5 8 9 10 1 2 1 3 4 6 7 8 2 4 7 8 9 10 3 4 5 6 7 10 Sex M M M F F F M M M M M F F F M M F F F F M M M F F F _____________ Observation?s)a N.O.A. N.O.A, N.O.A N.O.A, N.O.A, N.O.A, N.O.A N.O.A, N.O.A, N.O.A N.O.A, N.O.A, N.O.A, N.O.A, N.O.A N.O.A, N.O.A, N.O.A N.O.A N.O.A N.O.A, N.O.A N.O.A N.O.A N.O.A N.O.A aN,0.A. No Observable Abnormalities. Key: M male; F female. D 067819 CNFJOFNTTA! YZ0014474 H-12 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats dross Postmortem Observations - Day 21 Weanlings (Unselected) GroupLitter No. ppm III(cont.) 635 10 636 637 639 640 641 Pup No. 1 3 4 6 7 8 2 3 4 5 6 9 10 2 3 5 6 7 10 1 4 5 7 8 9 1 2 3 4 8 10 Sex Observation s)* M N.O.A. M N.O.A. M N.O.A. F N.O.A. F N.O.A. F N.O.A. M K1 dney - (Right) dilated renal pelvis (.5cm. dlam*). M N.O.A. M N.O.A. M N.O.A. F N.O.A. F N.O.A. F N.O.A. M N.O.A. M N.O.A. M N.O.A. F N.O.A. F N.O.A. F N.O.A. M N.O.A. M N.O.A. M N.O.A. F N.O.A. F N.O.A. F N.O.A. M N.O.A. M N.O.A. M N.O.A. M N.O.A. F N.O.A. F N.O.A. aN.O.A. No Observable Abnormalities. Key: M * male; F * female. DO 067870 CONFIDENTIAL YZ0014475 H--13 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) roup Litter No, ppm III(cont.) 642 10 643 644 645 646 Pup No, 2 4 5 8 9 2 4 5 7 8 9 1 4 5 6 9 2 3 S 7 8 9 1 2 5 6 8 10 Sex M F F F F M M M F F F M H M F F M M F F F F M M M F F F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N *0 a A* N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A, N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observation s) aN.O.A.- No Observable Abnormalities, Key: M - male; F * female. 067S?i C0^TDENTr^ YZOO14476 H-14 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm III(cont.) 647 10 648 649 650 IV 825 30 Pup No. 3 4 5 7 9 10 3 4 5 6 7 2 4 5 6 7 8 2 3 4 7 8 10 1 3 5 8 9 10 Sex M H M F F F M F F F F M M M M F F M M M F F F M H F F F F N.O.A. N.O.A, N.O.A, N.O.A. N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A, N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A N.O.A Observation s)a aN.O.A. No Observable Abnormalities. Key: M male; F female. Dl^ 0678?? CONFIDENT I Al, YZOO14477 ................ .... ---- ......... - - 1 1 H-15 79-2425 1 Appendix H (cont.) An Inhalation Female Fertility Study 1 with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) ft Grouo Litter No. Pup No. Sex Observation s)a ppm 1 IV(cont.) 826 1 M N.O.A. 30 4 F N.O.A. 1 6 F Liver: pale red-tan. 8 F N.oX 9 F N.O.A. I 10 F N.O.A. 827 2 M N.O.A. 3 M Kidneys (Both): dilated renal pelvis (approx. 0.3 x 0.2 cm). 1 5 M N.O.A. 6 F N.O.A. 7 F N.O.A. I 8 F N.O.A. 828 2 M N.O.A. 4 F N.O.A. I 6 F N.O.A. 7 F N.O.A. 9 F N.O.A. 1 10 F Kidney (Left): dilated renal pelvis a (0.4 cm. In diameter). 830 1 M N.O.A. 1 5 F N.O.A. 6 F. N.O.A. 7 F N.O.A. 1 9 F N.O.A. 831 1 M N.O.A. 4 M N.O.A. 1 5 M N.O.A. 6 M N.O.A. 9 F N.O.A. 1 10 F N.O.A. l AN0.A* No Observable Abnormalities Key: M male; F female. l 1 no 067833 l OONFIDENTlAl YZ0014478 H-16 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations Day 21 Weanlings (Unselected) Group Litter No. ppm IV(cont.) 835 30 837 838 839 840 Pup No. 1 2 3 6 8 9 3 4 2 4 5 7 9 10 1 3 4 7 9 10 1 2 3 7 9 10 Sex M M M F F F F F M M M F F F M M M F F F M M H F F F Observation s)a N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. liver: accessory lobe mottled dark red and brown. aN.O.A. No Observable AbnormalItles. Key: H * male; F female. DO 067824 C0NFI08NTTAI YZ0014479 H-17 79-242$ Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) roup Litter No. ppm IV(cont.) 841 30 842 843 844 846 847 Pup No. 1 2 4 7 8 9 2 5 6 8 9 10 3 4 1 4 6 7 9 10 2 4 5 7 8 1 4 5 6 7 10 Sex M M H F F F H F F F F F M F M F F F F F M M F F F M M M F F F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A N.O.A. Observation s)a aN.0.A. No Observable Abnormalities. Key: M male; F female. D0 0678^5 cNFroFNTjfl| YZ0014480 H-18 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm IV(cont.) 848 30 849 V 300 1026 1027 1028 1029 Pud No. 1 2 3 4 7 10 3 4 7 1 2 5 7 8 1 4 5 7 9 1 2 5 6 7 1 4 5 6 8 10 Sex M M M M F F M M F M M F F F M F F F F H M M M F M M M F F F Observation!s) N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Liver: visceral surface of accessory lobe dark red and brown. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.0.A. No Observable Abnormalities* Key: M malej F female. frO 067826 CONFIDENTIAL YZ0014481 H-l 9 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings {Unselected) Group Litter No. ppm V(cont.) 1032 300 1033 1034 1035 1036 1037 ' Pup No, 2 3 5 6 7 8 1 2 5 6 9 10 3 4 5 7 8 3 4 5 8 9 10 2 4 5 6 9 10 1 2 5 6 8 9 Sex M M M F F F M M M F F F M M F F F M M M F F F M M M F F F M M M F F F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observation s)* . aN.0.A.- No Observable Abnormalities. Key: M * male; F female. Oo CON? 6> 8?? Nj M/ YZOO14482 H-20 79-242S Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings {Unselected) oud Litter No. > pm V(cont.) 1038 300 1039 1040 1042 1043 1044 Pud No. 2 3 4 7 8 10 1 2 5 6 7 9 2 4 5 6 8 10 1 4 5 6 7 8 1 2 4 7 1 2 4 5 6 8 Sex M M M F F F M M F F F F M M M F F F M F F F F F M M M F M M M M M F Observation s)a N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A, N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A, Kidneys (Both): dilated renal pelvis (0.5 cm. In diameter). N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A N.O.A. N.O.A. N.O.A. *N.0.A. No Observable Abnormalities. Key: M male; F - female. DO 067828 OONFTDFNTTAL YZ0014483 H-21 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm V(cont 1045 300 1046 1048 1049 1050 Pup Wo. 1 2 5 2 3 4 7 9 10 2 2 3 4 6 8 10 2 4 5 6 7 9 Sex M K M M M M F F F M M M M M F F M M M M F F n.o.a. N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A N.O.A N.O.A N.O.A, N.O.A N.O.A, N.O.A N.O.A, N.O.A N.O.A N.O.A N.O.A Observations)8 aN.0.A.* No Observable Abnormalities. Key: M male; F - female. DO 067829 CONFTDENTTAt YZ0014484 I-1 79-2*25 Appendix I An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected) Preface Morphologic abnormalities observed grossly In the animals from this study occurred sporadically and do not appear to be compound-related. Do DOtyfr 067D30 TNTl4t YZ0014485 1-2 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)8 Group ppm I 0 Litter No. 225 226 227 228 229 230 Pud No. 1 2 4 5 4Vb lb 2 1 5 2 Sex M M M M M M M M M M M 4M 231 2 M 3M 233 1 M 2M 235 3 M 5M 236 1 M 2M 237 1 M 5N 238 3 M 6H 239 3 M 4M Observation sic N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Salivary gland (Right); red. Lungs: scattered clustered red foci on all lobes. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Selected for tissue preservation. bT1ssue$ Inadvertently placed In saline solution Instead of 10K neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A, No observable abnormalities. Key; M male; F female. do 067831 CONFTDFNTIAl YZOO14486 1-3 79-2425 Appendix I (cont.) An Inhalation Female Fertility study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)A Group Litter No. ppm I(cont.) 240 0 242 243 244 246 247 249 250 II 425 1 426 428 429 431 432 Pup No. 3 4 3 5 1 2 21Lb 1 3 1 4 1 3 2 3 1 3 1 2 1 4 1^ 2 4 5> 3 5 Sex M M M M M M M M M M M M M M M M M M M M M M M M M M H M 0bservat1on(s)c N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Liver: all lobes pale brown. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. "Selected for tissue preservation. ^Tissues Inadvertently placed In saline solution Instead of 10* neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A.- No observable abnormalities. Key: H male; F * female. YZ0014487 1-4 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter No. Pup No. Sex ppm II(cont.) 433 1 3 M N.O.A. 4 M N.O.A, 434 1 M N.O.A. 4 M N.O.A. 435 2 M N.O.A. 3 H N.O.A. 436 1 M N.O.A. 4 M N.O.A. 438 2 M N.O.A. 3 M N.O.A. 439 If M N.O.A. 4b M N.O.A. 440 2b M N.O.A. 5b M N.O.A. 441 lb H N.O.A. 3b M N.O.A. 442 2 M N.O.A. 5 H N.O.A. 443 1 M N.O.A. 3 M N.O.A. 444 5 M N.O.A. 6 M N.O.A. 445 4 H N.O.A. 5 M N.O.A. 447 5 M N.O.A. 6 M N.O.A. 448 4 M N.O.A. 7 M N.O.A. 0bservat1on(s)c Selected for tissue preservation. "Tissues inadvertently placed In saline solution Instead of 10* neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A.* No observabl abnormalities. Key: M male; F female. DO 067833 CONFTDFNT IAL. YZOO14488 1-5 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations Day 21 Weanlings (Selected)* Group litter No. ppn IJ(cont.) 449 1 450 Pup No. 1 2 1 3 Sex M M M M N.O.A. N.O.A. N.O.A. N.O.A. 0bservat1on(s)c III 625 10 626 627 628 630 631 632 633 634 635 1 M Eye (Left) - 751 opacity 2 M "Entire body: extremely small. 4Vb M N.O.A. M N.O.A. 3 M N.O.A. 5 M N.O.A. 2 M N.O.A. 3 M N.O.A. 2 M N.O.A. 3 M N.O.A. 1 M N.O.A. 3 M N.O.A. zj M Liver: Moderately pale red-brown. 5b M Liver: visceral surface, caudate and accessory lobes mottled dark red and brown. 1 M N.O.A. 3 M N.O.A. 1 M N.O.A. 2 M N.O.A. 2 M N.O.A. 5 M Liver: edges of left and median lobes slightly reddened. ^Selected for tissue preservation. "Tissues Inadvertently placed In saline solution Instead of 101 neutral buf fered formalin solution, these tissues were subsequently discarded. cN.0.A. No observable abnormalities. Key: M male, F female. DO 06.7834 CONF TDFNT T Al YZ0014489 1-6 79-2425 Appendix I (cont.) An Inhalation Female Fertility study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected) Group Litter No. ppm III(cont.>636 10 637 639 640 641 642 643 644 645 646 647 648 649 650 Pup No. 1 3 1 2 1 4 2b 3b 6b 1 3 1 3b 2 3 1 4 3 4b 1 2b 1L 2b lb 3b 1 5 Sex M M M M M M M H M M M H H M M M M M M M H M M M M M M H N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observation slc aSe1ected for tissue preservation. bT1ssues inadvertently placed In saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded. CN.D.A. No observable abnormalities. Her. H . 1; F - f.le. D0 06783!. CONFTDFNT T A! YZ0014490 1-7 79-2425 Appendix 1 (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected) Group ppm IV 30 Litter No. 825 826 827 828 830 831 835 837 838 839 840 841 842 843 Pup No. 24b*> 2 3 1 4 lb 3 2 3 2 3 4b 5b 1 2 1 3 2 5 4 5 3 5 lb 3b 1b 2b Sex M M H M M M H M M M M M M M M M M M M M M H M M K H M M Observation s)c N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Kidneys (Both): pale red-brown. N.O.A. N.O.A. ^Selected for tissue preservation. bTlssues Inadvertently placed In saline solution Instead of 10X neutral buf fered formalin solution; these tissues were subsequently discarded. cN.O.A. Ho observable abnormalities. Key: M m male; F female. 67836 CONFIDfTNTTAI _________ I YZ0014491 1-8 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations Day 21 Weanlings (Selected)* irouo Litter No. ppm IV(cont.) 844 30 846 847 . 848 849 V 1026 300 1027 1028 1029 1032 1033 Pup No. 2 3 ib 3b 2b 3b 5 6 2lbb 3 4 2 3 3 4 2 3 1 4 3 4 Sex M M M M M M M H M M M M K M K M M M M M M M 1034 1035 1b M 2M 1M 2M Observation!s)c N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Lungs: scattered, clustered red foci on all lobes. N.O.A. N.O.A. N.O.A. N.O.A. Selected for tissue preservation. bT1ssues Inadvertently placed In saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A." No observable abnormalities. Key: M male; F - female. DO 67837 CoNF TOFNTJai YZOO14492 1-9 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter No. ppm V(cont.) 1036 300 1037 1038 1039 1040 1042 1043 1044 Pup No. 1 3 3 4 1 5 3b 4 1 3 2 3 3 5 3 7 Sex M M M M M M M M M M M M M M M M 1045 3 M 4M 1046 1 M 5M 1048 1 K 3M 1049 1 M 5M 1050 1 M 3M Observationsic N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Lungs: few scattered red foci on all lopes. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Selected for tissue preservation. ^Tissues Inadvertently placed In saline solution Instead of lot neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A. No observable abnormalities. Key: M - male; F female. 067838 CONFTDFNTTAI YZ0014493 I-10 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)8 Group ppm I 0 Litter No. 225 Pud No. 5 6 Sex F F 226 7 F 10 F 227 7l F 9b F 228 8 F 9F 229 8 F 10 F 230 9 F 10 F 231 8 F 10 F 233 8' F 10 F 235 7 F 10 F 236 5 F 7F 237 7 F 8F 238 7 F 9F 239 9 F 10 F Observation s)c N.O.A. Lungs: multiple clustered red pin-point ' ?ocT on right anterior lobe. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. aSelected for tissue preservation. ^Tissues Inadvertently placed in saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded. cn.O.A." No observable abnormalities. M-male; F-female DO 067839 CONFTDFNTTAl YZ0014494 1-11 79-2425 Appendix I (cent.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter No. ppm I(cont.) 240 0 242 243 244 246 247 249 250 II 425 3 426 428 429 431 Pup No. 7 8 8 10 6 8 6b 7 5 6 7 7 9 8 10 6 10 5 .7 6 7 6b 7 7b 8b Sex ____________ Observations)c F N.O.A. F N.O.A. F N.O.A. F Kidneys (Both): pelvis extremely dilated; clear fluid-filled; little cortex present, F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F Lvmph nodes (mandibular): reddened. F N.O.A. F N.O.A. F N.O.A. F N.O.A. F Salivary oland (Left}.: posterior 2/3 red. F N.O.A. F N.O.A. F N.O.A. ^Selected for tissue preservation. ^Tissue Inadvertantly placed In saline solution Instead of 10% neutral buffered formalin solution; these tissues were subsequently discarded. cN.0.A. No observable Abnormalities. M-male; Ffemale DO 067840 OONFTOFNTTAt YZ0014495 1-12 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group litter No. Pup No. Sex ppm Observation!s)c II(cont.) 432 3 7 F N.O.A. 8 F N.O.A. 433 8 F N.O.A. 9 F N.O.A. 434 7 F N.O.A. 10 F N.O.A. 435 7 F N.O.A. 10 F N.O.A. 436 5 F N.O.A. 7 F N.O.A. 438 8b F N.O.A. 9b F N.O.A. 439 7 F N.O.A. 8 F N.O.A. 440 6 F N.O.A. 8b F N.O.A. 441 6b F N.O.A. 8 F N.O.A. 442 8 F N.O.A. 9 F N.O.A. 443 5 F N.O.A. 7 F N.O.A. 444 7 F N.O.A. 445 7 F N.O.A. 10 F N.O.A. 447 7 F N.O.A. 8 F N.O.A. 448 8 F N.O.A. 9 F N.O.A. 450 8 F N.O.A. 9 F N.O.A. Selected for tissue preservation. ^Tissues Inadvertently placed In saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded. CN.O.A.* No observable abnormalities. Key: M male; F - female. J on 067841 CONFTDFNTTAL YZ0014496 1-13 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group ppm III 10 Litter No. 625 626 627 628 630 631 632 633 634 635 636 637 639 Pup No. 3 4 9 10 7 10 6 7 4 5 4 5 9 10b 5 6 8 9 9b 10b 4 5 6 7 8 9 Sex F F F F F F F F F F F F F F F F F F F F F F F F F F Observation!*) N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Lymph nodes (mandibular): enlarged To.O x 0.3 cm); reddened. Selected for tissue preservation. ^Tissues Inadvertently placed In saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A.- No observable abnormalItles. Key: M male; F * female. DO 067842 OONFTOFNT TA1 YZ0014497 1-14 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)4 Group Litter No. ppm III(cont.) 640 10 641 642 643 644 645 646 647 648 649 650 IV 825 30 826 827 Pup No. 10b 7 gb 6 7 6b 10b 7 8 6 10 7b 9 6 8 8 9 gb 10b 6 9 6b 7b 5 7 9 10 Sex F F F F F F F F F F F F F F F F F F F F F F F F F F F F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observation s)c "Selected for tissue preservation. bTlssues inadvertently placed In saline solution Instead of 10% neutral buf- " fered formalin solution; these tissues were subsequently discarded. CN.O.A.- No observable abnormalities. Key: M male; F - female. n0 067841 p CONFIDFNTTAl ------------------------- - ___________ _________ J YZOO14498 1-15 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene in Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)1 Grouo Litter No. ppm IV(cont.) 828 30 830 831 835 837 838 839 840 841 842 843 844 846 847 Pup No. 5b 8 4 8 7b 8 7b 10b 5 6 6 8 6 8 6 8 6 10 4b 7b 5b 6b 5 8 gb gb Sex F F F F F F F F F F F F F F F F F F F F F F F F F F F F Observation!s)C N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Liver: pale red*brown. N.O.A. N.O.A. {Selected for tissue preservation. ,, "Tissues Inadvertently placed In saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded cN.0.A. No observable abnormalities. do 067844 Key: M - male, F female. oonftdfnttai YZ0014499 1-16 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter No. ppm !V(cont.) 848 30 849 V 1026 300 1027 1028 1029 1031 1032 1033 1034 1035 1036 1037 1038 Pup No. 8 9 5 6 6gbb 6 8 8 9 7 9 1 2 9 10 7 8b 6b 9 6 7 7 8 7 10 6 9 Sex F F F F F F F F F F F F F F F F F F F F F F F F F F F F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observation sK *Selected for tissue preservation. bT1ssues Inadvertently placed In saline solution instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A. No observable abnormalities. Key: M male; F female. DO 067845 CONFIDFIMTTAI YZOO14500 1-17 79-2425 Appendix I (cent.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group litter No. Pup No. Sex ppm Observation s)c V(cont.) 1039 8 F N.O.A. 300 10b F N.O.A. 1040 7 F N.O.A. 9 F N.O.A. 1042 9 10 F N.O.A. F N.O.A. 1043 6 F N.O.A. 8 F N.O.A. 1044 9 10 F N.O.A. F N.O.A. 1045 6 F N.O.A. 7 F N.O.A. 1046 6 F N.O.A. 8 F N.O.A. 1048 4 F N.O.A. 5 F N.O.A. 1049 7 F Salivary gland (Left) : moderately reddened. Lymph nodes (mesenteric): slightly reddened; enlarged approx. 1 1/2 x normal size. 9 F N.O.A. 1050 8 10 F N.O.A. F N.O.A. [Selected for tissue preservation. "Tissues Inadvertently placed In saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A.- No observable abnormalities. Key: M - male, F * female. DO 067846 OONFTDFNTIAl YZ0014501 Group J-l Appendix J An Inhalation Female Fertility Study with Benzene In Rats Mating Performance 79-2425 Female No. Mating Confirmation8 Day Found Mated1* Pregnancy Statusc 225 Yes 226 Yes 111 Yes 228 Yes 229 Yes 230 Yes 231 Yes 232 Yes 233 Yes 234 Yes 235 Yes 236 Yes 237 Yes 238 Yes 239 Yes 240 Yes 241 No 242 Yes 243 Yes 244 Yes 245 Yes 246 Yes 247 Yes 248 Yes 249 Yes 250 Yes 3 1 3 2 1 4 1 2 1 6 6 6 1 7 3 4 - 1 15 2 1 1 2 4 4 1 Yes Yes Yes Yes Yes Yes Yes Yes Yes NO Yes Yes Yes Yes Yes Yes No Yes Yes Yes No Yes Yes Yes Yes Yes 8Mat1ng confirmed on the basis of the following: vaginal plug, sperm In the vaginal smear, or evidence of pregnancy (l.e. pups, Implantation sites/scars). Represents mmber of days from initiation of mating till evidence of mating was observed. cPregnancy determined on the basis of the following: parturition. Implantation sites, or Implantation scars at terminal sacrifice. D 06784 7 CONFXDEnj- tal YZOO14502 Group ppm II 1 d-2 Appendix J (cont.) An Inhalation Female Fertility Study with Benzene In Rats Hating Performance 79-2425 Female No. Mating Confirmation Day Found Mated" Preonancv Status0 425 Yes 426 Yes 427 Yes 428 Yes 429 Yes 430 Yes 431 Yes 432 Yes 433 Yes 434 Yes 435 Yes 436 Yes 437 Yes 438 Yes 439 Yes 440 Yes 441 Yes 442 Yes 443 Yes 444 Yes 445 Yes 446 Yes 447 Yes 448 Yes 449 Yes 450 Yes 4 Yes 1 Yes 4 No 3 Yes 2 Yes 7 Yes 3 Yes 2 Yes 5 Yes 2 Yes 4 Yes 4 Yes d Yes 3 Yes 4 Yes 3 Yes 3 Yes 1 Yes 4 Yes 1 Yes 1 Yes d Yes 5 Yes 2 Yes 6 Yes 1 Yes aMating confirmed on the basis of the following: vaginal plug, sperm In the vaginal smear, or evidence of pregnancy (l.e. pups. Implantation sites/scars), "Represents number of days from Initiation of mating till evidence of mating was observed. cPregnancy determined on the basis of the following: parturition. Implantation sites, or Implantation scars at terminal sacrifice. dDay 0 of gestation was not Identified. 00 067848 OONF JDfTNTrAI. YZ0014503 . 1 0-3 79-2425 1 Appendix 0 (cont.) An Inhalation Female Fertility Study with Benzene in Rats 1 Mating Performance 4 1 Mating Day Found 1 Group Female No. Confirmation Mated*5 Pregnancy $tatusc ppn 1 III 625 10 626 627 628 1 629 630 631 1VP 632 633 634 11 635 636 637 1 638 639 fli 640 641 1 642 643 644 1 645 646 647 643 11 649 650 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 3 16 2 1 4 1 8 2 6 12 2 4 4 17 7 2 3 4 2 8 1 3 3 3 2 7 Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 1 ^Mating confirmed on the basis of the following: vaginal plug, sperm In the vaginal smear, or evidence of pregnancy (i.e. pups, implantation sites/scars)* 1 "Represents mmber of days from initiation of mating till evidence of mating was observed. cpregnancy determined on the basis of the following: parturition, implantation 1 sites, or implantation scars at terminal sacrifice. 1 1 1 / 1 DO 067849 CONFIDFNTTAL YZOO14504 J-4 Appendix 0 (cont.) An Inhalation Female Fertility Study with Benzene in Rats Hating Performance 79-2425 Group ppm IV 30 Female No. 825 826 827 828 82 9e 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849 850 Confirmation Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Matedb 2 7 5 2 - 1 8 2 1 1 2 5 1 8 5 2 5 2 2 1 2 2 2 4 2 2 Pregnancy Sta Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes NO Yes Yes Yes Yes No Mat1ng confirmed on the basis of the following: vaginal plug, sperm In the vaginal smear, or evidence of pregnancy (l.e. pups. Implantation sItes/scars). ^Represents nunber of days from Initiation of mating till evidence of mating was observed, cPregnancy determined on the basis of the following: parturition. Implantation sites, or Implantation scars at terminal sacrifice. *Animal was killed accidentally (l.e., dropped during handling) during Week 5 of the pre-mating treatment period. 067850 CONFIDENTS! YZ0014505 Group ppm V 300 0-5 Appendix 0 (cont.) An Inhalation Female Fertility Study with Benzene in Rats Mating Performance 79-2425 Female No. Mating Confirmation* Day Found Mated Preonancv Status6 1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 Yes 15f Yes 2 Yes 4 Yes 14 Yes 3 Yes 1 Yes 5 Yes 1 Yes 4 . Yes 2 Yes A Yes 1 Yes 1 Yes 1 Yes 2 Yes 5 Yes 1 Yes 4 Yes 5 Yes 3 Yes 6 Yes 1 Yes 1 Yes 1 Yes 7 Yes 1 Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes No Yes Yes Yes *Mat1ng confirmed on the basis of the following; vaginal plug, sperm In the vaginal smear, or evidence of pregnancy (l.e. pups, Implantation sites/scars)* bRepresents nunber of days from Initiation of mating till evidence of mating was observed. ^Pregnancy determined on the basis of the following; parturition. Implantation sites, or Implantation scars at terminal sacrifice. fDue to technician error, this female was not placed with a male on the 14th evening of the mating period. DO 067851 CONFIDENT TAl. YZ0014506 K-l Appendix K An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Postmortem Observations for Pups Culled from Litters on Day 4 of Lactation Group ppm I 0 Female No. 226 227 229 231 233 235 238 239 240 242 243 247 249 250 Pup No.* 1.2,3 9,15 7,8,13 4 7,8,9 5 4 7,11.12 5 4,7,9 4 2,5 1.4 12 4 7,8,10,13,15 10 3.7 12 10, 12 Sex M F F M F M M F M M M M M F M F F M F F Observation N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Key; M - Male, F * Female. N.O.A. - no observable abnormalities. Arbitrary nunbers Identifying a pups location within a partition troy for purposes of random culling; pups were not Individually Identify ' . YZOO14507 K-2 ' Appendix K (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Postmortem Observations for Pups Culled from Litters on Day 4 of lactation Group ppm II 1 Female No. 425 426 428 429 431 432 433 434 435 438 440 441 442 445 447 450 Pup No.a Sex Observation 2,3,8 M N.O.A. 12 F N.O.A. 5 F N.O.A. 7,8,10 F N.O.A. 4 M N.O.A. 7,8,10 F N.O.A. 1 M N.O.A, 7,13,14 F N.O.A. 7.8 F N.O.A. 4,5.7 M N.O.A. 2,6 M N.O.A. 5 F N.O.A. 2,4,7 M N.O.A. 2.4,7 M N.O.A. 11,12 F N.O.A. 3,4,6 M N.O.A. 13 F N.O.A. 1.8 M N.O.A. 7,8,13 F N.O.A. 2 M N.O.A. 1,4,8 M N.O.A. Key: M * Male, F Female. N.O.A. no observable abnormalities. DO 067853 1 OONFTOFNT TAl. I YZOO14508 K-3 Appendix K (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Postmortem Observations for Pups Culled from Litters on Day 4 of Lactation Group ppm III 10 Female No. 626 627 628 630 632 634 635 637 639 640 641 643 644 645 646 Pup No.a 1.3,8 1 1,4,6 5,6 8 2 11,12,13,14 5,7 9 1,2 9,13 3,4,7 1 9 8,9,13 1.8 2 10,11,12,13 4,6 8,9,15,16 9,10 2.5,8 10,12 Sex M M M M F M F M F M F M M F F M M F M F F M F Observation N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Key: M Male* F * Female. N.O.A. no observable abnormalities. aArb1trary numbers Identifying a pups location within a partition tray for purposes of random culling; pups were not Individually Identified during lactation. 067854 CONFIDENTIAL YZ0014509 K-4 Appendix K (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Postmortem Observations for Pups Culled from Litters on Day 4 of Lactation Group ppm III 10 (cont.) IV 30 Female No. 647 648 649 650 825 826 827 831 835 838 839 840 841 842 844 846 847 Pup No.a 9 5 1.4,5,7.8,10 1.2 11 6,12,13 4,12,13 1.3,7 10 4 1,3,6 13,15 5,6 10,11,14 1 9,10,13 4 1,2,7 5,9,13,14 4,10,12 5,7 1 6,11,13 Sex F F M M F F F M F M M F M F M F M M F F M M F Observation N.O.A* N.O.A. N.O.A, N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. No mllK In stomach N.O.A. Arbitrary numbers Identifying a pups location within a partition tray for purposes of random culling; pups were not Individually identified during lactation. DO 067855 OONFTDFNTTAl YZ0014510 K-5 Appendix K (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Postmortem Observations for Pups Culled from Litters on Day 4 of Lactation Group ppm IV 30 (cont.) V 300 Femal e No. 848 1026 1029 1032 1033 1034 1035 1036 1037 1038 1040 1044 1046 Pup No.* 5,6,8 3,6,7,8 12 5 1,4,5,8,9 7 5 2.4,8 1,4,6,8 4 8,9 6,10,12,13,15 3,4,7 10,12 2,5,10,11 5,6,8 10 2 12 Sex M M F M M F M M M M F F M F M M M F Observation N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. (L) testis red In color N.O.A. 1049 2,3,4,9,10 M N.O.A. 1050 2,5.9 M N.O.A. Key: M Male, F Female, N.O.A. - no observable abnormalities; L - left 'Arbitrary numbers Identifying a pups location within a partition tray for purposes of random culling; pups were not Individually Identified during lactation. OO 06785)6. CONFTDFNTTAL YZ0014511 Group ppm I 0 II I III 10 L-1 Appendix L An Inhalation Female Fertility Study with Benzene In Rats Dead Pup Observations________ Female Pup Day Found No. No. Sex Dead 230 A F 0 236 A F 14 237 AMO 244 A F 0 B M0 C F0 DF1 E F1 426 A M 0 BF2 434 A M 0 436 A F 0 440 A M 3 448 A M 0 625 A F 0 B F 16 C M 19 D M 19 E F 19 F U*D* . 20 G F 21 79-2425 Observation Autolyzed. Autolyzed. N.O.A. N.O.A. Kldne^JU: dark purple; Tall: S kink. Tall: S kink. Tall: S kink. Tall; S kink. N.O.A. Autolyzed. N.O.A. N.O.A. Autolyzed. N.O.A. N.O.A. Autolyzed. Autolyzed. N.O.A. N.O.A. Autolyzed. Thymus; small (one-fourth normal size). Key: L left, S slight, N.O.A. no observable abnormalities. M Hale F * Female, U.D. undetermined. 06 7857 confidential i YZ0014512 Group ppm III 10 (cont.) IV 30 1-2 Appendix L (cont.) An Inhalation Female Fertility Study with Benzene In Rats Dead Pup Observations Female Pup Day Found No. No. Sex Dead 628 630 637 639 641 642 648 842 846 AH 1 A N 11 a F 11 c U.D. 12 D F 14 AF0 BM1 AF3 8 F9 AF0 A M 0 B F 0 C F oa D F0 E M0 AF4 AM I AF0 B M0 C M9 79-2425 Observation N.O.A. N.O.A. Autolyzed. Partially can nibalized. N.O.A. N.O.A. Kldnev (R): dark red. N.O.A. N.O.A. N.O.A. N.O.A. Autolyzed. N.O.A. Autolyzed. Autolyzed. E pale In color head crushed. Testis (Rh mis- sing. N.O.A. N.O.A. N.O.A. Pups removed from litter prior to completion of parturition. Key: R - right, N.O.A. * no observable abnormalities, M * Hale F Female, U.D. * undetermined, E - extremely. DO 0678S8 CONF IDFNTTAl YZ0014513 Group ppm V 300 L-3 Appendix L (cont.) An Inhalation Female Fertility Study with Benzene In Rats Dead Pup Observations Femal e Pup Day Found No. No. Sex Dead 1025 A M 0 B M0 C M0 0 F0 EF1 FF1 G H1 HF1 1026 A M 13 1027 A F 0 1028 1031 1039 1044 B F0 AM3 B F4 C F5 A M Q B M Qfl C F 0 D F oa AM0 AF 1 79-2425 Observation N.O.A. N.O.A. N.O.A. N.O.A. Autolyzed. Autolyzed. Autolyzed. Autolyzed. Autolyzed: Ab- domlnal dis tension. Pup Is very paie; all tissues pale. N.O.A. N.O.A. Autolyzed. Autolyzed. N.O.A. N.O.A. N.O.A. N.O.A. Autolyzed. N.O.A. aPups removed from litter prior to completion of parturition. Key: N.O.A. * no observable abnormalities. M * Hale F * Female. 00 067859 CONFIDENTIAL YZ0014514 V 300 (cont.) L-4 Appendix L (cont.) An Inhalation Female Fertility Study with Benzene in Rats Dead Pup Observations________ Female Pup Day Found No. No. Sex Dead 1045 A M 0 BM 0 C F 15 79-2425 Observation N.O.A. N.O.A, N.O.A. Key; N.O.A. = no observable abnormalities, M - Male F Female. DO 067860 CONFTOFNTTAl YZ0014515 M-l Appendix H An Inhalation Female Fertility Study with Benzene In Rats Certified Feed Informat1ona 79-2425 Interval Acclimation Acclimatlon AcclImatlon Treatment period Treatment period Treatment period Treatment period Treatment period Treatment period Treatment period Treatment period Treatment period Treatment period Mating period Mating period Mating period Gestation/Lactation Gestation/Lactation Gestation/Lactation Day 21 Sacrifices Day 21 Sacrifices Date 12/19/79 12/26/79 1/2/80 1/9/80 1/16/80 1/23/80 1/30/80 2/6/80 2/13/80 2/20/80 2/27/80 3/5/80 3/12/80 3/19/80 3/26/80 4/2/80 4/9/80 4/16/80 4/23/80 4/30/80 5/7/80 Lot. Np. Oct 03792B Oct 22791D Oct 22791D Oct 22791C Oct 22791C Dec 6791A Dec 06791A Dec 06791A Dec 06791C Dec 20791C Dec 06791E Dec 27791C Dec 27792C Feb 14801E Feb 14801E Oan 318018 Feb 14801C Feb 14801C Feb 28801F Feb 28801F Feb 14801A aPur1na Laboratory Chow 5002 (Certified Diets) Mash; ad llbltun. DO 06786.1 CONFTDFNTTAl d YZ0014516 M-l Appendix N An Inhalation Female Fertility Study With Benzene In Rats 79-2425 Pre-test Date Collected: 12/3/1979 Freezing Point (*C) 5.5064 Purity (%) 99.96 Specific Gravity 0.8845 Total Sulfur by Mlcrocou- lometry -ppm <1.0 GC Analysis Sats ppm 42 Toluene ppm 28 Acetone ppm 2 Analysis of Benzene8 Study Interval Prior to Initiation of treatment l/7/19T' , Week 6 of the Treatment Period "TT7W7T 5.084 99.97 5.5192 99.98 0.8845 0.8843 <1.0 <1.0 42 38 28 26 2 0.4 Completion of Treatment 5/1T75T 5.4895 99.94 0.8843 <1.0 49 29 ^Analyses were performed at the Exxon Research and Engineering Company, Linden, N.O. Do 06786? CONFIDENT TAI. YZ0014517 0-1 Appendix 0 An Inhalation Female Fertility Study With Benzene In Rats 79-2425 Mean Pup Weights by Sex - (grams) - Group I - (Oppm) Female No. Day 0 MF A- A225 7.1 6.7 226 5.5 5.6 111 6.3 5.9 228 6.1 6.2 229 5.9 5.6 230 7.1 6.7 231 7.0 6.7 233 6.1 5.7 235 6.7 6.5 236 5.8 5.8 237 7.4 6.8 238 6.0 5.9 239 6.4 5.6 240 6.7 6.3 242 6.4 6.1 243 5.1 5.4 244 6.1 5.8 246 7.0 7.4 247 5.8 5.6 249 6.0 5.8 250 6.7 6.5 Mean: S.D.: N: 6.3 6.1 0.6 0.5 21 21 Day 4 Pre-Cull Post-Cul 1 M in M _zz A9.0 8.0 10.0 9.6 8.4 11.8 10.1 9.5 10.9 8.6 10.8 9.1 11.1 10.7 9.6 7.6 6.6 12.2 8.7 8.3 11.0 A8.5 8.0 9.6 9.7 8.2 10.8 9.5 8.9 10.7 9.1 9.9 8.9 10.5 9.9 9.2 7.9 6.3 12.9 8.5 8.0 11.1 A9.0 8.2 10.0 9.6 8.4 11.8 10.0 9.5 10.8 8.6 10.8 8.9 11.0 10.7 9.7 7.8 6.6 12.2 8.7 8.4 11.0 A8.5 7.9 9.5 9.7 8.3 10.8 9.5 9.0 10.7 9.1 9.9 8.9 10.5 9.9 9.2 7.7 6.3 12.9 8.5 7.9 11.2 9.6 9.3 ' 9.6 9.3 1.4 1.4 1.4 1.4 21 21 21 21 Day 14 Day 21 MF M F A22.3 23.0 21.9 22.3 21.3 26.0 23.5 23.1 26.6 20.0 25.0 21.9 24.7 25.2 24.1 22.1 11.8 27.6 22.5 22.5 25.7 A- A21.2 39.2 21.9 * 35.6 20.8 38.2 21.2 35.6 22.2 30.6 23.7 41.1 23.0 39.0 22.0 38.4 26.2 44.5 19.8 33.5 23.0 41.5 21.4 33.4 22.4 43.8 23.5 36.4 23.6 36.5 23.2 34.6 10.8 22.1 25.3 46.4 21.0 33.8 20.5 36.3 27.3 43.7 A37.9 34.7 38.3 36.9 38.2 36.2 38.1 38.9 43.3 33.9 38.9 32.5 39.2 35.5 35.6 37.6 20.8 42.0 31.3 33.1 45.3 23.0 3.2 21 22.1 3.2 2L 37.3 5.4 21 36.6 5.0 21 For explanation of statistical synbol: A-; see Appendix Q. Key: M Male F Female 0678^,3 OONF IDFNT Jfi,i YZ0014518 0-2 Appendix 0 (cont.) An Inhalation Female Fertility Study With Benzene In Rats 79-2425 Mean Pup Weights by Sex (grams) - Group II (1 ppn) Female No. Day 0 MF 425 6.5 6.1 426 6.5 6.0 428 6.7 6.3 429 6.2 5.8 431 5.8 5.4 432 5.9 5.4 433 6.6 6.3 434 6.3 5.7 435 6.4 5.9 436 6.6 5.7 438 5.9 5.9 439 6.1 5.5 440 6.0 5.6 441 6.7 6.1 442 6.9 6.4 443 6.9 6.6 444 6.9 4.9 445 6.9 6.4 447 6.6 6.6 448 5.3 5.1 449 7.3 450 6.7 6.3 Mean: S.D.: N: 6.4 5.9 0.5 0.5 22 21 ____ Pay *____ Pre-Cull Post-Cul 1* u--------r~ M F 9.1 10.9 10.3 9.6 8.9 8.7 8.6 9.0 8.9 12.4 10.3 10.3 9.4 8.7 9.6 11.4 12.3 10.6 10.3 9.7 12.4 11.1 8.9 10.2 10.5 8.7 8.1 8.0 8.5 8.3 8.8 10.7 9.2 9.7 8.7 6.1 9.1 11.0 9.0 10.4 10.0 9.2 - 10.8 9,2 10.9 10.3 9.8 8.7 8.7 9.0 9.0 8.9 12.4 10.2 10.3 9.6 8.2 9.5 11.4 12.3 10.6 10.2 9.7 12.4 11.2 8.8 10.2 10.6 8.5 8.1 8.0 8.5 8.3 8.8 10.7 9.2 9.7 8.6 6.1 9.1 11.0 9.0 10.5 10.0 9.2 - 10.8 10.1 1.2 22 9.2 1.2 21 10.1 1.2 22 9.2 1.2 21 Day 14 MF 24.4 24.9 22.5 24.7 21.9 21.2 20.3 22.6 22.8 27.1 27.1 20.6 21.9 22.3 24.7 20.3 26.6 25.6 24.6 20.8 16.3 29.3 22.7 23.8 23.3 22.2 21.7 19.7 20.0 21.7 20.1 24.6 23.8 19.7 20.2 16.5 24.8 19.7 22.0 25.1 23.2 20.3 - 28.7 23.3 2.9 22 22.1 2.6 21 Dav 21 MF 36.3 39.8 41.9 42.7 33.7 32.2 33.9 35.7 35.4 42.9 47.1 31.8 36.9 38.9 38.2 26.8 46.9 42.9 41.2 30.2 16.3 50.0 33.5 39.0 44.4 38.7 33.0 29.7 33.9 34.6 31.6 38.7 40.3 32.8 34.1 27.0 37.0 25.8 35.4 40.6 40.3 30.1 - 47.8 37.4 7.5 22 35.6 5.5 21 No statistically significant differences from the control group. Key: M * Male F * Female 00 067864 CONFTDFNTT Al YZ0014519 0-3 Appendix 0 (cont.) An Inhalation Female Fertility Study With Benzene In Rats 79-2425 Mean Pup Weights by Sex (grams) - Group III (10 ppm) Female No. Day 0 MF 625 7.1 6.3 626 6.4 6.4 627 5.7 5.3 628 6.1 5.2 630 6.3 5.9 631 7.2 6.9 632 6.3 6.3 633 6.9 6.2 634 5.8 5.8 635 6.7 6.3 636 8.0 7.6 637 6.2 6.0 639 6.9 6.4 640 6.5 6.3 641 6.4 6.4 642 7.2 6.9 643 6.5 6.4 644 5.5 5.2 645 6.2 6.1 646 5.6 5.0 647 7.4 6.7 648 6.8 6.5 649 6.4 6.3 650 6.1 5.5 Mean: S.D.: N: 6.5 6.2 0.6 0.6 24 24 Day 4 Pre-Cull "R----- ~T~ PMost-Cnul1r 11.0 11.1 8.3 9.2 8.4 13.0 9.2 12.2 10.3 10.0 16.0 9.3 10.4 8.9 9.3 12.7 10.1 8.1 9,1 8.5 10.2 12.5 9.7 9.8 9.9 10.7 7.7 8.1 8.3 13.0 8.9 11.1 10.5 9.3 15.5 8.7 10.5 8.5 8.9 11.6 9.3 7.5 8.9 8.0 10.1 11.8 9.9 9.0 11.0 10.8 8.2 9.2 8.2 13.0 9.1 12.2 10.1 10.1 16.0 9.2 10.4 8.9 9.4 12.7 10.0 8.0 9.1 8.6 10.2 12.5 9.7 9.7 9.9 10.7 7.7 8,1 8.3 13.0 8.9 11.1 10.6 9.4 15.5 8.7 10.3 8.9 8.9 11.6 9.5 7.6 9.0 8.3 10.2 11.8 9.9 9.3 10.3 1.9 24 9.8 1.8 24 10.3 1.9 24 9.9 1.8 24 Oay 14 MF 15.5 24.9 18.8 19.7 11.6 30.8 22.2 25.6 25.5 25.8 32.4 24.7 24.7 22.9 20.0 26.0 24.6 23.4 21.8 23.3 21.8 30.2 23.8 24.9 13.4 24.2 17.5 17.8 13.3 30.3 22.7 24.8 26.2 24.4 32.4 23.3 23,9 23.0 19.9 23.8 23.4 22.5 23.1 23.9 20.6 28.6 24.3 23.6 23.5 23.0 4.5 4.4 24 24 Day 21 MF 17.3 36.6 28.4 29.6 24,7 51.4 36.2 41.8 39.3 44.9 54.9 39.9 43.0 39.4 30.0 45.4 42.2 33.8 35.2 35.3 37.8 48.6 39.3 39.2 13.1 42.5 26.4 26.5 24.6 50.0 38.1 40.7 41.7 40.9 54.5 37.3 39.9 37.8 29.3 42.3 38.3 33.7 36.8 37.5 35.2 47.0 39.7 37.8 38.1 8.4 24 37.1 8.6 24 No statistically significant differences from the control group.. Key: M - Male F Female DO 06786S CONFTDFNTTAL YZ0014520 0-4 Appendix 0 (cont.) An Inhalation Female Fertility Study With Benzene In Rats 79-242$ Mean Pup Weights by Sex (grans) - Group IV (30 ppn) Female No. Day 0 MF 82$ 7.1 6.8 826 6.6 6.1 827 6.4 5.9 828 6.8 6.5 830 6.2 6.1 831 6.1 6.5 835 6.1 5.7 837 7.2 6.7 838 6.1 5.8 839 5.9 5.2 840 5.8 5.5 841 5.5 5.3 842 5.7 5.8 843 7.4 6.8 844 5.8 5.4 846 5.7 5.7 847 6.7 6.6 848 6.1 6.0 849 7.9 7.6 Mean: S.D.: N 6.4 6.1 0.7 0.6 19 19 Day 4 Pre-Cull Post-Cull MF M 9.4 10.2 10.7 10.6 11.3 9.4 8.7 11.3 9.6 9.1 9.3 8.3 8.5 13.8 8.7 7.7 9.4 9.3 14.1 9.0 9.7 10.2 10.0 11.3 9.5 8.3 11.9 8.7 8.3 8.5 7.8 8.2 12.3 8.3 8.0 9.6 9.3 13.6 9.4 10.2 11.0 10.6 11.3 9.5 8.6 11.3 9.8 9.2 9.2 8.3 8.5 13.8 8.7 7.9 9.4 9.3 14.1 8.9 10.0 10.1 10.0 11.3 9.5 8.1 11.9 9.1 8.1 8.5 7.8 8.4 12.3 8.2 8.0 9.6 9.3 13.6 10.0 1.7 19 9.6 1.6 19 10.0 1.7 19 9.6 1.6 19 Day 14 MF 21.9 24.4 25.6 18.6 26.3 18.8 21.9 26.3 25.1 21.2 18.7 20.8 19.8 29.2 20.7 17.9 18.7 19.1 29.4 20.4 24.4 24.7 20.0 26.7 19.9 20.6 26.7 23.2 20.1 18.0 19.6 19.4 26.1 20.6 19.4 18.9 21.3 29.1 22.3 3.7 19 22.1 3.2 19 Oa v 21 MF 35.2 38.3 39.5 31.2 37.8 29.2 33.7 42.4 40.1 31.4 27.3 31.0 30.4 45.9 29.0 29.4 30.6 30.3 45.9 33.1 37.4 37.0 32.5 41.5 31.8 31.3 40.8 35.8 30.6 26.5 29.5 30.7 41.9 30.1 31.4 31.5 33.6 43.6 34.7 34.2 5.9 4.8 19 19 No statistically significant differences from the control group. Key: M * Male F Female rn? 0678^6 cqnftden TTai YZ0014521 0-5 Appendix 0 (cont.) An Inhalation Female Fertility Study With Benzene In Rats 79-2425 Mean Pup Weights by Sex - (grams) Group V (300 ppm) Female No. Day 0 MF 1025 1026 1027 1028 1029 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1042 1043 1044 1045 1046 1048 1049 1050 6.5 6.0 5.8 5.4 6.9 6.4 5.9 5.9 5.8 5.4 7.0 5.5, 5.4 5.4 5.3 6.1 5.6 6.1 5.8 5.6 5.7 6.8 5.8 5.5 5.4 5.8 5.4 6.7 6.4 6.1 5.7 6.0 5.9 5.6 5.3 6.6 6.4 5.9 5.7 7.7 7.0 6.2 6.0 6.6 6.0 Mean: S.D.: N: 6.1 5.9 0.6 0.5 22 23 Day 4 Pre-Cull Post-Cull MF M Jll _ 9.4 11.2 6.4 9.4 - 8.2 9.6 9.0 10.0 8.4 9.8 8.5 10.3 9.8 10.9 9.4 8.5 10.7 8.8 14.1 10.4 10.1 9.0 10.4 5.8 9.1 13.1 8.1 9.1 8.6 9.6 8.4 9.1 8.1 9.6 9.1 10.0 10.0 8.4 8.9 8.2 13.6 9.8 9.5 9.2 11.2 6.4 9.3 - B.l 9.6 9.0 10.2 8.3 10.0 8.5 10.3 10.0 10.9 9.4 8.5 10.7 8.7 14.1 10.5 10.0 9.0 10.4 5.8 9.1 13.1 8.1 9.3 8.6 9.6 8.4 9.2 8.1 9.6 9.2 10.0 10.0 8.4 8.9 8.3 13.6 9.8 9.5 9.7 1.5 21 9.3 1.6 22 9.7 1.5 21 9.4 1.6 22 Day 14 HF 15.2 23.1 16.7 21.1 - 22.4 22.5 23.0 22.9 20.8 22.4 21.5 22.3 24.6 22.1 18.9 22.4 23.0 20.5 26.9 26.1 21.3 21.8 2.7 21 14.9 21.8 15.3 20.3 28.0 22.5 21.5 21.1 21.2 21.1 20.8 20.0 21.2 23.7 20.6 19.9 21.5 18.2 19.0 25.9 24.1 20.6 21.1 2.9 22 Day 21 MF - 24.5 39.9 24.1 27.9 33.2 37.5 33.7 36.6 30.5 35.9 32.9 34.6 41.3 35.5 30.0 34.6 37.2 29.5 43.4 43.5 34.9 24.5 35.2 23.2 28.3 46.8 33.2 36.5 30.1 32.5 31.3 33.1 30.7 31.1 40.0 33.4 31.3 33.9 36.5 27.8 40.3 36.9 32.7 34.3 33.2 5.4 5.2 21 22 No statistically significant differences from the control group. Key: M - Male F * Female DO 0 CONF t YZOO14522 P-1 Appendix P DETERMINATION OF POLLUTANTS IN DRINKING WAT.EH_ftl3HH TO ANIMALS FOR STUDIES NO. 79-2425 AND 79-7342 Report No.: 80023 Sponsor: Chemical Manufacturers' Association and American Petroleum Institute Washington, O.C. Prepared by: James C. Eschbach Date: September 3, 1980 Issued by: Blo/dynamlcs Inc. Department of Metabolism and Analytical Chemistry Environmental Sciences P.O. Box 43 Mettlers Road East Millstone, New Jersey 08873 SUMMARY The drinking water given to rats for Studies No. 79-2425 and 79-7342 was sampled and assayed for residues which could Interfere with the studies. The compounds assayed Included benzene, trace metals, pesticides and PCBs. The samples were assayed according to E.P.A. proposed and established pesti cide procedures using mass spectrometry, atomic absorption spectrometry and gas chromatography. The results obtained Illustrate that <1.0 ppb of benzene. < 10 ppb trace metals assayed, <1.0 ppb chlorinated pesticides, < 4.0 ppb carbamates and < 2.0 ppb of PCBs were deter mined In the drinking water samples collected from the animal rooms. Joseph S. O'Grodnlck, Ph.D. D1 rector Department of Metabolism and Analytical Chemistry 067868 conftdfntiai YZ0014523 P-2 Appendix P (cont.) 80023 P 2 of 1.0 INTRODUCTION Drinking water samples were collected at two intervals I from the rooms In which the animals for Studies No. 79-2425 and 79-7342 were housed. These samples were assayed for compounds 0 which could have adverse effects on the studies If.they were present in the drinking water. The samples were assayed for benzene, trac^ metals, pesticides and PCBs at the beginning and end of the studied 2-0 EXPERIMENTAL Water samples were collected and composited since they were from the same water source. An aliquot was taken for benzeneH for assay according to Method 624 for volatile organic compounds by purge and trap prior to g.c./mass spectrometry. This sample I was collected in an air-tight container to prevent volatilization prior to assay. Additional aliquots were collected for the ana- | lyses of pesticides, metals and PCBs. The assays were performed _ according to proposed or approved E.P.A. methodology. TM 3.0 RESULTS |' The data obtained Illustrate that <1.0 ppb of benzene,. . < 10 ppb trace metals, <1.0 ppb of chlorinated and <4.0 ppb carbamate pesticides and <2.0 ppb of PCBs were determined In the water samples assayed. Table I summarizes the data obtained In this study. Bi . I* OO 067869 CONFrDFNTTAl m wm--mmrn YZ0014524 P-3 Appendix P (cont.) 60023 P 3 Of * 4.0 ACKNOWLEDGEMENT This study was supported by both the Chemical Manufacturers' Association and the American Petroleum Institute. DO 067870 CONFTDFNTT Al. i , YZOO14525 P-4 Appendix P (cont.) 80023 P 4 Of TABLE 1. RESULTS OF DRINKING WATER ASSAYS FOB STUDIES NO. 7$-~S425 AnD METALS Antimony Beryllium Cadmium Arsenic Lead Mercury Seleril um Assayed 6/12/80 PPb 6.7b <1.0 <1.0 <1.0* 1,2 <0.5 < 8.3 Assayed 3/17/80 PPb < 1.3 <1.0 < 1.0 < 0.5 < 1.0 < 0.5 < 1.0 a. Samples assayed using metal hydride PESTICIDES Lindane Heptachlor TOT Dleldrln Malathlon Carbamate PCB BENZENE < 1.0 <1.0 <1.0 <1.0 <1.0 <1.0 <2.0 <1.0 < 1.0 < 1.0 < 1.0 < 1.0 <1.0 < 1.0 < 1,0 1.0 a. Level of detection high because graphite method of analysis used Instead of hybrid* method of analysis. b. Level of detection higher because of possible loss In lamp efficiency. DO 067871 CONFTOFNTTAL YZOO14526 Q-l Appendix Q An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Methodology and References Parameter Reference or Description Body Weights; 1. Pre-mating treatment period (weekly) - females INTEC Automatic Data Acquisition Sys tem. Body weights of animals re weighed vAen weights were question able, were taken using Torbal Torsion Balance. 2. Gestation and lactation body weights, dams and offspring Torbal Torsion Balance. Statistical Analysis of Data Results of analyses by the Indicated statistical procedures were reported for the following: Parameter Method 1. Body weights - Pre-mating Treatment Period (Weeks 1-10) 2. Body weight changes - PreMat tng Treatment Period (Weeks 1-10) 3. Maternal body weights and body weight changes gestation and lactation periods. A A A 1. Number of offspring (live, dead total - Day 0) 2. Mean pup weights distinguished by sex on a per-lltter basis 3. Pup organ weights and organ weight ratios 4. No. of Implantation scars 5. Unaccounted-for-Conceptl A A C A A 6. Pup Survival Indices (Days 0-4 and Days 4-21) 7. Pregnancy rate B B DO 06787? OONFrOFNTTAI.. YZ0014527 q-2 Appendix Q (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Methodology and References (cont.) Statistical Analysis of Data (cont.) Method Aa: Statistical evaluation of equality of means was made by the appropriate one-way analysis of variance technique, followed by a multiple comparison pro cedure If needed. First, Bartlett's test was performed to determine If groups had equal variances. If the variances were equal, parametric procedures were used; If not, nonparametrlc procedures were used. The parametric procedures were the standard one-way ANOVA using the F-dlstrlbutlon to assess significance. If significant differences among the means were Indicated, Dunnett's test was used to determine which means were significantly different from the control. If a nonparametrlc procedure for testing equality of means was needed, the KruskalWallls test was used, and If differences were Indicated a summed rank test (Dunn) was used to determine which treatments differed from control. A statistical test for trend In the dose level was also performed. In the parametric case (i.e. equal variance), standard regression techniques with a test for trend and lack of fit were used. In the nonparametrlc case, Jonckheere's test for monotonic trend was used. 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 IX two- sided risk levels. Snedecor, G.W., and Cochran, W.G., Statistical Methods. 6th ed.,Iowa State Unlv. Press (1967), Hollander and Wolfe, Nonparametrlc Statistical Methods. John Wiley and Sons, New York (1973), Dunnett. C.W. jrAm. Sta. Assn. . VoT. 50 (1955) and Biometrics, Vol . 20 (1964). Bartletts1s Test ANOVA Dunnett's Test Kruskal-Wallls Summed Rank Test (Dunn) Regression Analysis Trend Lack of Fit Jonckheere's Statistic pp. 296-2 98 pp. 277-279 pp. 1096-1121, 482 pp. 114-116 pp. 131 pp. 149-152 pp. 160-164 pp. 120-123 S&C ssc D K&U H&W S&C S&C H&W DO 067873 C0NFID8NTIAI YZ0014528 Q-3 Appendix Q (cent.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Methodology and References (cont.) Statistical Analysis of Data (cont.) Method B^: Statistical analysis of Incidence data was performed using contingency tables. First, a standard chi-square analysis was performed to determine If the proportion of Incidences differed between the groups tested. In keeping with standard statistical practice. If any one cell had an expected value of less than 5, this step was not reported. Next, each treatment group was compared to the control group using a 2x 2 Fisher Exact test and the significance level was corrected via the Bonferronl Inequality to assure an overall test of the stated significance level. Thirdly, Armltage1 s test for linear trend In the dosage groups was performed. bCh1-square: Snedecor, G.W., and Cochran, W.G., Statistical Methods, 6th ed., Iowa State Unlv. Press. Ames, Iowa, 1971, pp. 250-253. Fisher Exact Test: Bradley, J.V., Distribution Free Statistical Tests. Prentice Hall Englewood ClIffs', h.J., l&ofe, pp. 195-203. Bonferronl Inequality: Miller, R.G., Jr.. Simultaneous Statistical Inference McGraw-Hill Book Co., N.Y. 1966, p, 15. Armltage1 s Test: Armltage, P., "Tests for Linear Trends In Proportions and Frequencies". Biometrics. Sept. 1955, pp. 375-366. 00 067874 CONFTDFNTT Al YZ0014529 Q-4 Appendix Q (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Methodology and References (cont.) Statistical Analysis of Oata (cont.) Method Cc: ANALYSIS OF LITTER DATA The following analysis Is derived when data are taken from all pups In a litter, and each litter was delivered and weaned by a dam who Is associated with a specified treatment group. The data must be interval-type data (Including data formed by ratios which may be transformed before analysis)* Statistical analysis will be done using a nested analysis of variance (Ref. pg. 201, Gill) with pups nested within litters and litters nested within treatment groups. Statistical significance of differences between groups will be determined by the F ratio of treatment mean squares to litter mean squares. If significant differences are Indicated, treatment groups will be compared to control using the least significant difference test (Ref. pg. 178, Gill). The F test will be conducted at the 5% and IX of significance, the least significant difference only at the level of greatest significance. Reference: Gill, J. L. Design and Analysis of Experiments In the Animal and Medical Science. VolJ" I. 'tne lowa state university Press, Ames, Iowa, 1978.----------- I- DO 06,7875 V OONFIDFNT IAI, * YZOO14530 Q-5 Appendix Q (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Methodology and References (cont.) Statistical Analysis of Data (cont.) Statistical Notations Symbol__________________________ _________ Statistical Statement No Slg p<0.05 p<0.01 Absolute Data A- A A+ No statistical differences among the means (parametric ANOVA). * ** K* H" H+ tt tt Significantly different from control (Dunnett's). No statistical differences among the means (Kruskal-Wallls, nonpararaetrlc). A nested analysis of variance Q-4. Significantly different from control LSD test. Incidence Data # H Significantly different from control (Fisher Exact Test). DO 067R76 CONFIDENTIAL YZ0014531 R-l Appendix R An Inhalation Female Fertility Study with Benzene In Rats 79-2425 PERSONNEL DEPARTMENT/TITLE NAME DEGREE STUDY DIRECTOR Raymond E. Schroeder M.S. STUDY MONITOR/REPORT WRITER Loretta Bshasso B.A. SMALL ANIMAL: REPRODUCTION & TERATOLOGY SECTION MANAGER Raymond E. Schroeder M.S. SUPERVISOR Maureen Kenny B.A. TECHNICIAN-IN-CHARGE Barbara Bernard VETERINARIAN PATHOLOGY PATHOLOGIST Fred A. Hines Henry F. Bolte D.V.M. * D.V.M., Ph.D. DATA LOGISTICS SUPERVISOR B.J. Guth B.A. QUALITY ASSURANCE SUPERVISOR Craig M. Lamb B.A. DO 067877 OONFTDFNTTAl YZ0014532