Document 6bb4eDEnYj9KNB82VD4NByz5m

RECEIVED Bio/clynamics Inc. Division of Biology and Safety Evaluation PROJECT NO. 79-2425 'I . 4 : AN INHALATION FEMALE FERTILITY STUDY WITH BENZENE IN RATS Final Report Submitted To: Chemical Manufacturers Association Washington, D.C. 20009 Date: Decoder 1* 1980 ` DO 067673 CONFTOFNTTAl YZ0014328 Bio/dynamics Inc. z. PROJECT NO. 79-2425 AN INHALATION FEMALE FERTILITY STUDY WITH BENZENE IN RATS ABSTRACT This study ms 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 leveld^f 1* 10. 30 and 300 ppm. Female Charles River CD rats 26/group) were treated,, 6 hours/day. five days/week during a ten-week pre-mat ng treatment period end. ensuing mating period. Mated females were exposed dal ly (6 hours/day) during*. gestation to Day 20 and dally exposures resuned on Day 6 of lactation until f 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 wereri 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 (gettatfftn length, ntmber of live and dead pups at birth, sex distribution data). Pups were evaluated for survival, growth, organ weight data (absolute and relatlvOltO' Day 21 body weight) and gross postmortem observations. ? No treatment effect was evident In maternal mortality, body weight data* In-llfe observations or pregnancy rates. At parturition, a slight Increase In the mean nunber of dead pups was Sfin at the high-dose level; however, this difference was not statistically algnl-* flcant* A slight, although statistically significant, decrease In pup survival 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 tha 1 af$ 10 ppm levels. At 30 ppm, mean pup weights (both sexes) were slightly lowtr than control at Day 21 and, In the 300 ppm level, mean pup weights were lowef, than control at Days 14 and 21 of lactation. DO 067674 CONFIDENTIAl P.O. Box 43 MettlersRoad Earn Millstone, New Jersey 06873 (20l)87M0 Teton S44897 CeOtoiKNDYN YZ0014329 79-2426 - i't: Mean liver weights for the male pups (absolute and relative to body $ weights), were comparable to control at the 1 and 10 ppm levels and alight'1 lower than control at the 30 and 300 ppm levels; however, these latter dlf ces ware not statistically significant. Mean liver weights for the female were comparable to the control at the 1, 10 and 30 ppm levels and lower th control at the 300 ppm level. Mean llver/body weight ratios for the femjl pups were comparable between the control and treated groups. Mean kidney weights and kidney to body weight ratios for the treated female pups were sldered comparable to controls, although kidney to body weight ratios were statistically higher for Groups III, IV and V (10, 30 and 300 ppm), ratpec ly. / i. '-'JSHI 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, 10,3Qi ^ X . 300 ppm to female rats during a pre-mating and mating period and tb| eniulf gestation and lactation periods was without adverse effects on reprpdiidtt] A trend toward reduced mean body weights and certain mean organ weights wi observed In the Day 21 pups at the 30 and 300 ppm dose levels, fxcdptfo? single data point (reduced liver weight In the female pups at 300 p$m):.tM differences were not statistically significant. No treatment effects )M|rg In pup survival data during lactation and qross postmortem evaluations of pups on Day 21. ' i f\ M DO 067675 CONFIDFNTTAt Si.: SB i-:" YZOO14330 Bio/. -7952425/' aynonl Ins. TabTe 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 andMeasurements.............................. S 0. Postmortem...................... 6 K. Statistical Analysis....................... 8 III. Results and Discussion.................................................................. ............ 9 A. Maternal Data.................................. 9 1. Mortality.......................................... ... ............. .......... . 9 2. Body Weight Data - Pre-mating Treatment Period.................... 9 3. Physical In-L1fe 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 andBody 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 CONFIDFNTIAL YZ0014331 Bl^4ynmlM *79^242' Ttble of Contents (cont.) APPENDICES A. Inhalation Report................................................ ............ ....................... A-1 B. Individual and Mean Body Weight Data - Pre-Mating Treatment Period........ .................................................. B-1 C. Individual and Mean Maternal Body Weights - Gestation and Lactation................................................................... ....................... C-l D. Lltte/ Information......................................................................... .......... 0-1 E. Implantation Scar and Unaccounted-for-Conceptl Data........ . E-l F. Gross Postmortem Observations - Females........................................... F-l 6. Pup Organ and Body Weights and Organ/Body Weight Ratios........ G-l H. Gross Postmortem Observations - Day 21 Weanlings (Unselected)** H-l I* Gross Postmortem Observations - Day 21 Weanlings (Selected).*.. 1-1 J. Mating Performance..................... ............................. ..................... . 0-1 K. Postmortem Observations for Pups Culled from LI Iters on Day 4 of Lactation.................................................... ........................ K-1 L. Dead Pup Observations............................................................................... 1-1 M. Certified Feed Information............................................. ..................... H-l N. Analysis of Benzene................................................................................. N-l O. Mean Pup Weights.................................................................................... . 0-1 P. Water Analysis...................................................... ................................ P-1 Q. Methodology and References.................................................................... Q-l R. Personnel................................................................................ *................ R-1 00 067677 CONFrOETNTrAI. 1 YZOO14332 I. INTRODUCTION -1- dynamloa Ino. This study, conducted for the Chemical Manufacturers Association and the"Jflmr1fah Petroleun Institute, was designed to evaluate the fertility and reproductive performance of female rats when atfcnlnlstered 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. MATERIALS AND METHODS A. Test Substance: Benzene Supplier: 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: CD* (Sprague-Dawley derived). Justification of Animal Selection: Generally recognized standard laboratory rat. DO 06767B CONFIDENTIAL YZOO14333 -2- 79-2425 D1 fa'dyntml Ino. B. Te--st Ani-ma--ls (-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: ----------- Ro7 orm*------------------------ / Pre-Mating Treatment Females Sacrificed Group Dose Period (days)* Mated Post Weanlna" ppm Male Female MaleP Female I Chamber- N.T.C 70 Exposed 13 26 All II 1 N.T. 70 13 26 All III 10 IV 30 N.T. N.T. 70 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). oo ofc767<!*. CONFTOFNTlAl YZOO14334 3- (DIM Ino. m D. Assignment to Group: 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 I received so as to discard unhealthy females prior to distributing Into groups* A* E. Animal Identification Each female rat was Identified with e metal ear tag bearing Its animal nunber. The individual animal nunber plus the Blo/dynamlcs project number comprised a unique Identification number. F. Husbandry: Housing: 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). Food: Purina Laboratory Chow-5002 (Certified Diets); mash; females were without food during the exposure period. During the first week of acclimation, females were given Purina Laboratory Chow - 5001 pellets (certi fied diets used during study. See Appendix M). Water: ad libitun. By automated water system FTlzabethtown Water Conpany (none dur ing exposed period). Sfwclal 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. I DO 067680 rONFIDFNTTAl YZ0014335 F. Husbandry (cont.): Jtoter Jcont.); f-4- 79-2425 /dj'itRmio* fno,. Included In these water analyses were: Heavy metals: Cd, As. Pb, Hg, Se Be and Sb PCR's Organic Phosphate Pesticides - Mal- athlon Chlorinated hydrocarbons Including lindane, heptachlor. DDT and dleldrl Benzene Carbamate pesticide screen Environmental Conditions: / Temperature: 12 hour light/dark cycle Monitored twice dally. Humidity: 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 (154 days). It was found to be out of range approx- Imately 7t 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*-25t 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): Pre-mating Treatment Period: 7 Januar 1980 - 14 March 1980 Mating Period: 15 March 1980 - 6 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 Atmospheric Sampling: See Appendix A DO 067681 CONF XDFNT I At j YZ0014336 H. Estrous Cycle Determination: Mating: -5- 79-2425 'Oyntmloa ino. 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. 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* 1. 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. YZ0014337 -6- 79-2425 I. In-Life Observations and Measurements (cont*): Bio/<dyntmiot Bo|y VMqhts-(cont Litters: Pups were counted on Day 0, 4 (pre-cull and post-cull), 14 and 21 of lactation* Litters were observed twice daily; (morning:afternoon) 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 sax 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. J. Postmortem: Sacrifice Method: Overdose of ether. Evaluation; 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 nunber 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 Litter: 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 CONFTOFNTTAl YZ0014338 -7- 'dy namloa ins. J. 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 (Hay 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 CONFTDFNTTAl YZ0014339 8 - J. Postmortem (cont.): Saecl f1 ce-Xcont.): 79-2425 B,/<dyntmloi 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). 1 Iver 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 duodenun Heim kidneys (2) liver (2 sections) lung lymph nodes (mesenteric) mammary gland (right Inguinal) pancreas salivary glands seminal vesicles skeletal muscle (biceps femorls with sciatic nerve attached - right side) skin (with maimiary gland) spinal cord (cervical) spleen stomach thyroid (attached to trachea) urinary bladder uterus/prostate gross lesions tissue masses thymus pituitary Ho hlstopathologlcal evaluations were performed (maternal and offspring). K. Statistical Analysis: (See Appendix Q). ^Note 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"). DO 067685 CONFIDENTIAL YZ0014340 -9- 79-2425 *">/a< y nttmleib Inc. ._____ .1.11._ RESULTS AfJpJJISQlJSSIOil A. Maternal Data 1. Mortality: No mortality occurred In the control or treated Groups III (10 ppm) or 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 t Irregularities. In Group IV (30 ppm) one female (No. 829) died during Week 5 of the pre-mating treatment period. Death was accidental due to a handling problem. No treatment effect on mortality was Indicated. 2. Body Weight Data - Pre-mating Treatment Period: Individual female body weight data during the pre-mating treatment 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 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 physical evaluations were generally comparable between the control and treated groups throughout the study. During one week of study (lactation period) several treated females 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 (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 00 067686 CONFIDENT TAI YZ0014341 -10- 79-2425 --- /dyn m consistent with slalodacryoadenltls (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 J 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. data. No treatment effect was Indicated In gestation-lactation weight B. Litter Examination Data: 1. Gestation Length (Appendix D): Mean gestation lengths (Table 4. page 19) were comparable between the control and treated groups. o. 067607 DO conf tdp^ttA YZ0014342 -11- 79-2425 ------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------- ntmtoi Inn. No problem In delivery were noted In the treated females* In the -- . - control group^jane fqqgle iNo. 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 mmber of live and dead pups at birth (Day 0) are presented In Table 4 (page 19). These data are summarized from Individual female litter f data presented In Appendix D. The mean nunber of live pups at birth was comparable between the control and treated groups. The mean nunber 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. High-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 conparable between the control and treated groups (Table 4). Kean 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 C. The mean numbers of Implantation scars and UFC were comparable between the control and treated groups. Do DO/vp 6?6 88 YZOO14343 -12- 79-2425 D,% n*mlo ino. 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 Day 0-4 Interval were considered comparable between the control and treated groups. The Day 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 CONFIDENTIAL YZOO14344 -13- 79-2425 nio/, /dynamtoa tno. 5. Pup .JodyJ&l ght Data jAppendix 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^O, 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. 00 067690 CONFIDENTIAL YZ0014345 -14- 79-2425 Bio/r4ynmloi a. -- . In tJW"femeles,~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 10% 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. DO 067691 CONFTDFNTTAI VZOO14346 15- 79-2425 B,/ddynmloa tno. -- Evaluation-o_grois postmortem. observation;jaf 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. / faymdrid E. schroeder, M.5. Study Director Vice President of Toxicology DO 067692 CONFIDENTS YZ0014347 Table 1 An Inhalation Female Fertility Study with Benzene In Rats 79-2425 i Group ppm I Mean 0 S.D. N II Mean 1 S.D. N HI Mean 10 S.D. n IV Mean 30 S.D. N V Mean 300 S.D. N Heek: 0 159 10 26 160 11 26 160 9 26 160 10 26 161 12 26 Mean Female Body Heights and Height Gains - (grams) Pre-Mating Treatment Period v i{ __________________________________________________________________________ y Change In Weight 1 2 3 4 5 6 7 8 9 10 1-10 179 191 202 217 225 234 239 245 250 255 12 15 15 16 18 17 20 22 22 22 25a 26 26 26 26 26 26 26 26 26 179 193 205 219 229 236 239 244 252 255 12 14 15 16 17 16 16 18 20 18 26 26 26 26 26 26 26 26 26 26 179 192 204 218 228 235 238 243 252 254 12 12 13 13 17 17 16 17 20 19 26 26 26 26 26 26 26 26 26 26 177 193 205 217 227 234 241 246 253 257 12 13 13 14 16k 17 17 19 22 21 26 26 26 26 25b 25 25 25 25 25 180 194 205 219 227 234 238 245 251 253 14 16 19 20 21 22 24 24 24 24 26 26 26 26 26 26 26 26 26 26 76 , 14 25 75 11 26 75 10 r 26 f 79 U 25 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) "H equals 25 due to death of an animal. Key: S-D. - Standard deviation N Number of observations -16- o iu i u a p i 9 o -17Table 2 An Inhalation Female Fertility Stu4y ------------- wtttr Bumene-lrr Rat*------------- 79-2425 naralo* Ino. Pregnancy Rate Data Group m i 0 ii l hi 10 IV 30 V 300 Exposed to Males Number of Females Pregnant' Implan Impl ant tation Scars Parturition Onlyc Sites Only* Total 26 21 j 26 22 2 0 23 1 2 25 26 24 0 0 24 25 19 2 0 21 26 23 0 o 23 Pregnancy Rateb Ho. % 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. bTotal 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. D0 067694 CONFTDFNTTA! YZ0014349 !! OO zo ron O' O' ~i *0 Oi Table 3 An Inhalation fenale fertility Study with Benzene In Rats 79-2425 t Mean internal Body Heights and Body Height Gala - (grans) t ---------------- T- 6roup Gestation Pm: o 7 14 JL Change In Body Maloht --Tfl ' lactation JL" r l U TT~ Change la, --BodylUHejplmf ! Mean 0 SJ. B 253 273 300 375 n 22 22 23 22 32 22 HI? 284 289 311 322 23 25 23 24 23 22 21 21 21 21 19" 13 21 i II Naan 1 S.0. 8* 255 273 301 376 21 24 26 32 22 22 22 22 121 262 291 319 320 20 24 22 23 22 22 22 22 22 22 1 38 15 , 22 III Naan SJ. N* 251 282 311 388 19 20 23 30 a 24 24 24 126 288 298 325 325 21 24 26 23 24 24 24 24 24 24 37 19 24 ` IV Naan 30 SJ. 8* 2S4 273 301 384 21 23 25 30 19 19 19 19 130 289 294 316 328 23 . 25 26 25 19 19 19 19 19 39 12 19 V Nban 300 SJ. N> 254 273 301 377 28 28 29 39 23 23 23 23 126 289 .296 316 330 22 34 31 28 35 23 23 22 22 22 41 18 22 H statistically significant differences fro* control group. ft nay be than 26 fee to encluslon of nowpregiont anInals, death of an anleal or because no evidence of Mtlng was observed (Day 0 Indeterminable). Key: SJ. - standard devlatlan 8 - Ibder of observations -18- YZOO14350 79-2425 Table 4 nj . tn Tnh*1 t1nn Fna1 Fertility Study__________ /*> ml . mo. with Benzene In Rats . tm . ^ -- No. Of Group Litters ppm I 21 0 11 22 1 / III 24 10 IV 19 30 V 23 300 __ Mean Gestation Length (Days) 21.7 21.8 21.9 21.7 21.6 Parturition Data m i k Mean No. Puds 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. yFC 1.3 1.0 0.8 1.1 1.5 No statistically significant differences from control group. *UFC - unaccounted-for-conceptl - derived for each female by subtracting total nunber of pups at birth (live and dead) from niwber of Implant scars. 0 06769a COhtrneNT7M YZ0014351 -------------------------------- -JJ----------------------------------- Table 5 -An Inhalation Female Fertility Study with Benzene In Rats /eyn. n>lo* tne. 79-2425 Pup Survival Indices Group ppm I 9 ii i hi 10 IV 30 V 300 Davs b-4b No. Survival Indices* Days 4C-2I 1 No. J*, j 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* seeTCppendlx Q. Survival Indices are derived by dividing the total nunber of pups alive at the end of a time Interval by the total nunber alive at the beginning of the Interval, opre-cul 1. cPost-cul1. DO 067697 CONFTDFNTTAL YZ0014352 -21- Table 6 An Inhalation female Fertility Study with Benzene In Rats JCni 9-2425 'dynamlea Jno. Pup Sex Distribution Data* Group ppn 1 0 II 1 III 10 IV 30 V 300 Day 0 Mean No . fui>s Sex Ratio WT Male Femal e No. % 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 Mo. --(Cj--'ijil Day 21 (Weanlno) Sex Ratio NO. nr 102/95 107.4 101/94 107.4 111/95 116.8 111/95 116.8 112/117 95.7 108/108 100.0 80/98 81.6 79/98 80.6 103/99 104.0 101/97 104.1 aRat1os not analyzed statistically. Key: M/F Total No. Male Pups/Total No. of Female Pups. DO 067698 CONFTDFNTIAl YZ0014353 -22- Table 7 Inhalation Female Fertility-Study with Benzene In Rats b`7&'dyntmtet 79-2425 Kean Pup Weights (grams) - Distinguished by Sex Group ppm I 0 II 1 III 10 IV 30 V 300 Day 0 HF 6.3 6.1 / 6.4 5.9 6.5 6.2 6.4 6.1 6.1 5.9 Day 4 Pre-cull Post-Cull r 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 HF 23.0 22.1 Day 21 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 CONFrOFNTTAI YZOO14354 Table B An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Hean Pup Organ Heights. Pay 21 Body Heights and Organ/Day 21 Body Welgit Ratios - Hales . __ Group ppm Day 21 Body Wt.a " tfe " ____Organ Height (g) Testes Liver Kidneys (9) Is) (9) Organ/Day 21 Height Ratios x 10-2 Testes Liver Kidneys TsT* (9) (g) I Hean: 37.6 0.162 1.705 0.443 0 S.D.: 5.7 0.037 0.390 0.080 N 101 101 101 101 0.426 4.493 1.177 0.068 0.513 0.108 101 101 101 II Hean: 1 S.D.: N 38.2 7.2 111 0.178 1.711 0.467 0.051 0.435 0.101 111 no 111 0.470 4.438 1.226 0.145 0.479 0.145 111 110 111 III Hean: 10 S.D* it 38.0 7.7 108 0.169 1.693 0.469 0.043 0.465 0.099 108 108 108 0.443 4.435 1.241 0.059 0.665 0.125 108 108 108 IV Hean: 34.0 0.151 1.510 0.424 30 S.D.: 6.2 0.042 0.408 0.088 N 79 79 79 78 0.442 4.380 0.078 0.536 79 79 1.239 0.093 78 V Hean: 300 5*0. N 34.1 5.7 101 0.151 1.453 0.419 0.031 0.347 0.086 101 101 101 0.446 4.216 1.229 0.060 0.470 0.142 101 101 101 Do 067700 CO NFrDFNTIAl. 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 swmarlzed 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- (A ca Table 8 (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2*25 Mean Pup Organ Weights, Day 21 Body Weights and Organ/Day 21 Body Weight Ratios - Females Group ppm Day 21 Body Wt.a (9) I Mean: 36.3 0 5*D* 5.2 N 94 II Mean: 35.5 1 S.D.: 5.9 N 95 III Mean: 37.7 10 S.D.: 7.1 N 108 IV Mean: 33.B 30 $J).: 5.3 n 98 V Mean: 32.6 300 SJ>.: 5.1 n 97 Organ Weight (grams) Liver Kidneys (9) (9) 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 Organ/Day 21 Body Weight Ratio x 10`2 Liver Kidney s ig) (9) 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 !.295tt 0.103 108 4.601 0.507 98 1.330tt 0.115 98 4.442 0.469 97 1.333tt 0.136 96 DO 0 6 7 7 0 1 CONFTDFNTTAL Significantly different from control group: tp<0.05, tt p<0.01 see Appendix Q for explanation of statistical procedure. Key: S.D. Standard deviation N - Number of observations Bate not evaluated statistically - mean pup body weight data during lactation are presented In Tabl 7 and sunmarlzed In Appendix 0. Differences In mean pup body weight data between TabhK^ and 8 are due t analysis of Individual pup data (Table 8) versus mean litter^tota 1 A-1 79-2436 / , t----------------------------------------AppCTd^ ft---------------------------------------------------- /dyn.mto. In.. A Female Fertility Study In Rats with Benzene Inhalation 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 from 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 Group Kii 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) 0.6 (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) 298 (260-337) koger 0n*0y*e', wTLj bi oi. Director, Inhalatlonlbxlcology for George M. Rusch, Ph.D. Report Preparation: Cecelia A. Bozak, B.A. Study Monitor, inhalation DO 06770? rONFTDFNTTAI YZOO14357 A-4 mlei . ''***- ~ 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 Day 1 (January 7, 1980) through termination (May 14, 1980) of the study. EXPERIMENTAL DESIGN Group Pre-Mating Treatment Schedule (days)8 Exposure Treatment _M_ F Number of Rats Females Sacrificed Mated at weanlno Hp 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 during 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. C.O' YZ0014358 A-3- 79-2425 Bln Appendix A (Cont.) A Female Fertility Study In Rats with Benzene "mioi ina. 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 punped Into a heated 3-neck flask through a 3-1nch length of 1/8-1nch diameter teflon tubing from a glass syringe fitted with a 16 gauge stainless steel needle. Flask temperature was maintained at 50*C In Groups II. Ill, 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 punped using Sage Instrunents Model 220 and 341 syringe punps. 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 1pm for the duration of the six hour exposures. Oo ^OMp TOpN 11 A( YZOO14359 A-4 79-2425 Appendix A (Cont.) bio/ ---------------------- ^'PeinaTe pet ni fty study In Rata with Beneena------- /ynmio* Chamber Operation . , Thvstr1wless-steel and glass exposure-chambers In irfilch 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. Pally Nominal Concentration Ngmlnal exposure concentrations were calculated dally using the fol lowing equation: e"e- (pp"' At (4* * 307'78 TM 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 Instrunent Company, Ml ran Long Pathlength Infrared Analyzer Model IA (In-house Iden tification nunbers "L" and "4") or an on-line Tlracor Gas Chromatograph Model 550J 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. ^Mlran L was used from Day 1 (1/7/80) through Oay 66 (3/12/80) of the study. Ml ran 4 replaced Ml ran L on Day 67 (3/13/80) and wes 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 Tracor 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 CONFTDFNTTAl YZ0014360 A-5- 79-; /dynamloi Ine. Appendix A (Cont.) A Female Fertility Study In Rats with Benzene Ca1cuYat1on~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 ppm) 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. Ourlng 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. OONFTDFNTTAl. YZ0014361 A-6- --............... . .. -- 79'24$W, ydynamtoa Appendix A (Cont.) A Female Fertility Study In Rats with Benzene 'S tfii iT , T Calculation of Chamber Concentrations (cont.) 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. At the conclusion of the study, samples collected at each sampling 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.? 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, 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 actual correction factors are presented In Table 2. ?F-test and Student's t-test (modified using Cochrans approximation [tl when variances differ). Snedecor G.S., and W.G. Cochran, Statistical tethods. 6th ed., Iowa State University Press, Ames, 1967, pp Tof-ibe,ii4-ii9. oo CO/vf r At, YZOO14362 A-7 19'U2ii Adynamics Ino. Appendix A (cont.) A Female Fertility Study In Rats with Benzene Nominal vs. Analytical Concentrations (TaFTe 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 - 4/8/80) and when pas chronatoqraphlc 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 8% when gas chromatoqraphlc analysis was used. For 6roup 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. D0 067708 L YZ0014363 Appendix A (Coot.) 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 \t \ 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 l-5 6-48 49-55 56-109 Mean S.D. H Mean S.D. N Heart S.D. N Mean Background Absorbances (Group I) ________________________Sample Intervals: T72Tir--1-17? KF"'~mrw~"TT/2hF" 4-1/2 Hr 0.003 0.003 0.003 0.003 0.003 0.0128* 0.0030 43 O.OOfll* 0.0027 43 0.0068 0.0022 43 0.0066 0.0021 43 0.0061 0.0015 42 0.01I5ft 0.0090 0.0042 0.0048 77 0.0088 0.0044 7 0.0087 0.0034 7 0.0084 0.0035 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 CT/ZTir 0.0Q3 0.0061 0.0021 43 0.0085 0.0034 h 0.0049 0.0025 46 DO 0 6 7 7 0 9 C O N F ID E N T IA L t^Significantly different from succeeding values ((K0.05). "Different from succeeding values (p>0.05). The limited amount of data available did not allow for specific Interval correction. A-8 Appendix A (Cont.) Table 2 A Female Fertility Study In Rats with Benzene Correction Factors Appl led to measured Absorbance for Groups It and III 79-2425 Tine 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 Correction Factors Sanple Intervals: 2-1/2 hr 3-1/2 hr 4-172 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 4 * A-9 DO 0 6 7 7 1 0 CONFrOFNTrAI. u> ON C/I A-10 79-2425 Appendix A (Cont.) --> A-fiemale Fertility Study in Rets-mlth Benzene Infrared Analysis of Benzene CALIBRATION FOR: Molecular Weight: Density:, Benzene 78.11 amu 0.878 g/ml M1RAN 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 A (Groups I. II. Ill) 1.0 A (Groups IV. V) 1 mm 1 second x1 STANDARD: Measured volunes 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 volume. DO 067711 CONFIDENTIAL YZOO14366 A-11 79-2425 Appendix A (Cont.) A Female Fertility Stu<fy In Rats with Benzene Mlran Ambient Air Analyzer Closed Loop Calibrations Mlran L (1/14/80 - 3/12/80) Injection Range Volume Concentration O/ ul) (ppm) 0.1 X 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 Absorbance Al *2 A3 .... 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 Q.003 0.005 0.007 0.012 0.019 0.024 0.026 0.028 0.038 0.065 0.079 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 0.075 0.09 0.10 0.10 0.11 0.15 0.30 0.44 0.56 0.68 0.79 0.81 0.82 0.84 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 A4 ---- 0.001 0.002 0.003 0.006 0.014 0.021 0.027 0.030 0.033 0.043 0.074 0.088 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? CONFTDFNTTAt. L YZOO14367 N w o00\ t` U> so no 0A7714 C O N F ID E N T IA L . *N< .u. u-4> I A-1S 79-2425 Appendix A (Cont.) A Female Fertility Study In Rats with Oenzene Mlran Ambient Air Analyzer Closed Loop Calibrations Mlran 04 (3/13/60 - 5/14/80) Injection Range Volume Concentration C/ol) (ppm) 0.1 X 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 Absorbance "XT US----------- XT 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 X 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 26.8 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 0.07 0.07 0.09 0.08 0.08 0.09 0.09 0.09 0.10 0.09 0.09 0.10 0.10 0.10 0.14 0.14 0.14 0.27 0.26 0.26 0.38 0.38 0.37 0.48 0.48 0.46 0.57 0.58 0.55 0.65 0.66 0.62 0.66 0.68 0.63 0.67 0.68 0.64 0.68 0.70 0.65 0.71 0.73 0.68 0.75 0.76 0.71 0.77 0.79 0.75 V 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 CONFTDFNTTAl YZ0014371 Appendix A (Cent.) A Female Fertility Study In Rats 79-2425 u '-I ts> Appendix A (Cent.) A FeMale Fertility Study In Rats with Benzene 79-2425 DO 0 6 7 7 1 8 CONF TDENTTAL i ' -17- DO 0 6 7 7 1 9 conftdfnttai Appendix A (font.) 79-2425 k l r 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 (coot.) Table 3 A Female Fertility Study In Rats with Benzene Individual Exposure Record for Group I Pre-Mattnq Number of Exposures Nattnq 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 50 71-75 5 5 50 - - 50 71-76 5 50 71-72 2 SO 71-73 3 50 71-93 17 50 - - 50 71-84 10 50 71 1 50 - me SO - - 50 71 1 50 71-73 50 71-73 50 ' 3 3 Gestation Test (lays Number of of Exposure Exposures 73-93 71-91 73-93 72-92 71-91 74-94 71-91 72-92 71-91 76-96 76-96 76-96 71-91 77-97 73-93 74-94 m 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 17 17 17 17 17 17 17 17 17 17 17 17 17 17 97-113 111-127 99-115 b 98-114 98-114 b 101-117 98-114 17 17 17 17 17 17 17 79-2425 PostLactation Number of Exposures tumulbtive Total "T5fay-- Number Exposures 6 96 i 9 97 6 96 7 96 9 97 ` 5 96 8 96 72 8 96 76 5 98 5 98 8 96 6 99 r 7 97 6 97 67 10 98 98 8 97 71 9 97 9 98 74 6 97 9 97 AfoM not mated, sacrificed 4/9/80. DAn1maT 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 -" - Cumulative Mean Dally Dally InteTotal grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tration Exposure tratlon Concen- Date Day , Number tratlon SO Hours Hours Hours Hours 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 1/16/80 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 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 0.5 0.3 6 3.0 3.0 54 36.6 60 39.6 1.1 0.7 6 6.6 66 46.2 1.0 0.6 6 0.9 0.6 6 6.0 5.4 72 52.2 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.& 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 00 0t,77?\ CONFTDPNTTAl YZ0014376 A-21 79-2425 Appendix A (cont.) Table 4 (cont.) - ^Tj-'A FBmald"Fertility Study In Pats with Benzene Cumulative Exposure Record Pre-Mating Treatment Period Group II - 1 ppm (cont.) Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concert- Mean Test Exposure Concert- Exposure tratlon Exposure tratlon Concan- Date Day Number tratlon SO Hours Hours Hours Hours tratlon j 2/21/80 46 34 1.2 0.3 6 7.2 204 193.2 0.9 2/22/80 47 35 0.9 0.3 6 5.4 210 198.6 0.9 2/25/80 50 36 1.0 0.4 6 6.0 216 204.6 0.9 2/26/80 51 37 0.8 0.6 6 4.8 222 209.4 0.9 2/27/80 52 38 0.8 0.7 6 4.8 228 214.2 0.9 2/28/80 53 39 1.1 0.4 6 6.6 234 220.8 0.9 2/29/80 54 40 3.5 4.9 6 21.0 240 241.8 1.0 3/3/80 57 41 1.3 0.7 6 7.8 246 249.6 1.0 3/4/80 58 42 1.0 0.4 6 6.0 252 255.6 1.0 3/5/80 59 43 0.8 0.3 6 4.8 258 260.4 1.0 3/6/80 60 44 1.4 0.3 6 8.4 264 268.8 1.0 3/7/RO 61 45 0.9 0.8 6 5.4 270 274.2 1.0 3/10/80 64 46 1.1 0.7 6 6.6 276 280.8 1.0 3/11/80 65 47 1.2 0.5 6 7.2 282 288.0 1.0 3/12/80 66 48 1.0 0.4 6 6.0 288 294.0 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 4.8 294 298.8 1.8 300 300.6 1.0 1.0 D 067722 ConftdenTTai YZ0014377 A-22 79-2425 Appendix A (cont.) Table 5 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Mating Period Group II - 1 ppm Date ............ tumuiatlve Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Dav Number tratlon SD Hours Hours Hours Hours tratlon Ml ran 04 t 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 1.8 8.4 2.4 2.4 0.0 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 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 8S 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 4.8 6.0 7.8 4.2 6.6 4.8 6.0 4.2 5.4 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 4/4/80 89 69* 0.6 0.2 6 3.6 90 68.4 0.8 4/7/80 92 72 4/8/80 93 73 0.6 0.5 6 0.2 0.4 6 3.6 1.2 96 102 72.0 73.2 0.8 0.7 ^Exposure nunbers 56* 57, 63, 64, 70, and 71 for animals receiving exposure during the gestation period. DO 067723 CONFIOENTTAl YZOO14378 A-23 79-2425 Appendix A (eont.) Table 6 A Female Fertility Study In Rats with Benzene CunuTatlve Exposure Record Gestation Period Group II - 1 ppm -- ........ ---- ---------------------------- -- cumulative Kean Dally . Dally _. , Total Exposure Dally Concen- Total Concen- Test Exposure Concen- Exposure tratlon Exposure tratlon Oate Day Number tratlon SD Hours Hours Hours Hours. InJa* grated Mean Concentratlon Ml ran 04 3/17/80 3/18/80 3/19/BO 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 S3 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 1.0 0.4 6 4.8 6.0 48 30.0 0.6 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 067724 chftdenttai. YZ0014379 A-24 79-2425 Appendix A (cont.) Table 7 A Female Fertility Study In Rats with Benzene Cumulative Exposure Record Lactation Period Group 11-1 ppm Date ----------------------------------------------------------------- CSnulatTve Mean Inte- Dally Dally Total orated Exposure Dally Concert- Total Concen- Mean Test Exposure Concert- Exposure tratlon Exposure tratlon Concert- Day Number tratlon SO Hours Hours Hours Hours tratlon Ml ran 04 , 4/7/80 92 72 0.6 0.5 6 4/8/80 93 73 0.2 0.4 6 3.6 1.2 6 12 3.6 0.6 4.8 n.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 45.8 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 in 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 DO 067725 OONFTOFNTTAL YZOO14380 *j! Appendix A (cont.) Table 8 A Fewale Fertility Study In flats with Beneene 79*2425 t Individual Exposure Record for Group II i Pre-Hatlna* Mating* Gestation2 31 lactation-5 i-- Post-lactation Omul ative Total5 vOMtl ltiV0 Mean Test emulative Mean Test emulative Mean Test emulative Mean emulative Mean f emulative Mean An* of Exposure Days Nbnber Exposure Days 1 Gancen- of of Concetv- of of Exposure Days Timber Exposure Umber Exposure Concen- of of Goncen- of Goncen* of ' ECxopvoesnu-re Ho. Exposures tratlon EXoosure Exposures tratlon Exposure Ex nsures tratlon Exposure Exposures tratlon Exposures tratlon Exposures i tratlon (PM) (Win) (PM) (PM) (PM) ' <PM) /TpmT 425 428 427 428 429 438 431 432 433 434 435 435 437* 438 439 440 441 442 443 444 445 446* 447 448 449 450 50 50 50 so 50 so so so so so so 50 50 50 so SO 50 SO SO 50 50 SO SO SO so so 1.0 1.0 1.0 1.0 . 1.0 1.0 1.0 10) 10) 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 101 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 s 2 1 4 1 3 3 17 2 3 2 2 3 - 17 4 1 5 - 0.7 74-94 21 0.8 101-117 17 - 71-91 21 0.7 74-94 21 0.8 0.8 98-114 b 17m 0.9 73-93 21 0.7 100-116 17 0.3 72-92 21 0.8 99-115 17 0.5 77-97 21 0.9 b 0.9 73-93 21 0.7 99-115 17 0.3 72-92 21 0.8 98-1M 17 0.6 75-95 21 0.8 102-118 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 wo-m 17 0.7 74-9* 21 0.8 rno-m 17 0.9 73-93 21 0.7 100-116 17 0.9 73-91 21 0.7 100-116 17 - 71-91 21 0.7 74-94 21 0.8 96-114 17 0.8 10t-117 17 - 71-91 21 0.8 96-114 17 - 71-91 21 0.7 - 0.8 96-114 17 0.6 75-95 21 0.8 102-118 17 0.3 72-92 21 0.S 76-96 21 0.8 98-114 17 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 9S 1.0 8 1.3 95 J 1.0 74 ( 0.9 6 1.3 96 1 1.0 7 1.3 96 1.0 76 1 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 5 1.3 96 1.0 67 0.9 6 1.3 96 1.0 7 1.3 96 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 67 0.9 6 1.3 98 * 1.0 7 1.3 96 1.0 5 1.3 98 1.0 9 1.3 97 1.0 ro> o z^n O o oTt O'v'l Z-t N*ol >-i O' 1 Individual emulative exposure concentrations Men directly flron Tables 4 and 5 for the prewatlng and nattng period, respectively. `Individual emulative exposure concentrations ware calculated using Table 6 for the gestation period. Using anInal nwaber 42S as an atomic. a total of 21 P*nres *re received during Me oestatlon period (Days 74-94. Inclusive). During this period, a total of 126 exposure hours (144 - 18 - 126) S!.1. ,1.*^ Pfl* rtwce^ratlen heps [W^8 - 12.8 * 136.2) ten accmulated. liw emulative exposure concentration far this period ms 1.1 ppn (138.2 126 t.l). ^.pInCdPiIvNidoual emulative axpoiwre concentrations ware calculated using Table 7 for the lactation period using the procedure described for the gestation *rt ** dwwfln* the dally exposure concentrations that were obtained post-lactation for each anhaal. ^IJctSfifS 32JtlSrS 5^te tot!fl2e^,o!d^o^e^tJ, <0iM"rBl1- prMIng, -ti*. test* Mataal not noted, sacrificed 4/9/88. AataaA did not dettver pps, no mpasures received during lactation or post-lactation period. 4-25 YZ0014381 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 Date Cumulative Mean Inte* Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Dav 'Number tratlon SD Hours Hours Hours Hours. ....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 1/16/80 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 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 R.7 58.2 84 740.4 8.8 69.0 90 809.4 9.0 74.4 96 883.8 9.2 62.4 102 946.2 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,R 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 noA/p 0677p7 iofnttai YZ0014382 A-27 79-2425 Appendix A (cont.) " ' Table 9 (cont.) A Female Fertility Study In Rats with BeMene Cumulative Exposure Record Pre-mating Treatment Period Group III - 10 ppm (cont.) Date Cumulative Mean Inte* Dally Dally Total grated Exposure Dally Concen- Total Concert* Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Coneen- Day Number tratlon SD Hours Hours Hours Hours tratl 2/25/80 50 2/26/80 51 2/27/80 52 2/28/80 53 2/29/80 54 3/3/80 57 3/4/80 58 3/5/80 59 3/6/80 60 3/7/80 61 3/10/80 64 3/11/80 65 3/12/80 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 61.2 61.8 62.4 48.6 61.2 62.4 63.6 63.6 62.4 56.4 68.4 57.6 216 222 . 228 234 240 246 252 258 264 270 276 282 288 2088.6 2149.8 2211.6 2274.0 2322.6 2383.8 2446.2 2509.8 2573.4 2635.8 2692.2 2760.6 2818.2 9.7 9.7 9.7 9.7 9.7 9.7 9.7 9.7 9.7 9.8 9.8 9.8 9.8 Ml 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 00 067708 CONFIDENT TAI YZ0014383 A-2 8 79-2*25 Appendix A (cont.) Table 10 A Female Fertility Study in Rats with Benzene " emulative Exposure l&Cord Mating Period Group III - 10 ppm Date Mean Dally Dally Total Exposure Dally Goncen- Total Concen- Test Exposure Concen- Exposure tratlon Exposure tratlon Dav Number tratlon SD Hours Hours Hours Hours. Ml ran 04 3/17/80 3/18/60 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 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 $4.6 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 1H .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 Inte grated Mean Concentratlon 9.1 9.3 9.3 9.3 9.2 9.3 9.4 976 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. 00 c 0NF1 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 Humber 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 3/26/80 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 9.5 9.3 9.3 8.9 10.0 8.8 9.8 10.2 11.0 10.0 12.1 9.7 9.9 8.0 10.2 9.9 9.5 9.7 8.9 9.7 9.7 8.8 0.6 6 0.6 6 1.2 6 2.1 6 T.6 6 0.8 6 0.8 6 0.5 6 0.4 6 0.7 6 0.7 6 1.4 6 0.7 6 1.0 6 2.7 6 1.3 6 0.8 6 1.0 6 0.9 6 1.2 6 0.5 6 1.0 6 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 51.2 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 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 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 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 r-oNrn&> To?A/rr, YZ0014385 A-30 Appendix A (cont.) Table 12 A Female Fertility Study In Rats with Benzene 79-2425 Cumulative Exposure Record Lactation Period Group III - 10 ppm Date TM' Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Coneen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concerv- Day fomber tratlon SD Hours Hours Hours Hours tratlon Ml ran 04 / 4/7/80 92 4/8/80 93 72 73 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 4/27/80 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 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 42 499.8 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 067731 CONFTDFNTIAL YZOO14386 fakla"S13' .) * iMtt fertility Stair < btt vltk iMin MlrMwl Etwtart kreont fer Ctmp tl) fcll Ma fraJfcttM Mv af uaiiffm Hmo Eipnart Caacaatratlaa tpfaj 3t*t km f uKwrt ihtlaa P CwalattW On OmOop taaacara r Click* imwti tratlaa ' (wal last m *r Exaamra fettitm MOIm fea* Mhar Eirtnn * Caacaa- Eummtm tr*a# (*5"J (aaa) kit OSfS *f Emm Uctatlaa 1 baaimta ftoftir af Mm* Exoasara CBaraa Cmararai tratlaa lw>) feK-tactattaa' CmaTatKa Bra* Ciaaura af Caacaa Entum tratlaa (oa*) Omtlatlm total** f Cmcm-* Eimiitm trsttm -W.IT' cn M 474 W w SO Cl so ttt 50 Ul SO I3t SO (C so 33 so <34 M US 90 CM 90 ojj SO CM M I* M MO SO Ml so Ml sc M3 so MO so MS 90 CM so MT so MO so MS so CM M M n-n . n- Mn M Tl tl 71-73 tic 71 it Tl-TT US 71 hi 71-75 M 71-11 M 71 M n-n 11 Tl-73 t.5 71-54 M T1-TC fat 71 M 71-72 11 It-73 X5 71 t. 71-77 11 Tl Ia0 Tl-Tt *- 71-72 *. 71-72 M Tl TV-7k 2 14 3 5 1 1 1 3 13 1 2 3 1 1 - 2 2 2 1 I X3 73-53 21 1-7 as-m 21 t.t 72-52 21 72-52 21 5.3 74-54 21 72-52 21 5.2 bum 21 5.1 72-52 2! SU2 76-54 21 5-7 R-W2 21 5.1 72-52 21 5.3 74-54 21 Si 3 74-41 21 Xt 17-M7 21 5.2 77-57 21 1.1 72-52 21 X3 73-53 21 13 75-51 21 5.1 72-52 21 5l2 75-5k 21 - 72-52 21 5.3 73-51 21 5-3 73-53 21 5.3 73-53 21 5.1 72-52 21 5.2 77-57 21 5.7 105-1H IT tt.k 113-125 IT 5.7 55-114 IT 5.7 55-114 IT 5.5 1 5.7 55-114 IT n.s 155-121 IT 5.7 55-115 IT M.2 153-115 IT 11.1 105-125 IT 5.7 55-115 IT 5.i 102-115 IT 5.1 101-1)7 IT 11.7 m M.3 HH-120 IT 5.7 55-m IT 5.7 105-1K IT 5.1 102-115 IT 5.7 55-115 17 M.S 104-120 IT 5.7 5A-IM . IT 5.7 55-115 IT 5.7 K5-1M 17 5.7 MO-115 17 5.7 55-115 17 W.3 va-iis 17 13.0 13.0 12.5 12.5 U.k 13.5 12.5 12.5 13.1 12.5 13.5 1X0 1X0 12.5 13.0 13.0 12.5 1X0 12.5 12.5 13.5 1X5 12.5 12.5 1 13.5 a 14.1 H.1 5 H.l 3 H.2 7 H.l I M.0 0 H.l 5 H.O 5 H.0 i a.7 5 13.5 ? n.7 s H.5 5 1X5 5 13. T 5 13.5 5 1X5 ? 1X7 T 0.7 13.5 5 13.7 54 15.4 T 100 10.7 57 9J SC 10.7 j 71 9.0 54 M.7 96 10.0 90 M.0 55 M.I 97 10.7 97 10.0 90 10a0 90 10.1 94 55 n.f 97 10.7 9? u.f 51 10.0 97 T0.S 55 M.7 57 M.7 90 10*0 57 10a 0 57 M.4 57 M.7 55 M.4 HakHMaal caalatlra mm (MMtntbM UkM klractty fraa TaM I Md It fr D 'MkMtl malat1m mm-___ __a_a_c__aM__r__la__a_*__a__ra__c_i_lo__r_ii_t_a_k__aataa Tibia 11 fer tka anUttm *f H ftriTu n racatmk ttrtat tka amtattaa ktM (kay* 73 tKlaln). (Mi J S*??J):* ark I. Sa ilattra mi aattay racial. raaaacttmly. felkk Mini aatir CM a* aa aaamtt a taut I. a tatal r m atyasara haars (lSD-Ii-Uk) mi rattaa far tklt aartak mi* 1.7 aaa inkWtmi camlatlm mm itaf labia 17 far tka lactattaa aarlak atla tka Kacakart kaacrlkak fer tka yartattm twrtrtlrk cpatara "c*ara*caa*tr*at*l?aa" ^aa"tal`ari'itIek**ky4kawtk-l-m----t-k--a---f-a--t-a--l--c--w---a- l--atl.m, lactattaa. aak ank-lactatlaa airtaka ar tka tatat aaakar af-------fetkM kW aat katfmr am. aa i aktafaak aatf-lactattaa far aack aataal. ttaa af tka art Hln. aatlaa. yrrtitlaa, *-31 DO 0 & 7 7 3 ? C O N FID EN T! A-32 79-2425 Appendix A (cont.) _,, Table 14 TTema'le Fertility Study In Rats "with Benzene Cumulative Exposure Record Pre-Mating Treatment Period Group IV - 30 ppm cumulative Mean Inte- Dally Dally Total grated Exposure Dally Goncen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Date aDaaWvM Number tratlon 5D Hours Hours Hours Hours tratlon Ml ran L 1/7/80 T 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 2382.0 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 CONFIDENTIAL VZOO14388 A-33 79-2425 Appendix A (cont.) Table 14 (cont*) f>A FBl&le'Fertlltty Study In Rats With Benzene Cumulative Exposure Record Pre-Mating Treatment Period Group IV - 30 ppm (cont.) Date Cumulative Mean Inte- Dally Daily Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Goncen- Exposure tratlon Exposure tratlon ConcenDay 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 6 180.6 177.0 177.0 177.0 174.0 180.6 171.0 183.6 180.6 177.0 180.6 177.0 174.0 177.0 180.6 204 210 . 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 DO 067734 CONFIDENTIAL a YZ0014389 A-34 79-2425 Appendix A (cont.) - Table 15 A Female Fertility Study In Rats with Benzene emulative Exposure Record Mating Period Group IV - 30 ppm Date " cumulative Mean Into- Dally Dally Total grated Exposure Dally Goncen- Total Goncen- Mean Test Exposure Concen- Exposure tratlon Exposure tretlon Concen- Day . Number tratlon SD Hours Hours Hours Hours tratlon Ml ran 04 3/17/80 71 3/18/80 72 3/19/80 73 3/20/80 74 3/21/80 75 3/24/80 78 3/25/80 79 3/26/80 80 3/27/80 81 3/28/80 82 3/31/80 85 4/1/80 86 4/2/80 87 4/3/80 88 4/4/80 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 16B3.0 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 CONFIDENTIAL YZ0014390 A-35 79-2425 Appendix A (cont.) " - Table 16 A Female Fertility Study In Rats with Benzene Cunulative Exposure Record Gestation Period Group IV - 30 ppm Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Pate Day Humber tratlon SD Hours Hours Hours Hours tratlon Ml ran 04 3/17/80 71 3/18/80 72 3/19/80 73 3/20/80 74 3/21/80 75 3/22/80 76 3/23/80 77 3/24/80 78 3/25/80 79 3/26/80 80 3/27/80 81 3/28/80 82 3/29/80 83 3/30/80 84 3/31/80 85 4/1/80 86 4/2/80 87 4/3/80 88 4/4/80 89 4/5/80 90 4/6/80 91 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 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 1.8 6 30.7 3.1 6 30.7 2.2 6 31.9 2.8 6 30.2 2.6 6 32.4 4.2 6 30.1 1.4 6 30.7 0.0 6 31.3 1.4 6 32.4 2.9 6 29.6 1.8 6 30.2 2.6 6 30.2 2.6 6 31.3 1.4 6 29.6 1.8 6 31.3 3.4 6 31.3 1.4 6 30.1 1.4 6 30.7 2.2 6 31.3 5.0 6 31.3 1.4 6 30.7 2.2 6 29.6 1.8 6 31.9 2.8 6 30.7 2.2 6 31.3 3.4 6 29.6 1.8 6 30.2 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 CONFTDFNTTAI. YZ0014391 A-36 79-2425 Appendix A (cont.) Table 17 A Female Fertility Study In Rats with Benzene " Cumulative Exposure Record Lactation Period Group IV - 30 ppn Cumulative Mean Into- ' Oally Daily Total grated Exposure Oally Concen- Total Concen- Mean Test Exposure Concert- Exposure tratlon Exposure tratlon Concen* Date Day Number tratlon SD Hours Hours Hours . Jfrvri. 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 99 100 101 102 103 104 105 106 107 108 109 no 111 112 113 114 115 116 117 118 119 120 121 122 123 124 127 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 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 1.6 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 2.6 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 1475.4 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 YZ0014392 I Appendix * (cent.) Table 10 A Fenale Fertility Study In Oats with Inmc 79-2425 Individual Exposure Uncord for Group IV fre-Ftatine11 lbt!nqn GestationT?------------- Lactation1^ Past-Lactation14 Qmlitln Total1 - .L An. of emulative Neva Exposure Concen- hit Mys f Amber of emulative Mean Exposure Concen- Test Days of emulative Mean Umber Exposure of Concen- Test Roys of Amber of emulative Mean Exposure Umber Concen- of Cmil etlve ^Cumtatlve been ^ Men Exposure Umber Exposure Concen- of Conci lb. Exposures tratlon Exposure Exposures tratlon Exposure Exposures tratlon Exposure Exposeres tratlon Exposures tratlon Exposures , tratlon (PM) (PP) CM"! (PM) (M) (PC') nm)" 825 50 826 so 827 50 828 so 829 22 830 50 <31 so 832 50 833 50 834 so <35 so 836 50 837 50 838 50 839 SO 848 50 811 so M2 so 843 50 M4 50 MS 50 846 817 5so0 8*8 50 MS so 850 50 30.3 30.3 30.3 30.3 30.8 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 30.3 71 71-76 71-74 71 - 71-77 71 . 71 .71-74 - 71-77 71-74 71 71-74 71 71 71 71 71 71-73 71 71 1 5 4 1 m - 5 1 1 4 - 5 4 1 4 I 1 1 1 1 3 1 1 33.0 33.0 31.6 33.0 - 33. n 33.0 - 33.0 31.6 33.0 31.6 33.0 31.6 33.0 33.0 - 33.0 33.0 33.0 31.5 33.0 33.0 72-92 77-97 75-95 72-92 - 71-91 78-98 72-92 71-91 71-SI 72-92 75-95 71-91 78-98 75-96 72-92 75-95 72-92 72-92 71-91 72-92 72-92 72-92 74-94 72-92 72-92 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 31). 9 30.6 30.8 30.9 31.0 30.7 30.9 31.0 31.0 30.9 30.8 31.0 30.7 30.8 30.9 30.8 30.9 30.9 31.0 30.9 30.9 30.9 30,9 30.9 30.9 99-115 104-120 102-118 99-115 * 98-114 105-121 b b b 99*115 b 98-114 104-120 101-117 98-114 101-117 99*115 99-115 97b-113 99-115 99-115 101-117 99*115 * 17 17 17 17 17 17 . 17 17 17 17 17 17 17 17 17 17 17 17 17 - 30.8 30.8 30.8 30.8 30.8 30.7 30.8 30.8 30.8 30.8 30.8 30.8 30.8 10.8 30.8 - 30.8 30.8 30.8 30.8 " 7 30.8 a 30.7 5 31.1 7 30.8 8 30.7 3 30.9 7 30.8 8 30.7 4 30.7 5 31.1 8 30.7 5 31.1 7 30.8 7 30.6 9 30.6 7 30.8 7 30.8 5 31.1 7 30.8 - % ilB.1 97 / 30.6 97 1 30.6 96 30.6 22 130.8 96 30.6 96 30.6 72 30^5 71 30.5 71 ` 30.5 96 30.6 75 30.5 96 30.6 97 - 30.6 97 30.6 97 30.6 97 30.6 96 30.6 96 3IL6 97 30.6 72 30.5 96 * 30.6 96 30.6 96 30.6 96 30.6 72 30.5 _ ^ Tj <-< o 2^ 5 ;j hy n go 3> Individual emulative uqnsm concentration* taken directly fro* Tahirs 1* and IS for the prewtlng and noting periods, respectively. 'Individual emulative exposure concentrations uere calculated using Table 16 for the eestatlee period, Using anloal niauber 8?S as m exmale a total of 21 opanni wro received during oestatfoe (Beys 72-02. Incisive). Curing this period, a total of 126 exposore hours (132-6-126). and a total of ..MOB concentration hears (4066.0-198-M88) uere ate minted, lhe cosolatIve auposere concentration for this period eas MLS pen (38Mt126-30.0). i9IndtvMeal cmlatlve aupesare concentrations tore calculated using Table 17 for the 1octetloo period using the procedure described for the gestation J^Fvst^lactatleo cenennti atlana uere uhtalned by averagleg the dally exposure concentrations that uere obtained post-1octetten for each antail. iSThe total cmlatlve exposura concentration eas calcnlated by dividing the total cmlatlve cupesere concentration of the pre-autlng, eating, --f- tine, lactation, end post-lactation periods by the total amor of exposures. yccldtPtal death. 2/S/M. MrM did oat dal Ivor pps, no memos received daring lactation or pest-lactatloo parted. A-37 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 Cumulative Mean Oally Dally Total Exposure Dally Concern Total Concen- Test Exposure Concen- Exposure tratIon Exposure tratlon [)ate Dav Number tratIon SO Hours Hours Hours Hours Inte grated Mean Concen tration Ml ran L * 1/7/80 1 1 1/8/80 .2 . 2 1/9/80 3 3 1/10/80 4 4 1/11/80 5 5 1/14/30 8 6 1/15/80 9 7 1/16/80 10 8 1/17/80 11 9 1/18/80 12 10 1/21/80 15 11 1/22/80 16 12 1/23/80 17 13 1/24/80 18 14 1/25/80 19 15 1/28/80 22 16 1/29/80 23 17 1/30/80 24 18 1/31/80 25 19 2/1/80 26 20 2/4/80 29 21 2/5/80 30 22 2/6/80 31 23 2/7/80 32 24 2/8/80 33 25 2/11/80 36 26 2/12/80 37 27 2/13/80 38 28 2/14/80 39 29 2/15/80 40 30 2/18/80 43 31 2/19/80 44 32 2/20/80 45 33 2/21/80 46 34 2/22/BO 47 35 2/25/80 50 36 2/26/80 51 37 2/27/80 52 38 2/28/80 53 39 2/29/80 54 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 do 0fl77^^ CONFTOFNTIAI YZ0014394 A-39 79-2425 Appendix A (cont.) - -Table 19 (cont.) ..... A Female Fertility Study In Rats with Benzene emulative Exposure Record Pre-Mating Treatment Period Group V - 300 ppm (cont.) Date Cumulative Mean Inte* Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concern Day Number tratIon $D Hours Hours Hours HQurj tratIon 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 Ml ran 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 H67740 C-ONF TDf-NTTAl,. YZOO14395 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 ppn ----- - cumulatlve Mean Inte- Oally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- pate Dav Number tratlon SP Hours Hours Hours Hours tratlon Mlran 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 69 293 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 6 294 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 1,758 12 3,570 18 5,388 24 7,302 30 9,114 36 10,950 42 12,774 48 14,586 54 16,386 60 18,150 66 19,908 72 21.672 78 23,460 84 25,182 90 26,976 293 298 299 304 304 304 304 304 303 303 302 301 301 300 300 Exposure ninbers 56, 57, 63, and 64 for animals receiving exposure during the gestation period. DO 067741 CONFTDFNTTAl YZ0014396 A-41 Appendix A (cont.) Table 21 A Female Fertility Study In Rats with Benzene 79-2425 . - emulative Exposure Record Gestation Period Group V - 300 ppm " " .......... Cumulative Mean Inte- Dally Dally Total grated Exposure Dally Concen- Total Concen- Mean Test Exposure Concen- Exposure tratlon Exposure tratlon Concen- Pate 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 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 85 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 2 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 6 291 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 3oe 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 44,784 299 1758 156 46,542 298 1746 162 48,288 298 1680 168 49,968 297 1608 174 51,576 296 1560 180 53,136 295 1818 186 54,954 295 1758 192 56,712 295 1818 198 58,530 296 1764 204 60,294 296 1824 210 62,116 296 1734 216 63,864 296 0 067742 C NFTntNTTAt YZ0014397 A-42 79-2425 Appendix A (cont.) Table 22 A Female Fertility Study In Rats with Benzene Cunulatlve Exposure Record Lactation Period Group V - 300 ppm ------ --------- --------------------- -dumul ative Mean Oally Dally Total Exposure Dally Goncen- Total Concen- Test Exposure Concen- Exposure tratlon Exposure tratlon Date Day Number tratlon SD Hours Hours Hours Hours Integrated Mean Concen.tratlon 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 44,262 296 1734 156 45,996 295 1896 162 47,892 296 1758 168 49.650 296 1914 174 51,564 296 1752 180 53,316 296 1752 186 55,068 296 1854 192 56,922 296 1854 198 58,776 297 1890 204 60,666 297 1866 210 62,532 298 1806 216 64,338 298 00 067743 OONFTDFNTIAl. YZ0014398 Iu ;< OD O zn o -i o O"n O' m ZH Nl b U> vo VO Appendix A (cent.) Table 23 A Feuale Fertility Study ^ Rets with benzene Individual Ewtvre Record far Group V 79-2*25 I Fre-I*at1new totlne16 Gestation17 Lactation18 fost-Lactatlon'9 Cuauletdve Total20 emulative Omul stive Cwrlitlve Cumilatfve CumuIattve Cuuulattve Nusber Naan Exposure Test toys dauber Mean Exposure Test Days Mean Tost toaber Exposure Days Huwfur Mean , Exposure toaber toan i toan Exposure toaber .Exposure Amn.. of Exposures Concentretloo of f Exposure Exposures Concentratton IP1) IPto) of of ConcenExposure Ex wsures tratloa [OP") (Pte) of of ConcenExposure Exposures tretlon (opu) ef ConcenExposures tratton (wu> of ' ConcenExposures tratloa TGST" 1025 50 299 71-0* 10 303 85-105 21 291 f 297 8 296 88 1026 so 1027 50 299 71 299 71-73 i 3 293 72-92 21 299 74-91 21 300 99-115 17 299 101-117 17 296 300 7 5 296 296 96 96 1 298 299 1026 1029 1030 1031 1092 50 50 SO 50 50 299 71-83 10 299 71-72 2 299 - 299 71-74 4 299 - 303 M-104 21 298 73-93 21 - 71-91 21 304 75-95 21 - 71-91 21 291 111-127 17 299 99-115 17 300 297 103-119 17 300 97-113 17 306 296 301 294 98 299 7 296 97 298 71 299 5 296 97 299 9 296 97 ` 298 1033 50 1034 50 299 71-73 299 71 3 1 299 74-94 21 293 72-92 21 299 too-tw 17 300 99-115 17 298 296 6 296 97 299 7 296 96 298 1035 50 299 71-73 3 299 74-94 21 299 100-116 17 298 6 296 97 299 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 50 SO 50 50 50 so so so 50 50 299 299 299 - 299 71 299 71-74 299 299 71-73 291 71-74 299 71-72 299 71-75 - - 1 4 - 3 4 2 5 71-91 21 . 71-91 21 - 71-91 21 293 72-92 21 30* 75-95 21 71-91 21 299 74-94 21 304 75-95 21 290 73-93 21 304 76-96 21 300 97-113 17 300 98-114 17 300 97-113 17 no 99-115 17 297 103-119 17 300 a _ 299 100-1K 17 297 101-117 17 299 99-115 17 297 103-119 17 294 295 294 296 301 298 300 296 301 9 296 97 298 8 296 96 298 9 296 97 298 296 97 298 6 297 98 299 71 299 7 296 98 299 6 297 98 299 8 296 98 ; 298 6 297 99 ' 299 1046 1047 1048 1049 1050 SO 50 50 50 so 299 - 299 299 299 71-76 299 - 5 - - 71-91 21 . 71-91 21 71-91 21 304 77-97 21 - 71-91 21 300 97-113 17 300 a 300 99-115 17 296 104-120 17 300 98-114 17 29* 296 302 295 10 8 5 9 296 296 297 296 98 71 96 98 97 298 299 298 299 298 Ubdlvtteel cuMlotfee wwuri concentrations take* directly frua Tables 19 and 20 for tee pruMttoe aod settop period, respectively, lad1vtout emulative expesar* concentrations nero calcotatcd mine Table 21 tor tbe pastatloa period. Uslap antaal niter 1025 as an exanple a total f WWMH "ara received dnrtog pestattoe (toys 05.105, Inclusive). Oertop this period, a total of 126 exposure hours (Z10-M-126) and a total of ..*** eeacaeOrattoa beers (62118-2S422<>36896) uere accmlated. The cuariattve exposure ceaceatratloa tor this period is 291 pi (36696*326-291). ladhrMi! oMlatlvo exposure concentrations uere calculated uslnp Table 22 for the lactation period utlaq the procedure described tor the pest*tIon period. Itoest-lactation obtained by avareptop tee dally that uere obtained poet-lactattoe tor each an toil. "toe total cwlatteo calculated ty dtvWtop tea total ilatlvo exposure concentration af tee pro settop, settop, pestatloo. lactat1i. and pest-lactattoa btetoal dtt net deliver i by tee total mber of mu. ures ruectvsd durtop lactstli or post-lectattou period. M3 A-44 79-2425 Appendix A (Cont.) ^- Table 24 A Female Fertility Study In Rats with Benzene Dally Nominal Concentrations Date Nlran 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 Test Day 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 Exposure Number 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 Group 11 Group III Group IV Group V 0.6 7.8 0.2 6.1 0.8 8.2 2.2 8.3 0.9 9.1 0.7 8.1 0.7 8.1 1.0 8.5 0.9 8.4 1.3 8.2 1.3 8.2 1.4 8.2 1.4 8.0 1.5 8.8 1.4 10.9 1.5 6.1 1.3 10.6 0.7 10.7 1.6 10.4 1.4 10.2 1.4 5.1 1.3 9.9 1.5 8.5 1.8 9.0 2.0 11.5 a 1.0 9.1 0.8 9.1 1.9 12.7 0.8 10.4 1.2 11.3 1.3 10.3 1.1 10.1 1.1 9.5 1.1 10.6 26.5 25.7 30.1 31.6 28.3 29.8 30.7 29.0 28.5 30.6 28.9 27.9 28.2 30.7 31.4 25.9 32.7 31.3 31.3 29.5 25.2 30.2 29.8 30.2 30.6 23.5 30.3 31.1 30.9 28.6 30.0 29.7 28.7 28.3 29.1 329 276 304 287 328 316 305 337 302 307 321 310 290 300 300 299 290 317 312 317 302 312 320 324 319 308 319 314 329 321 325 317 326 315 320 4Nom1na1 concentration suspect due to possible weighing error, not Included In mean calculation. DO 067745 conftdfnttal YZ0014400 4-45 79-2425 Appendix A (Cont.) Table 24 (cont.) A Female Fertility Study In Rats with Benzene Pally Nominal Concentrations (cont.) Test Date Day Ml ran L (cont.) Exposure Number Nominal Concentration Group Group Group -U-- III Group 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/BO 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 67 68 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 49 50 51 52 S3 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 Nominal concentration suspect due to possible weighing error, not Included In mean calculation. DO 06^746 CONFTDENTTAl YZ0014401 A-46 79-2425 Appendix A (Cent.) Table 24 (cont.) A Female Fertility Study In Rats with Benzene ""** Dally Nominal Concentrations (cont.) Date 4/6/80 4/7/80 4/8/80 Test Exposure Day Number 91 71 92 72 93 73 Nominal Concentration Group Group Group JL- -UL IV 1.1 11.0 1.2 10.3 1.2 10.7 36.1 34.2 35.9 Group V 375 381 376 GC (Groups 11 and HI. 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 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 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 409 405 402 418 408 412 403 397 390 404 396 420 379 408 420 390 407 399 362 340 296 309 333 322 345 316 351 320 296 345 365 356 313 272 c c Mean S.O. N 1.2 0.3 103 10.4 1.6 108 32.7 3.5 105 346 39 107 bNon-exposure day. Exposures terminated. DO 067747 CONFTDFNTTAL YZ0014402 A-47 79-2425 Appendix A (cont.) Table 25 A Female Fertility Study In Rats with Benzene ' neaaJjAlly HgRMnarroncfntratlon vs. Mean Dally Anelytlcal 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 Mean S.D. N Mean S.D. N Mean S.D. N Mean S.D. N Nominal Cone. (PPM) 1.2 .3 71 1.3 .2 32 1.2 .3 104 9.8 1.4 72 Analytical Cone. (ppm) .92 .5 73 1.2 .9 32 1.1 .4 105 9.7 1.0 73 X Difference 24 8 9 1 4/9/80 - 5/14/80* 1/7/80 - 5/14/80 IV 1/7/80 - 5/12/80 V 1/7/80 - 5/12/80 Mean S.n. N Mean S.D. N Mean S.D. N Mean S.D. N 11.7 1.0 35 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 Mlran Infrared Analyzer. DAna1yt1ca1 concentrations measured using on-line Tracor gas chromatograph. DO 067748 CONFIDENTIAL YZ0014403 YZ0014404 o On ^o 5v ^ *. S --------------------------------------------------------------------------------------------- |i Group ppn I 0 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 Week: _0_ A" 169 176 157 155 160 164 158 161 151 171 174 139 158 140 150 161 153 162 158 168 166 162 147 172 145 159 Appendix B An Inhalation Female Fertility Study with Benzene In Rats U 79-2425 i ---------------------------------------------------------------------------------------------------------- --- Individual and Mean Body Height Data - (grams) Pre-Mating Treatment Period / * Change in 1 2 34 5 6 78 9 10 Wt^ j-10 A' A' A- A" A" A" A" A" A- A" 188 199 210 228 236 244 245 255 258 258 197 210 226 241 253 266 275 280 279 288 175 183 196 207 221 232 232 250 265 245 176 203 196 208 214 221 215 218 222 225 (128) 187 197 209 215 225 231 238 237 247 179 191 205 219 227 230 242 245 249 251 164 188 195 209 212 226 237 245 244 257 182 200 210 218 225 238 249 240 254 266 161 163 182 196 200 212 217 220 221 229 193 205 211 221 229 242 244 251 255 263 188 203 214 228 236 249 244 257 257 263 163 167 174 190 196 209 213 212 219 228 180 188 195 209 221 231 231 239 240 241 186 194 202 224 233 237 238 244 249 249 168 177 184 201 207 216 218 226 232 237 185 189 202 222 229 237 247 246 257 265 165 180 194 211 218 232 242 244 248 257 186 202 216 229 242 243 249 256 260 271 181 200 211 222 232 239 242 249 258 264 187 202 212 228 237 244 262 281 276 280 181 180 204 220 226 232 235 235 241 246 179 208 215 233 239 245 250 257 261 265 162 169 174 193 191 206 209 205 213 215 205 219 234 259 267 279 291 300 306 312 159 167 181 196 201 203 208 214 216 218 180 197 214 232 250 251 257 271 279 278 r A" If sf 70 49 (72) 72 93 84 68 70 75 65 61 63 69 80 92 85 83 93 65 86 53 107 59 98 Neon S.O. N 159 179 191 202 217 225 10 12 15 15 16 18 26 25 26 26 26 26 For explanation of statistical symbol: A-; see Appendix Q. Body weight Week 1 aooears incorrectlv rrcnrripd. utnht 234 239 245 250 255 17 20 22 22 22 26 26 26 26 26 76 14 25 ......... ------------------------------------ fin MwnHiw\ wr 4Vum ..1 -Inn- l Appendix B (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Body Height Data - (grams) Pre-Mating Treatment Period Animal thahtoe In Group Number Meek: 0 1 2 3 4 5 6 7 8 9 10 Mt.fl-10 PP II 425 1 425 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 153 172 182 199 213 225 229 233 241 244 245 160 172 191 198 213 228 229 234 237 240 251 159 194 192 208 219 229 240 236 248 247 248 181 202 214 227 244 253 261 257 267 273 279 158 176 188 198 206 213 221 226 228 233 239 147 190 169 208 185 223 195 240 215 256 226 263 235 271 231 244 274 284 248 309 256 293 168 191 206 224 236 248 258 264 266 280 289 167 187 210 227 239 250 249 262 273 278 280 149 166 184 195 196 213 222 225 222 233 242 155 169 174 185 206 209 212 218 224 224 221 167 187 201 207 221 232 233 238 237 241 243 172 190 210 222 235 236 251 252 257 263 261 156 174 193 214 218 225 239 245 239 253 255 157 170 172 184 196 200 207 213 219 222 226 160 177 195 196 232 261 241 234 244 259 261 151 171 184 195 211 219 225 226 234 241 246 163 187 197 205 222 237 257 253 257 255 264 164 172 190 204 216 224 231 242 241 256 249 140 156 170 179 194 200 209 214 218 222 231 165 192 208 215 230 243 248 248 275 273 273 155 177 191 205 216 229 232 240 241 252 258 166 183 201 207 226 235 245 247 253 261 264 144 162 167 181 196 214 217 218 223 231 232 161 187 198 208 220 230 236 247 243 260 257 154 173 187 200 211 223 233 235 239 244 254 79 54 77 63 87 85 98 93 76 52 56 71 81 56 8^ 75 77 77 75 81 81 81 70 70 81 Mean S.O. N 160 179 193 205 219 229 236 239 244 252 255 11 26 12 26 14 26 IS 26 16 26 17 26 16 26 16 18 26 26 20 26 18 26 75 11 26 00 067750 C O N FID EN TIAL VI .) ' on o 5v 5> X> Appendix B (cont.) An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Individual and Mean Body Height Data - (grams) Pre-Mating Treatment Period Animal Group Number Meek: _0_ ppn 1 2 3 4 5 6 78 9 Change in 10 Wt. V-jlO T III 625 10 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 648 649 650 174 194 202 215 233 239 249 249 259 265 267 162 180 192 210 218 231 241 241 250 259 263 160 159 175 165 188 185 196 185 219 209 216 207 224 224 224 223 221 220 237 230 244 238 141 159 166 179 194 201 205 213 217 221 221 148 170 180 192 201 206 214 219 220 224 236 152 166 183 194 206 213 219 229 228 240 237 153 175 186 198 211 215 229 237 235 242 249 157 174 190 207 218 231 242 243 244 257 258 158 184 194 210 222 238 240 250 250 264 268 167 180 194 210 223 235 241 237 244 253 251 173 191 209 218 238 250 257 258 263 267 269 156 164 177 190 205 210 209 220 225 229 229 158 176 185 194 209 212 221 218 232 236 237 152 166 181 189 200 208 211 216 223 227 227 165 178 190 208 215 227 235 239 242 252 255 165 186 192 202 222 231 235 240 251 265 267 161 183 190 213 223 228 236 243 250 254 251 161 188 203 213 220 236 244 246 252 263 271 153 187 209 225 235 257 259 271 274 284 281 156 169 178 196 207 213 220 225 228 228 232 161 177 189 197 211 223 228 230 237 249 247 170 190 201 214 228 242 245 246 252 261 263 176 201 215 226 245 260 267 269 279 293 295 177 207 220 231 233 256 261 264 264 284 285 152 175 190 204 224 237 244 244 251 268 266 73 j 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 26 12 26 12 26 13 26 13 26 17 26 17 16 17 26 26 26 20 26 19 26 75 10 26 No statistically significant differences frcm control. B-3 YZ0014406 Appendix B (cont.) An Inhalation Female Fertility Study with Benzene in Rats t 79-2425 1 f Individual and Mean Body Height Data - grams Pre-Mating Treatment Period "JGlial ' Group Number Week: _0_ ppm 1 23456 7 .8 9 Charge In 10 Ht. flt10 'f* IV 825 30 826 827 828 829*> 8X 831 832 S33 834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849 850 166 174 191 191 205 203 216 215 223 230 237 242 250 251 252 256 248 255 272 268 272 270 161 184 197 208 225 227 250 251 268 278 279 142 161 173 183 198 203 213 218 221 224 232 150 165 173 190 197 - 166 183 204 207 220 231 234 240 249 254 256 163 184 199 214 221 226 236 244 247 256 254 170 188 210 225 236 255 261 268 273 289 290 160 102 192 207 220 232 235 240 245 249 249 172 193 204 224 241 253 256 265 274 288 292 175 193 215 219 234 243 250 255 258 267 270 157 178 198 214 226 237 241 248 253 258 259 153 171 194 215 228 237 253 266 268 278 282 178 197 211 223 241 249 254 264 275 285 286 165 178 188 199 212 218 224 233 241 240 247 134 146 160 175 186 192 194 200 199 203 206 156 168 187 195 203 217 227 226 235 236 245 152 174 184 191 202 212 214 223 227 233 232 166 186 197 204 219 221 231 237 244 248 253 155 172 193 202 218 230 241 242 246 252 260 159 176 195 210 216 232 236 247 256 254 266 161 171 200 207 222 233 233 247 249 262 265 147 162 176 186 199 201 207 217 223 224 233 151 164 179 193 202 205 211 220 228 230 228 158 184 200 208 225 236 241 242 241 252 257 157 171 188 197 206 218 217 229 229 235 240 81, M 95 71* 73 70 102 G7 99 77 81 111 89 69 60 77, 58 67 88 90 94 71 64 73 69 DO 0 6 7 7 5 ? C O N FID E N T TAl Mem S.O. 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 14 25 1 Appendix B (cont.) An Inhalation Female Fertility Study with Benzene In Rats tT' 79-2425 '.! Individual and Mean Body Weight Data - (grams) Pre-Mating Treatment Period ** i " ~~ Change In Group Number Week: _0_ ppm 1 2 34 5 6 78 9 10 Wt. ilr 10 T V 1025 300 1026 1027 1028 1029 1030 1031 1032 1C33 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 oMozT) oo O 1046 1047 1048 1049 1) SJ 1050 2^ 165 187 206 221 233 242 254 256 256 271 270 148 165 178 187 201 213 220 222 227 229 238. 158 169 183 193 211 218 223 224 232 237 234 148 166 169 172 181 184 186 188 189 190 193 157 176 186 191 204 215 215 217 227 229 227 164 185 196 196 202 209 221 229 242 253 258 156 174 183 195 210 222 226 222 232 236 240 189 217 237 257 273 280 293 303 309 305 313 140 152 167 176 190 203 212 213 223 226 229 169 195 212 224 239 245 260 263 268 274 281 171 197 205 217 238 2S7 243 249 260 270 267 156 179 187 200 216 220 238 242 246 247 257 139 165 180 187 201 206 214 215 218 230 227 149 169 178 189 206 212 216 221 231 232 237 162 182 197 211 221 231 238 246 250 251 252 166 178 194 215 223 231 233 239 246 250 249 165 188 202 217 234 236 247 251 260 265 265 181 209 215 228 244 250 251 261 270 278 274 155 168 183 191 198 207 209 213 226 231 229 156 180 190 199 216 228 236 233 247 257 255 161 178 197 213 225 238 244 246 240 257 255 170 191 211 228 246 245 264 274 282 283 291 153 167 ' 182 194 206 215 226 230 235 242 244 169 181 201 214 223 233 246 250 253. 264 265 174 193 207 213 237 248 256 255 268 280 274 157 175 187 196 211 212 220 226 235 232 241 83, 67?* 27, 51 73 66 96 77 86 70 78 62 68 70 71 77 65 61 75 77 100 77 84 81 66 iH (*) ES Mean S.O. 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 B-5 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 OONFTDfrNTrA( YZ0014409 C-2 Appendix C (cont.) An Inhalation Female FertYTIty Study with Benzene In Rats 79-2425 Individual and Hean Maternal Body Weights and Weight Gains During Gestation - grams Group I - (0 ppm] No. Day: 225 226 227 228 229 230 231 232* 233 234& 235 236 237 238 239 240 241C 242 243 244 245b 246 247 248* 249 260 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 A274 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 53 140 (21) 115 93 130 127 120 147 - 140 128 136 (25) 97 118 (2?) 115 145 Mean S.D. 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 CONFIDENTIAL YZ0014410 C-3 Appendix C (cont.f " 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: 0 425 426 427b 428 429 4306 431 432 433 434 435 436 437C 438 439 440 441 442 443 444 445 446c 447 448 449 450 252 255 (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 - 387 316 316 390 Change In Body Weight 0-21 145 117 (2) 133 133 (22) 125 121 110 141 101 110 ** 123 111 155 132 108 131 118 148 . 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 CONFTOFNTTAl YZ0014411 C-4 Appendix C (cont.) An Inhalation Female FertFnty Study with Benzene in Rats 79-2425 Individual and Mean Maternal Body Weights and Weight Gains During Gestation - grains Group 111 (10 ppm) Change In An. Body Weight No. Day: 0 7 14 21 0-21 6Z5 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 ,0) 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 CONFTDFNTTAI.. YZ0014412 C-5 Appendix C (cont.) ArT 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: Change In Body Weight 14 21 0-21 825 826 827 828 829^ 830 831 832d 833|> 834** 835 836d 837 838 839 840 841 842 843 844 845b' 846 847 848 849 850b 287 251 203 246 228 251 258 (260) 261 227 236 263 (229) 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) 341 299 237 299 280 295 305 (282) 323 277 279 314 (252) 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) 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. D0 067758 CONFTOFNTIM 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 Gains During Gestation - grams Group V - (300 ppm) 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 Kean 254 S.O. 28 N 23 7 301 257 254 216 243 (267) 264 337 253 280 294 269 256 246 262 271 (279) 304 247 285 274 324 (261) 267 303 261 273 28 23 14 321 291 284 246 270 (276) 293 365 277 316 337 300 276 268 289 307 (280) 333 266 315 307 353 (261) 300 330 288 301 29 23 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 0) 118 86 131 103 158 (13) 87 154 127 377 126 39 22 23 23 No statistically significant differences from control. DO 067759 CONFTDFNTtAl. 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 0.21 225 226 227 228 229 230 231 232 233 234b 235 236 237 238 239 240 241c 242 243 244. 245b 246 247 248<* 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 . 29$ - 315 - 316 to 257 285 307 320 * . m to 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 . a* - - 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 to 18 56 41 to 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 OONFTDFNTTAI YZ0014415 C-8 Appendix C (cont*) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Individual and Mean Maternal Bo<ty Weights and Weight Gains During Lactation - grams Group II - (1 ppm) Change In An. Boiy Weight No. Day: 0 4 14 21 0-21 425 426L 427b 428 429 430<J 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 m * m 313 318 330 328 269 295 316 298 - . - ip 333 329 350 374 325 317 345 345 303 296 334 343 286 267 310 311 242 264 298 300 257 278 305 323 - ip - 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 - 32 40 25 49 56 48 29 64 - 39 40 13 32 Mean 282 291 319 320 38 S.D. 24 22 23 22 15 N 22 22 22 22 22 No statistically significant differences from control. DO CONFTOFNTTAl. YZ0014416 C-9 79-2425 Appendix C (cont.) ~ J^T-V ''"Mn inhalation Female Fertility-Study with Benzene In Rats Individual and Mean Maternal Body Weights and Weight Gains During Lactation - grams Group III - (10 ppm) Change in 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 m 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 m-- 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 288 298 325 325 37 S.D* 24 26 23 24 19 N 24 24 24 24 24 No statistically significant differences from control* DO 06776? CONFIDENTIAL YZ0014417 C-9 Appendix C (cont.) -v -Atr-Inhalation Female Fertility Study with Benzene In Rets 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 0-21 625 626 627 628 629* 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 ** m * 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 m* 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 m 55 38 38 51 55 30 40 42 46 13 50 20 Mean 288 298 325 325 37 S.D. 24 26 23 24 19 N 24 24 24 24 24 No statistically significant differences from control* DO 067767 CONFIDENTIAL 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 . 827 828 829* 830 831 832? 833b 834b 835 836<* 837 838 839 840 841 842 843 844. 845b 846 847 848 849 850b 299 306 332 351 292 313 348 328 306 324 332 332 269 265 282 308 -m 277 285 302 302 299 m 314 m 332 4* 340 m m - 4* m *--* 293 315 336 356 _ e 4t - 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 m--- 302 296 333 344 255 260 296 309 250 261 299 289 305 311 318 325 m m 44 4 52 36 26 39 25 41 - - - 63 * 39 38 51 23 28 53 45 32 42 54 39 20 - Mean S.O. N 289 294 318 328 23 25 26 25 19 19 19 19 39 12 19 No statistically significant differences from control* oo c0NF 067?63 TENTI4L YZ0014418 C-11 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 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 292 m 262 282 316 312 274 290 306 306 220 234 245 266 261 271 295 285 m *m zn 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 - m- 287 314 310 306 313 335 358 370 274 282 310 311 50 32 46 24 - 17 23 32 48 13 47 66 26 72 76 - $0 45 52 30 47 - 19 57 37 Mean S.O. N 289 296 316 330 34 31 28 35 23 22 22 22 41 18 22 No statistically significant differences from control. 00 067764 CONFrOENTTA! YZ0014419 0-1 - Appendix D An Inhalation Female Fertility Study with Benzene in Rats 79-2425 Litter Information Preface Footnotes: Males 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. Head colunn (Day 0) and Included In calculation of mean mmber 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 colunn and these pups are Included In calculation of mean number of dead pups. ^Animal 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). h0n 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, female 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 mmber dead pups. YZOO14420 { Appendix 8 (coot.) An Inhalation Female Fertility Study with Benzene In Rats Litter Information - Group I (0 ppn) TA25 i Dan Stn Gest. Total Wo. Mo.* Length bays P*JP lb. Naan No. Alive Dead Pup Wt. H F Total 9 ----- Pre-Cull-- bean Ho. Alive hit Wt. H F Total 9 Post-Cull Mean ft>. Alive Pud Wt. H" F TolaT 9 225 4 226 4 227 5 ta 5 229 6 230 6 231 7 232s,"7 233 0 234 8 235 9 236 9 237 10 236 10 239 11 240 11 241 242 12 243 5 244 13 245 15 246 IS 247 16 248s 16 249 17 ro> o >50 17 zo -n otal O can om O' ZM J>* Ea H O' -< O' 3> A' A" A" A' A" It" A* A" A" A' A" A' 22 6 2 4 6 0 6.8 2 4 6 8.7 2 4 6 21 15 a 7 T5 0 5.5 8 7 15 8.0 5 5 10 22 13 s 8 13 0 22 10 4 6 10 0 21 14 6 8 14 0 6.0 5 6.1 4 5.7 6 8 13 6 10 8 14 9.8 9.7 8.3 5 5 10 4 6 10 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 ntlng confirmed; evidence of parturitioni; one ieplantatlon scar noted at ter* sacrifice, 22 14 6 8 14 0 5.9 6 8 14 9.1 5 5 10 Mating confirmed; no evidence of parturition; no laplast scars at tern sacrifice- not pregnant.1 22 11 7 4 11 0 6.6 7 4 11 10.8 6 4 10 21 10 5 5 10 0 5.8 6 5 10 8.8 5 5M 22 10 s 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 10 fttleg not confirmed; female sacrificed post-mating- no 1mil ant scars not pregnant. 21 13 7 6 13 0 6.2 7 6 13 9.4 5 5 10 21 17 7 W 17 0 5.3 6 10 16 7.7 S 5 10 22 13 6 6 12 1 5.9 4 3 7 6.5 437 ifctlng confirmed; no evidence of parturition; no Implant sears 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; no evidence of parturition; however, 17 Implantation scars noted at term sacrifice. 22 13 7 8 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 a.7 8.1 9.8 9.7 6.3 11.4 9.8 9.3 10.8 8.8 10.4 8.9 10.6 10.3 9.4 7.8 6.5 12.4 6.5 8.2 11.1 45$ 21.7 0*5 0.1 21 246 11.7 2.7 0.6 21 123 5.9 1*5 0*3 21 120 5.7 2.0 0.4 21 243 11.6 2.7 0.6 21 3 0.1 0.4 0.1 21 130.5 6.2 0.5 0.1 21 120 5.7 1.6 0.4 21 116 5.S 2.1 0.5 21 236 11.2 2.8 0.6 21 198.9 9.5 1.4 0.3 21 102 4.9 0.9 8.2 21 95 4.5 1.1 0.2 21 197 9.4 1.5 0.3 21 199.0 9.5 1.4 0.3 21 Day 14 ifcan Alive Pup Wt. 9 A" 6 21.6 10 22.4 10 21.4 K> 22.2 10 21.8 10 25.1 10 23.3 10 22.6 10 26.4 8 19.9 9 24.1 10 21.7 10 23.8 10 24.3 10 23.9 10 22.6 7 11.4 5 27.2 10 21.6 10 21.5 10 26.5 195 9.3 1.5 0.3 21 475.3 22.6 3.2 0.7 21 Day 21 i Mo,. Aldve H -- F 1 TotiT A" A'f l A* $ 5f 6 10 5 5 K> 4 5 6 65 fi 4' 10 10 10 $ 59 iV 10 5 5 10 6 4 10 4 4. 8 549 6 4 10 6 4 10 5 5 10 5 5 10 5 5 10 437 415 4 6 10 5 5 r 10 5 5 10 101 4.8 0.9 0.2 21 94 4.5 1.1 0.2 21 195 9.3 1.5 0.3 21 Hran Pop Wt 9 38.3 35.2 38.3 36.4 31.7 39.1 38.5 38.7 44.0 33.7 40.3 33.0 42.0 35.9 36.1 36.1 21.5 45.5 32.3 34.7 44.5 775.8 36.9 5.3 1.1 21 .! Dan Sire No. No.* 425 18 426 18 427 428 19 429 21 439* 21 431 a 432 22 433 23 434 23 435 24 436 24 438 25 439 27 440 27 441 29 442 29 443 30 4a 30 445. 31 446* a? 32 448 32 o o 450* 33 z o _____ -n 3 52!' 3^5! -H ST1 S.E. i-i 'vi | X> Appendix 0 (cent.) An inhalation tattle Fertility Study with Benzene In Ret* Litter tnfonaatlon - Group II (1 ppa) Grit. Totef teneth Pups Per Q Alive T TeEiT ----- Per I ' tre-tuh dean T ~ATlivoetT Pop Wt. 9 'Toil-Col I lb. Alive ~ F Tdlir 2222 14 13 8 3 8 14 0 8.3 9 12 1 6.2 8 8 14 3 8 11 9.0 10.4 S 5 10 3 7 10 fating 22 22 ci1os3nflmedI;x 14 6 no ev8id0ence1Io3Vf 8 14 par0nturitio<6n.4; 0 6.0 no latc5ent 6 fating pi sc8ars atl1.3tens s1au0c..r4.ifice- 8 14 9.1 no-t rpreg-nant. 10 10 21 14 6 8 14 0 5.6 21 12 5 7 12 0 5.6 6 8 14 8.4 5 7 12 8.3 5 5 id 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 22 11 3 8 11 0 6.0 8 4 12 8.8 3 8 11 8.8 6 4 10 3 7 10 22 10 4 5 9 1 6.1 Nitlnf 22 21 22 22 22 22 22 22 13 10 10 5 16 9 14 8 12 9 10 4 76 13 5 3 13 0 5.9 5 10 0 5.6 7 16 0 6.9 6 14 a 6.5 3 12 0 6.8 6 10 0 6.8 1 7 0 6.6 8 13 0 6.6 fating not confined; f 4 5 9 11.4 459 13 l^lantatlon sites Observed. 10 3 13 10.0 7 3 10 5 4 9 10.0 549 8 7 IS 9.1 5 5 10 8 6 14 7.6 5 5 10 9 3 12 9.5 7 3 10 4 6 10 11.1 4 6 10 6 1 7 11.9 617 5 8 13 10.5 5 5W 15 talantatlon sites observed. 22 II 7 4 11 0 6.6 21 10 72 9 1 5.2 23 22 IS2 2 9 0 4 2 13 [92] 7.3 6.6 4 11 W.l 2 9 9.6 0 2 12.4 41 11.0 6 4 10 729 20 2 6 4 10 Neon T 9.0 10.4 10.5 9.1 8.4 8.4 8.8 8.6 8.8 11.4 9.9 M.0 9.1 1.2 9.4 11.1 11.9 10.6 W.l 9.6 12.4 11.0 21.8 0.5 0.1 22 260 11.8 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 95 206 4.3 9.4 1.7 1.8 0.4 0.4 22 22 215.9 9.6 1.3 0.3 22 f%HK far 14 To. ... Alive Pop Wt. 4*1 21 Hay Alive faan faoWl TotaT -f- 9 10 23.5 10 24.1 5 3 H> 35.1 10 39.3 10 22.9 S 10 43.2 10 23.5 5 5 10 40.7 1 10 21.8 10 20.5 5 5 5 10 33.3 5 10 30.9 10 20.2 5 5 10 33.9 J10 22.2 10 20.9 6 3 10 35.3 10 32.7 9 25.4 4 5 9 40.5 10 26.1 7 3 10 45.1 9 20.4 5 4 9 32.2 1100 21.0 19.4 5 5 5 tt 35.5 5 10 33.0 10 24.8 7 3 10 37.8 10 19.9 4 6 10 26.2 7 25.9 6 1 7 45.3 10 25.4 5 5 10 41.7 10 24.0 9 20.7 2 16.3 10 29.1 6 7 2 6 10 40.8 9 30.2 2 16.3 10 49.1 206 496.0 9.4 22.6 1.8 2.9 0.4 0.6 22 22 111 95 206 796.1 5.0 4.3 9.4 36.3 1.3 1.7 1.6 7.2 0.3 22 0.4 22 0.4 1.5 22 22 lb statistically significant differences frea the control Key: N - nele; f - famle. 0-3 IN K> N> Appendix 0 (coat.) An Inhalation Penile Fertility Study with Benzene In tats Litter Information - Cron III (TO ppn) tan Sire to. Jlfei IS 34 (26 44 627 35 (28 35 f 36 130 36 *31 37 (32 37 (33 39 (34 35 (3S 40 (36 40 (32 41 (38 44 (39 44 (40 44 (41 45 (42 45 M3 46 (44 46 (45 47 (46 47 (47 48 (48 48 (49 SO (SO so test. Total Length ftnn Days Oar 0 HDo Hein No. Alive Dead Pup ot. M F Total 9 ' Pn3eTI---- Post-Cull---- dean Neon H lo. Alive Pud Mt. f Total 9 No. Alive Pud Ht. . * i Total V- 22 u 4 6 10 1 6.4 4 6 10 10.3 4 6 10 22 13 8 5 13 0 6.4 8 5 13 H.O 5 5 10 21 11 7 4 11 0 S.S 7 4 11 8.1 6 4 10 22 14 9 S 14 0 5.5 8 5 13 8.8 5 5 10 Katlny confined-, no evidence of parturition: no implant scars at ten sacrifice- not i 22 13 7 6 13 0 6.1 6 13 8.3 5 5 10 22 S 3 2 5 0 7.1 3 2 S 13.0 3 2 5 22 IS 6 9 15 0 6.3 6 9 15 9.0 5 5 10 22 10 4 6 10 0 6.5 4 6 W 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 M 0 6.5 7 7 M 9.7 5 5 10 23 S 3 2 S 0 7.6 3 2 $ 15.8 3 2 5 22 IS 9 5 M 1 6.1 8 5 13 9.1 5 5 10 ttatlny confined; no evidence of parturition; no inplant scars at ten sacrifice- not |infnont e 22 13 ( 7 13 0 6.6 6 6 12 W.S 5 5W 22 13 S 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 s 7.0 3 6 9 12.0 36 9 22 15 6 9 IS 0 6.4 6 9 15 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 cn* 6.1 4 8 12 9.0 4 6w 21 15 8 7 IS 0 5.3 8 7 15 8.3 5 5 TO 22 11 5 6 11 0 7.0 5 6 11 10.1 5 5 TO 22 11 3 8 11 0 7.0 3 8 11 12.0 3 7 TO 22 K 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 TO 10.3 10.8 8.0 8.7 8.3 13.0 9.0 11.5 10.3 9.7 15.0 9.0 W.4 8.9 9.2 12.0 9.7 7.8 9.1 8.4 10.2 12.0 9.0 9.5 Oay 14 NO. dean Alive Pup Mt. 9 10 M.2 TO 24.5 10 18.3 TO 18.8 5 12.3 5 30.4 TO 22.5 TO 25.1 10 25.9 10 25.1 5 32.4 10 24.0 TO 24.3 TO 22.9 10 20.1 9 24.5 10 24.0 9 23.0 10 22.6 10 23.6 10 21.2 9 29.1 10 24.1 TO 24.3 --TD3a1y--2-1- dean W N-oT.igA-li--veTotal Pud Ut. 9 2 2 4 15.2 5 5. TO 40.5 6 4 10 27.6 5 9 u 26.0 3 2 5 24.7 3 2 S 50.8 5 5 TO 37.1 4 6 TO 41.1 S S TO 40.5 5 5 TO 42.9 3 2 S 54.7 S 5 TO 38.6 5 5 TO 41.5 $ 5 TO 38.6 6 4 TO 29.7 3 .6 9 43.3 $ S 10 40.2 5 4 9 33.8 4 6 TO 36.4 S S W 36.4 5 3 fI TO 9 36.5 47.6 6 4 10 39.5 5 5 TO 38.5 Total mtm S#9o 5-t. 8 (26 21.9 0.5 0.1 24 382 12.4 2.8 24 148 6.2 2.3 9.S 24 MS 6.0 2.0 0.4 24 293 9 12.2 0.4 2.9 1.0 0.6 0.2 24 151.9 6.3 0.6 0.1 24 146 6.1 2.2 0.5 24 144 6.0 2.0 0.4 21 290 12.1 2.9 8.6 26 241.2 10.1 1.0 Ot.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 W.1 1.0 0.4 24 222 9.3 1.7 0.3 24 557.4 23.2 4.4 0.9 24 we 4.S 1.1 0.2 24 108 4.S 1.3 0.3 24 216 9.0 2.0 0.4 24 903.7 37.7 0.4 1.7 24 in statistically significant dlffemnces fran the control group. Koyt H nale; F - foaoln. i Appendix 0 (coat.) An Inhalation Fault Fertility Study with Benzene tn tats 79-2425 Utter Infematim - Grot* IV (JO pm) |M Sire is*. No." sn SI 826 51 827 52 028 52 8JO 53 831 54 832* $4 833 55 83* 55 8JS 58 8J6 58 B37S 37 838 57 839 58 840 58 841 59 842 59 843 80 844 80 845 51 848 51 847 82 848 52 849 63 850 53 test. tout length Fes* beys 22 13 22 13 22 W 22 10 Dev 0 He. AtIve n F Total 4 9 13 3 10 13 8 6 14 3 7 10 Me. Main Dead Fup Vt. g _M 0 6.9 4 0 6.2 3 0 6.2 8 0 6.6 3 Pre-Col 1 Mo. Alive F Total ay* Kean Pup Mt. 9 M 9 13 9.1 4 n 13 9.8 3 6 14 10.5 5 7 10 M.2 3 Post-Coil No. Alive F Total 6W 7 10 S 10 7 10 Keae Poe Wt. 9 9.1 10.0 10.6 10.2 Oay 14 To. Kean Alive Pup Mt. 9 10 21.0 10 24.4 10 25.2 10 19.6 22 9 3 5 9 0 6.1 3 6 9 11.3 3 5 9 11.3 9 26.5 22 11 7 4 11 0 6.2 7 4 11 9.5 5 4 9.5 10 19.3 Bating confined; no evidence of parturition; however, 23 t^lantetfon scan noted at tern sacrifice. Kiting confined; no evidence of partorltion; no iMat scan at tern sacrifice* not pregnant flettng 22 cenflmed; 15 8 no evidence of 7 IS parturition; no 0 5.9 Inplant 8 scan 7 at tern 15 sacrifice8.5 not 5 pregnant 5 10 Kiting cenflmed; ne evidence of parturition; hewevter. 14 luplantatlon scan noted at tern sacrifice. 8.4 10 21.3 22 52 3 50 6.9 24 6 11.7 2 4 6 11.7 6 26.5 21 15 7 8 15 0 5.9 7 8 15 9.1 5 5 W 9.4 10 24.2 21 21 5 8 14 0 5.5 6 8 14 11 6 5 11 0 5.7 6 5 11 8.7 8.9 5 5 5 5 w10 8.5 10 20.7 8.8 w 18.4 21 13 8 5 13 0 5.4 8 5 13 8.1 5 5 10 8.1 10 20.2 22 15 4 11 15 0 5.7 3 11 14 8.3 3 7 N 8.4 10 20.0 22 6 3 3 8 0 7.1 3 3 6 13.1 3 3 6 13.1 6 27.7 21 13 3 10 13 0 5.5 3 10 13 8.4 3 7 10 8.4 10 20.6 Kiting cenflmed; no evidence of partorltion; ne taa>lnt scan at tern sacrifice- not pregnant 22 15 8 5 13 2 5.7 8 5 13 7.8 5 5 10 7.9 9 18.7 22 - 13 5 22 13 9 22 7 4 8 13 0 4 13 0 3 70 6.6 6.1 7.8 5 8 13 9 4 13 43 7 9.5 9.3 13.8 5 6 4 $ 10 4M 37 9.5 10 18.8 9.3 to 20.0 13.8 7 29.3 Meting cenflmed; ne evidence of parturition; no 1*Mint scan at tern sacrifice- not e Dir 21 Hoi Alive JL. Total 4 6 10 3 / 10 5 ft M 3 5n 3% 9 6 4 10 Heen Pud Wt. 9 34.0 37.7 38.2 32.1 .40.3 30.3 5 `5 10 246 5 5 10 5 5 10 5 5 10 5 5w 3 7 10 336 3 7 10 459 5 :s 10 6 f4 10 437 32.5 41.3 38.0 31.0 26.9 30.3 30.6 43.9 29.8 30.5 31.1 31.6 44.9 Total Mean S3. S3. N 413 21.7 8.5 8.1 19 225 W1 122 223 2 tn.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 8.7 8.5 0.6 0.7 0.1 0.2 19 19 19 19 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 SO 4.2 1.2 0.3 19 98 5.2 1.3 8.3 19 178 9.4 1.4 0.3 19 186.1 9.6 1.7 0.4 19 177 422.4 9.3 22.2 1.4 3.4 0.3 0.0 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 e statistically significant differences free the central creep. Key: A * cele; F - feoele. YZ001442 00 nr 11 i! ( Appendla 0 (cant.) An Inhalation Feaele Fertility Study with Hewane In Rats titter lafenaatlou Group V (300 ppa) Pm Sir* Bo. 00.4 102s 00 1025 64 1027 66 low 70 10a 66 1030 66 1031 67 1032 67 1033 60 1034 00 1033 a 1036 a 1037 70 1030 70 1039 71 1040 71 1041 72 1042 72 1043 73 1044 73 1046 74 1046 74 1047 75 1040 75 ioa 77 1090 77 test. TataT length Fans Oars Oav 0 HO. Naan No. H11 Dead tea Vt. H F Total 9 Dev 4 Past-Cull Dav 14 Ho. Alive Mean ten lit. Mu. Alive Keen te: Item tea vt. Alive tea Vt. it f Tetel 9 0 F mr 9 o 22 9 1 4 S 4 6.1 0 0 22 15 9 6 15 0 S.6 9 6 15 9.2 S 5 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 M 21 11 6 5 11 0 S.6 6 5 11 9.3 S S 10 Ml* confined; na evidence of parturition; no Inplant scars at tern sacrifice" not pregnant a 22 0 0 2 2 C6jc 7.0 0 2 2 13.1 0 2 2 21 IS 10 S IS 0 5.4 10 5 15 0.2 $ S W 21 It s 6 11 0 S.4 5 6 11 9.4 s S to 22 11 6 5 11 0 5.9 6 5 11 8.0 s 5 10 21 13 0 S 13 0 6.0 0 5 13 9.0 s S ID 21 14 9 S 14 0 5.6 9 5 14 0.4 s 5 10 22 13 6 7 13 0 6.2 6 7 13 9.4 s S 10 21 15 5 10 IS 0 5.5 5 10 15 8.3 5 5 10 22 It 4 6 10 1 5.6 4 6 10 9.0 4 6 10 22 0 7 IS 0 6.6 8 7 15 9.S S S 10 Hating couflmed; ae evidence of parturition; ne I %l at ter* sacrifice- not pregnant 21 10 3 7 10 0 5.0 3 7W W.3 3 7 10 21 21 22 0S IS 11 10 s 3 00 4 IS 0 3 02 S.6 5 s.s 11 6.S 5 30 3 14 30 9.0 0.5 10.0 5 7 S 30 3 10 38 21 16 10 6 16 0 5.8 10 6 H 8.6 S S 10 Hating conflmedj no evidence of parturition; no laplait scars at tern sacrifice- not 23 5 3 2 5 0 7.4 3 2 5 13.9 3 2 s 22 IS 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 .7 6.1 9.2 13.1 8.1 9.5 0.0 9.9 0.3 9.6 0.3 9.8 9.6 10.3 9.0 0.5 10.0 8.5 13.9 10.2 9.8 9 9 0 10 2 10 10 9 10 10 10 W 10 10 10 8 10 0 10 5 w 10 15.0 22.2 16.2 20.7 20.0 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 79H742S i' \ -------- 1---- Day 21 -------- rr Nee* Ha. Artve tee Vt _r_ TotaT 9 s( 9 6* 9 39 5' M 22 5 10 5 10 5' 9 5 10 5 to 5W 5M 6 10 5 10 7 10 30 3 10 2 5{ 7 10 25 4 to 4 10 24.5 36.0 23.0 28.1 46.0 33.2 37.0 31.7 34.6 30.9 34.5 31.9 32.5 40.6 34.0 30.4 34.4 37.0 20.7 42.1 40.9 31.0 Total HtM Soft* S.E. 1 497 21.6 0.6 0.1 23 276 12.0 2.9 0.6 23 144 6.3 3.1 0.6 23 117 S.1 1.0 0.4 23 261 11.3 3.0 0.0 23 IS 0.7 1.S 0.3 23 130.1 6.0 0.S 0.1 23 142 6.2 3.0 0.6 23 111 4.0 1.9 0.4 23 253 11.S 3.6 0.0 22 211.3 9.6 1.6 0.3 22 K3 4.7 1.4 0.3 22 99 4.S 1.3 0.3 22 282 9.2 2.0 0.4 22 211.1 9.0 1.6 0.3 22 190 9.0 2.0 9.4 22 475.3 21.6 2.9 0.6 22 M .6 .4 ' .3 22 97 4.4 1.4 0.3 22 190 9.0 2.0 0.4 22 749.3 34.0 5.5 1.2 22 itillitteltjr itfriflCMt differences froa the control m. toy: N air, F fanale. u YZ0014425 i AppendU D (cont.) A* Inhalation Fmle Fertility Study with Benzene tn Rets Utter Information - Group IV {30 ppn) Dm Sire BO. Wo.* 025 51 aw 51 827 $2 828 52 829d 830 S3 831 54 832*54 833 55 834 55 835 58 838 58 8379 57 838 57 839 58 840 58 841 59 842 59 843 SO 844 80 84$ 81 848 81 847 62 848 82 849 63 850 83 test. Total length Runt flays Oar 0 Ho. Hean Ho. Alive Oeed wp tft. H f tout 9 ----------F5T3TT-- Nean Ho. Alive Pup 1ft. H F TotaT 9 Post-Cut 1 Day 14 Hean he: flean Ho. Alive Pud ft. Alive Pun Wt. H , F TotaT 9 9 22 13 4 9 13 0 8.9 22 13 3 10 13 0 6.2 22 14 8 6 14 0 6.2 22 10 3 7 10 0 6.6 9 13 9.1 4 6 10 9.1 TO 21.0 10 13 9.8 a 7 TO W.O 10 24.4 6 14 10.5 5 5 10 TO.6 TO 25.2 7 10 10.2 3 7 10 W.2 TO 19.6 22 9 3 6 9 0 6.1 6 9 11.3 3 6 9 11.3 9 25.5 22 11 7 4 11 0 6.2 4U 9.5 6 4 10 9.5 TO 19.3 Hating confirmed; no evidence of parturition; however, 23 Implantation scars noted at term sacrifice. Hating confirmed; no evidence of parturition; no lop ant scars at term sacrifice* not pregnant. Hating confirmed; no evidence of parturition: no imp ant scars at term sacrifice- not pregnant. 22 15 8 7 15 0 5.9 7 IS 8.5 5 $ 10 8.4 TO 21.3 Hating confirmed; no evidence of parturition; heueve . 14 Implantation scars noted at tans sacrifice. 22 5 2 3 5 0 6.9 21 IS 7 8 15 0 5.9 4 6 11.7 2 4 6 11.7 8 W.5 8 IS 9.1 5 5 10 9.4 TO W.2 21 14 8 8 14 0 5.5 8w 8.7 5 5 IQ 8.6 10 20.7 21 11 8 5 11 0 5.7 5 11 8.9 5 5 10 8.8 TO 18.4 21 13 8 S 13 0 5.4 22 15 4 11 15 0 5.7 22 8 3 3 8 0 7.1 21 13 3 10 13 0 5.5 S 13 8.1 5 S 10 8.1 TO 20.2 11 14 8.3 3 7 10 8.4 TO 20.0 3 6 13.1 3 3 6 13.1 6 27.7 10 13 8.4 3 7 10 8.4 TO 20.6 Hating confirmed; no evidence of parturition; no Imp ant scars at term sacrifice- not pregnant. 22 IS 8 5 13 2 5.7 5 13 7.8 5 5 to 22 13 5 8 13 0 6.6 8 13 9.5 5 5 22 13 9 4 13 0 6.1 4 13 9.3 6 4 TO 22 7 4 3 7 0 7.8 3 7 13.8 4 3 7 7.9 9 TO. 7 9.5 TO 18.8 9.3 TO 20.0 13.8 7 29.3 Hating cenfirmed; no evidence of parturition; no 1^ ant scars at term sacrifice- not pregnant. Gay Vl Vi Hean Ho. tve Pun Ht. H Ft irota! 9 4 34.0 3 5 li sf 10 TO 37.7 38.2 3 7 10 32.1 3 6 9 40.3 6 4 TO 30.1 5 5 TO 32.5 2 4 6 41.3 5 5 . TO 38.0 5 5 10 31.0 5 5 10 W.9 5 5 TO 30.3 3 7 10 30.6 3 3 6 43.9 3 7 TO 29.8 4 5. 9 30.5 5 Sf 10 31.1 6 4 10 31.8 4 3 7 44.9 Total Hearn SJ. S.E. 8 413 21.7 0.5 0.1 19 225 101 122 223 2 m.o 11.0 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 H 19 19 19 , TOO 5.3 2.3 0.5 19 123 6.5 2.5 0.6 19 223 11.7 2.9 0.7 19 165.6 9.8 1.7 0.4 19 Re statistically significant differences fro* the control grasp. Kqn H * sole; F - fnelo 00 4.2 1.2 0.3 19 90 5.2 1.3 0.3 19 178 9.4 1.4 0.3 19 TO6.1 177 422.4 9.0 9.3 22.2 1.7 1.4 3.4 6.4 0.3 0.8 19 19 19 79 4.2 1.2 0.3 19 98 5.2 1.3 0.3 19 177 9.3 1.4 0.3 19 655.0 34.5 5.3 119 .2 1t YZ0014426 '1 ** H- \ Appendix D (cant.) An InlulitlM Fcnale Fertility Study with ianrene In Rati Utter Infomatlon - trap V (300 ppn) Oaw Sire Sett, total No. Jfci length N tityZ------ _ H Oar 0 Sol KST . fi* np wt. F Total | Pre-tail PayT "K&M1 10S 68 1026 64 1027 65 102* 70 1029 66 1030 66 1031 67 1032 67 1033 68 1036 68 103S 69 1036 69 1037 70 1038 70 1039 71 1040 71 1041 72 1042 72 1043 73 1044 73 1045 74 1046 74 1047 75 1048 75 1049 77 1050 77 22 9 1 4 54 6.1 0 0 22 15 g 6 15 0 5.6 9 6 15 9.2 5 5 M 22 22 11 12 3 7 6 92 5 12 0 6.6 5.9 3 6 69 4 10 10.7 6.1 3 6 69 4 10 21 11 6 5 11 0 5.6 6 5 11 9.3 5 5 10 mtlng coeflroed; no evidence of parturition; no Inplant pears at tom sacrifice- Mt m ZZ 8 0 2 2 16F 7.0 0 2 2 13.1 0 2 2 21 15 to 5 15 0 5.4 W 5 15 8.2 5 5 10 21 11 5 6 11 0 5.4 5 6 11 9.4 5 5 10 22 It 6 5 11 0 5.9 6 5 11 8.8 5 5 10 21 13 8 5 0 6.0 8 5 13 9.8 5 5 w 21 14 9 5 14 0 5.6 9 S M 8.4 5 5 10 22 13 6 7 13 0 6.2 6 7 13 9.4 5 5 10 21 15 5 10 15 0 5.5 5 10 15 8.3 5 5 ID 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 IS 9.5 5 5 10 Hating confined; no evidence of parturition; no Inplant scars at tem sacrifice- not prewnt. Z1 10 3 l ID 0 5.8 3 7 to 10.3 3 7 10 21 8 5 3 80 5.6 5 3 8 9.8 5 3 8 21 15 11 4 15 9 5.5 11 3 14 6.5 7 3 10 22 21 10 5 16 10 3 82 6 K0 6.5 5 5.8 38 6 16 10.0 8.6 5 5 38 5 10 Hating conftnatd; no evidence of parturition; no fe^lant scars at tarn sacrifice- not pf09Mnt 3 z 50 7.4 3 2 5 13.9 3 2 5 22 15 11 4 15 0 6.1 11 4 15 10.3 6 4 22 13 9 4 13 0 6.4 9 4 13 9.9 6 4 10 79-2|ttS t/* Oar 14 So. Mean No Wt. Alive Pop Pt. 19 *" ah.^N^Artre TOST 9.1 n.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 10 2 10 10 9 10 10 10 10 10 10 8 10 6 10 5 K> 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 4 3 6 5 0 5 5 4 5 5 5 5 4 5 3 5 7 5 5 3 6 6 51 9 69 3i 9 5 10 22 5 5 10 59 5 10 5 10 5. n 5 10 6 to 5w 7 to 36 3 10 2. 7 5f W 25 4W 4 10 24.5 36.8 23.8 28.1 46.6 33.2 37.0 31.7 34.6 30.9 34.5 31.8 32.5 40.6 34.0 30.4 34.4 37.0 28.7 42.1 40.9 34.0 Total Mean Ss.3c.. N 497 21.6 0.C 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 IS 0.7 1.5 0.3 23 138.1 6.0 0.5 0.1 23 M2 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 M 0.3 22 190 9.0 2.0 0.4 22 748.3 34.0 5.5 1.2 22 No statistically significant differences fron Ue control grasp. Mgr: N - ante; F - fenslc. *lUL^ YZ0014427 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. 22$ , 226 227 228 229 230 231 232C 233 234> 235 236 237 238 239 240 241b 242 243 244 245b 246 247 248* 249 250 No. of Implantation Scars ft" 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 Unaccowtedfor - Conceotl K- 1 1 1 0 0 0 1 0 1 4 1 2 1 4 0 1 2 2 I 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. `Female 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. female Initiated delivery; one pup noted In vaginal canal. This pup was apparently cannablllzed prior to Day 0 litter examination. DO 067773 CONFIDENTIAL YZ0014428 E-2 Appendix E (cgnt.) 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*' 426 427*> 428 429 430* 431 432 433 434 435 436 437*1 438 439 440 441 442 443 444 445. 446*1 447 448 449 450 No. of Implantation Scars ft Total 7 7 14 6 8 14 (0) (0) (0) 5 8 13 8 6 14 (2) (0) 78 (2) 15 5 7 12 5 9 14 5 8 13 7 4 11 8 2 10 (8) (5) (13) 7 6 13 8 4 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. Puds 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 - Concent1 0 1 . 0 0 (2) 1 0 1 0 0 0 m 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. "Female 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. 00 0^7774 CONFTDENTTAl YZ0014429 E-3 Appendix E (cont.) An Inhalation'Female Fertility Study with Benzene In Rats 79-242$ Implantation Scar and Unaccounted-for-Conceptl Data Group III - (10 ppm) Female No. 625 ' 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 No. of Implantation Scars RL 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 Unaccounted for - 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. JCey: R right uterine horn; L * left uterine horn, "Female did not deliver a litter; data In parentheses excluded from cal culations. DO 067775 CONFIDENTIAL YZOO14430 E-4 Appendix E (corrt.) An Inflation Female Ferttllty Study with Benzene In Rats 79-2425 Implantation Scar and Unaccounted for-Conceptl Data Group IV - (30 ppm) Female No. / 825 826 827 828 829 830 831 832* 833 834b 835 836* 837 838 839 840 841 842 843 844 845>> 846 847 848 849 850 No. of Implantation Scars______ lL Total 7 6 13 11 3 14 9 7 16 3 8 11 65 85 (i? S(12) (0] 87 (9) (5) 71 79 77 66 87 6 11 60 77 (0) (0) 88 58 86 26 (0) (0) 11 13 1 15 (14) 8 16 14 12 15 17 6 14 w 13 14 8 (0) Total No. Pups at Birth 13 13 14 10 9 11 S02,i (0 15 (0) 5 15 14 11 13 15 6 13 (0) 15 13 13 7 (0) Unaccounted" for - Concept1 0 1 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 too statistically significant differences from control. Key: R right uterine horn; l - left uterine horn. *Fema1e did not deliver a litter; however. Implantation scar(s) w ob served at term sacrifice; data In parentheses excluded from calculations. Female 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 CONFTDFNTTAl YZ0014431 E-5 Appendix E (contT) Inhalation Female Fertility.Study with Benzene In Rats 79-2425 Implantation Scar and Unaccounted-for*Concept1 Data Group V - (300 ppm) Female No. 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 No. of Implantation Scars R L total 11 0 87 n6 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 n 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 Unaccountedfor - Conceotl 9 15 IV 12 n (0) 8 15 11 11 13 14 13 15 11 15 . (0) 10 8 15 10 16 (0) 5 15 13 2 0 6 0 1 m 8 0 2 2 0 1 2 0 1 1 0 4 1 ^0 1 i 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 calculatlons. 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 CONFTDFNT T Al YZOO14433 F-2 * Appendix F (cont4~ An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Females Group ppm I 0 An. No. 225 . 226 227 226 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 Type of Death* 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. Observations)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 (0.4 X 0.3 cm.) filled with yellowlsh 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 CONFIDENTIAL YZOO14434 F-3 Appendix F (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Females Group "ppn II 1 (cont.) An. No. 435 436 , 437 438 439 440 441 442 443 444 445 446 447 448 Tvoe of Death3 T T P-M T T T T T T T T P-M T M 449 450 Ill 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 papn la. Lungs; all lobes slightly red. Eye (Right): 20% opacities. Eye (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. *T Terminal; M * Moribund; P-M post-mating. &N.0.A. * No observable abnormalities. DO 067780 CONFIDENTIAL YZ0014435 F-4 Appendix F (cont.) -An Inhalation-Female Fertility Study with Benzene In Rats 79-2425 Gross Postmortem Observations - Females Group ppn 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 Deathi 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. T Terailnali A Accidental. "N.O.A. - No observable abnormalities. DO 067781 CONFIDFNTTA! YZ0014436 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 Type of Death8 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 T Terminal. "N.O.A. No observable abnormalities. Observation?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 lunig; 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 Luna: Masses 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 (Left): tan mass subcutaneous (i.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 06.778? CONFIDENTIAL YZOO14437 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 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 Type of Death> T T T T T 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. Lungs: greenish-tan round nodule (apprbx. 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 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; Hasses on lobes; adhered to thoracle cavity; filled with a green caseous material. N.O.A. N.O.A. N.O.A. N.O.A. Axillary Area (left): 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. ^N.O.A. * No observable abnormalities. DO 067783 OONFTDFNTTAl YZOO14438 Appendix G An Inhalation Female Fertility Stuc(y With Benzene In Rats Pup Organ Weight Data Preface L/BW ratio of liver weight to bo<Jy weight (Day 21). K/BW ratio of kidney weight to bo<1y weight (Day 21). / T/BW ratio of testes weight to botfy weight (Day 21). 79-2425 DO 067784 CONFIDENTIAL YZOO14439 sex LITTER r> oo ^Tf o fOn js\j 2 SJ *--4i UCDl l 1 . 1lT i i i ii i i i i ii ii i i ii i i i i ii ii t i tt it ii it ii * X s X 225 222222656 H 226 X 226 X 226 X 227 XX 222277 X K 222277 X 229 X 223 M X 222233 XX X X XX 229 229 229 229 222192 XX 223:03 X 2:0 X 230 X X 2?3 2fl X X X 2223:;111 X X 222l1l X 211 X 2-; XX X XX 22553: `.'5 2^*.55 X s 2:5 * <- :5 G-l Appeals fi (com.) Am Mulatto* FmuIk Fortuity St*4y ltk IHKM 10 lots w-2s POP jpttyiot 1 r.us 2 0. iil 1 r.i?i 2> i'o US MU $ 0.222 5 C.1J9 1 i:. 133 2 0.211 3 =. 151 1 r.i53 5t 03..115552 2s 0.145 00..116209 1 C. 151 2 0.1:3 0.l5t i 0.10l| c % C0..11:559 2 0.153 L3 0.137 0.179 5 3.131 6 C.i3| 1 0.162 2 0.161 k c.ifc? 0.171 51 30..127072 2s* 51 * 6 r. 169 0.16? 00*00..1197I26I 0o m.2b.t:?* 0.1*6 5 LIVER T5T 1.3)- 'l1..T5.7rr.??i9i *.6ir 1.236 1.25* 1.3;:* 2.0*3 1.611 1.535 1.551 1.753 1.150 21.-237509 1.115 1.222 1.371 0.900 0.975 t*"27 2.002 1.903 1.?I2 2.149 21..270453 1.630 1.005 2.010 1.955 11..737014 1. i;4 1.773 1.VJ3 l.f-51 2*.`.*1ir2v72 2fXc .5.. *.**5.i RIDRET3 M f.4. 00..4*7*34 0.-93 0.SC4 3 0 * 124 l0.4.492* 0.1-39 C.U1 r0..3;3*45 0. *45 J.27 0.543 CC.. 1i*i7;7 00..353019 0.456 0.436 00,.463910.530 00..552580 0.620 0.470 P00...44449766: 0.622 o.>92 0.6:9 0.425 1.517 :0:-.55155: :*.V6 .*.?! MBT NT. (9) 41.6 J'|O*.l3 ;6. 5 ?5.3 *4.i 52.6 40.2 42. 3 35.3 37-6 ?4.C 222..50 36-C 41.9 *>20-.91 29.7 30.1 63C0..4C 3599-.60 61.1 62.6 4;.2 37*..45 33.9 39.3 40.2 6 t.O *3.7 *5.6 40.0 *6.9 46953...306 6**5C?.5*i` T/BW r lev o.rntroroo r3..O0P=44J53447612; 00..0002665022926-15 0.20426330 C.0065,:224 00..O05P642519753236 0.50620210.00447977 C.00667692 02..0o0r43553;i?2?5: 0.50531562 C.30653967 00..0000643563344732 0.00545515 0O..0C0C624947057090 C.CC393990 3.00463672 0.0043552? e.0C62433? 0.00421611 0.00620779 0.20377005 00..10*00347279369625 00..000044690226939? C.CC4?6693 0.ret57305 C.C0430000 0C..cCeP464746792665 r.orttoroc 0.0=663*29 0.01626174 1.005*-04; L/BW \* 0,0453596 0.0467297 P0..006401067S3211 r.rti?tc3 r. 03732:5 0.0334665 0.04437:5 00..0046753050=050 0.0621011 0.0442636 C.P56C92? 0C0...0r0455541>16173283596 0.0333293 P.0405930 0.0160636 0P..002?92902T=243 O.C4;175= P.0505556 0.0476)93 C.C465237 20..C055C140446)C7 3.0454026 0.0449193 0.0439717 0.0605025 O.C436*13 O0..CC446471945412 0.0J74719 CC..C04449435iO0?0 00..0P45910P240414 3.0633940 C.055736? P.05091:0 K/B* 0.0115700 0.0123103 0.0114372 0.0101152 0.0112369 00..=0009*994:3172 0.0122335 0.011261? 0C..C03IO96306.1519 P9..0P1I 123113594 9.P105C2C C.009533? C0..CC11CC51797359 3.025269 0.021956 C.016*10? 0C.C.0121567C2C93 C.C122T2? 0P..P0121:7505?92 0.02441; P.P123704 3.0155065 0.0112299 0r..0o20133324?4 0C..00112023373360 C.01C9364 P. 01012 0C..001059177560 CC..0012292339399 3.013884 0.0152767 0.0121*C4 t>0 V { i f .u 00 067786 C O N FID EN TIAL mm sex linen x x XX RM N H 235 235 236 236 X X NK 223376 XI I X XI X N 237 N HM H M 237 237 237 236 238 H 238 ! N N il R H M R 236 239 239 239 M 239 N n R 239 in H H H H 260 2*0 260 260 H n 226622 H 262 R 262 H 2J2 R 263 R R 226633 RH HH 2*3 22266*366 H R 226666 X R 266 6-2 tofmdl* ( (cent.) An MwUtton tatli Fertility Stdy with Itimin In tots H-242S UVER T5T SlORCtS WTRT. fir T/Bff L/BW K/Btf 61 2 0.234 0.069 0.164 2.434 0.932 4.564 0.617 0.258 0.4C7 47.0 23-7 39.5 0.00491469 0.00291139 0.00407595 0.0517672 0.03932*9 0.0395949 C.01312T7 00..00110083606318 3 0.422 1.359 0.397 34.4 0,00357771 0.0398534 0.0116*22 6 1 0.168 0.176 1.515 1.824 0.628 0.494 2 0.166 2.134 0.556 36.7 40.0 45.6 0.00403270 0.00445000 0.00410460 0.0412607 0.04S6000 C.0465939 C.0116621 0.0123500 0.0120961 3 C.497 1.644 0.505 4C.5 0.00486420 0.0455309 0.0126691 6 0.206 1.991 C.486 51 0.178 0.152 2.041 1.360 0.494 C. 387 62.1 39.0 34.9 0.00484561 0.C0456H0 0.00476489 0.0472922 0.0523??} 0.0426332 0.0115639 0.0126667 0.0121317 2 0.456 1.664 0.441 33.C 0.00472727 0.0504242 0.0133636 3 0.159 1.89? 0.4P3 35.7 0.00445378 0.0475910 0.0112865 6 5 0.166 0.462 4.398 1.539 S:llt 66 2 0.452 0.494 0.192 1.571 2.435 1.914 0.381 0.546 0.523 3 0.476 1.616 0.452 6 0.206 2.002 0.482 5 0.499 2.307 0.545 64 2 0.166 0.467 0.485 2.248 1.452 4.646 0.496 0.414 0.452 3 6 0.461 0.432 4.728 4.522 0.429 0.44T 5 0.470 4.534 0.433 42 0.165 0.466 !*! 1.668 0.400 0.502 32.0 33.2 34.6 42.9 41.8 40.9 42.6 45.0 49.7 35.6 37.3 34.9 36.0 36.0 34-1 37.9 0.00462500 0.00427711 0.00439306 0.004*5221 0.00459330 0.00430318 0.00478873 0.00442222 0.00370224 0.00*69101 0.00495979 0.00404014 0.00366667 0.00*47388 0.00425220 0.00390504 0.0436675 0.0463554 0.0454046 0.0567599 0.0457895 0.0444499 0.0469953 0.0512667 0.0452314 0.0407665 0.0441623 0.0495129 0.0422778 0.0403664 0.0361877 0.0440106 0.0423750 0.0127406 0.0140416 00..00112205128200 0.0440513 0.0443146 0.0124444 0.0099799 0.0145649 0.0424160 0.0422923 0.0424167 0.0443947 0.0417302 0.0132456 0.4T2 1.603 0.439 36.6 0.00469945 0.0437978 0.0419945 $ 4 2 63 5 4 2 0.152 0.167 0.466 0.430 0.439 0.436 0.453 1.592 1.939 1.7*9 1.599 1.333 4.691 1.*55 0.83* 0.610 00..880*67 2.289 0.468 36.9 0.644 37.0 0.440 39.7 0.396 36.4 0.358 31.0 0.425 34.7 O.394 33.3 0.216 20.9 0.246 23.2 0.234 0.264 .5 0.596 *6.3 0.00414924 0.00454351 0.00418436 0.00377907 0.00448367 0.00397695 0.00*59459 0.00277542 0.00244207 0.00053333 0.00250000 0.00421166 O.Q434436 0.0524054 0.0440554 0.0464826 0.0430000 0.0467320 0.0436937 0.03990*3 0.0349136 0.0358667 0.03907*4 0.0*94384 0.0426629 0.0419169 0.0140631 0.0445416 0.0415484 0.0422676 0.0416316 0.0106306 0.0406697 0.0106000 0.0422222 0.0429156 warn six iirnt I X I I X I I X X I I X I X I X X HEAR S.O. N 2** M 2*6 N 2*6 K 2*T K 2*7 M 2*7 M 2*7 M 2*9 It 2*9 K 2*9 M 2*9 N 2*9 H 250 M 250 n 250 It 250 N 250 6-3 fai fepmfla 0 (cant.) Mulatto FcmIc Fertility Stwtfjr with Bmucot fa Bits F9-212S nr w 2 0.479 *3 0.191 0.472 i 0.4*6 2 0.439 3* 0.452 0.4*2 4 -*3* 2 0.4*0 3 0.17* * 0.4*7 54 0.152 0.243 2 0.493 3 0.266 * 0.1*5 5 0.487 ~nr 1.913 2.357 2.080 1.321 1.339 4. *39 4.*56 4.267 1.57* 1.771 1.61T 4.812 2.065 2.117 2.122 4.916 2.060 timers --TF~ 0. *95 0.576 0.5*0 0.359 0.3T1 0.*13 0.?79 0.34* 0.402 0.459 0.520 0.478 0.550 0.498 0.491 0.502 0.502 MOT MT. "Til *9.0 46.0 44.3 32.7 31.9 35.9 34.5 33-7 36.9 39.3 34.6 37.0 *5.9 *3.0 *4.9 *4.3 *3.5 T/8W 0.00365306 0.00*15247 0.00308262 0.00**6*83 0.00*35737 0.00*23398 0.00*1459* 0.00397626 0.00379*0* 0.00**27*8 0.00*2*855 0.00*108*1 0.00*6*052 0.00**6837 0.00596862 C.0C351099 0.00*29865 L/BWV 0.0390*06 0.0512391 0.0*69526 0.0*03976 0.0*197*9 0.0400836 0.0422609 0.037596* 0.0426556 0.0450636 0.04673*1 0.0*89730 0.0**9891 0.0*92326 0.0*72606 C.0*6**0? 0.0*73563 K/8H 0.9104020 0.0125217 0.0124896 0.0109786 0.0416301 0.01150*2 0.0109855 0.01020T7 0.01089*3 0.041679* 0.0450289 0.0429189 0.0449826 0.0145844 0.0109354 0.0121550 0.0145*02 0.162 1.705 0.443 0.037 0.390 0.080 101 101 101 37.6 0.00426 5.7 0.00068 101 101 0.04493 0.01177 0.00513 0.00108 101 101 r> oa zT1 o -t o Z> Ovj' Z--H1>I VN00Il cnr r> o7 ^ ^o o Tl s^j 2 N/ -< a) i> 00 iz ii n ii ii ii ii ii ii ii XI XI ii ii ii IX II II XX XX zz II IZ II ZZ IZ II IZ XI XI ZI 11 n XI XX zz IX XX zz ' II XX XI so M K Kn H H N (1 It H M H N K N N K N M N N M H H H M N Nn M ft N N N N H H N H mn m tmor I2S <25 <25 <25 <26 <26 <26 <26 <26 <28 <26 <28 <29 <29 <29 <29 WJ <31 <31 <3< <3< <34 <32 <32 <32 <32 <32 <33 <33 <33 533 <33 <3< <3< 53< <3< < < <35 6-4 tantlt ( (cant.) ta Inhalation talc taittlr Sta with taM im Rats 79-W2S nr W 1 0-45T 2 0.462 3 0.176 < 0.172 5 0.162 1 0.190 2 0.199 3 0.209 1 0.159 2 0.20< 3 0.476 < 0.165 5 0.470 4 0.254 2 0.233 3 0.161 < 0.469 5 0.167 1 0.452 2 0.17< 3 0.119 < 0.410 5 0.455 4 0.165 2 0.496 3 0.432 < 0.483 5 0.242 4 0.459 2 0.456 3 0.457 < 0.4<5 5 0.462 < 0.479 2 0.446 3 0.196 4 e.47< 5 0.167 6 0.406 4 0.167 2 0.444 3 0.454 ** 1.751 4.581 4.537 4.630 1.<33 1.9<0 4.938 1.8T6 1.561 2.210 2.216 4.775 2.081 2.014 2.157 4.830 4.56< 2.430 1.350 4.6<3 1.229 4.161 1.363 1.2<9 4.3<9 4.189 4. <55 4.453 4.335 4.2<9 4.281 4.207 4.619 4.562 1.483 4.267 4.67< 4.<T< 1.690 4.562 4. <18 1.373 tlKIS (9) 0.<57 0. <52 0.385 0.478 0.<3i 0.446 0.<7 0.457 0.398 0.504 0.533 Q.<35 0.437 0.500 0.579 C.508 0.534 0.495 0.456 0.510 0.372 0.385 0.481 0.391 0.406 0.359 0.428 0.334 0.362 0.387 0.367 0.359 o.io< 0.374 0.399 0.194 0.400 0.412 0.438 0.414 0.368 0.362 MOV 0T. (iJ 37.0 35.9 36.3 37.5 34.8 39.6 40.0 39.6 16.3 46.0 46.9 37.3 <3.2 <3.5 46.5 44.8 36.6 43.0 33.0 39.7 29.6 30.3 35.7 33.3 33.9 29.9 33.3 30.7 33.2 36.5 33.0 3<.0 35.6 34.8 3<.o 35.4 36.7 35.6 37.5 36.0 35.2 32.9 T/BW C.00424324 0.00451253 0.00484848 0.00458667 0.00<65517 0.00479798 0.ec<97500 0.00525126 0.00436017 0.004<3476 0.00379531 0.00442359 0.00393519 0.00577011 0.00501075 0.00433014 0.00437824 0.00434884 0.00460606 0.00438267 0.00399329 0.00363036 0.00434474 0.00555556 0.00578171 0.00441472 0.00549550 0.00690554 0.00476916 0.00432677 0.00475758 0.00467742 0.00455056 0.00514368 0.00429412 0.00559322 0.004741 0.00466480 0.00496000 0.00439474 0.00409091 0.00456967 L/BW K/BV 0.04732<3 0.0440390 0.0423416 0.0434667 0.0411782 0.0489699 0.0464500 0.0471859 0.043CC26 0.0460435 0.0472495 0.0475874 0.9481743 0.0462299 0.0463871 0.0437799 0.0405161 0.0495349 0.0409091 0.0443654 0.0412446 0.0363166 0.0381793 0.0375075 0.0397935 0.0397659 0.0436937 0.0375570 0.0402408 0.0342192 0.0388162 0.0389355 0.0454775 0.0448851 0.0436176 0.0357910 0.0456131 0.0M4732 0.0450667 0.0411053 0.0402841 0.0417325 0.0123514 0.0125905 0.0106061 0.012746T 0.0125862 0.0112626 0.0419750 0.0114824 0.0109642 0.0109565 0.0143646 0.0416622 0.0404457 0.0444943 0.0424516 0.0121534 0.0138342 0.0115416 0.0138482 0.0428463 0.0424632 0.0427063 0.0434734 0.0417447 0.0149764 0.0120067 0.0126529 0.0107818 0.0109036 0.0106027 0.0111242 0.0115806 . 0.0113483 0.0107471 0.0117353 0.0444299 0.0108992 0.0445004 0.0116800 0.0406947 0.0104545 0.0410030 sa IITTDI zz zz H *36 R *36 1Z M *36 ZZ H *36 ZZ N *38 ZZ . N *38 ZZ H *38 zzzz K *38 N *38 II H *38 II H *38 II R *39 XI M *39 II R *39 II II II M *39 H N 45*20* II r **0 II it MO II H *40 II It **0 XI R Ml II II H M 5M2*l II zz N 4*4 N *44 IZ H M2 II R M2 1z1z N M2 M M2 zzzz N n **2 **2 II zz zzzz zz IZ n n **2 **3 RH **3 RH 5M52l ZZ II R R ****<* IzIz HH *** M* 6-5 topmMs fi (cont.) ta Iriutitf* Fcailt fertility Stwty it* Iww 1 Mtt 19-HTi Ww 1 0.475 2 0.196 3 0.205 0.175 1 0.209 2 0.218 1* 0.203 0.197 5 0.498 6 0.223 7 0.214 4 0.1*2 2 0.436 1 * 0.155 0.420 5 0.1** 1 0.153 2 0.122 9 0.150 * 0.160 5 0.167 1 0.260 2 0.1*9 3 0.225 * 0.223 5 0.439 4 0.076 2 0.234 *3 0.47* 0.247 5 0.169 6 0.459 7 0.498 4 0.096' 2 0.416 *3 0.413 0.095 4 0.497 2 0.22T *3 5 0.23* 0.233 0.225 ItltR tst 1.6*1 *.856 1.966 1.89* 2.0*6 2.280 2.146 2.327 2.216 2-315 2.27* 1.312 1.412 4.6*3 1.276 4.298 4.523 1.691 1.695 1.797 1.689 1.835 4.469 2.470 2.172 1.361 4.856 *3*5 *.*18 4.9*0 1.592 4.709 4.04* 4.442 4.431 0.995 2.429 2.*40 2.533 2.26* 2.337 tratis ~Tir e.*35 0.504 0.519 C.*88 0.552 0.523 0.553 0.5T5 0.762 0.626 0.578 0.361 0.417 0.423 0.?57 0.361 0.?76 C.**6 0,431 0.458 0.447 0.504 0.401 0.556 0.563 0.362 0.556 0.4*5 0.382 0.436 0.503 0.427 0.493 0.330 0.2*0 0.369 0.3*8 0.58* 0.606 0.802 0.670 0.677 lew W. () 0.9 *3.6 *5.0 *1.9 *6.* 8.6 **.9 *7.3 *5.7 5C.0 *6.8 31.8 37.0 3.2 28.9 29.1 3*.8 37*9 36.6 38.2 37.0 39.9 *6.8 *6.9 32.0 29.0 39.1 39.0 32.5 37.8 *2.0 37.0 39.8 25.8 27.* 27.6 26.2 *2.4 *9.0 50.9 *T.5 *9.0 T/BW' 0.00*27873 C.004*9544 0.00*55556 0.00*17661 0.00*50*31 0.00**8560 0.00*52146 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*00211 0.00*09836 C.00*188*8 0.00*51351 0.0*151629 0.0031838 0.00*797* 0.0069687 0.00*7931 0.0019*37 0.0059234 0.0053538 0.0057*07 0.00*5000 0.00*2973 0.00*97*9 1.0037209 0.00*2336 0.00*09*2 0.0036260 0.00*6*62 0.00*6327 0.00*5972 0.00*9053 0.00*5911 l/BW *\ 0.0404222 0.0*25668 0.0**4333 0.0*52029 0.0*409*8 0.0*64136 0.0*77951 0.0*91966 0.0*85339 0.0*63000 0.0*85897 0.0*42579 0.0*27879 0.0*S386T 0.0**1522 0.0*460*8 0.0*3764* 0.0**617* 0.0*67415 0.0*70*19 0.0*56*86 C.0*59900 0.0318162 0.0*62687 41.0678750 0.0*693*0 0.0*75897 0.0*438*6 0.0375132 0.0*61905 0.0*30270 0.0*29397 0.0393023 0.0*05839 0.0*09783 0.03T9T74 0.0502423 0.0*94837 0.0*976*2 0.0*76632 0.0*76939 K/BH . 0.0406357 0.044*906 0.0445333 0.0416*68 0.0418966 0.0107643 0.0123163 0.0421564 0.01667*0 0.0125200 0.012350* 0.0443522 0.012636* 0.0116651 0.0123529 0.012*055 0.01060*6 0.0117676 0.0117760 0.0119895 0.0120811 0.0126316 0.008568* 0.0148550 0.0182187 0.012*628 0.01*2199 0.044*103 0.0147538 0.01453** 0.0419762 0.0445*05 0.0123669 0.0127907 0.008759* 0.0433696 0.043282* 0.0437736 0.01*0000 0.045756* 0.04*4053 0.0431463 oo 067789 C O N FID EN TIAL 4U^ Ih mm n ii ii ii 31 II ZI IX II XX XI XI II ZI IX II XI II XX IZ II IX II II II XI XX MEAN S.D. II SEX H N H M H K n H N H N H H H KH M n K M M H R M M H M mm S Hi S i Hi HT **7 HT **7 HT ht MB HI HI HI HI MB HI M9 *50 *50 *S0 JM *50 *50 6-6 . totonih 6 (cant.) to MiUtlm Feaatc Fertility Stair with Bcwmc to tots 7*-2S m inns "rar 6 0.199 4 0.479 2 0.171 2 0.248 * . 0.478 s 0.202 4 0.477 2 0.472 3 0.195 * 0.492 5 0.168 6 0.473 4 0.135 2 0.419 3 0.135 1 0.465 5 0.437 6 0.532 7 0.429 1 0.071 2 0.06S f 0.2*6 2 0.209 3 0.2*2 * 0.217 5 0.208 6 0.213 W 2.136 4.863 4.8*6 2. *32 4.732 2.437 2.206 4.734 2.210 4.925 4.996 4.765 4.26* 4.468 4.173 1.401 4.321 4.239 4.1*1 0.71* 0.789 2.276 2. *38 2.406 2.388 2.539 2.6M KIMC1S (it 0.565 0.513 0.*59 0.536 0.507 0.513 0.568 0.559 0.637 0.52* 0.*89 0.486 0.429 0.367 0.390 0.305 0.*31 0.395 0.376 0.272 0.250 0.596 0.608 0.5*6 0.525 0.598 0.702 0.178 1.711 0.467 0.051 0.435 0.101 111 110 111 boot in. T/BW L/BW- K/Blf *2.7 *3.0 39.9 *7.0 *0.3 **.4 *4.5 37.7 *3.7 *0.9 *5.0 38.6 30.9 30.0 26.9 32-4 34.1 29.0 29.7 *6.5 16.0 50.5 51.2 *6.* 50.0 *6.9 53.2 0.00*660* Q.C0M626 0.00*2657 0.00*6383 0.00**169 0.00*5805 0.00*2651 0.00*5623 0.00**622 0.00*69** 0.00*1776 0.00**619 0.00*3689 0.0039667 0.00*6713 0.0051*02 0.00**051 0.0183**8 0.00*3*3* 0.00*3030 0.00*0625 0.00*6713 0o..0o0os*0o6o2c0o 0.00*3*00 0.00**350 0.00*0038 0.050023* 0.0*33256 0.0*62657 0.0517**7 0.0*29777 0.0*6*580 0.0531566 0.0*59151 0.0505721 0.0*70660 0.0**3556 0.0*5725* 0.0*1553* 0.0389333 0.0*05882 0.03*2991 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*tT600 0.05*1365 0.053*586 0.0132319 0.0149302 0.0445038 0.014*0*3 0*0125806 0.0146327 0.0136867 0.04*8276 0.01*5767 0.0128147 0.0408667 0.0126*25 0.0438635 0.0122333 0.043*9*8 0.0419938 0.0138565 0.0136207 0.0126599 0.016*8*6 0.0456250 0.0448020 0.0448750 0.0412810 0.0105000 0.0127505 0.0431955 38.2 0.00470 0.04438 0.01226 7.2 0.00145 0.00479 0.00145 111 111 110 111 \/ 0 067790 C O N F IP F N T T A L 00 067791 CONFIDENTIAL sa HI 111 111 111 111 in 111 111 ZZI ZII 1ZZ ZZI ZZI ZIZ III ZZZ III ZII ZZI III ZIZ III III ZZZ ZII III ZIZ III ZII ZZI ZZZ III ZIZ III III III ZZZ ZZZ ZIZ IZZ ZZZ ZII HH M N R H N H N M K N * M N N H M H N H K H H N H N H N M N H II H M R H N R H H UTTER m 625 626 626 626 626 626 627 627 627 627 627 627 626 628 628 628 628 ' 630 630 630 631 631 634 632 632 632 632 632 633 633 633 638 634 638 638 635 635 635 635 6-7 t.* Militlo e tea*.) FckIc Fertility Stud* Hk kutM ta tits 79-2428 *_LJ9I* tt K~IMrEaTSr M-UrtNT". T/BH L/BW % K/BW f 6.63$ 0.768 0.253 2 1 2 0.055 C.131 0.175 0.323 1.964 2.036 0.235 0.545 0.5*2 13 C0..127023 0.2*4 2.010 0.676 0.567 51 2 0.462 0.122 0.123 1.367 1.260 1.167 0.522 0.3*5 O.310 3 4 0.424 0.127 1.093 1.276 0.305 0.356 5 0.122 1.040 0.326 6 1 0.137 0.428 1.134 0.922 0.346 0.297 2 0.150 1.146 0.232 3 0.488 1.199 0.339 * 0.129 1.097 C.33T 5 4 0.439 0.142 1.247 1.160 0.366 0.362 2 3 0.072 0.071 0.816 0.893 0.268 0.294 4 0.205 2.864 0.506 2 13 2 0.229 0.229 0.161 0.147 2.336 2.569 1.538 1.142 0.636 0.658 0.492 0.656 i 0.114 MU 4.182 1.781 0.357 0.505 5 0.216 1.843 0.482 0.467 1.982 0.507 0.196 2.322 0.536 0.498 2.405 0.515 0.182 2.418 0.526 0.207 1.623 0.425 0.187 1.661 0.449 0.453 1.875 0.805 0.485 1.770 0.899 0.477 1.872 0.513 0.221 2.281 0.590 0.199 1.832 0.850 l 0.200 0.218 2.185 2.006 0.528 0.525 16.0 13.5 34.0 4*.0 46.3 32.6 6.6 30.3 27.2 27.8 29.3 27.4 28.6 26.0 30.8 31.4 29.0 30.8 29.5 21.0 22.8 51.1 53.1 50.0 37.9 36.7 20.9 30.3 39.0 41.0 40.1 45.0 41.0 42.0 39.8 31.0 42.7 41.0 49.6 43.3 45.4 44.4 0.0023750 0.0029730 . 0.0053235 0.0040693 0.CO43376 0.0052761 0.0044262 0.0040264 0.00452206 0.00446043 0.00433447 0.00450105 C.00479021 0.00492308 O.OO407O13 0.00598726 0.00444828 0.00451299 0.00379661 0.00330275 0.00311404 0.00401174 0.00431262 0.00458000 0.00424802 0.00318804 0.00384083 0.00386423 0.00553046 0.00456098 0.00488778 0.00440000 0.00443902 0.00492857 0.00469849 0.00493548 0.00433255 0.00431707 0.00847368 0.00859588 0.00880529 0.00801982 0.0465000 0.0447563 0.C57T647 0.0435116 0.0050000 0.0616564 O.C51CtC9 C.0415342 0.0829064 0.0393165 0.0835495 0.0383764 0.0396503 0.0354615 0.0372078 0.0381847 0.0378276 0.0804870 0.0393220 0.0374312 0.0391667 0.0682192 0.0839925 0.0513800 0.0805805 0.031 MT2 0.0408997 0.0865013 0.0864872 0.0883415 0.0579052 0.0667778 0.0516098 0.0386829 0.0617337 0.0475W6 0.0844520 0.0856585 0.0864761 0.0423095 0.0872867 0.0451002 0.0453125 0.0154054 0.0160294 0.0126279 0.0144444 0.0173926 0.0142623 0.0113361 0.0413971 0.0109T12 0.0121502 0.0120295 0.0120979 0.0114231 0.0075325 0.0107962 0.0116207 0.0118031 0.0122712 0.0132410 0.0128947 0.0144677 0.0119774 0.0131600 0.0129815 0.0151499 0.0123529 0.0131854 0.0123590 0.0123659 0.0133666 0.0114448 0.0128293 0.0401190 0.0412818 0.0130685 0.0416862 0.0125122 0.0419833 O.C103926 0.0415819 0.0117793 DO 0 6 7 7 9 2 C O N FID EN T! sa HI n III H III II III H ZII H III K III M III N III M III M ZII H III N III H III H III H III H III n III It III H III H III N m H H in n in N hi n ZII H III 11 nz N hi It ZII It ZIZ II ZII II III H III H III H III N 111 H III N 111 M mN XXI n umi 635 636 636 636 637 637 637 637 637 639 639 639 639 639 640 640 640 640 640 641 641 83 641 641 642 642 642 643 643 643 643 643 644 644 644 644 644 645 81 645 6-8 . ****** * An IAmIiUm Fmlt Fertility St4y fHli Aemem tn tots 79.2425 rotes Tin 5 0.196 1 0.247 2 0.346 3 0.304 1 0.172 2 0.147 3 0.156 6 0.453 5 0.162 1 0.466 2 0.215 ;3 0.461 nu 1 0.446 2 0.460 1 0.209 0.490 51 2 0.175 0.433 0.437 3 4 0.140 O.434 5 0.126 6 0.444 4 0.230 2 0.212 3 0.235 1 0.201 2 0.170 3 0.173 4 0.470 5 0.4T? 4 0.160 2 0.44$ 3 0.412 4 0.140 5 0.16$ 1 0.461 2 8.18 3 4 0.419 IfVOt ~W 1.909 1.964 2.704 2.497 9.730 4.667 4.632 1.825 1.7T3 2.444 2.350 4.926 4.189 2.009 4.784 1.717 4.726 1.859 1.734 4.465 4.157 1.502 1.240 1.159 1.082 2.307 1.812 2.183 4.650 2.402 2.426 4.945 1.945 4.9*5 4.525 4.062 4.340 4.636 4.628 4.596 4.272 4.475 KlWglS (9> 0.540 0.540 0.692 0.690 0.476 0.444 0.484 0.496 0.494 0.546 0.574 0.516 0.546 0.521 0.457 0.456 0.465 0.506 0.480 0.374 0.384 0.404 0.377 0.350 0.341 0.574 0.492 0.598 0.561 0.597 0.506 0.526 0.557 0.529 0.433 0.365 0.419 0.452 0.542 0.446 0.493 0.378 MOTWT. (9) 44.9 48.6 59.6 56.4 39.1 37.7 39.9 41.9 40.9 41.6 47.8 40.2 44.7 40.9 40.0 36.0 37.0 <1.9 39.9 29.4 26.6 34.2 31.4 29.6 26.8 47.6 40.2 46.2 44.9 44.0 42.6 41.4 40.9 42.1 36.6 28.0 30.2 36-T :! 26.6 T/BH 0.00472554 0.00506148 0.00533557 0.00539007 0.00439696 0.00389920 0.00390977 0.00365455 0.00396068 0.00451923 0.00449791 0.00400496 0.00387025 0.00405666 0.00365000 0.00421053 0.00564865 0.004534(1 0.00438596 0.00452361 0.00475694 C. 00409357 0.00426752 0.00425676 0.00414179 0.00484172 0.00527363 0.00467552 0.00479714 0.00366364 0.00406103 0.00410626 0.00432763 0.00427553 0.00394022 0.00400000 0.00463576 0.00523610 0.00438692 0.00614706 0.00371359 0.00413194 L/BW 0.0455609 0.0402459 0.0453691 0.0442730 0.0442455 0.0442475 0.0459146 0.0435561 0.0433496 0.0507452 0.0491632 0.0479104 0.0265996 0.0491496 0.0445250 0.0454842 0.0467027 0.0443675 0.0434586 0.0403061 0.0401736 0.0439181 0.0394904 0.0391554 0.040373* 0.0462636 0.0450746 0.0452905 9.0444527 0.047T72T 0.0499061 0.0469807 0.0475550 0.0461995 0.0414402 0.03T9286 0.0443709 0.0519365 0.0443597 0.0470000 0.0300736 0.0407966 K/BW 0.0126676 0.0140656 0.0116107 0.0122340 0.0422251 0.0116976 0.0120551 0.0148654 0.0120782 0.0131731 0.0120064 0.0128856 0.0122595 0.0127384 0.0114250 0.0120000 0.0132162 0.0120286 0.0120301 0.0126190 0.0132292 0.0116129 0.0120064 0.0118243 0.012T239 0.0120064 0.0122386 0.0124066 0.0133690 0.0135662 0.0419249 0.0127536 0.0436466 0.0425653 0.0447663 o.ot3035T 9.0436742 0.9443492 o.ot39540 0.0422944 9.0449660 0.0434250 MV sn IXZ III III III III III III III III III III III 1X1 III III III III III III III III III III III HEM $.0. n K N N N M N M N II n H H N N M H M N K M H N -N N UTTER ns 6*6 6*6 6n*s6 6*7 6*7 6*7 6*7 6*7 6*6 6*6 6*6 6*9 6*9 6*9 6*9 6*9 6*9 659 659 659 659 659 6-9 pw<l 6 (coot.) All ItfuUttM Fm1* Fertility StMy irttk Imm hi Rats n-tm W TESTES (*) 1 9.169 2 9.169 3 0.465 * 0.181 5 0.4*1 1 9.455 2 9.467 3 0.169 * 0.46* 5 0.4*3 1 0.190 2 0.2*7 3 0.233 1 0.186 2 0.472 3 0.165 * 0.472 5 0.179 6 0.200 1 0.174 2 0.468 3 0.476 * 9.427 5 0.204 0.169 0.043 108 unto uT 4.775 4.692 4.492 4.266 4.46$ 4.739 4.920 4.965 2.15T 4.849 2. *9* 2.*77 2. 3*T 4.769 4.662 4.719 4.606 4.8*1 2.458 4.599 2.933 4.619 2.420 4.769 UttttTS Ttr' 0.*97 0.459 0.3*6 0.383 0.356 9.427 0.483 0.495 0.529 0.415 0.676 0.570 0.634 0.463 0.467 0.417 0.468 0.4*6 0.565 0.432 0.461 0.462 0.519 0.475 1.893 0.469 0.485 0.099 108 108 ROOT vt. to) *2.7 37.* 33.6 33.9 28.9 35.5 *0.2 37.5 *0.5 35. t *7.6 *9.* 48.8 36.2 38.9 37.9 39.9 36.9 *2.0 36.0 *1.9 38.9 *0.2 *0.9 T/BW 0.00*245*6 9.00*27607 0.00*91974 0.00533923 0.00487889 0.09*36629 9.00*45*23 0.00*50667 0.00*9*936 0.00*97*07 0.00399460 0.00590000 0.00*77*59 0.00*66914 0.00**2159 0.00466127 0.00*31078 0.0046045* 0.00*76199 0.00*75000 0.00*09756 0.00*52**2 9.00315920 0.00502509 L/6W 9.9*15691 9.9*52406 0.935*762 0.03799*1 9.0*03*1* 0.9*69659 0.0*77612 0.052*000 0.9532593 9.051623* 0.0523950 0.0501417 0.0*809*3 0.0*63089 0.0*78663 0.0*53562 0.0*52632 0.0*73265 0.9513810 0.0**4167 0.0*95654 0.0*67609 0.9527363 0.0**2250 */bu 9.0146393 0.0422727 0.0102976 0.0442979 0.0123163 0.0*20262 0.0*201*9 0.0132000 0.0130647 0.041823* 0.04*2*37 0.0415365 0.0129946 0.0126**0 0.0120051 0.0410026 0.0147293 0.944*653 0.013*52* 0.0120000 0.01IT31T 0.9116766 0.9126066 0.0418750 38.0 O.OOM3 7.7 0.00059 108 108 0.04435 0.01241 0.00865 0.00125 108 108 * t oo o *< N zn o o>T-1< o N1 2M H vO ^ jJ 4^ OO G-10 (cent.) M ftMte Fertility St# wftk Omim m liti N4US SEX LITTER no TESTES TiT W EBB Wgt (Vi ifi T/BW~ L/BVl K/BW IV zr IV IT IV IV IV IV IV IV IV IV M 625 M <25 M 625 H 625 H 626 K 826 M 626 N 627 M 827 N 827 N 827 H 627 1 0.463 1.559 0.474 2 0.166 *.379 0.419 3 0.442 *.639 0.466 4 0.17* 4.617 0.453 1 0.174 1.476 0.409 2 0.452 4.713 0.445 3 0.465 1.93* O.499 1 0.212 2.132 0.509 2 0.191 4.604 0.422 3 0.103 4.667 0.464 4 0.203 2.067 0.492 5 0.490 1.819 0.475 36.4 33.0 35.3 36.4 35.6 36. T 42.5 44.7 36.7 3T.5 41.5 39.9 0.00651534 0.00569697 0.00402366 0.00469760 0.00486034 0.00414469 0.00435294 0.00506393 0.00520436 0.00466000 0.00489*57 0.00476190 0.043*656 0.0417879 0.0464306 0.0499176 0.0412291 0.0466757 0.0455059 0.0511271 0.0437057 0.0444533 0.0496072 0.0455690 0.0434302 0.0426970 0.0432014 0.042M54 0.0114246 0.0121253 0.0117412 0.0122062 0.0114906 0.0122933 0.0116554 0.0119040 If IV H 626 H 626 1 0.(26 4.415 0.369 2 0.454 4.773 0.444 30.6 36.9 0.00409094 0.00417344 0.0459416 0.0480468 0.0126299 0.0120325 IT IV H 626 H 630 3 4 0.442 0.465 1.071 4.622 0.333 0.503 25.9 39.6 0.00546263 0.00467172 0.0443514 0.0460101 0.0128571 0.0127020 IV H 830 2 0.195 4.445 0.534 36.0 0.00513156 0.0360263 0.0140526 IT M 630 3 0.2fe 1.361 0.449 35.6 0.00796069 0.0360166 0.0125419 IV IT XV IV M JJ1 M 63* K 63* H 631 1 0.127 4.236 0.342 2 0.4*6 4.096 0.295 3 4 0.417 0.155 1.347 1.732 0.353 0.429 26.1 26.* 30.0 34.0 0.00451957 0.00444444 0.00390000 0.00455662 0.0439656 0.0449923 0.0449000 0.0509412 0.0121708 0.0113027 0.0117667 0.0126176 IT IT XV IT IV IT XV IT IV IT IT XT M 634 M 63* H 635 H 835 H 635 H 635 H 835 H 837 H n 522 836 K 636 N 838 5 0.130 1.60? 0.395 ( 0.401 4.417 * 0.442 1.637 0.455 2 0.449 1.903 0.462 3 0.138 4.387 0.402 4 0.444 1.696 0.407 5 0.157 4.600 0.426 * 0.402 2.495 0.555 2 0.202 2.127 0.561 1 0.449 4.645 0.528 2 0.16? 4.967 0.556 3 0.433 4.761 0.469 32.1 25.0 35.0 34.0 30.6 33.5 35.4 41.6 43.0 36.0 42.0 39.0 0.00404984 0.00404000 0.004057*4 0.00436235 0.00446052 0.00429851 0.00447293 0.00435407 0.00469767 0.00392405 0.00397619 0.00341026 0.0500623 0.0446600 0.0467T14 0.0559706 0.0450325 0.0506666 0.05*2621 0.0596690 0.0494651 0.0465526 0.0473095 0.0451536 0.0123053 0.0130000 0.0135682 0.0130519 0.0424493 0.0*24366 0.0132775 0.0135416 0.0*36947 0.0132657 0.0120256 IT IT IT IT IT XV XV XT N M 13 K M 8 H M 522 839 H H !8 4 0.154 4.763 0.461 5 0.4*9 1.693 0.ST9 1 0.133 0.345 2 0.435 0.412 3 4 0.444 0.444 1.053 4.402 0.393 0.328 5 0.106 1.2*7 0.353 * 0.456 4.476 0.367 36.1 43.2 33.0 33.4 31.9 26.9 29.9 20.0 0.00404499 0.00344907 0.00403030 0.00404192 0.00347962 0.00364063 0.00364204 0.00557443 0.0462730 0.0436194 0.0394646 0.0439620 0.0330094 0.0406997 0.0017057 0.04207*4 0.0*20997 0.0134028 0.0104545 0.0123353 0.0*23197 6.01*3495 0.0**6060 0.013*07* CM* sot UTIOt p) oD 2^ n it IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT IT M MO N MO K MO N MO Nn 640 Ml H 844 H 844 * Ml M M2 H M2 K M2 N M M3 K M 584S42 H 844 H M4 M N 846 M6 N 846 N 846 N M7 tt M mt 847 M 847 N 847 H 848 K M8 H 846 II M6 M M8 K M6 H 849 H M9 H 49 H M9 oS ^ SJ ~2i sj vO MEM nS.O. I> VI 6-11 AppcatfU C (cont.) M tNMlatlw FcmIc fertility Stdr wit* Nww Ik Rats -Ha Wnr 2 0.113 3 0.139 4 0.120 5 0.429 4 0.138 2 0.443 3 0.135 4 0.152 5 0.080 0.4(4 2 0.094 3 0.430 0.245 2 0.484 3 0.176 1 0.138 2 0.468 3 0.431 1 0.083 2 0.094 3 0.127 4 0.095 1 0.125 2 0.159 3 0.159 4 0.428 5 0.433 1 C.158 2 0.106 3 0.109 4 O.O94 5 0.103 6 0.424 1 0.20T 2 0.268 3 0.278 4 0.268 W 4.082 4.431 1.401 4.407 1.086 4.280 4.266 4.245 4.020 4.470 0.969 1.069 2.377 2.423 2.173 1.435 4.127 1.037 1.000 1.357 1.399 1.161 1.413 4.144 4.492 4.662 4.657 1.839 4.444 0.745 1.425 !:SS 4.988 2.494 2.366 2.387 0.151 1.510 0.042 0.406 79 79 MONETS () 0.357 0.394 0.330 0.248 O.35* 0.407 0.396 0.384 0.345 0.427 0.366 0.359 0.607 0.517 0.557 0.307 0.361 0.335 0.346 0.419 0.433 0.378 0.355 0.324 0.328 S:8l 0.608 0.326 0.299 im0.333 0.557 0.588 0.632 0.593 8007 trr. <iT 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 34.9 29.4 30.7 27.9 30.0 33.7 30.9 43.4 28.3 24.8 28.8 25.1 31.4 42.7 45.3 48.5 46.9 T/BH 0.00118549 0.00501805 0.00447761 0.00476015 0.004T7S09 0.00440000 0.00410334 0.00475000 0.00277778 0.00466667 0.00376000 0.00410095 0.00450734 0.00402222 0.00391411 0.00470990 0.00569492 0.00464539 0.00319234 0.00309214 0.00398419 0.00323129 0.00407166 0.00569892. 0.00530000 0.00379822 0.00430424 0.00364055 0.00374558 0.00439546 0.00326389 0.00410359 O.OO394904 0.0M847T8 0.0059*611 0.00573196 0.0056T464 L/BW 0.0400^41 0.0408303 0.0410821 0.0408487 0.0375779 0.0393846 o.0386802 0.0389062 0.0356167 0.0426087 0.0387600 0.0337224 0.0498323 0.0471778 0.0482889 0.0387372 0.0382034 0.0367730 0.0384615 0.0446382 0.0438558 0.0394898 0.0460261 0.0410036 0.0397333 0.0493175 0.0536266 0.0423733 0.0404260 0.0300403 0.0390625 0.0413944 0.0346497 0.0465574. 0.0484327 0.0487835 0.0508955 K/BW 0.0132222 0.0161455 0.0123434 0.0091543 0.0423183 0.0425234 0.0420365 0.0149062 0.0419792 0.0423768 0.0147200 0.0113249 0.0427254 0.0444889 0.0423778 0.0104778 0.0122373 0.0148794 0.0133077 0.0437829 0.0135737 0.0128574 0.0115635 0.0116129 0.0109333 0.0116617 0.013*392 0.0140092 0.0145194 0.0420565 0.0445625 0.0128685 0.0410191 0.0430445 0.042900* 0.0130309 0.0426439 0.424 0.068 78 94.0 0.00442 6.2 0.00078 79 79 0.04380 0.00536 79 0.01239 0.00093 78 M. i! \i 1 trt \ DO 0 8 7 7 9 ft C O N FID EN TIAL sci tint* H 1026 It 1026 H 1026 H 1026 II 1027 K 1027 M 1027 H 1026 M 4026 h 1026 K 4026 K 4026 M 4026 M 4029 M 4029 M 4029 n 4029 H 4029 N 1032 If 4032 Int 4032 1032 K 4032 1033 " 1033 It 4033 K 1033 H 1033 N 403% H 403% K 103% N 403% * 1035 H 4035 * 1035 H 1035 * 1035 II 1036 If 1036 H 1036 If 1036 6--12 Appcnft* C (cant.) Iihititln Fmilc FerlflHr Stwty wttk tam to tuts I*-H TCSICS 73T LIVER "nr 4 0.133 0.999 2 0.097 0.614 3 0.096 0.942 4 0.403 0.736 4 0.14$ 2.001 2 0.450 1.999 3 0.149 4.667 4 0.422 0.975 2 0.400 0.855 3 0.446 0.732 4 0.136 0.855 5 0.436 4.407 6 0.106 0.755 4 0.432 4.447 2 0.443 1.479 3 0.423 0.957 4 0.145 1.247 S 0.449 1.253 4 0.441 4.278 2 0.422 4.228 3 0.154 4.539 4 0.442 4.337 5 0.126 4.288 4 0.444 4.794 2 0.098 4.766 3 0.141 4.819 4 0.148 ' 1.745 5 0.129 1.610 4 0.124 4.053 2 0.456 4.618 3 0.129 1.560 4 0.120 1.288 1 0.123 1.281 2 0.4*8 1.733 3 0.126 1.628 4 0.421 4.456 5 0.1*5 1.664 1 0.136 1.236 2 0.13* 1.302 3 0.165 1.206 4 0.191 4.315 moors ~nr 0.269 0.279 0.331 0.265 0.510 0.536 0.480 0.267 0.266 0.275 0.328 0.351 0.247 0.347 0.316 0.318 0.373 0.3*0 *. 357 0.350 0.435 0.392 *353 0.(49 0.505 0.4JI 0.446 0.420 WS 0.444 0.387 0.415 .%53 0.446 *.361 C.447 0.402 0.445 0.274 0.1*0 MSV HI. "i*r~ 26.9 23.0 25.1 23.0 %4.8 39.9 37.9 25.6 22.9 2%.T 28.3 23.0 20.0 27.7 2T.9 25.0 28.0 30.9 32.9 30.9 36.7 3%.0 34.5 %0.9 36.2 36.7 39.9 33.6 31.% 35.0 36.7 31.7 32.6 37.7 35.7 29.7 %7.2 32.0 31.9 29.9 29.8 T/BW 0.00*9**24 0.00421739 0.00362%70 0.00447826 0.00356459 0.00375940 0.00393140 0.00476562 0.00436661 0.00477733 0.0048T633 0.00600000 0.00530000 0.0047653% 0.00512545 0.00492000 0.00517657 0.00482201 0.00426574 0.00394622 0.00441444 0.0041764? 0.00400000 0.00352076 0.00270718 0.00384196 0.00370927 0.00363929 c.00394904 0.0044571% 0.00351499 0.00378549 0.00377301 0.00392573 0.00356543 0.00407407 0.00307203 0.00*31250 0.00420063 0.00551639 C.00439597 L/Bl^ 0.0371375 0.0353913 0.0375299 0.0320000 0.0478708 0.0504003 0.0439842 0.0360859 0.0373362 0.0296356 0.0302120 0.0461304 0.0377500 0.0414079 00..00432622586010 0.044535T 0.0405502 0.0366450 0.0397444 0.0419346 0.0393235 0.0406669 0.0436634 0.0487645 0.0495640 0.0437343 0.0479167 0.0335350 0.0462286 0.0430518 0.0406309 0.0392945 0.0459662 0.0456022 0.0369899 0.0352542 0.0386875 0.0408150 0.04033*4 0.0441275 K/BW 0.0400000 0.0424304 0.0131873 00..00112223091103 0.0434336 0.0426649 0.0142409 0.0447031 0.0141336 0.0415901 0.0452609 0.0123500 0.0125274 0.0413262 0.0127200 0.0133214 0.0140032 0.0108541 0.0113269 0.0110529 0.011529% 0.0112063 0.0109760 0.0439503 0.0117439 0.0141779 0.0125000 0.0107643 00..00142204956714 0.0122062 0.01273** 0.0120T59 0.0424930 O.C126263 0.0094703 0.0125625 0.0139496 0.0125064 0.0046960 on sa Nn K M H K MM NH M n H N It M n H K N NH H M N H HN M N MM NN N n HH H n nM iiTin 1036 <037 1037 <037 <037 <037 <030 <036 <030 <038 <038 <039 <0J9 <039 <019 <040 <040 <040 <040 <040 <042 <042 <042 <043 <043 <043 <043 <043 <044 <044 <044 <044 <044 1044 <045 1045 4045 <045 <045 <048 6-13 Appndli 6 (coat.) An Inhalation fmlt Fertility Stnly with BeniMa In Utt 79*2425 TTESTrE~S <5 0.1T5 0.<4< 2 0.170 3 0.474 4 0.184 5 0.465 < 0.165 2 0.167 1 0.136 0.159 51 0.186 0.196 2 0.156 3 0.431 4 4 0.439 0.220 2 0.202 3 0.203 4 0.182 5 0.235 < 0.157 2 0.457 3 0.159 < 0.422 2 0.429 3 0.422 4 0.127 5 0.444 < 2 Q.469 0.474 l 0.439 0.457 0.484 0.153 0.4T3 0.166 0.482 0.470 0.461 0.148 2 0.454 TLivieTn 4.132 4.632 2.059 4.611 4.444 1.831 4.420 4.360 4.322 4.693 4.536 <1.359*39 4.074 1.252 1.854 <-905 1.815 4.674 2.026 1.705 4.571 1.313 4.227 4.284 4.446 1.262 1.186 1.595 1.779 1-313 1.650 1.666 4.628 4.138 1.644 4.T44 4.637 4.653 4.542 4.087 4.446 MONETS (it 0.407 Q.4t2 0.496 0.451 0.398 0.735 0.426 0.418 0.390 0.451 0.439 0.317 0.434 0.363 0.364 0.503 0.512 0.505 0.485 0.511 0.470 O.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 0.4T5 0.507 0.476 0.467 0.366 0.393 "MOTTirV~T. 28.9 32.2 39.3 36.0 34.7 37.5 31.9 31.9 30.2 34.5 36.4 36.0 37.9 33.2 31.3 43.0 44.6 41.9 37.1 42.9 38.2 34.6 33-8 30.8 30.4 28.0 30.8 29.9 35.6 38.7 30.3 35.3 36.9 36.0 34.6 37.4 37.i8 38.0 37.0 3&.< 27.9 29.9 T/BW 0.0019T924 0.00437088 0.00432570 O.OC483333 0.00521614 0.00440000 0.00517241 0.005235K 0.00450334 0.00460870 0.00515235 0.00544444 0.00441609 0.00394578 0.00444089 C.00514628 0.00485577 0.00484407 0.00490566 0.00547766 0.00410995 0.0045375? 0.00470414 0.00396104 0.00424342 0.00435714 0.00442338 0.00374237 0.00474719 0.00449612 0.00458746 0.00444759 0.00482385 0.00541476 0.00484477 0.00466307 0.00439153 0.00478947 0.00459459 0.00445983 0.00530466 0.00505047 L/BW V 0.0391696 0.0506632 0.0523919 0.0447500 0.0446138 0.048826? 0.0445141 0.0426332 0.0437748 0.0490725 0.0425485 0.0388611 0.0407424 0.0323494 0.0400000 0.0434463 0.0457933 0.0433474 0.0451243 0.0472261 0.0446335 0.0454046 0.0388462 0.0398377 0.0421382 0.0398574 0.0409740 0.0396656 0.0448034 0.0459690 0.0433333 0.0467422 0.0454491 0.0478824 0.036042? 0.0443427 0.0461376 0.0430769 0.0466757 0.042744? 0.0389606 0.0383278 K/BW 0.0140830 0.0127950 0.0126209 0.0125276 0.0114697 0.0196000 0.0133542 0.0131034 0.0131786 0.0130T25 0.0121607 0.00880S6 0.0143720 0.0109337 0.011629* 0.0146977 0.012307? 0.0120525 0.0130726 0.0149144 0.042303T 0.0425434 0.0417456 0.0149156 0.0144445 0.0430357 0.0129545 0.0143376 0.0114886 0.0128424 0.0431353 0.0422380 0.0126287 0.0129706 0.0124367 0.0120755 0.0125661 0.0433424 0.0428649 0.0429363 0.0434183 0.0134438 oo 067797 c o n f id e n t tai. CJI 6-14 MUM!* 0 (cent.) M IMulltlw FWit Fertility ftady wIUOmim la Rats 79-2425 SO utm wr W IIKI rt MONETS MOT NT. "fir () T/BW L/BK. K/BW HN N N N N KK NM M M H MII 0I( 1046 4046 4040 4040 4040 1049 4049 1059 4049 1049 4049 4050 1050 4050 3 0.444 4.429 0.394 4 0.443 4.066 0.366 5 0.4 30 0.953 0.320 4 0.257 4.02 0.570 2 0.155 4.060 0.540 3 0.224 4.625 0.536 4 0.222 2-074 0.557 2 0.202 2.059 0.546 3 0.194 4 0.107 2.102 2.442 0.590 0.555 5 0.197 4.902 0.533 6 0.473 2.039 0.529 4 0.454 4.405 0.443 2 0.150 3 0.449 4.495 1.294 0.436 0. 391 30.9 29.3 29.6 42.0 42.7 45.5 41.4 43.0 42.8 45.2 42.6 35.6 37.0 31.7 0.00466019 0.00406055 0.00466216 0.00614905 0.00362996 0.00485744 0.00483660 0.00491464 0.00444186 0.00436916 0.00435644 0.00404206 0.00424157 0.00427027 0.00470032 0.0365372 0.0363623 0.0321959 0.0452857 0.0440281 0.0357143 0.0451852 0.0500973 0.0468037 0.0500467 0.0420796 0.0476402 C.0394663 0.0404054 0.0400202 0.0427508 0.0132423 0.0410811 0.0135744 0.0126337 0.014T802 0.0121351 0.0132847 0.0439070 0.0129673 0.0417920 0.0123598 0.0124438 0.0417030 0.0123344 4050 4 0.444 4.642 0.452 37.0 0.00369189 0.0435676 0.0422162 4050 5 0.406 1.367 0.416 32.5 0.00326154 0.0420615 0.0128000 H 1050 6 0.155 4.542 0.453 35.4 0.00437853 . 0.042T419 0.0427966 iiao S.D. N 0.151 1.453 0.419 0.031 0.347 0.086 101 101 101 34.1 5.7 01 0.00446 0.00060 101 0.04216 0.00470 101 0.01229 0.00142 101 DO 0 6 7 7 9 8 CONFTDFNTTi 3> 6-1S AppandU G (cant.) An Inhalation Famila Fortuity Study with lomonc In Riti 79-I4JS GROUP SEX LITTER PUP LjPER Kl^gYS 40^ 7T, L/BW K/BW 1 ~~r~--------- jn------------ 3 i .1 It "eTTiT ------1771------ C .0413444 1.it Mill 1 r 104 4 1*013 0.44* 3* .0 0.0414030 *110110 1 F ffC i------- r.yfi-- C.lll It .4 0.0444740 --pnifli 1 * ; s>t 1.000 0.414 . l*.t 0.0*41410 i.eiiiiio 1 "T 111 ~i--ran "lint 7171 C *0404409 --177114131 1 f tt * 1*003 0*401 30.1 ' 4.0144001 4.0110444 1 i lit 1*30* 0.144 14.4 0*011000* vt ....' w IM l*OOC 10 f.4jl 0.401 0.0*0 14.0 34*0 0.04*4011 0*0110004 t.tliooSl- 4*01114*1 I t It* i.tot 0.410 1**1 ' 0.0440104 0*0110000 4 9 117 1 1.411' 49.1 1.1411431' --1.41 user l 0 11* 1 F It* 1 1*014 * 1*400 4tf o.4il lf.0 lf* 0.000(414 .(Oft?* _ 0.0113441 i t F 11* F in 10 I.OOC 1------- j.4i* 0.401 l.Stf IT.t ' " 34 .4 0*4(0*000 1.74*0400 1.0| 10001 i.4iu3r l f III C 1*311 0.1*4 41.f .0(4140 0*0110414 i I1 HI 7 1*040 0*414 ------ 7171------ i.niinr --iiii cur l * 110 * 1.141 ItUT 40.4 .141**1 0*0110004 l 9 *10 1 1*030 T.*iir out 4.#4(0*14 --irruiWi i F III 10 0.004 0.400 14.1 (.0(41401 0.010104* i 0 til t 1.440 C .444 il*4 (414001 *.4110*44 i * III * t.OI* 0*443 14.0 0.044030* 0.0140000 i f 114............ 1 O.TIT 4 3f 9 44*0 VtBiimv ~ ~4.4io4Ui i F it 4 1.001 9ft 11.4 4* 01 *1034 *m 10 1*000 i*ni 11*0 414100 iTfflitto I f no t f 110 1 l.*l< ( 1*000 0.4*7 0.4*1 14.4 34.0 0.041100# *4(1744 4* 4130004 iTifiooof l f 110 1 1.411 0.401 34.4 0.0411140 4. 013001* i 9 130 T5 i .411 TT79T1 nil (.1(01141 --1.411401-------- i f III i F 131 < 1.01* * 1**44 0.4*1 14.4 0.0400404 *110103 4.4*0 ------ 3*71------ ~f7 olioiil --4.va4n-- i F III 4 1*700 0*000 10.0 ' 0.0440*04 0*01 * i F in i niii in'll-- "577* 0.4179347 1.0174111 i F 111 10 1*011 0.440 34.4 o. 04*1003 0*01 tom 1 F 111 4 1.04* aii-- 7777 .041(101 01 IV1IV 1 F 111 1 1*700 0*441 34*4 0.04(4141 #11909? i # 131 "1 rati 0.104 9777 TTii'iVSi-------k'Hmn-- I F 133 0 1*0*1 0.444 17.0 (.OCOOOfC 4. 0144400 i P ' ITJ------------- 7* 171T* T.OI------ 41.0 0.4411414 Kimill-------- l F 13* * 0*300 0*400 44*0 0.0030110 '* 0130004 1 9 11V " 4 0*404 Tf.lo * 41*1 i.mmr"THIIIW-------- l f 130 0 1*100 4.(43 41.0 0.4110010 *130414 t F ~TSi 74 1.041'' '.*----- --i;i--"l.'MHiil-------77777(979---------- i f in t 1.43* 0.43* 34*1 0.0414101 0.010*00* t r ilo 1 i .17T .m-- o**l -~o. 73 i<331------- 7*Ti'49fl--------- l lie V 1.341 0*431 34.1 011000V 0.0110001 1 -l 1 lie "1 1 .IK i.in-- '11*4 *431471 "4:4i inn--------- 1 S3T 4 1*704 0.4*4 14.7 0.04**000 4*4100*00 i 13* ~i------- nm r.n*---- 4171------- "Miiuir.. l i f - 1J3)*f - 4 1.0*0 0.410 --r.7f--------- 7.TTI 10.4 0.04410*1 0.0100000 " *971------- _.*Vi76r-'T.4f3im t F 130 * 1 *000 4.414 31.4 C.C40110C *0100010 I T1 191 l.rif 1*431 '31.< 1 i.imn i-- 1*4114171":-- I F ' 130 0 1.004 0.1*4 '34.0 O.04IOOOI 0*0110104 1 "# ' ill ' ii i.4*r l.ili it'.t 0.4411141 4. 4l'i444? DO 06.7799 OONFIOFNTTAL YZ0014454 6-16 Appendix G (eont.) An inhalation Fonalt Fertility Study with Banian* in Rats 79-242S GROUP SEX UTTER Pi* LjgR Xl^gTS IQD^tfT. L/BW K/BW I 9 an 7 l*4< 41 1 9 t 1.434 440 1 p *s* 4 1.414 o.ita I r iia It 1.433 3.1*3 --r~ # iao C 1.477 rm 9 / let l 1.434 ? i r tat c 1.440 0.414 i p tat 4 1.707 .414 i p *ao --t,--------------rr --------- <m41------- It 1.477 < nan* t.447 0.443 7-- --nm r r tat < i fin _ (.Ml ip --tj--------------tT" tat at iat 4 t.ott It I.4t4 < 1 .443 (10 . . --(!------------- rr--------- tax ns-- ------7| 1.043 1.017 .400 4.440 i p ax 4 1.407 444 i r <43 It <.44t 0.431 ip i ----------- T" 44 4 1 1.034 __ .334 t.044 1(4 ip --1--------------F~--------- <r4n4-----------7f-- 0.000 i.oH <41 ----- riil-- i p a? f 1**07 *.3*7 i p <47 T.*44 *347 i p ar 7 1*117 C.33C i ff 147 I.4CC *4<0 --ji-- 47 4 I.333 p --------- |TJ------ ' ' Yl -- 1.310 0.7(7 C.40( i P 44 1.414 .313 i r 44 7 1.347 O.llt t 9 <44 3.010 0.473 i p <44 4 1.317 e.3tt i p 44 It l.OOt 0.4(1 i p 10 itiii *. i 1 1" --~p < < 7 1.471 t 1.430 430 *470 i p < 4 t.130 *( i p lit It i.i *4 41.4 * 30.7 l*j 1771 .4 33.7 33.4 41.4 33.1 la .1 31.0 37.1 34.3 3t .4 30.0 30.4 37.7 <> 34.4 14.4 43.0 31.4 31.1 30.0 34.3 37.4 im 31.0 <0.7 37.4 31.3 37.0 44*0 34.0 4( .0 40.7 40*7 .4773 .44IM43 .(31071 !*! 0.0473344 .0*43013 ' 0.0434104 O.MMtPt 0.04710X0 0.0tl477X i.iaiilii 0.030040 40UX 0.0413407 *3374 Mllllll .((030 0414040 433770 343403 0.037300J --rririinr 000740 3(7034 0174144 .04(3740 43X0t 0*43103 O.tMOOOO 0.443*440 (Of 037 .4414434 0(11X01 4144X4 407737 .413144 0.04(7177 0.0404004 0.0130078 Jtimw... 0.0143411 .ououx *101031.. 0*0133044 0.0133304 0*0180010 } 0.0137400 tfyiifwt____ .HOMO 4* 1111411 t.0117773 '.oiioioi 0.011044X o. limit l.itr<vr 0*0101017 _ #01 00100 *0110104 0*0184731 4* oixllil 0.0103101 0.0110(74 0. 0137(07 0.0I34MX ?*fi?*i?? 0.0I844O8 O.OIflflf 0. 01 04300 0.013331 0.01 (3444 MEAN 1.C90 0.444 36.3 0.04626 0.01223 S.D. N 0.355 0.075 94 94 5.2 0.00546 0.00103 94 94 94 no 0fc7800 CONFlOrHTTW YZ0014455 G-17 Appendix G (cont.) An Inhalation Final* Fertility Study with Benzene In Katt 79-2425 GROUP SEX LITTER PUP W Ki^Kjrs L/BH K/BW --ff T a----------" inInivinnniiniitttttttIi-------------------------.----'.----.-.----.----.---.----.----------'->fF9P#iFpP1PP*------------------/---------"--"Ta4aelaaaaaamaipaaBtttittiiddeeteaeeeell--------------"------ -.-.-.-.-..-.-.-.-ttI-eoaeat4a4ote7 ~--"`*ttlIiriri1liiin*..do.r**..*i.Otaes3eeT*oawlilfoi4ea98ii1etaia84j*t3*1*?rrir'---------------"T------rH04aol**0C0pTT."**.*T*.....447ai434nil4HanTa40Tl(i*1(CGan3v4a3l5*rII------------------ 14*1 31t*.7a1 it.i 31.4 30.4 ea.,0la40iz*4o1i*f "0(((*.*.`*oo4itfv3ti"Ttd(a3ai0aed0*i-r" 9a***De1lli4ilTtT0#ie14l0oDI0vil '*n.v11i0iM407ir 37.7 30*1 -0*.0a*u4B40w(7r- 0a*.d01ite14d3O4B0 IT31*1 *!-------- t*a3lti.*a4i 40.0 0li*M04U31V3C30I lio. OMtfi1m10*i |0.0|44313T310111 Il0og.0I1iIiI0nI0I7nI0I0i V#9**9DDIll IIftD1ft7IODFDD#I `4lO1*3if *"iV*oWr"'o.*iiosii ~~trit "iiItniiiitIttii tttitttil< itiiIttiIi 1iIIIt1IIi iitt 1K1l 1it1 1it1 II TIitIi 1 " " - 11 P "#..... ... P 9 P $ pp pp--#...... tpp p F ' Fp Fp P P " fPVF PF F ' 9' P "9 P 9p --"""444a4444a4adaa444da4aaOi4a44aaaadaTa433J333333S3s33Ia133litttitttiOtnttltdtddaea1dee3434C3s43*4d11a*af*lltIii.-"..-_..-.._-..-.._..-.._-.*-.----'."._.._.._.1"I1i.1t_"VDd,a1aa1a4cli01taa0eat4aeaa01a_--"1~"_""_1"_"1 --T10erfi11i1Ii1Wi1ii11Iiiitln11ii1il.1iti...*t7*.S*...****.**...am.*a.a..*.*.zOa073rt44414334.0Ma1340i4Mmi*aaaaoaand0eaI00714404t100V***IraTaaoa4*10d0100*00ro31T*J0iV?IItttrrr^r""-"----------e0li40i4a0C0*0l0i00V100ieic010*r00eTr.**.*..*.**********..**.......HT3o3c3443J30434444t4dt40fI344a1a44m4va100e08Taa114303r*M4(Meni(io*n(4*HTvde14d0a71314301440*31liCTC**i*i--" ---.-..-..-~.--"-i31IS1a33*o333*33333r3314343333t3331r3714401P40334m3144C10014004i0011ail**l*,**.7*..*..***..***,...*....i..3434033*10003494100400l401411*ilr-------_--_"-_-"-_---TTT`"`"l00(eiad0Ba*m(09(C.0a*f*0....i.**to**......**.*.*...1.*0ali'V<e<.oi*OO0o0000*D00040dtW41t4lie43f494444444ia43443(d0amf41J0iteli0a33d1H((3I*(1B(0(i70iil0I3o41iMH0fi40a011a311i0iTWt1(0i*iM0134nl1oa37303*7oo*104a*l*3VtIOiI00014n343004300lia4*I1H*in*ilIoif1o013a1104li340303*0i7*(lI07tifr"--"_-----_l__0afoa0u0i0Oi000Iai90i0I0Ed0M.*.Ti*.*..*.l.*.*n.*...r*.#..**o0iolo0oo0i9io000000O0i00l0i104ulI1rtU1iiMti11l1mil11n111i1aalIi(1i1t1O3taid3lTo31K3li330131a31lloHoiI13t9aOm0fcH91**o7107441oMi1Iti0aMii3o0iMMdaRuBo0Dm0*430M30*m1o3t7io1v7330074e310130liaii0aIrSI*4o9o3eo07030l300310B--0ri0liI1-------" 00 067S0J T FNTTAl YZ0014456 **'*->, --* a. * G-18 Appendix G (cont.) An lnheletlon Ftuli Fertility Study Hith Benzene In Rett 79*2425 BMW SEX Limn PUP W AfiOYwT. l/BW K/BH n--------- r Uf 0 f.too o.eee 191 4*.* o.ocooato 0*0130*00 u e 111 1# 0*443 30.0 *0411031 0*01 *0000 "ii 1 OB d leV* 1*414 " 3 ITT r. i44 in r- 1*5111011-- ri p ti----r~--------- 3*------------7f 1 )** 0.4*1 31.* 0*0441340 0.0130*10 -------T.ill------ ----- 1374-- ~n-------- Kinm-- _nii---------jfp. 4OBlt-------- ,--- ----- l*OOt i.T4f--------- 1.4(1 9.311'------- 30*0 ]4.9------ " 0*0413143 0*0130000 ~*. Bilim--inni<-- 11 p MO 7 1*003 0*43* 30*0 0.0404330 0*0103101 I! " 1 Mo 1 1.113" 0*433 31 *T --r. on itt*----a. inr<4T ii n p eoo " "P""------- 40 I.TU 0*41* 3**1 *110410 oiaaoio n----r.Kt * T.r ` iiir- O.ceUIW--"T.Tnwr- ii "ir F t- _ 44 ----- 7< -- ..... l.tIO 0".04* 0*331 I.li1 1*0 0.0441010 0*01*0104 n.*-' 0* C434404-- 1.010*4*1 ` ii P Mt i i.eti 0*34* 30*0 0.04C1000 0110(0* IF" "" F '" 1""" lalll 0*3l --in--~nrnm-- o.siimo-- --irir~ - p P M| Ml----- 10 1*010 0*401 ' i ----- i.ool' " 4.4*1 30.1 0*040*010 0*01 *0**3 " iiai " ' 0.04*3*41 ~*. 11*3134 ii H ii it H i u it "Ii ii 'll ' ii ii ti ' Ti "" ii " i r" it ti " " it ti " ii "11 ... Ii F ee* * eei * HI F 443 A J * 443 * 443 F 443 r 444 e 440 P 4*0 p 440 p 440 p 440 >' 44* p 443 F " 449 p 44* * 440 p 440 A 400 p 400 V "TO-- p 410 i i .Til * 10 1*001 < i*oie c 1 *604 i i*oti < t*oee < 0.001 10 i..ii|_ * i*c* c i.oei i 1*140 c 1*030 1 *.041 10 l*OTC * i.ooi c 1**03 4 --r.m 10 0 *044 e i.ii* 0 I*t00 1*340 e f*lf* B" I .ill -" 10 1.041 0.413 *.4* 0.390 0*300 r.jii 0*34* 0.340 0*310 O.CI* 0.0*0 4.0*1 0*43* 0*0*7 0*4*0 4*1*4 0*4*0 4.471 0*0*0 1.3*1 0*3*4 ooa* *000 fall* 0.03* il^" C.040010* TITRiiT 30 *.043*|3* 0*013(3*0 *0.0 0*0*000 * 0*01**413 0*1 oeiooao --T*n-- 0*0300004 0*0141.033 umiii 0*3 0*04**134 0*01*01*0 10*0 0.030*400 o.oiaoooF^ - Hit. 31*4 0.0431414 0.04*0004 0.0133f*0 . 0*0144033 43*1 43*0 0301*00 laoiiiilr 0*01101*4 i.irrim 30.0 0*04400*0 0.0110300 43*0 .0403ii 0*0114000 ** in 0*04(003* ` WHIM .4(3(10 oiaotol 40*0 430300 .lOKOO ` "11*4 " uunnr" l.irilill' 3*0 30*4 0 *04(0.00* 0*0403(li ftlClftfl i. 01*1*11 _ **.* o.4**oir oiooho 40*4 0*04*Sot * 0130133 40.0 043*041 o.o*omo 43 .T 1 - II4TI4AT ciiinio-- _.l 0*0030*00 0*0130*00 MEAN S.D N 1,587 0.444 0.403 0.075 95 94 35.5 0.04430 0.01256 5.9 0.00574 0.00095 95 95 94 Do cO NF 0&7802 Tr>FNTTAL YZ0014457 -_ 6-19 Appondlx C (cont.) An Inhalation FfmfIf Fortuity Study with Itnunt In Rtt 79*2M CROUP SEX LITTER wW "IS "SB*1* L/BW K/BW ltl o an 1 ( !IF 11. (..iiFTrr"* .atoaua III r in --f------ in --m--------- --ninr--~9f------ U _ in r *< in at* III >t M FIT FIT F 4.411 ( !. I.1F1 F ` i.iii" i.at* to .* I I.M1 ( i.iid 0*111 o.ata ((3 e.tii a.tai O.ITl 0.310 (Tin ll.I FO.t F3. 31.1 FI .F eo.i IF .F t.i F.ttOFFFF 0.(4(4030 .FtFFFI4 * (.4(44414 .14(0401 0.04IOFI0 O.FlFtlOT .aotilfr ti'.um- 0.0I4T4TT 0.(1JliTF ><** *oii)0a .oiiatoi TTiiaiFit --min--------- 9 ~f------- FIT ii? F in r (IF F --rn-------- f ....Hi 1 ijynj-- Fit III -- -------- i- --min--------- ------- (IF FTF --------I-Fj|-- t.oaa O.tli i.ifi d.iiT a*iia IFF *w O.tOl I.1FF (.IFF r.nr --T.TH i.oat 0.1IT i;r niii ia.F 1.0 n.i it.a n.a i.t F.F .a 0.04 10104 i.tiwir .tltFFIF i.iiiiiir F.F4KTF4 a o iir< 0.0400404 T.IJIIUT a. Flail 0.4111111 o.aiiTto* fTVtltVoo 4. oi too* i. tiToiat 0.1111111 (.Fill 410 in nr-- in m--------- 9 f * 9 (IF Oil (31 (Si 0 I* IF (.lit IF .4 4 -*.Fi~ -------O.Tid" I.OtT *( aa.a i *t4i i.iii * ita o.oiFoaai .Fill 10* * o.oFifFfr O.'Ol*0)04 a.F4iiFFa ' a.anaa*a 8.04(1434 ^.OiiiilF in 9 Fit hi f 31 !*(( I.FFF it.a T" t.ttt --rm-- It.l O.OFttOTt .mm 0.4(4(011 't'K'iiniiV" in 9 tit F a.oia O.tfO IF.I 0.4(1IIT 4.F114040 " '11 " r" m If 1.1FB f.<n 1C * 4.14110*0 0.0111144 III .....Tff-- " "W..... in iJJ ` t i.aai F i.ift O.FFI ,t4JJ FI.F 41.0 *(41(043 .anaiat (.01 Of(4T in 111 " (ll ESS I I .OOF 4 I *93? 111 i.fU 41.0 Al.i F.CfOFlia i (iTii i~ .at tom Ull'lini in 9 (13 F i.iif O.FFI 41.0 O.f-t If OFF 0.0110144 III 9 Ui------ ------- It " '"'. " 'a.4ot 'Ja'.O C.CtltTir ~t.FI 01(31 --ill in -------in in III 9 " 9 "T1 (IF* (3 OF (IF 414 F l.FTF T I .DIO t ' i .no F i.oit If" Tr o.fIf" " a.aia O.FFI 0.(01 e.Fto fI.f 44.4 f.i 41.0 FI.f (.04(1(41 C.44(1318 "434%ft 0.04IT31T "i.ujinr o.oi4i9?T .ataana '4. 01I4ttl 0.0113(03 d.fiiTaal in 4 (it it i 4 (If ( I.TFt i.FIF c.aoe 40. (.'iff-- 4 l.T F.fFlCFai .infra a.04ia(i3~------0.OI334I1 Til III III --m--------- in iii ' f 1 f 9 F 9 (it (it CJC tic FIT ------------- 10 F a a i.ora i.s I.BTC 1 .FDD I.TOI ivwr IT '.Fit ' O.Ftt *CC O.TIF 0.(04 44.0 'fo.o------it.a i.i at.y 10.1 .4ia(0F F.SFtFl 0.0411(11 o.f(ftiu 0.04TC04I (.044111) 81taC4 Mlilili ' 0.01FF*T k.diilUO o.ai KlitffO'i-- in ..."ill"..... --irnir.... 9 F' . F "3------- FIT (it IT CJT T .a*T a r.fr 1**01 Tl" "W F.FFI f.Ifl .FFF O.FFI l.l ia.F if i II.1 0.0414044 o.iFiiiir (F(IOF t.MMHr ' 0.011F01T umni-- hilllNT 1.1111141'" in in in in in " in "" in F ~i ~ 9 F .t F IF IF1 IF (H itiice, FFF I.FFI T T.i3 I.T*F d i*jrF*" la t.lOI i1 " 1 .III T I.TFO a.aio air O.FIF a.lio a.(Fi f FO O.FFI IT.F J .0111008 *.0118008___ 41.1 naff f; at to ifI a.T 0413418 0.01103*1 99 *1 Cf4C944C ' tIJflll Ft.t .0(11431 .*1440*0 B444I4F -----8. 4114111 if.a____ 0.04(1100 0114804 67803 conftofNTTa| YZ0014458 6-20 Appendix G (cont.) An IntulitfoA Femil* Fertility Study with Oenxene In lleti 79-2425 CROUP SEX UTTER PUP I t p a a III III rp --in 4 14 111 p --m----9------ --emi-----------r? hi ----PrS---- <41 --rn-- hi f 14 W 1*444 1*444 1.174 1*144 1*4*4 1 *<* 1 >)i] 19) 4.444 4.444 ran 4.374 ran a.3f< i.iil ICPrjfft (a) 31.4 34.7 ill.? *.* 11*9 aa.a ii.i L/BW .4471441 .*<7314 i.ai-liilT' *(311444 1.1110491 C *4444441 i.niiiir K/BW 4.4113477 4. 4111144 i.iiriiH 4.4117141 nans ! OllillT | --imn------,9------ 41 "111----- - --imn-- 9 9 <41 " III in 9 <41 ' is i 9 44* it i 9 443 111 " 9 443 --imn------p9-----------IT4S2------ 4 *444 * ' 1.934 4 1*444 | --17111" I f *443 4 < !? ? --rare < 1.444 " < i.iod 4.114 i.lil 4*441 4*471 4.111 i.ili a.444 ran <<74 *<* 43 *1 41.* 4i.a 44 .4 41.* n;r i.< I*i 44*1 II. 1 4.441(774 1*0413011 " *.44a*7T* <*0494111* 1.4443441 iiinr" 4.44(1344 i*fifn*r *471317 nranr 4.41*1174 ItiiMDl M 4.4131144 .(iivin 1 4* 4111441 l.llfJllf"- 1*4441 i.Tt1l44tf 4. 4143(41 i.iniHi in iir in n~.... in 9 43 14 f------ ii < P P" r --<a4444i-----------<71 1.71* a.4*4 34.1 4.4474141 (.4134114 _ r.444 T.4II ld.*~ liiiifilP *.#i*i*7* 1 *4 71 a.4 37.1 4.4414143 4. 4111*44 --raw --i;n--------.t* * i.mmr--I.ll9llir 1.344 <*314 31.f 4.C411144 *1*14*1 --m------F------ in P <44 < 4 in 9 `*4... 1 ---inimini i------9rpi----m<<4441----------------1-1r(0 .. 1 i7( a.m 31*9 .mini" II III?*" i.4?a a*4i 34*1 44(7441 ___*.4139447 tan 4 to4 41 .7 *<*4471 4.4134134 1 .*43 4*143 34*( 4444111 4. 4134431 I.TII' ' ` <.< ir.i~ " t.t4f00(R 1131443 1 .111 4.44* 31.3 4 *41774(1 4.4l3el I * 04 --ran-- J4.C (.04(1(31 4.0114*17 WP _ | in 9 4< 9------ He 7C i.rat --1*>3 4.44* 1 .441 34.4 4.(4(1144 4.41*44*1 li.l '".14(4141"' '4.tll<eiP ill F 44 4 l*4l 4.41* 37. 4.4411411 *.4111*41 in ill F p <44 44? 14 1*711 4 I.444 4.411 4.314 34*4 31.1 4.4474(14 4.44134(1 4.4113441 4. 41 *3444 III ill 9 9 44? <4 " 1 1*444 a -----1.7*4 4.444 4.447 * 34.4 *1134(1 i.ialiiii 4.4111*34 _ iilnl 9 P <4? Tr ill P <44 4 104 in P 44 a ill III -----P---- 441 444 < ------ 9" III P 444 tit --- P---- 444 III P 44 4?f ..in1" P in P --m-- P 444 449 149 1 14 in 9 <44 in 9 444 1 il*l 9 -----m444----- 9 a in * 444 ta a1*.4a4i44 I.T74 4*414 J3*t7i4l4l 1*444 3.341 *444 1.4*7 1.43* 1 *410 4.041 a1..4444i 1.444 1.474 4.C44 4.414 4.4K 4.(41 *.(1 9.4(1 a.<<* *(74 a.tia 4*44? 4.4(4 rati 4.413 4.441 <(*< 4.4(4 (.447 17.7 33.4 Il.l 44.C 4407*.14 44.1 44*4 34.4 43.7 31.7 ic.i 41.1 34.1 44.1 34.4 >4.4 1 | r a.aaiiiia a.atiaati .ili3< 4. 41 4.41*43*4 4. 4131147 (.1(41744 4. 4134443 4. 44 74411 3.4144144 --0.4(11911 .(((a a.((ia*4 C.4C49113 4.4lltJ71 4. 41 34441 .4143444 4. 41344*4 a. aiaaiai 4.4I44H4 *.*474144 .*11731* --i.miirr--i.iiiyirr 4.4144144 ((mi *(444M7 .I ' 4.4111444 4.41 *1(77 ( 4117114 -4.413474* " m | |h m | MEAN s.o. N 1.763 0.431 108 0.488 0.102 108 37.7 7.1 108 0.04700 0.00492 108 0.01295tt | 0.00103 108 Dn 067R04 CONFIDENT TAl YZOO14459 6-21 Apptndl* Q (cont.) An Inhilitlon Ftnula Fertility Stu4y with Bonztn* In MU 79-2425 GftOI/P SEX UTTEA PUP " "!9 "" F if-..... I* P Ill tv P t*a IV P as* I* p IK IV f It* IV P 626 " IV P at* IV * IV - p etc IV P itt IV P IC "" # 43* tv p CCT IV p IIT tv p tv P J7 IV P 2I IV "A lie" ` IV I V *" ..... f . .... ee "ait------- IV P eta IV P...... ea IV P aia iV f 921 ... IV P eso IV p *36 IV P aje IV tio IV P HI IV p sit IV P *31 ;hIV IV IV Fr r 531 S31 IV r IV IV IV IV IV IV r r r t rr m w 3T II? HiIV IV rr IV r 525 IV r 639 HiIV F IV F HiIV F IV F IV F 939 IV F 939 IV IV F F in ft f ? 10 * a t ? 4 t to e ? a 1 to a e ~a T -"6 1 14 a ( e "1 c % f 9 <0 .6 7 9 109 56 6 ,1 6 9 'I W L/BW K/BW vftl T.4II------ "i.m-- If.T 0.464I961---irinnvi i.aaa I.44C a.aia a.4ij ac.o 30.4 a.ai03 *4toal 0.0137301 1.31104(0 1.341 1.70* MU t .441 *0.3 33.1 C.*4|?t?0 0.0143(03 t.*114314 0.01 >0(40 1.111 a.I4i 30.* t.*4<4*e 0.3140*10 i .ill--",<n-- MN 4.414 I.44I 1671 --6.6461166 40.1 _ 4<141301? 41.1 I.IIHijl 1; Nil 996 o.otaooio .ft 334*1 1.000 f.evi 37.0 0.4437037 0.01 Of10? 1 .0*4 0.411 1.037 0.4*4 T.Oli------ 6.631----- 31.1 34.0 4*.7 0.44(14(0 *(034*0 6.0414449 0.0133001 O.014II0V .143700 1.41* O.fll II * 0.0447170 0.0133033 1 .421 4.3(0 ai.e 6.*4403 1 4 0.41146*3 I.M( 1.447 t.aii 1 .of i 0.440 *6.4 1) t.441 6.46c 40.J 30.4 la.* 0.444M00 0.0114144 l.Miiiir--67 ill *716 0*0443437 0.0111000 0.031170* 4.6i 16111 1.3ft i.Di c.ec? 4.40* ir.i 0(..0(44(144400616--tMBR 1.3*3 i.na " .* i .117 " t.3C( 4.310 0.414 0.404 31.1 ii.r 30.* --im-- 0.0430403 t.ooiolil 0.0414400 .0441100 0.013 tut 6. 61 iieio 0.0160*01 0.01 SliTI i.oao C.Cft 43.1 0.*444031 3. 0133300 T.06I " T.------- --ir.i~ 6. (Mill]--------nUlifi-------- i.rai o.eco a* .a *043(034 .0144301 1.044 o.caa 44.1 IlUYUQI '.6116466-------- 1.444 1 >*N 1.444 C.011 AtCvo *! 44.f 43.4 31. 6o0H4t 6.641 fill --R3. *i1r1n13i0n3-- (.4(00304 3.0140133 4.727 1.333 4.592 1.539 !:HI 4.321 2.233 2.291 4.939 2.153 1.199 4.513 1.964 4.151 1.932 1.116 1. J30 4.270 1.301 4.169 1.203 0.106 0.324 0.160 0.450 0.425 0.430 0.369 0.570 0.593 0.512 0.595 0.431 0.509 0.575 S:1H 0.412 00..33T517 26.4 33.4 11:1 34.0 31.7 25.7 41.6 44.0 35.7 44.7 32.4 31.0 41.0 36.2 35.9 34.9 31.5 31.2 30.7 2277..95 0.0661(36 0.0402719 0.0476506 0.0453019 0.0577419 0.0512934 0.04(1324 0.0536779. 0.0559512. 0.0457555 0.0517506 0.0466975 0.0534539 0.0479024 0.0400329 0.0496655 0.0443997 0.0429571 0.0407051 0.042*779 0.04if996 0.0439273 0.0155556 0.0097993 0.0439554 0.0141509 0.0137097 0.0135647 0.0429571 0.0137019 0.0142195 0.0132300 0.0141007 0.0134269 0.01(4494 0.0140244 0.0109116 0.01*7769 0.0139971 00..001121291619$3 0.0134202 0.013S710 0.0134909 DO 067805 CONFIDENTIAL YZ0014460 G-22 Appendix G (cont.) Am Inhibition FomTo Fertility Study with Benzene In Ret* 79.2*25 GROUP V IV IV " ' IV IV IV H TM" tv iv IV IV IV rv tv Iv .... IV IV IV ~"IV "l-- tv IV IV re IV IV IV --rv----------IV IV " - lIyV IV rv " iv IV IV IV Iv " " IV tv IV IV IV X UTTER PUP w Kl^WEYS MOL L/BW K/BW (9) 1 14 B '' .... , 1 allB 4.311 IVal --mowr i. It III o.oto e.iii * c.474aa * ff.i4*ia I'll------ i.ii* --i.in-- If.4 i.njiiir* CTilTili eve 10 i.iti in 7.1 444447 .*14*131 1 i.iei i.iii * .44iiiTT" IlilMf 41 .... 1*1 --- 7|- i.tii --mtr I.ITI rin Off.3 0447431 ` * T* nn-- 1.HI HU 1 4.ll44l---- 41 ill io - 1*131 1.1*3 *34l 34*4 ` 1.1)]------ 14.7 I443f 4. *13169* .mr Vi7lfV*` ' it 4 t.eii *3* 41.1 I44*l 13319* *4> " --i.fir------- I.Ti'I------- Jll# i.imtn i.Tiifiii-- 41 4 lt4U *4 33*4 4444I4* 13*1*3 ' `"1*1 l.ffffff 4.34 I 14.1 1.14lie*7 i.iiurn-- 41 < !* 0.444 34.4 41S **i sant "1*1 7.*ji-------- "76.1----- --irenm-- 41 ie 1*340 0*411 ll.l 4.443*441 *.1447*1 (4l 4 1*14* i.Til 41.J i.*it4irf" 174111143' ' 43 1.471 4.II* 43*1 c.oecaiav .tat*** 1*3 I 8 <114 4.111 41 VI 1.1411T 91 --i.vniui-- 44 *WI --f4 . 1 .303 "'lilll e.iii l.iir 34.4 "3t;r .44447* **14**6* t.imirr"THTHMI 4* 1.343 i.iit !* 4.44C4744 .13*1*4 ----- f*V -- > r.r ~n.r .iiflirr- *. *134~7V) 44 l*l4 *343 3**3 C.4I4?* 4.4II7M* lit------ Tiiii B.I]J 34.1 4.4* 47443 4.41 44444 44 ' *44 -----110 . `" 1*601 i .J0 4*430 (ill*' 11.1 31. C.C4|434 *134*0* .4476*--i.tmui 46 c 1.1*7 0*374 If.I 441434V (.I3IHI 4* 7 ` 1.111 C.3C0 f .4 * 4.(4f(43*" *.4I4I*4 44 I.SCS 4*111 34.3 4.44134*4 .II4* ' 146 i .see rein 31.1 S*I4X%439 " 1.1111111 .. (4? < 1.441 4.430 33.4 1.114407* 4.ait(ii *4? 1 1*4 0*414' 11.< t.141441*"' `**.13171* iii C 1.3*4 1.341 14.1 4.(441133 4. 413*434 47 c i.ari 4.344 33.1 141*734 .131191 47 ic !<?' l.iii 34.7 *ii* "* 413443* ' ie 1.3 40 *443 31.1 .lt*<*4 *.4131444 46 ( i.eiv 1.441 il.J i.iiiUn- - 4** 4 4* .. * . ie * 1.311 !*< !. 1 * C*34t I.IIT 4.411 4*4t4 33. 34*4 44 .1 44.7 I.C4Itost 494034 *110134 4.44*4477 *.*l 11374 741177*3 4. *1433*1 4.4134364 4* 7 1*107 44.4 i.iiimi *414*3*3 MEAN S.D. H 1.560 0.326 96 0.450 0.084 98 33.8 5.3 98 0.04601 0.00507 98 0.01330 ft 0.00115 98 DO 067806 CONFIDENTIAL YZ0014461 Appendix 6 (coni.) An Inhalation fowl* Fertility Study with Sonzona In IUU 79*242$ GROUP ------ 5------ % I 7 % 7 1 \ \ \ V t V V 7 _ *^ % V * % V V V V % * V % V V 1 * * V V \ V i V % % V % V V SEX "r r r r a r F F F r f F "V F F F F F 'F F F r 9 F F P F F F F f F P F F r F F ' F ` #' P F P F P F F r F 4 F 1 F LITTER PUP "HP IMJOl IOJ L/BW K/BW r. ~ren-- 470TT 0.171" 55.4 175555573' 575113000" INI a **47 0.3*1 M.l a.oiaoaia ' ' 01 31001 INI 7 1.101 0.3*0 31.4 I.I1UII0 0.01 34700 iota ; iota ( 1 .1*3 Mil 0.313 0.130 14.1 it.a 04*1*04 - * 01*4030- 0.0311170 0.0110707 1017 4 1.07a 0*004 30.0 0.0000401 0.0130W lbl7 c MIS' V *4 JP *' ir.T" A.4441130 0.0111737 1017 a 1.7*1 a,*47 34.1 a.0440111 .013(401 INT * t.aoo 0.400 31.1 otioooi 0.01440M IN7 r 1.710 0.4*0 34*7 0.0447111 0.0113343 1017 i.a*a *.44* 37.0 0.040J431 0.0131073 1010 7 0.077 --rm-- a i.iio 0.*** i.iii 1.3 --H.5" 0.4411737 1.'5511571" 0.0131304 0.01 11104 iota a 0.01* 13.7 l.43107ai 1010 a 10*0 a.aio 3573 0.4413311 --*. 4154554" INI f i.too *4*0 *4.3 4.0411471 O.OI40MO IP( a 1.1*1 a.iaa 14.4 0*0441134 4.0144341 lOfl 0 1.1*4 0.3*1 0.0 o.04iaiao 0.0134141 iii* "15 1.1*1 r.457 id.4 o.dAnooa d. oi oil a " tan iiii i *.300 3 1.0*4 a.tt* 0.40* 47.0 40.0 0103100 .0*4440* 0.0111414 7 All 1430 101* a 1^*1 a.4io ** .4011*3 1.0117(30 ili t 1.441 0.411 *a.i .0441041 ' 0. 41 34*01 10** 1535 a 1.4 13 o.aas 4 ran- a.lib 3*.7 Jl.i .043*110 .0.0130011 "575155755" 0.0lbl477 101* te 1.313 o.ioa 31.3 0.04l0a31 o.onoaoo 10*1 1 * 1.7*0 0.414 3a .5 o.aaaaTaa 0.0110*74 1033 7 1.03* 0.30* 30.0 0.0431040 0.11 07404 1533 1 i*4ia 0.1*4 if.o 0.044(143 SToi iIoti 1031 T5I3 4 1.73a id t .41* 0.4*0 iiiii -----J1J7-.*,------- 4.0440004 i.iiiiiia 0.0113307 O.Olif ! 1030 1030 e 1.000 *.341 a .4 0.0400104 0.0110300 i 1.CFO* 0.37* " ~n.r ~ 0.(41*555-------- Miltaof 1 1034 1 t .oca 0.3*4 30 .3 (.0401143 0.0130004 1034 1034 nsi a 1.444 * 0.410' ' 34.1 (.caiifto diilooo 1.33* C.344 31.1 0.0414407 ' 0111340 "I 1.1 IT" 1.34* il.d "575551517"----- 1.5113457 1030 1045 1030 1535 103* ran I03C 103* 7 0.00* " "`T " l.OIV a 1.4 a* io ~nj?r a 1*004 7 - '"1.101 C 1.1*4 ' 1.471 * *301 17.1 0.0340431 0.0110007 0.455------ "35.5"- o.iaiiiir 'i.iriiiir 0.401 11.3 .aaoioa 0.4110310 57551 sa.c "5755T555T 4.4111 Ml" 0.417 .Ada JO .a il*i 0.0411*41 o.oiaaaia i.uitni --5.1133101 a.370 31.1 0.0341411 0*411(071 *a.4t< * ~ ii.a a.aaaadol 0.4141(73 103* 1037 iW 1*37 iol* " 1*17 1*3* 1*3* 1*3* 103* i* a i' a t 1C C 7 a * I.34C ------- 57551-------- 1.04* .444 1.300 57515 I.*** 0.041 1.704 57755 1.411 0.400 T3iF 57553 1.040 0.410 1.4 40 4.4 id 1411 0.311 00.7 *13100 .diaoaio 34.1 1575 0.0(3071 i.iaioida 0.0144430 5.1111710" 33.4 o.otooiai 0.0141114 35.5 ~ "TII BBI " >i.i (.oaooao* 0.0141 MO 5575-------- ildawdr ~ OTOialiOO " 31.0 0.0414041 0.0130000 il.4 . 4.044170J HiSiaoa *7.4 0.0440011 0.0114101 DO 067** r,oMF TDf^TTAl YZ0014462 - G-24 Apptndlx fi (cont.) 4n InhiUtlen Ftmli Fart titty Study with Banzant In Ritt 79*2425 CROUP V a a a V a a a a s a * a a V a a a a % a a a a a V a a V a a V a a' -- \ a SEX P 11 3 a a a * a-' a a a a F P a a a a a P a a a1"1 a "1.... a F a a a5 a P P P a P a a- a *3" ** a UTTER PUP LIVER ItT KiyH|TS SWL L/BW K/BU INI IT" --1 .119 --mn----nn 3.3413331 3* 3113171 103* 1**9* 0.3*3 33.3 3.3414310 *31313*3 103* i !*>. O.Jll *1.1 O.lliitOi 3.8V3814* 1030 i !>* *.3*1 33.3 3.343*037 4. 3133*1* "Tffi r- " 1.1Jt 3.377 31.1 114J11#1 1I9I1IJ 1*39 1110 ii" 1.3*7 ran-- 0.40* 3.3 4.3*4 --nn 3.34*3411 * 0.3117333 1.(41000* '1. Illllll 1 1040 3 f .1*3 *033 4J.I .its* 1 0.3130(47 1040 1.0 If ff7*f* 33.1 4.31*3140 1*4* iST* *.*33 r iTffi 0.31* r.*n 43.3 *434343 4. 4133333 37.1 irTiYtili 1040 i* I.TOO 4.31* 33.3 3433333 .3I33*M 104 V 4 i *ij 0 .303 91 # ~ 0.0441771 "" 1.8141X11 1043 * 1.741 0*33* 33.1 .3431137 3.3144341 104* r r*vi riii J4.i T.ftfiiii 3.014*111 104* t 1.0*3 0.433 33.3 0.343I434 ' 3. 3143331 1*43 t I4li fTfil H.i' liitiiti o.ii3Ym I04| % 1.33* 3.4*0 3T.3 44437V ' **171*3* mi 1043 ii < rar--ran-- 31.4 --ranmn-- F. 11 fill*" 1.333 3.413 33.3 3.3410343 3. 013*1*1 It** r --rail 0.434 '--ir.i-- --i; inmr- 1*4* mi * 1.3 VO 0.4*0 i itHI " 0.4*1 33.3 3.0434143 *.131034 ii.l #414911 #*#I9|#9# 1044 * 1.33* *.43* 33.3 313333 0.3131310 1044 ii --raw" 0.414 31.4 1*1431918 1.1(41419-- 104* it* -- I.4V3 *44* nnr --8.41-- 13.3 "Tfi"i-- 3.3431714 0.3138303 r.*4 im--iarmr~ 1*4* 104* * 1.04T *343 33*1 .3343134 0.0130101 t nn* i;ni " 'Il.f Y.Miifii--"pirnn 104* 1046 * 1.144 3.3ft 1.1*1 " 0.311 St.l 343711T 3.3133403 14.1 --1.IS<1111-- .oii*48 1044 i 1.033 3.330 4.3 *.3414313 3.3141133 104* 'CM* -~ i.r` " `3 .'0*88898-----KTiWIT* 104* * I o'.9 3 1040 ITT* 1 1.T1T 1.041 0.117 31.3 0.0433334 3. 313*333 ---- .l--- 3.(4iim--f.83*4-- I.TIO 0.403 F.IC3 " 0.4*3 33.7 3.044*140` 3. 31314*0 34.3 --V.HI9118" - 3. 01 43181 104* nn 10 1 *907 *.344 utr " ran-- 3*.* un ~'3U.(44(1it3m13--` "c0.0ir14n34u00i-- 10*0 * I.040 0.337 33.1 3.343143V 0*013371* nn-- 1010 1* --l.>4f 1.331 - -T.IA-- C.41S "19.1" " 33.1 i; mm?--Kinna 3.0417333 3.31143*4 MEAN S.D. N 1.^21 0.339 0.079 97 96 3r.6 5.1 97 0.04442 0.004CP 97 0.133319 0.07136 96 DO 067808 OONFTDFNTTAI. YZ0014463 H-l Appendix H An Inhalation Female Fertility Study With Benzene In Rats 79-2425 Gross Postmortem Observations - Day 21 Vfeanllngs (Unselected) PREFACE Do 067809 confideTNTTAl YZ0014464 H-2 79-2425 'w* " Appendtx H (cont.) *-- "" An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) iGfilpirHpomfuiCpl 1 0 Litter No. 225 2$6 227 228 229 Puo No. 3 4 1 2 3 6 8 9 2 3 5 6 8 10 3 4 5 6 7 10 2 3 4 6 7 9 Sex F F H M M F F F H M M F F F M M F F F F H 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 Observation! s)* N.O.A.- No Observable Abnormalities* Key: M male; F female. DO 067S10 1 CONFIDENT I Al I YZOO14465 H-3 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 ppn I(cont.) 230 0 / 1 H N.O.A. 3 M N.O.A. 5 M N.O.A. 6 M N.O.A. 7 F N.O.A. 8 F N.O.A. 231 1 M N.O.A. 4 M N.O.A. 5 M N.O.A 6 F N.O.A. 7 F N.O.A. 9 F N.O.A. 233 3 M N.O.A. 4 M N.O.A. 5 H N.O.A 6 F N.O.A. 7 F N.O.A. 9 F N.O.A. 235 1 M N.O.A. 2 H N.O.A. 4 M N.O.A. 6 M N.O.A. 8 F N.O.A. 9 F N.O.A. Observation^)* aN.O.A. No Observable Abnormalities. Key: M - male, F female. oo COA/p- 06?Sl 7 Tai YZOO14466 H-4 79-2425 Append tx 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 H M F F H M M M F F M 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. Observation^)8 aN.0.A. No Observable Abnormalities. Key: M - male; F female. I________________________ _____________ 00 06781? CONFIDENTIAL, YZ0014467 K-5 79-2425 --5^ . - 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 Wo. 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 H 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 8N.0.A. No Observable Abnormalities. Key: M male; F female. 00 067813 C0NFrD8NTrA[ YZ0014468 H-6 79-2425 -- - Appendix H (cont.) .... "-- An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings {Unselected) GroupUtter Wo. ppn 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 H M M F F F Observation^)* 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 JtldneyfRIoht): pelvis moderately dilated} filled witfi 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. aN.O.A. No Observable Abnormalities. Key: M male; F - female. D 067814 CONFrDFNTrA! YZ0014469 H-7 79-2425 Appendix H (cont.) ^ An' fnhalatlon Female Fertll1ty*$tudy with Benzene in Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter Ho. Pup Ho. Sex ppm Observations)* II(cont.) 429 3 M N.O.A. 1 4 K N.O.A. 5 M N.O.A. 8 F N.O.A. 9 F N.O.A. 10 F N.O.A. 431 1 M N.O.A. 2 M N.O.A. 3 M N.O.A. 6 F N.O.A. 9 F N.O.A. 10 F N.O.A. 432 1 M N.O.A. 2 M N.O.A. 4 M N.O.A. 6 F N.O.A. 9 F N.O.A. 10 F N.O.A. 433 1 M N.O.A. 2 N N.O.A. 5 M N.O.A. 6 F N.O.A. 7 F N.O.A. 10 F N.O.A. 434 2 M N.O.A 3 M N.O.A. 5 M Tall: blunt 6 M TTXA. 8 F N.O.A. 9 F N.O.A. *N.0.A. No Observable AbnormalItles. Key: M male; F female. DO 067815 CONFIDENT TAI. YZ0014470 H-8 79-2425 --w " --- . - .Appendix H (cent.) _ An Inhalation Female Fertility Study with Benzene in Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter Wo. ppm II(cont.) 435 1 436 438 439 440 Pup No. 1 4 5 6 8 9 2 3 6 8 9 1 4 S 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 M M M M M F 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. N.O.A. Observation s)* *N.0.A. No Observable Abnormalities. Key: M * male; F female. DO 067816 CONFTDFNTTAI, I YZ0014471 H-9 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study wKh Benzene In Rats*- Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. Pup No. ppm II(cont.) 441 1 2 4 5 7 9 10 442 1 3 4 6 7 10 443 2 4 6 8 9 10 444 1 2 3 4 445 1 2 3 6 8 9 Sex M M H F F F H H M H M F M M F F F F M M H 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. gye j^Left): 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. N.O.A.- No Observable Abnormalities. Key: M male; F female. DO 067817 CONFIDENTIAL YZ0014472 H-10 79-2425 ^ **-- - Appendix H (cont.) *- An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 tfeanllngs (Unselected) Group Litter No. ppm II(cont.) 447 1 448 450 III 626 10 627 Pup No. Sex 1M 2M 3M 4M 9F 10 F 1M 2M 3M 5M 6M 2H 4M 5M 6M 7F 10 F 2M 3M 5M 6F 7F 8F 1M 2N 4H 6M 8F 9F _____________ 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. N.O.A. N.O.A. N.O.A. BN,0.A,> No Observable Abnormalities. Key: N male; F * female. rCnoMnifr ^0o67e8n3tt8ai, YZ0014473 H-11 79-2425 --w * . - Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm HI (cont.) 62$ 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 N M F F F N M M M M F F F M M F F F F M M H F F F _____________ Observation s)l N.O.A N.O.A N.O.A N.O.A. N.O.A N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.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* 00 067819 chfideNTtai YZ0014474 H-12 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study -Jt. ^ ,, with Benzene Injats,^ W-- Gross Postmortem Observations - Day 21 Weanlings (Unselected) Group Litter No. ppm III(cont.) 635 10 636 637 639 640 641 Pup No. 1 3 4 6 7 8 2 3 4 5 8 9 10 2 3 5 6 7 10 1 4 5 7 8 9 1 2 3 4 8 10 Sex M M M F F F M M M M F F F M M M F F F M M M F F F M M H M F F Observation s)* N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Kidney - (Right) dilated renal pelvis (.5cm. 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. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. 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 * male; F - female. DO 067820 CONFIDENTIAt- YZ0014475 H-13 79-2425 Appendix H (cont.) An Inhalation Female Fertility Study "**" *" with Benzene In Rats *" Gross Postmortem Observations Day 21 Weanlings (Unselected) !rouo Litter No. ppm III(cont.) 642 10 643 644 645 646 Pud No. 2 4 5 8 9 2 4 5 7 8 9 1 4 5 6 9 2 3 5 7 8 9 1 2 5 6 8 10 Sex M F F F F M M M F F F N M M F F M M F F F F M M K 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^)8 8N.0.A.- No Observable Abnormalities. Key: M male; F * female. ^0 0678 CONFTDENTTAt YZ0014476 H-14 79-2425 ~" Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rets Gross Postmortem Observations Day 21 Weanlings (Unselected) arouo Litter No. pm 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 H M H F F F M F F F F M M M M F F M M M F F F M M 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. Observations)1 *N,0.A. Ho Observable Abnormalities. Key: M - male; F female. DO 067822 confidential YZ0014477 H-15 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.) 826 30 827 828 Pup No. 1 4 6 8 9 10 2 3 5 6 7 8 2 4 6 7 9 10 Sex M F F F F F M M N F F F H F F F F F 830 1 5 6 7 9 831 1 4 5 6 9 10 M F F. F F M H N M F F Observation s)*_ N.O.A. N.O.A. Liver: pale red-tan. N.oTK. N.O.A. N.O.A. N.O.A. Kldnevs (Both): dilated renal pelvis (approx. 0.3 x 0.2 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. Kldnev (Left): dilated renal pelvis (0.4 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.O.A.- No Observable Abnormalities. Key: M - male; P female. Oo 067823 confidential YZ0014478 H-16 79-2425 _^ Appendix H (cont.) -- An Inhala'tlon Female Fertility Study with Benzene In Rats Gross Postmortem Observations Day 21 Weanlings (Unselected) Srouo 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 H H F F F Observation?sV N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. 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 Abnormalities. Key: H - male; F * female. DO 067824 confidential YZ0014479 H-17 79-2425 - --^ . - Appendix H (coot.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Unselected) iroup Litter No. ppm IV(cont.) 841 30 / 842 843 844 846 847 Pud 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 M F F F M F F F F F M F M F F F F F H 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. Observatlon(s)* aN.0.A. No Observable Abnormalities. Key: M male; F female* 06782S CONFTDE-NTrSL YZOO14480 H-18 79-2425 --^ " Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rat* Gross Postmortem Observations - Oay 21 Weanlings (Unselected) Group Litter No. Ppm IV(cont.) 848 30 849 P 100 1026 1027 1028 1029 Pup 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 H M F F M M F M M F F F N F F F F M M M M 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, Liver: darTi N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A, N.O.A. N.O.A, N.O.A. 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. DO 067826 confidential YZ0014481 H-19 79-242$ . - Appendix H (cont.) .... " An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 weanlings {Unselected) Group Litter No. Pud No. Sex ppm V(cont.) 1032 2 M N.O.A. 300 3 M N.O.A. 5 H N.O.A. J 6 F N.O.A. 7 F N.O.A. 8 F N.O.A. 1033 1 2 5 6 9 10 M N.O.A. M N.O.A. H N.O.A. F N.O.A. F N.O.A. F N.O.A. 1034 3 M N.O.A. 4 M N.O.A. $ F N.O.A. 7 F N.O.A. 8 F N.O.A. 1035 3 4 5 8 9 10 M N.O.A. M N.O.A. M N.O.A. F N.O.A. F N.O.A. F N.O.A. 1036 2 4 $ 6 9 10 M N.O.A. H N.O.A* M N.O.A. F N.O.A. F N.O.A. F N.O.A. 1037 ' 1 2 5 6 8 9 K N.O.A M N.O.A. M N.O.A. F N.O.A. F N.O.A. F N.O.A. aN.0.A.* No Observable Abnormalities. Key: M - male; F female. Observation^)* Oo COisip 0$?, rO<TA/ riAL YZ0014482 H-ZO 79-2425 --w - -Appendix H (cont.)* " * An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations Oay 21 weanlings {Unselected) Group fitter No. ppm V(cont.) 1038 300 ' 1039 1040 1042 1043 1044 Pup Mo. 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 N M F F F M F F F F F M M H F M N K 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.O.A.- No Observable AbnormalItles. Key: M - male; F - female. DO 067828 CONFIDENTIAL YZ0014483 H-21 79-2425 --w " " """* - - Appendix H (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations Day 21 Weanlings (Unselected) litter No. Pup No. Sex Observation s)a 1045 300 1046 1048 1049 1050 1 2 5 2 3 4 7 9 10 2 2 3 4 6 8 10 2 4 5 6 7 9 M N.O.A. M 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. F N.O.A. M 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. M N.O.A. M N.O.A. H N.O.A. H N.O.A. F N.O.A. F N.O.A. aN.0.A.- No Observable Abnormalities. Key: M male; F - female* DO 067829 CONFIDENTIAL YZOO14484 1-1 79-2425 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. YZ0014485 1-2 79-2425 ( , Appendix I (cont.l .<; An" Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter No. Pup No. Sex PP Observation!s)c I 225 0 1 M N.O.A. 2 M N.O.A. tip 4 M N.O.A. 5 M N.O.A. 227 1. M N.O.A. 4b M N.O.A. ' 228 lb M N.O.A. 2 M N.O.A. 229 1 M N.O.A. 5 M N.O.A. 230 2 M Salivary aland (Right): red. Lungs: scattered clustered red foci on aTTlobes. 4 H N.O.A. 231 2 M N.O.A. 3 M N.O.A. 233 1 N N.O.A. 2 M N.O.A. 235 3 N N.O.A. 5 H N.O.A. 236 1 M N.O.A. 2 M N.O.A. 237 1 M N.O.A. 5 M N.O.A. 238 3 M N.O.A. 6 M N.O.A. 239 3 M N.O.A. 4 M N.O.A. Selected for tissue preservation* DT1ssue$ 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 067831 CONFIDENTIAL YZOO14486 1-3 79-2425 Appendix I (cent.) ---^.tDhalatlqn Female Fertility,Study * --* with Benzene in Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter No. ppm l(eont.) 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 2Vb 1 3 1 4 1 3 2 3 1 3 1 2 1 4 1*> 2 4C 5b 3 5 Sex M M M M M M M H M M M H M H M M M M M H H M H H H M M M Observations)6 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. 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,- Ho observable abnormalities. Key: H male; F - female. <-^783? coSfioenti*. YZ0014487 1-4 79-2425 -- - Appendix I (cant.) _ --An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)a Group Litter Ho, ppm II(cont.) 433 1 434 435 436 438 439 440 441 442 443 444 445 447 448 Pup Wo* 3 4 1 4 2 3 1 4 2 3 l 4b 2b 5b lb 3b 2 5 1 3 5 6 4 5 5 6 4 7 Sex M M M H M M M M H H H M M M M M M M M H M M M M M M M M N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. 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. bT1ssue$ 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 067803 CONFIDENTIAL YZ0014488 Appendix I (cont.) An Inhalation Female Fertility Study --^ . - with Benzene In Rat*... Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter No. ppn II(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. 0bsen/at1on(s)c III 625 10 626 627 628 630 631 632 633 634 635 1 M Eye (left) - 75% opacity 2 K Entire body: extremely mail. 1. M N.O.A. 4*> M N.O.A. 3 N 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. 2j> M Liver: Moderately pale red-brown. 5b N tTver: visceral surface, caudate and accessory lobes mottled dark red and brown. 1 H N.O.A. 3 N N.O.A. 1 M N.O.A. 2 M N.O.A. 2 H N.O.A. 5 M Liver: edges of left and median lobes slightly reddened. `Selected for tissue preservation. bT1ssues Inadvertently placed In saline solution Instead of 10S neutral buf fered formalin solution^ these tissues were subsequently discarded. cN.0.A. No observable abnormalities. Key: M male, F * female. DO 067834 CONFIDENT I Al- YZOO14489 1-6 79-2425 Appendix I (cont.) ~ TV ^ArTInhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Oay 21 Weanlings (Selected)* Group Litter No. ppm llI(cont.)636 10 6?7 639 640 641 642 643 644 645 646 647 648 649 650 Pud No. 1 3 1 2 1 4 Z 3b 5 6b 1 3 r 3b 2 3 1 4 3. 4b 1 2b 2rb lb 3b 1 5 Sex N M M M M M M H M M H M M M M M M M M M M H N M M M M M N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. 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 *Se1ected 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. D0 06783S CONFTDFNT I Al YZOO14490 1-7 79-2425 Appendix I (cont.) ~ ""Xh fnhalatldn Female FertllIty^Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)8 Group ppm IV 30 Litter No. 825 825/ 827 828 830 831 835 837 838 839 840 841 842 843 Pup No. 2b 4b 2 3 1 4 lb 3 2 3 2 3 4t 5b 1 2 1 3 2 5 4 5 3 5 3lj>b 1b 2b Sex H M H M M M M H M M M M H H M M M M M H M H M M K M H M Observation slc N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. 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. ^Tissues inadvertently placed in saline solution Instead of lOf neutral buf fered formalin solution; these tissues were subsequently discarded. cN.O.A.- No observable abnormalities. Key: M - male; F - female. 00 067836 CONFIOlrNTTAI YZ0014491 1-8 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 Observation s1c IV(cont.) 844 30 2 M N.O.A. 3 H N.O.A. 846 ib H N.O.A. 3b M N.O.A. *847 . 2b 3b M N.O.A. M N.O.A. 848 5 M N.O.A. 6 M N.O.A. 849 lb M N.O.A. 2b M N.O.A. V 1026 300 3 H N.O.A. 4 H N.O.A. 1027 2 M N.O.A. 3 M N.O.A. 1028 3 M N.O.A. 4 M N.O.A. 1029 2 M N.O.A. 3 M N.O.A. 1032 1 M N.O.A. 4 M N.O.A. 1033 3 M N.O.A. 4 M Lunos: scattered, clustered red foci on aTTlobes. 1034 1b M N.O.A. 2 M N.O.A. 1035 1 H N.O.A. 2 M 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 067g37 CONF TdENTTA[ YZ0014492 1-9 79-2425 Appendix I (cont.) ,, -- '**An tnhalatlen Female Fertility-Study ~ with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)8 Group Litter No. Pud No. Sex ppm 0bservat1on(s)c Y(cont.) 1036 1 M N.O.A. 300 3 H N.O.A. 1037 3 H N.O.A. 4 M N.O.A. 1038 1 5 N N.O.A. M N.O.A. 1039 3b M N.O.A. 4 H N.O.A. 1040 1 M N.O.A. 3 M N.O.A. 1042 2 M N.O.A. 3 M N.O.A. 1043 3 M N.O.A. 5 M N.O.A. 1044 3 M N.O.A. 7 M Lungs: few scattered red foci on all iooes. 1045 3 M N.O.A. 4 M N.O.A. 1046 1 M N.O.A. 5 N N.O.A. 1048 1 M N.O.A. 3 N N.O.A. 1049 1 5 M N.O.A. M N.O.A. 1050 1 M N.O.A. 3 M N.O.A. "Selected for tissue preservation. ^Tissues Inadvertently placed in saline solution Instead of 10X neutral buf fered formalin solution; these tissues were subsequently discarded. cN.0.A. No observable abnormalities. Key: H male; F female. DO 067838 CONFTDFNTrA! YZOO14493 I-10 79-2425 Appendix I (cont.) --w -An Inhalation female Fertility Study " ' with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)* Group Litter Wo. Pup Wo. Sex _____________ Observation!fig. 225 5 F N.O.A. 6 F Lungs; multiple clustered red pin-point FocT on right anterior lobe. 226 7 F N.O.A. 10 F N.O.A. 227 7g.b F N.O.A. F N.O.A. 228 8 F N.O.A. 9 F N.O.A. 229 8 F N.O.A. 10 F N.O.A. 230 9 F N.O.A. 10 F N.O.A. 231 8 F N.O.A. 10 F N.O.A. 233 8* F N.O.A. 10 F N.O.A. 235 7 F N.O.A. 10 F N.O.A. 236 5 F N.O.A. 7 F N.O.A. 237 7 F N.O.A. 8 F N.O.A. 238 7 F N.O.A. 9 F N.O.A. 239 9 F N.O.A. 10 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. M-male; Ffemale DO 067839 CONFIDENTIAL YZOO14494 1-11 79-2425 --w - 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 Observation$)5 I(cont.) 240 0 7 F N.O.A. 8 F N.O.A. 242 8 F N.O.A. 10 F Kldnevs (Both): pelvis extremely dilated; clear fluid-rilled; little cortex present. 243 6 F N.O.A. 8 F N.O.A. 244 6b F N.O.A. 7 F N.O.A. 246 5 F N.O.A. 247 6 F N.O.A. 7 F N.O.A. 249 7 F N.O.A. 9 F N.O.A. 250 8 F N.O.A. 10 F N.O.A. II 425 6 F N.O.A. 3 10 F Lvmph nodes (mandibular): reddened. 426 5 .7 F N.O.A. F N.O.A. 428 6 F N.O.A. 7 F N.O.A. 429 6b F Salivary gland (Left): posterior 2/3 red. 7 F N.OX 431 7b F N.O.A. 8b F N.O.A. Selected for tissue preservation. bT1ssue 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; F-female DO 067840 CONFIDFNTTAl YZ0014495 1-12 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study _ _ with Benzene In Rats Gross Postmortem Observations - Oay 21 Weanlings (Selected)* Group Litter No. Pup Wo. Sex _____________Observation!s)c_ ppm II(cont.) 432 3 7 F NeOeAe 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 NeO*A* 439 7 F N.O.A. 8 F N.O.A. 440 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. 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. K.y: H - M1.i F f--lt. D0 067841 CONFIDENTIAL YZ0014496 1-13 79-2425 --v " - 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 9l 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!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. N.O.A. N.O.A. N.O.A, N.O.A. N.O.A, N.O.A. N.O.A. 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 (mandlbularl: enlaroed (6.0 x 0.3 cm); 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 067842 CONFIDENT TAl YZ0014497 1-14 79-2425 Appendix 1 (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Oay 21 Weanlings (Selected)8 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. 6j 10b g7bl 6 7 6b 10b 7 8 6 10 7b 9 6 8 8 9 9b 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. Observations)0 Selected for tissue preservation, bT1ssues 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 06784? CONFTDFNTTAl YZ0014498 1-15 79-2425 r Appendix I (cont.) An Inhalation Female Fertility Study with Benzene In Rats Gross Postmortem Observations - Day 21 Weanlings (Selected)1 Grouo Litter No. Puo No. Sex ppm Observations)6 IV(cont.) 828 30 5> F N.O.A. 8 F N.O.A. 830 4 F N.O.A. 8 F N.O.A. 831 7b F N.O.A. 8 F N.O.A. 835 7b F N.O.A. 10b F N.O.A. 837 5 F N.O.A. 6 F N.O.A. 838 6 F N.O.A. 8 F N.O.A. 839 6 F N.O.A. 8 F N.O.A. 840 6 F N.O.A. 8 F N.O.A. 841 6 F N.O.A. 10 F N.O.A. 842 4b F N.O.A. 7b F N.O.A. 843 $b F N.O.A. 6b F N.O.A. 844 5 F N.O.A. 8 F N.O.A. 846 6b F N.O.A. 9b F liver; pale red-brown. 847 8l F N.O.A. 9b F N.O.A. Selected for tissue preservation. ,, "Issues Inadvertently placed In saline solution Instead of 10% neutral buf fered formalin solution; these tissues were subsequently discarded cN.0.A. No observable abnormalities. no Key: M male. F female. conftdenttai YZOO14499 1-16 79-2425 Appendix I (cont.) An Inhalation Female Fertility Study 'V - -with Benzene In Rate Gross Postmortem Observations - Day 21 Weanlings (Selected)8 Group Litter No. ppm lV(cont.) 848 30 849 V 1026 300 1027 1028 1029 1031 1032 1033 1034 1035 1036 1037 1038 Pup Wo. Sex 8F 9F 5F 6F 6b gb F F 6F 8F 8F 9F 7F 9F 1F 2F 9F 10 F 7 8b F F 6b F 9F 6F 7F 7F 8F 7F 10 F 6F 9F N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. N.O.A* N.O.A. NlO.A* N.O.A. N.O.A. N.O.A. N.O.A. N.O.A. Observations)c Selected for tissue preservation. ^Tissues Inadvertently placed in saline solution Instead of 10ft neutral buf fered formalin solution^ these tissues were subsequently discarded. cN.0.A.- No observable abnormalities. Key: M male-. F female. DO 067845 CONFIDENT TAI YZ0014500 1-17 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 Wo. Sex ppm Observation^)6 V(cont.) 1039 F N.O.A. 300 10b F N.O.A. 1^40 7 F N.O.A. 9 F N.O.A. 1042 9 10 F N.O.A. F N.O.A. 1043 6 e F N.O.A. 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 8 F N.O.A. F N.O.A. 1048 4 5 F N.O.A. F N.O.A. 1049 7 9 F Salivary qland (Left): moderately reddenM. Lymph nodes (mesenteric): slightly reddened; enlarged approx. 1 1/2 x normal size. 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.O.A. No observable abnormalities. Key: M - male. F female. DO 0fe7846 CONFIDENTIAL YZ0014501 Group ppm I 0 J-l Appendix J An Inhalation Female Fertility Study - with Benzene in Ratj^, Hating Performance 79-2425 Female No. Hating Confl matIon* Day Found Hated6 Preonancv Statusc 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 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes 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 Hating 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. ^0 067847 CONFIDENTIAL YZ0014502 Group ppm II 0-2 'Appendix 0 (cont.)**An Inhalation Female Fertility Study with Benzene In Rats Hating Performance 79-2425 nale No. Mating Confirmation Day Found Mated Preonancv Status 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 Mat1ng confirmed on the basis of the following: vaginal plug, sperm In the vaginal smear, or evidence of pregnancy (l.e* pups. Implantation sltes/scars). ^Represents nunber of days from Initiation of mating till evidence of meting 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 confidential YZ0014503 J-3 Appendix J (cont.) An Inhalation Female Fertility Study w.1th Beozene InRatv.. Mating Performance 79-2425 Group ppm III 10 Female No. 625 626 627 628 > 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 643 649 650 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 Yes Matedb 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 Pregnancy St) 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 ^Mating 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. DO 067849 CONFIDENTIAL / YZ0014504 J-4 Appendix 0 (cont.) Z> An Inhalation Female Fertility Study with Benzene In Rats Mating Performance 79-2425 Group ppm IV 30 Female No. 825 826 827 628 82 * 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 846 847 648 849 850 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 Mated** 2 7 S 2 - 1 8 2 1 1 2 5 1 8 5 2 5 2 2 1 2 2 2 4 2 2 Preonancy Stati 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 Mating 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 Meek 5 of the pre-mating treatment period. no 067850 confidential I"' I YZOO14505 "V1 Group ppn V 300 0-5 Appendix 0 (cent.) An Inhalation Female Fertility Study with Benzene In Rate Bating Performance ** 79-2425 Female No. 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 Mating 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 Yes Day Found Mated 15' 2 4 14 3 1 5 1 4. 2 4 1 1 1 2 6 1 4 5 3 6 1 1 1 7 1 Pregnancy Status Yes Yes Yes Yes Yes Ho Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes No Yes Yes Yes aMat1ng confirmed on the basis of the following; vaginal plug, sperm In the .vaginal smear, or evidence of pregnancy (1*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. f[)ue to technician error, this female was not placed with a male on the 14th evening of the mating period. DO 067851 CONFIDENTIAL YZOO14506 K-l - Appendix KAn 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 N 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 tray for purposes of random culling; pups were not Individually Identlf' ' ' n,-)oo lactation. CdOoNFIDFNTIAI- YZ0014507 K-2 t Appendix K (cont.) An Inhalation Female Fertility Study with Benzene In Rats 79-2*25 Postmortem Observations for Pups Culled from Litters on Day 4 of Lactation Group ppm II 1 Female No. *25 426 428 429 431 432 433 434 435 438 440 441 442 445 *47 450 Pup No.* 2.3,8 12 5 7,8,10 4 7,8,10 1 7,13.14 7,8 4,5,7 2.6 5 2,4,7 2.4.7 11,12 3,4,6 13 1,8 7,8,13 2 1.4,8 Sex Observation M N.O.A. F N.O.A. F N.O.A. F N.O.A. M N.O.A. F N.O.A. M N.O.A. F N.O.A. F N.O.A. M N.O.A. M N.O.A. F N.O.A. M N.O.A. M N.O.A. F N.O.A. M N.O.A. F N.O.A. M N.O.A. F N.O.A. M N.O.A. M N.O.A. Key: M Male, F Female, N0.A. * no observable abnormalities* ]DO 067853 CONFTDFNITIAl YZOO14508 K-3 79-2425 mu ii. "! Appendix K (cont.) An Inhalation Female Fertility Study with Benzene in Rats ..r ' i n "*i --- -- *' ' Postmortem Observations for Pups Culled from Litters on Day 4 of Lactation Group ?ST 10 Female No. 626 627 628 630 632 634 635 637 639 640 641 643 644 645 646 Pup No.* 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 N 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: N - Male. F - Female. N.O.A. no observable abnormalities. Arbitrary numbers Identifying a pups location within a partition tray for purposes of random culling; pups were not individually Identified during lactation. DO 067854 CONFIDENT IAI YZ0014509 K-4 Appendix K (eont.) 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 H F F F M F M M F M F M F M H F F H 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 milk 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 CONFIDENTIAL YZOO14510 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 Female 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,<,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 H F F H 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 ?actat1* f random cu^1n8 PUP* W8r* not Individually Identified during 00 067856 CONFIDFNTrAL YZ0014511 m Group ppm I 0 L-1 Appendix t An Inhalation Female Fertility Study with Benzene In Rats "-w - Dead Pud Observations.,- Female Pup Day Found No. No. Sex Dead 230 A F 0 236 237 * 244 A F 14 AM0 AF0 B M0 II 426 1 434 436 440 448 III 625 10 C F0 DF1 EF1 AM0 BF2 AM0 AF0 AM3 AM0 A F0 B F 16 C M 19 D M 19 E F 19 F U.D. . 20 G F 21 79-2425 Observatlqp Autolyzed. Autolyzed. N.O.A. N.O.A. Kidney _g|: 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. Thveus: small (one*fourth normal size), Key: L left, S slight. N.O.A. - no observable abnormalities, M * Hale F Female, U.D. undetermined* 067857 CONFIDETNT IA(. YZ0014512 Group ppn III 10 (cont.) IV 30 L-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 AM 1 A M 11 B F 11 C U.D. 12 D F 14 AF0 BM1 AF3 B F9 A F0 A M Oa B F 0 C F Oa D F0 E M0 AF4 AH1 AF0 B M0 C M9 79-2425 Oly$ervAt1on N.O.A. N.O.A. Autolyzed. Partially can* nlballzed. N.O.A. N.O.A. Kidney (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 (Rl: 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, N Male F Female, U.D. * undetermined, E * extremely. DO 067858 CONFIDFNTIAI I YZ0014513 I "M L-3 Appendix L (cont.) An Inhalation Female Fertility Study with Benzene In Rats - - Dead Pup Observations 79*2425 Female Pup Day Found Group No* No. Sex Dead Observation ppm 1025 A K 0 N.O.A. V 300 BM0 N.O.A* C M0 N.O.A. D F0 N.O.A. / E F1 Autolyzed. FF1 Autolyzed. GM1 Autolyzed. HF1 Autolyzed. 1026 A M 13 Autolyzed: Ab dominal dlstension. 1027 A F 0 Pup Is very pale; all tissues pale* B F0 N.O.A. 1028 A M 3 N.O.A. B F4 Autolyzed. C F5 Autolyzed. 1031 A M 0 N.O.A. B M 0 N.O.A. C F 0 N.O.A. D F 0* N.O.A. 1039 A M 0 Autolyzed. 1044 A F 1 N.O.A. apups removed from litter prior to completion of parturition. Key; N.O.A. - no observable abnormalities, N Hale F- Female. 00 067859 CONFIDENTIAL YZ0014514 Group ppm V 300 (cont.) L-4 Appendix L (cont.) . -An Inhalation Female fertility Study with Benzene In Rats Dead Pud 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. H Male F * Female. DO 067860 CONFIDENTIAL YZ0014515 M-l ' Appendix H*-- An Inhalation Female Fertility Study with Benzene In Bats Certified Feed Information 79-2425 Interval Acclimation Acclimation * Acclimation 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/B0 5/7/80 Oct 03792B Oct 227910 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 Jan 318018 Feb 14801C Feb 14801C Feb 28801F Feb 28801F Feb 14801A `Purina Laboratory Chow 5002 (Certified Diets) Hash; ad Hbltun. DO 067861 CONFIDENTTAl YZ0014516 N-l Appendix N Apt Inhalation Female Fertility Study With Benzene In Rats 79-2425 Pre-test Date Collected: 12/3/1979 Freezing Point (*C) * 5.5064 Purity (X) 99.96 Specific Gravity 0.8845 Total Sulfur by Mlcrocoulometry -ppm <1*0 GC Analysis Sats ppm 42 Toluene ppm 28 Acetone ppm 2 Analysis of Benzene* Study Interval Prior to Initiation of treatment 1/7/1980 Week 6 of the Treatment Period ------11/13/79 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 s/i 5.4895 99.94 0.8843 <1.0 49 29 aAnalyses were performed at the Exxon Research and Engineering Company, Linden, N.O. D 06786? confident tai YZ0014517 Vywb^.H^r 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 5.6 227 5.3 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 6.6 238 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____ nP--re---Curl~l --r~POSt-Cul 1 A- A- A- A9.0 8.5 9.0 8.5 8.0 8.0 8.2 7.9 10.0 9.6 10.0 9.5 9.6 9.7 9.6 9.7 8.4 8.2 8.4 8.3 11.8 10.8 11.8 10.8 10.1 9.5 10.0 9.6 9.5 8.9 9.5 9.0 10.9 10.7 10.8 10.7 8.6 9.1 8.6 9.1 10.8 9.9 10.8 9.9 9.1 8.9 8.9 8.9 11.1 10.5 11.0 10.5 10.7 9.9 10.7 9.9 9.6 9.2 9.7 9.2 7.6 7.9 7.8 7.7 6.6 6.3 6.6 6.3 12.2 12.9 12.2 12.9 8.7 8.5 8.7 8.5 8.3 8.0 8.4 7.9 11.0 11.1 11.0 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 A- A- A- A22.3 21.2 39.2 37.9 23.0 21.9 ` 35.6 34.7 21.9 20.8 38.2 38.3 22.3 21.2 35.6 36.9 21.3 22.2 30.6 38.2 26.0 23.7 41.1 36.2 23.5 23.0 39.0 38.4 23.1 22.0 38.4 38.9 26.6 26.2 44.5 43.3 20.0 19.8 33.5 33.9 25.0 23.0 41.5 38.9 21.9 21.4 33.4 32.5 24.7 22.4 43.8 39.2 25.2 23.5 36.4 35.5 24.1 23.6 36.5 35.6 22.1 23.2 34.6 37.6 11.8 10.8 22.1 20.8 27.6 25.3 46.4 42.0 22.5 21.0 33.8 31.3 22.5 20.5 36.3 33.1 25.7 27.3 43.7 45.3 23.0 22.1 37.3 36.6 3.2 3.2 5.4 5.0 21 2U 21 21 For explanation of statistical symbol: A-; see Appendix Q. Key: M Male F * Female 00 067863 confidential YZ0014518 0-2 Appendix 0 (cont.) An Inhalation Female Fertility Study - With Benzene In Rets 79-242S Mean Pup weights by Sex (grams) - Group II (1 ppm) 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 Day 4____ Pro-Cull n--------- r~ HPo-s--t--C---url 1-* 9.1 8.9 9.2 8.8 10.9 10.2 10.9 10.2 10.3 10.5 10.3 10.6 9.6 8.7 9.8 8.5 8.9 8.1 8.7 8.1 8.7 8.0 8.7 8.0 8.6 8.5 9.0 8.5 9.0 8.3 9.0 8.3 8.9 8.8 8.9 8.8 12.4 10.7 12.4 10.7 10.3 9.2 10.2 9.2 10.3 9.7 10.3 9.7 9.4 8.7 9.6 8.6 8.7 6.1 8.2 6.1 9.6 9.1 9.5 9.1 11.4 11.0 11.4 11.0 12.3 9.0 12.3 9.0 10.6 10.4 10.6 10.5 10.3 10.0 10.2 10.0 9.7 9.2 9.7 9.2 12.4 12.4 11.1 10.8 11.2 10.8 10.1 9.2 10.1 9.2 1.2 1.2 1.2 1.2 22 21 22 21 Day 14 MF 24.4 22.7 24.9 23.8 22.5 23.3 24.7 22.2 21.9 21.7 21.2 19.7 20.3 20.0 22.6 21.7 22.8 20.1 27.1 24.6 27.1 23.8 20.6 19.7 21.9 20.2 22.3 16.5 24.7 24.8 20.3 19.7 26.6 22.0 25.6 25.1 24.6 23.2 20.8 20.3 16.3 29.3 28.7 23.3 22.1 2.9 2.6 22 21 Dev 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 m 47.8 37.4 35.6 7.5 5.5 22 21 No statistically significant differences from the control group* Key: M Male F Female 00 067864 CONFIDFNTTAl. YZ0014519 0-3 Appendix 0 (cont.) An Inhalation Female Fertility Study W.1th Benzene 1nRat*_ 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 *.1 5.2 630 6.3 5.9 631 7.2 6.9 63? 6.3 6.3 633 6.9 6.2 634 5.6 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____ "hP---r-e----C--url~l Post-Cull r--r~ 11.0 9.9 11.0 9.9 11.1 10.7 10.8 10.7 8.3 7.7 8.2 7.7 9.2 8.1 9.2 8.1 8.4 8.3 8.2 8.3 13.0 13.0 13.0 13.0 9.2 8.9 9.1 8.9 12.2 11.1 12.2 11.1 10.3 10.5 10.1 10.6 10.0 9.3 10.1 9.4 16.0 15.5 16.0 15.5 9.3 8.7 9.2 8.7 10.4 10.5 10.4 10.3 8.9 8.5 8.9 8.9 9.3 8.9 9.4 8.9 12.7 11.6 12.7 11.6 10.1 9.3 10.0 9.5 8.1 7.5 8.0 7.6 9.1 8.9 9.1 9.0 8.5 8.0 8.6 8.3 10.2 10.1 10.2 10.2 12.5 11.8 12.5 11.8 9.7 9.9 9.7 9.9 9.8 9.0 9.7 9.3 10.3 9.8 10.3 9.9 1.9 1.8 1.9 1.8 24 24 24 24 Day 14 HF 15.5 13.4 24.9 24.2 18.8 17.5 19.7 17.8 11.6 13.3 30.8 30.3 22.2 22.7 25.6 24.8 25.5 26.2 25.8 24.4 32.4 32.4 24.7 23.3 24.7 23.9 22.9 23.0 20.0 19.9 26.0 23.8 24.6 23.4 23.4 22.5 21.8 23.1 23.3 23.9 21.8 20.6 30.2 28.6 23.8 24.3 24.9 23.6 23.5 23.0 4.5 4.4 24 24 Da y 21 MF 17.3 13.1 36.6 42.5 28.4 26.4 29.6 26.5 24.7 24.6 51.4 50.0 36.2 38.1 41.8 40.7 39.3 41.7 44.9 40.9 54.9 54.5 39.9 37.3 43.0 39.9 39.4 37.8 30.0 29.3 45.4 42.3 42.2 38.3 33.8 33.7 35.2 36.8 35.3 37.5 37.8 35.2 48.6 47.0 39.3 39.7 39.2 37.8 38.1 37.1 8.4 8.6 24 24 No statistically significant differences from the control group.. Key: M Male F Female DO 06786-S confidfnttal YZ0014520 0-4 Appendix 0 (cont.) An Inhalation Female Fertility Study - With Benzene in Rata 79-2425 Mean Pup Weights by Sex (grams) - Group IV (30 ppn) Female No. Day 0 HF 825 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: N: 6.4 6.1 0.7 0.6 19 19 Day 4 Pre-Cull Post-Cull XT F ~r~ F 9.4 9.0 9.4 8.9 10.2 9.7 10.2 10.0 10.7 10.2 11.0 10.1 10.6 10.0 10.6 10.0 11.3 11.3 11.3 11.3 9.4 9.5 9.5 9.5 8.7 8.3 8.6 8.1 11.3 11.9 11.3 11.9 9.6 8.7 9.8 9.1 9.1 8.3 9.2 8.1 9.3 8.5 9.2 8.5 8.3 7.8 8.3 7.8 8.5 8.2 8.5 8.4 13.8 12.3 13.8 12.3 8.7 8.3 8.7 8.2 7.7 8.0 7.9 8.0 9.4 9.6 9.4 9.6 9.3 9.3 9.3 9.3 14.1 13.6 14.1 13.6 10.0 9.6 10.0 9.6 1.7 1.6 1.7 1.6 19 19 19 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 22.1 3.7 3.2 19 19 Dav 21 MF 35.2 33.1 38.3 37.4 39.5 37.0 31.2 32.5 37.8 41.5 29.2 31,8 33.7 31.3 42.4 40.8 40.1 35.8 31.4 30.6 27.3 26.5 31.0 29.5 30.4 30.7 45.9 41.9 29.0 30.1 29.4 31.4 30.6 31.5 30.3 33.6 45.9 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 067866 C0NFIDENTTfi,i YZ0014521 . m* mm*- 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. Da y 0 MF 1025 1026 1027 1028 1029 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1042 1043 1044 104S 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 Kean: S.D.: N: 6.1 5.9 0.6 0.5 22 23 Day 4 Pre-Cull Post-Cul 1 "R-- r --R F^ m to to 9.4 9.0 9.2 9.0 11.2 10.4 11.2 10.4 6.4 5.8 6.4 5.8 9.4 9.1 to 13.1 9.3 9.1 to 13.1 8.2 8.1 8.1 8.1 9.6 9.1 9.6 9.3 9.0 8.6 9.0 8.6 10.0 9.6 10.2 9.6 8.4 8.4 8.3 8.4 9.8 9.1 10.0 9.2 8.5 8.1 8.5 8.1 10.3 9.6 10.3 9.6 9.8 9.1 10.0 9.2 10.9 10.0 10.9 10.0 9.4 10.0 9.4 10.0 8.5 8.4 8.5 8.4 10.7 8.9 10.7 8.9 8.8 8.2 8.7 8.3 14.1 13.6 14.1 13.6 10.4 9.8 10.5 9.8 10.1 9.5 10.0 9.5 9.7 9.3 9.7 9.4 1.5 1.6 1.5 1.6 21 22 21 22 Day 14 HF 15.2 23.1 16.7 21.1 to 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 to 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 21.8 21.1 2.7 2.9 21 22 Da y 21 MF to 24.5 39.9 24.1 27.9 to 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 YZOO14522 P-1 Appendix P , DOERMTftATTON OF POLLUTANTS IN DWHKIWS WATER. filVEN TO ANIMALS FOR STUDIES NO. 79-2425 AND 79-7342 Report No.: 80023 Sponsor: f Prepared by: Chemical Manufacturers' Association and American Petroleum Institute Washington, O.C. James C. Eschbach Date: September 3, 1980 Issued by: Blo/dynamlcs Inc. Department of Metabolism and Analytical Chemistry Environmental Sciences P.0. 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. Director Department of Metabolism and Analytical Chemistry DO 067868 CONFIDENTIAL YZOO14523 P-2 Appendix P (cont.) 80023 P 2 Of 1.0 INTRODUCTION Drinking water samples were collected at two Intervals from the rooms In which the animals for Studies No. 79-2425 and 79-7342 were housed. These samples were assayed for compounds which could have adverse effects on the studies if.they were prase In the drinking water. The samples were assayed for benzene, trac metals, pesticides end PCBs at the beginning and end of the studle 2.0 EXPERIMENTAL Water samples were collected and composited since they were from the same water source. An aliquot was taken for benzene for assay according to Method 624 for volatile organic compounds by purge and trap prior to g.c./mass spectrometry. This sample 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. 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. I* DO 067869 CONFIDENTIAL YZOO14524 P-3 Appendix P (cont.) 80023 P 3 Of 4 4.0 ACKNOWLEDGEMENT This study was supportad by both tht Chemical Manufacturers' Association and the American Petroleum Institute. / DO 067870 CONFIDENTIAL __ J YZ0014525 P-4 Appendix P (cont.) TABLE I. RESULTS OF PRINKING MATER ASSAYS FOR STCBIIS NO. 75-2425 m 79-7342 METALS Antimony Beryl llun Cadmium Arsenic Lead Mercury Selenium Assayed 6/12/80 m <6.7b <1.0 <1.0 <1.0a 1.2 <0.5 <8.3 Assayed 3/17/80 fiok < 1.3 < 1.0 < 1.0 < 0.5 < 1.0 <0.5 < 1.0 a. Sandies assayed using metal hydride PESTICIDES Lindane Heptachlor DDT 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 80023 P 4 of a. Laval of detection high because graphite method of analysis used Instead of hydride method of analysis. b. Level of detection higher because of possible loss In lamp efficiency. DO 067871 CONFIDFNTTAl YZ0014526 Q-l Appendix Q An Inhalation Female Fertility Study .with Benzene In Rate 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 when 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 - PreMating 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-litter 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 067872 DONFrOFNTTAI. 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 wire 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 wis 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 sunned 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 (l.e. equal variance), standard regression techniques with e 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 It, two-sided risk level. All other statistical tests were conducted at the 5t and It twosided risk levels. Snedecor, G.W., and Cochran, U.G., Statistical Methods. 6th ed.,lowa State Unlv. Press (1967), Hollander and dolfe. Nonparametrlc Statistical Methods. John Wiley and Sons, New York (1973), Dunnett. C.W..J. Am. 15ta. Assn,. Yol. 50 (1955) and Biometrics, Yol. 20 (1964). Bartletts's Test ANOVA Dunnett's Test Kruskal-Wallls Summed Rank Test (Dunn) Regression Analysis Trend Lack of Fit Jonckheere's Statistic pp. 296-296 pp. 277-279 pp. 1096-1121, 482 pp. 114-116 pp. 131 pp. 149-152 pp. 160-164 pp. 120-123 SBC SBC D HAW HAW SBC SBC HAW DO 06*7873 CONFIDENTIAL YZ0014528 Q-3 . - .Appendix Q (cont.)*fc An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Methodology and References (cont.) Statistical Analysis of Data (cont.) Method Bb: Statistical analysis of Incidence data was performed using contingency tables. FtYst, 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, Armltage's test for linear trend In the dosage groups was performed. bChl-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, N.J., pp. 195-203. Bonferronl Inequality: Miller, R.G., Jr.. Simultaneous Statistical Inference McGraw-Hill Book Co., k.Y. 1966, p. 15. Armltage's Test: Armltage, P., "Tests for Linear Trends In Proportions and Frequencies". Biometrics. Sept. 1955, pp. 375-386. DO 067874 CONFIDENTIAL YZ0014529 q-4 --_ Appendix Q (cont.) --^ An Inhalation Female Fertility Study with Benzene In Rats 79-2425 Methodology and References (cont.) Statistical Analysis of Data (cont.) Method Cc_: ANALYSIS OF LITTER DATA s 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 1% 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 ras.-na:Medical Science, vol. I. the lowa state University Press. Ames. I- DO 067875 1 CONFIDENTIAL 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 Rotations No Slg Symbol '(><0.05 p<0.01* * A- A A+ * ** KH- H+ ft tt Statistical Statement Absolute Data No statistical differences among the means (parametric ANOVA). Significantly different from control (Ounnett's). No statistical differences among the means (Kruskal-Wa111s nonparametrlc). A nested analysis of variance Q-4. Significantly different from control LSD test. Incidence Data # ## Significantly different from control (Fisher Exact Test). DO 06.7876. CONFIDENTIAL YZ0014531 R-l ___ _ Appendix R ^ ^""An"inhalation Female FertllltJTStudy 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 A TERATOLOGY SECTION MANAGER Raymond E. Schroeder M.S. SUPERVISOR Maureen Kenny B.A. technician-in-charge Barbara Bernard VETERINARIAN Fred A. Hines D.V.M. PATHOLOGY PATHOLOGIST DATA LOGISTICS SUPERVISOR Henry F. Bolte B.J. Guth D.V.M., Ph.D. B.A. QUALITY ASSURANCE SUPERVISOR Craig M. Lamb B.A. DO 067877 CONFIDENTIAL YZ0014532