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TSCA SANITIZED P-1 filili- 5% 33 CHARLES RIVER LABORATORIES (M in k a ! Services 29 May 2007 Steven C Gordon, P h D ., D A B I -- 3 h fC orporateT oxicology& R egulatory'Seivices 3M M edical Department 3M Center, Bldg. 220-6E -03 S t Paul, MN 55144-1000 Tel: 651.736.5485 Fax: 651.733.1773 E-mail: scgordon@ mmm.oom .............. ..... ........... ............................ RE: Protocol ZXA00077 - Oral (Gavage) Developm ental Toxicity Screening Study o f M ID 6675 in Rats Sponsor's Reference N o. 06-376 Dear Dr. Gordon: Enclosed are unaudited draft summary tables from the a id o f the in -life phase o f the screening study. The follow ing information summarizes the results o f this study M ethodology - FO Generation Reta Sixty presumed pregnant Crl:CD(SD) rats, 10 per group, were randomly assigned to six dosage groupe. Formulations o fth e test article, M TDID 6675C J, and/or tire vehicle, reverse osm osis membrane processed deionized water (R.D.. deionized water), were administered once daily via oral gavage at dosage levels olf0 (V ehicle), 1 0 ,3 0 ,9 0 ,2 7 0 and 500 mg/kg/day. The dosage volum e was 5 m L/kg, adjusted daily on the basis of the individual body w eights recorded immediately before intubation. Fem ale rats were administered the test article and/or the vehicle once daily beginning on day 0 o f presumed gestation (DG 0 ) through the day o f delivery or DG 24 (rats drat do not deliver a litter) Checks for viability were m ade tw ice daily Clinical observations w ere recorded w eekly during the acclim ation period, once prior to randomization during the predosage period and daily before administration during the dosage period Posltdosage observations were recorded at approximately hourly intervals for the four hours and at the end o fth e normal working day for the first nine days o fth e dosage period. Beginning on the tenth day o fth e dosage period, postdosage observations w ere reoorded within 1 to 2 hours ofd osage and at the end o fth e normal working day. Maternal behavior w as evaluated daily and recorded on days 1 ,4 and 6 o f lactation (DLs 1 ,4 and 6 ) Abnormal behavior w as recorded daily upon observation. 905 Sheehy Drive, Bldg A, Horsham, PA 19044 215443 8710 FAX:21544.38587 www.crivercom TSCA SANITIZED P-2 Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 2 o f 16 Body weights were recorded weekly during the acclimation period and on DG 0, daily during the dosage period, daily during the postdosage period and on the day o f euthanasia. Feed consumption values were recorded on DG 0, daily during the dosage and postdosage periods, and the remaining feed value was recorded on the day o f euthanasia. Beginning on DG 21, F0 generation female rats were continually evaluated (12 hours per day; 0800 to 2000, and at 2300,0200 and 0500) for the following parameters: clinical observations during parturition (time each pup is observed was recorded); duration o f gestation (DG 0 to the time the first pup is observed); length o f parturition (time of observation o f last pup minus the time o f observation o f the first pup divided by N -l pups in each litter); litter size (defined as all pups delivered); and pup viability at birth. Clinical signs and the time o f death for each pup were recorded. These observations continued to be recorded through the first 24 hours after parturition on the previously defined schedule. On DLs 2 through 5, clinical signs and the times o f any deaths were recorded at least three times each day. Whenever parturition was complete after 1800 hours, the following day was considered DL 1. Any pups found partially cannibalized or that were in the process o f being cannibalized were euthanized, as needed, and the carcass was retained for possible future evaluation in the appropriate fixative for the age o f the pup. Rats that were found dead or were euthanized before scheduled termination were ftvamiWH for gross lesions on the day the observation was made. The lungs, trachea and esophagus were perfused and saved in neutral buffered 10% formalin for possible future evaluation. When not precluded by autolysis, the heart, liver, kidneys, stomach and spleen were retained in neutral buffered 10% formalin for possible histological evaluation. Pregnancy status and uterine contents o f female rats were recorded. Conceptuses in ntero and/or delivered pups were examined to the extent possible. Uteri o f apparently nonpregnant rats were stained with 10% ammonium sulfide to confirm the absence o f implantation sites. Rats that did not deliver a litter were euthanized on DG 25 and examined for gross lesions. Uteri o f apparently nonpregnant rats were stained with 10% ammonium sulfide to confirm the absence o f implantation sites. After completion o f a 5-day postpartum period, all surviving female rats were euthanized via carbon dioxide asphyxiation on DL 6, and a gross necropsy o f the thoracic, abdominal and pelvic viscera was performed. The number and distribution o f implantation sites were recorded. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 p .3 TSCA SANITIZED Protocol 2XA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 3 of 16 Methodology - FI Generation P uds FI generation pups were not directly given the test article or the vehicle but may have been exposed to the test article or the vehicle during maternal gestation (in utero exposure) or via maternal m ilk during the lactation period. Litters were observed for dead pups at least three times daily. The approximate times o f death were recorded. The pups in each litter were counted three times daily, except on DL 1, in cases where parturition was complete after 1800 hours and on DL 6, when pups in each litter were counted once prior to euthanasia. Clinical observations were recorded at least three times daily during the preweaning period. Body Weights were recorded on postnatal days l, 4 and 6 (PNDs 1 ,4 and 6). Pups that died before examination o f the litter for pup viability were evaluated for vital status at birth. The lungs were removed and immersed in water; pups w ith lungs that did not float were identified as stillborn and pups with lungs that did float were identified as livebom, and to have died shortly after birth. Pups were preserved in Bourn's solution for possible future evaluation. Pups that died or were euthanized prior to scheduled termination were examined for cause o f death or condition and gross lesions on the day the observation was made. Pups found on PNDs 2 to 4 were preserved in Bouin's solution for possible future evaluation. Surviving pups were euthanized via intraperitoneal injection o f sodium pentobarbital on PND 6 and examined for gross lesions. Necropsy included a single cross-section o f the head at the level o f the frontal-parietal suture, and examination o f the cross-sectioned brain for apparent hydrocephaly. Results M ortalities Two F0 generation female rats assigned to the 500 mg/kg/day dosage group were found dead on DG 2 (day 2 o f dosing). Dosage administration was subsequently terminated for the 500 mg/kg/day dosage group due to these deaths and adverse clinical observations that were occurring. The remaining eight F0 generation female rats in this dosage group were euthanized. Four F0 generation female rats assigned to the 270 mg/kg/day dosage group were found dead on either DG 3 or DG 5, and one rat in this dosage group was euthanized due to adverse clinical condition on DG 21. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 P-4 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 4 of 16 All o f these mortalities were attributed to MTDID 6675 because the incidences were dosage dependent. One F0 generation female rat in the 10 mg/kg/day dosage group was euthanized on DG 23 due to adverse clinical condition. The dam apparently had problems in delivering its litter, resulting in the fetuses dying in utero, leading to its adverse clinical condition. This single event was not considered related to the test material because it did not occur in a dosage-dependent manner and problems in delivery are known to occur in this strain o f rat. Information for these female rats is included in the table on subsequent pages. All other F0 generation rats survived to scheduled euthanasia. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 P-5 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 PageS o f 16 Dosage Group 500 MKD Rat Day of Number Gestation Mode o f Death 23960 DG 1 Scheduled Euthanasia - Early Termination 23959 DG1 Scheduled Euthanasia- Early Termination 23958 DG1 Scheduled Euthanasia - Early Termination Number of Doses Administered 1 1 1 Clinical Observations, Body Weights, Feed Consumption, Necropsy Observations and Uterine Contents Clinical Observations: Localized alopecia (limbs) and cold to touch (DGs 0 and 1); dehydration, hunched posture and decreased motor activity (D G 1). Body Weights: Body weight loss of 33 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: Spleen appeared small; all other tissues appeared normal. U teriae Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Localized alopecia [limbs (DGs 0 and 1)]; urine-stained abdominal fur and cold to touch (DG 1). Body W eights: Body weight loss of 16 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: All tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Dehydration (DG 1). Body W eights: Body weight loss of 19 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: All tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 P-6 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 6 of 16 Dosage Group 500 MKD Rat Day of Number Gestation Mode of Death 23957 DG 1 Scheduled Euthanasia - Early Termination 23956 DG 1 Scheduled Euthanasia - Early Termination 23955 DG 2 Scheduled Euthanasia - Early Termination Number of Doses Administered 1 1 2 Clinical Observations, Body Weights, Feed Consumption, Necropsy Observations and Uterine Contents Clinical Observations: Urinestained abdominal fur and cold to touch (DGs 0 and 1); and rales (DG 1). Body Weights: Body weight loss of 28 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: All tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Dehydration and cold to touch (DG 1). Body W eights: Body weight loss of 23 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: All tissues appeared normal. Uterine Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Rales (DG 1); and dehydration (DGs 1 and 2). Body W eights: Body weight loss of 6 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 2. Necropsy Observations: All tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 P-7 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 7 o f 16 Dosage Group 500 MKD Rat Number 23954 23953 23952 Day of Gestation DG 2 DG2 DG 2 Mode of Death Scheduled Euthanasia - Early Termination Found Dead Scheduled Euthanasia - Early Termination Number o f Doses Administered 2 2 2 Clinical Observations, Body Weights, Feed Consumption, Necropsy Observations and Uterine Contents Clinical Observations: Urine- stained abdominal fur and dehydration (DGs 0 and 1); ungroomed coat, cold to touch, and decreased motor activity (DG 1). Body W eights: Body weight loss of 34 g from DG 0 to DG 2. Feed Consam ption: Feed consumption reduced from DG 0 to DG2. Necropsy Observations: Stomach distended with gas; all other tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Urinestained abdominal fur (DGs 0 to I); rales, dehydration, cold to touch, pale extremities, ptosis and decreased motor activity (DG 1). Body W eights: Body weight loss of 33 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: Stomach distended with gas; all other tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Dehydration and cold to touch (DGs 1 and 2); ungroomed coat and decreased motor activity (DG 2). Body W eights: Body weight loss of 39 g from DG 0 to DG 2. Feed Consumption: Feed consumption reduced from DG 0 to DG2. Necropsy Observations: Stomach distended with gas; all other tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 p .8 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 8 o f 16 Dosage Group 500 MKD 270 MKD Rat Day of Number Gestation Mode of Death 23951 DG 2 Found Dead 23950 DG 3 Found Dead Number of Doses Administered 2 3 Clinical Observations, Body Weights, Feed Consumption, Necropsy Observations and Uterine Contents Clinical Observations: Urinestained abdominal fur (DGs 0 and 1) and dehydration (DG 1). Body Weights: Body weight loss of 30 g from DG 0 to DG 1. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: Thymus contained red areas too numerous to count, ranging in size from pinpoint to 0.2 cm x 0.1 cm; all other tissues appeared normal. Uterine Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Rales (DG 0); dehydration and cold to touch (DGs 1 and 2); urine-stained abdominal fur and ungroomed coat (D G 2). Body Weights: Body weight loss o f 36 g from DG 0 to DG 2. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: All tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 P-9 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 9 o f 16 Dosage Group 270 MKD Rat Number 23947 23946 Day of Gestation Mode of Death DG 5 Found Dead DG 3 Found Dead Number o f Doses Administered 5 4 Clinical Observations, Body Weights, Feed Consumption, Necropsy Observations and Uterine Contents Clinical Observations: Urinestained abdominal fur (DGs 1 through 3); cold to touch (DGs 1 through 4); dehydration (DGs 1 through 5); ungroomed coat (DGs 2 through 4); pale extremities, and decreased motor activity (DG 3). Body W eights: Body weight loss of 30 g from DG 0 to DG 4. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: Stomach distended with gas; all lobes o f the lungs mottled red and dark red; lungs appeared to be inflated prior to perfusion; trachea and esophagus contained a pink foamy substance; all other tissues appeared normal. U terine Contents: Pregnancy status could not be confirmed due to early gestational age. Clinical Observations: Urinestained abdominal fur (DG 0 ,2 and 3); dehydration and cold to touch (DGs 1 through 3); rales (DG 2); ungroomed coat, bradypnea, perioral substance, pale extremities, discoloration, ptosis, perinasal substance, decreased motor activity, and impaired righting reflex (DG 3). Body W eights: Body weight loss of 60 g from DG 0 to DG 3. Feed Consumption: Feed consumption reduced from DG 0 to DG 1. Necropsy Observations: Stomach distended with gas; spleen appeared small; mucosal surface of the fiindic region o f the stomach contained red areas too numerous to count ranging in size from pinpoint to 0.4 to 0.S on; renal pelvis o f both kidneys red; both adrenals red; abdominal adipose tissue pink; all other tissues appeared normal. Uterine Contents: Pregnancy status could not be confirmed due to early gestational age. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 10 of 16 Dosage Group 270 MKD Rat Number 23945 23941 Day o f Gestation Mode o f Death DG 21 Unscheduled Euthanasia DG3 Found Dead Number of Doses Administered 22 3 Clinical Observations, Body Weights, Feed Consumption, Necropsy Observations and Uterine Contents Clinical Observations: Ungroomed coat (DGs 0,1 and 2); dehydration (DGs 1 through 4 and 21); urine-stained abdominal fur (DGs 2,4 and 6); cold to touch (DGs 3 through 6 and 21); rales (DG 4); red perioral substance, pale extremities, low carriage and decreased motor activity (DG 21). Body Weights: Body weight loss of36 g from DG 19 to DG 21. Feed Consumption: Feed consumption reduced from DG 19 to DG 21. Necropsy Observations: All tissues appeared normal. Uterine Contents: There were 12 dead fetuses and one early resorption in utero. All fetuses appeared normal for developmental age. Clinical Observations: Dried feces, urine-stained abdominal fur, dehydration, cold to touch, pale extremities, lacrimation and decreased motor activity (DG 2). Body Weights: Body weight loss of 55 g from DG 0 to DG 2. Feed Consumption: Feed consumption reduced from DG 0 to DG 2. Necropsy Observations: All tissues appeared normal. Uterine Contents: Pregnancy status could not be confirmed due to early gestational age. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 11 o f 16 Dosage Group 10MKD Rat Number 23919 Day o f Gestation Mode of Death DG23 Unscheduled Euthanasia Number of Doses Administered 23 Clinical Observations, Body Weights, Feed Consumption, Necropsy Observations and Uterine Contents Clinical Observations: Localized alopecia on limbs (DGs 14 through 16); alopecia no longer apparent (DG 17); cold to touch, pale extremities, perivaginal substance (DG 23). Body W eights: Body weight gain of 1S2 g from DG 0 to DG 23. Feed Consumption: Feed consumption reduced from DG 22 to DG23. Necropsy Observations: Red gelatinous material present in the right hom o f the uterus at the cervix; all other tissues appeared normal. U terine Contents: There were 2 live and 14 dead fetuses in utero. One fetus had tire left hindlimb rotated medially; all other fetuses appeared normal for developmental age. C linical O bservations Clinical observations in rats in the 500 mg/kg/day dosage group were described previously in the mortality table. Clinical signs observed in rats in the 270 mg/kg/day dosage group included decreased m otor activity, impaired righting reflex, chromorhinorrhea, ptosis, lacrimation, perinasal substance, low carriage, dehydration, cold to touch, pale extremities, discoloration, perioral substance, rales, bradypnea, urine-stained abdominal fur, ungroomed coat and dried feces; all o f these signs were attributed to treatment with the test article because the signs occurred in the highest surviving dosage group. Urine-stained abdominal fur was also observed in the 90 mg/kg/day dosage group and was attributed to MTDID 6675. Cold to touch and pale extremities were observed in the 10 mg/kg/day dosage group but were not attributed to MTDID 6675 because: 1) the incidences o f these clinical signs in this dosage group did not demonstrate a dosage-dependent pattern o f effect; and 2) both clinical signs occurred in only one rat in this group. Chromodacryorrhea, perivaginal substance, sparse hair coat (limbs, back and/or underside) and soft or liquid feces were observed in the 0 (Vehicle), 10,30 and 90 mg/kg/day dosage groups and were not attributed to MTDID 6675 because: 1) the incidences for these findings did not demonstrate a dosage-dependent pattern o f effect; and/or 2) the clinical sign occurred in a limited number o f rats in any dosage group. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED ProtocolZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 12 o f 16 During the lactation period, sparse hair coat (limbs, back and/or underside) and localized alopecia (limbs) were observed in the 0 (Vehicle), 10,30 and/or 90 mg/kg/day dosage groups. These clinical observations were not attributed to treatment with MTDID 6675 because: 1) the signs were observed after completion o f the dosage period; and 2) the incidences of these findings did not demonstrate a dosage-dependent pattern o f effect. Necropsy Observations With the exception o f gross lesions described previously in the mortality table, necropsy examinations revealed no additional gross lesions. Body W eiehts/Bodv Weight Changes Following the initiation o f the dosage period, an overall body weight loss occurred on DGs 0 through 3, and body weight gains were reduced on DGs 3 through 6 in the 270 mg/kg/day dosage group, in comparison with the respective control group values. However, body weight gain began to rebound in this dosage group on DGs 6 through 9. Reductions in body weight gains also occurred in the 90 mg/kg/day dosage group on DGs 0 through 3 and DGs 6 through 9, in comparison with the respective control group values. Body weight gains were reduced in the 90 and 270 mg/kg/day dosage groups during the overall gestation dosage period (calculated as DGs 0 through 20). On DG 20, mean body weights were 97.8%, 98.7%, 96.4% and 85.7% o f the control group value in the 10,30,90 and 270 mg/kg/day dosage groups, respectively. During the overall lactation period (calculated as DLs 1 through 6), body weight gains were increased over the control group value in the 90 and 270 mg/kg/day dosage groups. On DL 6, mean body weights were 98.6%, 101.1%, 98.4% and 95.7% o f the control group value, in the 10,30,90 and 270 mg/kg/day dosage groups, respectively. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 13 o f 16 Absolute fg/davl and Relative (g/kc/dav) Feed Consumption Values Absolute (g/day) and relative (g/kg/day) feed consumption values could not be recorded accurately for die 270 mg/kg/day dosage group on DGs 0 through 3 and 3 through 6 because the rats in this dosage group were provided with moistened feed during these periods at the recommendation o f the veterinary staff. Absolute (g/day) and relative (g/kg/day) feed consumption values were reduced in the 90 and 270 mg/kg/day dosage groups during the gestation dosage period (calculated as DGs 0 through 20), in comparison with the respective control group values, as well as most o f the intervals within the gestation dosage period. During the overall gestation dosage period (calculated as DGs 0 through 20), absolute feed consumption values were 99.1%, 100.0%, 94.1% and 8k.9% and relative feed consumption values were 100.5%, 100.6%, 96.1% and 93.0% o f the Control group means in the 10,30,90 and 270 mg/kg/day dosage groups, respectively. Absolute and relative feed consumption values were reduced during the overall lactation period (calculated as DLs 1 through 6) in the 10,30,90 and 270 mg/kg/day dosage groups, in comparison with the respective control group values. On DLs 1 through 6, absolute feed consumption values were 92.0%, 92.6%, 92.0%, and 76.1% and relative feed consumption values were 91.6%, 90.7%, 93.7% and 79.8% o f the control group value, in the 10,30,90 and 270 mg/kg/day dosage groups, respectively. Natural Delivery and Litter Parameters Nine, eight, ten, ten and five dams delivered litters with one or more livebom pups in the 0 (Vehicle), 10,30,90 and 270 mg/kg/day dosage groups, respectively. There were 2 ,3 ,2 ,1 and 1 dams with stillborn pups in each o f the 0 (Vehicle), 10,30,90 and 270 mg/kg/day dosage groups, respectively. One dam in the control group and two dams in the 270 mg/kg/day dosage group had all pups die between t)L s 1 through 4. The numbers o f stillborn pups, pups found dead or presumed cannibalized on DL 1 and on DLs 2 through 4 were increased, and the number o f livebom pups, viability index, the number o f surviving pups on DLs 1,4 and 6, live litter sizes and pup weights per litter on DLs 1,4 and 6 were reduced in the 270 mg/kg/day dosdge group, in comparison with the respective control group values. Mean pup weights per litter were also reduced in the 90 mg/kg/day dosage group on DLs 1,4 and 6. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 14 of 16 Mean length o f parturition was reduced in the 270 mg/kg/day dosage group, in comparison with the control group mean. Information on the length o f parturition is included below in the table. Dosage Level (mg/kg/day) Number o f Rats Per Group Number Mated Number Pregnant Parturition Parameters - Mean S.D. (minutes) 0 (Vehicle) 10 30 90 10 10 10 10 10 10 10 10 9 9 10 10 Length o f Parturition (N) 7.572.57 (2) Time Between Deliveries - 9.904.06 Partial (N) ____(6) Time Between Deliveries - 7.572.57 Complete (N) (2) N - Number of dams evaluated 13.006.55 (5) 19.99tl0.90 (3) 13.00fct6.55 (5) 9 .98 .24 (4) 9.633.71 (6) 9.981.24 (4) 9.272.86 (5) 8.963.04 (5) 9.272.86 (5) 270 10 10 6 5.041.83 (2) 6.180.0 (1) 5.041.83 (2) 500 10 10 Not applicable Not applicable Not applicable Not applicable Pup weights per litter were considered reduced in the 90 and 270 mg/kg/day dosage groups. On PND 1, average pup weights were 96.8%, 93.7%, 87.3% and 73.0% o f the control group value, and on PND 6, average pup weights were 100.9%, 99.1%, 90.1% and 74.8% for the 10,30,90 and 270 mg/kg/day dosage groups, respectively. The values in the 90 and 270 mg/kg/day dosage groups on DL 1 (5.5 and 4.6, respectively) were below the historical control range (6.0g to 6.8 g) for this Testing Facility based on data collected from June 2004 to January 2006. The duration o f gestation was generally comparable among the dosage groups. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED Clinical and Necropsy Observations - FI Generation Puns Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 15 o f 16 Two pups from two litters in the 270 mg/kg/day dosage group had body regions that were discolored purple; the lower midline, both hindlimbs and tail were discolored purple in one pup, and the right hindlimb and hindpaw were discoloiled purple in the other pup. The nose was discolored purple in three pups from one litter in 3b mg/kg/day dosage group. One pup from the 10 mg/kg/day dosage group and two littermates in the 90 mg/kg/day dosage group were cold to touch. One o f the two pups from the 90 mg/kg/day dosage group was also observed on DL 4 as pale, not nesting and not nursing One pup from the 30 mg/kg/day dosage group was missing the tip o f the tail. Purple discoloration o f body regions in the pups in the 270 mg/kg/day dosage group was attributed to MTDID 6675 because: 1) the clinical observation occurred in the highest surviving dosage group; and 2) the discoloration was more extensive in these pups. All other clinical observations were not attributed to treatment with the test article because the incidences did not demonstrate a dosage-dependent pattern o f effect. All other p ip s appeared normal. Among pups that were found dead, 0 , 0 , 1 , 1 and 10 pups in the 0 (Vehicle), 10,30,90 and 270 mg/kg/day dosage groups, respectively, had no milk present in the stomach. The increased incidence in the 270 mg/kg/day dosage group was attributed to MTDID 6675. 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED Protocol ZXA00077 Sponsor's Reference No. 06-376 29 May 2007 Page 16 of 16 Conclusion M ortalities, adverse clinical signs and decreases in maternal body weight and feed consumption occurred during gestation at 90 and/or 270 mg/kg/day; body weight rebounded during the lactation period in these dosage groups, but feed consumption remained reduced. A reduction in pup weight occurred in the 90 mg/kg/day dosage group, and doses o f 270 mg/kg/day also produced reproductive and developmental toxicity as evidenced by shortened parturition time, pup death and decreased pup weights. Therefore the no-observable-adverse-effect-level (NOAEL) for both maternal toxicity and developmental toxicity was 30 mg/kg/day o f MTDID 6675. If you have any questions, please do not hesitate to contact me. Sincerely, AMH:mbc Attachments Alan M. Hoberman, Ph.D., DABT, Fellow ATS Director o f Research Study Director 905 Sheehy Drive, Bldg. A, Horsham, PA 19044 215.443.8710 FAX 215.443.8587 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 1 (PAGE 1) : CLINICAL OBSERVATIONS - SUMMARY TABLE RANGE :: GESTATION PERIOD DOSAGE GROUP I II MAXIMUM POSSIBLE INCIDENCE 219/ 10 223/ 10 APPEARS NORMAL 211/ 10 167/ 9 FOUND DEAD SCHEDULE SACRIFICED UNSCHEDULED SACRIFICED SACRIFICED - DAY 25 OF (PRESUMED) GESTATION 00 00 01 11 III 213/ 10 203/ 10 0 0 0 0 IV 212/ 10 162/ 9 0 0 0 0 DECREASED MOTOR ACTIVITY IMPAIRED RIGHTING REFLEX CHROHODACRYORRHEA CHROMORHINORRHEA PTOSIS IACMMATION PERINASAL SUBSTANCE LON CARRIAGE DEHYDRATION COLD TO TOUCH PALE EXTREMITIES H W C H E D POSTURE DISCOLORATION DELIVERING - NOT DOSED DELIVERING PERIVAGINAL SUBSTANCE ALOPECIA NO LONGER APPARENT PERIORAL SUBSTANCE RALES BRADYFNEA URINE-STAINED ABDOMINAL FUR UNGROOMED COAT SPARSE HAIR COAT: LIMB(S) LOCALIZED ALOPECIA: LIMB(S) SPARSE HAIR COAT: BACK SPARSE HAIR COAT: UNDERSIDE DRIED FECES SOFT OR LIQUID FECES 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 or 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 8/ 1 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 1/ 1 or 0 or 0 i/ 1 2/ 2 i/ 1 i/ 1 or 0 0/ 0 or 0 0/ 0 0/ 0 32/ 3 23/ 2 0/ 0 0/ 0 or 0 or 0 N/N - TOTAL NUMBER OF OBSERVATIONS/NUMBER OF ANIMALS WITH THE OBSERVATION MAXIMUM POSSIBLE INCIDENCE - (DAYS x ANIMALS)/NUMBER OF ANIMALS EXAMINED PER GROUP 0/ 0 0/ 0 0/ 0 or 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 or 0 or 0 0/ 0 i/ 1 or 0 0/ 0 or 0 or 0 or 0 or 0 or 0 0/ 0 10/ 1 or 0 0/ 0 0/ 0 or 0 or 0 or 0 or 0 0/ 0 or 0 or 0 or 0 or 0 0/ 0 or 0 or 0 or 0 or 0 0/ 0 or 0 0/ 0 0/ 0 0/ 0 0/ 0 or 0 2t 2 or 0 8/ 2 43/ 3 17/ 1 or 0 or 0 i/ 1 V 148/ 10 118/ 10 4 0 i 0 4/ 4 1/ 1 or 0 i/ i i/ 1 i/ 1 i/ 1 i/ 1 34/ 10 34/ 10 4/ 4 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 2/ 2 6/ 6 1/ 1 18/ 9 11/ 6 or 0 or 0 or 0 0/ 0 i/ 1 0/ 0 VI 25/ 10 9/ 9 2 8 0 0 4/ 4 0/ 0 or 0 0/ 0 i/ 1 0/ 0 0/ 0 0/ 0 ii/ 8 10/ 7 1/ 1 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 or 0 3/ 3 0/ 0 9/ 5 2/ 2 0/ 0 4/ 2 0/ 0 0/ 0 0/ 0 0/ 0 p. 17 I ( 1I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 2 (PAGE 1) : CLINICAL OBSERVATIONS - SUMMARY TABLE RANGE : LACTATION PERIOD DOSAGE GROUP I II MAXIMUM POSSIBLE INCIDENCE APPEARS NORMAL 49/ 9 37/ 7 48/ 8 30/ 5 SCHEDULE SACRIFICED SACRIFICED - NO SURVIVING PUPS 88 10 DELIVERING - NOT DOSED DELIVERING SPARSE HAIR COAT: LIMB(S) LOCALIZED ALOPECIA: LIMB(S) SPARSE HAIR COAT: BACK SPARSE HAIR COAT: UNDERSIDE 5/ 5 1/ 1 1/ 1 6/ 1 0/ 0 6/ 1 4/ 4 1/ 1 12/ 2 6/ 1 0/ 0 0/ 0 N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF ANIMALS WITH THE OBSERVATION MAXIMUM POSSIBLE INCIDENCE - (DAYS x ANIMALS)/NUMBER OF ANIMALS EXAMINED PER GROUP III 60/ 10 53/ 9 10 0 6/ 6 3/ 3 0/ 0 7/ 2 0/ 0 0/ 0 IV 60/ 10 42/ 7 10 0 4/ 4 4/ 4 1/ i 18/ 3 6/ 1 0/ 0 V 20/ 5 20/ 5 3 2 1/ 1 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 VI 0/ 0 0/ 0 0 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 p. 18 ! TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE TABLE 3 (PAGE 1) NECROPSY OBSERVATIONS - SUMMARY - FO GENERATION FEMALE RATS (See footnotes on the last page of this table.) DOSAGE GROUP DOSAGE (MG/KG/DAY) a RATS EXAMINED MORTALITY FOUND DEAD UNSCHEDULED SACRIFICE APPEARED NORMAL UTERUS: RIGHT HORN, AT CERVIX, RED GELATINOUS MATERIAL STOMACH: DISTENDED WITH GAS N N N N N N N FUNDIC REGION, MUCOSAL SURFACE, NUMEROUS RED AREAS SPLEEN: SMALL N N KIDNEYS: BILATERAL, PELVIS, RED. ADRENAL GLANDS: BILATERAL, RED N N ABDOMINAL ADIPOSE: PINK LUNGS: ALL LOBES, MOTTLED RED AND DARK RED N R APPEARED TO BE INFLATED PRIOR TO PERFUSION N I 0 (VEHICLE) 10 0 0 0 10 0 0 0 0 0 0 0 0 II 10 10 1 0 lh 9 lh 0 0 0 0 0 0 0 III 30 10 0 0 0 10 0 0 0 0 0 0 0 0 IV V 90 270 10 10 05 0 4b-e 0 li 10 8 00 0 2c, d 0 lc 0 lc 0 lc 0 lc 0 ic 0 Id 0 IV 10 10 2i,g 8j-q 5 0 3g,j,k 0 iq 0 0 0 0 0 p. 19 I i- i TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 3 (PAGE 2): NECROPSY OBSERVATIONS - SUMMARY - F0 GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) a I 0 (VEHICLE) II 10 III 30 IV 90 RATS EXAMINED N 10 10 10 10 MORTALITY FOUND DEAD UNSCHEDULED SACRIFICE N0 N0 N0 10 00 lh 0 0 0 0 TRACHEA AND ESOPHAGUS: CONTAINED PINK FOAMY SUBSTANCE N 0 0 0 0 THYMUS: NUMEROUS RED AREAS N0 0 0 0 a. Dosage occurred on day 0 of presumed gestation through the day of delivery. b. Rat 23941 was found dead on day 3 of presumed gestation. c. Rat 23946 was found dead on day 3 of presumed gestation. d. Rat 23947 was found dead on day S of presumed gestation. e. Rat 23950 was found dead on day 3 of presumed gestation. f. Rat 23951 was found dead on day 2 of presumed gestation. g. Rat 23953 was found dead on day 2 of presumed gestation. h. Dam 23919 was*sacrificed on day 23 of gestation due to adverse clinical observations. i. Dam 23945 was sacrificed on day 21 of gestation due to adverse clinical observations. j. Rat 23952 was sacrificed on day 2 of presumed gestation due to adverse clinical observations. k. Rat 23954 was sacrificed on day 2 of presumed gestation due to adverse clinical observations. L. Rat 23955 was sacrificed on day 2 of presumed gestation due to adverse clinical observations. m. Rat 23956 was sacrificed on day 1 of presumed gestation due to adverse clinical observations. n. Rat 23957 was sacrificed on day 1 of presumed gestation due to adverse clinical observations. o. Rat 23958 was sacrificed on day 1 of presumed gestation due to adverse clinical observations. p. Rat 23959 was sacrificed on day 1 of presumed gestation due to adverse clinical observations. q. Rat 23960 was sacrificed on day 1 of presumed gestation due to adverse clinical observations. V 270 10 5 4b-e li Id 0 IV 500 10 10 2f,g 8j-q 0 If p. 20 II TSCA SANITIZED PROTOCOL ZXA00077 AR G U S R E S E A R C H L A B O R A T O R I E S , IHC. ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY Or MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 4 (PAGE 1) i MATERNAL BODY WEIGHTS - GESTATION - SUMMARY DOSAGE GROUP DOSAGE RATS TESTED PREGNANT MATERNAL BODY WEIGHT (G) N N (%) I II 0 (VEHICLE) MKD 10 (4KD 10 10 9( 90.0) 9( 90.0) III 30 MKD 10 10(100.0) IV 90 MKD 10 10(100.0) DAY 0 DAY 3 DAY 6 DAY 9 DAY 12 DAY IS DAY 18 DAY 20 MEANiS.D. MEAN1S.D. MEANiS.D. MEANiS.D. MEANiS.D. MEANiS.D. MEANiS.D. MEANiS.D. 233.1 i 10.4 247.0 i 9.7 260.9 1 13.1 276.2 i 16.4 297.9 17.0 321.7 i 19.6 353.3 24.5 386.0 i 24.3 THIS TABLE RESTRICTED TO PREGNANT ANIMALS DAY - DAY OF GESTATION 233.4 i 13.9 250.1 13.9 262.6 i 14.4 273.8 i 16.1 291.3 i 16.6 314.6 18.7 347.7 i 22.6 377.7 24.3 233.2 i 10.9 247.4 10.5 263.5 i 13.4 278.0 12.9 293.5 i 17.5 318.3 20.1 352.4 i 19.0 381.0 25.3 237.4 i 10.9 245.8 10.0 259.1 9.2 269.2 i 12.2 288.6 i 15.8 311.4 i 18.3 344.4 25.8 372.2 i 27.3 V 270 MKD 10 6( 60.0) 235.8 11.9 218.3 1 8.3 227.7 9.8 246.5 8.0 268.3 1 7.3 287.2 11.0 313.2 14.9 330.8 26.4 VI 500 MKD 10 0 TSCA SANITIZED PROTOCOL ZXA00077 A R G U S R E S E A R C H L A B O R A T O R I E S , INC. ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 5 (PAGE 1) MATERNAL BODY WEIGHT CHANGES - GESTATION - SUMMARY DOSAGE GROUP DOSAGE RATS TESTED PREGNANT MATERNAL BODY WEIGHT CHANGE (G) N N<%> Iu 0 [VEHICLE) MKD 10 MKD 10 10 9( 90..0) 9( 90..0) III 30 MKD 10 10(100,.0) IV 90 MKD 10 10(100..0) DAYS 0 - 3 DAYS 3 - 6 DAYS 6 - 9 DAYS 9 - 12 DAYS 12 - 15 DAYS 15 - IB DAYS 18 - 20 nAYS o - 20 MEAN+S.D. MEAN+S.D. MEANtS.D. MEANtS.D. MEAN+S.D. MEANtS.D. MEANtS.D. MEANtS.D. +13.9 5.7 +13.9 4.6 +15.3 t 3.9 +21.7 t 5.4 +23.8 3.7 +31.7 11.0 +32.7 10.2 +152.9 15.4 THIS TABLE RESTRICTED TO PREGNANT ANIMALS. DAYS DAYS OF GESTATION +16.7 6.8 +12.4 t 4.5 +11.2 4.2 +17.6 6.9 +23.2 6.8 +33.1 i 4.6 +30.0 + 4.3 +144.2 17.0 +14.2 6.6 +16.1 5.3 +14.5 + 2.0 +15.5 i 10.5 +24.8 7.5 +34.1 6.9 +28.6 10.3 +147.8 25.5 +8.4 7.0 +13.3 5.9 +10.1 + 5.3 +19.4 8.6 +22.8 t 8.7 +33.0 8.2 +27.8 7.0 +134.8+ 23.3 V 270 MKD 10 6( 60..0) -17.5 + 14.5 +9.3 + 6.6 +18.8 8.5 +21.8 + 2.3 +18.8 5.9 +26.0 i 4.9 +17.7 i 12.9 +95.0 20.6 10 0 p. 22 1f ~ l TSCA SANITIZED ARGUS R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 66(SPONSOR'S REFERENCE NO. 06-376) TABLE 6 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - SUM4ARY DOSAGE ____ ANIMALS - TESTED PREGNANT DELIVERED MATERNAL BODY WEIGHT (G) N(%) N(%) 0 (VEHICLE) MKD 10 MKD 10 10 9( 90.0) 9( 90.0) 9(100.0) 8( 88.9) 30 MKD 10 10(100.0) 10(100.0) 90 MKD 10 10(100.0) 10(100.0) 270 MKD 10 6{ 60.0) 5( 83.3) DAY 1 DAY 2 DAY 3 DAY 4 DAY 5 DAY 6 MEANtS.D. 289.1 1 18.4 MEAN1S.D. 283.0 16.3 [ 8] MEANtS.D. 286.0 1 19.0 1 8] MEANS,D. 293.5 19.2 t 8] MEANtS.D. MFIAHtS D . 298.6 17.5 [ 8] 313.0 15.3 [ 8] 285.6 17.8 283.2 1 21.9 285.6 20.7 293.6 25.0 297.9 24.6 309.4 t 24.8 291.4 13.9 285.1 12.9 291.6 i 15.4 292.6 13.9 301.7 15.5 317.4 15.3 276.7 18.2 273.6 20.1 282.1 19.3 286.2 19.6 290.2 20.2 308.9 21.8 264.2 12.1 270.3 5.8 t 3] 270.0 3.6 [ 3) 283.0 9.2 ( 3) 283.7 12.7 [ 3) 300.3 14.0 THIS TABLE RESTRICTED TO ANIMALS DELIVERING NATURALLY [ ] Number of values averaged. Animals with no surviving pups excluded. 10 0 0 p. 23 I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAYAGEJ DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-316) TABLE 7 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY DOSAGE 0 (VEHICLE) MKD 10 MKD 30 MKD 90 MKD ANIMALS - TESTED 10 10 10 10 PREGNANT N(%> 9( 90.0) 9( 90..0) 10(100..0) 10(100..0) DELIVERED N(%) 9(100.0) 8 ( 88. 9) 10(100..0) 10(100..0) MATERNAL BODY WEIGHT CHANGE (G) DAYS 1 - 2 MEANiS.D. -3.2 10.8 [ 8) -2.4 13.3 -6.3 6.0 -3.1 8.9 DAYS 2 - 3 MEAN+S.D. +3.0 6.2 [ 8] +2.4 5.3 + 6.5 4.6 +8.5 9.2 DAYS 3 - 4 MEANS.D. +7.5 3.7 [ 81 +8.0 6.1 +1.0 4.5 +4.1 6.5 DAYS 4 - 5 MEAN+S.D. +5.1 7.2 [ 8] +4.2 6.3 +9.1 4.8 +4.0 5.2 DAYS 5 - 6 MEANiS.D. +15.1 + 6.0 [ 8] +11.5 7.7 +15.7 4.7 +18.7 4.6 DAYS 1 - 4 MEAN+S.D. +7.2 16.4 [ 8] +8.0 14.2 +1.2 10.0 +9.5 10.6 DAYS 4 - 6 MEANiS.D. +20.2 + 8.8 [ 8] +15.8 8.2 +24.8 5.4 +22.7 6.6 DAYS 1 - 6 MEANiS.D. +27.5 14.4 [ 8] +23.8 13.4 +26.0 9.4 +32.2 9.8 THIS TABLE RESTRICTED TO ANIMALS DELIVERING NATURALLY. [ ] NUMBER OF VALUES AVERAGED, EXCLUDING ANIMALS WITH NO SURVIVING PUPS. 270 MKD 10 6( 60. 0) 5 ( 83. 3) +3.0 8.5 t 3] -0.3 6.0 [ 3] +13.0 6.1 [ 3] +0.7 5.1 { 3] +16.7 3.5 [ 3] +15.7 5.5 [ 3] +17.3 5.0 t 3] +33.0 10.5 [ 3) 500 MKD 10 0 0 p. 24 ai TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 8 (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - GESTATION - SUMMARY DOSAGE GROUP DOSAGE RATS TESTED PREGNANT N N (%) I II 0 (VEHICLE) MKD 10 MKD 10 10 9( 90.0) 9{ 90.0) III 30 MKD 10 10(100.0) IV 90 MKD 10 10(100.0) V 270 MKD 10 6( 60.0) VI 500 MKD 10 0 MATERNAL FEED CONSUMPTION (G/DAY) DAYS 0 - 3 DAYS 3 - 6 DAYS 6 - 9 AYS 9 - 12 DAYS 12 - 15 DAYS 15 - 18 DAYS 18 - 20 DAYS 0 - 20 MEANS.D . MEANIS.D. MEANiS.D. MEANiS.D. MEANiS.D. MEANIS.D. MEANIS.D. MEANIS.D. 18.9 21.2 1 24.0 i [ 8) 24.2 1 26.4 i 25.3 t 23.8 i 23.4 1.1 2.4 3.8 3.4 2.2 3.8 2.8 1.5 19.4 23.0 22.0 24.6 1 26.2 i 24.4 23.2 1 23.2 2.0 2.2 3.1 2.4 2.8 1.7 2.9 1.8 18.5 22.5 1 23.9 24.3 25.6 [ 9] 25.2 23.3 23.4 2.2 3.0 2.6 2.4 2.1 2.3 3.2 1.6 THIS TABLE RESTRICTED TO PREGNANT ANIMALS. DAYS - DAYS OF GESTATION [ ] - NUMBER OF VALUES AVERAGED a. Rats were provided with moistened feed; feed consumption values not recorded. 18.3 20.3 21.0 t 2.6 2.5 2.6 22.8 3.2 25.0 t 3.8 24.9 21.8 1 22.0 4.2 2.9 2.5 a a 18.9 1 21.6 1 21.8 1 21.8 21.8 1 19.4 t 1.2 1.6 1.4 2.6 3.1 1.2 TSCA SANITIZED PROTOCOL ZXA00077 ARGUS R E S E A R C H L A B O R A T O R I E S , I N C . ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 9 (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - GESTATION - SUMMARY DOSAGE GROUP DOSAGE RATS TESTED PREGNANT MATERNAL FEED CONSUMPTION (G/KG/DAY) N N (%) I II 0 (VEHICLE) MKD 10 MKD 10 10 9( 90.0) 9( 90.0) III 30 MKD 10 10(100.0) IV 90 MKD 10 10(100.0) V 270 MKD 10 6( 60.0) VI 500 MKD 10 0 DAYS 0 - 3 DAYS 3 - 6 DAYS 6 - 9 DAYS 9 - 1 2 DAYS 12 - 15 DAYS 15 - 18 DAYS 18 - 20 DAYS 0 - 2 0 MEANS.D . MEANiS.D. MEANiS.D. MEANiS.D. MEANiS.D. MEANiS.D. MEANiS.D. MEANiS.D. 78.6 83.3 89.3 i [ 8] 84.4 85.5 5.2 7.3 12.6 11.7 5.9 75.1 64.4 i 80.0 9.7 7.6 3.3 80.3 89.4 i 82.3 86.9 86.3 73.8 64.1 i 80.4 + 6.4 5.9 8.6 6.7 8.0 5.2 8.0 4.2 77.0 i 87.9 i 88.4 7.7 9.2 8.2 84.6 i 83.1 i t 9] 75.7 63.8 80.5 5.6 5.6 10.5 10.3 6.0 THIS TABLE RESTRICTED TO PREGNANT ANIMALS. DAYS - DAYS OF GESTATION [ ) - NUMBER OF VALUES AVERAGED a. Rats were provided with moistened feed; feed consumption values not recorded. 75.6 10.3 80.4 9.2 79.8 7.5 81.8 9.3 83.5 10.6 75.7 i 60.6 76.9 9.2 6.2 6.4 a a 79.7 + 5.6 83.8 7.0 78.6 + 4.9 72.6 i 67.1 74.4 i 7.1 5.6 4.2 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 10 (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - LACTATION - SUMMARY 0 (VEHICLE) MKD 10 MKD ANIMALS - TESTED 10 10 PREGNANT N(%) 9( 90.0) 9( 90.0) DELIVERING LITTERS N(l 9(100.0) 8( 88.9) MATERNAL FEED CONSUMPTION (g/day) 30 MKD 10 10(100.0) 10(100.0) 90 MKD 10 10(100.0) 10(100.0) 270 MKD 10 6( 60.0) 5( 83.3) DAYS 1 - 2 MEANtS.D. 20.8 * 6.2 I 7] 19.0 i 6.8 DAYS 2 - 3 MEANtS.D. 29.6 1 5.0 [ 8) 27.5 3.9 DAYS 3 - 4 MEANS.D. 40.0 7.3 ( 8] 34.1 6.9 DAYS 4 - 5 ' MEANtS.D. 39.9 4.5 ( 8) 39.5 1 8.4 DAYS 5 - 6 MEANtS.D. 44.1 4.9 [ 8] 41.8 6.0 DAYS 1 - 4 MEANtS.D. 30.5 3.9 [ 8] 26.9 5.0 DAYS 4 - 6 MEANtS.D. 42.0 4.4 [ 8] 40.6 6.3 DAYS 1 - 6 MEANtS.D. 35.2 3.5 [ 8] 32.4 5.4 THIS TABLE RESTRICTED TO ANIMALS DELIVERING NATURALLY. [ ] NUMBER OF VALUES AVERAGED 16.7 t 4.5 28.2 5.7 32.1 1 3.6 40.2 1 6.6 43.7 [ 9] 25.7 3.7 3.9 42.4 [ 9) 32.6 [ 9] 4.6 4.1 15.1 5.8 28.9 4.8 33.5 6.2 39.6 6.6 44.7 5.2 25.8 4.4 42.2 5.8 32.4 1 4.8 14.7 2.1 [ 3] 22.3 4.2 [ 3] 28.7 5.0 [ 3) 35.3 6.6 ( 3] 33.0 4.4 [ 3] 21.9 2.7 [ 3] 34.2 1 5.0 t 31 26.B 3.5 [ 31 10 0 0 p. 27 I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 11 (PAGE X) : MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - LACTATION - SUMMARY DOSAGE ANIMALS - TESTED PREGNANT N (%) DELIVERING LITTERS N(%) MATERNAL FEED CONSUMPTION (g/Kg/day) 0 (VEHICLE) MKD 10 MKD 10 10 9( 90.0) 9( 90. 0) 9(100.0) 8 ( 38. 9) 30 MKD 10 10(100. 0) 10(100. 0) 90 MKD 10 10(100.0) 10(100.0) 270 MKD 10 6 ( 60. 0) 5 ( 83. 3) 500 MKD 10 0 0 DAYS 1 - 2 DAYS 2 - 3 DAYS 3 - 4 DAYS 4 - 5 MEANS.D. MEAN+S.D. MEANiS.D. MEAN+S.D. 73.8 23.2 [ 71 104.0 15.7 ( 8) 138.5 27.4 E 8] 135.4 18.7 ( 8] 66.3 22.8 96.5 9.4 116.9 + 15.8 132.8 21.0 DAYS 5 - 6 DAYS 1 - 4 DAYS 4 - 6 MEANS.D. MEAN1S.D. MEAN+S.D. 144.3 15.7 l 8) 106.4 13.2 [ 8] 139.5 16.3 [ 8] 137.4 14.4 93.1 12.4 134.8 t 13.4 DAYS 1 - 6 MEAN+S.D. 120.2 12.4 110.1 11.6 [ B] THIS TABLE RESTRICTED TO ANIMALS DELIVERING NATURALLY. [ ] NUMBER OF VALUES AVERAGED 57.8 14.8 97.5 18.1 110.0 12.1 135.0 + 19.1 139.8 11.4 ( 9] 88.4 12.3 138.1 13.8 [ 9) 109.0 13.0 [ 9] 54.1 18.8 103.9 14.6 117.6 18.6 136.9 16.9 148.9 9.4 92.1 11.9 142.4 12.6 112.6 11.7 54.5 + 7.2 E 3] 82.6 15.3 1 3) 103.5 + 16.6 t 3] 124.3 19.4 ( 3] 113 .'I 15.6 [ 3) 80.3 8.9 [ 3) 118.1 14.7 [ 3) 95.9 10.8 [ 3) I' O ro 00 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAfiE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 12 (PAGE 1) : NATURAL DELIVERY OBSERVATIONS - SUMMARY DOSAGE 0 (VEHICLE) MKD 10 MKD 30 MKD 90 MKD 270 MKD DURATION OF GESTATION MEANtS.D. 22.4 1 0.5 t 9] 22.6 i 0.5 ( 8} 22.3 1 0.5 [ 10] 22.2 0.4 [ 10] 22.6 0.5 [ 5] DAMS WITH STILLBORN PUPS N(t) 2( 0.0) 3( 0.0) 2( 0.0) 1( 0.0) 1( 0.0) DAMS WITH NO LIVEBORN PUPS N 0 0 0 0 0 DAMS WITH ALL PUPS DYING DAYS 1-4 POSTPARTUM N(%) K 11.1) 0 0 0 2( 40.0) [] - Number of values averaged. DURATION OF GESTATION - NUMBER OF DAYS FROM DAY 0 OF GESTATION UNTIL THE DAY THE FIRST POP NAS OBSERVED INCLUDES ONLY DAMS WITH CONFIRMED DATES OF MATING. 500 MKD 0 0 p. 29 I I ! TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STODY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 13 (PAGE 1): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY DOSAGE 0 (VEHICLE) MKD 10 MKD 30 MKD 90 MKD 270 MKD 500 MKD DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 9 8 10 10 5 0 PUPS DELIVERED (TOTAL) N MEANiS.D. 136 15.1 i 1.4 110 13.8 2.6 142 14.2 3.8 146 14.6 2.3 68 13.6 2.8 0 LIVEBORN NEANiS.D. 14.9 1.3 N(%) 134( 98.5) 13.2 2.4 106 ( 96.4) 14.0 3.8 140( 98.6) 14.5 2.2 145( 99.3) 11.0 5.7 55( 80.9) 0 STILLBORN MEANiS.D. N(%) 0.2 0.4 2( 1.5) o.5 o.e 4( 3.6) 0.2 0.4 2( 1.4) 0.1 t 0.3 K 0.7) 2.4 5.4 12( 17.6) 0 UNKNOWN VITAL STATUS N 0 0 0 0 1 0 CULLED N0 0 0 0 0 0 SACRIFICED N 16 0 0 0 0 0 PUPS FOUND DEAD OR PRESUMED CANNIBALIZED DAY 1 DAYS 2- 4 DAYS 5- 6 N / N (%) N/N(%) N/N(%) 0/1341 0.0) 1/118( 0.8) 0/117( 0.0) 0/106{ 0.0) 1/106( 0.9) 0/105( 0.0) 0/1401 0.0) 3/140( 2.1) 0/137( 0.0) 0/145( 0.0) 2/1451 1.4) 0/1431 0.0) VIABILITY INDEX a % 87.3 N/N 117/134 99.0 105/106 97.8 137/140 98.6 143/145 DAY(S) - DAY(S) POSTPARTUM a. NUMBER OF LIVE PUPS ON DAY 4 POSTPARTUM/NUMBER OF LIVEBORN PUPS ON DAY 1 POSTPARTUM. 21/ 55( 38.2) 8/ 34( 23.5) 0/ 26( 0.0) 47.3 26/ 55 0/ 0( 0.0) 0/ 0( 0.0) 0/ 0( 0.0) 0. o 0/ 0 p. 30 I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 13 (PAGE 2): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY DOSAGE 0 (VEHICLE) MKD 10 MKD 30 MKD 90 MKD DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 9 8 10 10 SURVIVING PUPS/LITTER a DAY 1 DAY 4 DAY 6 MEANtS.D. MEANtS.D. MEANtS.D. 14.9 t 14.6 t [ 8] 14.6 t [ 8) 1.3 1.2 1.2 13.2 t 2.4 13.1 t 2.2 13.1 t 2.2 14.0 t 3.8 13.7 + 3.6 13.7 + 3.6 14.5 + 2.2 14.3 2.3 14.3 2.3 PERCENT MALE PUPS PER NUMBER OF PUPS SEXED DAY 1 DAY 4 DAY 6 MEANtS.D. MEANtS.D. MEANtS.D. 50.8 10.3 51.9 10.8 [ 8] 51.9 10.8 [ 8] 44.2 14.1 44.4 + 13.8 44.4 t 13.8 41.9 t 17.1 42.0 i 17.2 42.0 + 17.2 51.8 + 12.4 51.3 + 12.3 51.3 12.3 [) = Number of values averaged. DAY = DAY POSTPARTUM a. AVERAGE NUMBER OF LIVE PUPS PER LITTER, INCLUDING LITTERS WITH NO SURVIVING PUPS. 270 MKD 5 11.0 + 5.7 5.2 + 5.2 5.2 + 5.2 58.9 i 26.3 43.0 i 13.4 [ 3] 43.0 t 13.4 [ 3] 500 MKD 0 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 13 (PAGE 3): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY DOSAGE 0 (VEHICLE1) MKD 10 MKD 30 MKD 90 MKD DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N LIVE LITTER SIZE AT WEIGHING 9 8 10 10 DAY 1 DAY 4 DAY 6 MEANiS.D. MEANiS.D. MEANiS.D. PUP WEIGHT/LITTER (GRAMS) 14.6 [ 8] 14.6 + [ 8] 14.6 + [ 8] 1.3 1.2 1.2 13.2 2.4 13.1 2.2 13.1 2.2 14.0 + 3.8 13.7 3.6 13.7 3.6 14.5 2.2 14.3 2.3 14.3 2.3 DAY 1 DAY 4 DAY 6 MEANiS.D. MEANiS.D. MEANiS.D . 6.3 [ 8] 8.7 [ 8] 11.1 [ 8] 0.5 0.9 1.3 6.1 0.5 8.7 0.6 11.2 0.8 5.9 0.6 8.6 i 1.3 1.7 5.5 0.3 7.7 0.8 10.0 1.0 +i i O1 [] = Number of values averaged. DAY = DAY POSTPARTUM 270 MKD 5 10.0 + 6.0 [ 4] 8.7 i 3.0 [ 3] 8.7 3.0 [ 3] 4.6 0.3 [ 4] 6.2 0.5 [ 3] 8.3 0.7 [ 3] 500 MKD 0 TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 14 (PAGE 1): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 7 OF LACTATION - SUMMARY - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) a LITTERS EXAMINED .(N) I 0 (VEHICLE) 9 II 10 e III 30 10 IV V 90 270 10 5 TRANSIENT CLINICAL OBSERVATIONS: b TOTAL FREQUENCY (DAYS X PUPS)/LITTERS HITH OBSERVATIONS COLD TO TOUCH N/N 0/0 i/i 0/0 2/1 0/0 NOT NURSING N/N 0/0 0/0 0/0 1/1 0/0 NOT NESTING N/N 0/0 0/0 0/0 1/1 0/0 PALE N/N 0/0 0/0 0/0 1/1 0/0 NOSE, LEFT AND/OR RIGHT HINDLIMB, RIGHT KINDPAN, TAIL AND LONER MIDLINE: PURPLE N/N 0/0 0/0 8/1 0/0 5/2 PERSISTENT CLINICAL OBSERVATIONS: b TOTAL FREQUENCY (DAYS X PUPS)/LITTERS NITH OBSERVATIONS TIP OF TAIL: MISSING N/N 0/0 0/0 6/1 0/0 0/0 a. Dosage occurred on day 0 of presumed gestation through the day of delivery. b. Tabulation restricted to adverse observations; all other pups appeared normal. p. 33 t' TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 15 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)a I 0 (VEHICLE) LITTERS EXAMINED N 9 TOTAL PUPS STILLBORN, MORIBUND SACRIFICED OR FOUND DEAD b,c N STILLBORN FOUND DEAD N N NO MILK IN STOMACH d N (%) 0( 3 2 1 0.0) PUPS SACRIFICED AND NECROPSIED ON DAY 6 POSTPARTUM c II 10 8 4 4 0 0{ 0.0) III 30 10 4 2 2 1( 50.0) IV 90 10 2 1 1 1(100.0) V 270 5 38 12 26 10( 41.7)e IV 500 0 ---- LITTERS EXAMINED PUPS EVALUATED APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE N N N(%) N(%) 8 117 8(100.0) 117(100.0) 8 105 8(100.0) 105(100.0) 10 137 10(100.0) 137(100.0) 10 143 10(100.0) 143(100.0) 3 26 3(100.0) 26(100.0) 0 0 Dosage occurred on day 0 of presumed gestation through the day of delivery. " b. Restricted to pups in which complete necropsies were performed. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded full evaluation. pups ln wnicn c. Refer to the individual pup clinical observations table (Table 26) for external clinical observations confirmed at necroosv d. Analysis restricted to pups found dead and necropsied. conrirmea at necropsy. Excludes two pups that did not have stomach contents recorded of gestation. p. 34 I TSCA SANITIZED PROTOCOL ZXAG0077 : ORAL (GAVASE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 1): CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP ]t GROUP I 0 (VEHICLE) MKD DATE RANGE Aug 1, 2003 to Fab 1, 2007 RAT 1 DESCRIPTION 23901 23902 23903 23904 23905 23906 23907 23908 23909 23910 DL( i ) DL( 6 ) DL( 6 ) DG( 13- 20) DL{ 1" 6) DL( I ) DL( 6 ) DL( 6 ) DG( 25 ) DG( 20 ) DL{ 1- 6) DL( 1 ) DL( 6 ) DL( 6 ) DL{ 1 ) DU 6 ) DL{ 1 ) DL( 6 ) DL( 1 ) DL( 1 ) DL( 6 ) DELIVERING - NOT DOSED SCHEDULE SACRIFICED SPARSE HAIR COAT: LINB(S) SPARSE HAIR COAT: UNDERSIDE SPARSE HAIR COAT: UNDERSIDE DELIVERING SCHEDULE SACRIFICED SCHEDULE SACRIFICED SACRIFICED - DAY 25 OF (PRESUMED) GESTATION LOCALIZED ALOPECIAl LIMB(S) LOCALIZED ALOPECIA: LIMB(S) DELIVERING - NOT DOSED SCHEDULE SACRIFICED SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING - NOT DOSED g&TBTrrrRft SURVIVING PUPS SCHEDULE SACRIFICED DS - DAY OF STUDY DG - DAY OF PRESDMED GESTATION DL DAY OF LACTATION DO DAY OF OBSERVATION p. 35 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP II GROUP II 10 MKD DATE RANGE Aug 1, 2003 to Feb 1, 2007 RAT # DESCRIPTION 23911 23912 23913 23914 23915 23916 23917 23916 23919 23920 DL ( 1 ) DL( 6 ) DL( 1 ) DL( 6 ) DL( 1 ) DM 6 ) DG( 6- 21) DL( 1- 6) DL( 6 ) DG( 25 ) DL( 1 ) DL{ 6 ) DG( 8- 21) DL( 1- 6) DG( 21 ) DL( 6 ) DG( 21 ) DL( 1 ) DL ( .6 ) DG( 14- 16) DG( 17 ) DG( 23 ) DG( 23 ) DG( 23 ) DG( 23 ) DG( 0- 1) DG( 2- 21) DELIVERING SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED SPARSE HAIR COAT: LIMB(S) SPARSE HAIR COAT: LIMB(S) SCHEDULE SACRIFICED SACRIFICED - DAY 25 OF (PRESUMED) DELIVERING - NOT DOSED SCHEDULE SACRIFICED SPARSE HAIR COAT: LIMB(S) SPARSE HAIR COAT: LIMB(S) DELIVERING SCHEDULE SACRIFICED DELIVERING - NOT DOSED DELIVERING - NOT DOSED SCHEDULE SACRIFICED LOCALIZED ALOPECIA: LIMB(S) ALOPECIA NO LONGER APPARENT COLD TO TOUCH PALE EXTREMITIES PERIVAGINAL SUBSTANCE UNSCHEDULED SACRIFICED SPARSE HAIR COAT: LIMB(S) LOCALIZED ALOPECIA: LIMB(S) GESTATION DS " DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION DO = DAY OF OBSERVATION p. 36 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 3) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP II GROUP II 10 MED RAT * DESCRIPTION 23920 DL( 1- 6) DG( 21 ) DG( 0 ) DL( 6 ) LOCALIZED ALOPECIA: DELIVERING CHROMODACRYORRHEA SCHEDULE SACRIFICED LIMB(S) DS - DAY OF STUDY DG - DAY OF PRESUMED GESTATION DL - DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Fab 1, 2007 p. 37 I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 4): CLINICAL OBSERVATIONS - INDIVIDUAL DATA ________ I " _______________ _________________ T E ^ C T A u g ' ^ . ' l o w ' i r ^ b ' i r ^ O I RAT # DESCRIPTION 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 __ DL( 1 ) DL< 6 ) DL( 1 ) DL( 6 ) DL{ 1 ) DL( 6 ) DL ( 6 ) DL( 1 ) DL{ 6 ) DL( 1 ) DL< 6 ) DL( 1 ) DL( 6 ) DL( 1 ) DL( 6 ) DL( 1 ) DL( 6 ) DG{ 12- 21) DL( 1- 6) DG( 21 ) DL ( 6 ) DL( 1 ) DL( 6 ) DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED LOCALIZED ALOPECIA: LIMB(S) DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING SCHEDULE SACRIFICED DELIVERING SCHEDULE SACRIFICED DELIVERING " NOT DOSED SCHEDULE SACRIFICED LOCALIZED ALOPECIA: LIMB(S) LOCALIZED ALOPECIA: LIMB(S) DELIVERING SCHEDULE SACRIFICED DELIVERING SCHEDULE SACRIFICED DAY OF STUDY DG = DAY OF PRESUMED GESTATION DAY OF LACTATION DO " DAY OF OBSERVATION p. 38 I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 5) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP IV GROUP IV 90 MKD RAT # DESCRIPTION 23931 23932 23933 23934 23935 23936 23937 23938 23939 DL1 DL( DL< DL( DL( DG( DG( DG( DG( DL( DL( DL( DL( DG( DL{ DL( DL( DL( DL< B8t DU DG( DL( DL{ DL( DL( 6) 1) 6) 1) 6) 2) 13 ) 8) 9- 20) 1- 6) 1) 6) 6) 5) 1) 6) 1) 6) 6 ) 0- 21) 1- 6) 5- 21) 1- 6) 1) 6) 1) SCHEDULE SACRIFICED DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING SCHEDULE SACRIFICED SOFT OR LIQUID FECES URINE-STAINED ABDOMINAL FUR SPARSE HAIR COAT: LINB(S) LOCALISED ALOPECIA: LIMB(S) LOCALIZED ALOPECIA: LIMB(S) DELIVERING - NOT DOSED SCHEDULE SACRIFICED SCHEDULE SACRIFICED URINE-STAINED ABDOMINAL FUR DELIVERING SCHEDULE SACRIFICED DELIVERING SCHEDULE SACRIFICED SPARSE HAIR COAT: LIMB(S) LOCALISED ALOPECIA; LTHBfS) LOCALIZED ALOPECIA: LIMB(S) SPARSE HAIR COAT: BACK SPARSE HAIR COAT: BACK DELIVERING - NOT DOSED SCHEDULE SACRIFICED DELIVERING - NOT DOSED DS - DAY OF STUDY DG - DAY OF PRESUMED STATION DL - DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Feb 1, 2007 p. 39 [ I i -i TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 6): CLINICAL OBSERVATIONS - INDIVIDUAL DATA ^ DOSAGE GROUP IV GROUP IV 90 MKD RAT * DESCRIPTION 23939 23940 DL.( 6 ) DG( 5- 11) DG( 12- 20) DL( 1- 6) DL( 1 ) DL( 6 ) SCHEDULE SACRIFICED SPARSE HAIR COAT: LIMB(S) LOCALIZED ALOPECIA: LIMB(S) LOCALIZED ALOPECIA: LIMB(S) DELIVERING SCHEDULE SACRIFICED DS = DAY OF STUDY DG - DAY OF PRESUMED GESTATION DL DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Feb 1, 2007 p. 40 I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (SAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 7): CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP V GROUP V 270 MKD RAT * DESCRIPTION 23941 23942 23943 23944 DG{ 2 ) DGl 2 ) DGl 2 > DG( 2 ) DGl 2 ) DG( 2 ) DG( 2 ) DG( 3 ) DG( 3 ) DG( 1- 7) DG( 1 ) DG( 3- 5) DL( 1 ) DG( 1 ) DL( 6 ) DG( 6- 7) DG( 1 ) DG( 1- 2) DG( 4 ) DGt 2 ) DG( 4- 5) DL{ 1 ) DM 6 ) DG( 4 ) DG( 1- 2) DG( 4 ) DRIED FECES URINE-STAINED ABDOMINAL FUR DEHYDRATION COLD TO TOUCH PALE EXTREMITIES LACRIMATIOM DECREASED MOTOR ACTIVITY FOUND DEAD RALES DEHYDRATION COLD TO TOUCH COLD TO TOUCH DELIVERING CHR0M0RHINORRHEA SCHEDULE SACRIFICED URINE-STAINED ABDOMINAL FUR RALBS DEHYDRATION DEHYDRATION COLD TO TOUCH COLD TO TOUCH DELIVERING - NOT DOSED SCHEDULE SACRIFICED URINE-STAINED ABDOMINAL FUR DEHYDRATION DEHYDRATION DS - DAY OF STUDY DG - DAY OF PRESUMED GESTATION DL - DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Feb 1, 2007 IV 'd ; TSCA SANITIZED PROTOCOL 2XA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 i(PAGE 8) ! CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP V GROUP V 270 MKD RAT # DESCRIPTION 23944 23945 23946 DG( 3- 6) DL( 1 ) DG( 2 ) DG( 4 ) DG( 6 ) DG( 0- 2) DG( 4 ) DG( 21 ) DG( 1- 4) DG( 21 ) DG( 3- 6) DG( 21 ) DG( 21 ) DG( 21 ) DG( 21 ) DG( 21 ) DG( 0 ) DG( 2- 3) DG( 3 ) DG.( 2 ) DG( 3 ) DG( 3 ) DG( 1- 3) DG( 1- 3) DG( 3 ) DG( 3 1 DG< 3 ) COLD TO TOUCH SACRIFICED - NO SURVIVING PUPS URINE-STAINED ABDOMINAL FUR URINE-STAINED ABDOMINAL FUR URINE-STAINED ABDOMINAL FUR UNGROOMED COAT RALES PERIORAL SUBSTANCE DEHYDRATION DEHYDRATION COLD TO TOUCH COLD TO TOUCH PALE EXTREMITIES LOW CARRIAGE DECREASED MOTOR ACTIVITY UNSCHEDULED SACRIFICED URINE-STAINED ABDOMINAL FUR URINE-STAINED ABDOMINAL FUR UNGROOMED COAT RALES BRADYPNEA PERIORAL SUBSTANCE DEHYDRATION COLD TO TOUCH PALE EXTREMITIES DISCOLORATION PTOSIS DS - DAY OF STUDY DG - DAY OF PRESUMED GESTATION DL = DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Feb 1, 2007 O P ro TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 9) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP 'V GROUP V 270 MKD RAT * DESCRIPTION 23946 23947 23948 23949 23950 DG( DG( DG.( DG( DG< DG( DG{ DG( DG( DG ( DG( DG( DG( DG( DG ( DG( DG ( DL< DG{ DG( DG.( DG( DL( DG( DG( DG ( 3) 3) 3) 3) 1- 3) 2- 4) 1- 5) 1- 4) 3) 3) 5) 2) 5- 6) 2- 3) 5) 2- 3) 1- 4) 6) 2) 2) i- 3) i- 4) i) 2) 2) 0) PERINASAL SUBSTANCE DECREASED MOTOR ACTIVITY IMPAIRED RIGHTING REFLEX POUND DEAD URINE-STAINED ABDOMINAL FUR UNGROGNED COAT DEHYDRATION COLD TO TOUCH PALE EXTREMITIES DECREASED MOTOR ACTIVITY FOUND DEAD URINE-STAINED ABDOMINAL FUR URINE-STAINED ABDOMINAL FUR UNGROOMED COAT RALES DEHYDRATION COLD TO TOUCH SCHEDULE SACRIFICED URINE-STAINED ABDOMINAL FUR UMWIU1B1/ U M T DEHYDRATION COLD TO TOUCH SACRIFICED - NO SURVIVING PUPS URINE-STAINED ABDOMINAL FUR UNGROOMED COAT RALES DS - DAY OF STUDY DG - DAY OF PRESUMED GESTATION DL - DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Fab 1, 2007 p. 43 II TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 10): CLINICAL OBSERVATIONS - INDIVIDUAL DATA ________ ____________________ V RAT # __ 270 MKD DESCRIPTION 23950 DG( 1- 2) DG ( 1- 2) DG( 3 ) DEHYDRATION COLD TO TOUCH POUND DEAD DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL - DAY OF LACTATION DO - DAY OF OBSERVATION nATE RANGE *ug 1, 2003 to Feb 1, 2007 p. 44 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 16 (PAGE 11) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP VI GROUP VI 500 HKD RAT * DESCRIPTION 23951 23952 23953 23954 23955 23956 DG( DG( DG< DG< DG< DG( DG( DG( DG( DG( DG( DG( DG( DG( DG( DG( DG( DG( DG( not DG( DG ( DG( DG( DG( DG( o- 1) 1) 2) 2) 1- 2) 1- 2) 2) 2> 0- 1) 1) 1) 1) 1) 1) 1) 2) i- 2) 2) 1- 2) 2) 2) 2) 1) 1- 2) 2) 1) URINE-STAINED ABDOMINAL FUR DEHYDRATION FOUND DEAD UNGR00MED COAT DEHYDRATION COLD TO TOUCH DECREASED MOTOR ACTIVITY SCHEDULE SACRIFICED URINE-STAINED ABDOMINAL FUR RALES DEHYDRATION COLD TO TOUCH PALE EXTREMITIES PTOSIS DECREASED MOTOR ACTIVITY FOUND DEAD URINE-STAINED ABDOMINAL FUR UNGROOKD COAT DEHYDRATION COLD TO TOUCH DECREASED MOTOR ACTIVITY SCHEDULE SACRIFICED RALES DEHYDRATION SCHEDULE SACRIFICED DEHYDRATION DAY OF STUDY DG - DAY OF PRESUMED GESTATION DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Feb 1, 2007 p. 45 I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376} TABLE 16 (PAGE 12): CLINICAL OBSERVATIONS - INDIVIDUAL DATA DOSAGE GROUP VI GROUP VI 500 MKD RAT * DESCRIPTION 23956 23957 23958 23959 23960 DG( DG( DG( DG ( DG! DG { DG ( DG ( DG ( DG ( DG( DG( DG( DG( DG ( DG( DG( DG( 1) 1) 0- 1) 1) 0- 1) 1) 1) 1) 1) 0- 1) 1) 1) 0- 1) 1) 0- 11 1) 1) 11 COLD TO TOUCH SCHEDULE SACRIFICED URINE-STAINED ABDOMINAL FUR RALES COLD TO TOUCH SCHEDULE SACRIFICED DEHYDRATION SCHEDULE SACRIFICED URINE-STAINED ABDOMINAL FUR LOCALIZED ALOPECIA: LIMB(S) COLD TO TOUCH SCHEDULE SACRIFICED LOCALIZED ALOPECIA: LIMB(S) DEHYDRATION COLD TO TOUCH HUNCHED POSTURE DECREASED MOTOR ACTIVITY SCHEDULE SACRIFICED DS DAY OF STUDY DG DAY OF PRESUMED GESTATION DL = DAY OF LACTATION DO - DAY OF OBSERVATION DATE RANGE Aug 1, 2003 to Feb 1, 2007 p. 46 i TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 17 (PAGE 1): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F0 GENERATION RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSES NECROPSY STATUS ADMINISTERED OBSERVATIONS I 0 (VEHICLE) 23901 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23902 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23903 DL 6 P 22 ALL TISSUES APPEARED NORMAL. 23904 DG 2b NP 25 ALL TISSUES APPEARED NORMAL. 23905 DL 6 p 21 ALL TISSUES APPEARED NORMAL. 23906 DL 6 p 22 ALL TISSUES APPEARED NORMAL. 23901 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23908 DL 6 p 22 ALL TISSUES APPEARED NORMAL. 23909 DL 1 p 21 ALL TISSUES APPEARED NORMAL. 23910 DL 6 P 22 ALL TISSUES APPEARED NORMAL. II 10 23911 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23912 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23913 DL 6 P 22 ALL TISSUES APPEARED NORMAL. 23914 DL 6 P 22 ALL TISSUES APPEARED NORMAL. 23915 DG 25 NP 25 ALL TISSUES APPEARED NORMAL. 23916 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23917 DL 6 P 22 ALL TISSUES APPEARED NORMAL. 23918 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23919 DG 23 P 23 UHSCHEDUUP SACRIFICE OH DAT 23 OF GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS. UTEROS: RIGHT HORN, AT CERVIX, RED GELATINOUS MATERIAL. ALL OTHER TISSUES APPEARED NORMAL. UTERINE CONTENTS: 16 IMPLANTATION SITES (TWO LIVE FETUSES AND 14 DEAD FETUSES IN UTERO) .a 23920 DL 6 P 22 ALL TISSUES APPEARED NORMAL. DG - DAY OF PRESUMED GESTATION P - PREGNANT Np - NOT PREGNANT DL DAY OF LACTATION a. One dead fetua had the left hindlimb rotated medially; All other fetuses appeared normal for developmental age. p. 47 i TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVA6E) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 17 (PAGE 2): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FO GENERATION RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER III 30 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 IV 90 23931 23932 23933 23934 23935 23936 23937 23936 23939 23940 DG = DAY OF PRESUMED GESTATION P - PREGNANT NP - NOT PREGNANT DAY OF PREGNANCY DOSES NECROPSY STATUS ADMINISTERED DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 P P P P P P P P P P 21 21 22 21 22 21 21 21 22 21 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 DL 6 P P P P P P P P P P DL = DAY OF LACTATION 22 21 21 21 21 21 21 22 21 21 OBSERVATIONS ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. I ri p -P 00 TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOFMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 17 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FO GENERATION RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) V 270 RAT NUMBER 23941 DAY OF PREGNANCY DOSES NECROPSY STATUS ADMINISTERED DG 3 a 3 OBSERVATIONS FOUND DEAD ON DAY 3 OF PRESUMED GESTATION (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL FOR SLIGHT DEGREE OF AUTOLYSIS. 23942 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23943 DL 6 P 21 ALL TISSUES APPEARED NORMAL. 23944 DL 1 p 22 SACRIFICED ON DAY 1 OF LACTATION DUE TO NO SURVIVING PUPS. ALL TISSES APPEARED NORMAL. 23945 DG 21 P 22 UNSCHEDULED SACRIFICE ON DAI 21 OF GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS (2 HOURS AND 17 MINUTES AFTER DOSAGE ADMINISTRATION) . ALL TISSUES APPEARED NORMAL FOR SLIGHT DEGREE OF AUTOLYSIS. UTERINE CONTENTS: 13 IMPLANTATION SITES (12 DEAD FETUSES AND ONE EARLY RESORPTION IN UTERO) .b 23946 DG 3 FOUND DEAD ON DAY 3 OF PRESUMED GESTATION (DEATH OCCURRED ONE HOUR AND IT MINUTES AFTER DOSAGE ADMINISTRATION). STOMACH: DISTENDED NITH GAS; FUNDIC, REGION MUCOSAL SURFACE, NUMEROUS RED AREAS (PINPOINT TO 0.4 CM TO 0.5 CM). SPLEEN: SMALL (0.27 g) . KIDNEYS: BILATERAL, PELVIS, RED. ADRENAL GLANDS: BILATERAL, RED. ABDOMINAL ADIPOSE: PINK. ALL OTHER TISSUES APPEARED NORMAL. 23947 DG 5 a 6 FOUND DEAD ON DAY 5 OF PRESUMED GESTATION (DEATH OCCURRED 46 MINUTES AFTER DOSAGE ADMINISTRATION). STOMACH: DISTENDED NITH GAS. LUNGS: ALL LOBES, MOTTLED RED AND DARK RED; LUNGS APPEARED TO BE INFLATED PRIOR TO PERFUSION. TRACHEA AND ESOPHAGUS: CONTAINED PINK FOAMY SUBSTANCE. ALL OTHER TISSUES APPEARED NORMAL. DG DAY OF PRESUMED GESTATION DL - DAY OF LACTATION P PREGNANT NP - NOT PREGNANT a. Unable to accurately determine pregnancy status due to early gestational age. b. All fetuses appeared normal for developmental age. p. 49 I TSCA SANITIZED PROTOCOL ZXA00077: ORAL (SAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 17 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F0 GENERATION RATS DOSAGE GROUP DOSAGE [MG/KG/DAY) V (CONT.) 270 RAT NUMBER 23948 DAY OF PREGNANCY DOSES NECROPSY STATUS ADMINISTERED DL 6 P 22 OBSERVATIONS ALL TISSUES APPEARED NORMAL. 23949 DL i P 22 SACRIFICED ON DAY 1 OF LACTATION DUE TO NO SURVIVING PUPS. ALL TISSUES APPEARED NORMAL. 23950 DG 3 a 3 FOUND DEAD ON DAY 3 OF GESTATION (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL FOR SLIGHT DEGREE OF AUTOLYSIS. DG - DAY OF PRESUMED GESTATION P - PREGNANT NP - NOT PREGNANT DL = DAY OF LACTATION a. unable to accurately determine pregnancy status due to early gestational age p. 50 TSCA SANITIZED PROTOCOL ZXA00077: ORAL (SAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 17 (PAGE 5) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FO GENERATION RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSES NECROPSY STATUS ADMINISTERED OBSERVATIONS VI 500 23951 DG 2 a 2 FOUND DEAD ON DAY 2 OF PRESUMED GESTATION (DEATH OCCURRED OVERNIGHT) . THYMUS: NUMEROUS RED AREAS (PINPOINT TO 0.2 CM X 0.1 CM). ALL OTHER TISSUES APPEARED NORMAL. 23952 DG 2 a 2 UNSCHEDULED SACRIFICE ON DAY 2 OF PRESUMEDGESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS STOMACH: DISTENDED WITH GAS. ALL OTHER TISSUES APPEARED NORMAL. 23953 DG 2 a 2 FOUND DEAD ON DAY 2 OF PRESUMED GESTATION (DEATH OCCURRED OVERNIGHT). STOMACH: DISTENDBD WITH GAS. ALL OTHER TISSUES APPEARED NORMAL FOR SLIGHT DEGREE OF AUTOLYSIS. 23954 DG 2 a 2 UNSCHEDULED SACRIFICE ON DAY 2 OF PRESUMED GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS. STOMACH: DISTENDED WITH GAS. ALL OTHER TISSUES APPEARED NORMAL. 23955 DG 2 a 2 UNSCHEDULED SACRIFICE ON DAY 2 OF PRESUMED GE8TATION DUE TO ADVERSE CLINICAL OBSERVATIONS. ALL TISSUES APPEARED NORMAL. 23956 DG 1 a 1 UNSCHEDULED SACRIFICE ON DAY 1 OF PRESUMED GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS. ALL TISSUES APPEARED NORMAL. DG - DAY OF PRESUMED GESTATION P - PREGNANT NP - NOT PREGNANT DL - DAY OF LACTATION a. Unable to accurately determine pregnancy status due to early gestational age. p. 51 1 li TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER 06-376) TABLE 17 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FO GENERATION RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSES NECROPSY STATUS ADMINISTERED OBSERVATIONS VI (CONT.) 500 23957 DG 1 a 1 UNSCHEDULED SACRIFICE ON DAY 1 OF PRESUMED GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS. ALL TISSUES APPEARED NORMAL. 23958 DG 1 a 1 UNSCHEDULED SACRIFICE ON DAY 1 OF PRESUMED GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS. ALL TISSUES APPEARED NORMAL. 23959 DG 1 a l UNSCHEDULED SACRIFICE ON DAY 1 OF PRESUMED GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS. ALL TISSUES APPEARED NORMAL. 23960 DG 1 a 1 DG - DAY OF PRESUMED GESTATION P = PREGNANT NP - NOT PREGNANT DL = DAY OF LACTATION UNSCHEDULED SACRIFICE ON DAY 1 OF PRESUMED GESTATION DUE TO ADVERSE CLINICAL OBSERVATIONS SPLEEN: SMALL (0.21 g) . ALL OTHER TISSUES APPEARED NORMAL -- ----------- a. Unable to accurately determine pregnancy status due to early gestational age p. 52 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 1): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 0 1 RAT # DOSAGE GROUP I 2 3 GROUP I 4 5 23901 P 23902 P 23903 P 23904 NP 23905 P 23906 P 23907 P 23908 P 23909 P 23910 P 230. 239. 230. 235. 238. 215. 252. 230. 239. 225. 235. 236. 239. 234. 244. 225. 256. 240. 246. 224. 240. 244. 243. 237. 237. 230. 260. 249. 247. 231. 245. 245. 245. 238. 241. 234. 266. 249. 258. 240. 250. 250. 240. 244. 252. 236. 271. 256. 261. 238. 256. 261. 257. 246. 244. 239. 284. 264. 269. 239. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). 67 0 (VEHICLE) MKD 261. 263. 261. 248. 255. 243. 286. 262. 272. 245. 266. 270. 271. 258. 254. 251. 292. 268. 279. 251. 8 270. 271. 270. 262. 258. 256. 297. 275. 287. 259. 9 276. 281. 281. 268. 268. 255. 307. 276. 288. 254. 10 283. 283. 286. 267. 280. 264. 318. 286. 300. 264. 11 286. 292. 295. 274. 282. 270. 319. 292. 304. 276. 12 2QR 299 2R0 294. 274 317 7Q*. 31* 284. p. 53 I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 2) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - IN D IV ID U A L DATA PREGNANCY STATUS DAY 13 14 15 16 17 18 RAT # DOSAGE GROUP I GROUP I 23901 P 23902 P 23903 P 23904 NP 23905 P 23906 P 23907 P 23908 P 23909 P 23910 P 300. 307. 307. 282. 300. 278. 339. 302. 320. 276. 307. 314. 312. 283. 310. 203. 348. 310. 326. 294. 314. 325. 322. 275. 321. 290. 358. 320. 341. 304. 321. 334. 337. 278. 334. 304. 364. 322. 350. 315. 334. 353. 350. 285. 353. 317. 376. 328. 357. 305. 356. 356. 364. 276. 362. 323. 392. 345. 371. 311. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . 19 20 21 22 0 (VEHICLE) MKD 367. 369. 382. 272. 384. 341. 410. 361. 380. 350. 385.DELIVERED 386. 399. DELIVERED 392. 410.DELIVERED 274. 274. 276. 395.DELIVERED 355. 361.DELIVERED 436.DELIVERED 363. 384.DELIVERED 398.DELIVERED 364. 386.DELIVERED 23 270. 24 276. 25 284. p. 54 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 3) : MATERNAL BODY HEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 0 i 2 3 4 5 RAT DOSAGE GROUP II GROUP II 23911 P 23912 P 23913 P 23914 P 23915 HP 23916 P 23917 P 23918 P 23919 P 23920 P 218. 253. 228. 231. 224. 218. 253. 231. 246. 223. 228. 254. 238. 231. 217. 219. 259. 234. 250. 237. 233. 264. 233. 237. 219. 216. 263. 241. 256. 244. 237. 265. 245. 244. 226. 225. 266. 251. 264. 254. 241. 272. 250. 248. 224. 227. 270. 254. 267. 257. 248. 277. 257. 255. 228. 228. 275. 258. 273. 266. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) . 6 10 MED 252. 281. 260. 254. 231. 235. 280. 266. 266. 269. 7 258. 285. 253. 260. 233. 239. 285. 268. 274. 260. 8 262. 294. 255. 257. 234. 240. 286. 281. 273. 261. 9 263. 296. 267. 261. 234. 247. 294. 278. 284. 274. 10 266. 304. 271. 272. 236. 254. 296. 285. 276. 279. ii 274. 312. 276. 280. 239. 263. 304. 295. 293. 288. 12 282. 320. 281. 286. 244. 266. 310. 303. 288. 286. TSCA SANITIZED PROTOCOL ZXA00077 A R G U S R E S E A R C H L A B O R A T O R I E S , INC. : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 4): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 13 14 RAT * DOSAGE GROUP II 15 16 17 GROUP II 18 23911 P 23912 P 23913 P 23914 P 23915 NP 23916 P 23917 P 23918 P 23919 P 23920 P 291. 324. 292. 293. 241. 270. 314. 309. 292. 302. 298. 337. 293. 300. 246. 280. 325. 318. 306. 316. 303. 342. 296. 307. 248. 286. 334. 327. 310. 326. 314. 354. 306. 317. 249. 295. 345. 336. 326. 336. 326. 372. 317. 336. 245. 308. 353. 348. 329. 341. 336. 379. 323. 338. 249. 313. 375. 363. 345. 357. P = PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). 19 10 MKD 348. 392. 331. 350. 252. 322. 387. 374. 362. 371. 20 21 22 365. 375.DELIVERED 413.DELIVERED 343. 367. 255. 351.DELIVERED 388.DELIVERED Mfl. 9*1 347.DELIVERED 405. 425.DELIVFRRD 393.DELIVERED 379. 388. 4DD 387. 406.DELIVERED 23 24 25 252. 255 261. 398.DEAD DAY 23 O Ol 0> TSCA SANITIZED ARGUS R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-37) TABLE 18 (PAGE 5): MATERNAL BODY HEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 0 1 RAT * DOSAGE GROUP III 2 34 GROUP III 5 23921 P 23922 P 23923 P 23924 P 23925 P 23926 P 23927 P 23928 P 23929 P 23930 P 224. 244. 229. 235. 239. 217. 252. 235. 237. 220. 227. 244. 230. 233. 243. 223. 256. 238. 247. 230. 238. 243. 240. 236. 248. 232. 258. 251. 251. 230. 237. 261. 248. 234. 248. 235. 262. 254. 255. 240. 239. 269. 249. 245. 253. 243. 268. 261. 256. 248. 243. 276. 252. 249. 260. 239. 278. 266. 260. 250. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) . 6 30 MKD 248. 287. 262. 252. 264. 251. 284. 270. 262. 255. 7 257. 286. 263. 254. 272. 256. 287. 275. 263. 258. 8 260. 289. 268. 256. 277. 259. 294. 278. 272. 266. 9 262. 297. 274. 267. 279. 266. 300. 286. 278. 271. 10 268. 303. 280. 269. 279. 275. 307. 295. 288. 283. 11 270. 314. 286. 278. 277. 282. 318. 293. 292. 285. 12 276. 312. 293. 282. 267. 286. 327. 303. 294. 295. p. 57 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 6) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21 22 23 24 25 RAT # DOSAGE GROUP III GROUP III 30 MKD 23921 P 23922 P 23923 P 23924 P 23925 P 23926 P 23927 P 23928 P 23929 P 23930 P 284. 328. 295. 291. 269. 295. 336. 308. 305. 297. 289. 337. 303. 296. 280. 305. 337. 312. 312. 305. 302. 347. 309. 314. 282. 314. 350. 319. 328. 318. 317. 352. 318. 320. 300. 325. 359. 332. 337. 325. 332. 361. 327. 336. 310. 344. 365. 342. 342. 334. 347. 368. 340. 354. 311. 352. 384. 359. 360. 349. 348. 388. 348. 367. 319. 371. 400. 379. 380. 366. 364. DELIVERED 406.DELIVERED 359. 376.DELIVERED 388.DELIVERED 324. 328.DELIVERED 393. 404.DELIVERED 404. 429.DELIVERED 390.DELIVERED 398. 412.DELIVERED 384. 398.DELIVERED P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES} DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . p. 58 II TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 7): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 0 1 2 3 4 5 RAT 1 DOSAGE GROUP IV GROUP IV 23931 P 23932 P 23933 P 23934 P 23935 P 23936 P 23937 P 23938 P 23939 P 23940 P 235. 242. 231. 235. 220. 253. 233. 249. 250. 226. 239. 245. 231. 233. 215. 257. 239. 248. 250. 232. 243. 250. 242. 238. 226. 262. 244. 250. 246. 239. 243. 251. 246. 242. 227. 264. 251. 254. 242. 238. 252. 258. 253. 251. 232. 264. 254. 259. 241. 249. 252. 263. 255. 253. 232. 271. 258. 267. 240. 248. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROH AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). 6 90 MKD 266. 254. 266. 256. 242. 270. 262. 270. 254. 251. 7 270. 256. 267. 260. 237. 277. 265. 273. 254. 243. 8 273. 256. 270. 264. 237. 277. 271. 279. 256. 252. 9 276. 265. 274. 274. 242. 276. 276. 286. 260. 263. 10 290. 274. 282. 280. 248. 286. 279. 280. 267. 266. ii 297. 276. 289. 286. 257. 297. 287. 293. 276. 262. 12 303. 285. 296. 296. 260. 308. 293. 297. 284. 264. p. 59 r TSCA SANITIZED A R G O S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 8) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 13 14 15 16 17 18 RAT # DOSAGE GROUP IV GROUP IV 23931 P 23932 P 23933 P 23934 P 23935 P 23936 P 23937 P 23938 P 23939 P 23940 P 313. 295. 299. 300. 262. 314. 292. 302. 287. 268. 322. 301. 307. 311. 265. 316. 305. 311. 297. 284. 337. 315. 319. 316. 274. 331. 303. 321. 298. 300. 349. 324. 327. 332. 280. 346. 309. 329. 308. 310. 362. 343. 347. 347. 291. 350. 315. 342. 310. 315. 377. 345. 354. 354. 296. 378. 328. 361. 324. 327. P PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . 19 90 MKD 382. 367. 371. 368. 308. 392. 346. 374. 332. 343. 396. 405.DELIVERED 384.DELIVERED 394. 401.DELIVERED 383. DELIVERED 323. 404. 324.DELIVERED 410.DELIVERED 352. 366.DELIVERED 391. 398.DELIVERED 347.DELIVERED 348. 352.DELIVERED 23 24 p. 60 TSCA SANITIZED A R G O S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 ; ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 9) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 0 1 2 3 4 RAT f DOSAGE GROUP V GROUP V 23941 NP 23942 P 23943 P 23944 P 23945 P 23946 NP 23947 NP 23948 P 23949 P 23950 NP 234. 254. 231. 236. 222. 250. 232. 245. 227. 220. 204. 233. 216. 221. 209. 227. 229. 229. 222. 200. 179. 220. 204. 226. 216. 207. 204. 220. 202. 184. DEAD 212. 211. 233. 218. 190. 195. 222. 214. DEAD 206. 223. 234. 219. DEAD 202. 227. 216. 56 270 MKD 202. 227. 238. 221. 211. 230. 241. 226. 203. 228. 224. DEAD 231. 227. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) . 7 226. 230. 246. 228. 240. 235. 8 241. 238. 252. 229. 243. 239. 9 246. 246. 260. 236. 249. 242. 10 256. 250. 267. 250. 260. 252. ii 260. 259. 275. 254. 267. 254. 12 268. 267. 280. 261. 273. 261. p. 61 TSCA SANITIZED ARGUS R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 18 (PAGE 10) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21 22 23 24 25 RAT * DOSAGE GROUP V GROUP V 270 MKD 23941 NP 23942 P 23943 P 23944 P 23945 P 23946 NP 23947 NP 23946 P 23949 P 23950 NP DEAD 280. 273. 289. 266. DEAD DEAD 277. 263. DEAD 287. 281. 297. 276. 277. 268. 294. 289. 304. 276. 265. 275. 300. 292. 317. 286. 294. 284. 311. 303. 324. 294. 296. 286. 326. 318. 331. 294. 312. 298. 345. 334. 358. 305. 318. 308. 359. 363.DELIVERED 336.DELIVERED 361. 371.DELIVERED 293. 269.DEAD DAY 21 320. 316. 322.DELIVERED 318.DELIVERED P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . p. 62 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSORS REFERENCE NO. 06-376) TABLE 18 (PAGE 11) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAY 0 1 2 3 4 5 6 7 8 9 10 11 RAT # DOSAGE GROUP VI GROUP VI 500 MKD 23951 NP NP NP NP NP NP NP NP NP NP 229. 241. 229. 232. 214. 251. 230. 237. 250. 226. 199. 215. 196. 210. 208. 228. 202. 218. 234. 193. DEAD 202. DEAD 198. 205. DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD P - PREQ4ANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . p. 63 TSCA SANITIZED ARGUS RESEARCH ,L A B O R A T O R I E S INC. PROTOCOL 2XA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS ISPONSOR'S REFERENCE NO. 06-376) TABLE 10 (PAGE 12): MATERNAL BODY WEIGHTS - PRESUMED G ESTATIO N - IN D IV ID U A L DATA PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21 22 23 24 25 RAT # DOSAGE GROUP VI GROUP VI 500 MKD 23951 NP 23952 NP 23953 NP 23954 NP 23955 NP 23956 NP 23957 NP 23958 NP 23959 NP 23960 NP DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD P = PREGNANT NP' = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). p. 64 ! TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 ! ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 19 (PAGE 1) : MATERNAL BODY HEIGHTS - LACTATION - INDIVIDUAL DATA DAY 1 2 3 4 5 6 DAM # DOSAGE GROUP I GROUP I 0 (VEHICLE) MKD 23901 23902 23903 23904 23905 23906 23907 23908 23909 23910 292. 296. 290. NOT PREGNANT, 296. 260. 310. 265. 312. 261. 275. 270. 280. 283. 289. 297. 293. 293. 301. DEAD DAY 25 (GESTATION) 285. 279. 283. 253. 258. 261. 310. 322. 326. 288. 294. 303. 277. 283. 297. 289. 291. 314. 290. 275. 332. 300. 298. 309. 316. 332. 301. 291. 338. 311. 312. ALL HEIGHTS ARE RECORDED IN GRAMS DAY - DAY OF LACTATION p. 65 TSCA SANITIZED A R G O S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 19 (PAGE 2): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA DAY 1 2 3 4 5 6 DAM # DOSAGE GROUP II GROUP II 10 MKD 23911 23912 23913 23914 23915 23916 23917 23918 23919 23920 273. 254. 260. 258. 324. 313. 321. 329. 276. 276. 281. 284. 271. 280. 278. 288. NOT PREGNANT, DEAD DAY 25 (GESTATION) 274. 252. 260. 263. 297. 300. 303. 316. 286. 296. 291. 305. PREGNANT, DEAD DAY 23 (GESTATION) 284. 295. 291. 306. 260. 328. 295. 296. 269. 329. 300. 306. 276 352 308 307 280 328 303, 321, ALL WEIGHTS ARE RECORDED IN GRAMS DAY = DAY OF LACTATION TSCA SANITIZED A R G O S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDD 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 19 (PAGE 3) : MATERNAL BODY HEIGHTS - LACTATION - INDIVIDUAL DATA DAY 1 2 3 4 5 6 DAM * DOSAGE GROUP III GROUP III 30 HKD 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 280. 314. 279. 297. 282. 294. 316. 280. 282. 290. 268. 307. 274. 283. 275. 287. 306. 280. 289. 282. 266. 318. 286. 289. 278. 290. 315. 292. 293. 289. 266. 317. 285. 293. 284. 293. 307. 295. 300. 286. 271. 321. 299. 302. 290. 303. 325. 309. 305. 292. 295. 344. 313. 311. 305. 321. 340. 322. 317. 306. ALL HEIGHTS ARE RECORDED IN GRAMS DAY - DAY OF LACTATION p. 67 TSCA SANITIZED ARGUS R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 19 (PAGE 4): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA DAY 1 2 3 4 5 6 DAM * DOSAGE GROUP IV GROUP IV 90 MKD 23931 23932 23933 23934 23935 23936 23937 23938 23939 23940 291. 291. 288. 299. 244. 291. 268. 274. 267. 254. 294. 288. 274. 285. 235. 295. 256. 286. 271. 252. 299. 295. 279. 285. 238. 309. 268. 285. 280. 283. 301. 301. 295. 291. 244. 311. 271. 295. 272. 281. 306. 302. 299. 293. 242. 317. 279. 290. 285. 289. 330. 326. 320. 317. 258. 332. 299. 305. 302. 300. ALL WEIGHTS ARE RECORDED IN GRAMS DAY = DAY OF LACTATION p. 68 TSCA SANITIZED i A R G U S R E S E A R C H L A B O R A T O R I E S , ISC . PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 19 (PAGE 5) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA DAY 1 2 3 QAM # GROUP V 23941 23942 23943 23944 23945 23946 23947 23948 23949 23950 NOT PREGNANT, 272. 265. 275. DEAD DAY 267, 267. 3 (GESTATION) 273. 293. 266. 275. PREGNANT, DEAD DAY 21 (GESTATION) HOT PREGNANT, DEAD DAY 3 (GESTATION) NOT PREGNANT, DEAD DAY 5 (GESTATION) 265. 277. 271. 281. 244. NOT PREGNANT, DEAD DAY 3 (GESTATION) 56 270 MKD 295. 270. 315. 287. 286. 299. ALL WEIGHTS ARE RECORDED IN GRAMS DAY - DAY OF LACTATION p. 69 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 19 (PAGE 6): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA DAY I 2 3 4 5 6 DAM # DOSAGE GROUP VI GROUP VI 500 MKD 23951 23952 23953 23954 23955 23956 23957 23958 23959 23960 NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY NOT PREGNANT, DEAD DAY 2 (GESTATION) 2 (GESTATION) 2 (GESTATION) 2 (GESTATION) 2 (GESTATION) 1 (GESTATION) 1 (GESTATION) 1 (GESTATION) 1 (GESTATION) 1 (GESTATION) ALL WEIGHTS ARE RECORDED IN GRAMS DAY - DAY OF LACTATION p. 70 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 0 - 1 1-2 2-3 RAT DOSAGE GROUP I 3-4 4-5 GROUP I 5-6 23902 P 23903 P 23904 NP 23905 P 23906 P 23907 P 23908 P 23909 P 23910 P 20. 21. 21. 23. 21. 23. 16. 19. 18. 22. 25. 24. 21. 19. 17. 16. 27. 21. ie.19. 16. 16. 20. 19. 22. 22. 13. 20. 14. 20. 18. 20. 18. 19. 19. 16. 15. 20. 20. 21. 22. 24. 16. 23. 21. 22. 22. 21. 17. 17. 25. 24. 26. 24. 16. 18. 20. 16. 18. 22. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) . 6-7 7-8 0 (VEHICLE) MKD 23. 21. 27. 26. 25. 25. 23. 23. 22. 24. 20. 22. 24. 26. 24. 21. 26. 27. 24. 23. 8- 23. 45. 41 95. 16 91 . 27. 18. 9 - 1 0 1 0 - 1 1 11 - 12 12 13 43. 4. 24. 24. 5. 28. 28. 27. 5. 25. 26. 26. 22. 22. 24. 23. 29. 27. 31. 28. 22. 22. 24. 22. 28. 24. 27. 28. 24. 26. 23. 25. 29. 28. 28. 31. 23. 25. 26. 23. I p. 71 I II TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 2): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25 RAT * DOSAGE GROUP I GROUP I 0 (VEHICLE) MKD 23901 P 23902 P 23903 P 23904 NP 23905 P 23906 P 23907 P 2390B P 23909 P 23910 P 24. 25. 24. 27. 28. 21. 21. DELIVERED 31. 27. 31. 34. 21. 26. 22. DELIVERED 28. 27. 30. 32. 25. 30. 22. 23. DELIVERED 24. 15. 19. 20. 14. 13. 16. 16. 17. 14. 20. 19. 33. 27. 32. 36. 24. 27. 21. DELIVERED 23. 22. 24. 26. 18. 23. 19. 16. DELIVERED 27. 27. 27. 23. 28. 26. 28. DELIVERED 23. 27. 24. 16. 23. 22. 18. 22. DELIVERED 26. 27. 30. 22. 21. 24. 23. 50. DELIVERED 27. 28. 31. 7. 20. 29. 27. DELIVERED P = PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS * DAYS OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) . p. 72 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 3): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 0 - 1 1- 2 2-3 3-4 4-5 5-6 RAT # DOSAGE GROUP II GROUP II 23911 P 23912 P 23913 P 23914 P 23915 NP 23916 P 23917 P 23918 P 23919 P 23920 P 20. 21. 18. 21. 18. 21. 21. 19. 20. 27. 23. 25. 21. 11. 23. 22. 26. 25. 16. 18. 23. 21. 24. 23. 15. 15. 18. 14. 17. 19. 15. 11. 20. 19. 19. 18. 19. 19. 23. 22. 24. 24. 19. 22. 24. 22. 25. 27. 20. 25. 21. 25. 26. 18. 15. 18. 22. 24. 26. 25. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G). 6-7 10 MKD 20. 26. 17. 21. 20. 21. 25. 25. 20. 16. 7-8 20 29 20 18, 18, 19, 21, 30. 20. 17. 8-9 18. 26. 28. 21. 15. 20. 24. 23. 29. 21. 9 - 1 0 1 0 - 1 1 11 - 12 12 - 13 18. 23. 23. 25 27. 26. 30. 28 24. 22. 26. 28 25. 26. 27. 25 18. 20. 20. 17 20. 2S. 24. 23 23. 25. 25. 23 28. 27. 30. 30 18. 31. 24. 26 22. 25. 20. 31 p. 73 I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 4) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL nATA PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 RAT # DOSAGE GROUP II 16 - 17 17 - 18 GROUP II 18 - 19 19 - 20 10 MKD 20 - 21 21 - 22 22 - 23 23 - 24 23911 P 23912 P 23913 P 23914 P 23915 NP 23916 P 23917 P 23918 P 23919 P 23920 P 2 3 . 2 1 . 2 2 . 2 3 . 2 2 . 1 4 . 2 2 . 21. DELIVERED 3 0 . 2 7 . 3 3 . 3 0 . 2 1 . 2 8 . 2 6 . DELIVERED 2 7 . 2 5 . 2 7 . 2 6 . 22. 22. 3 0 . 1 9 . DELIVERED 2 5 . 2 5 . 2 7 . 2 7 . 2 0 . 2 3 . 1 6 . 2 4 . DELIVERED 2 1 . 2 0 . 2 0 . 1 5 . 1 5 . 1 7 . 1 9 . 1 5 . 1 6 . I.S. 1ft 2 3 . 2 5 . 2 4 . 2 6 . 2 1 . 2 2 . 2 4 . DELIVERED 20. 2 4 . 2 6 . 2 6 . 1 8 . 2 4 . 2 5 . 2 2 . 2 3 . DELIVERED 2 5 . 2 9 . 3 1 . 2 0 . 2 6 . 2 5 . 2 5 . 2 6 . DELIVERED 23. 32. 25. 32. 27. 29. 19. 18. 25. 24. 24. 25. 22. 22. 17. 23. 2 6 . DELIVERED 2 . DEAD DAY 23 P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . p. 74 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDZD 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 0 - 1 1-2 2-3 3-4 4- 5 5-6 RAT # DOSAGE GROUP 111 GROUP III 23921 P 23922 P 23923 P 23924 P 23925 P 23926 P 23927 P 23928 P 23929 P 23930 P 18. 21. 16. 19. 20. 19. 20. 15. 26. 27. 27. 28. 18. 20. 19. 16. 22. 23. 18. 12. 14. 21. 21. 20. 23. 20. 21. 24. 30. 28. 17. 12. 17. 21. 18. 24. 19. 17. 19. 23. 24. 26. 18. 22. 21. 23. 24. 23. 19. 20. 22. 16. 22. 21. 16. 15. 21. 22. 22. 21. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . 6-7 30 HKD 23. 26. 20. 20. 34. 25. 26. 22. 20. 23. 7-8 20. 26. 24. 19. 28. 23. 27. 22. 26. 25. 8-9 21. 26. 24. 23. 26. 25. 24. 21. 24. 24. 9 - 1 0 10 - 11 11 - 12 12 - 13 23. 18. 23. 25. 25. 26. 24. 29. 20. 24. 24. 23. 20. 22. 24. 23. 30. 19. 15. 14. 23. 25. 26. 24. 28. 28. 30. 29. 25. 24. 26. 26. 27. 27. 24. 27. 26. 25. 27. 25. p. 75 r i TSCA SANITIZED AR G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 6) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 18 18 - 19 19 - 20 20 - 21 21 - 22 22 RAT # 23921 P 23922 P 23923 P 23924 P 23925 P 23926 P 23927 P 2392B P 23929 P 23930 P DOSAGE GROUP III 24. 28. 29. 31. 21. 22. 25. 27. 50. 27. 25. 24. 28. 21. 24. 24. 27. 28. 26. 31. 28. 24. 26. 34. 27. 28. 26. 27. 25. GROUP III 27. 28. 25. 17. 26. 21. 27. 20. 33. 23. 30. 20. 21. 25. 20. 25. 20. 25. 22. 24. 30 MKD 13. 20. DELIVERED 26. 24. DELIVERED 20. 23. 20. DELIVERED 24. 21. DELIVERED 28. 25. 23. DELIVERED 27. 28. 24. DELIVERED 27. 18. 25. DELIVERED 24. 18. 21. DELIVERED 25. 23. 23. DELIVERED 26. 26. 23. DELIVERED P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . 23 23 24 24 - 25 p. 76 TSCA SANITIZED PROTOCOL ZXA00077 = ^ ARGUS R E S E A R C H L A B O R A T O R I E S , INC. ^^^ XOXICITV SCREENING STUDY OF TDID 6675 IN RATS TABLE 20 (PAGE 7) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA 1M 11 1 PREGNANCY STATUS DAYS o 1-2 2-3 1 11 1 RAT DOSAGE GROUP IV 3-4 4-5 GROUP rv 5-6 23931 P 23932 P 23933 P 23934 P 23935 P 23936 P 23937 P 23938 P 23939 P 23940 P 19. 20. 15. 24. 20. 29. 21. 18. 19. 19. 22. 18. 19. 20. 21. 21. 21. 23. 18. 15. 19. 22. 23. 21. 14. 15. 13. 20. 16. 20. 16. 21. 23. 16. 23. 22. 19. 21. 21. 19. 22. 20. 17. 21. 18. 21. 21. 23. 12. 15. 14. 13. 11. 20. 21. 25. 18. 22. 16. 21. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G). 6- 90 MKD 27. 19. 22. 18. 23. 21. 22. 20. 13. 7-8 8-9 24. 24. 18. 21. 23. 23. 24. 26. 16. 18. 21. 19. 22. 20. 25. 24. 18. 18. 20. 9 - 1 0 1 0 - 1 1 11 - 12 12 13 28. 24. 23. 25. 20. 23. 20. 16. 19. 20. 27. 24. 24. 24. 20. 23. 20. 24. 24. 17. 31. 27. 24. 28. 19. 26. 22. 22. 23. 18. 30. 29. 24. 25. 20. 27. 25. 25. 24. 20. p. 77 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 8) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25 RAT # DOSAGE GROUP IV GROUP IV 90 MKD 23931 P 23932 P 23933 P 23934 P 23935 P 23936 P 23937 P 23938 P 23939 P 23940 P 32. 32. 33. 34. 31. 21. 22. 22. DELIVERED 32. 29. 30. 32. 22. 28. 23. DELIVERED 24. 23. 28. 28. 21. 25. 24. 19. DELIVERED 29. 26. 31. 31. 24. 29. 23. DELIVERED 20. 21. 20. 22. 17. 18. 20. 13. DELIVERED 23. 28. 29. 19. 28. 24. 19. 20. DELIVERED 20. 14. 21. 19. 19. 22. 17. 23. DELIVERED 24. 27. 28. 20. 27. 23. 22. 19. DELIVERED 23. 19. 24. 16. 21. 17. 18. DELIVERED 27. 28. 30. 18. 23. 24. 16. 19. DELIVERED P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) . p. 78 TSCA SANITIZED argus research la bo rat ori es , i n c . PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 9) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 0 - 1 1 - 2 2-3 RAT DOSAGE GROUP V 23941 NP 23942 P 23943 P 23944 P 23945 P 23946 NP 23947 NP 23948 P 23949 P 23950 NP 1. DEAD 12. 0. 11. 1. 9. 2 10. I. i. DEAD 8. DEAD 6. 6. 1. DEAD 3-4 4-5 GROUP V 5-6 14. 16. P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL HEIGHTS NERE RECORDED IN GRAMS (G). 6-7 270 MKD 17. 17. X3. 16. 20. 20. 7-8 22. 20. 18. 16. 21. 19. 8-9 21. 18. 18. 21. 21. 17. 9 - 1 0 10 - 11 -- 24. 24. 21. 20. 21. 18. 23. 21. 12 - 13 -- ---- -- 24. 24. 22. 21. 22. 23. 24. 23. 22. 22. 22. 23. 19. 21. 19. 22. p. 79 :I I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 10): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 1 7 - 1 8 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25 RAT # DOSAGE GROUP V GROUP V 270 MKD 23941 NP DEAD 23942 P 26. 23. 24. 24. 26. 26. 26. 20. DELIVERED 23943 P 23. 23. 23. 25. 23. 25. 20. DELIVERED 23944 P 21. 19. 24. 23. 20. 27. 22. 21. DELIVERED 23945 P 23. 19. 24. 24. 16. 25. 12. 0. DEAD DAY 21 23946 NP DEAD 23947 NP DEAD 23948 P 21. 20. 21. 20. 23. 23. 19. 18. DELIVERED 23949 P 19. 20. 18. 16. 18. 20. 17. 18. DELIVERED 23950 NP DEAD P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). p. 80 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF NTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (RAGE 11): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 0 - 1 1- 2 2-3 RAT # DOSAGE GROUP VI 23952 NP 23953 NP 23954 NP 23955 NP 23956 NP 23957 NP 23958 NP 23959 NP 23960 NP 2. DEAD 4. 0. DEAD l. DEAD 7. l. DEAD 7. l. DEAD 2. DEAD 2. DEAD 1. DEAD 7. DEAD 0. DEAD 3-4 4-5 GROUP VI 5-6 P - PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) . 6-7 500 HKD 7-8 8 - 9 9-10 10-11 11-12 12-13 p. 81 I TSCA SANITIZED ARGUS R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 20 (PAGE 12) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - IS 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25 RAT # DOSAGE GROUP VI GROUP VI 500 MKD 23951 NP 23952 NP 23953 NP 23954 NP 23955 NP 23956 NP 23957 NP 23958 NP 23959 NP 23960 NP DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD P PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . P- 82 TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 21 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA DAY 2 - 3 3 - 4 DAM # DOSAGE GROUP 1 GROUP I 23901 23902 23903 23904 23905 23906 23907 23908 23909 23910 628. 28. DEAD 16. 18. 19. 22. 30. 27. 25. 31. 25 24. 26. 35. 31. 38. 55. 34. 45. 35. 33. 41. 36. 41. ALL HEIGHTS ARE RECORDED IN GRAMS. 4-5 5-6 1-4 0 (VEHICLE) MKD 39. 42. 95. 38. 40. 687. 42. 52. 104. 45. 43. 75. 38. 42. 77. 33. 41. 95. 37. 41. 89. 47. 52. 109. DAY - DAY OF LACTATION 4-6 81. 78. 94. 88. 80. 74. 78. 99. 1- 176 765 198 163 157, 169. 167, 208. p. 83 I I! TSCA SANITIZED AR G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL {GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDD 6675 IN RATS (SPONSORS REFERENCE NO. 06-376) TABLE 21 (PAGE 2): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA DAY 1 - 2 2 - 3 3-4 4-5 5-6 1-4 DAM # DOSAGE GROUP II GROUP II 10 MKD 23911 23912 23913 23914 23915 23916 23917 23918 23919 23920 10. 27. 23. 29. 42. 60. 21. 32. 44. 45. 54. 97. ii. 24. 32. 2B. 35. 67. 27. 25. 37. 40. 42. 69. DEAD 25 13. 23. 26. 38. 35. 62. 21. 34. 39. 54. 44. 94. 22. 29. 36. 40. 39. 87. DEAD DAY 23 27. 26. 36. 42. 43. 1 00 I \D ALL WEIGHTS ARE RECORDED IN GRAMS. DAY - DAY OF LACTATION 4-6 71. 99. 63. 82. 73. 98. 79. 85. 1-6 131. 196. 130. 171. 135. 192. 166. 174. p. 84 I' ! TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 21 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA DAY 1 - 2 2-3 3-4 4-5 5-6 1-4 DAM * DOSAGE GROUP III GROUP III 30 MKD 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 14. 22. 29. 32. 65. 23. 34. 31. 44. 45. 88. 13. 30. 36. 43. 43. 79. 21. 30. 28. 47. 44. 79. 14. 19. 30. 33. 37. 63. 11. 23. 28. 35. 40. 62. 14. 29. 33. 41. 43. 76. 17. 36. 36. 43. 50. 89. 24. 34. 38. 51. 47. 96. 16. 25. 32. 33. 44. 73. ALL HEIGHTS ARE RECORDED IN GRAMS. DAY - DAY OF LACTATION 4-6 89. 86. 91. 70. 75. 84. 93. 98. 77. 1-6 177. 165. 170. 133. 137. 160. 182. 194. 150. TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077. : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 21 (PAGE 4): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA DAY 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6 1 - 4 DAM # DOSAGE GROUP IV GROUP IV 90 MKD 23931 23932 23933 23934 23935 23936 23937 23936 23939 23940 27. 34. 16. 29. 13. 29. 15. 21. 8. 23. 18. 35. 11. 30. 17. 33. 19. 24. 7. 31. ALL WEIGHTS ARE RECORDED IN GRAMS. 37. 32. 42. 29. 25. 39. 36. 38. 23. 34. 48. 49. 98. 41. 47. 77. 49. 52. 84. 34. 44. 65. 30. 34. 56. 43. 49. 92. 35. 42. 77. 45. 47. 88. 33. 41. 66. 38. 42. 72. DAY = DAY OF LACTATION 4-6 97. 88. 101. 78. 64. 92. 77. 92. 74. 80. 1-6 195. 165. 185. 143. 120. 184. 154. 180. 140. 152. TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 21 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA 23941 23942 23943 23944 23945 23946 23947 2394B 23949 23950 DAY 1 - 2 2 - 3 3 - 4 DOSAGE GROUP V GROUP V DEAD 14. 13. 3 27. 19. 34. 28. DEAD DAY DEAD DEAD 17. 21 3 5 21. 24. DEAD 3 4-5 43. 32. 31. 5-6 270 MKD 36. 35. 28. ALL WEIGHTS ARE RECORDED IN GRAMS. DAY DAY OF LACTATION -6 1-6 79. 156. 67. 127. 59. 121. p. 87 - ; I ) TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 21 (PAGE 6): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA DAY 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6 1 - 4 DAM * DOSAGE GROUP VI GROUP VI 500 MKD 23951 23952 23953 23954 23955 23956 23957 23956 23959 23960 DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD DEAD 2 2 2 2 2 1 1 1 1 1 ALL WEIGHTS ARE RECORDED IN GRAMS. DAY = DAY OF LACTATION 4-6 1-6 p. 88 I f I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (SAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 22 (PAGE 1): NATURAL DELIVERY,, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA MATERNAL DOSAGE GROUP I GROUP I 0 (VEHICLE) MKD RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN NNN 1 MF NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 46 MF MF 23901 23902 23903 23905 23906 23907 23908 23909 23910 22 22 23 22 23 22 23 22 23 17 14 14 15 15 16 14 16(5) 13 0 0 0 1 0 1 0 0 0 17 14 14 16 15 17 14 16 13 6 il 86 77 96 69 88 77 56 94 6 il 86 77 96 69 87 77 -- 94 6 il 86 77 96 69 87 77 -- 94 M - MALE F - FEMALE ( ) - NUMBER OF PUPS DYING PRIOR TO NEIGHING ON DAY 1 POSTPARTUM. TOTAL IMPLANTATIONS N 0 0 0 0 0 0 0 0 0 p. 89 I I -I I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 22 (PAGE 2) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA MATERNAL DOSAGE GROUP II GROUP II RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N 23911 23912 23913 23914 23916 23917 23918 23920 22 22 23 23 22 23 23 23 M MALE F = FEMALE LITTER DELIVERED LIVE STILL TOTAL BORN BORN BORN NNN 13 2 15 14 1 15 608 14 0 14 13 0 13 16 1 17 15 0 15 13 0 13 i MF 49 4 10 44 86 85 4 12 78 76 10 MKD NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 46 MF MF 49 4 10 44 86 85 4 11 78 76 49 4 10 44 86 85 4 11 78 76 TOTAL IMPLAN TATIONS N 0 0 0 0 0 0 0 0 p. 90 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 22 (PAGE 3) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA MATERNAL DOSAGE GROUP III GROUP III RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL TOTA) BORN BORN BORN NNN 1 MF 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 M - MALE 22 22 23 22 23 22 22 22 23 22 F - FEMALE 15 14 13 IS 4 15 16 18 16 14 0 15 0 14 0 13 0 15 04 0 15 0 16 0 18 1 17 1 IS 5 10 86 58 78 -4 78 79 8 10 79 95 30 MKD NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 46 MF MI 5 10 86 58 78 -4 68 79 88 79 95 5 10 86 58 78 -4 68 79 88 79 95 TOTAL IMPLAN TATIONS 0 0 0 0 0 0 0 0 0 0 p. 91 I ! TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 22 (PAGE 4) NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA MATERNAL DOSAGE GROUP IV GROUP IV RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN NNN 1 MF 23931 23932 23933 23934 23935 23936 23937 23938 23939 23940 M - MALE 23 22 22 22 22 22 22 23 22 22 F = FEMALE 15 14 17 13 11 18 15 16 14 12 0 15 0 14 0 17 0 13 0 11 0 18 0 15 1 17 0 14 0 12 78 77 89 85 56 8 10 87 79 68 10 2 90 MKD NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 46 MF MF 78 77 89 85 56 8 10 87 69 68 92 78 77 39 85 56 8 10 87 69 68 92 TOTAL IMPLAN TATIONS N 0 0 0 0 0 0 0 0 0 0 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF HTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) RATS TABLE 22 (PAGE 5)! NATURAL DELIVERY. IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA MATERNAL DOSAGE GROUP V GROUP V 270 MKD RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N 23942 23943 23944 23948 23949 22 22 23 23 23 LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 16(4) 13 15(15) 9 2(2) 0 0 0 0 12 16 13 15 9 1511] 1 MF 75 58 36 - NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 46 MF MF 75 35 75 35 24 24 M - MALE F - FEMALE ( ) - NUMBER OF PUPS DYING PRIOR TO NEIGHING ON DAY 1 POSTPARTUM. ( I - NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. TOTAL IMPLAN TATIONS N p. 93 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 23 (PAGE 1): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA MATERNAL DOSAGE GROUP I GROUP I 0 (VEHICLE) MKD RAT/ LITTER NUMBER DAY 1 M FT DAY 4 M FT DAY 6 M FT 23901 23902 23903 23905 23906 23907 23908 23909 23910 5.7 5.4 5.5 6.4 6.0 6.2 7.4 6.8 7.1 5.8 5.6 5.7 6.8 6.0 6.3 6.3 6.1 6.2 7.1 6.4 6.7 NO SURVIVING PUPS 6.6 6.2 6.5 7.2 8.4 9.7 8.3 9.3 9.0 9.2 10.2 7.0 7.1 8.0 8.2 9.2 9.5 7.8 8.1 8.6 8.8 8.9 9.0 8.8 9.0 9.6 10.0 9.5 10.8 12.1 11.2 11.3 11.4 11.9 8.1 10.8 11.7 10.6 9.7 11.2 11.2 0.6 10.8 11.9 11.0 10.4 11.3 11.6 13.3 13.0 13.2 M - MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. p. 94 II TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) 1N BATS TABLE 23 (PAGE 2) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA MATERNAL DOSAGE GROUP II GROUP II 10 MKD RAT/ LITTER NUMBER DAY 1 M FT DAY 4 M FT DAY 6 M FT 23911 23912 23913 23914 23916 23917 23918 23920 6.0 5.8 5.9 6.2 5.5 5.7 6 . 6 6 . 2 6.4 6.7 6.4 6 . 6 5.4 5.1 5.3 6.2 5.5 5.7 6.2 6.1 6.2 6.9 6.7 6 . 8 7.9 8.0 7.9 10.6 10.2 10.3 8.5 7.9 8.1 11.5 10.7 10.9 9.4 9.4 9.4 11.5 11.8 11.7 8.8 8.4 8.6 11.0 10.6 10.6 8.4 8.1 8.3 10.5 10.2 10.4 9.5 8.6 8.8 12.1 10.7 11.1 9.2 9.2 9.2 11.6 11.5 11.5 9.9 9.3 9.6 13.0 12.1 12.6 M - MALE F - FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (SUM OF PUP WEIGHTS/NUMBBR OF LIVE PUPS) DAY - DAY POSTPARTUM (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. p. 95 I ' 1 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 23 (PAGE 3) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA i MATERNAL DOSAGE GROUP III GROUP III 30 MKD RAT/ LITTER NUMBER DAY 1 M FT DAY 4 M FT DAY 6 M FT 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 5.8 5.3 5.5 6.1 6.0 6.0 5.9 5.6 5.7 6.0 5.8 5.9 -- 7.6 7.6 5.4 5.4 5.4 5.8 5.6 5.7 5.9 5.3 5.6 5.6 5.6 5.6 5.8 5.6 5.8 8.0 7.4 7.6 8.9 8.6 8.8 9.3 8.8 9.0 8.7 8.2 8.4 -- 12.1 12.1 7.9 7.3 7.6 8.2 8.0 8.1 8.0 7.7 7.9 7.8 8.1 8.0 8.5 8.2 8.4 10.0 11.4 12.2 11.1 -- 9.8 9.9 10.4 10.7 na 9.4 li.i 11.5 10.6 15.4 9.3 9.8 10.0 11.0 10.8 9.6 11.2 11.8 10.9 15.4 9.6 9.8 10.2 10.9 11.0 M - MALE F - FEMALE T - TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. p. 96 TSCA SANITIZED PROTOCOL ZXA00077 ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 23 (PAGE 4) : PUP BODY HEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA MATERNAL DOSAGE GROUP IV GROUP IV 90 MKD RAT/ LITTER NUMBER DAY 1 M FT DAY 4 M FT DAY 6 MFT 23931 23932 23933 23934 23935 23936 23937 23938 23939 23940 6.5 6.0 6.2 10.0 9.6 9.8 12.0 11.4 11.6 5.7 5.4 5.6 7.8 7.7 7.8 10.1 9.9 10.0 5.3 5.1 5.2 7.2 6.8 7.G 9.2 9.1 9.2 5.7 5.3 5.6 8.5 7.8 8.2 11.2 10.6 10.9 5.8 5.3 5.5 7.0 7.4 7.2 9.2 8.4 8.7 5.4 5.2 5.3 7.4 7.0 7,2 9.1 9.0 9.0 5.5 4.9 5.2 7.3 6.4 6.9 9.9 8.4 9.2 5.9 5.3 5.6 7.9 7.4 7.6 10.8 10.2 10.4 5.2 5.0 5.1 7.5 7.2 7.4 10.0 9.7 9.8 5.7 5.4 5.7 7.9 7.8 7.9 11.1 11.4 11.2 M - MALE F - FEMALE T - TOTAL (SUM OF PUP HEIGHTS/NUMBER OF LIVE PUPS) DAY - DAY POSTPARTUM ALL HEIGHTS HERE RECORDED IN GRAMS <G) . MEAN LITTER HEIGHTS INCLUDE ONLY HEIGHTS OF LIVE POPS. p. 97 ii TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 23 (PAGE 5): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA MATERNAL DOSAGE GROUP V GROUP V 270 MKD RAT/ LITTER NUMBER DAY 1 M FT DAY 4 M FT DAY 6 M FT 23942 23943 23944 23948 23949 4.3 4.4 4.4 5.7 6.4 6.0 7.2 7.9 7.5 4.7 4.7 4.7 6.6 6.8 6.7 8.4 8.8 8.7 4.6 4.2 4.4 NO SURVIVING PUPS 5.0 4.9 5.0 6.4 5.6 5.8 9.2 8.2 8.6 NO SURVIVING PUPS M = MALE F = FEMALE T - TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY - DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. p. 98 I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE I) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP * 1 2 3 21 22 23 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER * 23901 23902 23903 23905 23906 23907 23908 23909 23910 MATERNAL DOSAGE GROUP I GROUP I 0 (VEHICLE) MKD LACTATION DAY 1 5.4 6.2 7.2 5.6 6.5 7.6 MX 1 5.9 5.8 6.8 7.7 5.6 6.5 6.0 7.1 MX 1 6.4 5.7 6.3 7.3 5.6 7.4 6.3 6.8 MX 1 6.5 5.6 6.3 7.1 6.3 7.0 6.7 6.8 MX 1 7.2 5.8 6.3 7.3 5.4 7.0 5.7 7.0 MX 1 7.0 5.7 6.8 7.6 6.0 6.3 6.5 7.2 FX 1 7.4 5.4 5.6 7.4 5.7 5.7 5.9 7.1 FX 1 5.8 5.7 6.5 7.0 6.4 6.6 6.8 6.9 FX 1 6.9 5.4 6.3 7.3 MS 6.1 MS 6.0 FX 1 6.8 5.7 5.7 6.3 MA 5.7 6.3 6.5 FX 1 5.9 5.5 6.2 6.8 5.8 4.2 5.9 5.9 FX 1 6.2 5.5 6.0 6.5 5.4 6.4 6.7 6.6 UX 1 6.3 5.4 5.9 6.8 5.6 6.2 6.0 6.3 UX 1 6.6 5.5 5.9 7.2 5.7 6.6 5.6 6.9 UX 1 5.4 5.3 6. A 6.3 UX 1 5.6 6.1 UX 1 5.3 6.1 S S S S li unde n TM r keights inclode CANNIBALIZED,. X-OTHER p. 99 ! I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 2): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA POP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # 23911 23912 23913 23914 23916 23917 23918 23920 MATERNAL DOSAGE GROUP II GROUP II 10 MKD LACTATION DAY 1 5.6 6.1 6.2 6.1 MS 5.6 5.7 5.9 5.6 6.2 6.0 5.6 5.8 5.9 FS 5.9 6.1 6.2 6.5 5.7 5.6 5.5 5.4 5.8 5.5 5.7 5.2 5.0 5.2 FS 6.8 7.1 6.0 6.5 6.3 5.7 6.5 6.5 6.5 6.5 7.1 7.5 6.0 6.7 6.7 6.8 6.7 6.2 6.2 6.3 6.5 6.2 5.4 6.0 5.2 5.4 5.2 5.0 5.6 5.4 5.2 4.8 5.1 5.1 5.4 6.8 6.6 5.2 6.2 MS 4.8 5.3 6.1 5.2 6.2 5.7 6.1 5.0 5.9 5.5 6.0 4.7 5.4 6.1 5.7 7.1 7.3 6.4 5.8 5.0 5.8 6.5 6.5 6.4 6.2 6.2 6.4 7.4 6.7 6.8 7.0 6.8 7.1 6.6 6.1 6.5 6.8 7.2 6.2 7.3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. p. 100 t I II TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DBVELOPMBHTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 3): PUP BODY HEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP # 1 2 3 21 22 23 4 5 6 7 8 9 10 ii 12 13 14 15 16 18 19 RAT/ LITTER # 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 MATERNAL DOSAGE GROUP III GROUP III 30 MKD LACTATION DAY 1 6.0 6.0 6.1 6.0 6.3 4.8 5.3 5.8 6.1 5.8 6.6 5.9 5.8 6.0 6.4 4.6 6.1 5.3 5.5 5.8 5.9 5.7 6.3 5.3 5.7 6.0 5.8 5.8 5.8 5.6 5.2 5.7 5.6 5.4 6.2 5.4 5.3 6.5 5.5 5.1 5.7 4.4 5.8 7.5 6.1 7.6 6.3 7.6 5.9 7.8 6.0 5.8 6.2 5.5 5.5 5.9 5.3 5.9 5.8 6.1 6.0 5.7 5.6 6.0 5.4 6.1 6.0 6.0 6.5 5.4 6.1 5.7 5.9 5.9 5.9 6.1 5.6 5.5 5.3 5.4 5.7 5.5 5.9 5.9 5.8 5.7 3.8 5.9 6.0 6.1 5.6 5.7 5.7 5.9 5.5 5.8 5.7 5.2 6.0 5.0 5.6 4.8 5.5 5.5 6.3 6.0 5.3 6.0 6.0 5.8 MS 5.7 5.6 4.9 5.8 5.6 5.4 5.6 5.8 5.2 5.7 5.2 6.3 4.9 6.4 5.4 5.8 5.3 4.8 5.3 5.7 5.0 5.5 5.5 5.3 5.4 5.5 51 54 5.0 iiiJ!Ei S S TM WEREuREC0RDED IN GRM1S (G> MEAN LITTER HEIGHTS INCLUDE ONLY HEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE NUMBER rnTrnuTTir U_UHCERTAIN' D_DIED. C-CULLBD, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20 p. 101 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 4): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 22 23 RAT/ LITTER f 23931 23932 23933 23934 23935 23936 23937 23938 23939 23940 MATERNAL DOSAGE GROUP IV GROUP IV 90 MKD LACTATION DAY 1 6.6 7.0 6.3 6.8 6.5 5.8 6.6 6.6 6.3 5.8 5.5 6.1 6.1 5.8 5.6 6.0 5.5 5.9 5.7 5.4 5.6 6.1 5.3 5.9 5.1 5.1 5.4 5.6 5.4 5.3 5.2 5.2 5.5 4.8 6.0 4.9 5.2 4.9 5.5 4.7 5.3 5.5 4.8 5.3 5.4 4.7 5.4 6.6 5.7 6.0 6.2 4.6 5.6 5.8 4.8 5.1 5.6 5.3 5.9 5.7 6.3 6.0 5.4 5.8 5.2 5.6 5.3 5.1 5.0 5.4 5.6 5.8 4.9 5.4 5.5 5.9 5.1 5.4 5.4 4.9 5.3 5.2 4.5 5.1 5.2 5.8 5.1 5.2 5.6 5.4 5.8 5.4 5.6 5.7 5.3 5.4 4.5 5.0 5.3 5.4 4.7 4.4 5.3 5.8 5.7 6.2 5.8 6.0 5.8 5.9 4.4 5.2 5.9 5.4 5.5 5.0 5.5 5.2 5.5 FS 5.2 4.9 4.8 5.5 4.9 5.6 4.8 4.9 4.9 5.0 5.2 5.2 4.9 5.1 5.5 5.8 6.0 5.7 5.4 5.5 5.9 5.9 5.4 6.0 5.1 5.8 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20 p. 102 TSCA SANITIZED PROTOCOL 2XA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 {PAGE 5): PUP BODY HEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP # 1 2 3 21 22 23 4 5 6 7 8 9 10 ii 12 13 14 15 16 RAT/ LITTER * 23942 23943 23944 23948 23949 MATERNAL DOSAGE GROUP V 4.9 4.6 4.6 MD 1 4.5 4.5 MO 1 5.4 MD 1 4.6 4.9 MD 1 5.0 MS 4.2 4.6 MD 1 5.3 MS 4.3 4.6 MD 1 5.0 MS GROUP V 4.1 4.6 MD 1 4.5 MS 4.1 4.6 MD 1 4.5 FS 4.3 4.8 MD 1 5.0 FS 270 MKD 4.4 4.5 MD 1 5.3 FS 4.4 4.7 4.2 FS 4.1 4.6 FD 1 FS 4.3 4.6 FD 1 PS LACTATION DAY 4.1 4.9 FD 1 4.7 FD 1 4 _S FD 1 FS FS UU 1 A . fi p. 103 I i TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 6) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP I GROUP I 0 (VEHICLE) MKD LACTATION DAY 4 23901 23902 23903 23905 23906 23907 23908 23909 23910 7.5 8.7 9.8 8.4 8.5 9.1 9.6 MX 1 10.1 7.6 9.0 10.0 8.5 9.6 8.9 9.5 MX 1 9.7 6.9 7.6 10.2 9.2 8.4 10.2 9.1 MX 1 10.3 7.3 8.5 10.0 7.5 9.5 9.4 8.8 MX 1 10.2 6.9 9.2 8.9 8.0 9.7 9.1 9.4 MX 1 11.8 7.3 8.5 9.9 8.2 10.1 9.6 9.3 FX 1 9.7 7.0 7.4 9.4 8.2 6.0 8.2 8.9 FX 1 10.6 6.4 8.4 8.6 9.0 8.9 7.9 8.9 FX 1 10.5 6.7 8.5 9.1 MS 8.6 MS 8.7 FX 1 8.9 7.0 7.9 9.4 8.0 9.4 8.7 8.7 FX 1 9.5 6.9 7.6 9.3 8.2 8.4 9.2 8.5 FX 1 9.7 7.3 8.1 9.6 8.0 9.0 9.1 8.8 UX 1 9.5 7.5 8.1 9.4 7.4 8.4 8.8 8.7 UX 1 9.9 7.5 8.0 9.2 7.9 9.4 9.3 9.1 UX 1 6.5 7.7 8.9 8.7 UX 1 7.3 7.8 8.8 UX 1 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) , X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. p. 104 I TSCA SANITIZED PROTOCOL ZXAQ0077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 7): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP # 1 2 3 21 22 23 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER # 23911 23912 23913 23914 23916 23917 23918 23920 MATERIAL DOSAGE GROUP II GROUP II 10 MKD LACTATION DAY 4 8.1 8.1 7.6 7.7 MS 8.1 7.5 7.9 8.1 8.2 8.3 7.8 7.8 7.9 FS 8.0 8.9 8.5 8.7 7.8 8.5 7.6 7.9 8.2 7.9 8.1 7.5 7.8 7.5 FS 10.2 9.1 8.7 9.8 8.8 9.1 9.9 9.8 7.8 6.7 8.6 9.5 8.2 9.7 8.8 9.0 7.9 8.4 8.6 8.7 8.4 8.4 8.4 7.7 8.8 8.6 8.3 8.2 9.0 8.3 8.0 7.9 8.3 7.7 6.4 9.8 9.2 9.9 9.7 8.4 9.5 9.8 9.3 MS 8.5 9.1 9.3 8.3 10.0 9.8 9.3 8.9 7.5 8.3 9.6 8.3 8.9 8.7 9.3 7.7 9.5 8.3 9.7 7.5 9.4 8.2 FM 3 10.2 9.9 10.2 10.6 9.2 9.4 10.0 9.1 8.9 10.0 9.7 9.7 8.3 WERE REC0RDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALB, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCTRRED. CANNIBALIZED), X OTHER p. 105 I 1 ' 1 TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVEI/JPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 8) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA 0 1 OM I1 PUP # 1 2 3 4 5 6 7 8 21 22 23 11 12 13 14 15 16 17 18 RAT/ LITTER # 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 MATERNAL DOSAGE GROUP III GROUP III 30 MKD LACTATION DAY 4 8.2 7.9 89.. 86 12.0 7.9 9.3 9.5 7.7 8.9 9.5 8.2 9.3 8.3 8.0 9.4 8.5 7.0 9.5 9.0 7.4 7.8 8.4 7.5 8.2 9.0 8.3 8.7 8.7 87.. 66 8.8 7.2 9.5 9.3 6.7 88.. 84 6.7 8.2 7.2 8 . 6 8.7 8 . 2 9.2 8.4 8.4 8 . 8 8 . 2 7.5 8.3 8.5 7.5 8 . 0 12.1 12.7 88.. 24 7.6 8.0 7.9 8.7 7.1 8.1 8.1 MD 2 7.7 8.8 7.1 7.9 7.3 8.0 6.7 8.6 7.5 8.4 7.1 8.6 87.. 81 7.7 7.6 7.8 6.9 7.0 7.6 7.9 8 . 1 7.2 8.9 8.4 8.3 7.1 8 . 2 7.1 7.9 8.7 8 . 0 7.4 7.2 FD 2 FD 2 8.1 8.0 7.8 8.7 8.0 8.0 8.0 8.4 7.3 8.4 8.3 7.5 9.1 7.9 7.7 8.6 8.6 MS 7.4 7.8 9.2 8.2 8.5 8.1 87.. 84 7.8 8 . 6 7.9 S ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. X-OTHER 19 20 p. 106 II TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 9) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP # I 2 3 21 22 23 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER * 23931 23932 23933 23934 23935 23936 23937 23938 23939 23940 MATERNAL DOSAGE GROUP IV GROUP IV 90 MKD LACTATION DAY 4 10.1 10.4 7.7 8.1 6.7 7.4 8.8 . 8.1 6.8 7.1 11.2 7.5 7.2 8.8 7.4 9.9 8.0 7.4 8.5 6.8 9.2 10.2 8.1 7.8 7.4 6.6 9.3 9.4 7.1 7.4 9.4 7.3 7.4 6.4 7.6 9.6 8.7 7.5 8.5 7.3 9.6 7.6 6.8 9.0 7.1 9.0 7.5 7.0 8.0 7.1 9.8 10.4 10.6 7.6 7.9 7.1 6.3 7.4 6.6 7.2 8.5 6.5 7j 9.4 7.7 7.4 8.1 6.3 6.9 6.9 7.7 7.8 7.8 8.0 7.9 6.3 7.0 7.6 7.6 7.8 8.1 7.6 8.6 7.3 8.5 7.8 6.9 7.9 7.5 8.1 7.6 8.0 7.8 7.4 6.9 8.2 6.6 7.1 6.9 7.6 MD 2 7.4 7.2 8.4 8.2 6.9 7.3 7.2 6.8 7.6 7.0 6.6 5.4 6.6 7.4 7.1 7.1 7.3 7.5 MM 2 7.4 5.4 7.6 7.4 7.9 5.7 6.9 8.6 7.9 7.8 7.0 7.3 6.1 6.4 7.7 6.1 6.9 7.6 7.9 7.3 7.8 6.8 7.8 7.1 FS " RS?E TM W- - ^ S " ? - ^ f u - s U N D E T ^ L TER "EIGHTS INCLDE NLY WEIGHTS F LIVE TOPS- SS CANNIBALIZED,. X-OTHER p. 107 I 1 : :[ TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 10) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # 23942 23943 23944 23948 23949 MATERNAL DOSAGE GROUP V GROUP V 270I MKD LACTATION DAY 4 4.5 5.9 MD 1 6.9 MD 1 5.9 6.3 MD 1 5.9 MD 1 6.0 7.5 MD 1 MM 3 MS 5.5 MD 2 MD 1 6.5 MS 5.7 MD 2 MD 1 7.5 MS 5.6 6.9 MD 1 4.3 MS 6.6 7.0 MD 1 4.0 FS MD 1 6.9 MD 1 EM 2 FS MD 1 6.5 MD 1 FM 2 FS MD 1 6.6 FD 1 FS 6.5 FD 2 FD 1 FS 6.1 FD 2 FD 1 FS 6.3 FD 2 FD 1 FS 7.1 FD 1 FS 5.9 FD 1 UU FD 1 p. 108 TSCA SANITIZED PROTOCOL ZXA00077 s ? ^ N s" ^ r e TM T T^-3?6iCITY SCREENING STUDY F MTDID 6675 IN RATS TABLE 24 (PAGE 11) POP BODY HEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PI- * 1 2 3 4 5 21 22 23 8 9 1 H 12 13 H 15 16 17 IB 19 20 RAT/ LITTER 23901 23902 23903 23905 23906 23907 23908 23909 23910 MATERNAL DOSAGE GROUP I 9.6 11.6 10.7 11.9 12.0 12.3 12.0 MX 1 13.5 8.3 11.3 12.4 11.1 10.9 11.4 12.6 MX 1 11.7 9.6 11.0 12.3 10.8 12.3 10.1 11.7 MX 1 14.3 11.2 11.6 11.4 10.7 11.2 12.3 MX 1 14.2 9.9 8.6 12.8 11.8 11.0 11.2 11.3 MX 1 13.5 GROUP I 9.9 11.5 13.0 11.4 11.0 11.8 12.1 FX 1 13.4 8.6 10.0 12.2 10.8 11.0 10.2 11.3 FX 1 14.0 7.8 li.i 11.7 11.4 10.7 12.6 11.6 FX 1 12.3 0 (VEHICLE) MKD 7.8 11.1 11.1 MS 5.0 MS 10.9 FX 1 12.7 7.8 10.9 11.8 10.1 11.0 11.6 11.2 FX 1 13.4 7.8 10.8 11.3 11.0 10.3 11.6 10.9 FX 1 12.5 7.8 10.0 12.1 10.8 10.7 11.0 11.5 UX 1 12.9 LACTATION DAY 6 7.8 11.2 12.1 10.2 11.2 11.7 11.1 UX X 13.0 7.8 10.8 11.8 9.7 10.8 10.8 11.5 UX 1 7.8 11.3 6.8 10.8 UX 1 9.1 10.7 10.7 UX 1 X-OTHER p. 109 I - I TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 12): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA POP * 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 16 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP II GROUP II 10 MKD LACTATION DAY 6 23911 23912 23913 23914 23916 23917 23918 23920 10.9 12.7 11.7 11.5 n .i 12.3 10.9 12.8 10.8 12.3 12.4 11.5 10.3 12.9 10.6 13.3 10.3 11.5 11.3 10.8 10.1 12.7 12.2 12.2 10.2 9.6 10.7 11.6 10.5 10.4 12.5 12.4 MS 11.0 11.2 10.2 10.3 MS 10.9 13.6 9.6 10.8 12.3 10.2 10.6 10.4 11.4 13.1 10.2 10.4 11.5 10.7 10.3 11.7 12.7 13.6 10.4 11.3 12.2 11.7 10.6 12.2 12.3 12.8 10.1 10.6 n .i 10.4 11.5 11.4 11.5 10.2 11.2 10.2 10.0 11.7 9.8 13.2 10.9 10.7 11.0 9.5 9.6 11.8 11.5 10.1 11.0 10.7 10.7 8.8 10.8 11.4 10.7 10.1 10.3 10.6 10.9 12.5 12.4 10.1 9.6 10.3 11.1 10.9 FS FS 9.7 12.2 ALL WEIGHTS WERE RECORDED IN GRAMS <G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A "ALIVEr S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. p. 110 - TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (SAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 13): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP * 1 2 3 21 22 23 56 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER I 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 MATERNAL DOSAGE GROUP III GROUP III 10.0 11.5 12.2 10.3 16.0 10.4 11.2 10.1 10.9 10.7 10.3 9.9 13.3 11.4 14.7 10.5 10.3 11.3 11.9 11.0 9.9 11.5 11.8 11.6 15.6 8.8 10.0 11.8 9.5 11.0 9.7 11.9 12.5 10.6 15.2 10.0 11.0 9.9 10.8 10.9 10.3 10.4 11.0 11.2 9.9 10.0 9.5 11.0 11.8 7.9 11.8 11.3 11.6 9.5 8.3 10.7 10.3 10.6 8.9 11.9 11.5 11.3 MD 2 8.7 10.3 10.6 11.9 9.9 12.0 11.2 10.9 10.2 9.6 9.6 10.7 11.2 30 MKD 9.4 10.3 11.9 10.8 9.1 11.0 11.5 10.9 8.9 10.6 10.7 11.9 10.6 9.2 8.7 9.3 11.5 MS 10.1 11.3 11.3 9.3 9.5 9.3 10.7 10.2 11.3 9.8 11.1 12.2 10.2 10.0 10.2 9.1 12.2 10.6 LACTATION DAY 6 9.7 10.8 11.2 11.5 8.7 12.0 10.3 10.3 11.3 9.4 9.6 10.2 12.4 11.0 8.4 10.1 9.8 9.9 10.6 9.0 9.6 9.7 9.9 10.7 10.2 10.6 10.7 FD 2 S FD 2 REC0RDED IN GRAMS (G) . MEAN LITTER HEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER A - ALIVE, S-STILLBORN, U - UNCERTAIN, D--DIED, C-CULLED, M--MISSING (PRESUMED C A N N I R A L T P K t i ) y r y nypn NUMBER FOLU W I N G "SECOND LETTER" INDICATES THE DAY POSTPARTUM THe I ^ N T CCURRED. CANNIBALIZED), X-OTHER 19 20 P. 111 I I :^ TSCA SANITIZED PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 14): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP # 1 2 3 21 22 23 56 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # 23931 23932 23933 23934 23935 23936 23937 23938 23939 23940 MATERNAL DOSAGE GROUP IV 11.3 9.9 9.6 12.1 9.9 9.2 10.0 11.7 10.2 11.6 11.8 10.1 9.2 11.1 8.8 8.5 9.9 10.8 9.8 9.2 11.4 10.6 8.6 10.8 8.7 10.0 10.4 10.4 9.8 11.6 11.6 10.5 10.0 11.2 9.4 8.9 9.4 10.6 10.2 11.2 12.7 9.8 9.6 8.5 9.1 9.9 9.5 10.5 9.8 11.1 GROUP IV 12.4 9.9 8.9 12.6 8.7 7.8 10.2 10.6 10.4 10.9 12.6 9.9 9.7 11.8 8.1 8.7 10.3 MD 2 8.8 11.7 12.1 10.7 8.0 11.1 8.6 9.6 9.5 10.2 10.4 11.8 90 NKD 9.2 9.8 9.4 12.3 8.2 9.5 9.4 9.0 9.9 11.1 12.3 9.6 9.5 8.9 8.1 8.1 8.5 10.2 9.4 MM 2 10.7 9.9 9.7 10.7 8.5 9.1 9.6 9.6 8.8 11.4 12.1 9.5 8.9 11.4 7.3 6.7 10.4 10.1 11.5 LACTATION DAY 6 10.8 10.3 8.7 9.7 11.6 9.7 9.4 12.2 10.1 8.3 10.0 8.2 10.0 10.8 8.7 7.9 10.5 9.4 9.5 8.8 10.1 8.7 12.2 ft.n 9.2 10.3 FS ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE y??TER " A~ALIVE' S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 19 20 p. 112 1 i TSCA SANITIZED PROTOCOL ZXA00077 ORAL (GAVAGE) DEVEU)M E N T A L TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 24 (PAGE 15) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA POP RAT/ LITTER * 23942 23943 23944 23948 23949 12 3 21 22 23 4 5 6 7 8 9 10 11 12 13 14 15 16 MATERNAL DOSAGE GROUP V GROUP V 270 MKD 7.1 7.0 mu i 8.5 MD 1 6.7 8.1 MD 1 10.0 MD 1 8.9 9.4 MD 1 MI 3 MS 8.1 MD 2 MD 1 9.9 MS 7.6 MD 2 MD 1 5.7 MS 5.1 9.5 MD 1 10.9 MS 7.0 8.7 MD 1 6.3 FS MD 1 8.3 MD 1 FM 2 FS MD 1 9.1 MD 1 FM 2 FS MD 1 8.6 FD 1 FS 7.3 FD 2 FD 1 FS 8.3 FD 2 FD 1 FS LACTATION nAY 7.9 8.2 7.7 FD 2 FD 1 FD 1 FD 1 FS FS uu 6 20 p. 113 II TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 25 (PAGE 1) : PUP VITAL STATUS AND SEX PROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP # RAT/ LITTER # 123 45 6 MATERNAL DOSAGE GROUP I 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 GROUP I 0 (VEHICLE) MKD 23901 23902 23903 23905 23906 23907 23908 23909 23910 M A M A M A M A M A M A FA FA FA FA FA FA FA FA FA F A FA M A M A M A M A M A M A M A M A FA FA FA FA FA FA M A M A M A M A M A M A M A FA FA FA FA FA FA FA M A M A M A M A M A M A M A M A M S M A FA FA FA FA FA FA M A M A M A M A M A M A FA FA FA FA FA FA FA FA FA M A M A M A M A M A M A M A M A M S F A F A F A F A F A F A F A FD 2 M A M A M A M A M A M A M A FA FA FA FA FA FA FA MX 1 MX 1 MX 1 MX 1 MX 1 FX 1 FX 1 FX 1 FX 1 FX 1 FX 1 UX 1 UX 1 UX 1 UX 1 UX 1 M A M A M A M A M A M A M A M A MA FA FA FA FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. p. 114 I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OE MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 25 (PAGE 2) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP II GROUP II 10 MKD 23911 23912 23913 23914 23916 23917 23918 23920 M A M A M A M A M S FA FA FA FA FA FA FA FA FA F S M A M A M A M A FA FA FA FA FA FA FA FA FA FA F S M A M A M A M A FA FA FA FA M A M A M A MA M A M A M A M A FA FA FA FA FA FA M A M A M A M A M A M A M A M A FA FA FA FA FA HA M A M A M A M S FA FA FA FA FA FA FA FA FA FA M A M A M A M A M A M A M A FA FA FA FA FA FA FA FA M A M A M A M A M A M A H A FA FA FA FA FA FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. p. 115 I TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXAG0077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 25 (PAGE 3) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP * 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 IS 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUPIII GROUP III 30 MKD 23921 23922 23923 23924 23925 23926 23927 23928 23929 23930 M A M A M A M A M A FA FA FA FA FA FA FA FA FA FA M A M A M A M A M A M A M A M A FA FA FA FA FA FA M A M A M A M A M A FA FA FA FA FA FA FA FA M A M A M A M A M A M A M A FA FA FA FA FA FA FA FA FA FA FA FA M A M A M A M A M A M A MD 2 F A F A F A F A F A F A F A F A M A M A M A M A M A M A M A FA FA FA FA FA FA FA FA FA M A M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A FD 2 FD 2 M A M A M A M A M A M A M A FA FA FA FA FA FA FA FA FA U S M A M A M A M A M A M A M A M A M A M S FA FA FA FA FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. p. 116 II TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 i ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OP MTDID 6675 IN RATS {SPONSOR'S REFERENCE NO. 06-376) TABLE 25 (PAGE 4): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA l l *-- -!?!-!____ ____?____ ____ ____*____________ 8 9 10 11 12 13 14 15 16 RAT/ LITTER # MATERNAL DOSAGE GROUP IV GROUP IV 90 KKD 17 ~18 IS 202l"22 23932 mooa H ill ""7 2io39n3f __ 23940 2 2 2 2 2 a 2 a 2 a 2 * " * F A F A F A F A F A F A~"f "a ~ T a MA MA MA MA MA MA M A FA FA FA FA FA FA FA 2 2 2M A M A M A M A M A M A M A M A F A F A F A F A F A F A F A a a a ma ma ma ma ma fa fa fa fa fa MA MA MA MA M A FA FA FA FA FA FA MA MA MA MA MA M A MA MA FA FA FA FA MA MA m a m a m a m a m a m a f a f a f a f a 22 22 22 22 22 2 2 22 A M A M A M A M A M A " FS A FF AA FF AA FF AA FF AA FF AA M A M A M A M A M A M A M A M A M A MM 2 F A F A FA FA fa fa FF AA FF AA FA fa fa FA FA FA FA fa f s fa FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE = J 5 5 2sS \ S 2 ^ " 2^ CANNIBALIZED), X-OTHER p. 117 II TSCA SANITIZED A R G U S R E S E A R C H L A B O R A T O R I E S , INC. PROTOCOL ZXA00077 : ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NO. 06-376) TABLE 25 (PAGE 5) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA PUP * RAT/ LITTER 1 12345 6 MATERNAL DOSAGE GROUP V 7 8 9 10 il 12 13 14 15 16 17 18 19 20 21 22 23 GROUP V 270 MKD 23942 23943 23944 23948 23949 M A M A M A M A M A M A M A MD 1 MD 1 1MD 1 F A F A F A F A F A FD 1 M A M A M A MD 2 MD 2 F A F A F A F A F A FD 2 FD 2 FD 2 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 iMD 1 MD 1 FD 1 FD 1 FD 1 FD 1 FD 1 FD 1 M A M A MM 3 F A F A F A F A FM 2 EM 2 MD 1 MD 1 M S M S M S M S F S F S F S F S F S F S F S F S U U FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 00 TSCA SANITIZED PROTOCOL ZXAQ0077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 26 (PAGE 1 ): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 6 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I 0 (VEHICLE) II 10 III 30 IV 90 LITTER NUMBER 23914 23921 23930 23938 DAY (S) POSTPARTUM _ 2 1- 6 1 2- 3 1 4 OBSERVATIONS a 1/14 PUPS: COLD TO TOUCH. 1/15 PUPS: TIP OF TAIL: MISSING.b 2/14 PUPS: NOSE: PURPLE. 3/14 PUPS: NOSE: PURPLE. 1/16 PUPS: COLD TO TOUCH. 1/15 PUPS: COLD TO TOUCH; PALE; NOT NESTING; NOT NURSING. 270 23942 2- 5 1/12 PUPS: RIGHT HINDLIMB AND HINDPAN: PURPLE. 23948 2 1/ 7 PUPS: LONER MIDLINE, BOTH HINDLIMBS AND TAIL: VI --------------5--0--0---- --- ------ ------- ------ a. b. Tabulation restricted to Observation confirmed at advera observations; necropsy. all other pups appeared normal. PURPLE. p. 119 I ; I -I TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 27 (PAGE 1): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I 0 (VEHICLE) LITTER NUMBER 23901 23902 23903 DAY POSTPARTUM OBSERVATIONS a 6 17 PUPS: APPEARED NORMAL. 6 14 PUPS: APPEARED NORMAL. 6 14 PUPS: APPEARED NORMAL. 23905 23906 23907 23908 23909 23910 i i PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 15 PUPS: APPEARED NORMAL. 6 15 PUPS: APPEARED NORMAL. 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 2 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 6 15 PUPS: APPEARED NORMAL. 6 14 PUPS: APPEARED NORMAL. 1 1 PUPS: FOUND DEAD. PARTIALLY CANNIBALIZED. SEX COULD NOT BE DETERMINED. ALL OTHER TISSUES APPEARED NORMAL. 9 PUPS: MORIBUND SACRIFICED. PARTIALLY CANNIBALIZED. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 2 PUPS: MORIBUND SACRIFICED. PARTIALLY CANNIBALIZED. ALL OTHER TISSUES APPEARED NORMAL. 4 PUPS: MORIBUND SACRIFICED. PARTIALLY CANNIBALIZED. NO MILK IN STOMACH. SEX COULD NOT BE DETERMINED. ALL OTHER TISSUES APPEARED NORMAL. 6 13 PUPS: APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded full evaluation Refer to the individual pup clinical observations table (Table 26) for external clinical observations confirmed at necropsy. p. 120 r i TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF KTDID 6615 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-316) TABLE 27 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS I MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM OBSERVATIONS a 23911 1 2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 13 PUPS: APPEARED NORMAL. 23912 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 14 PUPS: APPEARED NORMAL. 23913 23914 23916 6 8 PUPS: APPEARED NORMAL. 6 14 POPS: APPEARED NORMAL. 6 13 PUPS: APPEARED NORMAL. 23917 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 15 PUPS: APPEARED NORMAL. 23918 23920 6 15 PUPS: APPEARED NORMAL. 6 13 PUPS: APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded full evaluation. Refer to the individual pup clinical observations table (Table 26) for external clinical observations confirmed at necropsy. p. 1 2 1 II TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVAGE) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 27 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY POSTPARTUM OBSERVATIONS a III 23921 6 15 PUPS: APPEARED NORMAL. 23922 6 14 PUPS: APPEARED NORMAL. 23923 6 13 PUPS: APPEARED NORMAL. 23924 6 15 p u p s : APPEARED NORMAL. 23925 6 4 PUPS: APPEARED NORMAL. 23926 2 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL 6 14 PUPS: APPEARED NORMAL. 23927 6 16 PUPS: APPEARED NORMAL. 23928 2 1 PUP: FOUND DEAD. PARTIALLY CANNIBALIZED. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 6 16 PUPS: APPEARED NORMAL. 23929 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 16 PUPS: APPEARED NORMAL. 23930 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 14 PUPS: APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded full evaluation. Refer to the individual pup clinical observations table (Table 26) for external clinical observations confirmed at necropsy. p. 122 i~ TSCA SANITIZED PROTOCOL ZXA00077: ORAL (GAVA6E) DEVELOPMENTAL TOXICITY SCREENING STUDY OF MTDID 6675 IN RATS (SPONSOR'S REFERENCE NUMBER: 06-376) TABLE 27 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a IV 0 23931 6 15 PUPS: APPEARED NORMAL. 23932 6 14 PUPS: APPEARED NORMAL. 23933 6 17 PUPS: APPEARED NORMAL. 23934 6 13 PUPS: APPEARED NORMAL. 23935 6 11 PUPS: APPEARED NORMAL. 23936 6 18 PUPS: APPEARED NORMAL. 23937 6 15 PUPS: APPEARED NORMAL. 23938 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 2 1 PUP: POUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 6 15 PUPS: APPEARED NORMAL. 23939 23940 6 14 PUPS: APPEARED NORMAL. 6 11 PUPS: APPEARED NORMAL. V 270 23942 2 4 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 6 12 PUPS: APPEARED NORMAL. 23943 2 5 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 6 8 PUPS: APPEARED NORMAL. 23944 1 9 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 6 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 23948 6 6 PUPS: APPEARED NORMAL. 23949 1 12 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 2 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL.b VI 500 - a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded full evaluation. Refer to the individual pup clinical observations table (Table 26) for external clinical observations confirmed at necropsy. b. Stomach contents were not recorded. p. 123 !I
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