Document zbdQ9Yq0j3oa7v91vB3oRdLbg

AR226-2816 TRADE SECRET Study Title J'^--^--^^--^--t--mVYOEAR ORAL TOXICrTY-ONCOGENICtTY STUDY IN RATS "PEER REVIEW OF OVARIES Authors Peter C. Mann, D.V.M. Experimental Pathology Laboratories, Inc. (EPL) PO Box 474 Hemdon,VA 20172-0474 Steven R. Frame, D.V.M., Ph.D. E. I. du Font de Nemours and Company Haskell Laboratory for Health and Environmental Science Elkton Road, P. 0. Box 50 Newark, DE 19714-0050 Test Guideline: Not Applicable Date Completed: June 25,2004 Laboratory Project ID: DuPont-15261 Work request Number.'yim^j Service Code Number'^WQ SubmittedBy: E. L du Font de Nemours and Company Haskell Laboratory for Health and Environmental Science Elkton Road, P. 0. Box 50 Newark, DE 19714-0050 S*"1iltte*-" Coi.tOP^ DuPont-15261 Authors ^ u^ <^. Peter C. Mann, D.V.M., Diplomate A.V.C.P. Veterinary Pathologist ^ ^ Date ^00<f -f/oL^^ yy"v^4^< Steven R. Frame, D.V.M., Ph.D., Diplomate A.V.C.P. Principal Research Pathologist and Research Manager, Pathology S^-J^^ Date 3^ ^ ^ ^ CSldVf9 ,^nTSC^ DuPont-15261 'wo Year Oral Toxicity-Oncogenicity Study in Rats Peer Review of Ovaries The slides from the ovaries fromj------^fwYoear Oral Toxicity-Oncogenicity Study in Rats were peer reviewed by two veterinary pathologists:Peter C. Mann, DVM, Diplomate, American College of Veterinary Pathologists and Steven R. Frame, D.V.M., Ph.D, Diplomate, American College of Veterinary Pathologists. The slides were originally examined and reported by Dr. Robert Geil (study pathologist) for Riker Laboratories, Inc., 3M (Project Number 0281CR0012). The peer review focused on proliferative lesions of the ovary. The peer review pathologistsdiscussed issues related to diagnostic nomenclature and criteria and reached agreement on lesion diagnoses and grading, as well as interpretation of the peer review findings. This agreement is reflected in the following report. Materials and Methods All slides listed as available by the study pathologist were made available for the peer review. The ovaries from a few animals were not present at the time of the initial evaluation, and these same ovaries were not available for peer review. The original diagnoses and the peer review diagnoses for the ovaries for each animal are given in Appendix A. In those cases where the peer review pathologist agreed with the study pathologist, the peer review diagnosis is listed as "Agree". For the purposes of analysis, the data are separated into those animals that died on or before 53 weeks on study, and those animals that died after 53 weeks on study. The animals that died on or before 53 weeks on study included those sacrificed at the interim sacrifice and early deaths. Since none of these animals had any proliferative lesions in the ovaries in either the initial or peer review evaluations, they were not included in the reporting or analysis of data below. Criteria for Diagnosis of Proliferative Changes in the Ovary In the normal aging ovary of rats, senescent corpora lutea develop into interstitial glands. This gonadal stromal change presents as small glands, lined by cuboidal cells. In some cases, these cells may become more columnar and have a sertoliform appearance. In addition, luteal cells may appear in the ovarian stroma. These (luteal) cells may also appear to form glands, but they have a characteristic fine granular, foamy appearance which is not present in interstitial glands, although the latter cells may have a macrovesicular vacuolar cytoplasm. The above changes are normal for aging rats, and should not be diagnosed as proliferative changes. Proliferative lesions (hyperplasia or neoplasia) intrinsic to the ovary are generally classified as either epithelial, gonadal stromal (sex cord-stromal) or germ cell in origin (Dixon et al, 1999; Peluso and Gordon, 1992; Alison et al., 1990). Proliferative lesions observed in the ovaries from the current study were all gonadal stromal in origin. This category includes lesions composed ofgranulosa, thecal, luteal or sertoli-like cells, or ^a-n^001 C1-".".S^-0-' 3 DuPont-15261 mixed populations of these cell types (Dixon et al, 1999; Peluso and Gordon, 1992). It has been recommended that for the purposes of analysis and evaluation of carcinogenic risk, tumors derived from gonadal stromal cells be combined (Peluso and Gordon, 1992). Thus, for this peer review, hyperplasia and neoplasia were diagnosed as gonadal stromal hyperplasia and gonadal stromal adenoma, respectively (Peluso and Gordon, 1992). Gonadal stromal hyperplasia is present when the interstitial and/or sertoliform cells (but not the normal luteal cells) form discrete or diffuse areas containing enlarged clusters or tubular profiles of stromal cells with or without an increase in fibrous connective tissue. Hyperplasia was graded from 1-4, depending on the relative size of the proliferation (increasing grade with increasing size). Typically, there are no clear cytological features that distinguish gonadal stromal hyperplasia from gonadal stromal adenoma. Therefore, to allow for some consistency in diagnosis, me criteria established for gonadal stromal adenoma is based primarily on the somewhat arbitrary feature of two-dimensional size. Gonadal stromal adenomas are diagnosed if the diameter of the lesions is greater than 3mm (Dixon et al, 1999). This corresponds to about a single field using the 1Ox microscope objective. If an animal had both adenoma and hyperplasia present, only the adenoma was recorded. Since size is the primary criterion differentiating hyperplasia from tumor, the assessment of incidence data for these lesions included an evaluation based on the total incidence ofproliferative gonadal stromal lesions (combined hyperplasia and adenoma). Many of the ovaries diagnosed with gonadal stromal hyperplasia during the peer review of this study contained very small areas of proliferation which would probably not be diagnosed during a routine evaluation (Dixon et al, 1999; Peluso and Gordon, 1992). However, to ensure that no subtle dose-effect was overlooked, all possible proliferative changes were diagnosed during me review. Incidences ofproliferative lesions (gonadal stromal hyperplasia, adenoma, or hyperplasia/adenoma combined) were evaluated by the Cochran-Armitage trend test and the Fisher's exact test. Statistical significance was judged at P < 0.05. Results The presence of all proliferative lesions in the ovaries of individual rats is presented in Appendix A. The incidence of gonadal stromal hyperplasia and/or adenoma in the ovaries of all rats on study beyond the one-year (53-week) interim sacrifice is shown in Text Table 1. Rats sacrificed at the one-year interim sacrifice, as well as rats that died prior to the interim sacrifice, were not considered "at risk" for tumor development. This is reflected in the fact that the number of animals/group, as given is Table 1, is less than 50 (as appears in the original report) and varies slightly among groups based on the number of deaths in each group that occurred before the interim sacrifice. The number of animals examined per group also reflects animals for which no ovary was available for review. Incidences of ovarian lesions based on the original microscopic evaluation can be found in the original study report (Sibinski, 1987) nTSC^081 _,,^o-lttc'>tal CorW^' 4 DuPont-15261 Table 1 Incidence of Gonadal Stromal Hyperplasia and Adenoma in Rats' Dose 0 No. Examined 45 Hyperplasia (Total No.) 8 - Grade 1 6 -Grade2 2 -Grades 0 -Grade 4 0 Adenoma 4 30 300 47 46 16 15 7 5 3 1 5 6 1 3 0 2 Adenoma and/or Hyperplasia 12 16 17 Animals on study beyond the interim (53-week) sacrifice There were no statistically significant increases in hyperplasia (total number), adenomas, or hyperplasia/adenoma combined in treated groups compared to controls. Some evidence of increased lesion grade for proliferative lesions was observed in the 300 ppm group. For example, incidences of proliferative lesions diagnosed with a grade of 3 or more (that is, grade 3,4, or adenoma) was 4/45,6/47 and 11/46 in the 0,30, and 300 ppm groups, respectively. The incidences of lesions of grade 3 and above were statistical significant at 300 ppm (P = 0.046 and 0.048 for the Cochran Annitage and Fisher's test, respectively). However, treatment-related progression of proliferative lesions to the size criteria established for adenoma did not occur, as incidences of adenoma were highest in controls. Discussion and Conclusions The slides of ovaries of rats from a two-year feeding study with|l------^vepreeer reviewed with emphasis on proliferative lesions of the ovary. Lesions diagnosed by the peer review pathologists as gonadal stromal hyperplasia or gonadal stromal adenoma corresponded to the diagnoses of tubular hyperplasia or tubular adenoma by the study pathologist (one granulosa cell tumor-a type of gonadal stromal tumor-was also diagnosed by the study pathologist). The diagnostic terms used by the peer review pathologists were based on more recently published nomenclature, and the more generic designation of gonadal stromal lesions better reflected the spectrum of morphologic changes observed in the proliferative lesions. Furthermore, based on current diagnostic nomenclature, tubular hyperplasia or adenoma would suggest an origin from ovarian surface epithelium rather than from ovarian stromal cells. Except for differences in diagnostic nomenclature, results of the peer review were similar to those of the original study for the 300 ppm group. More disparate results occurred for me control and 30 ppm groups where more hyperplasticlesions (irrespective of the -o^---"^"' c^*-"^ DuPont-15261 nomenclature used) were observed by the peer review pathologists. Based on the results of the peer review, there were no statistically significant increases in gonadal stromal hyperplasia, adenoma, or adenoma and hyperplasia combined in treated groups relative to controls. Some evidence of increased lesion grade, which would correspond to an increase in size of stromal lesions, was observed in the 300 ppm group. However, adenomas occurred in greater incidences in the control group than in either of the treated groups. References Alison RH, Morgan KT, and Montgomery Jr. CA (1990). Ovary. In Boonnan GA, Eustis SL, Elwell MR, Montgomery Jr. CA, and Mackenzie WF, (eds) Pathology of the Fisher Rat. Academic Press, San Diego, pp429-442 Dixon D, Leininger JR, Valerio MG, Johnson AN, Stabinski LG and Frith CH (1999). Proliferative lesions of the Ovary, Uterus, Vagina, Cervix and Oviduct in Rats. URG-5. m: Guides for Toxicologic Pathology. STP/ARP/AFIP, Washington, DC. Peluso JJ and Gordon LR (1992). Nonneoplastic and Neoplastic Changes in the Ovary. In: Mohr U, Dungworth DL, and Capen CC (eds) Pathobiology of the Aging Rat, Vol 1. ILSI Press, Washington, DC, pp 351-364. Sibinsld, LJ (1987). Two Year Oral (Diet) Toxicity /Oncogenicity study of Fluorochemical PC-143 in Rats. Riker Experiment No. 0281CR0012, Riker Laboratories, Inc./3M Company. ^ ^.nTSC^1 DuPont-15261 Appendix A: Individual Animal Peer Review Results Company SrWxd. 0<x ra cuiilrin TSCA CBf DuPont-15261 WKS ANIMAL ON TEST IR-4676 25 IR-4607 40 IR-4580 52 IR-4578 53 IR-4582 53 IR-4585 53 IR-4588 53 IR-4589 53 IR-4580 53 IR-4601 53 IR-4608 53 IR-4610 53 IR-4620 53 IR-4629 53 IR-4830 53 IR-4631 53 IR-4632 53 IR-4640 53 0 ppm (Group 1) ORIGINAL DX WITHIN NORMAL LIMITS MALIGNANT LYMPHOMA, LYMPMOCYT1C WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WTTHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WTTHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS CYST. UNILATERAL WITHIN NORMAL UMITS PEER REVIEW OX AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE IR-4577 IR-4579 IR-4581 IR-4583 IR-4584 IR-4586 IR-4587 IR-4591 IR-4592 IR-4593 IR-4594 IR-4595 IR-4596 IR-4597 IR-4598 IR-4599 IR-4600 99 WITHIN NORMAL UMITS 84 WITHIN NORMAL UMITS 85 WITHIN NORMAL UMITS AGREE AGREE AGREE GONADAL STROMAL ADENOMA, 105 TUBULAR ADENOMA, UNILATERAL UNILATERAL 105 WITHIN NORMAL UMITS AGREE 105 NOT EXAMINED, MISSING AGREE 105 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE 88 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS WITHIN NORMAL UMITS, ONE OF PAIR 79 MISSING AGREE AGREE GONADAL STROMAL HYPERPLASIA, MINIMAL, 105 WITHIN NORMAL UMITS UNILATERAL 78 WrmiN NORMAL UMITS AGREE GONADAL STROMAL 105 TUBULAR ADENOMA, UNILATERAL ADENOMA, UNILATERAL GONAOALSTROMAL 105 TUBULAR ADENOMA ADENOMA, UNILATERAL 102 MAUQNANT LYMPHOMA, HISTIOCYTIC AGREE 99 CYST. UNILATERAL AGREE ^o^SCACBl Company SsnttMA^ DuPont-15261 t 0 ppm (Group 1) - continued WKS ANIMAL ON TEST ORIGINAL OX PEER REVIEW DX IR-4602 105 IR-4603 105 IR-4604 105 WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS CYST, UNILATERAL QONADAL STROMAL HYPERPLASIA. MINIMAL, UNILATERAL AQREE AGREE IR-4605 77 IR-4606 105 CYST, UNILATERAL NOT EXAMINED. MISSING GONADAL STROMAL HYPERPLASIA. MINIMAL, UNILATERAL AGREE IR4809 105 IR-4611 105 IR-4612 105 IR-4613 89 IR-4614 105 IR-4615 105 1R-4616 105 IR-4617 73 IR-4618 93 IR-4619 64 IR-4621 99 IR-4622 62 IR-4623 96 IR-4624 100 IR-4625 100 IR^626 105 WITHIN NORMAL LIMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WrTHIN NORMAL UMITS WITHIN NORMAL UMITS CYST, UNILATERAL LBOMYOMA WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS CYST, UNILATERAL WITHIN NORMAL UMITS WITHIN NORMAL UMITS GONADAL STROMAL HYPERPLASIA, MINIMAL, UNILATERAL AQREE AGREE AGREE AGREE AGREE AGREE NOT PRESENT ON SLIDE, ONE 0V 18 WITHIN NORMAL UMITS AGREE AGREE GONADAL STROMAL HYPERPLASIA, MILD, BILATERAL AGREE AGREE GONAOAL STROMAL HYPERPLA81A, MILD, UNILATERAL AGREE AGREE IR-4627 105 TUBULAR ADENOMA, UNILATERAL CYST BILATERAL GONAOAL STROMAL ADENOMA, UNILATERAL; CYST BILATERAL IR-4628 105 IR-4633 63 IR-4634 105 WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS GONADAL STROMAL HYPERPLASIA, MINIMAL, UNILATERAL AGREE AGREE Company ^^^^cwwnwACBl DuPont-15261 0 ppm (Group 1) - continued ANIMAL* WKS ON TEST IR-4635 94 IR-4636 105 IR-4fl37 82 IR-4638 105 IR-4638 56 ORIGINAL DX WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL UMITS WITHIN NORMAL LIMITS PEER REVIEW DX GONAOAL3TROMAL HYPERPLA31A, MINIMAL, UNILATERAL AQREE AGREE AOREE AGREE Company l>li(l. Do-- (Ml ontafn TSCA CBI 10 30 ppm (Group 6) DuPont-15261 IR-4706 IR-4707 IR-4708 IR-4709 IR-4710 IR-4711 IR-4712 IR-4713 IR-4714 IR-4715 IR-4716 IR-4717 IR-4718 IR-4719 IR-4720 IR-4721 IR-4722 IR-4723 IR-4724 IR-4725 IR~4726 IR-4727 IR-4728 72 WITHIN NORMAL LIMITS AGREE QONADAL 8TROMAL HYPERPLASIA, 90 WITHIN NORMAL LIMITS-ONE OF PAIR PRESENT MILD, UNILATERAL 105 WITHIN NORMAL LIMITS AGREE 99 WITHIN NORMAL LIMITS AGREE 105 CYST AGREE 105 WITHIN NORMAL LIMITS AGREE 94 CYST AGREE 97 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE 105 CYST, UNILATERAL AGREE 105 CYST, UNILATERAL AGREE QONADAL STROMAL HYPERPLASIA, MINIMAL, 105 WITHIN NORMAL UMITS UNILATERAL 94 WITHIN NORMAL UMITS AGREE 96 CYST, UNILATERAL AGREE QONADAL 8TROMAL HYPERPLASIA, MINIMAL, 105 WITHIN NORMAL UMITS UNILATERAL 95 WITHIN NORMAL UMITS-ONE OP PAIR PRESENT AGREE 83 WITHIN NORMAL UMITS AGREE GONAOAL STROMAL HYPERPLASIA, 105 TUBULAR HYPERPLASIA, MODERATE MODERATE, UNILATERAL GONADAL STROMAL HYPERPLASIA, MODERATE, 105 TUBULAR HYPERPLASIA, BILATERAL, MILD BILATERAL 94 WITHIN NORMAL UMITS AGREE GONADAL STROMAL HYPERPLASIA, MINIMAL, 105 WITHIN NORMAL UMITS UNILATERAL GONADAL STROMAL HYPERPLASIA, MINIMAL, 105 CYST UNILATERAL 84 WITHIN NORMAL UMITS AGREE Company SanitizfL Do- note^ain TSCA CBI DuPont-15261 30 ppm (Group 6) - continued WKS ANIMAL ON TEST ORIGINAL DX PEER REVIEW DX IR-4729 105 WITHIN NORMAL UMrTS AGREE IR-4730 74 WITHIN NORMAL UMITS AGREE IR-4731 99 MALIGNANT LYMPHOMA, HISTIOCYTIC LYMPHOMA QONADAL 3TROMAL HYPERPLASIA, IR-4732 99 WITHIN NORMAL UMITS MINIMAL, UNILATERAL IR-4733 105 WITHIN NORMAL UMITS AGREE IR-4734 IR-4736 IR-4737 95 WITHIN NORMAL UMITS AGREE GONAOAL STROMAL HYPERPLASIA, 105 WITHIN NORMAL UMITS MILD. UNILATERAL GONADAL 8TROMAL HYPERPLASIA, MODERATE, 105 TUBULAR HYPERPLASIA, BILATERAL, MODERATE BILATERAL IR-4738 101 WITHIN NORMAL UMITS AGREE IR-4739 105 WITHIN NORMAL UMITS AGREE IR-4740 105 WTTHIN NORMAL UMITS AGREE IR-4741 97 WITHIN NORMAL UMITS AGREE IR-4742 83 WITHIN NORMAL UMITS AGREE IR-4743 97 IR-4746 105 WTTHIN NORMAL UMITS TUBULAR HYPERPLASIA, UNILATERAL, MODERATE GRANULOSA CELL TUMOR, BENIGN. UNILATERAL AGREE GONAOAL 8TROMAL HYPERPLASIA, MODERATE. UNILATERAL IR-4746 87 IR-4747 105 WITHIN NORMAL UMITS CYST, UNILATERAL AGREE GONADAL STROMAL HYPERPLASIA, MINIMAL, UNILATERAL; CYST IR-4748 81 IR-4749 82 WITHIN NORMAL UMITS WITHIN NORMAL UMITS AGREE QONADAL 8TROMAL HYPERPLASIA, MINIMAL, UNILATERAL IR-4750 1R-4752 IR-4753 97 WITHIN NORMAL UMITS AGREE GONADAL STROMAL HYPERPLASIA, CYST, BILATERALTUBULAR HYPERPLASIA, SEVERE, 105 BILATERAL. MODERATE BILATERAL QONADAL STROMAL HYPERPLASIA, MODERATE, 105 TUBULAR HYPERPLASIA, BILATERAL. MODERATE UNILATERAL IR-4754 IR-4755 105 CYST, UNILATERAL AGREE GONADAL STROMAL HYPERPLASIA, 105 TUBULAR HYPERPLASIA, BILATERAL, MODERATE MILD, BILATERAL Company SawfittA Does rwt contain TSCA CBi DuPont-15261 WKS ANIMAL ONTES1 IR-4878 49 IR-4642 53 IR-4652 53 IR-4655 53 IR-4856 53 IR-4664 53 IR-4666 53 IR-4669 53 IR-4871 53 IR-4874 53 IR-4676 53 IR-4687 53 IR-4889 53 IR-4692 53 IR-4699 53 IR-4704 53 300 ppm (Group 5) ORIGINAL OX WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL LIMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS WITHIN NORMAL UMITS PEER REVIEW DX AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE AGREE IR-4641 IR-4643 IR-4644 IR-4645 IR-4646 IR-W47 IR-4648 IR-4649 IR-4650 IR-4851 IR-4663 IR-4654 IR-4657 IR-4858 IR-4659 IR-4660 IR-4661 IR-4662 IR-4663 73 NOT EXAMNED. MISSING AGREE 78 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE QONAOAL STROMAL HYPERPLASIA, MODERATE, 105 TUBULAR HYPERPLASIA, MODERATE UNILATERAL 105 CYST. UNILATERAL AGREE 88 WITHIN NORMAL UMITS AGREE QONAOAL STROMAL HYPERPLASIA, 105 TUBULAR HYPERPLASIA, BILATERAL MODERATE SEVERE, BILATERAL QONADAL 8TOOMAL HYPERPLASIA, SEVERE, 104 TUBULAR HYPERPLASIA. BILATERAL. MODERATE BILATERAL 96 NO DIAGNOSIS. INADEQUATE SECTION AGREE 87 WITHIN NORMAL UMITS AGREE 57 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE 105 CYST. UNILATERAL AGREE 105 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE 105 WITHIN NORMAL UMITS AGREE Company San;*i<d. OM not contain TSQfQHj 13 DuPont-15261 300 ppm (Group 5) - continued WKS ANIMAL ONTES1 ORIGINAL DX IR-4665 94 TUBULAR HYPERPLASIA, MODERATE IR-4687 105 IR-4668 81 IR-4670 92 TUBULAR HYPERPLASIA. MILD WITHIN NORMAL UMITS WITHIN NORMAL LIMITS IR-4872 1R-4873 IR-4675 105 rUBULAR HYPERPLASIA. UNILATERAL, MODERATE 79 WITHIN NORMAL UMITS 105 WITHIN NORMAL UMITS IR-4677 105 TUBULAR ADENOMA. UNILATERAL IR-4679 105 TUBULAR HYPERPLASIA, BILATERAL. MILD IR-4680 104 TUBULAR HYPERPLASIA. MODERATE IR-4681 97 IR-4662 94 TUBULAR HYPERPLASIA, MODERATE NOT EXAMINED. MISSING 105 TUBULAR HYPERPLASIA, BILATERAL, MODERATE IR-4684 103 IR-4685 75 TUBULAR HYPERPLASIA, MODERATE WITHIN NORMAL UMITS IR-4686 105 WITHIN NORMAL UMITS PEER REVIEW DX GONADAL 8TROMAL HYPERPLASIA, MODERATE, BILATERAL GONAOAL STROMAL HYPERPLA8IA, MINIMAL, BILATERAL AGREE AGREE GONADAL STROMAL HYPERPLA8IA, MODERATE, BILATERAL AGREE AGREE GONADAL STROMAL ADENOMA, UNILATERAL GONAOAL STROMAL HYPERPLASIA, MODERATE, BILATERAL GONADAL STROMAL HYPERPLASIA, MINIMAL, BILATERAL GONADAL STROMAL HYPERPLA8IA, MODERATE, UNILATERAL AGREE GONADAL STROMAL HYPERPLA8IA, MODERATE, BILATERAL QONADAL STROMAL HYPERPLA8IA, MINIMAL, UNILATERAL AGREE GONAOAL STROMAL HYPERPLASIA, MINIMAL, UNILATERAL OBipany ^^nTSC^CBl 14 DuPont-15261 300 ppm (Group 5) - continued ANIMAL # WKS ON TEST IR-4888 105 IR-4690 105 IR-4691 100 IR-^693 105 IR-4694 105 IR-4695 105 IR-46B6 105 IR-4697 105 IR-4898 105 IR-4700 96 IR-4701 105 IR-4702 87 IR-4703 106 IR-4705 62 ORIGINAL DX TUBULAR HYPERPLASIA, MODERATE WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS CYST. UNILATERAL WITHIN NORMAL LIMITS CYST, UNILATERAL WITHIN NORMAL LIMITS CYST, UNILATERAL TUBULAR HYPERPLASIA. MARKED WITHIN NORMAL LIMITS TUBULAR HYPERPLASIA, MODERATE WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS PEER REVIEW DX QONADAL STROMAL HYPERPLASIA, SEVERE, UNILATERAL AGREE AGREE AGREE AGREE QONADAL STROMAL HYPERPLASIA, MINIMAL, UNILATERAL AGREE AGREE QONADAL STROMAL HYPERPLASIA, MILD, BILATERAL QONAOAL STROMAL ADENOMA, UNILATERAL AGREE AGREE AGREE AGREE ,,,ed. Doe, not contain TSCACB1 15