Document MMq1R2JRerKB24K7dXkOaKaN7

EPL EXPERIM ENTA L PA THO LO G Y LA BO RATOR IES, INC. Report Title PATHOLOGY PEER REVIEW AND PATHOLOGY WORKING GROUP REVIEW OF MAMMARY GLANDS FROM A CHRONIC FEEDING STUDY IN RATS WITH PFOA PWG REPORT Data Requirement N/A Author Jerry F. Hardisty, D.V.M. Date June 17, 2005 Performing Laboratory Experimental Pathology Laboratories, Inc. P.O. Box 12766 Research Triangle Park, NC 27709 Sponsor DuPont Haskell Laboratory for Health and Environmental Sciences 1090 Eikton Road P.O. Box 50 Newark, DE 19714 Project ID EPL Project No. 129-060 VOLUME 1 OF 1 PAGE 1 OF 74 1 EPL EXPERIM ENTA L PA TH O LO G Y LA BO RATOR IES, INC. PATHOLOGY PEER REVIEW AND PATHOLOGY WORKING GROUP REVIEW OF MAMMARY GLANDS FROM A CHRONIC FEEDING STUDY IN RATS WITH PFOA CERTIFICATION OF GOOD LABORATORY PRACTICES This Pathology Working Group Review (PWG) does not constitute a study. Therefore, Good Laboratory Practice Standards (40 CFR, Part 160) do not apply to this report. However, all appropriate documentation of the review process has been maintained. Signature: ate EPL E X P E R IM E N TA L P A TH O LO G Y LA B O R A TO R IES, INC. PWG PARTICIPANTS: JERRY F. HARDISTY, D.V.M.N Diplomate ACVP (Chairperson) GABRIELLE A. WILLSON, B.V.M.S., MRCVS F.R.C. Path (Reviewing Pathologist) W. RAY BRO^ Ph.D. Diplomate AC^ (Consulting Pathologist) . ~yv\c ERNEST E. MCCONNELL, D.V.M., M.S. Diplomate ACVP, ABT (Consulting Pathologist) 3 EPL EXPERIM ENTAL PATHO LO GY LABORATORIES, INC. PATHOLOGY PEER REVIEW AND PATHOLOGY WORKING GROUP REVIEW OF MAMMARY GLANDS FROM A CHRONIC FEEDING STUDY IN RATS WITH PFOA TABLE OF CONTENTS TITLE PAGE CERTIFICATION OF GOOD LABORATORY PRACTICES PWG PARTICIPANTS' PAGE TABLE OF CONTENTS NARRATIVE APPENDIX A PWG Consensus Diagnoses for Individual Animals Reviewed in Each Group APPENDIX B Statistical Analyses of Mammary Tumors in Rats Fed PFOA APPENDIX C Curriculum Vitae Page 1 2 3 4 5 14 19 21 4 EPL EXPERIMENTAL PATHO LO GY LABORATORIES, INC. PATHOLOGY PEER REVIEW AND PATHOLOGY WORKING GROUP REVIEW OF MAMMARY GLANDS FROM A CHRONIC FEEDING STUDY IN RATS WITH PFOA EPL PROJECT NO. 129-060 NARRATIVE SUMMARY INTRODUCTION Hematoxylin and eosin stained and trichrome stained microscopic slides of mammary gland from female rats used in a chronic feeding study in rats with PFOA were received from DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware by Experimental Pathology Laboratories, Inc. (EPL), Research Triangle Park, North Carolina. The study was conducted by the 3M Corporation and the tissues from the study had previously been examined and the results reported by Dr. Robert Geil, the Study Pathologist (SP), for the 3M Corporation. A summary of the group design according to the protocol for the study is summarized in Table 1 below: Table 1. Experimental Design for a Chronic Feeding Study in Female Sprague-Dawley Rats with PFOA Dietary Level of Group No. Test Material (ppm) 1 Control (0) 6 Mid (30) 5 High (300) Number of Female Rats Interim Sacrifice Terminal Sacrifice 15 50 0 50 15 50 Dr. Gabrielle Willson, the Reviewing Pathologist, reexamined all sections of mammary gland from all female rats in all groups, all previously reported mammary neoplasms and all previously reported subcutaneous neoplasms. Prior to the reexamination of the slides, the necropsy records were compared to the reported microscopic findings to ensure that all grossly described mammary and subcutaneous masses were sectioned and 5 EPL EXPERIM ENTAL PATHOLOGY LABORATORIES, INC. examined microscopically. The purpose of the peer review was to validate the accuracy and consistency of the initial histopathologic examination and to identify the issues that needed to be addressed during the review. The preliminary review of the data indicated that all masses were sectioned and examined microscopically. Following the reexamination of the histopathology findings of all sections of the mammary gland by the Reviewing Pathologist, a Pathology Working Group (PWG) was convened for the purpose of providing a consensus diagnosis for all neoplastic lesions involving the mammary gland which were diagnosed either by the Study Pathologist or the Reviewing Pathologist. The PWG members consisted of the Reviewing Pathologist, Dr. Willson, and the two consultant board-certified veterinary pathologists with extensive experience in the microscopic evaluation and interpretation of lesions observed in chronic toxicity and oncogenicity bioassay studies conducted in rodents. The original Study Pathologist was not available for the PWG meeting. The PWG's task was to provide a consensus diagnosis for each of the mammary gland neoplasms reported by either the Study or Reviewing Pathologist and to determine the toxicologic significance of the incidence of mammary gland neoplasms present in the female rats treated with PFOA in the diet. Conduct of the Reviewing Pathologist's Examination The mammary gland and all subcutaneous masses were evaluated for histopathologic changes during the Reviewing Pathologist's examination conducted by Dr. Willson. Although all microscopic findings in the mammary gland were reviewed, particular emphasis was given to neoplastic lesions. All slides containing sections of mammary tissue with a primary neoplasm of the mammary gland diagnosed by either the Study or Reviewing Pathologist were organized for the PWG review. 6 EPL EXPERIM ENTAL PATHO LO GY LABORATORIES, INC. Conduct of the Pathology Working Group Review The Pathology Working Group was chaired by Dr. Jerry F. Hardisty, Experimental Pathology Laboratories, Inc. (EPL), who organized and presented the material to the panel of three pathologists. Curricula vitae for the PWG Chairperson and each of the PWG participants are present in Appendix C. The PWG review was performed on May 19, 2005, at Experimental Pathology Laboratories in the Research Triangle Park, North Carolina. Individuals attending or participating in the PWG review are listed below: Dr. Jerry F. Hardisty, Diplomate, A.C.V.P. Dr. Gabrielle Willson, FRC Path Dr. W. Ray Brown Diplomate, A.C.V.P. Dr. E.E. McConnell Diplomate, A.C.V.P. (PWG Chairman) (Reviewing Pathologist) (PWG Participant) (PWG Participant) Dr. Steven R. Frame Diplomate, ACVP Mr. Gerald Kennedy (Observer) (Observer) The PWG examined coded slides without knowledge of treatment group. Each participant recorded his/her diagnoses and comments on worksheets which were prepared by the PWG Chairperson. The PWG examined the mammary gland only for neoplastic lesions and did not consider other lesions which may have also been present. Each lesion was discussed by the group, reexamined if necessary, and the final opinions were recorded on the Chairperson's worksheets. The consensus diagnoses of the PWG were reached when at least two of the three PWG participants were in agreement. During the PWG review, the nomenclature and diagnostic criteria recommended by the Society of Toxicological Pathologists was used by the PWG to classify the proliferative lesions (Mann, et. al., 1996). A summary of the diagnostic criteria and nomenclature used by the PWG participants for proliferative lesions of the mammary gland of rats is presented below: 7 ERL EXPERIM ENTA L PA TH O LO G Y LA BO RATORIES, INC. Nomenclature and Diagnostic Criteria for Proliferative Lesions of the Mammary Gland in Rats LOBULAR HYPERPLASIA Dilatation of ducts or ductules usually present. Evidence of epithelial or glandular proliferation. May contain mild cellular pleomorphism and mitotic activity. FIBROADENOMA Composed of glandular epithelium and fibrous connective tissue. Epithelium is generally single layered and uniform and may contain lipid vacuoles. Connective tissue distributed within and between lobules ranges from well-differentiated to dense hyalinized collagen with few interspersed fibrocytes . Epithelium often forms ductules, alveoli or small cysts. Focal areas of atypia and/or cellular pleomorphism may be present. Mast cells may be frequent. ADENOMA Discrete nonencapsuiated mass consists of proliferating alveolar structures in clusters separated by scanty connective tissue septa. Alveoli have a single layer of low cuboidal to columnar epithelium with small nuclei and a single nucleolus; epithelium often vacuolated. Alveolar lumina may be empty or filled with minimal secretion (tubular pattern) or may be widely distended by proteinaceous secretion (secretory pattern). Luminal surface of epithelium generally round, may be smooth or serrated. Focal areas of atypia and/or pleomorphism may be present. Papillary projections of epithelium may occur, either protruding into dilated ductal lumina (papillary pattern) or into cystic spaces which may be simple or multiloculated (cystic papillary pattern). ADENOCARCINOMA May be noninvasive or invasive. 8 EPL EXPERIM ENTAL PATHO LO GY LABORATORIES, INC. May have distant metastases. Neoplastic epithelial cells from 1-4 or more layers thick. Uniform epithelial cells basophilic to eosinophilic with round to oval centrally located nuclei. Chromatin clumped, single small nucleolus. Numerous mitotic figures. Multiple branching papillae covered by cuboida! to columnar epithelium (papillary pattern). Closely packed, generally empty, tubular structures which may be round or elongated (tubular pattern). Neoplastic epithelial proliferation in a solid sheet with the formation of secondary lumina (cribriform pattern). Distended ductules lined by a multilayered epithelium surrounding a central core of necrotic tumor cells (comedo pattern). ADENOCARCINOMA ARISING IN FIBROADENOMA Adenocarcinomatous change within a fibroadenoma. Histologic pattern of fibroadenoma component variable. Typical histologic appearance of adenocarcinoma present. After the PWG completed the slide review and the diagnoses were recorded by the PWG Chairperson, the slides were decoded by treatment group. PWG consensus diagnoses for individual animals reviewed in each group are presented in Appendix A. A summary of the incidence of neoplasms in the mammary gland of female rats is tabulated in Table 2. 9 EPL EXPERIM ENTA L PA TH O LO G Y LA BO RATORIES, INC. Table 2. Chronic Feeding Study in Female Sprague-Dawiey Rats with PFOA: Incidence of Mammary Gland Neoplasms in Female Rats Group 1 Group 6 Group 5** SP PWG SP PWG SP PWG MAMMARY GLAND - Number Necropsied 50 50 50 50 50 50 Adenocarcinoma (%) 8 9 14 16 5 5 (16%) (18%) (28%) (32%) (10%) (10%) Fibroadenoma (%) 8 16 13 16 19 20 (16%) (32%) (26%) (32%) (38%) (40%) Fibroadenoma, Multiple (%) 2 _L4%) 2 6 62 (4%) (12%) (12%) (4%) 3 (6%)_ Adenoma (%) 3 10 00 0 (6%) (2%) (0%) (0%) _(0%) (0%) liSlIlSSI ' ItaSlllS . No. of Animals with Benign Tumors 13 19 19 22 21 23 No. of Animals with Malignant Tumors 8 7 / ' . ' ::SR : . -, 9 .: 14 : ....1.6 , . 55 . : . ' No. of Animals with Both Benign and 2 2 4 7 3 Malignant Tumors : ' . v . : , - . ;' 3 No. of Animals with Mammary Tumors 19 24 29 31 23 25 (Benign or Malignant)* *Some affected had more than one tumor type. ** Two Group 5 female rats had fibroadenoma present in the interim sacrifice group. DISCUSSION AND CONCLUSION The results of the PWG Review generally supported the Reviewing Pathologist's findings. The primary difference between the original reported findings and the PWG results involved changes in the mammary gland that were initially reported as lobular hyperplasia by the Study Pathologist which the PWG felt had features more characteristic of mammary gland fibroadenoma. This difference involved six Group 1, two Group 6 and two Group 5 female rats. Although there were a few differences concerning the classification of benign 10 EPL EXPERIM ENTAL PATHO LO GY LABORATORIES, INC. and malignant neoplasms, the majority of the other neoplasms reported by the Study Pathologist were confirmed during the PWG review of mammary gland neoplasms in female rats from this study. Although the incidence of neoplasms varied among the control and treated groups, there were no statisticaily-significant differences when evaluated using the Fisher's Exact Test for pairwise comparison for fibroadenoma, adenocarcinoma, total benign neoplasms or total malignant neoplasms. The PWG noted that although it is not recommended that benign and malignant neoplasms be combined since there was no histologic evidence of tumor progression from benign to malignant (McConnell, 1986). However, even if combined in this study, there was no significant difference between control and treated groups. The only statistically significant difference (<0.01) involved a negative pairwise comparison in the incidence of adenocarcinoma in Group 6 (30 ppm) compared to Group 5 (300 ppm). Statistical analyses of mammary tumors in rat fed PFOA conducted by Dr. David W. Gaylor are presented in Appendix B. There was no increase in tumor multiplicity or incidence with dose between control and treated groups. The morphologic appearance of the neoplasms present in treated groups was similar to those observed in the control groups indicating that treatment did not affect the phenotype of the neoplasms in the study. The incidence of mammary gland neoplasms observed in this study is similar to historical control data for mammary gland neoplasms in untreated Crl:CD female Sprague-Dawley Rats in 104 week studies in the open literature (Inveresk Research, 2002; Giknis and Clifford, 2001; Giknis and Clifford, 2004; Chandra, et al., 1992; McMartin, et al., 1992; Stevens, et al., 1994; and Sykes G, 1987) presented in Table 3. Table 3. Historical Control Data In Untreated Crl:CD Female Sprague-Dawley Rats In 104 Week Studies ADENOMA Average (Range) 3.6% (0-18%) 8.4% (1.7-32.0%) 6.9% (1.1-32.0%) FIBROADENOMA ADENOCARCINOMA REFERENCE Average (Range) 47.2% (26-68%) 41.1% (13.3-61.2%) 38.1% (13.3-62.3%) Average (Range) 8.5% (0-20%) 23.7% (8.6-58.3%) 22.2% (8.6-58.3%) Inveresk, 2002 Giknis MLA and Clifford CB, 2001 Giknis MLA and Clifford CB, 2004 11 EPL EXPERIM ENTA L PA TH O LO G Y LA BO RATO R IES, INC. ADENOMA 3.54% (NA) 6.5% (2.9-11.4%) 1% (0-7) 5% (0-15) 2% (3-11) 4% (0-31) 1.9% (0-9.1%) *NA = Not available FIBROADENOMA ADENOCARCINOMA REFERENCE 18.96% (NA) 31.3% (20.0--43,3%) 33% (36-48) 34% (2-75) 30% (20-43) 23% (11-57) 37.4% (24.2-54.0%) 8.80% (NA) 16.8% (6.7-30.0%) 17% (3-19) 14% (0-25) 18% (7-30) 6% (3-16) 14.1% (6.5-24.5%) Chandra M, et al., 1992 McMartin DN, et a!., 1992 Stevens, JT, et al., 1994, Atrazine Stevens, JT, et al., 1994, Propazine Stevens, JT, et a!., 1994, Simazine Stevens, JT, et al., 1994, Terbuthylazine Sykes G, 1987. US EPA Administrative Record 226-1917 CONCLUSION The PWG concluded that the incidence of mammary gland neoplasms in this study was not affected by chronic dietary administration of PFOA. The morphologic appearance, overall incidence and distribution of the neoplasms observed in treated and control groups were similar. JEfRY FAJ-1ARD1STY, D.V:\ Diplomate, ACVP Chairperson g-v^JL X \ ( 7-00 12 EPL EXPERIM ENTA L PA TH O LO G Y LA BO RATO R IES, INC. REFERENCES Chandra M, Riley MGI and Johnson DE (1992) Spontaneous neoplasms in aged SpragueDawley rats. Arch Toxicol, 66: 496-502. Giknis MLA and Clifford CB (2001) Compilation of spontaneous neoplastic lesions and survival in Crl:CD (SD) BR rats from control groups. Charles River Laboratories. Giknis MLA and Clifford CB (2004) Compilation of spontaneous neoplastic lesions and survival in Crl:CD (SD) rats from control groups. Charles River Laboratories. Inveresk Research (2002) Background Tumour Incidences CD Sprague-Dawley rats. Mann PC, Boorman GA, Lollini LO, McMartin DN and Goodman DG (1996) Proliferative lesions of the mammary gland in rats, IS-2. In Guides for Toxicologic Pathology. STP/ARP/AFIP, Washington, D.C. McConnell EE, Solleveld HA, Swenberg JA and Boorman GA (1986) Guidelines for combining neoplasms for evaluation of rodent carcinogenesis studies. JNCL, Vol. 76, No. 2., 283-289. McMartin DN, Sahota PS, Gunson DE, Hsu HH and Spaet RH (1992) Neoplasms and related proliferative lesions in control Sprague-Dawley rats from carcinogenicity studies. Historical data and diagnostic considerations. Toxicologic Pathology, Vol. 20, Number 2, 212-225. Stevens JT, Breckenridge CB, Wetzel LT, Gillis JH and Luempert III LG (1994) Hypothesis for mammary tumorigenesis in Sprague-Dawley Rats exposed to certain triazine herbicides. Jurnal of Toxicology and Environmental Health, 43:139-153. Sykes G (1987) Two-year Toxicity/Carcinogenicity Sudy of Fluorochemical FC-143 in Rats. US EPA Administrative Record 226-1917. 1-6. 13 EPL EXPERIM ENTAL PATHO LO GY LABORATORIES, INC. APPENDIX A PWG Consensus Diagnoses for Individual Animals Reviewed in Each Group 14 APPENDIX A Chemical Name: PFOA Mammary Glands from the Chronic Feeding Study in Rats with PFOA Animal Study Pathologist's Reviewing Pathologist's Pathology Working Group No. Diagnosis Diagnosis Consensus Diagnosis Group 1 (Female) - 0 ppm 1R-4577 Lobular Hyperplasia Fibroadenoma Fibroadenoma 1R-4581 Adenocarcinoma Adenocarcinoma Adenocarcinoma 1R-4583 Fibroadenoma Fibroadenoma Fibroadenoma 1R-4587 Lobular Hyperplasia Fibroadenoma Fibroadenoma 1R-4595 Lobular Hyperplasia Fibroadenoma Fibroadenoma 1R-4596 Fibroadenoma Fibroadenoma Fibroadenoma 1R-4600 Lobular Hyperplasia Fibroadenoma Fibroadenoma Adenoma, Papillary Adenocarcinoma Adenocarcinoma 1R-4606 Adenocarcinoma Adenocarcinoma Adenocarcinoma 1R-4609 Carcinoma No Slide Adenocarcinoma* - Fibroadenoma Fibroadenoma 1R-4611 Fibroadenoma Fibroadenoma Fibroadenoma 1R-4612 Fibroadenoma, Two Fibroadenoma, Two Fibroadenoma, Multiple 1R-4613 Lobular Hyperplasia Fibroadenoma Fibroadenoma 1R-4614 Adenocarcinoma Adenocarcinoma Adenocarcinoma 1R-4621 Fibroadenoma Fibroadenoma Fibroadenoma 1R-4623 Fibroadenoma Fibroadenoma Fibroadenoma 1R-4624 Adenocarcinoma Adenocarcinoma Adenocarcinoma Fibroadenoma Fibroadenoma Fibroadenoma 1R-4625 Fibroadenoma Fibroadenoma Fibroadenoma 1R-4627 Adenocarcinoma Adenocarcinoma and Fibroadenoma Fibroadenoma 1R-4628 Adenoma, Papillary Adenocarcinoma Adenocarcinoma 1R-4633 Adenocarcinoma Adenocarcinoma Adenocarcinoma 1R-4634 Fibroadenoma, Two Fibroadenoma, Two Fibroadenoma, Multiple 1R-4635 Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenoma Adenoma Adenoma 1R-4636 Lobular Hyperplasia Fibroadenoma Fibroadenoma 1R-4639 Fibroadenoma Fibroadenoma Fibroadenoma *No slide available for reexamination, so defaulted to Study Pathologist's reported diagnosis. 15 APPENDIX A Chemical Name: PFOA Mammary Glands from the Chronic Feeding Study in Rats with PFOA Animal No. Study Pathologist's Diagnosis 1R-4706 1R-4707 1R-4708 1R-4710 1R-4711 1R-4712 1R-4714 1R-4717 1R-4718 1R-4719 1R-4720 1R-4721 1R-4723 Adenocarcinoma Adenocarcinoma Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Fibroadenoma Adenocarcinoma, Papillary 1R-4726 1R-4727 1R-4729 1R-4730 1R-4731 1R-4732 1R-4734 1R-4737 Not Remarkable Fibroadenoma Fibroadenoma, Two Adenocarcinoma Fibroadenoma Fibroadenoma, Two Lobular Hyperplasia, Cystic Fibroadenoma, Two 1R-4740 Lobular Hyperplasia 1R-4741 Lobular Hyperplasia 1R-4742 Fibroadenoma, Two Reviewing Pathologist's Diagnosis Group 6 (Female) - 30 ppm Adenocarcinoma Adenocarcinoma Fibroadenoma, Two Fibroadenoma Fibroadenoma Adenocarcinoma Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Fibroadenoma Adenocarcinoma, Papillary and Fibroadenoma Fibroadenoma Fibroadenoma, Two Fibroadenoma, Two Adenocarcinoma Fibroadenoma Fibroadenoma, Two Fibroadenoma Adenocarcinoma and Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma and Fibroadenoma Pathology Working Group Consensus Diagnosis Adenocarcinoma Adenocarcinoma Fibroadenoma, Multiple Fibroadenoma Fibroadenoma Adenocarcinoma Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Fibroadenoma Adenocarcinoma and Fibroadenoma Lobular Hyperplasia Fibroadenoma, Multiple Fibroadenoma, Multiple Adenocarcinoma Fibroadenoma Fibroadenoma, Multiple Fibroadenoma Adenocarcinoma and Fibroadenoma Fibroadenoma Lobular Hyperplasia Adenocarcinoma and Fibroadenoma 16 APPENDIX A Chemical Name: PFOA Mammary Glands from the Chronic Feeding Study in Rats with PFOA Animal No. 1R-4743 1R-4744 1R-4745 1R-4746 1R-4747 1R-4748 1R-4750 1R-4753 1R-4754 Study Pathologist's Diagnosis Fibroadenoma Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma, Two Adenocarcinoma Fibroadenoma Fibroadenoma, Two Fibroadenoma Adenocarcinoma 1R-4641 1R-4644 1R-4645 1R-4646 1R-4649 1R-4654 1R-4657 1R-4659 1R-4660 1R-4662 1R-4663 1R-4665 1R-4673 1R-4677 1R-4679 1R-4682 1R-4685 1R-4686 1R-4694 Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma and Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma, Two Fibroadenoma Fibroadenoma Lobular Hyperplasia, Moderate Adenocarcinoma Fibroadenoma, Two Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Reviewing Pathologist's Diagnosis Fibroadenoma Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma, Two Adenocarcinoma Fibroadenoma Fibroadenoma, Two Fibroadenoma Adenocarcinoma Group 5 (Female) - 300 ppm Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma and Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma, Two Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma Fibroadenoma, Two Fibroadenoma, Two Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Pathology Working Group Consensus Diagnosis Fibroadenoma Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma, Multiple Adenocarcinoma Fibroadenoma Fibroadenoma, Multiple Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma and Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma, Multiple Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma Fibroadenoma, Multiple Fibroadenoma, Multiple Fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma 17 APPENDIX A Chemical Name: PFOA Mammary Glands from the Chronic Feeding Study in Rats with PFOA Animal No. 1R-4695 1R-4696 1R-4698 1R-4700 1R-4702 1R-4703 Study Pathologist's Diagnosis Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma Lobular Hyperplasia 1R-4664 Fibroadenoma 1R-4671 Fibroadenoma Reviewing Pathologist's Diagnosis Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma Fibroadenoma Group 5/INT (Female) - 300 ppm Fibroadenoma Fibroadenoma Pathology Working Group Consensus Diagnosis Adenocarcinoma Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Fibroadenoma Adenocarcinoma Fibroadenoma Fibroadenoma Fibroadenoma 18 EPL EXPERIM ENTAL PATHOLOGY LABO RATORIES, INC. APPENDIX B Statistical Analyses of Mammary Tumors in Rats Fed PFOA 19 6/12/05 Statistical Analyses of Mammary Tumors in Rats Fed PFOA David W. Gaylor, Ph.D. Gaylor and Associates, LLC Introduction Female Sprague-Dawley rats were fed PFOA in a chronic bioassay. The incidence of animals with mammary tumors reported by the Pathology Working Group are listed in Table 1. The denominators are the effective number of animals at risk (adjusted for survival) as calculated by the National Toxicology Program Poly-3 procedure (Portier and Bailer, 1989). Table 1. Incidence of mammary tumors in female rats fed PFOA. Tumor type 0 ppm 30 ppm 300 ppm Adenocarcinoma Fibroadenoma Adenoma Fibroadenoma/Adenoma Adenocarcinoma/ Fibroadenoma/Adenoma 9/40.4 18/41.4 1/38.4 19/41.7 24/42.9 16/43.4 22/41.1 0/38.5 22/41.1 31 / 44.7 5/41.4 23/44.3 0/41.4 23 / 44.3 25/45.3 Results None of the tumor types or combinations of tumor types listed in Table 1 exhibited statistically significant survival adjusted dose-response trends. No statistically significant survival adjusted pair-wise increases in tumor incidence compared to controls were noted. All P-values exceeded 0.10. References Portier, CJ and Bailer, AJ. Testing for increased carcinogenicity using a survival-adjusted quantal response test. Fundamental Appl Toxicol. 12:731-737(1989). 20 EPL EXPER IM EN TA L PA TH O LO G Y LA BO RATOR IES, INC. APPENDIX C Curricula Vitae 21 KEPI. Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY PRESIDENT/VETERINARY PATHOLOGIST EDUCATION: Iowa State University, Pre-Veterinary, 1965-1967 Iowa State University, D.V.M., 1971 Certified by the American College of Veterinary Pathologists, 1976 Adjunct Associate Professor at the School of Veterinary Medicine, NC State University, 1983 PRESENT POSITION AND EXPERIENCE: 1998 - Present. President and Pathologist, Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina Responsible for overall management and direction of contract research pathology laboratories in Virginia and North Carolina. The company serves both government and university research and the safety assessment programs of the pharmaceutical, chemical, and cosmetic industries. 1994 - 1998. Vice President, Operations and Pathologist, Experimental Laboratories, Inc., Research Triangle Park, North Carolina Responsible for overall management and direction of pathology research laboratories in North Carolina and Virginia. 1978 - 1994. Director and Pathologist, Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina Responsible for the project management, direction and technical supervision of the North Carolina branch of EPL. Responsible for the microscopic evaluation of toxicological studies. Responsible for the National Toxicology Program's Pathology Quality Assessment Program and Operations of the NTP Archives. 1976 -1978. Pathologist/Project Manager, Experimental Pathology Laboratories, Inc., Herndon, Virginia Responsible for the management of EPL's Carcinogenesis Support Laboratory. Project Manager of a program to provide Tracor Jitco with Quality Assurance in the NCI Carcinogenesis Testing Program. Technical supervision of a program to provide pathology support services to the Carcinogenesis Program of the National Cancer Institute. Responsible for the microscopic evaluation of tissues from experimental animals used in a variety of toxicological studies. 22 yEPL Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY, D.V.M. - Continued PRESENT POSITION AND EXPERIENCE - Continued 1972-1976 Research Pathologist, Veterinary Pathology Branch, Biomedical Laboratory, Edgewood Arsenal, Maryland Dr. Hardisty was a preceptee in the U.S. Army preceptorship program in Veterinary Pathology. During this time he performed gross and microscopic diagnoses of spontaneous disease and changes produced by experimental procedures in laboratory animals. He prepared reports describing and interpreting these experimental results. During this time he was principal investigator for the reproductive, mutagenic, teratogenic studies performed at the laboratory. This work consisted of revising previous experimental protocols and designing new experimental protocols to be utilized at the laboratory. The experimental design employed required the gross examination of pregnant female rats and fetuses for evidence of fetal toxicity and teratogenesis. He trained biological technicians to perform timed matings in rats* examine serially sectioned fetuses for malformations, and to examine fetal skeletons for prenatal abnormalities. 1971-1972 Attending Veterinarian, Division of BioSensor Research, Walter Reed Army Institute of Research Dr. Hardisty studied the radiographic and morphologic lesions of several musculoskeletal diseases of the German Shepherd Dog. In association with Dr. Wayne Riser, he investigated the pathogenesis and possible genetic relationship of canine hip dysplasia, eosinophilic panosteitis and ununited anconeal processes in an attempt to reduce their incidence through a selective breeding program. PROFESSIONAL MEMBERSHIPS: Diplomate, American College of Veterinary Pathologists ACVP Subspecialty in Toxicologic Pathology American College of Toxicology Society of Toxicology Society of Toxicologic Pathologists British Society of Toxicologic Pathologists International Academy of Toxicologic Pathology American Veterinary Medical Association North Carolina Society of Toxicology Charles Louis Davis, D.V.M. Foundation The Society of Phi Zeta The Society of Gamma Sigma Delta The Fraternity of Alpha Zeta The Fraternity of Omega Tau Sigma American Association for the Advancement of Science 23  Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY, D.V.M. - Continued PROFESSIONAL ACTIVITIES: Standardized System of Nomenclature and Diagnostic Criteria (SSNDC), The Society of Toxicologic Pathologists, 1987-1995. Executive Committee, The Society of Toxicologic Pathologists, 1994-1998. Executive Committee Chairman, The Society of Toxicologic Pathologists, 1997-1998. Joint Committee for STPs/ILSI on International Standardization of Nomenclature and Diagnostic Criteria for Toxicologic Pathology, 1994-1995, Co-Chairman 1995-Present. President-Elect, The Society of Toxicologic Pathologists, 1999-2000. President, The Society of Toxicologic Pathologists, 2000-2001. Past President, The Society of Toxicologic Pathologists, 2001-2002. Long Range Planning Committee, American College of Toxicology, 2002. North American Director, International Academy of Toxicologic Pathology, 2002. FDA Clinical Pharmacology Subcommittee of the Advisory Committee for Pharmaceutical Sciences, FDA Center for Drug Evaluation and Research, 2003. EDITORIAL REVIEW BOARD: International Agency for Research on Cancer (WHO), Classification of Rodent Tumors, Part II, The Mouse, 1995-2001. Editorial Review Board for Fundamental and Applied Toxicology, Society of Toxicology Board of Publications, 1996-1998. Editorial Review Board for Toxicological Sciences, Society of Toxicology Board of Publications, 1998-2004. Editorial Review Board for Experimental and Toxicologic Pathology, 2000. PUBLICATIONS AND PAPERS: Factors predisposing to urolithiasis in feedlot cattle. Hardisty JF and Diliman RC. The Iowa State University Veterinarian, Iowa State University, Ames, Iowa, 33(2), 77-81, 1971. Reduction of frequency of hip dysplasia in military dogs. Riser WH, Hardisty JF and Castleberry MW. In Proceedings. Canine Hip Dysplasia Symposium and Workshop, OFA, Columbia, MO. 1972. Genetic influence of the male on the incidence of canine hip dysplasia. Hardisty JF, Scalera SE., Castleberry MW and Riser WH. In Proceedings. Canine Hip Dysplasia Symposium and Workshop, OFA, Columbia, MO. 1972. 24 ^ epl Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY, D.V.M. - Continued PUBLICATIONS AND PAPERS - Continued Evaluation of the effects of chemical compounds on the reproductive system of rats. Hardisty JF. Presented at the Biomedical Laboratory Review and Analysis, April 1975. Reproductive studies with quint essence compounds. Hardisty JF, Presented at the Biomedical Laboratory Review and Analysis of Quint Essence, January 1976. Effects of KZ/IP mixture on the reproductive system. Hardisty JF and Peilerin RJ. Edgewood Arsenal Technical Report, 1976. Reproductive studies with diisoproplymethyiphosphate in rats. Hardisty JF, Peilerin RJ, Biskup RF and Manthei JH. Edgewood Arsenal Technical Report ARCSL TR 77037, May 1977. Quality assurance in pathology. Hardisty JF, Ward JM and Griesemer RA. NCI-NCTR Pathology Workshop, Bethesda, MD, June 1978. Mononuclear cell leukemia in Fischer 344 rats. Hardisty JF. NCI-NCTR Pathology Workshop, Bethesda, MD, June 1978. Quality assurance for pathology in rodent carcinogenesis tests. Ward JM, Goodman DG, Griesemer RA, Hardisty JF, Schueler RL, Squire RA and Strandberg JD. Journal of Environmental Pathology and Toxicology, 2, 371-378, Nov.-Dee. 1978. Neoplasms and pigmentation of the thyroid gland in F-344 rats exposed to 2,4diaminoanisole sulfate, a hair dye component. Ward JM, Stinson, SF, Hardisty JF, Cockrell BY and Hayden DW. Journal of the National Cancer Institute, Vol. 62, No. 4, April 1979. Renal carcinogenic and nephrotoxic effects of the flame retardant TRIS[{2,3dibromopropyl) phosphate] in F-344 rats and B6C3F1 mice. Reznik G, Ward JM, Hardisty JF and Russfield A. Journal of the National Cancer Institute, Vol. 63, No. 1, July 1979. Correlation between gross observations of tumors and neoplasms diagnosed microscopically in carcinogenesis bioassays in rats. Kulwich BA, Hardisty JF, Gilmore CE and Ward JM. Journal of Environmental Pathology and Toxicology, 3, 281-287, December 1979. Evaluation of procedures suggested for reducing the pathology workload in a carcinogenesis testing program. Hardisty JF, Ward JM, Douglas JF and Fears TR. Journal of Environmental Pathology and Toxicology, 3, 167-176, December 1979. 25 Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY, D,VJVI. - Continued PUBLICATIONS AND PAPERS - Continued Cancer induction following single and multiple exposures to a constant amount of vinyl chloride monomer. Hehir RM, McNamara BP, McLaughlin Jt Willigan DA, Bierbower G and Hardisty JF. Presented for the conference to re-evaluate the Toxicology of Vinyl Chloride Monomer, Polyvinyl Chloride and Structural Analogues on March 20-21, 1980, at the National Institute of Health, Bethesda, MD. Cancer induction following single and multiple exposures to a constant amount of vinyl chloride monomer. Hehir RM, McNamara BP, McLaughlin J, Willigan DA, Bierbower G and Hardisty JF. Environmental Health Perspectives, 41, 63-72, October 1981. Carcinogenesis bioassay of 2,6-Xyiidine in rats. Hardisty JF, Montgomery CA and Kornreich M. The Toxicologist, Vo! 3, No. 1, March 1983. Chronic toxicity and oncogenicity bioassay of inhaled toluene in Fischer 344 rats. Gibson JE and Hardisty JF. Fundamental and Applied Toxicology, 3: 315-319, 1983. Quality assurance in pathology for rodent carcinogenicity tests, by GA Boorman, CA Montgomery, JF Hardisty, SL Eustis, MJ Wolfe and EE McConnell. In: Handbook of Carcinogen Testing. (H Milman and E Weisberger, eds), pp. 345-357. New Jersey: Noyes Publications, 1985. Systemic effects following inhalation of fog oil obscurant. Hardisty JF, Stead AG, Grose EC and Selgrade MJ. Presented at the North Carolina Chapter of the Society of Toxicology Meeting on February 2, 1985. Factors influencing laboratory animal spontaneous tumor profiles. Hardisty JF. Toxicologic Pathology , 13, 91-104, 1985. Pulmonary and hepatic health effects of inhalation of petroleum smoke. Grose EC, Stevens MA, IHing JW, Jaskot RH, Hardisty JF and Stead A. The Toxicologist, Vol 6, No. I, March 1986. National Toxicology Program Pathology Quality Assurance Procedures, by J.F.Hardisty and GA Boorman. In: Managing Conduct and Data Quality of Toxicology Studies. (BK Hoover, JK Baldwin and AF Uelner. NIEHS/NTP - CE Whitmire, CL Davies and DW Bristol, eds), pp 263-269. New Jersey: Princeton Scientific Publishing Co. Inc., 1986. Pulmonary effects due to short term exposure to oil fog. Selgrade MJK, Hatch GE, Grose EC, IHing JW, Stead AG, Miller FJ, Graham JA, Stevens MA and Hardisty,JF. J. Toxicol. & Environ. Health 21: 173-185, 1987. Arsine: Toxicity data from acute and subchronic inhalation exposures. MP Moorman, CR Moorman, JF Hardisty, SL Eustis, RE Morrissey, HR Sanders and BA Fowler. The Toxicologist, Vol 7, No. 1, February 1987. 26 Experimental Pathology Laboratories, inc. JERRY F. HARDISTY, D.V.M. - Continued PUBLICATIONS AND PAPERS - Continued Chronic toxicity and oncogenicity study of 2,6 diethylaniline. TG Pullin, RW Naismith, JF Hardisty, EB Whorton Jr. and GL Ter Haar. The Toxicologist, Vol 8, No. 1, February 1988. Peripheral nerve sheath tumors, rat, by DM. Walker, V.E. Walker, J.F. Hardisty, KT Morgan and JA Swenberg. In: ILSI Monographs on Pathology laboratory animals, nervous system. Vol 6, (TC Jones, U Mohr and RD Hunt, eds), New York, SpringerVerlag, 1988. Pulmonary effects due to subchronic exposure to oil fog. MK Selgrade, GE Hatch, EC Grose, AG Stead, FJ Miller, JA Graham, MA Stevens and JF Hardisty. Toxicology and Industrial Health, Vol 6, No. 1, 1990. Thyroid gland, by JF Hardisty and GA Boorman. In: Pathology of the F344 Rat. (G Boorman, S Eustis, C Montgomery, M Elwell and W MacKenzie, eds), San Diego, Academic Press, 1990. Oral cavity (pharynx, tongue, gingival teeth), esophagus and stomach, by HR Brown, JF Hardisty and SL Eustis. In: Pathology of the F344 Rat, (G Boorman, S Eustis, C Montgomery, M Elwell and W MacKenzie, eds), San Diego, Academic Press, 1990. Toxicological pathology: a critical stage in study interpretation, by JF Hardisty and SL Eustis. In: Progress in Toxicology. (D Clayson, I Munro, P Shubik and J Swenberg, eds), Amsterdam, Elsevier, 1990. Tumors of the skin in the HRA/Skh mouse after treatment with 8-methoxypsoralen and UVA radiation. JK Dunnick, PD Forbes, SL Eustis and JF Hardisty. Fund. & Appl. Tox., Vol 16, 92-102, 1991. Proliferative lesions of the mouse lung: Progression studies in Strain A mice. JF Foley, MW Anderson, GD Stoner, BW Gaul, JF Hardisty and RR Maronpot. Experimental Lung Research, Vol.17, 157-168, 1991. Lesions of the rodent liver. Hardisty JF. Presented at the Dose Response Relationships for Hepatocarcinogenesis in Medaka Exposed to Waterborne N-Nitrosodietylamine. Workshop on December 15, 1993. Procedures for peer review in toxicologic pathology. Hardisty JF. Presented at The Society of Toxicologic Pathologist 13ih International Symposium on June 5-9, 1994. Necropsy and histology in toxicologic pathology. Hardisty JF. Presented at Industrial Toxicologic Pathology, University of Illinois at Urbana-Champaign, July 27, 1994. 27 EEPL Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY, D.V.M. - Continued PUBLICATIONS AND PAPERS - Continued A comparison of liver tumor diagnoses from seven PCB studies in rats. Moore John A, Hardisty Jerry F, Banas Deborah A and Smith, Mary Alice. Regulatory Toxicology and Pharmacology, Vol 20, 362-370, 1994. Neoplastic lesions of questionable significance. Hardisty JF. Presented at the 1994 Toxicology Roundtable on October 3, 1994. Use of nasal diagrams to record nasal lesions. Hardisty JF. Presented at the 1994 Toxicology Roundtable on October 4, 1994. Morphologic assessment of pathologic changes in the rat larynx. Hardisty JF. Presented at the 1994 Toxicology Roundtable on October 4, 1994. Pathology peer review and PWG. Hardisty JF. Presented at the 1995 Toxicology Roundtable in Nashville, TN on October 23, 1995. Peer review in toxicology pathology. Ward JM, Hardisty JF, Hailey JR and Street CS. Toxicologic Pathology 1SSN:0192-6233, Vol. 23, No. 2, 1995 Computerized pathology data - summary vs. individual. Hardisty JF. Presented at the 1995 Toxicology Roundtable in Nashville, TN on October 24, 1995. An evaluation of changes in the olfactory epithelium and liver peroxisome proliferation in mice after inhalation exposure to methylethylketoxime. Newton PE, Bolte HF, Lake BG, Derelanko M, Rinehart WE and Hardisty JF. The Toxicologist, Vol 30, No. 1, Part 2, March 1996. Peer review of histopathology data. Hardisty JF. Presented at the American College of Toxicology 17thAnnual Meeting in King of Prussia, PA on November 11, 1996. Pathology peer review in assessing carcinogenicity studies. Hardisty JF. Presented at the American College of Veterinary Pathologists' Thirty- First Annual Meeting in Seattle, Washington on December 5, 1996. Value of the mouse carcinogenicity bioassay (Summary). Hardisty JF. Toxicologic Pathology ISSN:0192-6233, Vol. 24, No. 6, 1996, pp. 720-721. Interaction of consultants, contract laboratories and industry-Panel Discussion with HE Black, AM Dahlem, JF Hardisty, TG Terrell. Presented at Industrial Toxicologic Pathology, University of Illinois at Urbana-Champaign, May 19, 1997. Controversial issues in anatomic pathology. JF Hardisty. Presented at industrial Toxicologic Pathology, University of Illinois at Urbana-Champaign, May 20, 1997. 28 EPL Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY, D.V.M. - Continued PUBLICATIONS AND PAPERS - Continued Phenolphthalein induces thymic lymphomas accompanied by loss of the p53 wild type allele in heterozygous p53-deficient (+) mice. Dunnick JK, Hardisty JF, Herbert RA, Seely JC, Furedi-Machacek EM, Foley JF, Lacks GD, Stasiewicz S and French JE. Toxicologic Pathology, Vol. 25, No. 6., 533-540, 1997. Diagnostic dilemmas in toxicologic pathology. Hardisty Jerry. Presented at The 22nd Annual CL Davis DVM Foundation Continuing Education Symposium at North Carolina State University, College of Veterinary Medicine in Raleigh, North Carolina on June 14-18,1998. Thyroid and parathyroid glands, by JF Hardisty and GA Boorman. In: Pathology of the Mouse. (RR Maronpot, GA Boorman and BW Gaul, eds), Vienna, IL, Cache River Press, 1999. Rodent leydig cell tumorogenesis: a review of the physiology, pathology, mechanisms, and relevance to humans. Jon C Cook, Gary R Klinefelter, Jerry F Hardisty, Richard M Sharpe and Paul MD Foster, Critical Reviews in Toxicology, 29(2): 169-261, 1999. The nomenclature of cell death: recommendations of an ad hoc committee of Society of Toxicologic Pathologists. Levin S, Bucci TJ, Cohen SM, Fix AS, Hardisty JF, Legrand EK, Maronpot RR and Trump BF. Toxicol Pathol. 1999 Jul-Aug;27(4):484~490. Controversial issues in anatomic pathology. Hardisty Jerry. Presented as a course entitled Industrial Toxicology and Pathology for the American Registry of Pathology at the Ramada Inn in Bethesda, MD on September 28, 1999. Histopathology of nasal offactory mucosa from selected inhalation toxicity studies conducted with volatile chemicals. Hardisty JF, Garman RH, Harkema JR, Lomax LG and Morgan KT. Toxicologic Pathology, Vol.27, No. 6, pp. 618-627, 1999. Pathology Working Groups: Current Concepts. Hardisty JF. Presented at the16ih Annual Meeting of the Society of Quality Assurance in Montreal, Canada on October 9-13, 2000. Blind Pathology - When and When Not. Hardisty JF. Presented at the 51st Annual Toxicology Roundtable Program in Asheville, NC on October 15-18, 2000. Short-Term, Subchronic, and Chronic Toxicology Studies, by NH Wilson, JF Hardisty and JR Hayes. In: Principles and Methods of Toxicology. 4th Edition. (Wallace Hayes, ed), ISBN 1-56032-814-2, 2000. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology. Garman RH, Fix AS, Jortner BS, Hardisty JF, Claudio L and Ferenc S. Environmental Health Perspectives, Voi. 109, pp. 93-100, March 2001. 29 M lrrnli Experimental Pathology Laboratories, Inc. JERRY F. HARDISTY, D.V.M. - Continued PUBLICATIONS AND PAPERS - Continued A chronic inhalation toxicity/oncogenicity study of methylethylketoxime in rats and mice. Newton PE, Wooding WL, Boite HF, Derelanko MJ, Hardisty JF and Rinehart WE. Inhalation Toxicology, 13:1093-1116, 2001. Carcinogenic assessment of premafloxacin in rats and mice. White KA, Daniel EM, Botta JA, Clare LJ, Barnett D, Fliidebrandt P, Hardisty JF and Lucas MJ. Presented as a poster for the Society of Toxicologic Pathology and the International Federation of Societies of Toxicologic Pathologists in Orlando, Florida on June 24-28, 2001. Quality review procedures necessary for rodent pathology databases and toxicogenomic studies: The National Toxicology Program Experience. Boorman GA, Haseman JK, Waters WD, Hardisty JF and Sills RC. Toxicol. Pathol. 30, 88-92, 2002. Inhalation toxicology of octamethylcyclotetrasiloxane (D4) following a 3-month nose-only exposure in Fischer 344 rats. Burns-Naas LA, Meeks RG, Kolesar GB, Mast RW, Elweil MR, Hardisty JF and Thevenaz P. International Journal of Toxicology, ISSN 1091-5818, Vo!. 21, No. 1, pp 39-53, 2002. Diagnostic dilemmas in toxicologic pathology. Presented at the 5th Industrial Toxicology and Pathology Course and symposium in Chicago, IL on July 9, 2002. Histologic artifacts & diagnostic dilemmas. Presented at the RTP Rodent Pathology Course, Research Triangle Park, NC on September 8-10, 2002. Comparative prevalence, multiplicity, and progression of spontaneous and vinyl carbamate-induced liver lesions in five strains of male mice. Takahashi K, Dinse GE, Foley JF and Maronpot RR. Toxicologic Pathology, Vol 30, No. 5, pp 599-605, 2002. Propylene glycol monomethyl ether (PGME): inhalation toxicity and carcinlgenicity in Fischer 344 rats and B6C3F1 mice. Toxicologic Pathology, Vol 30, No. 5, pp 570-579, 2002. An evaluation of changes and recovery in the olfactory epithelium in mice after inhalation exposure to methylethylketoxime. Newton PE, Boite HF, Derelanko MJ, Hardisty JF and Rinehart WE. Inhalation Toxicology, 14:1249-1260, 2002. The pathologist and pathology data. Hardisty JF. Presented at NIEHS, RTP, NC on February 29, 2002. The pathologist and pathology data. Hardisty JF. Presented at the SOT Meeting in Nashville, TN on March 2002. The pathologist and pathology data. Hardisty JF. Presented at FDA CEDR on May 31, 2001. 30 Experimental Pathology Laboratories, Inc. JERRY F. HARD1STY, D.V.M. - Continued PUBLICATIONS AND PAPERS - Continued Histologic artifacts and diagnostic dilemmas. Hardisty JF. Presented at NCTR in Jefferson, AR on October 31, 2002. The pathologist and pathology data. Hardisty JF. Presented at NCTR in Jefferson, AR on October 31, 2002. The pathologist and pathology data. Hardisty JF. Presented at Health Canada in Ottawa, Canada on December 2, 2002. Necropsy and histology techniques. Hardisty JF. Presented at FDA on January 9, 2003. Current approaches to Peer Review and PWG. Hardisty JF. Presented at Battelle in Columbus, OH on June 5, 2003. Characterization of intrathoracic mesothelioma in Fischer 344/N rats. Willson G, Clayton N, Hardisty J, and Pearse G. Presented as a poster for the Society of Toxicologic Pathology, 22ndAnnual Meeting In Savannah, Georgia on June 15-19, 2003. Transplacental carcinogenicity of azidothymidine in B6C3F1 mice and F344 rats. Walker DM, Hardisty JF, Ruecker FA, Funk KA, Wolfe MJ and Walker VE. Abstract No. 548. 2004 Itinerary Planner. Baltimore, MD: Society of Toxicology. Comparison of automated software with conventional histopathoiogy of liver step sections in an NTP Subchronic Bioassay. Willson GA, Joron TA, Lesniak D, Pearse G and Hardisty JF. Presented a poster at the STP Meeting in Salt Lake City, UT, June, 2004. Automated Pathology Systems - Human Versus Machine Vision. Hardisty JF: Toxicology Roundtable, Augusta, Ml. Sept. 2004. Comparative hepatic toxicity: prechronic/chronic liver toxicity in rodents. Hardisty JF and Brix AE. Toxicologic Pathology, 33:35-40, 2005. ACT/STP Pathology Course for Non-Pathologists. Hardisty JF. Speaker at ACT/STP Meeting, Lincolnshire, IL, May 10-13, 2005. 31 EPL EXPER IM EN TA L PATH O LO G Y LA B O RATO RIES, INC. GABRIELLE A. WILLSON VETERINARY PATHOLOGIST EDUCATION: Glasgow University Veterinary School B.V.M.S., 1973-1977 MRC Path (Membership of the Royal College of Pathologists), 1985 FRC Path (Fellowship of the Royal College of Pathologists), 1995 PRESENT POSITION AND EXPERIENCE: 01/04 - Present. Veterinary Pathologist, Experimental Pathology Laboratories, Inc., Research Triangle Park, NC Provides pathology support to CUT, Centers for Health Research in Research Triangle Park, on a part-time basis. This involves interaction with staff at all levels and participation in many diverse areas ranging from the technical aspects of tissue processing and necropsy techniques to study design, photography, poster preparation, image analysis, confocal microscopy, electron microscopy and immunohistochemistry in addition to the routine necropsy and interpretation of pathological lesions. 09/00 - Present. Veterinary Pathologist, Experimental Pathology Laboratories, Inc., Research Triangle Park, NC Duties as a staff pathologist in present position at EPL include histopathologic interpretation of tissues from various laboratory animals and audits of pathology data and specimens used for toxicity and carcinogenicity studies. 03/00 - 07/00 Anatomic Pathologist, IDEXX Veterinary Services, West Sacramento, CA Responsibilities included performing histopathology on research studies submitted by independent biotechnology companies, pharmaceutical companies and university departments. Also, in part, provision of diagnostic histopathology service for veterinary clinicians. 12/96 -12/99 Veterinary Surgeon, The Animal Care Centre in Sharjah, United Arab Emirates Functioned in a clinical capacity as a veterinary surgeon. 10/91 -12/96 Independent Toxicological Pathologist, Histo-Logic, Stalybridge, Cheshire UK 32 EPL E X P E R IM E N TA L P A TH O LO G Y LA B O R A TO R IES, INC. GABRIELLE A. WILLSON, B.V.M.S., MRC Path, FRC Path - Continued PRESENT POSITION AND EXPERIENCE - Continued Since August 1991, functioned as a consultant pathologist establishing Histo-Logic, an independent pathology consultancy. Performed pathology on a number of studies and also performed peer reviews of studies for Glaxo Wellcome (Ware). These studies were either performed in house (Ware) or at contract facilities and of necessity involved close liaison with the other scientists involved. Read a variety of studies in rats, mice, dogs and minipigs for contract and other pharmaceutical laboratories in both the United Kingdom and elsewhere in Europe. Histo-Logic was accepted into the United Kingdom Department of Healths GLP Compliance programme. 10/77 - 06/91 Senior Pathologist, Unilever Research, Sharnbrook, Bedford UK Responsibilities included postmortem and histological assessment of short, medium and long term tests in rodents. Acted as Study Director for all teratogenicity studies for several years conduced both in house and at contract laboratories. Management of the Teratology Department with direct responsibility for a staff of four. Achievements During This Period: Completion of a large number of tests encompassing feeding, inhalation, intratracheal instillation, intrapleural and intraperitoneal injection, intravaginal instillation and topical application. Ultrastructural examination and histochemical assessment were frequently required as part of the evaluation process. Sole responsibility for the histological assessment of a vast and complex intrapleural study investigating the lifetime effects of fibrous minerals. Production of reports, most of which were submitted to Regulatory Authorities. Overseeing a successful collaborative project with the Anatomy Department of Leicester University Medical School in the area of in-vitro techniques for the assessment of embryo culture. This technique was later transferred to the Environmental Safety Laboratory at Unilever where it was used in the assessment of potential teratogens. Formal presentations of results of studies both within Unilever and to the operating companies. Carrying out background research to maintain the health of the breeding colonies of rats, mice, guinea pigs, rabbits and investigation of specific problems. 33 EPL E X P E R IM E N TA L P A TH O LO G Y LA B O R A TO R IES, INC. GABRIELLE A. WILLSON, B.V.M.S., MRC Path, FRC Path - Continued PRESENT POSITION AND EXPERIENCE - Continued 07/77 -10/77 Locum work, Henderson & Keywood Veterinary Surgeons Surbiton, surrey UK Locum work in a busy small animal practice. Duties included consultations, surgical procedures, etc. PROFESSIONAL MEMBERSHIPS: Fellow of the Royal College of Pathologists British Society of Toxicological Pathology Charles Louis Davis, D.V.M. Foundation Society of Toxicologic Pathology PRESENTATIONS AND POSTERS: Induced Mesothelioma in the Wistar Rat. Willson, G, presented at the Industrial Histology Discussion Group, 22nd Meeting, Llandudno, North Wales, September 1992. Spontaneous and Induced Pathology of the Salivary Glands and Oesophagus. Willson G, presented at the BSTP Modular Education Programme in Toxicological Pathology, Cambridge, England, July 20,1993. Cardiovascular System: Spontaneous Rodent Pathology. Willson, G., presented at the BSTP Modular Education Programme in Toxicological Pathology, Cambridge, England, July 9-12, 2001. Hepatoblastomas in Mice in the US National Toxicology Program {NTP) Studies. Turusov VS, Torii M, Sills RC, Willson GA, Herbert RA, Hailey JR, Haseman JK and Boorman GA, presented at the STP Meeting in Denver, CO, June 2-6, 2002. Characterization of Intrathoracic Mesothelioma in Fischer 344/N Rats. Willson G, Clayton N, Hardisty J and Pearse G. Presented as a poster for the Society of Toxicologic Pathology, 22nd Annual Meeting in Savannah, Georgia on June 15-19, 2003. Toxicologic Pathology of the Integumentary System and the Mammary Gland. Willson G. Presented to the Health Products and Food Branch, Office of Continuing Education, Ontario, Canada on January 20, 2004. The Use of Automated Pathology Software to Confirm the Results of Pathological Evaluation of NTP Studies. Pearse G, Joron TA, Lesniak D, Willson GA and Hardisty JF, presented a poster at the STP Meeting in Salt Lake City, UT, June, 2004. 34 cCoriL E X P E R IM E N TA L PA TH O LO G Y LA B O R A TO R IES, INC. GABRIELLE A. WILLSON, B.V.M.S., MRC Path, FRC Path - Continued PUBLICATIONS AND PAPERS: Comparison of Automated Pathology Software with Conventional Histopathology of Liver Step Sections in an NTP Subchronic Bioassay. Willson GA, Joron TA, Lesniak D, Pearse G and Hardisty JF, presented a poster at the STP Meeting in Salt Lake City, UT, June, 2004. Module 13: Musculoskeletal System, Skin, Subcutis and Mammary Gland. Willson G (organized the programme), BSTP Modular Education Programme in Toxicological Pathology, Cambridge, England, July 5-9, 2004. Corneal Lipoidosis in a Dog with Bilateral Thyroid Carcinoma. Harrington GA and Kelly DF. Vet Pathol. 1980 Jul;17(4):490-3. A Lymphomatoid Granulomatosis of the Lungs in Young Dogs. Lucke VM, Kelly DF, Harrington GA, Gibbs C and Gaskeil CJ. Vet Pathol. 1979 Jul:16(4):405-12. Hepatoblastomas in Mice in the US National Toxicology Program (NTP) Studies. Turusov VS, Torii M, Sills RC, Willson GA, Herbert RA, Hailey JR, Haseman JK and Boorman GA. Toxicologic Pathology, Vol. 30, No. 5, pp 580-591. GABRIELLE A. WILLSON, B.V.M.S., M.R.C.V.S., FRC. Path. <ept-e/^be/ I%rici{ Date 35 CURRICULUM VITAE - 2004 NAME W. Ray Brown, D.V.M., Ph.D. Diplomate, American College of Veterinary Pathologists PRESENT POSITION Consultant in Toxicologic, Pharmacologic & Experimental Pathology President, Research Pathology Services, Inc. 438 East Butler Avenue, New Britain, PA 18901 Telephone: 215-345-7070 Fax: 215-345-4326 e-mail: WRBRPS@concentric.net EDUCATION Dearee Year Pennsylvania State University University Park, Pennsylvania New York State College of Veterinary Medicine Cornell University Ithaca, New York New York State College of Veterinary Medicine Cornell University-Veterinary Pathology Ithaca, New York B.S. D.V.M. Ph.D. 1961 1964 1967 PREVIOUS POSITIONS Independent Consultant in Toxicologic, Pharmacologic and Experimental Pathology 1973 - present Director of Toxicology and Pathology Merck Institute for Therapeutic Research West Point, Pennsylvania 1972 -1973 Director of Pathology Merck Institute for Therapeutic Research West Point, Pennsylvania 1970 -1972 Senior Research Fellow of Pathology Merck Institute for Therapeutic Research West Point, Pennsylvania 1969 -1970 Research Fellow of Pathology Merck Institute for Therapeutic Research West Point, Pennsylvania 1967 -1969 36 Curriculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. PREVIOUS POSITIONS (Continued) Laboratory Instructor, Veterinary Pathology New York State College of Veterinary Medicine Cornell University Ithaca, New York NiH Trainee in Veterinary Pathology New York State College of Veterinary Medicine Cornell University Ithaca, New York ACADEMIC AFFILIATION Assistant Professor, Department of Pathology Jefferson Medical College Thomas Jefferson University Philadelphia, Pennsylvania PROFESSIONAL SOCIETIES American College of Veterinary Pathologists American Veterinary Medical Association Pennsylvania Veterinary Medical Association International Academy of Pathology American Society of Veterinary Clinical Pathologists Society of Toxicology Society of Toxicologic Pathologists International Union of Pharmacology (Section of Toxicology) Charles Louis Davis, DVM Foundation Sigma Xi Phi Zeta National Veterinary Honorary Society Omega Tau Sigma Professional Veterinary Society OTHER SPECIALTY Director, Electron Microscopy Laboratory Department of Safety Assessment Merck Institute for Therapeutic Research West Point, Pennsylvania 1964 - 1967 1964 - 1967 37 Curriculum Vitae - 2004 W. Ray Brown, Ph.D. CONTINUING EDUCATION/PROFESSIONAL MEETINGS American College of Veterinary Pathologists Annual Meeting Baltimore, MD - October 31-November 3 Mouse Pulmonary Carcinogenesis Symposium National Toxicology Program - NIEHS Research Triangle Park, NC - March 27-28 Society of Toxicology Annual Meeting Miami Beach, FL - February 12-15 American College of Veterinary Pathologists Annual Meeting Phoenix, AZ - December 10-13 Society of Toxicology Annual Meeting Dallas, TX - February 25-28 Drug Information Association Recent Considerations on the Design, interpretation and Evaluation of Rodent Carcinogenicity Studies Rockville, MD - September 30-October 1 American College of Veterinary Pathologists Annual Meeting Orlando, FL - December 9-13 Society of Toxicology Annual Meeting Seattle, WA - February 24-27 Society of Toxicologic Pathologists XI International Symposium Toxicologic Pathology of the Hematopoietic System Phoenix, AZ - May 31-June 4 National Research Council Role of Toxicologic Pathology in Safety Assessment Washington, DC - February 8-9 38 1989 1990 1990 1990 1991 1991 1991 1992 1992 1993 Curriculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. CONTINUING EDUCATION/PROFESSIONAL MEETINGS (Continued! Society of Toxicology Annual Meeting New Orleans, LA - March 15-19 Society of Toxicologic Pathologists Xll International Symposium Regulations Governing Toxicologic Pathology Washington, DC - June 27-July 1 Growth Factors and Tumor Promotion: Implications for Risk Assessment (7th International Conference on Carcinogenesis and Risk Assessment) Austin, TX - December 1-4 International Life Sciences Institute 5thWorkshop on Mouse Liver Tumors Arlington, VA - November 7-9 Society of Toxicology Annual Meeting Baltimore, MD - March 5-9 Society of Toxicologic Pathologists 14th International Symposium San Diego, CA-June 11-15 Staging of Rat Testes Two-day short course by Dr. L. Russel! Rohm and Haas Company Spring House, PA - February 26-27 Mid-Atlantic Chapter, Society of Toxicology Spring Scientific Meeting Kenilworth, NJ - April 25 Society of Toxicologic Pathologists 15th International Symposium Toxicologic Pathology and Risk Assessment St. Louis, MO - June 9-13 American College of Toxicology Annual Meeting Valley Forge, PA- November 11-13 1993 1993 1993 1994 1995 1995 1996 1996 1996 1996 39 Curriculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. CONTINUING EDUCATION/PROFESSIQNAL MEETINGS (Continued) Society of Toxicology Annual Meeting Cincinnati, OH - March 9-13 Society of Toxicologic Pathologists 16th International Symposium Toxicologic Pathology of the Kidney and Urinary Bladder Beaver Creek, CO - June 22-26 American College of Veterinary Pathologists Annual Meeting Albuquerque, NM - November 16-21 Society of Toxicology Annual Meeting New Orleans, LA - March 14-18 Society of Toxicology Annual Meeting Philadelphia, PA - March 19-23 Society of Toxicology Annual Meeting Nashville, TN - March 17-21 Charles Louis Davis, DVM Foundation Alternatives to the Rodent Biosassay in Assessing Carcinogenicity New Brunswick, NJ - April 5 American College of Veterinary Pathologists Annua! Meeting New Orleans, LA - December 7-11 Charles Louis Davis, DVM Foundation Dermatopathology Symposium New Orleans, LA - December 7 American College of Veterinary Clinical Pathologists Annual Meeting New Orleans, LA - December 7-11 1997 1997 1997 1999 2000 2002 2002 2002 2002 2002 40 Currculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. CONTINUING EDUCATION/PROFESSIONAl. MEETINGS (Continued) Charles Louis Davis, DVM Foundation Gastrointestinal Toxicologic Pathology New Brunswick, NJ - April 25 2003 PATHOLOGY WORKING GROUP (PWG1 PARTICIPANT -National Toxicology Program -Dioxin- Re-evaluation of hepatic tumors from the 1978 Kociba rat study (1990) -Dioxin- Participant at the Banbury Conferences (Cold Spring Harbor) on the results of the re-evaluation of the rat liver tumors (1990) -PCBs-Re-evaluation of the rodent liver tumors from the Aroclor 1254 and 1260 and Clophen A30 and A60 chronic/onco- genicity rat studies (1991) -Several industrial-sponsored PWGs on chemicals, agrochemicals and pharmaceuticals HISTOPATHOLOGY PEER REVIEW Peer review of histopathology slides and data have been and are being performed for several domestic and international pharmaceutical and chemical companies, trade groups, and consortiums on toxicity and carcinogenicity studies. EXPERIENCE IN TOXICOLOGY AND PATHOLOGY Activities as a consultant in toxicologic and pharmacologic pathology have included the design, supervision, evaluation, and reporting of toxicity and carcinogenicity studies involving various chemical and potential therapeutic or biologic substances. Laboratory animals used in these studies include rodents (rats, mice, hamsters, guinea pigs, rabbits), cats, dogs, non-human primates (Rhesus, cynomolgus and African green monkeys and marmosets), various avian species (chickens, ducks, turkeys, quail), and miniature swine. The types of experiments in the areas of involvement have been oral toxicity experiments, inhalation exposure studies, parenteral studies (intravenous, intramuscular, dermal, ocular and subcutaneous irritation studies), carcinogenicity experiments, reproduction/teratology studies, and histologic evaluation for safety tests of various vaccine preparations. Responsibilities in these various experiments have included evaluation, in terpretation and detailed reporting of antemortem data (clinical signs of toxicologic and pharmacologic effects), electrocardiology, hematology, serum biochemistry, urinalysis, and postmortem data (organ weights), gross and microscopic tissue examinations, histochemistry and electron microscopy. 41 Curriculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. Reporting of the above data has included preparation of summarizations of the methods and results, conclusions, and safety assessment of the various agents based on the results. These reports are written in appropriate formats for submission to international and domestic regulatory agencies, e.g., suitable for submission for Investigational New Drug (IND) and New Drug Application (NDA) with the Food and Drug Administration, U. S. Department of Agriculture, National Cancer Institute and Environmental Protection Agency. In addition to primary project participation and monitoring, peer review experience has included selection as the Society of Toxicology Task Force pathologist to perform an independent pathology review of the urinary bladder and hepatic neoplasms in the FDA/NCTR ED01mouse carcinogenicity study and participation in several select panels and committees for review and interpretative opinions on pathology slides and data for various sponsors, as well as international and domestic regulatory agencies. Many of these reviews and representations have involved findings and interpretation of hepatic and endocrine toxicity and potential oncogenicity. 42 Curriculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. PUBLICATIONS: 1. Christian, M.S. and Brown, W.R., Control Primordial Follicle Counts in Multigeneration Studies in CRL Sprague-Dawley ("Gold Standard") Rats, Toxicologic Sciences, 66:1-S, 233 (2002). 2. York, R.G., Brown, W.R., Girard, M.F., and Dollarhide, J.S., Two-Generation Reproduction Study of Ammonium Perchlorate in Drinking Water (in press). 3. Cruzan, G., Cushman, J.R., Andrews, L.S., Granville, G.C., Johnson, K.A., Bevan, C., Hardy, C.J., Coombs, D.W., Mullins, P.A. and Brown, W.R., Chronic Toxicity/Oncogenicity Study of Styrene in CD-1 Mice by Inhalation Exposure for 104 Weeks. J. Applied Toxicology 21:185-198 (2001). 4. Cruzan, G., Cushman, J.R., Andrews, L.S., Granville, G.C., Johnson, K.A., Hardy, C.J., Coombs, D.W., Mullins, P.A. and Brown, W.R., Chronic Toxicity/Oncogenicity Study of Styrene in CD Rats by Inhalation Exposure for 104 Weeks. Toxicol. Sci. 46:266-281 (1998) 5. Forbes, P.D., Takizawa, T., Hashimoto, K., Yamashita, S, Hoberman, A.M., Sambuco, C.P., Brown, W.R., and Parker, R.M., 78-Week Photocarcinogenesis Study of Grepafioxacin and Comparator Articles Administered Orally to Hairless Mice. Toxicological Sciences, 42:1-S, 50-51, 1998. 6. Sambuco, C.P., Powers, W. J., Dempster, M., Hoberman, A.M., Forbes, P.D., Brown, W.R., Stahle, P.L., Streeter, A.J. and Parker, R.M., 13-Week Subchronic Phototoxicology Study of levofloxacin, A Quinolone Antibiotic, Administered Orally to Hairless Mice. Toxicological Sciences, 42:1-S, 51, 1998. 7. Parker, R.M., Powers, W.J., Dempster, A.M., Hoberman, A.M., Sambuco, C.P., Brown, W.R., Stellar, S.M., Streeter, A.J. and Forbes, P.D., 120Month Oral (Gavage) Photocarcinogenicity Study of Levofloxacin in Hairless Mice. Toxicological Sciences, 42:1-S, 51, 1998. 8. Manley, A., Brown, W.R., and Mennear, J.: Dichlorvos and Mononuclear Ceil Leukemia in Fischer 344 Rats: Lack of Effect of Chronic Administration on Progression of the Disease. International Journal of Toxicology, 16:1-7, 1997. 9. Brown, W. R.: Comparative Histopathologic Evaluation of Animal Studies: Murine Studies with L-tryptophan and Constituents. Journal of Rheumatology (23, Supplement 46), 99-110 (1996). 10. Patterson, D.R., Hamlin, M.H., Hottendorf, G.H., Gough, A. and Brown, W.R., Proliferative lesions of the adrenal glands in rats. In Guides for Toxicologic Pathology, STP/ARP/AFIP (1995). 11. Brown, W. R., Fetter, A. D., Van Ryzin, R.J. and Langloss, J.M.: Effects of Calcitonin on the Rat Pituitary. Toxicologic Pathology 21(1): 81-86 (1993). 43 Curriculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. PUBLICATIONS (Continued! 12. McGee, J. H., Butler, W.H., Willigan, D. A., Brown, W. R., and Sofia, R. D.: Critique of the Toxicology and Carcinogenesis Studies of lodinated Glycerol in F344/N Rats and B6C3F1 Mice. Regulatory Toxicology and Pharmacology 18, 169-180 (1993). 13. Newberne, P. M., Carlton, W. W., and Brown, W. R.: Histopathological Evaluation of Proliferative Liver Lesions in Rats Fed trans-Anethole in Chronic Studies. Food and Chemical Toxicology 27(1): 21-26 (1989). 14. Hagan, J. V., Fisher, J. R., Brown, W. R. and Baldwin, R. C.: Comparison of the TwoWeek Whole-Body and Nose-Only Inhalation Toxicity of Mancozeb in Rats. The Toxicologist 7(1): 196 (1987). 15. Mizens, M., Brown, W. R., Laveglia, J., Killeen, J. C. and Ignatoski, J. A.: Combined 30Day Feeding Study and One-Generation Reproduction Study in Rats with Ethyl 5Cyano-3,4-Dipheny!-6-OXO-1[6H]-Pyridazine-acetate (DS-29399). The Toxicologist 4:17(1984). 16. Ford, W. H., Auletta, C. S., Brown, W. R., Laveglia, J,. Killeen, J. C. and Ignatoski, J. A.: A 30-Day Toxicity Study in Dogs with Ethyl 5-Cyano-3,4-Diphenyl-6-OXO-1[6H]Pyridazine-acetate (DS-29399). The Toxicologist 4:18 (1984). 17. Gongwer, L. E., Auletta, C. S., Rinehart, W. E., and Brown, W. R.: Mannitol II: Lifetime Feeding Study of A-132-1320 in Three Strains of Female Rats, Report of ICI Americas, Inc., Wilmington, DE and Bio/dynamics, inc., East Millstone, NJ. Docket No. 74-21185 (4 volumes), Dockets Management Branch, FDA, Rockville, MD (1978). 18. Emery, J. B., House, J. A., and Brown, W. R.: Cross-Protective Immunity to Canine Adenovirus Type 2 by Canine Adenovirus Type 1 Vaccination. American Journal of Veterinary Research 39(11): 1778-1783 (1978). 19. Goldlust, M. B., Rich, L. G., and Brown, W. R.: Immune Synovitis in Rabbits. Effects of Differing Schedules for Intra-articular Challenge with Antigen. American Journal of Pathology 91(2): 329-343 (1978). 20. Apostolou, A., Saidt, L., and Brown, W. R.: Effect of Overnight Fasting of Young Rats on Water Consumption, Body Weight, Blood Sampling, and Blood Composition. Laboratory Animal Science 26(6): [Part 1], 959-960 (1976). 21. Zwickey, R. E., Brown, W. R. et a/.: Preclinical Toxicology Studies of Carbidopa and Levodopa. Toxicology and Applied Pharmacology 29: 181-195 (1974). 22. Brown, W. R., Rubin, L., Hite, M. and Zwickey, R. E.: Experimental Papilledema in the Dog Induced by a Salicylanilide. Toxicology and Applied Pharmacology 21(4): 532-541 (1972). 23. Brown, W. R.: Significance of Spontaneous Diseases of the Central Nervous System in Laboratory Animals used in Pharmacology Research. The Laboratory Animal in Drug Testing. Fifth International Committee on Laboratory Animals Symposium, Hanover Germany, 1972. 44 Curriculum Vitae - 2004 W. Ray Brown, D.V.M., Ph.D. PUBLICATIONS (Continued) 24. Watson, L. S., Riley, R. L., Connelly, M. T., Russo, H. F, Brown, W. R. and Baer, J. E.: The Electrolyte Excretion Pattern of Amiloride Following Ureteral Retrograde Intraluminal injection. Federation Proceedings 30: 337 (1971). 24. VanArman, C. G., Carlson, R. P., Brown, W. R. and Itkin, A.: Indomethacin Inhibits the Local Schwartzman Reaction. Proceedings of the Society for Experimental Biology and Medicine, 134(1): 163-168 (1970). 25. Whitlock, R. H. and Brown, W. R.: Chronic Cholangiohepatitis in the Dairy Cow. Cornell Veterinarian UX(4): 515-524 (1969). 26. Brown, W. R., Krook, L. and Pond, W. G.: Atrophic Rhinitis in Swine. A nutritional disease. Der Tierzuchter 20: 546-647 (1968). 27. Scott, M. L., Olson, G., Krook, L.,Brown, W. R.: Selenium-responsive Myopathies of Myocardium and of Smooth Muscle in the Young Poult. Journal of Nutrition 91 (4); 573583(1967). 28. Brown, W. R., Krook L., Pond, W. G.: Atrophic Rhinitis in Swine. Etiology, Pathogenesis and Prophylaxis. Cornell Veterinarian LVI. Supplement No. 1, 1-128 (1966). 29. Brown, W. R., Krook, L. and Pond, W. G., A New Look at Atrophic Rhinitis. Modern Veterinary Practice 47(9): 39-45, August 1966. 30. Krook, L., Pond, W. G. and Brown, W. R.: Dietary Calcium and Phosphorus and Atrophic Rhinitis. I. Nutrition. Proceedings of the 57thAnnual Meeting of the American Society for Animal Science. J. Animal Science 24: 892 (1965). 31. Pond. W. G., Krook, L. and Brown, W. R.: Dietary Calcium and Phosphorus and Atrophic Rhinitis. Proceedings for the 1965 Cornell Nutrition Conference for Feed Manufacturers. Buffalo, New York (1965). Book Chapter 1. Brown, W. R., Implications of the Reexamination of the Liver Sections from the TCDD Chronic Rat Bioassay in "Biological Basis for Risk Assessment of Dioxins and Related Compounds", Banbury Report 35, Gallo, M. A., Scheupiein, R. J., and van der Heijden, C. A. (eds.), Cold Spring Harbor Laboratory Press, 1991, pp. 13-26. Date j 45 1 June 2003 CURRICULUM VITAE Name: Ernest E. McConnell, DVM, MS (Path) 3028 Ethan Lane Raleigh, NC 27613 Date & Place of Birth: November 14, 1937 OrrviUe, Ohio Citizenship: United States Education: 1955 - 1957 - Preveterinary Medicine, The Ohio State University 1957-1961 - D.V.M., The Ohio State University 1964 -1966 - M.S., Department of Pathology, Michigan State University 1965 - 1967 - Resident, Veterinary Pathology Division, Armed Forces Institute of Pathology, Washington, DC Board Certification: Diplomate, American College of Veterinary Pathologists, 1968 Diplomate, American Board of Toxicology, 1980 Brief Chronology of Employment: Jun 1961 - Aug 1961 Small Animal Practitioner, Becker Small Animal Hospital, Columbus, OH Aug 1961 - Aug 1961 First lieutenant, U.S. Air Force, Gunter AFB, Montgomery, Al Oct 1961 - Sep 1964 Base Veterinarian, Hill Air Force Base, Ogden, UT Sep 1964 - Sep 1965 Graduate Student, Department of Pathology, Michigan State University, East Lansing, Ml Sep 1965 - Oct 1967 Resident, Veterinary Pathology Division, Armed Forces Institute of Pathology, Washington, DC Oct 196/ - May 1969 Veterinary Pathologist, Aerospace Pathology Branch, Armed Forces Institute of Pathology, Washington, DC May 1969 - Aug 19/2 Veterinary Pathologist, Geographic Pathology Division, Armed Forces Institute of Pathology, Washington, DC with duty in the Pathology Department, Veterinary Research Institute, Onderstepoort, Republic of South Africa 46 Aug 1972 - Aug 1974 Chief, Pathology Branch, Toxic Hazards Div., 6570 Aerospace Medical Research Lab., Wright-Patterson AFB, OH Aug 1974 - Nov 1978 Veterinary Pathologist (Grade 05), U.S. Public Health Service, Research Pathologist and Head, Comparative Pathology Section, National Institute of Enviromnental Health Sciences (NIEHS), Research Triangle Park, NC. Nov 1978-Jan 1984 Veterinary Director (Grade 06), NIEHS, Chief, Chemical Pathology Brandi, Toxicology Research and Testing Program, Research Triangle Park, NC Sep 1985 - Jan 1985 Veterinary Director (Grade 06). NIEHS, Acting Director, Toxicology Research and Testing Program, Research Triangle Park, NC Jan 198 - Oct 1988 Veterinary Director (Grade 06). NIEHS, Director, Division of Toxicology Research and Testing Program, Research Triangle Park, NC Oct 1988 - present President, ToxPath, Inc., 5028 Ethan Lane, Raleigh, NC Military Service: Aug 1961 - Aug 1974: U.S. Air Force Aug 1974 - Oct .1988: U.S. Public Health Service Current Society Memberships: American Veterinary Medical Association American Association for the Advancement of Science. American College of Veterinary Pathologists Amcrican Board of Toxicolo gy American Registry of Pathology, AFIP Commissioned Officers Association, U.S. Public Health Service North Carolina Chapter of the Society of Toxicology Society of Toxicology Society of Toxicologic Pathologists Charter Member, Alumni Society, Armed Forces Inst, of Pathology Honors & Special Scientific Recognition: Distinguished Citizens Award, Hill AFB, Utah, 1964 National Defense Service Medal, 1967 U.S. Air Force Meritorious Service Medal, Wright-Patier son AFB, Ohio, 1974 Adjunct Associate Professor, School of Veterinary Medicine, North Carolina State University, 1978 to present U.S. Public Health Service Commendation Medal, N1H, Washington, DC, 1978 Study Section-Agent Orange, Veterans Administration, June 1982 Chairman, Natural Exposure Study of Animals in Enviromnental Health Research Workshop, National Research Council, National Academy of Sciences, April 1985 47 U.S. Public Health Outstanding Service Medal, NIH, Washington, DC, 1985 Panelist-Speaker, Conference on the Implications of the Bhopal Tragedy, The Workers Policy Project, Newark, New Jersey, March 1985 Task Force Leader, Study of Chemical Tracking Agent (NPPD) used by the Soviet KGB, Moscow, 1985 Panel Member, IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans - Some Chemicals Used in Plastics and Elastomers, Lyon, France, June 1985 Study Director for the NTP Methyl Isocyanate Study, 1985 Board Member, American Board of Toxicology, 1985-1989 Panel Member, Refractory Ceramic Fiber Animal Studies, TIMA, 1986 Panel Member, IARC Working Group on rhe Evaluation of the Carcinogenic Risk of Chemicals to Humans - Silica and Some Silicates, Lyon, France, June 1986 Panel Member, DHHS Committee to Coordinate Environmental and Related Programs "Report on Cancer Risks Associated with the Ingestion of Asbestos", 1987. President, American Board of Toxicology, 1987-1988 Panel Member, Health Consequences of Occupational Exposure to Man-Made Mineral Fibers, TIMA, London, England, January 1987 Panel Member, IARC Working Group to update 1ARC Monographs: Chemicals and Industrial Processes Associated with Cancer in Humans, Lyon, France, March 1987 Vice Chairman, IARC Working Group on Man-Made Mineral Fibers and Radon, Lyon, France, June, 1987 Panel Member/Rapporateur, IPCS/MARC Task Group Meeting on Man-Made Mineral Fibers, London, England, September 1987 Distinguished .Alumnus, College of Veterinary Medicine, The Ohio State University, June, 1988 Panel Member, National Research Council, Board on Environmental Studies and Toxicology-, Subcommittee on "Animals as Monitors of Environmental Hazards", 1987-1989 Co-Chairman, Review of EPA Cancer Assessment Guidelines, 1988-1989 Consultant, SAB (Drinking Water Committee and Environmental Health Committee, Environmental Protection Agency, 1988. Member, Committee on Toxicology, National Research Comidi, Board on Environmental Studies on Toxicology, 1989-1994. Lecturer, Brookings Institute, 1989 Panel Member (ad hoc), EPA-FIFRA Scientific Advisory? Panel, 1989 Panel Member/Rapporateur, IPCS/MARK Task Group Meeting on Benzene, Hannover, Germany, December, 1991. Panel Member, EPA-FIFRA Scientific Advisory Panel, 1992-2000 FDA Group Recognition Award, Nitrofuran Hearing Team, 1992. Panel Member, IPCS Task Group Meeting on Synthetic Organic Fibers, London, England, September, 1992. Panel Member, WHO European Programme for Occupational HcaLth, "Validity of Methods for Assessing the Carcinogenicity of Man-Made Fibers", Copenhagen, Denmark, 1992 Chairman, EPA-FIFRA Scientific Advisory Panel, 1993Member, EPA Science Advisory? Board Executive Committee, 1993-1999 48 Panel Member, EPA Science Advisory Board, Dioxin Review Committee (Health Panel), 1995 Panel Member/Rapporateur, IPCS/MARK Task Group Meeting on Phosgene, London, England, March, 1996. Panel Member,, IPCS/MARK Task Group Meeting on Chloroethers, London, England, March, 1996. Panel Member, National Research Council, Commission on Life Sciences, Subcommittee on "Toxicological and Performance Aspects of Oxygenated Motor Vehicle Fuels", 1996 Panel Member, EPA Scientific Advisory Board, Committee on Environmental Health, Ad Hoc member for Neurtoxicology Guidelines; Chair - Thyroid Carcinogenesis Guidelines, 1996 Panel Member, EPA Food Quality Protection Act Advisory Board, 1996 Member, ILSI Risk Science Institute Working Group on Dose Selection, 1996 Panel Member, EPA Science Advisory Board, EPA Proposed Guidelines for Carcinogenic Risk Assessment, 1997 Panel Member,, 1PCS Workshop on Issues in Cancer Risk Assessment. Hannover, Germany, January 1998 and January, 1999. CoChair, EPA SAB/SAP Joint Meeting `Testing of Pesticides in Human Subjects', Dec 1998 and Nov 1999. CoChair, EPA SAB/SAP Joint Meeting `Endocrine D isrupters', March 1999. Panel Member, National Research Council, Commission on Life Sciences, Subcommittee on "Review of the US Navy's Exposure Limits for Manufactured Vitreous Fibers", 1999-2000. Invited Expert Testimony on Trichloroethylene, Australian Solicitor General, Melbourne, Australia, Nov. 1999. Panel Member, International Conference of the World Health Organization. "Advancing Knowledge on Regulating Tobacco Products", Oslo, Norway, February, 2000. Moderator, 2000 Society of Toxicology "Issue" Session, "The Value and Ethics of Using Human Data for the Registration of Pesticides", Philadelphia, PA, March 2000. Chair, Review of the Toxicology Program, Lovelace Respiratory7Research Institute, Albequerquc, NM, April 2001. Rappatour, ILSI Agricultural Chemical Safety Assessment, Workgroup #1, April, 2001. Session Chair, Risk Assessment Methods, "2001 Asbestos Health Effects Conference", Oakland, CA, May 2001. Member, Lovelace Respiratory7Research Institute's "Research Programs Oversight Committee', 2002Member, ATSDR Expert Panel on Health Effects of Asbestos and Synthetic Fibers (SVF: The influence of Fiber Length. New York, NY. 29-30 October 2002. Testimony before NRC/NAS Committee on the Use of Third Party Toxicity Research with Human Research Participants. Washington, DC. 19 March 2003. Member, International Symposium on the Health Hazard Evaluation of Fibrous Particles Associated with Taconite and the Adjacent Duluth Complex. Member, EPA Asbestos Mechanisms of Toxicity Workshop, Chicago, IL. 12-13 June 2003. Chair, Subcommittee on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminents. National Academy of Sciences. 2003-2005. Member, ILSI HESI Technical Committee on Agricultural Cemical Safety Assessment. 2003-2004. Editorial Boards: 49 Medical Research Council of Canada, 1982-1984 Enviromnenral Health Perspectives, 1983-1990 Drug and Chemical Toxicology, 198CM994 Fundament al and Applied Toxicology, 1989-1995 Inhalation Toxicology, 1995- Revicwer: Science Annals of Occupational Hygiene Toxicological Sciences Papers Published: 1. McConnell, E.E.: Case for diagnosis. Yaba monkey virus. Military Medicine 132:838, 8G9, 1967. 2. McConnell, E.E.: Gamer, F.M. and Kirk, J.H.: Hartmanellosis in a bull. Pathologia Veterinaria 5:1-6. 1968. 3. McConnell, E.E., Cashell, I.G. and Garner, F.M.: Visceral leishmaniasis with ocular involvement in a dog. TAVMA 156:197-203, 1970. 4. McConnell, E.E., Van Rensburg, I.B.J. and Van Wyk, J.A.: A case of adenocarcinoma of the olfactory mucosa of a sheep of possible infectious origin. T.S. African Vet, Med. Assoc. 41:9-12, 1970. 5. Van Rensburg, I.BJ., Roos, C.J. and McConnell, E.E.: Diverficulosis in a cow. T.S. African Vet. Med. Assoc. 41:76, J970. 6. Bosnian, P.P., McConnell, E.E. and Schutte, A.P.: Bovine abortion caused by Aspergillus sp. T.S. African Vet. Med. Assoc. 41:134, 1970. 7. McConnell, E.E. and Tustin, R.C: Pancreatic calculi in a cow. T.S. African Vet. Med. Assoc. 41:352, 1970. 8. McConnell, E.E., DcVos, AJ., Basson, P.A. and dcVos, V.: Isopora papionis n. sp. (Eimcriidac) of the Chaana baboon Papio ursinus {Kerr, 1972). 1, Protozool. 18:28-32, 1971. 9. McConnell, E.E., Van Rensburg, I.B.J. and Minne, J.A.: A rapid test for the diagnosis of strychnine poisoning. T.S. African Vet. Med. Assoc. 42:81-84, 1971. 10. McConnell, E.E.: Foot and m outh disease in South Africa - Report of the 1969 outbreak. AF Med. Scrv, Digest 22:29-34, 1971. 11. McConnell, E.E., Smit, J.D. and Venter, H.J.: Melanoma in the larynx of a dog. T.S. African Vet. Med. Assoc. 42:1.89-191, 1971. 12. Schutte, A.P., McConnell, E.E. and Bosnian, P.P.: Vibrionic abortion in ewes in South Africa: Preliminary report. T.S. African Vet. Med. Assoc. 42(3):223-226, 1971. 13. McConnell, E.E., Basson P.A. and Finaar, J.G.: Pneumocystosis in a domestic goat. Onderstenoort I. Vet. Res. 38(2):117-12tt, 1971. 50 14. Coffee, G.M., Van Aswegen, PJ.M., McConnell, E.E. and Basson, P.A.: Description of a new nasal mite (Acaria: Halorachnidae) and a new record from the Chacina baboon. Zeitschrift Fur Ansewandte Zoologic 58(21:185-190, 1971. 15. McConnell, E.E., Basson, P.A. and deVos, V.: Nasal acariasis in the Chacma baboon (Papio ursinus, Kerr, 1972). Onderstepoort T. Vet. Res. 58:207-214,1971. 16. Coffee, G.M. and McConnell, E.E.: Pneumonyssus vocalis n. sp. (Acaria: Halarachnidae) a new mite from the laryngeal ventricles of the Chacma baboon (Papio ursinus, Kerr). Zeitschrift Fur angowandte Zooloirie 58:265-270, 1971. 17. Bartsch, R.C., Wessells, B.C. and McConnell, E.E.: Myocardial tuberculoma in a Chacma baboon (Papio ursinus, Kerr, 1972). Lab Animals 6:41-47.1972. 18. McConnell, E.E., Basson, P.A. and deVos, V.: Laryngeal acariasis in the Chacma baboon. TAVMA 161: 678-682, 1972. 19. McConnell, E.E., Tustin, R.C. and deVos, V.: Anthrax in an African buffalo (Syncerus caffcr) in the Kruger National Park. LS. African. Vet. Med. Assoc. 43:181-187,1972. 20. McConnell, E.E., Basson, P.A., Thomas, S.E. and deVos, V.: Oocysts of Isospora Papionis in the skeletal muscles of chacma baboons. Onderstepoort T. Vet, Res. 39:113-110, 1972. 21. McConnell, E.E., Basson, P.A., Wolstenhobne, B., deVos, V. and Malherbe, H.: toxoplasmosis in "free-ranging" Chacma baboons (Papio ursinus) from the Kruger National Park. Trans. R. Soc. Trop. Med, Hyg. 67:851-855, 1973. 22. deVos, V., van Kiekert, C.A.W.J. and McConnell, E.E.: A survey of selected bacteriological infections of the Chacma baboon (Papio ursinus) from the Kruger National Park. Koedoe 10:1-10, 1973. 23. McConnell, E.E.: Lesions found in animals exposed to coal tar aerosols. Proceedings of 4th Annual Conference on Environmental Toxicology. (AMRL-TR-73-1251:189-198. 1973. 24. McConnell, E.E., Basson, P.A., deVos, V,, Myers, BJ. and Kuntz, R.E.: A survey of diseases among 100 free-ranging baboons (Papio ursinus) from the Kruger National Park. Onderstepoort I. Vet. Res. 41:97-168, 1974. 25. MacEwcn, J.D., McConnell, E.E. and Back, K.C.: The effects of 6-month chronic low level inhalation exposures to hydrazine on animals. Proceedings 5th Annual Conference on Environmental Toxicology. AMRL-TR-74-12 5:225-235. 1974. 26. H am s, A.M., Horton, M.L., Lei scher, R.M., McConnell, E.E. and New, A.E.: Enzootic Brucella cards - an occult disease in a research canine colony. Lab. Lab. Anim. Sei. 24:769-799,1974. 27. Stuart, D.D., Buck, G.E. and McConnell, E.E.: Necrotic dermatitis of mice caused by Lancefield Group G. Streptococci. Lab. Anim. Sei. 25:296-302, 1975. 28. McNutt, N.S., Amstcr, R.L., McConnell, E.E. and Morris, F.: Hepatic pathology in mice after continuous inhalation exposure to 1,1 .l-trithloroethylene. Lab. Invest. 32:642-654, AMRL-TR-74-60,1975. 51 29. Thigpen, J.E., Faith, R.E., McConnell, E.E. and Moore, J.A.: Increased susceptibility to bacterial infection as a sequela of exposure to 2,:L7,8-rctrachlorodibenZd-p-dioxin. Infect. Innnun 12:1319-1324, 1975. 30. McConnell, E.E. and Talley, F.A.: Intracytoplasinic hyaline globules in the adrenal medulla of laboratory animals. Vet, Path. 14:435-440,1977. 31. McConnell, E.E.: Parasitic diseases observed in free-ranging and captive baboons. Comp. Path. Bull. 9(3):3, 1977. 32. McConnell, E.E., Moore, J.A. and Dalgard, D.W.: Toxicity of 2,3,7,8-tctrachlorodibenzo-p-dioxm (TCDD) in rhesus monkeys (Macaca mulatta) following a single oral dose. Toxicol. ApdL Pharmacol 43:175-187, 1978. 33. Hass, J.R., McConnell, E.E. and Harvan, D.J.: Chemical and toxicologic evaluation of Fircmaster BP-6: a preliminary report, i. Acr. Food Chem. 26:94-99. 1978. 34. McConnell, E.E., Moore, J.A., Haseman, J.K. and Harris, M.W.: The comparative toxicity of chlorinated dibenzo-p-dioxins in mice and guinea pigs. Toxic. AdpI. Pharmacol. 44:335-356, 1978. 35. McConnell, E.E., Hass J.R., Altman, N.H. and Moore, J.A.: A spontaneous outbreak of polychlorinated biphenyl (PCB) toxicity in rhesus monkeys (Macaca mulatta): toxicopathology. Lab. Anim. Sd. 29(5):666-673, 1979. 36. Altman, N.H., New, A.E., McConnell, E.E. and Ferrell, T.L.: A spontaneous outbreak of polychlorinated biphenyl (PCB) toxicity in rhesus monkeys (Macaca mulatta): clinical observations. Lab. Anim. Sci. 29(5):661-G65, 1979. 37. McConnell, E.E., Wilson, R. and Moore, J.A.: Dose response of 1,2-diniethylhydrazine and methylazoxymethanol acetate in the F344 rat. Cancer Letters 8:271-278,1980. 38. Van Logtcn, M.J., Gupta, B.N., McConnell, E.E. and Moore, J.A.: Role of endocrine system in the action of 2,3,7,8-tetrachlorodibenzo-p-dioxm on the thymus. Toxicology15:135-144, 1980. 39. Fowler, B.A., Kimmel, C.A., Woods, J.S., McConnell, E.E. and Grant, L.D.: Chronic low-level lead toxicity in the rat. HI. An integrated approach to the assessment of long-term lead toxicity. Toxicol Annl. Pharmacol. 56:59-77, 1980. 40. McConnell, E.E., Moore, J.A., Gupta, B.N., Rakes, A.J., Luster, ML, Goldstein, J.A., Haseman, J.K. and Parker, C.E.: The chronic toxicity of technical and analytical pentachlorophenol in cattle. I. Clinicopathology. Toxicol. A nnl Pharmacol. 52:468-490, 1980. 41. Parker, C.E., Jones, W.A., Matthews, H.B., McConnell, E.E. and Hass, J.R. The chronic toxicity of technical and analytical pentachlorophenol in cattle. I. Toxicol. A nnl Pharmacol 55:359-369, 1980. 42. McRec., D.I., Faith, R. and McConnell, E.E.: Effects of long-term 2450 MH2 microwave radiation on rabbits. T. Microwave Power 15(l):45-52,1980. 43. McConnell, F..E., Harris, M.W. and Moore, J.A.: The lack of effectiveness of activated charcoal and cholestyramine in reducing the body burden of polybrominated biphenyls. Drug Chem. Tox. 3(3):277-292, 1980. 52 44. Schiller, c.M., Curley, W.H. and McConnell, E.E.: Induction of colon rumors by a single oral dose of 1,2-dimethylhydr azinc. Cancer Letters 11:75-79, 1980. 45. Bimbaum, L.D., Decad, G.M., Matthews, H.B. and McConnell, E.E.: Fate of 2,3,7,R-retrachlorodihenzofuran in the monkey. Toxicol. Annl. Pharmacol. 57:189-196, 1981. 46. Gupm, B.N., McConnell, E.E., Harris, M.W. and Moore, J.A.: Polybrominated biphenyl toxicosis in the rat and mouse. Toxicol. Annl. Pharmacol. 57:99-118, 1981. 47. Lamb, J.C., Marks, T.A., McComiell, E.E., Abcywickrama, K. and Moore, J.A.: Toxicity of chlorinated phenoxy acids in combination with 2,3,7,8-TCDD in C57BL/6 male mice. I. Tox. En\iron. Hlth. 8:815-824, 1981. 48. Van Logten, M.J., Gupta, B.N., McConnell, E.E. and Moore, J.A.: The influence of m alnutrition on the toxicity of 2,3,7,8-tctrachlorodibenzo-p- dioxin (TCDD) in rats. Toxicology 21:77-88,1981. 49. Dunnick, J.K., Prejean, J.D., Haseman, J.IC., Thompson, R.B., Giles, H.D. and McConnell, E.E.: Carcinogenesis bioassay of ally! isothiocyanatc. Fund. Annl. Toxicol. 2:114-120,1981. 50. McConnell, E.E.: NTP Technical report on the carcinogenesis bio assay of amosite asbestos in Syrian golden hamsters. NTP Technical Report No. 249, NIH Publication No. 84-2050, 1983. 51. Rluwc, W.M., McConnell, E.E., Huff, J.F.., Haseman, J.K., Douglas, J.F. and Moore, J.A.: Carcinogenicity testing of phthalate esters and related compounds by the NTP. Environ. Health Persn. 45:129-132,1982. 52. Feldman, D.B., McConnell, E.E. and Knapka, J.J.: Growth kidney disease and longevity of Syrian golden hamsters (Mcsocricetus auratus) fed varying levels of protein. Lab. Animal Sci. 32(6):613-618,1982. 53. Drew, R.T., Boorman, C.A., Haseman, jX , McConnell, E.E., Buscy, W. and Moore, J.A.: The effect of age and exposure duration on cancer induction by a known carcinogen in rats, mice and ham sters. Toxicol. Apnl. Pharmacol. 68:120-130, 1983. 54. Gupta, B.N., McConnell, E.E., Goldstein, J.A., Harris, M.W. and Moore, J.A.: Effects of a polybrominated biphenyl mixture in the rat and mouse. I. Six-month exposure. Toxicol. Ap p L Pharmacol. 68:1-18,1983. 55. Gupta, B.N., McConnell, E.E., Moore, J.A. and Haseman, J.K.: Effects of a polybrominated biphenyl mixture in the rat and mouse. II. Lifetime study. Toxicol. A nnl Pharmacol. 68:18-35, 1983. 56. McConnell, E.E.: Pathology' requirements in rodent carcinogenesis studies. I. A review of current procedures. Toxicol. Pathol. ll(l):60-64, 1983. 57. McConnell, E.E.: Pathology requirements in rodent carcinogenesis studies, n. Alternative approach. Toxicol. Pathol. ll(l):65-76, 1983. 58. McConnell, E.E.: NTP Technical report on the carcinogenesis bioassay of chrysotilc asbestos in Syrian golden hamsters. NTP Teclinical Report 249, 1983. 59. McConnell, E.E., Rutter, H.A., Ulland, B.M. and Moore, J.A.: Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats. Envrion. Health Persn.. 53:27-44, 1983. 60. McConnell, E.E., Shefner, A.M., Rust, J.H. and Moore, J.A.: Chronic effects of dietary exposure to amosite and chrysolite asbestos in Syrian golden hamsters. Environ. Health Persia.. 53:11-25,1983. 53 61. Sollcvdd, H.A., Hascman, J.K. and McConnell, E.E.: The natural histoiy of body weight gain, survival and neoplasia in the Fischer 344/N rat. T. Natl. Cancer Inst., 72(4):929-940,1984. 62. McKinney, J.D., Chae, IC., McConnell, E.E. and Bimbaum, L.S.: Stnictm*e-induction versus structure-toxicity relationsliips for polychlorinated biphenyls and related aromatic hydrocarbons. Environ. Health Fersp. 1984. G3. Sollcveld, FLA. and McConnell, E.E.: The significance of interim sacrifice and lifespan data in experimental oncogenesis. Toxicol. Pathol 72:929-940, 1984. 64. McConnell, E.E., Luder, G.W., Rmnbaugh, R.C., Albro, P.W., Harvan, D.J., Hass, j.R. and Harris, M.W.: Dioxin in soil: Bioavailability after ingestion by rats and guinea pigs. Science 223:1077-1079, 1984. 63. Dunnick, J.K., Davis, W.E., Jorgenson, T.A., Rosen, V.J. and McConnell, E.E.: Subchronic toxicity in rats administered oral 8-methoxypsoralen. Natl. Cancer Inst. Monocr. 66:91-95,1984. 66. Hascman, J.K., Crawford, D.D., Huff, J.E., Boorman, G.A., and McConnell, E.E.: Results from 86 Two-year Carcinogenicity Studies Conducted at the National Toxicology Program. T. Tox. Environ. Health 14:621-639, 1984. 67. Huff, J.E., Bates, R., Eustis, S., Hascman, J.D., and McConnell, E.E.: Malathion and Malaoxon: Histopathology Re-examination of the National Cancer Institute's Carcinogenesis Studies. Environ. Res. 37:154-173, 1985. 68. McConnell, E.E.: Comparative Toxicity of PCB's and Related Compounds in Various Species of Animals. Environ. Health Fersp.. 60:29-33, 1985. 69. Huff, J.D., McConnell, E.E., and Hascman, J.K.: Letter to the Editor on the Proportion of Positive Results in Carcinogenicity Studies in Animals. Environmental Mutagenesis 7:427-428, 1985. 70. Sollevcld, H.A., and McConnell, E.E.: The Value and Significance of Life Span and Scheduled Termination Data in Long-term Toxicity and Carcinogenesis Studies. Tox. Path. 13:128-134,1985. 71. Hascman, J.K., Huff, J.E., Rao, G.R, Arnold, J.E., Boorman, G.A., and McConnell, E.E.: Neoplasms Observed in Untreated and Com Oil Gavagc Control Groups of F344/N Rats and B6C3F1 Mice, T. Natl. Cancer Institute 75(51:975-984. 1985. 72. McConnell, E.E.: Toxicology and Carcinogenesis Studies of Chrysotilc Asbestos in F344/N Rats (Feed Studies). NTP Technical Report No. 295, 1985. 73. McConnell, E.E., Sollcveld, H.A. and Boorman, G.A.: Guidelines for Combining Neoplasms as Evidence of Carcinogenicity- in Long-term Toxicity and Carcinogenesis Studies. T. Natl. Cancer Institute 76(2):283-289, 1986. 74. Maronpot, R.R., Montgomery Jr., C.A., Boorman, G.A., McConnell, E.E.: National Toxicology Program Nomenclature for Hepatoprolifcrativc Lesions of Rats. Tox. Path. 14:263-273, 1986. 75. Hascman, J.K., Harrington, E.C., Huff, J.E., McConnell, F..E.: Comparison of Sitc-Spccific and Overall Tumor Incidence Analyses for 81 Recent National Toxicology Program Carcinogenicity Studies. Regulatory7 Toxicol. Pharmacol 6:155-170. 1986. 54 76. McConnell, E.E., Bucher, J.R., Schweiz, B.A., Gupta, B.N., Shelby, M.D., Luster, M., Brody, A.R., Boorman, G.A., Richter, C.: The Toxicity of Methyl Isocyanate. Environ. Science Technol.. 21:188-193, 1986. 77. McConnell, E.E.: NTP Teclmical report on the carcinogenesis bioassay of diglycidyl resorcinol ether in Fischer 344/N rats and B6C3F1 mice (gavage study). NTP Technical Report No. 257,1986. 78. Bucher, J.R., Schweiz, B.A., Shelby, M.D., McConnell, E.E.: Introduction to the Proceedings of the Toxicity of Methyl Isocyanate Conference. Environ. Health Pcrsn. 72:3,1987. 79. McConnell, E.E., ct al. (Prepared by a Working Group for the DHHS Committee to Coordinate Environmental and Related Programs, Subcommittee on Risk Assessment): Report on Cancer Risks Associated with the Ingestion of Asbestos. Environ. Health Pcrsn. 72:253-265, 1987. 80. McConnell, E.E.: Letter to the Editor on Cancer Phobia. Science 238:59-60, 1987. 81. Haseman, JJC, Huff, J.E., Zcigcr, E., McConnell, E.E.: Comparative Results of 327 Chemical Cardiiogenicity Studies. Environ. Health Fersp. 74:229-235, 1987. 82. Huff, J.E., McConnell, E.E., Haseman, J.K., Boorman, G.A., Eustis, S.L., Schwctz, B.A., Rao, G.N., Jameson, W., Hart, L.G., Rail, D.P.: Carcinogenesis Studies: Results of 398 experiments on 104 chemicals from the U.S. National Toxicology Program, in Living in a Chemical World. Aunal N.Y. Acad. Sci. 534:1-30,1988. 83. Hoel, D.G., Haseman, J.K., Hogan, M.D., Huff, J., McConnell, E.E.: The impact of toxicity on carcinogenicity studies: implications for lisk assessment. Carcinogenesis 9:2045-2052, 1988. 84. McConnell, E.E.: NTP Technical report on the carcinogenesis bioassay of crocidolite asbestos in Fischer 344/N rats (feed study). NTP Technical Report No. 335, 1988. 85. Mclnick, R.L., Huff, J.E., Haseman, J.K., McConnell, E.E.: Chronic toxicity results and ongoing studies of 1,3-Butadiene by the National Toxicology Program. Ann. N.Y. Acad. Sciences 534:648-662, 1988. 86. McConnell, E.E.: The maximum tolerated dose: The debate. T. Am. Coll. Toxicol.. 6:1115-1120,1989. 87. McConnell, E.E.: NTP Technical report on the carcinogenesis bioassay of trem olitc in Fischer 344/N rats (feed study). NTP Teclmical Report No. 277, March 1990. 88. Murthy, A.SX, McConnell, EE., Huff, J.E., Russfield, A.B. and Good, A.E.: Forestomach neoplasms in Fischer F344/n in rats and R6C3F1 mice exposed to diglycidyl resorcinol ether - An epoxy resin. Food Chem. Toxic.. 28:723-729, 1990. 89. McConnell, E.E.: NTP Technical Report on the carcinogenesis bioassay of chrysotilc asbestos in Syrian golden ham sters (feed study). NTP Technical Report No. 246, July 1990. 90. McConnell, E.E.: NTP Teclmical report on the carcinogenesis bio assay of amosite asbestos in Fischer 344/N rats (feed study). NTP Technical Report No. 279, November 1990. 91. McConnell, E.E., Hall, L. and Adkins, B.A.: Studies on the toxicity (inhalation) of wollastonite in Fischer 344 rats. Inhalation Toxicol.. 3:323-337, 1991. 92. McConnell, E.E.: NTP Carcinogens - Intrerprerational Problems. Environ. M utagenesis. 248:233-237, 1991. 55 93. McConnell, EE, Huff, J.E., Hejtmancik, M., Peters, A.C. and Parsing, R.: Toxicology and carcinogenesis studies of two grades of pentachlorophcnol inB6C3FI mice. Fund. Ap p I. Toxicol.. 17:519-532, 1991. 94. Ibraliim, M.A., Bond, G.G., Burke, T.A., Cole, PMDost, F.N., Enterline, P.E., Gougli, M. Greenberg, R.S., Halperin, W.E., McConnell, E.E., Munro, I.C., Swcnberg, J.A., Zahm, S.H. and Graham, J.: Weight of the evidence on the human carcinogenicity of 2,4-D. Environ. Health Pcrsn.. 96:213-222, 1991. 95. McConnell, E.E.: Thyroid follicular cell carcinogenesis: Results from 343 two-year carcinogenicity studies conducted by the NCI/NTP. Reg. Toxicol. Phami- 16:177-188,1992. 96. Hesterberg, T.W., McConnell, E.E., Miller, W.C., Hamilton, R. and Bunn, W.B. Pulmonary toxicity of inhaled polypropylene fibers in rats. Fund. Ann!. Toxicol.. 19:358-366, 1992. 97. Hesterberg, T.W., Muller, W.C., McConnell, E.E., Chevalier, J., Hadley, J., Bernstein, D.M., Thevenaz, P. and Anderson, R. Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats. Fund. Ap p I. Toxicol.. 20:464-476,1993. 98. McConnell, E.E. and Swcnberg, J.A. Styrene and styrene oxide: Results of studies on carcinogenicity in experimental animals. In Butadiene and Styrene: Assessment of Health Hazards, IARC Scientific Publications, Vol. 127: 323-333,1993. 99. McConnell, E.E. and Eustis, S.A. Peer review in carcinogenicity bioassays - Uses/abuses. Toxicologic Pathology. 22:141-144, 1994. 100. Lucas Luijckx, N.B., Rao, G.N., McConnell, E.E., Wurtzcn, G. and Kroes, R The intake of chemicals related to age in long-term toxicity studies - Considerations for lisk assessment. Reg. Toxicol. Phannocol.. 20:96-104, 1994. 101. McConnell, E.E. Kanistrup, O., Mussehnan, R., Hesterberg, T.W., Chevalier, J., Mller, W.C. and Thevenaz, P. Chronic inhalation study of size-separated rock and slag wool insulation fibers in Fischer 344/N rats. Inhalation Toxicol.. 6:571-614, 1994. 102. Hesterberg, T.W., Mller, W. C., Mast, R., McConnell, E.E., Bernstein, D.M. and Anderson, R. Relationship between lung biospersistcncc and biological effects of man-made vitreous fibers after chronic inhalation in rats. Environ. Hlth. Persia,. 102:133-137. 1994. 103. McConnell, E.E. Synthetic vitreous fibers - Inhalation studies. Reg. Toxicol. PhannocoL. 20 (2):S22S 3 4 ,1994. 104. Mast, R.W., Hesterberg, T.W., Glass, L.R., McConnell, E.E., .Anderson, R. and Bernstein, D.M. Chronic inhalation and biopersist en ce of refract oit ceramic fiber in rats and hamsters. Environ. Health Perso.. 102:207-210, 1994. 105. McConnell, E.E. Historical review of the rodent bioassay and future directions. Reg. Toxicol. Phannocol.. 21:38-43, 1995. 106. McConnell, E.E., Mast, R.W., Hesterberg, T.W., Chevalier, j., Kotin, P., Bernstein, D.M., Thevenaz, P., Glass, L.R. and Anderson, R. Chronic inhalation toxicity of a kaolin based refractory ceramic fiber (RCF) in Syrian golden hamsters. Inhalation Toxicol. 7:503-532, 1995. 56 107. Mast, R.W., McConnell, E.E., Anderson, R., Chavalier, J., Kotin, PMBernstein, D.M., Thevenaz, P., Glass, L. R., Mller, W.C. and Hesterberg, T.W. Studies on the chronic toxicity (inhalation) of four types of refractory ceramic fiber in male Fischer 344 rats. Inhalation Toxicol. 7:425-467,1995. 108. Mast, R.W., McConnell, E.E., Hesterberg, T.W., Chevalier, J., ICotin, P., Thevenax, P., Bernstein, D.M., Glass, L.R., Mller, W. and .Anderson, R. A multiple dose chronic inhalation toxicity study of size-separated kaolin refractory ceramic fiber (RCF) in male Fischer 344 rats. Inhalation Toxicol. 7:469-502, 1995. 109. McConnell, E.E. Advantages and limitations of in vivo screening tests. Ann. Occun. Hvg. 39:727-735, 1995. 110. McConnell, E.E. Fibrogcnic effect of wollastonitc compared with asbestos dust and dusts containing quartz. Occiip. Environ. Med.. 52:621-624, 1995. 111. McConnell, E.E. The maximum tolerated dose hi particulate inhalation studies: A pathologist's point of view. Inhalation Toxicol.. 8 (Suppl):ll L-123, 1996. 112. McConnell, E.E., Hesterberg, T.W., Chevalier, J., Thevenaz, P., Kotin, P., Mast, R., Musselman, R., Kamstrup, O., and Hadley, J. Results of life-time inhalation studies of glass, mineral and slag wools and refractory ceramic fibers in rodents, f. Occupt. Health Safety: Australia and New Zealand. 12:327-332, 1996. 113. Hesterberg, T.W., McConnell, E.E., Mller, W.C., Chevalier, J., Everitt, J., Thevenaz, P., Fleissner, H. and Obcrdorster, G. Use of lung toxicity and lung particle clearance to estimate the maximum tolerated dose (MTD) for a fiber glass chronic inhalation study in the rat. Fund. Appl. Toxicol. 32:31-44,1996. 114. Hesterberg, T.W., xten, C, McConnell, E.E., Oberdorster, G., Everitt, J., Mller, W., Chevalier, JMJ., Chase, G.R., and Thevenaz, P. Chronic inhalation study of fiberglass and amosite asbestos in the Syrian golden hamster: Twelve m onth preliminary? results. Sixth International Conference on Natural and Man made Fibrous and Non-fibrous particles, Lake Placid, N.Y. 15-19 Sept 1996. Environ. Health Pcrsn. 105:1223-12290, 1997. 115. Mayes, B.A., McConnell, E.E., Neal, B.H., Brunner, J.J., Hamilton, S.B., SuHivan.T.M., Perters, A.C., Ryan, M. J., Toft, J.D., Singer, A.W., Brown, J.F. Jr., Menton, R.B. and Moore, J.A. Comparative Cardnogenicity in Spraguc-Dawley Rats of the Polychlorinated Biphenyl Mixtures Arodors 1016,1242,1254 and 1260. Toxicol. Sri. 41:62-76, 1998. 116. Hesterberg, T.W., McConnell, E.E., Mller, W.C., Chevalier, J., Everitt, J., Thevenaz, P., Fleissner, H. and Oberdorster, G. Use of lung toxicity and lung particle clearance to cstknate the maximum tolerated dose (MTD) for a fiber glass chronic inhalation study in the rat. Fund. Appl. Toxicol. 32:31-44,1996. 117. Hesterberg, T.W., xten, C., McConnell, E.E., Harr, G.A., Mller, W., Chevalier, J., Everitt, j., Thevenaz, P. and Oberdorster, G. Studies on the inhalation toxicology of tw7o fiberglasses and amosite asbestos in the Syrian golden hamster. Part 1. Results of a subchronic study and dose selection for a chronic study. Inhal. Toxicol. 11:747-784, 1999. 118. McConnell, E.E., xten, C., Hesterberg, T.W., Chevalier, J., Mller, W., Everitt, J., Oberdorster, G., Chase, G.R., Thevenaz and Kotin, P. Studies on the inhalation toxicology* of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part 2. Results of chronic exposure. Inhnb Toxicol. 11:785-836, 1999. 57 119. McConnell, E.E. and Carbone, M. A comparison of pleural mesotheliomas induced by asbestos and SV40 virus in Syrian golden hamsters. Inhalation Toxicol. 12:173-181, 2000. 120. McConnell, E.E. A science-based paradigm for the classification of synthetic vitreons fibers. Reg. Toxicol. Pharmacol. 32: 14-21, 2000. 121. Mast, R.W., Yu, C.P., Obcrdorstcr, G., McConnell, E.E., and Utell, M.J, A retrospective review of the carcinogenicity of regractory ceramic fiber in two chronic Fischer 344 rat inhalation studies: An assessment of the MTD and implications for risk assessment. Inhalation Toxicol. 12:1141-1172, 2000. 122. Freeman, G.B., Singer, A.W., Lordo, R.A., Peters, A.C., Neal, B.H., McConnell, E.E., and Mayes, B.A. Chronic Neurotoxicity of A rodor Mixtures Administered in Diet to Spraguc-Dawley Rats. Fund. Anpl. Toxicol. 53:377-391, 2000. 123. Ramstrup, O., Ellenhauge, A., Chevalier, J., Davis, J.M.G. McConnell, E.E and Thevena z, P. Chronic inhalation studies of two types of stone wool fibers in rats. Inhalation Toxicol. 13:603-622, 2001. 124. Maxim, L.D. and McConnell, E.E. Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: A weighr-of-thc-evidc.nce approach. Reg. Toxicol. Pharmacol. 33:1-24, 2001. , 125. McConnell, E.E. The value of human testing of pesticides. Human and Ecological Risk Assess. 7:15751581,2001. 126. McConnell, E.E. and J.M.G. Davis. Quantification of fibrosis in the lungs of rats using a morphometric method. Inhalation Toxicol. 14:101-110, 2002. Papers in Preparation/Sub-mitied/Accepted/In Press: Gray, G.M., Cohenj J.T., Cunha, G., Hughes, C., McConnell, E.E., Rhomber, L., Sipes, I.G. and Mattison, D. Weight of the evidence evaluation of low-dose reproductive and developmental effects of Bisphenol A. Book Chanters. Published Symposia, Reviews: 1. McConnell, E.E.: A study of 70 canine hem angiosarcomas recorded at Michigan State University from 1950-1965 {Thesis - 1965). 2. McConnell, E.E.: Yaba virus tumors. National Cancer Institute Monograph 32:239-224,1969. 3. Diamond, S.S. and McConnell, E.E. Veterinary pathology in toxicology research. AE Med. Svc. Dig. 7:36-37, 1973. 4. Bartsch, R.C., McConnell, E.E., lines, G.D. and Schmidt, J.M.: A review of exertional rhabdomyolysis in wild and domestic animals and man. Vet. Pathol. 14:314-324, 1977. 5. McConnell, E.E. and Moore, J.A.: The toxicopathology of TCDD. In: F. Cattabeni (ed.) Proc. Workshop on TCDD. Milano, Italy, October 1976, Chapter 13, pp. 137-141. Spectrum Publications, Holliswood, NY, 1978. 6. McConnell, E.E. and Moore, J.A.: Toxicopathology characteristics of the halogenated aromatics. Ann. NY Acad. Sci. 320:138-150, 1979. 58 7. Moore, J.A., McConnell, E.E., Dalgard, D.W. and Hams, M.W.: Comparative toxicity of halogcnated dibenzofurans. Ann. Nv Acad. Sri. 320:151-103. 1979. 8. McConnell, E.E.: Acute and chronic toxicity, carcinogenesis, reproduction, teratogenesis and mutagenesis. In: R. Kimbrough (ed.) Halogcnated Biphenyls. Terphenvls. Naphthalenes. Dibenzodioxins and Related Compounds. Elsevier North Holland, pp. 109-150, 1980. 9. McKinney, J. and McConnell, E.E.: Structural specificity and the dioxin receptor. In: 0. Hutzingcr, R.W. Frei, E. Merian, F. Pocchiari, (eds.) Chlorinated Dioxins and Related Compounds - Impact on the Environment. Pergamon Press, New York, pp. 367-381, 1982. 10. Huff, J.E., Haseman, J.K., McConnell, E.E. and Moore, J.A.: The National Toxicology Program, toxicology data evaluation techniques and the long-term carcinogenesis bioassay. Proceedings of the Symposium on Safety Evaluation of Drugs and Chemicals. Iowa State University, Ames, 1A, June 1981. 11. McConnell, E.E., Wagner, J.C., Skidmore, J.W. and Moore, J.A.: A comparative study of the fibrogcnic and carcinogenic effects of UJCC Canadian chrysotilc B asbestos and glass microfibre (JM 100). hi: Biological Effects of Man-made Mineral Fibres. World Health Organization, 1984, pp. 234-252. 12. McConnell, E.E.: Comparative toxicity of PCBs and related compounds in various species of animals. Proceedings of CCERP Conference on Potential Health Effects of PCBs and Related Persistent Halogcnated Hydrocarbons. National Institute of Environmental Health Sciences and Finland. 1984. 13. McConnell, E.E.: The dinicopathologic changes in various species of animals caused by dibenzo-p-dioxin. In: M. Ramrin (ed.) Dioxins in the Environment. Hemisphere Publishing Corp., pp. 225-230, 1985. 14. McConnell, E.E.: Clinicopathologic Concepts of Dibcnzo-p-dioxin Intoxication, ha: Banbury Report 18: Biological Mechanisms of Dioxin Action, pp 27-37,1984. 15. McConnell, E.E.: Issues Raised by the National Toxicology Program Ad Hoc Panel on Chemical Carcinogenesis Testing and Evaluation. In: Proceedings of 15th Conference on Environmental Toxicology October 30. 31. and November 1. 1984. University of California, Irvine, Wright-Patterson Air Force Base, Ohio, AFAMRL-TR-84-002, pp 136-143, 1985. 16. Boorman, G.A., Montgomery, C.A., Jr., Eustis, S.L., Wolfe, M.J., McConnell, E.E., and Hardisty, J.F.: Quality assurance in pathology for rodent carcinogenicity studies. In: Handbook of Carcinogen Testing (H.A, Milman andE.IC. Weisburger, eds.)t pp. 345-357, 1985. 17. McConnell, E.E.: Quality and the Nat ional Toxicology Program. In: Managing Conduct and Data Quality of Toxicology Studies. Princeton Scientific Publishing Co., Inc., pp 9-12,1986. 18. Mcnncar, j., Maronpot, R., Boorman, G., Eustis, S., Huff, J., Haseman, J., McConnell, E., Ragan, H.f Miller, R.: Toxicologic and Carcinogenic Effects of Inhaled Tetrachlorocthylene in Rats and Mice. Proceedings of the 4th International Congress on Toxicology, In: New Concents and Developments in Toxicology. Elsevier Science Publishers B.V. (Biomedical Division), pp 201-210, 1986. 19. Huff, J.E., Haseman, J.K., McConnell, E.E., and Moore, J.A.: The National Toxicology Program, Toxicology Data Evaluation Techniques, and Long-Term Carcinogenesis Studies. In: Safety Evaluation of Drugs and Chemicals. Llyod, W.E., ed., Hemisphere Publishing Company, Washington, D.C., 487 pages, 1986. 59 20. Lemen, R., Becking, G.C., Cantor, K, Chenier, J.H., Cordle, F., Groth, D., Keller, C., Lybarger, J., McConnell, E.E., Mcinhardt, T,, Millettc, J.R., Patel, Y,, Sonich-mullin, C. and Tollcfson, L. Report on Cancer Risks Associated with the Ingestion of Asbestos. Environ. Health Pcrso. 72:253-265, 1987. 21. Huff, J.E., McConnell, E.E., Haseman, J.K., Boorman, G.A., Eustis, S.L., Schwctz, B.A., Rao, G.N., Jameson, C.W., Hart, L.G., and Rail, D.P.: Carcinogenesis Studies Results of 398 Experiments on 104 Chemicals from the U.S. National Toxicology Program. Proceedings of the Collegium Ramazzini Conference on "Living in a Chemical World." N.Y. Acad. SdL 584: 1-80, 1988. 22. McConnell, EJL: Mouse liver tumors: the problem, hi: Mouse Liver Carcinogenesis: Mechanisms and Species Comparisons. Alan R. Liss, Inc., New York, NY, 1-8, 1990. 23. Swell, M.R. and McConnell, E.E.: Small and large intestine. In: Pathology of the Fischer Rat. Academic Press, New York, NY, 1990. 24. Hesterberg, T.W., Vu, V., McConnell, E.E., Bunn, W.B. and .Anderson, R.: Use of animal models to study man-made fiber carcinogenesis. In: Cellular and Molecular Aspects of Fiber Carcinogenesis, cds. B. Brinkley, J, Ledmer and C. Harris. Banbury Report, 183-205, 1990. 25. Hesterberg, T.W., Mast, R., McConnell, E.E., Chevalier, J., Bernstein, D.M., Bunn, W.B. and Anderson, R. Chronic inhalation toxicity of refractory ceramic fibers in Syrian hamsters. Proceedings of International Workshop on Mechanisms of Fibre Carcinogenesis. .Albuquerque, NM, Oct. 1990. 26. Animals as Sentinels of Environmental Health Hazards. Board on Environmental Studies and Toxicology, National Research Council, National Academy Press, 1991. 27. Bell, R.H., Feigley, C.E., Gaulden, M.E., Halperin, W., H am s, E., Kiminel, C.A., Kodell, R.L., McConnell, E.E. and Taylor, K.C. Review of the U.S. Army Environmental Hygiene Agency Toxicology Division. Committee on Toxicology, National Research Council, National Academy Press, 1991. 28. Government Accounting Office. Reproductive and Developmental Toxicants: Regulatory Actions Provide Uncertain Protection. GAO/PEMD-92-3, Washington, D.C. October, 1991. 29. McConnell, EJE. Comparative responses in carcinogenesis bioassays as a function of age at first exposure. In: Similarities and Differences Between Children and Adults: Implications for Risk Assessment. Eds. P.S. Guzelian, C.J. Henry- and S.S. Qlin, ILS1 Press, 1992. 80. McConnell, E.E. Ethylene thiourea (ETU): Comparative response in rodent carcinogenesis studies as a function of age at first exposure. In: Similarities and Differences Between Children and Adults: Implications for Risk Assessment. Eds. P.S. Guzelian, CJ. Homy and S.S. Olin, ILSI Press, 1992. 31. Validity of Methods for Assessing the Carcinogenicity of Man-made Fibers. European Programme for Occuapational Health, World Health Organization, Copenhagen, Denmark, May 1992. 32. Hesterberg, T.W., McConnell, E.E., Muller, W.C. Hadleys, J.G., Bernstein, D.M., Mast, R. and Anderson, R. Relationship between lung biopcrsistencc and biological effects of man-made vitreous fibres after chronic inhalation in rodents., Lyon, France, Sept., 1992. 33. Hesterberg, T.W., McConnell, E.E., Muller, W.C., Hadley, J.G., Bernstein, D.M., Bunn, W.B. and Anderson, R. Chronic Inhalation Toxicity of Fibrous Glass in Rats. Proceedings of the Eighth International Conference on Lung Diseases, Prague, Czechoslovakia, Sept. 1992. 60 34. McClellan, R.O., Miller, F.J., Hesterberg, T.W., Warheit, D.B., Bunn, W.B., Kane, A.B., lippm ann, M., Mast, R.W., McConnell, E.F.. and Reinhardt, C.F. Approaches to Evaluating the Toxicity and Carcinogenicity of Man-Made Fibers: Summary of a Workshop Held November 11-13,1991, Durham, North Carolina. Reg. Toxicol. Pharm.. 1(1:321-3(14, 1992. 35. Selected Synthetic Organic Fibres. Environmental Health Criteria #151, International Programme on Chemical Safety, World Health Organization, 1993. 36. McConnell, E.E., Chevalier, H.J., Hesterberg, T.W., Hadley, J.G. and Mast, R.W. Comparison of the effects of chrysotilc and crocidolitc asbestos in rats after inhalation exposure for 24 months, hi: Toxic and Carcinogenic Effects of Solid Particles in the Respiratory Tract. ILSI Press, Washington, DC., 1994. 37. Wagner, B.M., Burt, B.A., Cantor, K.P., Krcwski, D., Levy, S.M., McConnell, E.E., and Whitford, G.M. Health Effects of Ingested Fluoride. Committee on Toxicology, National Research Council, National Academy Press, 1993. 38. Hesterberg, Midler, W.C., McConnell, E.E., Bernstein, D.M., Thevenaz, P. and Anderson, R. Chrome Inhalation Toxicity of Man-made Vitreous Fibers: Relationship to Lung Burden and Lung Retention. In: Toxic and Carcinogenic Effects of Solid Particles in the Respiratory Tract. ILSI Press, Washington, DC., 1994. 39. McConnell, E.E., Greaves, I., Kimmel, C.A., Kodell, R.L., Roller L. Medinsky, M. and Wolven-Garret, A. Health Effects of Pcrmethrin-Imnromated Army Battle-Dress Uniforms. Committee on Toxicology, National Research Council, National Academy Press, 1994. 40. McConnell, E.E. and Sweiibcrg, J.A. Review of Styrene and Styrene Oxide : Long-term Animal Studies. Crit. Rev. Toxicol.24:S49-S55, 1994. 41. McConnell, E.E., Response to theses and questions submitted by Federal Health Office to the invited experts at the hearing on man-made mineral fibres, Berlin 9/10 December 1993. Excerpt in Krcbsgefahrdung durch kunstliche Mineralfascem. (Ed. M. Fisher), pp.63-C5, Bga-Schriften 94,4, MMV, Medizen-Verl., Muchen, Germany. 42. Film, W.F., Hems treet III, G.P., /\llen, B.C., Anderson, R.L., Berndt, W.O., Epstein, F.H., Foulkes, E.C., Fowler, B., Gottschalk, C.W., McConnell, E.E., Noble, B., Parker, J.C. and Porter, G.A. Biologic Markers in Urinary Toxicology. Board on Environmental Studies and Toxicology, National Research Council, National Academy Press, 1995. 43. NRC. Lippmann, M., Chiazzee, L, Coultas, D.B., Driscoll, K.E., Kane, A.B., Lockey, J.E., McConnell, E.E., Oberdorstcr, G., Rhombcrg, L.R., Utell, M., and Warheit, D.B. Report on the Expert Panel on Health Effects of Asbestos and Synthetic Vitreous Fibers: The Influence of Fiber Length. Board on Environmental Studies and Toxicology, National Research Council, National Academy Press, pp. 1-80, 2000. 44. ATSDR. Report of the Expert Panel on Health Effects of Asbestos and Synthetic Vitreous Fibers: The Influence of Fiber Length. ATSDR, Div. Health Assess Consult., Atlanta, GA. March 17, 2003. Book Chanters. Published Symposia. Reviews: (Submitted/in press) Abstracts. Letters to Editor: 61 1. Van Stce, E.W., McConnell, E.E., Patel, J.A. and Hamlin, R.L.: The inhalation toxicity of the refrigerant, chiorodifluoromethane (F-22). Proceedings First International Congress on Toxicology. Academic Press, New York, p. 602, 1978. 2. Khnmei, C.A., Grant, L.D., Fowler, B.A., McConnell, E.E. and Woods, J.S.: An integrated approach to the assessment of chronic lead toxicity. Proceedings First International Congress on Toxicology. Academic Press, New York, p. 572, 1978. 3. McConnell, E.E. and Moore, J.A.: The comparative toxicity of chlorinated dibenzo-p-dioxin isomers in mice, guinea pigs. Toxicol. AupI. Pharmacol. 37:14(1, 1976. 4. McConnell, E.E., Moore, J.A., Harris, M.W. and Ha soman, J.D.: The toxicity of chlorinated dibenzo-p-dioxin in mice and guinea pigs and rhesus monkeys. Environ. Health Persp. 20:245, 1977. 5. Thigpen, J.E., McConnell, E.E., Moore, J.A. and Faith, R.E.: Effects of 2,3,7,8-tetrachlorodibcnzo-p-dioxin (TCDD) on host resistance to infectious agents. Environ. Health Persp. 20:245,1977. 6. McConnell, E.E. and McKiimeyJ.D.: Exquisite toxicity in the guinea pig to structurally similar halogcnatcd dioxins, furans, biphenyls and naphthalenes. Toxicol. Appl. Pharmacol. 45:298, 1978. 7. Moore, J.A., Luster, ML, Gupta, B.N. and McConnell, E.E.: .Toxicological and immunological effects of a commercial polybrominated biphenyl mixture. Toxicol. Annl. Pharmacol. 45:176,1978. 8. McConnell, E.E. and Moore, J.A.: Toxicopethology characteristics of the halogenatcd aromatics. 45th Mecring of the Interagency Collaborative Group on Environmental Carcinogenesis. National Cancer Insti tut.e, May 2 3, 1979, Bethe sda, MD. 9. Boorman, G.A., McConnell,E.E., Cockrell, B.Y., Drew, R.T., Stone, C.J., Haseman, J.K. and Moore, J.A.: The comparative effects of an animals age at time of exposure and exposure duration on vinyl chloride carcinogenesis. Federation of American Societies for Experimental Biology, Anaheim, CA, April 13-18, 1980. 10. McKinney, j.D. and McConnell, E.E.: Structural specificity and the dioxin receptor. Workshop on Impact of Chlorinated Dioxins and Related Compounds on the Environment, Rome, Italy, October 22-24, 1980. 11. McConnell, E.E. and Shoaf, C.R. (1981) Studies of the mechanism of 2,3,7,8-tetradriorodibenzo-p-diioxin (TCDD) toxicity-lipid assimilation. I. Morphology. Pharmacologist. 23:176. 12. McConnell, E.E.: Histopathology workload in carcinogenesis bioassays. How m uch is necessary? The Toxicology Forum, Washington, DC, 1983. 13. McConnell, E.E.: Proliferative lesions of the exocrine pancreas in male F344 rats - the effect of com oil. The Toxicology Forum, Washington, DC, 1983. 14. Sollcvcld, H.A., Haseman, J.K. and McConnell, E.E.: Lifespan on two-year studies for carcinogen testing: An easy choice when using the Fischer 344 rat as a test animal. American College of Veterinary Pathologists, San Antonio, TX, 1983. 15. McConnell, E.E., Harris, M.W., Hamm, D.J., Albro, P.W. and Hass, J.R.: Studies on the bio availability in guinea pigs of dioxin in soil. Society of Toxicology, Atlanta, GA, 1984. 62 16. Solleveld, H.A. and McConnell, E.E.: Time-age associations in experimental oncogenesis. Third International Symposium of the Society of Toxicologic Pathologists, Arlington, VA, 1984. 17. McConnell, E.E.: Quality and the National Toxicology Program. NTP - Industry Joint Conference on Managing Conduct and Data Quality of Toxicology Studies, Raleigh NC, 1985. 18. McConnell, E.E.: Guidelines for Combining Neoplasms for Evaluation of Rodent Carcinogenesis Studies. International Life Sciences Institute Histopathology Seminar, Hanover, Germany, 1985. 19. Adkins Jr., B., McConnell, E.E.: Inhalation Carcinogenesis Study of Wollastonitc in Rats. Second U.S.-Dutch International Symposium: Aerosols, Williamsburg, Virginia, 1985. 20. McConnell, E.E.: Options for Aggregation of Incidence Data. Interdisciplinary Discussion Group on Carcinogenicity Studies, Chapel Hill, North,Carolina, 1986. 21. McConnell, E.E.: Fiber Toxicity: Beyond the Stanton Hypothesis. American Society of Mining Engineers, Phoenix, Arizona, 1988. 22. McConnell, E.E., Hcjtmancik, M., Peters, A.C., Persing, R. Chronic Toxicity of Pentachlorophenol. Ann. Meet., Soc. Toxicol., Atlanta, GA., 1989. 23. Adkins, B., McConnell, E.E., Hall, L. Carcinogenicity Studies of Wollastonite in Rats. Aim. Meet., Soc. Toxicol., Atlanta, GA.P1989. 24. McConnell, E.E., Ha soman, J.A. and Boorman, G.A.: Proliferative Lesions of the Thyroid Gland: A Review of the National Toxicology' Program Data Base. .Ann. Meet., Soc. Toxicol., Maimi, FL., 1990. 25. McConnell, E.E. Comparative Responses in Carcinogenic Bioassay^s as a Function of Age at First Exposure, in Similarities and Differences Between Children and Adults: Implications for Risk Assessment, ILSI/RSI, Hunt Valley, MD, November, 1990. 26. Hesterberg, T.W., Mast, R., McConnell, E.E., Vogel, O., Chevalier, J., Bernstein, D.M. and Anderson, R. Chronic Inhalation Toxicity and Oncogenicity Study of Refractory Ceramic Fibers (RCF) in Fischer 344 Rats. Ann. Meet., Soc. Toxicol., Dallas, TX, 1991 also The Toxicolocist 11:85 (254), 1990. 27. McConnell, E.E., Hesterberg, T.W., Hadley, J.G., Bernstein, D.M. and Mast, R.W. A Comparison of the Effects of Chrysotilc and Croridolitc Asbestos in Rats After Inhalation for 10 Months. Ann. Meet., Soc. Toxicol., Seattle, WA, 1992, also The Toxicolonist 12:90 (274), 1992. 28. Glass, L.R., Mast, R.W., Hesterberg, T.W., Anderson, R. and McConnell, E.E. Inhalation Oncogenicity Study of Refractory' Ceramic Fiber (RCF) in Rats - Final Results. Ann. Meet., Soc. Toxicol., Seattle, WA, 1992, also The Toxicologist 12:377 (1477), 1992. 29. Mast, R.W., McConnell, E.E., Glass, L.R., Hesterberg, T.H., Anderson, R. and Bernstein, D.M. Inhalation Oncogenicity Study of Kaolin Refractory Ceramic Fiber (RC.F) - Final Results. Ann. Meet., Soc. Toxicol., Seattle, WA, 1992, also The Toxicologist 12:377 (1478), 1992. 30. McConnell, E.E., Chevalier, J., Hesterberg, T.W., Hadley, J.G., and Mast, R.W. A Comparison of the Effects of Chrysotilc and Crocidolite Asbestos in Rats after Inhalation, in Toxicologic and Carcinogenic 63 Effects of Solid Particles in the Respiratory Tract. 4th International Inhalation Symposium, Hannover, Germany, 4 March 1993. 31. Hesterberg, T.W., Millier, W.C., McConnell, E.E., Hadley, J.G., Bernstein, DM., Thevenaz, P. and Anderson, R. Chronic Inhalation Toxicity of Fibrous Glass in Rats, in Toxicologic and Carcinogenic Effects of Solid Particles in the Respiratory Tract. 4th International Inhalation Symposium, Hannover, Germany, 3 March 1993. 32. Mast, R.W., Glass, L.R., McConnell, E.E., Hesterberg, T.W., and Anderson, R. Chronic Inhalation, intratracheal and Biopersistcnce Studies of Refractory Ceramic Fibers, in Toxicologic and Carcinogenic Effects of Solid Particles in the Respiratory Tract. 4th International Inhalation Symposium, Hannover, Germany, 3 March 1993. 33. Mast, R.W., McConnell, E.E., Glass, L.R. and Hesterberg, T.W. A Multiple Dose Chronic Inhalation toxicity' Study of Kaolin Refractory Ceramic Fiber (RCF) in Male Fischer 344 Rats. The Toxicologist 13:43 (63), 1993. 34. McConnell, E.E., Hesterberg, T.W., Hadley, J.G., and Mast, R.W. A Comparison of the Effects of Chrysotilc and Crocidolite Asbestos in Rats after inhalation - 24 Month Results. The Toxicologist 13:43 (67)' 1993. 35. Mayes, B.A., Neal, J.H., Peters, A.C., Hamilton, S.B., McConnell, E.E. and Moore, J.A. Chronic Toxicity' of Aroclor Mixtures Administered in the Diet to Spraguc-Dawkcy Rats for Six Months. The Toxicologist 14:371 (1458), 1994. 36. Hadley, J.G., McConnell, E.E. and Johnson, N.F. Fiber Inhalation Studies, Lung Burdens and Biological Responses. The Toxicologist 14:420 (1(365), 1994. 37. McConnell, E.E., Hesterberg, T.W., Hadley, J.G. and Musselman, R. A Comparison of the Effects of Chrysotile and Crocidolite Asbestos in the Lungs of Rats after inhalation. Hie Toxicologist 14:42i (1666), 1994. 38. Mayes, B.A., Neal, BJ-L, Peters, A.C., Hamilton, S.B., McConnell, E.E. and Moore, J.A. Chronic toxicity of Aroclor mixtures administered in the diet to Spraguc-Dawley rats for twelve m onths. The Toxicologies. 1995. 39. McConnell, E.E. Letter to Editor: Cambelova and Juck. Qccup. Environ. Med.. 52:1995- 40. Hesterberg, T.W., McConnell, E.E., Mhller, W.C., Chevalier, J., Everitt, J., Hievenaz, P., Heissner, H., and Obcrdorstcr, G. Estimating the Maximum Tolerated Dose (MTD) for a Fiber Chronic Inhalation Study in Rodents. The Toxicologist. 30:#91, 1996. 41. McConnell, E.E. Commentary on "Fibrous Glass and Lung Cancer", Am. T. Ind. Med.. 1996. 42. Hesterberg, T.W., McConnell, E.E., Miiller, W.C., Chevalier, J., Everitt, J., Hievenaz, P., and Oberdorster, G. "Inhalation Toxicity of Synthetic Vitreous Fibers Compared to Amositc Asbestos in the Hamster", (scheduled for Sept. 199G). 43. McConnell, E.E. "Commentary on "Fibrous Glass and Lung Cancer", Am. 1. hid. Med.. 30:111-112,1996. 64 44. McConnell, E.E., Mller, W., Hesterberg, T.W., Thevenaz, P. and xten, C. A comparison of the effects of chrysotilc and amosite asbestos in ham sters after inhalation: Interim results. The Toxicologist. 36:6 (33), 1907. 43. Hesterberg, T.W., McConnell, E.E., Mller, W., Chevalier, J., Everitt, J.,Thevena z, P., Fleissner, H., Hart, G. and Oberdorster, G. Subchronie inhalation study of fibrous glass in the Syrian golden hamster. The Toxicolotrist. 36:6 (35), 1997. 46. Mayes, B.A., Neal, B.H., Peters, A.C., Brown, J. R, Hamilton, S.B., McConnell, E.E. and Moore, J.A. Tumor responses in Sprague-Dawley rats fed Aroclilors 1016, 1042 1254 and 1260 for two years. The Toxicologist. 36:158 (804), 1997. 47. McConnell, E.E., Mller, W., Hesterberg, T.W., Thcvenaz, P. and xten, C. A comparison of the oncogenic effects of various types of asbestos in rodents after lifetime inhalation, th e Toxicologist, 42:177(876), 1998. 48. Hesterberg, T.W., xten, t\, Hadley, J., McConnell, E.E., Mller, W., Chevalier, J., Everitt, J., Thevenaz, P. and Oberdorster, G. Estimating the maximum tolerated dose of fiber glass for a chronic inhalation study using Syran golden hamsters. The Toxicologist. 42:177 (877), 1998. 49. xten, C., McConnell, B.E.. Hesterberg, T.W., Hadley, J.G., Mler, W., Thevenaz, P. and Chevalier, J. Chronic inhalation toxicity of two types of fobrous gfass and amosite asbestos asbestos in Syrian golden hamsters. The Toxicologist. 42:177 (880)," 1998. ' 50. Kamstrup, O., Daris, Ellcnhaugc, A. and Guldbcrg, M. Pathogenicity of man-made vitreous fibers after long-term inhalation. The Toxicologist. 48(1-5), 1999. 51. McConnell, E.E. Use of the rodent diaphragm and thoracic wall to determine transpleural migration of fibers after inhalation exposure. Proceedings of the 7,!t International Symposium on Particle Toxicology. Maastricht, The Netherlands. 13-15 October 1999. 52. McConnell, E.E. A comparison of pleura! mesotheliomas induced by asbestos and SV-40 varus in Syrian golden hamsters. Proceedings of the 7thInternational Symposium on Partide Toxicology. Maastricht, The Netherlands. 13-15 October 1999. 53. xten, C.W., Hadley, J., Hesterberg, T., McConnell, E.E. and Mller. Fiber biopersistence as an indicator of potential pathophysiology - Results of a chronic inhalation study. Proceedings of the 7thInternational Symposium on Partide Toxicology. Maastricht, The Netherlands. 13-15 October 1999. 54. Thevenaz, Ph., Jones, A.D., Mller, W., Axten, C.W., Hestergerg, T.W., Hadley, J., McConnell, E.E. and Dotti, A. Influence of methodology on reported lung burden and fiber concentrations for inhalation studies with man-made fibers: Part 1 - Aerosol generation and exposure methods. Proceedings of the 7th International Symposium on Partide Toxicology. Maastricht, The Netherlands. 13-15 October 1999. 55. McConnell, E.E. A Science-based Approach to the Classification of Synthetic Vitreous Fibers. #FP 44, 26thInternational Congress on Occupational Health, Singapore, 27-1 September 2000. 56. Developing Strategics for Agricultural Chemical Safety Evaluation; A Report from an April 22-23, 2001 Workshop. HES1, International Life Sciences Institute, Washington, DC, September 2001. Oral Present ation/Inri ted Lectures: 65 1. "Lymphosarcoma in Domestic Animals," .Armed Forces Institute of Pathology, Washington, DC, March 1 9 0 (1. 2. "The Clinician and Pathologist," South Africa VMA (MTS) Congress, May 1970. 3. "Experiences with Animals at the Kruger National Park," Veterinary Faculty, Onderstepoort, September 1970. 4. "The Role of a Veterinarian in the U.S. Air Force," Eastern Transvaal Veterinary Medical Association, Pietersburg, October 1970. 5. "Anthrax in an African Buffalo from the Kruger National Park," Congress of the South African VMA, September 1971. 6. "Respiratory Acariasis in Chacma Baboons," Science Week-1972, MTS University, Johannesburg, June 1972. 7. "Pathological Observations in 100 Baboons from the Kruger National Park," Veterinary Faculty and Staff of the Veterinary Research Institute, Onderstepoort, July 1972. 8. "Lesions in Free-Ranging Baboons," Pathology of the Diseases of Laboratory Animals, Armed Forces Institute of Pathology, September 1972. 9. "Lesions Found in Animals Exposed to Coal Tar Aerosols," 4th Annual Conference on Environmental Toxicology, Wright-Patierson AFB, September 1973. 10. "Anthrax in an African Buffalo," American College of Veterinary Pathologists Annual Meeting, San /Antonio, TX, December 1973. 11. "The Comparative Toxicity of Chlorinated Dibcnzo-p-dioxin Isomers in Mice and Guinea Pigs," Society of Toxicology Annual Meeting, Atlanta, GA, March 1976. 12. "The Toxicopathology of TCDD," Workshop on TCDD, Milan, Italy, October 1976. 13. "Toxicological Research Programs at the National Institute of Environmental Health Sciences," University of California, Davis, October 1977. 14. "Training of Comparative Pathologists for a Career in Toxicology," University of California, Davis, October 1977. IS. "Exquisite Toxicity in the Guinea Pig to Structurally Similar Halogenated Dioxins, Furans, Biphenyls and Naphthalenes," 17th Annual Meeting, Society of Toxicology1, San Francisco, CA, March 1978. 10. "Toxicopathology7Characteristics of Halogenated Aromatics," Science Week, New York Academy of Sciences, New York, NY, June 1978. 17. "Pathology7and Toxicology' of Chlorodibenzodioxins in Laboratory'Animals," Ohio State University, Columbus, OH, May 1979. 18. "Chronic Toxicity of Technical and Analytical Grade Penta chioroph enei in Cattle," Ohio State University, Columbus, OH, May 1979. 66 L9. "Comparative Toxicity of Related Halogenated Hydrocarbons," Aimed Forces Institute of Pathology, Washington, DC, May 197<). 20. "The Toxicology of Dibenzofurans and Dibenzodioxins,,, 45th Meeting of the Interagency Collaborative Group on Environmental Carcinogenesis, National Cancer Institute, Bethesda, MD, May 1979. 21. "Comparative Toxicity of Technical and Analytical Pcntaclilorophcnol in Cattle," NIEHS Science Fair, North Carolina State University, Raleigh, NC, June 1979. 22. "The Lesions Induced by Related Halogenatcd .Aromatics in Various Species of Animals," 1979 Wildlife Disease Association Meeting, University of Oklahoma, Norman, OK, August 1979. 23. "Essentials of Routine Pathotoxicology Evaluation," Consensus Development of hnrnunotoxicology Meeting, NIEHS, Research Triangle Park, NC, November 1979. 24. "Toxicopathological Syndrome Induced by Related Halogenated Polycyclic Hydrocarbons," Ohio Agricultural Research and Development Center, Wooster, OH, August 1980. 25. "The National Toxicology Program," Conservative Trends in Laboratory Animal Science, Eighth Annual District IV AALAS Seminar, Raleigh, NC, March 1981. 20. "NTP Testing Results with Emphasis on Bioassays of DEHP, DEHA and Butyl Benzyl Phthalate," Phthalate Ester Conference, Washington, DC, June 1981. 27. "Effects of Subchronic Chlordccone Exposure on the Fertility of Female Rats," North Carolina Chapter of the Society of Toxicology, Research Triangle Park, NC, January 1982. 28. "Evaluation of Pathology Requirements/' Third .Annual Meeling of the American College of Toxicology, Washington, DC, December 1982. 29. "NIEHS Asbestos Feeding Study - Hamsters and Rats," Summary Workshop on Ingested Asbestos, USEPA, Cincinnati, OH, November 1982. 30. "Histopathology Workload in Carcinogenesis Bioassays - How much is necessary?" The Toxicology Forum Annual Winter Meeting, .Arlington, VA, February 1983. 31. "Proliferative Lesions of the Exocrine Pancreas in Male F344 Rats - The Effect of Com Oil," The Toxicology Forum 1983 Annual Winter Meeting, Arlington, VA, February 1983. 32. "Toxic Oil Syndrome," WHO Meeting, Madrid, Spain, March 1983. 33. "An Improved Protocol for Bioassay Studies," 2nd International Symposium of the Society of Toxicologic Pathologists, Crystal City, VA, May 1983. 34. "Chronic Toxicity of PCBs and Related Compounds in Various Animal Species," CCERP Conference on Potential Health Effects of Polychlorinaied Biphenyls and Related Persistent Halogenated Hydrocarbons, NIEHS, Research Triangle Park, NC, September 1983. 35. "Toxicity of PCBs, Polychlorinated Dibenzofurans and Dibcnzo dioxins/' International Workshop on Occupational Hazards Caused by Polychlorinated Biphenyls (PCBs) and Chlorobenzenes in Capacitors and Transformers, Espoo, Finland, September 1983. 67 36. "Dioxins in the E nvironm entH um an Health and Toxicity Workshop, Michigan State University, East Lansing, MI, December 1983. 37. "Toxic and Carcinogenic Responses in Experimental Animals Administered Dibenzo-p-dioxms and Dibonzofurans," Federation of American Societies for Experimental Biology, St. Louis, MO, April 1984. 38. "Lesions in Animals Exposed to EDB," North Carolina Chapter of the Society of Toxicology Spring Meeting, Durham, NC, April 1984. 39. "Studies on the Bioavailability in Guinea Pigs of Dioxin in Soil," Society of Toxicology Meeting, Atlanta, GA, March 1984. 40. "NTP Program Update," European Toxicology Forum, Geneva Switzerland, September 1984. 41. "The Response of NTP to the Recommendations of The Ad Hoc Panel," 15th Conference on Environmentai Toxieology, Dayton, Ohio, October 1984. 42. "National Toxicology Program Status and New Initiatives," The Toxicology Forum 1985 Annual Winter Meeting, Washington, D.C., February 1985. 43. "Relevant Non-Stafisfical Bioassay Issues," Symposium on long-term Animal Carcinogenicity Studies: A Statistical Perspective, .American Statistical Association, Washington, D.C., March 1985. 44. "The Short and Long Term Health and Environmental Impacts," Conference on the Implications of the Bhopal Tragedy, Tire Workers Policy Project, Newark, New jersey, March 1985. 45. "Ad Hoc Report on Chemical Carcinogenesis Testing and Evaluation," Environmental Health Seminar, University of Cincinnati, Ohio, May 1985. 46. "Challenges and Opportunities for Pathologists in the National Toxicology Program," ILSI Histopathology Seminar on the Reproductive System of Laboratory Animals, Hanover, Germany, September 1985. 47. "The Justification for Combining Benign and Malignant Tumors (or Not Combining Them) in Statistical Analysis Lesions in the Rat," ILSI Histopathology Seminar on the Reproductive System of Laboratory Animals, Hanover, Germany, September 1985. 48: "Methyl Isocyanate - Preliminary Study Results," ILSI Histopathology Seminar on the Reproductive System of Laboratory Animals, Hanover, Germany, September 1985. 49. "Overview of the National Toxicology Program in the United States and Findings in Selected Studies," C.L. Davis Sixth Annual Symposium, Cheshire, England, September 1985. 50. "Carcinogenesis Studies Results from the U.S. National Toxicology Program and the U.S. National Cancer Institute: 1976-1985," Collegium Ramazzini, Living in a Chemical World, Bologna, Italy, October 1985. 51. "Methylene. Chloride, Methylchloroform and Trichloroethylene," Collegium Ramazzini, Living in a Chemical World, Bologna, Italy, October 1985. 52. "liver Foci Formation During Aflatoxin Carcinogenesis in Rat: A Quantitative Study," Collegium Ramazzini, Living in a Chemical World, Bologna, Italy, October 1985. 68 53. "The Toxicity of Methyl Isocyanate in Rats and Mice," New Delhi and Madras, India, February 1986. 54. "Response to the Integration of Recommendations of the Ad Hoc Panel on Carcinogenesis Testing and Evaluation," Society of Toxicology' .Annual Meeting, New Orleans, La., 1986. 55. "NTP Strategy' for Combining Neoplasms for Evaluation of Carcinogenesis Studies," Office of Pesticides & Toxic SubsMunces Seminar Program, EPA, Washingtt >n, D.C., April 1986. 56. "Environmental Toxicology' in the Mid-Eighties: Interfacing with the Toxicologist," FASEB 70th Annual Meeting, St. Louis, Missouri, April 1986. 57. "NTP's Response to the Ad Hoc Panel Recommendations,1' FEMA Annual Meeting, Palm Beach, Florida, April 1986. 58. "Studies on the Toxicity of Methyl Isocyanate, the Chemical Responsible for the Bhopal Disaster," North Carolina State University Microbiology' Seminar Series, Raleigh, North Carolina, April 1986. 59. "Options for Aggregation of Incidence Data," Interdisciplinary Discussion Group on Carcinogenicity' Studies (ILS1NF), Chapel Hill, North Carolina, June 1986. 60. "NTP Evaluation of Experimental Studies," The Toxicology' Forum 1986 Annual Summer Meeting, Aspen, Colorado, July' 1986. 61. "NTP Response to the Report of the Ad Hoc Panel on Chemical Carcinogenesis Testing and Evaluation," The Toxicology' Forum 1986 Annual Summer Meeting, Aspen, Colorado, July 1986. 62. "Inhalation Study of Wollastonite in Rats," SAE's 4th Annual Colloquium on Brakes, Atlantic City7, NJ, October, 1986. 63. "Considerations in Determining the Estimated Maximum'Tolerated Dose," Pharmaceutical Manufacturers' Association Drug Safety Subsection meeting, Nashville, TN, November, 1986. 64. "Current Status of the Issue of Maximum Tolerated Dose (MTD) within the U.S. .National Toxicology Program," 26th Annual Meeting of the Society of Toxicology7, Washington, D.C., February7, 1987. 65. "Federal Perceptions of Board Certification," Spring Meeting and Reception for Members of Association of Government Toxicologists, Bcthcsda, MD, May, 1987. 66. "Gavage Studies in Mice and Rats," Paradichlorobenzene Symposium (Sponsored by COT and Chlorobenzene Producers Association), Washington, D.C., July 1987. 67. "NTP Database," Meeting of the Ad Hoc Working Group on Carcinogenicity Testing, Washington, D.C., July 1987. 68. Rapporateur at Mouse Liver and Rat Kidney Tumors Workshop, EPA Science Advisory Board, Environmental Health Committee and Halogenafed Organics Subcommittee, Washington, D.C., August 1987. 69. "Toxicology Learned the Hard Way," Principles of Toxicology7, Boston Univ., August, 1988. 69 /O. "Mouse Liver Tumors: The Problem," Mouse Liver Carcinogenesis Conference, Austin, TX, November, 1988. 71. "Biology Issues in the Statistical Evaluation of Rodent Carcinogenicity Studies," Course on Biostatistics, International Agency for Research on Cancer, Lyon, France, December, 1988. (2. "Pitfalls in Carcinogenesis Testing," North Carolina State University, Graduate Course VMS 643 "Rodent Toxicologic Pathology", December, 1988. 73. "Maximum Tolerated Dose: The Debate," Brookings Institute, Washington, D.C., May, 1989 and Research Triangle Chapter, Society for Risk Analysis, Research Triangle Park, NC, May, 1989. 74. "The Search for Adequate Bioassay Data: Crude Biolog)' Versus Statistics," Trace Substances in Environmental Health, Annual Meeting of the Society for Environmental Geochemistry and Health, Cincinnati, OH, May, 1989. 75. "Animal Bioassays: Using Protocols and Interpreting Results," Regional Risk Assessment Workshops, Workshop 1, Chicago, IL, June, 1989; Atlanta, GA, December 1989. 76. "Target Organ Toxicity in Carcinogenesis," Annual Summer Toxicology Forum, Aspen, CO, July, 1989. 77. "Toxicity Testing and Evaluation - Practical Considerations," International Training Workshop on Risk Assessment and Management, Chulubhom Research Institute, Bangkok, Thailand, December 1989. 78. "Update on the Search for Adequate Bioassay Data: Crude Biology Versus Statistics," Annual Meeting of the Society of Toxicology, Miami, FL, February, 1990. 79. "Biological Effects of Dietary Restriction: An International Conference", Washington, D.C., March 1990. 80. "Principles of Route-to-Route Extrapolation," (Rapporteur), Hilton Head, SC, March 1990. 81. "Molecular Mechanisms of Fiber Cytotoxicity and Carcinogenesis," Banbury Center, Cold Spring Harbor Laboratory, NY, March 1990. 82. "NTP Carcinogens - Interpretational Problems," International Workshop: Early Indicators of Nongenotoxic Carcinogenesis, World Health Organization, Brussels, Belgium, June 1990. 83. "Principles of Carcinogenesis," School of Pharmacy, Campbell University, Buies Creek, NC, October, 1990. 84. "Comparative Responses in Carcinogenesis Bioassays as a Function of Age at Fust Exposure," Similarities and Differences Between Children and Adults: Implications for Risk Assessment, ILSI/RSI, Hunt Valley, MD, November, 1990. 85. "Ethylene Thiourea: A Case Study," Similarities and Differences Between Children and Adults: Implications for Risk Assessment, ILSI/RSI, Hunt Valley, MD, November 1990. 86. "Problems and Considerations in the Design and Interpretation of Rodent Carcinogenesis Studies", Lectures as part of "Toxicologic Pathology" course, VMS 643, College of Veterinary Medicine, NCSU, December, 1990. 70 8 /. "Toxicologic Studies", Man-made Mineral Fibers: Status of Health Risk Assessment", Johns Hopkins University, March, 1991. 88. "Fiber Toxicity - Background and Historical Perspective", Society of Toxicologic Pathologists, Research Triangle Park, May 1991. 89. ''Animat Bioassay IssuesAlso, of QRA", International Society of Regulatory7Toxicology and Pharmacology workshop "A Review of Risk Assessment and OMB's Report on its Application in Regulatory Agencies", Crystal City, VA, June 1991. 90. "The Design, Conduct and Interpretation of Fiber Toxicity Studies", A. L. Bortrce Lecture Series, Veterinary Science Dept., Pennsylvania State University, PA, September 1991. 91. "Fiber* Toxicology' in Experimental Animals: Results of Studies with Natural and Man-Made Mineral Fibers", Intramural Fiber Research Workshop, National Institute for Occupational Safety and Health, Morgantown, WVA, September 1991. 92. "Conduct and Interpretation of Inhalation Studies of the Toxicity and Carcinogenicity of Man-Made Fibers", Workshop: Approaches to Evaluating the Toxicity and Carcinogenicity of Man-Made Fibers. Durham, NC, November 1991. 93. "Man-Made Fibers: Review of Toxicology Data", '92 Annual Toxicology? Forum, Washington, D.C., February 1992. 94. Invited testimony before the German MAK Commission on MMVF's. Munich, Germany, May 1992. 95. "Man-Made Fibres: Validity of Methods for Assessment of Carcinogenicity of Fibres", WHO Regional Office for Europe, Copenhagen, 19-20 May, 1992. 96. "Evaluation of Reduced Protocols for Carcinogenicity Testing of Chemicals", EPA, Washington, DC, 2223 Sept 1992. 97. "Comparative Pathology of Cbrysotilc and Crocidolitc Asbestos", TIMA/NAIMA Fiber Science W orkshop, St. Petersburg, FL, 20 Jan 1993. 98. "Relationship Between Pulmonary Fibrosis and Cancer", TIMA/NAIMA Fiber Science Workshop, St. Petersburg, FL, 20 Jan 1993. 99. "The Toxicologic Pathologist in 2000 A.D.: Needs for Industry, Government and Academia", Role of Toxicologic Pathology7in Safety Assessment. National Academy of Science, Washington, DC, 10 Feb 1993. 100. "A Comparison of the Effects of Chrysotile and Crocidolitc Asbestos in Rats after Inhalation", Toxicologic and Carcinogenic Effects of Solid Particles in the Respiratory? Tract. 4th International Inhalation Symposium, Hannover, Germany, 3 March 1993. 101. "Styronc/styrcnc oxide - Results of animal carcinogenicity studies", International Symposium on Health Hazards of Butadiene and Styrene, Helsinki, Finland, 21 April 1993. 102. "The Impact of Toxicity Studies in the Regulatory? Process", Dept, of Toxicology? Seminar Scries, Michigan State University?, 3 June 1993. 71 103. 'The Toxicopathology of Inhaled Fibers", Department of Pathology, Michigan State University, 3 June 1993. 104. "Peer Review in Carcinogenidty Bioassays - Uses/Abuses", Society of Toxicologic Pathologists 12th International Symposium, Alexandria, VA, 28 June 1993. 105. McConnell, E.E., Kamstrup, O., Musselinan, R., Hesterberg, T.W., Chevalier, J. andThevenaz, P. Chronic Inhalation Study of Size-separated Man-made Vitreous Fibers in Fischer 344/N Rats. 24th International Congress on Occupational Health, Nice, France, 30 October 1993. 106. McConnell, E.E. Invited expert testimony before the German Ministry of the Environment on MMVF's. Berlin, Germany, 9-10 December 1993. 107. McConnell, E.E. "Fiber-induced pathology in experimental animals. Physiology and Cell Biology Conference, University of Rochester Pulmonary and Critical Care Unit, 20 December 1993. 108. McConnell, E.E. Talc: Consumer Uses ancl Health Perspectives" Panel Discussant, International Society of Regulatory Toxicology and Pharmacology, Bethesda, MD, 31 Jan -1 Feb 1994. 109. McConnell., E.E. "Advantages and limits of in vivo screening tests", Assessment of Toxicity of Man made Fibres, Paris, France, 2 Feb. 1994. 110. McConnell, E.E. "Inhalation Studies: Methodologies Used and Current Studies", Symposium on Synthetic Vitreous Fibers: Scientific and Public Policy' Issues. Crystal City. VA, 2-3 March 1994. 111. McConnell, E.E. "Historical Review of the Bioassay and Future Directions", Design and Interpretation of Animal Carcinogenidty Studies, Great Lakes Discussion Group of the Sodety of Toxicologic Pathologists, Cincinnati, OH, 24 March 1994. 112. McConnell, E.E. Panel member "Workshop on Data Needs for Cancer Risk Assessment of MTBE", Baltimore, MD, 4 March 1995. 113. McConnell, E.E. "Maximum Tolerated Dose versus Lung Burden: A Pathologists Point of View", Partide Overload in the Rat Lung: Relevance for Human Risk Assessment. MIT Toxicology Symposium, Cambridge, MA, 29-30 March 1995. 114. "Dose Selection in Inhalation Studies", U.S. EPA Workshop, Chapil Hill, NC, 9-10 May 1995. 115. "U.S. EPA Science Advisory Board Dioxin Reassessment Review", Herdon, VA, 15-16 May 1995. 116. "FIFRA SAP Review, Chairman, Aquatic Risk Assessment and Mitigation, Crystal City, VA, 1 / July 1995. 117. "EUROTOX-SOT DEBATE "Dose Setting for Cardngenirity Studies Should be Based on the Maximum Tolerated Dose", Prague, Chech Republic, 29 Aug 1995 and Anaheim, CA 12 March 1996. 117. "Results of Life-time Inhalation Studies of Glass, Mineral and Slag Wools and Refractory Ceramic Fibres in Rodents", Symposium on the Health Effects of Fibrous Materials (excluding asbestos) Used in Industry7. Sydney, Australia, 30-31 October, 1995. 118. "The Rodent Bioassay in Perspective", 1Orh International Conference on Carcinogenesis & Risk Assessment, Austin, TX, 4 December 1996. 72 119. McConnell, E.E., Mller, W.t Hesterberg, T.W., Thevcnaz, P. and xten, C. A comparison of the effects of chrysotilc and amosite asbestos in ham sters after inhalation: Interim results. Society of Toxicology Annual Meeting, Cindnnatti, OH, 1997. 120. McConnell, E.E. Selecting Doses for Chronic Rodent Bioassays. Brookings Institution. Washington, D.C. 3 April 1997. 121. McConnell, E.E. Regulatory Toxicology: lecture for "Principles of Pharmacology", Medical College of Virginia, 28 April, 1997. 122. McClain, M. and McConnell, E.E. "Workshop on Screening Methods for Endocrine Disruptors in the Thyroid Function: Thyroid Hisopathology and Serum Hormone Analysis" Duke University, Durham, NC, 24 June 1997. 123. McConnell, E.E. Update on the 10X Childrens Safety Factor. Pesticide Program Dialogue Committee, Alexandria, VA 16 April 1998. 124. McConnell, E.E. Cancer and Non-Cancer Responses to Inhaled Fibers, Validity of Animal Models for Human Respiratory Diseases. Lovelace Respiratory Research In stitu te symposium, Santa Fe, NM, 29 September 1998. 125. McConnell, E.E. A Science-based Paradigm for the Classification of Synthetic Vitreous Fibers. 7th International Symposium on Particle Toxicology*. Maastricht, The Netherlands. 13-15 October 1999. 12(3. McConnell, E.E. Similarities and Dissimilarities of Mesotheliomas Induced by Asbestos and SV40. Experimental Pathology7Branch, National Institute of Environmental Health Sciences (NTH), RTP, NC. 27 October 1999. 127. McConnell, E.E. A Comparison of Asbestos and Simian Virus 40 Induced Mesotheliomas in Animals. Defense Research Institute's 20,!l .Annual Asbestos Medicine Meeting, Las Vegas, NV. 12 November 1999. 128. McConnell, E.E. A Science-based Approach to the Classification of Synthetic Vitreous Fibers. 26th International Congress on Occupational Health, Singapore, 50 August 2000. 129. McConnell, E.E. Foot and Mouth Disease: A Review Lesions. North Carolina State University7, April, 2001 and National Institute of Environmental Health Sciences, NIH, 0 June 2001. 130. McConnell, E.E. Animal Cancer Studies of Sodium Nitrite: Historical Review and Recent National Toxicology- Program Bioassay Rrcsults. Institute of Food Technologists annual meeting, New Orleans, LA, 24 June 2001. 131. McConnell, E.E. Animal Testing and Chrysotilc. Defense Research Institute's 22nd Annual Asbestos Medicine Meeting,.Phoenix, AZ. 2 November 2001. 132. McConnell, E.E. Anthrax in South Africa. National Institute of Environmental Health Sciences, Research Triangle Park, NC. 14 November 2001. 133. McConnell, E.E. Anthrax in South Africa. College of Veterinary Medicine, NCSU, Raleigh, NC. 17 November 2001. 73 134. McConnell, E.E. "The Value of Human Testing of Pesticides." Pesticide Testing in Humans: Ethics and Public Policy. New York Academy of Medicine., NYC, NY. 27 February 2002. 135. McConnell, E.E. "Human Data in Risk Assessment", Current Topics in Pesticide Toxicology: An Intensive Workshop. North Carolina State University, 9 April 2002. 136. McConnell, E.E. "Science and Politics in Human Testing of Pesticides", Pesticides in the Molecular Age. l l rhNorth American ISSX Meeting, 25 October 2002. 137. McConnell, E.E. "How do Animal/Experiment Data Augment our Understanding of Human Health Effects?" ATSDR Expert Panel on Health Effects of Asbestos and Synthetic Fibers (SVF: The Influence of Fiber Length. New York, NY. 29-30 October 2002. 138. McConnell, E.E. "The Value of Human Testing." NRC/NAS Committee on the Use of Third Party Toxicity Research with Human Research Participants. Washington, DC. 19 March 2003 139. McConnell, E.E. "Ingestion Studies of Asbestos and Non-Asbestos Particles in Experimental Animals to Evaluate Carcinogenic Potential." International Symposium on the Health Hazard Evaluation of Fibrous Particles Associated with Taconite and the Adjacent Duluth Complex. 140. McConnell, E.E. "Influence of Fiber Type, Size and Exposure in the Cancer and Non-cancer Response to Asbestos Fibers (Animal Studies)." Asbestos Mechanisms of Toxicity Workshop, Chicago, 31. 12-13 June 2003. 74