Document GKkRyD7JJByRmzeY95o9NZa4

*r Chemical Industry Institute of Toxicology icirri Roger O. McClellan, D.V.M. President P.O. Box 12137 6 Davis Drive Research Triangle Park, North Carolina 27709 (919) 558-1200 FAX (919) 558-1300 December 7, 1995 Dr. Hashmukh C. Shah Manager, Vinyl Chloride Panel Chemical Manufacturers Associatione 2501 M Street, N.W. Washington, DC 20037 Dear Dr. Shah: The Chemical Industry Institute of Toxicology (CUT) with our partner, Research Triangle Institute (RTI), is pleased to provide one original and one bound copy of a technical and cost proposal in response to the Chemical Manufacturer Asssociaton's (CMA) request addressed on November 15,1995 to Dr. Rochelle Tyl at the Research Triangle Institute. Our bid is for a Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats. Our study proposals related to the developmental toxicity of vinyl chloride in rats and reproductive toxicity of vinyl chloride in rats represent a joint partnership with our colleagues at the Research Triangle Institute (RTI). RTI will serve as the CUT Subcontractor for these two studies. These two research proposals build upon the respective strengths of both organizations. We are confident that high quality data sets will emerge from the partnership between CUT and RTI. For the submitted research proposals CUT should be considered to be the Contractor. CUT has carefully considered the costs associated with the conduct of these studies. The lump sum, fixed price for the project is $520,824. In closing, let me note that my colleagues at both CUT and RTI are very enthusiastic about the opportunity to carry out this important research for CMA. The proposed vinyl chloride work is closely related to Cl IT's ongoing research in inhalation developmental and reproductive toxicology. Dr. Frank Welsch, the proposed study director, has extensive experience in developmental toxicology. Dr. Rochelle Tyl, the co-study director who is now at RTI, has had extensive experience conducting inhalation studies concerned with developmental/reproduction/fertility effects. Dr. Brian Wong, who will be responsible for overseeing the inhalation exposures, is an experienced inhalation toxicologist. We are confident that this team of experienced investigators at CUT and RTI will carry out the proposed research in an exemplary manner. R&S 147154 Dr. Hasmukh C. Shah December 7,1995 Page 2 If you should have questions on any of the submitted technical and cost proposals, please call me at (919) 558-1202, or Dr. James Bond at (919) 558-1327. My colleagues and I appreciate the opportunity to present this proposal and look forward to carrying out a meritorious research effort on behalf of the CMA. Sincerely, (55 ^--t Roger O. McClellan, D.V.M. President FW:ROM:ksm Enclosures'. Two (2) Technical and Cost Proposals cc: Dr. James Bond Dr. Fred Miller Mr. Dave Althaus R&S147155 CHEMICAL INDUSTRY INSTITUTE OF TOXICOLOGY RESPONSE TO REQUEST FOR PROPOSAL FROM THE CHEMICAL MANUFACTURERS ASSOCIATION FOR A VINYL CHLORIDE COMBINED INHALATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS Submitted on behalf of the Chemical Industry Institute of Toxicology Roger O. McClellan, D.V.M. President Date Restricted Distribution and Use TABLE OF CONTENTS Rage 1.0 SUBJECT.......................................................................................................................... 4-5 2.0 DEFINITIVE INHALATION DEVELOPMENTAL TOXICITYSTUDY IN RATS WORK PLAN........................................................................................................................ 5 2.1 Objectives................................................................................................................. 5 2.2 Research Tasks....................................................................................................... 5 2.3 Data Treatment......................................................................................................... 5 3.0 DEFINITIVE INHALATION REPRODUCTIVE TOXICITY STUDY: WORK PLAN........................................................................................................................ 6 3.1 Objectives................................................................................................................. 6 3.2 Research Tasks....................................................................................................... 6 3.3 Data Treatment......................................................................................................... 6 4.0 MANPOWER REQUIREMENTS................................................................................... 7 4.1 Manpower CUT........................................................................................................ 7 4.2 Manpower RTI......................................................................................................... 7 5.0 PROGRAM DURATION................................................................................................... 8-13 5.1 Proposed Experimental Schedule........................................................................ 8 5.2 Developmental Toxicity Study in Rats................................................................. 9 5.3 Reproduction/Fertility Study in Rats................................................................... 9-11 5.4 Quality Assurance Schedule.................................................................................. 12 5.5 Proposed Payment Schedule................................................................................. 13 6.0 COST................................................................................................................................ 14 6.1 Projected Budget..................................................................................................... 14 7.0 PROJECT ADMINISTRATION........................................................................................ 15-32 7.1 Organization Chart CUT........................................... '........................................... 15 7.2 Biographical Sketches CUT................................................................................. 16-30 7.3. Organization Chart RTI........................................................................................... 31 7.4 Biographical Sketches RTI...................................................................................... 32 8.0 CORPORATE QUALIFICATIONS.................................................................................. 33-39 8.1 Organization Chart CUT.......................................................................................... 33 8.2 Organization Chart RTI.......................................................................................... 34 8.3 Liability Statement................................................................................................... 35 8.4 Research Facilities CUT........................................................................................ 35-37 8.5 Research Facilities RTI........................................................................................... 38 8.6. Related Research Capabilities............................................................................... 38 8.6.1 Quality Assurance at CUT..................................................................................... 38 8.6.2 Related Research Activities.................................................................................... 39 R&S147157 Restricted Distribution and Use 2- - \ TABLE OF CONTENTS List of Appendices Appendix 1 Appendix 2 Appendix 3 Appendix 4 Appendix 5 Letter from Dr. Tyl Decembers, 1995 Detailed CVs of RTI Personnel SOP Listings from RTI including Quality Assurance RTI Reproductive and Developmental Toxicology Wing CUT Experimental Design Figure and CIIT/RTI Task Sharing Tables R&S147158 Restricted Distribution and Use -3- f 1.0 SUBJECT The Chemical Manufacturers Association has requested a technical and cost proposal to conduct an inhalation toxicology study with vinyl chloride (monochloroethylene; vinyl chloride monomer). There are two purposes of the proposed studies. One is to conduct a developmental toxicity study in CD rats. The second objective is to perform a Two-Generation Reproduction and Fertility Effects Study in CD rats. Both studies will be conducted in accordance with the Food and Drug Administration (FDA) Good Laboratory Practice Regulations for NonClinical Studies (FDA, 1988), the EPA TSCA Good Laboratory Practice Standards (EPA, 1990), the OECD Good Laboratory Practice Procedures (OECD, 1982), and the Standard Operating Procedures of The Toxicology Research Laboratory of The Dow Chemical Company. Test protocols will follow the new draft EPA Health Effects Test Guidelines OPPTS 870.3700 (Developmental toxicity study) and EPA Health Effects Test Guidelines OPPTS 870.3800 (Reproduction and fertility effects) and will be conducted in accordance with EPA's Good Laboratory Practice Regulations(40 CFR Part 792) and quality control procedures to ensure valid test data of high quality. For each animal test, well-accepted approaches will be used to quarantine and screen animals prior to testing, uniquely identify animals placed on test, and randomly assign animals to test groups. The inhalation exposures will be conducted at CUT, and all test animals will be housed at CUT throughout the duration of the in-life portions of the studies. All animals test protocols will be reviewed by both the CUT and RTI Institutional Animal Care and Use Committees. All studies involving animals are conducted in AAALAC accredited facilities. . However, all studies will be done in very close collaboration and task sharing with the scientific and support staff at the Center for Life Sciences and Toxicology of the Research Triangle Institute (RTI) that is located in close proximity to CUT. A complete description of the evaluations to be conducted by RTI can be found in the Appendix #1. In each study, animals will be exposed to vinyl chloride gas in inhalation chambers of appropriate aerodynamic design to sustain a dynamic air flow of 12 to 15 air changes per hour to ensure an oxygen content of 19 percent and to deliver an evenly distributed exposure atmosphere. Studies for chamber uniformity of vinyl chloride concentration will be performed prior to the initiation of animal exposures. The cage placement pattern will be changed weekly in a predetermined manner within each chamber to compensate for possible, but undetected, variations in chamber exposure conditions. Chamber temperature and relative humidity will be maintained at 22 2C and 40 to 60 percent, respectively. During the exposure period, vinyl chloride concentrations will be verified at least hourly by sweeping breathing zone air to an infrared spectrophotometer calibrated for vinyl chloride measurement. During non-exposure R&S147159 Restricted Distribution and Use -4- periods, water and food will be available to the animals ad libitum. Food and water will be withheld during the 6-hour exposure periods. 2.0 VINYL CHLORIDE INHALATION DEVELOPMENTAL TOXICITY STUDY: WORK PLAN 2.1 Objectives The objectives of the combined inhalation two-generation reproduction and developmental toxicity study outlined in this protocol are to evaluate the effects of the test material on parental toxicity, reproductive capability, in utero development, and neonatal growth and survival in rats. This study will be conducted to meet the requirements of the Environmental Protection Agency (EPA): TSCA Test Guidelines (EPA, 1985), the Organisation for Economic Co-Operation and Development (OECD), Guidelines, for Testing of Chemicals, Section 4: Health Effects, (OECD, 1981), and the European Economic Community (EEC), Methods for the Determination of Toxicity (EEC, 1988). 2.2 Research Tasks Test protocols will follow the new draft EPA OPPTS Health Effects Test Guidelines. For each animal test, well accepted approaches will be used to quarantine and screen animals prior to testing. The time frame during which the definitive developmental toxicity study will be conducted and the task sharing between CUT and RTI staff are described in the Proposed Experiment Schedule as well as in Figure 1 and Table 1, respectively (Appendix #5). This study will be conducted while the inhalation exposures for the Two-Generation Reproductive Toxicity are ongoing in the first prebreeding exposure phase (Figure 1, Appendix #5). 2.3 Data Treatment Data will be recorded, condensed, tabulated, summarized and statistically processed according to standard procedures. Final reports will document the test design, exposure conditions, measurement parameters, in-life study results, necropsy results (e.g., gross lesions), and fetal evaluations. Reports will describe the results in terms of statistical and apparent biological significance, and they will attempt to identify causative mechanisms for the compound-related effects found. The biological and statistical analyses of all the data generated during the course of the proposed studies will be performed with the Teratology Standard Operating Procedures of RTI (Appendix #3). Restricted Distribution and Use -5- -r 3.0 VINYL CHLORIDE INHAI ATION REPRODUCTIVE TOXICITY STUDY: WORK PLAN 3.1 Objectives The objectives of this study will be to conduct an inhalation study in rats of both sexes; three (3) concentrations of vinyl chloride and a control group will be evaluated. 3.2 Research Tasks Test protocols will follow the EPA OPPS Health Effects Test Guidelines. For each animal shipment standardized tests on sentinel animals and well accepted approaches will be used to quarantine and screen animals prior to testing. The time frame for the definitive reproductive toxicity study (July 1996 - November 1997) is described in the Proposed Experiment Schedule and also in Figure 1 (Appendix #5). The task sharing between CUT and RTI staff is detailed in Table 2 (Appendix #5). The definitive reproduction/fertility study will require about 18 months to complete and is projected to start with purchase of the animals in July 1996 and actual inhalation exposure beginning immediately after quarantine as shown in Figure 1 (Appendix #5). The task sharing for this study is described in Table 2 (Appendix #5). 3.3 Data Treatment Data will be recorded, condensed, tabulated, summarized and statistically processed according to standard procedures. Final reports will document the test design, exposure conditions, measurement parameters, in-life study results, necropsy results (e.g., gross lesions), and histopathology findings definitive study. Reports will describe the results in terms of statistical and apparent biological significance, and they will attempt to identify causative mechanisms for the compound-related effects found. The biological and statistical analyses of all the data generated during the course of the proposed studies will be performed with the Teratology Standard Operating Procedures of RTI (Appendix #3). R&S147161 Restricted Distribution and Use -6- 4.0 MANPOWER REQUIREMENTS 4.1 Manpower CUT Key Personnel Scientist Frank Welsch Brian Wong Jeff Everitt Paul Ross Technical TBA TBA Labor Category Developmental Toxicologist Inhalation Scientist Pathologist/Lab Animal Veterinarian Animal Care Supervisor Animal Care Technician Inhalation Technician 4.2 Manpower RTI Key Personnel Scientist Rochelle Tyl Patricia Fail John Seely Technical Melissa Marr Christina Myers Tsai-Ying Chang TBA Stephanie Taulbee Labor Category Developmental Toxicologist Reproductive Endocrinologist Veterinary Pathologist Reproductive and Developmental Toxicology Lab. Supervisor Reproductive and Developmental Toxicology Specialist Histotechnologist Animal Care Technicians Quality Assurance R&S147162 Restricted Distribution and Use -7- 5.0 PROGRAM DURATION 5.1 Proposed Experimental Schedule 5.1.A. Definitive Developmental Toxicity Study in Rats The Definitive Developmental Toxicity Study in Rats will be conducted as illustrated in the Proposed Experiment Schedule below and in Figure 1 (Appendix #5). Rats will be purchased in August 1996 and mated as soon as the quarantine is completed. Three different inhalation exposures concentrations will be used, 10,100,1100 ppm and a chamber air control. The inhalation phase will be completed in September 1996. 5.1 .B. Definitive Reproductive Toxicity Study in Rats The Definitive Reproductive Toxicity Study in Rats will start with quarantine of the test animals in July 1996 as illustrated in the Proposed Experimental Schedule below. The in life phase will require 41 weeks (Figure 1, Appendix #5). The proposed experimental sequence is described in the schedule below: VINYL CHLORIDE INHALATION DEVELOPMENTAL AND REPRODUCTION/FERTILITY PROPOSAL Proposed Experimental Schedule DATE Year Month Event 1. Definitive Developmental Toxicity Study in Rats 1996 April Protocol to Sponsor July/August Order Animals August Initiate Exposures September Complete In-Life Phase 1997 January Submission of Draft Report March Final Report 2. Definitive Reproductive Toxicity Study in Rats 1996 April Protocol to Sponsor July Order Animals August Initiate Exposures 1997 April Complete In-Life Phase September Submission of Draft Final Report November Final ReDort R&S147163 Restricted Distribution and Use -8- The study designs proposed by RTI and CUT are as follows: 5.2 Definitive Developmental Toxicity Study in Rats A total of 170 virgin female rats will be purchased and mated 1:1 to the males in the CUT breeding colony. The date of insemination (dropped copulation plug, vaginal sperm or vaginal copulation plug) will be designated gestational day (gd) 0. A total of 100 sperm-positive female rats ("dams") will be employed in four groups (three chemical and one vehicle control groups), 25 dams per group. The rats will be exposed to vinyl chloride by inhalation six hours per day, on gd 6 through 19 at exposure concentrations of 0,10,100 and 1100 ppm (as provided in Dow's protocol). These exposures will occur during the first prebreed exposure period of F0 animals in the two-generation study. Clinical observations will be documented daily (twice daily during the exposure period), and dams will be weighed on gd 0, 6, 9,12,15,18,19 and 20. Feed consumption will be documented on individually housed dams on a schedule corresponding to times of maternal body weight collection. At scheduled sacrifice on gd 20 at RTI, dams will be weighed and maternal liver and gravid uterine weights will be recorded. Maternal gross lesions will be retained in fixative. Ovarian corpora lutea will be counted and the status of uterine implantation sites will be recorded (live fetuses, dead fetuses, early and late resorptions). Any apparently nonpregnant uteri or uteri with apparent single horn pregnancies will be stained with ammonium sulfide to confirm pregnancy status and identify any early postimplantation pregnancy losses. All live fetuses will be counted, sexed, weighed and examined externally for malformations (including cleft palate) and variations; approximately 50% of the fetuses in each litter will be examined for visceral alterations, and decapitated and the heads fixed and decalcified for soft tissue craniofacial examinations (including the fetal brain). All fetuses will be eviscerated, cleared and stained with alizarin red S (for ossified bone) and alcian blue (for cartilaginous bone); intact fetuses (50% per litter) will be examined for skeletal malformations and variations. Placental weights will be recorded. A draft report will be submitted within four months of the last sacrifice date. 5.3 Definitive Reproductive Toxicity Study This study is designed to conform to new draft OPPTS Testing Guidelines as requested. Route of administration will be inhalation exposure, six hours/day, five days/week during the F0 and FI 10-week prebreed exposure periods, and seven days/week during mating, gestation and lactation of F0 and FI parental animals; exposure may also occur to FI and F2 offspring during gestation via transplacental processes and/or during lactation by transnational transfer. Restricted Distribution and Use -9- R&S147164 4 One hundred forty (140) weanling (4-5 week old) CD (Sprague-Dawley) male and female rats will be ordered. During the two-week quarantine, 5/sex will be evaluated for serum viral antibody titers and parasites; all will be examined by the CUT veterinarian. At study start, 120 rats per sex, designated the F0 generation, will be distributed by randomization procedures stratified by body weight into four groups, 30 animals/sex/group (with exposure concentrations of 0,10,100 and 1100 ppm as specified in the Dow protocol). Animals will be exposed by inhalation, six hours per day, five days/week for 10 weeks. The 10 weeks (70 days) corresponds to one complete spermatogenic cycle and allows for any bioaccumulation. Animals will be weighed weekly. Feed consumption will also be measured weekly; clinical observations will be recorded twice daily, morning and afternoon. Seven weeks into the 10-week F0 prebreed exposure period, the F0 females will be subjected to daily vaginal lavages for three weeks to determine estrous cyclicity. The three weeks correspond to at least three complete estrous cycles (which last 4-5 days in rats). They will be weighed, and feed consumption and clinical observations documented as described above for males. At the end of the 10 week F0 prebreed exposure period, animals will be cohabited 1:1 (one male:one female) within groups for two weeks (as specified by OPPTS; re-pairing unsuccessful animals within groups after one week of cohabitation will not be done.) Exposures for both sexes will continue now at seven days/week; body weights will be taken weekly in males and weekly until insemination occurs in females. Feed consumption will not be recorded during cohabitation. Females will be checked daily for dropped or vaginal copulation plug and/or vaginal sperm by lavage and for estrous cyclicity during the two-week mating period or until evidence of insemination. The date of evidence of copulation will be designated gd 0. F0 males will be necropsied at the end of the gestation period with reproductive organs, liver, kidneys (2), spleen, thymus, adrenal glands (2), brain, and pituitary weighed and retained (one testis per male will be frozen for spermatid head counts, one testis will be fixed for histopathologic examination), and any gross lesions retained in fixative. Sperm assessments (number, morphology and motility) will be done from the cauda epididymis and homogenization-resistant testicular sperm will be evaluated from the testis from all F0 males at necropsy. Presumed pregnant females (dams) will be weighed and feed consumption measured on gd 0, 7,14, and 20. Dams usually litter on gd 22 or 23; the date of parturition will be designated as postnatal day (pnd) 0. Offspring of F0 parents will be designated the FI generation. Pregnant females will not be exposed on gd 20 through pnd 4, with exposure to the dams resuming on pnd 5. Dams and their litters will be weighed and feed consumption measured on pnd 0, 4, 7,14, and 21. Pups will be counted, sexed, weighed individually and examined externally also on pnd 0, 4, 7, 14 and 21. Anogenital distance will be recorded for all pups on pnd 0. On pnd 4, litters will be randomly R&S147165 Restricted Distribution and Use -10- culled to eight pups with as equal a sex ratio as possible; natural litters of eight or less pups will not be culled. On pnd 21, each litter will be weaned; the FO dams will then be necropsied (with stage of estrus at sacrifice documented) with reproductive tract, liver, kidneys (2), spleen, thymus, adrenal glands (2), brain, and pituitary weighed and retained, and any gross lesions retained in fixative. A total of 30 FI weanlings per sex per group will be randomly selected from the maximum number of litters as FI parents for the next generation. They will be exposed to vinyl chloride by inhalation, five days/week, beginning on pnd 22 (the day after weaning); when the last litter is weaned, the formal 10-week prebreed exposure period for the FI animals will begin (the youngest pups will be 13 weeks old at the end of this exposure period). In addition, three FI weanlings/sex/litter will be necropsied with reproductive organs, liver, kidneys (2), spleen, thymus, adrenal glands (2), brain, and pituitary weighed and retained, and any gross lesions retained in fixative. Remaining non-selected FI weanlings will be examined externally and euthanized with the concurrence of the Sponsor. The date of acquisition of vaginal patency in females (pnd 28-45) and of preputial separation (pnd 35-50) in males will be recorded in the FI pups selected as parents until all available pups have reached criterion. At the end of the FI 10-week prebreed exposure period (with a three-week evaluation of FI females for estrous cyclicity), mating, gestation and lactation (with pairing of non-sibling animals within groups) will be performed as described above for FO animals. Necropsy of FI parental animals will occur as described above for FO parents. Offspring of FI parents will be designated the F2 generation. At weaning of F2 litters, three F2 weanlings/sex/litter will be necropsied as described above for FI weanlings; remaining unselected F2 weanlings will be examined externally and euthanized with concurrence of the Sponsor. Organs of FO and FI parental animals to be weighed (all groups) include ovaries (2), uterus, testes (2), epididymides (2), seminal vesicles (2) with coagulating glands, prostate, spleen, kidneys (2), liver, adrenal glands (2), thymus, brain and pituitary. Organs of these animals to be retained in fixative include the above (one testis per male will be frozen for homogenization-resistant spermatid head count), plus cervix and vagina in females. Organs of the top dose and control group parental animals, plus any animals in mid and low dose groups which die on study or were not reproductively successful, will be examined histologically. Ovaries from FO and FI parental females (high dose and control) will have five (5) sections taken at least 100 pm apart from the inner third of each ovary with enumeration of the total number of primordial follicles from these 10 sections per female. F0 and FI parental males (all doses) will have sperm assessments (number, morphology, motility) performed from the cauda epididymis and homogenization-resistant spermatid head counts performed from the testis. Organs of FI and F2 weanlings will be retained in fixative for possible subsequent histopathologic assessment if gross examination and/or organ weights indicate possible treatment-related effects. A draft final report will be submitted within five months of the last necropsy date. R&S147166 Restricted Distribution and Use -11- 5.4. Quality Assurance Schedule SCHEDULE FOR QUALITY ASSURANCE AUDITS AND INSPECTIONS ON PROPOSED VINYL CHLORIDE INHALATION DEVELOPMENTAL TOXICITY AND REPRODUCTION/FERTILITY STUDY AUDIT/INSPECTION* OF "TEtsnrV^^^^^^I^ITX^ASSUFIANiL^E UNIT *: ^^yi^TiES:A'PR'#&ED TO bCCUR *; DURING MONTH(S) 1. Definitive Developmental Toxicity Study in Rats Protocols April, 1996 In-Life Critical Phases August/September, 1996 Review Raw Data/Draft Report January 1997 Final Report March, 1997 2. Reproduction/Fertility Definitive Study in Rats Protocol In-Life Critical Phases Review Raw Data/Draft Report Final Report April, 1996 July 1996-April 1997 September, 1997 November, 1997 * In-Life Critical Phases will be identified from the written protocols R&S147167 Restricted Distribution and Use -12- 5.5 Proposed Payment Schedule Projected Date 4/30/96 11/1/96 11/15/96 1/17/97 3/31/97 4/30/97 9/15/97 11/30/97 Project Benchmarks Submission of protocol for developmental toxicity and reproduction studies Completion of in-life portion of developmental toxicity study Completion of 20 weeks of in-life portion of reproductive/fertility study Submission of draft final report on developmental toxicity study Submission of final report on developmental toxicity study Completion of in-life portion of reproductive/fertility study Submission of draft final report on reproductive/fertility study Submission of final report for reproductive/fertility study Payment Schedule 5% 10% 20% 5% 5% 25% 25% 5% R&S147168 Restricted Distribution and Use -13- 6.0 COST 6.1 Projected Budget CUT proposes to conduct an inhalation developmental toxicity study in rats with vinyl chloride and an inhalation reproductive/fertility study in rats with vinyl chloride for a total lump sum price of $520,824. R&S147169 Restricted Distribution and Use -14- I % 7.0 PROJECT ADMINISTRATION 7.1 Internal Organization Chart I Cancer Research Program (Bond) President - McClellan I Non-Cancer Research (Miller) Quality Assurance Program (Pomerleau) Vinyl Chloride Developmental and Reproductive Toxicology CUT Staff RTI Staff Frank Welsch, Developmental Toxicologist Study Director Brian Wong, Inhalation Toxicologist Jeffrey Everitt, Laboratory Animal Veterinarian Arden James, Lab. Supervisor, Inhalation Exposure Unit Rochelle Tyl, Developmental Toxicologist Patricia Fail, Reproductive Endocrinologist John Seely, Veterinary Pathologist Melissa Marr, Reproductive & Developmental Toxicology Lab. Supervisor Christina Myers, Reproductive & Develop mental Toxicology Specialist Tsai-Ying Chang, Histotechnologist Quality Assurance Stephanie Taulbee, Manager 7.2 Biographical Sketches of Kev CUT Personnel Frank Welsch Brian Wong Jeffrey Everitt Patricia O'Brien Pomerleau R&S147170 Restricted Distribution and Use -15- FRANK WELSCH Senior Scientist, Chemical Industry Institute of Toxicology EDUCATION: 1959 1959-64 1964 1965 1965 Graduation from High School (Gymnasium) in Berlin Veterinary student at the Veterinary Schools in Munich, Vienna and Berlin State Board examination and graduation as veterinarian in Berlin Licensed veterinarian after fulfillment of internship requirements Promotion to Doctor of Veterinary Medicine (Dr. med. vet.) after presentation of doctoral thesis to the Veterinary School of Freie Universitat, Berlin PROFESSIONAL LICENSURE AND CERTIFICATION: American Board of Toxicology, Diplomate EXPERIENCE: 1993-present 1982-1992 1971-82 1977-78 1968-71 1967-68 1964-67 Senior Scientist, Head of the Teratology Laboratory, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina Scientist, Department of Experimental Pathology and Toxicology, Head of the Teratology Laboratory, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina Instructor to Full Professor, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan Visiting Scientist, Institute of Toxicology and Embryopharmacology, Freie Universitat Berlin, Berlin, Germany (Sabbatical leave) Research Associate, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee Research Associate, Laboratory of Neurochemistry, Columbia University College of Physicians and Surgeons, New York City Research Associate, Department of Veterinary Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universitat Berlin ACADEMIC AFFILIATIONS: 1982-present 1982-present 1992-present Adjunct Professor, School of Veterinary Medicine, North Carolina State University, Raleigh, NC Adjunct Associate Professor, Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC , Adjunct Professor, Integrated Toxicology Program, Duke University, Durham, NC ADVISORY APPOINTMENTS: 1986-1992 1987-1991 Member, Science Review Panel for Health Research, Environmental Protection Agency Member, Review Committee on Health Effects - Electric Power Research Institute R&S147171 Restricted Distribution and Use -16- Welsch. Frank 1987-1991 Member, Developmental Toxicity Profile Organizing Committee, Environmental Protection Agency 1987-1992 1994 1994 Member, Reproductive and Developmental Toxicology Program Review Subcommittee of the National Toxicology Program Board of Scientific Counselors Ad Hoc Reviewer for NIH Grants, NIH Toxicology Study Section, Subcommittee 2, Bethesda, MD, February 16-18. Member of the Scientific Organizing Committee, International Symposium on Glycol Ethers, Nancy, France, April 19-22. EDITORIAL APPOINTMENTS: 1982-86 1989-94 1989198919921995- Associate Editor, Teratology Member, Editorial Board for Fundamental and Applied Toxicology Associate Editor, Teratogenesis, Carcinogenesis, and Mutagenesis Member, Editorial Board for Archives of Toxicology Member, Editorial Board for Toxicology Section Editor, Teratology PROFESSIONAL AFFILIATIONS: Society of Toxicology American Society for Pharmacology and Experimental Therapeutics The Teratology Society American Association for the Advancement of Science German Society for Pharmacology and Toxicology European Teratology Society AWARDS AND HONORS: 1977-78 Alexander von Humboldt Foundation Research Fellowship Award (sabbatical leave) AREAS OF INTEREST Placenta function; placental drug transfer and metabolism, effect of drugs on placenta and fetus. Effects of pregnancy on pharmacokinetics and pharmacodynamics, physiologically based pharmacokinetics; extrapolation between species and to humans, risk assessment. Role of chemical metabolism for the expression of embryotoxicity/teratogenicity and to explain species differences in embryotoxic response. Teratology including manifestations of the effects of prenatal exposure to chemicals at the gross structural, micromorphological and biochemical/functional level. Development of new testing methods to predict developmental toxicity hazard. Application of in vitro methods involving embryo organ culture and whole embryo culture to study mechanisms of teratogenesis. SELECTED PUBLICATIONS: Dr. Welsch is author or co-author of more than 70 peer-reviewed publications. Among recent publications are: R&S147172 Restricted Distribution and Use -17- Welsch. Frank Sleet, R.B., J.A. John-Greene and F. Welsch: 'The Relationship of Embryotoxicity to Disposition of 2-Methoxyethanol in Mice." Toxicol. AppI. Pharmacol. 93:195-207 (1988). Stedman, D.B. and F. Welsch: "Inhibition of DNA Synthesis in Whole Embryo Culture by 2Methoxyacetic Acid and Attenuation of the Effects by Simple Physiological Compounds," Toxicol. Lett. 45:111-117(1989). Mebus, C.A. and F. Welsch: 'The Possible Role of One-Carbon Moieties in 2-Methoxyethanol and 2-Methoxyacetic Acid-Induced Developmental Toxicity," Toxicol. Apol. Pharmacol. 99: 98109(1989). Mebus, C.A., F. Welsch and P.K. Working: "Attenuation of 2-Methoxyethanol-lnduced Testicular Toxicity by Simple Physiological Compounds." Toxicol. ApdI. Pharmacol. 99:110-121 (1989). Kavlock, R.J., J.A. Greene, G.L. Kimmell, R.E. Morrissey, E. Owens, J.M. Rogers, T.W. Sadler, H.F. Stack, M.D. Waters, and F. Welsch: "Activity Profiles of Developmental Toxicity: Design Considerations and Pilot Implementation." Teratology 33:159-185 (1991). Schwetz, B.A., R.E. Morrissey, F. Welsch, and R.A. Kavlock: "In Vitro Teratology." Environ. Health Perspect. 94:265-268. Mebus, C.A., D.O. Clarke, D.B. Stedman, and F. Welsch: "2-Methoxyethanol Metabolism in Pregnant CD-I Mice and Embryos," Toxicol. AppI. Pharmacol. 112:87-94 (1992). Clarke, D.O., J.M. Duignan, and F. Welsch: "2-Methoxyacetic Acid Dosimetry-Teratogenicity Relationships in CD-I Mice Exposed to 2-Methoxyethanol," Toxicol. AppI. Pharmacol. 114:77-87 (1992). Clarke, D.O., C.A. Mebus, F.J. Miller, and F. Welsch: "Protection Against 2-Methoxyethanolinduced Teratogenesis by Serine Enantiometers: Studies of Potential Alteration of 2Methoxyethanol Pharmacokinetics," Toxicol. AppI. Pharmacol. 110:514-526 (1992). Sumner S.C.J., D.B. Stedman, D.O. Clarke, F. Welsch, and T.R. Fennell: "Characterization of Urinary Metabolites from [1,2-methoxy-13c]2-methoxyethanol in CD-I Mice Using ^C Nuclear Magnetic Resonance Spectroscopy," Chem. Res. Toxicol. : 553-560 (1992). Welsch, F.: "In Vitro Approaches to the Elucidation of Mechanisms of Chemical Teratogenesis," Mebus, C.A., D.O. Clarke, D.B. Stedman, and F. Welsch: "2-Methoxyethanol Metabolism in Pregnant CD-I Mice and Embryos," Toxicol. AppI. Pharmacol. 112: 87-94 (1992). Bolon, B., D.C. Dorman, D. Janszen, K.T. Morgan, and F. Welsch: "Phase-Specific Developmental Toxicity in Mice Following Maternal Methanol Inhalation." Fundam. AppI. Toxicol. 21: 508-516 (1993). Clarke, D.O., B.A. Elswick, F. Welsch, and R. Conolly: "Pharmacokinetics of 2-Methoxyethanol and 2-Methoxyacetic Acid in the Pregnant Mouse: A Physiologically-Based Mathematical Model," Toxicol. AppI. Pharmacol. 121: 239-252 (1993). R&S147173 Restricted Distribution and Use -18- Welsch. Frank Terry, K.K., B.A. Elswick, D.B. Stedman, and F. Welsch: "Developmental Phase Alters Dosimetry-Teratogenicity Relationship for 2-Methoxyethanol in CD-I Mice." Teratology 49: 218227(1994). Bolon, B., F. Welsch, and K.T. Morgan: "Methanol-Induced Neural Tube Defects in Mice: Pathogenesis During Neurulation." Teratology 49: 497-517 (1994). Terry, K.K., B.A. Elswick, F. Welsch, and R.B. Conolly: "Development of a PhysiologicallyBased Pharmacokinetic Model Describing 2-Methoxyacetic Acid Disposition in the Pregnant Mouse." Toxicol. AodI. Pharmacol. 132:103-114 (1995). Sumner, S.C.J., D.B. Stedman, S.-Y. Cheng, F. Welsch, and T.R. Fennell: "Dose Effects on the Excretion of Urinary Metabolites of [1,2-Methoxy-13C]2-methanol," Toxicol. Appl. Pharmacol., in press (1995). Dorman, D.C., B. Bolon, M.F. Struve, K.M.D. LaPerle, B.A. Wong, B. Elswick, and F. Welsch: "The Role of Formate in Methanol-Induced Exencephaly in CD-I Mice," Teratology 52: 30-40 (1995). Sumner, S.J., D. Stedman, S. Cheng, F. Welsch, and T. Fennell: "Characterization of Urinary Metabolites Produced Following Administration of [1,2-methoxy-'l3C]-2-methoxyethanol to Male F-344 Rats and Pregnant CD-I Mice," Proceedings of International Symposium on Health Hazards of Glycol Ethers, Nancy, France, Occup. Hyp., in press (1995). Terry, K.K., B.A. Elswick, F. Welsch, and R.B. Conolly: "A Physiologically-Based Pharmacokinetic Model Describing 2-Methoxyacetic Acid in the Pregnant Mouse," Proceedings of International Symposium on Health Hazards of Glycol Ethers, Nancy, France, Occup. Hvq.. in press (1995). Welsch, F., K.K. Terry, D.B. Stedman, and B.A. Elswick: "Linking Embryo Dosimetry and Teratogenic Response to 2-Methoxyethanol at Different Stages of Gestation in Mice," Proceedings of International Symposium on Health Hazards of Glycol Ethers, Nancy, France, QccupJHvg.. in press (1995). BOOK CHAPTERS (selected from 9 book chapters) Welsch, F.: "Disruption of Cell-Cell Channels as an Event Common to the Potential Mechanism of Action of Some Chemicals with Activity in Teratogenesis and Carcinogenesis," In Progress in Cancer Research and Therapy. Vol. 34, "Tumor Promoters: Biological Approaches for Mechanistic Studies and Assay Systems" (R. Langenbach, J.C. Barrett, and E. Elmore, eds.), Raven Press, pp. 113-130 (1988). Welsch, F.: 'Teratogens and Cell-to-Cell Communication," jn "Cell Intercommunication" (W.C. De Mello, ed.), CRC Press, pp. 133-160 (1990). Welsch, F.: "Short Term Methods of Assessing Developmental Toxicity Hazard: Status and Critical Evaluation," In: "Issues and Reviews in Teratology", Vol. 5 (H. Kalter, ed.), Plenum Press, pp. 115-153 (1990). R&S147174 Restricted Distribution and Use -19- BRIAN A. WONG Scientist I, Chemical Industry Institute of Toxicology EDUCATION: Ph.D., Environmental Engineering Science, California Institute of Technology, Pasadena, CA. 1991. M.S., Environmental Engineering Science, California Institute of Technology, Pasadena, CA, 1984. B.S., Chemistry, Harvey Mudd College, Claremont, CA, 1974. EXPERIENCE: 1991-present Scientist I, Chemical Industry Institute of Toxicology, Research Triangle Park, NC. 1983-1991 Research Assistant, California Institute of Technology, Pasadena, CA. 1979-1983 Senior Research Technologist, Inhalation Toxicology Research Institute, Albuquerque, NM. 1974-1979 Laboratory Technologist, Inhalation Toxicology Research Institute, Albuquerque, NM. PROFESSIONAL AFFILIATIONS: American Association for the Advancement of Science Association for the Advancement of Aerosol Research AREAS OF INTEREST: Aerosols - physical, optical, thermodynamic properties. Combustion - kinetics and chemistry of coal combustion and fly ash formation, inhalation Toxicology - biological effects of air pollution, hazardous wastes. Atmospheric Chemistry - air pollution formation, abatement. Cleanroom Technology - application of aerosol science to cleanrooms. PEER REVIEWED PUBLICATIONS: 1. G. J. Moser, B. A. Wong, D. C. Wolf, O. R. Moss and T. L. Goldsworthy (1995). Comparative short-term effects of methyl tertiary butyl ether and unleaded gasoline vapor in female B6C3F1 mice. Toxicol. Appl. Pharmacol., submitted as of 4/95. 2. R. J. Han, O. R. Moss and B. A. Wong (1995). Application of an analytic solution of the mass transfer equation to the case of forced convective flow around a cylindrical and a spherical particle. J. Aerosol Sci., in press. 3. T. R. Gelzleichter, E. Bermudez, J. B. Mangum, B. A. Wong, O. R. Moss, and J. I. Everitt. (1995). Pulmonary and pleural responses in Fischer-344 rats following short-term inhalation of a carcinogenic synthetic vitreous fiber. II. Pathobiologic responses. Fundam. Appl. Toxicol., in press. 4. T. R. Gelzleichter, E. Bermudez, J. B. Mangum, B. A. Wong, J. I. Everitt, and O. R. Moss (1995). Quantitation of pulmonary and pleural fiber burdens in Fischer-344 rats following short-term inhalation of a carcinogenic synthetic vitreous fiber. Fundam. Appl. Toxicol., in press. R&S147175 Restricted Distribution and Use -20- t W_Qiia,_BrianA 5. D. C. Dorman, B. Bolon, M. F. Struve, K. M. D. LaPerle, B. A. Wong, B. Elswick, and F. Welsch (1995). The role of formate in methanol-induced exencephaly in CD-I mice. Teratology 52:30-40. 6. D. C. Dorman, B. A. Wong, M. F. Struve, R. A. James, K. M. D. LaPerle, M. W. Marshall, and B. Bolon (1995). Development of a mouse whole-body exposure system from a directed-flow, rat nose-only system. Inhalation Toxicol., in press as of 5/95. 7. C. D. Brown, B. A. Wong, and T. R. Fennell (1995). In vivo and in vitro kinetics of ethylene oxide metabolism in rats and mice. Toxicol. Appl. Pharmacol., Submitted as of 8/94. 8. B. A. Wong, G. R. Gavalas, and R. C. Flagan (1995). The effect of char formation temperature on the densification of a bituminous coal char during gasification. Energy and Fuels 9: 493-499. 9. B. A.Wong, G. R. Gavalas, and R. C. Flagan (1995). Laser ignition of levitated char particles. Energy and Fuels 9:484-492. 10. A. A. J. J. L. Rutten, E. Bermudez, J. B. Mangum, B. A. Wong, O. R. Moss, and J. I. Everitt (1994). Mesothelial cell proliferation induced by intrapleural instillation of man-made fibers in rats and hamsters. Fundam. Appl. Toxicol. 23:107-116. 11. R. J. Han, O. R. Moss, and B. A. Wong (1994). Airborne fiber separation by electrophoresis and dielectrophoresis. Aerosol Sci. Technol. 21:241-258. 12. J. I. Everitt, E. Bermudez, J. B. Mangum, B. A. Wong, O. R. Moss, D. Janszen, and A. A. J. J. L. Rutten (1994). Pleural lesions in Syrian hamsters and Fischer-344 rats following intrapleural instillation of man-made ceramic or glass fibers. Toxicol. Pathol. 22:229-236. BOOK CHAPTERS. MONOGRAPHS AND PROCEEDINGS: 1. B. A. Wong (1995). Generation and characterization of gases and vapors. In: Concepts in Inhalation Toxicology, R. O. McClellan and R. Henderson, eds., Taylor and Francis, Washington, DC, in press as of 2-95. 2. T. R. Gelzleichter, J. B. Mangum, E. Bermudez, B. A. Wong, O. R. Moss and J. I. Everitt (1995). Pulmonary and pleural leukocytes from F344 rats produce elevated levels of fibronectin following inhalation of refractory ceramic fibers. Proceedings, 5th International Inhalation Symposium, Hannover, Germany, February 19-24,1995. 3. O. R. Moss, B. A. Wong, and B. Asgharian. (1994). Bimodal bivariate log-normal distributions in the application of inhalation toxicology specific to the measurement of fiber and particle dosimetry. In: Toxic and Carcinogenic Effects of Solid Particles in the Respiratory Tract., U. Mohr, D. L. Dungworth, J. L. Mauderly, and G. Oberdoerster, eds., ILSI Press, Washington, DC, p. 623-628. 4. F. J. Miller, S. Anjilvel, B. Asgharian, J. S. Kimbell, E. Bermudez, M. N. Godo, T. R. Gelzleichter, B. A. Wong, and O. R. Moss (1994). A strategy for combining experimental, large-scale, and site-specific models to determine fiber deposition in animals and humans. In: Toxic and Carcinogenic Effects of Solid Particles in the Respiratory Tract., U. Mohr, D. L. Dungworth, J. L. Mauderly, and G. Oberdoerster, eds., ILSI Press, Washington, DC, p. 619-622. Restricted Distribution and Use -21- R&S147176 Wona. Brian A. 5. J. I. Everitt, E. Bermudez, J. Mangum, B. Wong, F. Miller and O. Moss (1994). Acute pleural response of hamsters and rats to inhaled ceramic fibers. In: Toxic and Carcinogenic Effects of Solid Particles in the Respiratory Tract., U. Mohr, D. L. Dungworth, J. L. Mauderly, and G. Oberdoerster, eds., ILSI Press, Washington, DC, p. 599-602. 6. A. Rutten, E. Bermudez, J. Mangum, B.Wong, O. Moss and J. Everitt (1994). Pleural pathology in hamsters and rats exposed to instilled man-made vitreous fibers. In: Toxic and Carcinogenic Effects of Solid Particles in the Respiratory Tract., U. Mohr, D. L. Dungworth, J. L. Mauderly, and G. Oberdoerster, eds., ILSI Press, Washington, DC, p. 595-598. R&S147177 Restricted Distribution and Use -22- JEFFREY EVERITT Scientist II, Chemical Industry Institute of Toxicology EDUCATION: Biological Science, Cornell University, Ithaca, NY, 1973 D.V.M., Veterinary Medicine, Cornell University, Ithaca, NY, 1977 Certificate of Residency, Veterinary Pathology, University of Pennsylvania, Philadelphia, PA, 1980 PROFESSIONAL LICENSES AND SPECIALTY CERTIFICATIONS: Licensed to practice veterinary medicine in NY, PA, and NC American College of Veterinary Pathologists, Diplomate, 1982 American College of Laboratory Animal Medicine, Diplomate, 1988 EXPERIENCE: 1993-present Scientist II, Department of Experimental Pathology and Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 1985-1993 Scientist I, Department of Experimental Pathology and Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 1981-1985 Teaching Associate, Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 1980-1981 Lecturer in Pathology, University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Kennett Square, PA 1977-1980 Resident in Pathology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA ACADEMIC AFFILIATIONS: 1987-Present Adjunct Assistant Professor of Pathology, School of Veterinary Medicine, North Carolina State University, Raleigh, NC ADVISORY POSITIONS: Member, Pathology Working Groups, National Toxicology Program, NIEHS, Research Triangle Park, NC (1985 -) Member, NIH DRG Special Study Section (1992, 1993) Ad hoc consultant in laboratory animal medicine for the American Association for the Accreditation of Laboratory Animal Care (AAALAC) (1990-present) Ad hoc consultant in laboratory animal medicine, Veterans Administration, Department of Defense (1994-present) R&S147178 Restricted Distribution and Use -23- Everitt. Jeff PROFESSIONAL AFFILIATIONS: American Veterinary Medical Association American College of Veterinary Pathologists Co-chairperson Pulmonary Specialty Group, 1991; Chairman, 1992 United States and Canadian Academy of Pathology American Association for Laboratory Animal Science Committee on Public Policy, 1987-1990; Chairman, 1991 Abstract Review Committee, 1989 District IV Meeting Chairman, 1989-1990 American Society of Laboratory Animal Practitioners Society of Toxicologic Pathologists American College of Laboratory Animal Medicine North Carolina Chapter of the Society of Toxicology North Carolina Academy of Laboratory Animal Medicine Board of Directors, 1989-1990 President-elect, 1992; President, 1993 Association of Primate Veterinarians Association of American Pathologists HONORS: NSF Undergraduate Research Program, Jackson Laboratory, 1972 Anna Olafson Sussex Pathology Award, Cornell University, 1976 Co-Author 1992 Research Paper of the Year published in Fundam. Appl. Toxicol. AREAS OF INTEREST: Comparative Medicine (Laboratory animal issues in toxicology studies) Toxicologic Pathology (Lung and kidney carcinogenesis) Pulmonary Toxicology (Pathobiology of fiber-induced disease) SELECTED PUBLICATIONS: Dr. Everitt is the author or co-author of more than 60 publications. Hesterberg, T.W., Boreiko, C.J., Maness, S.C., Iglehart, J.D., Mangum, J.B. Everitt, J.I.: Carcinogen-induced unscheduled DNA synthesis (UDS) in xenotransplanted human tracheobrohchial epithelium: Comparison with rat tracheal epithelium. Carcinogenesis 9:467-472, 1988. Everitt, J.I., Boreiko, C.J., Mangum, J.B., Martin, J.T., Iglehart, J.D., Hesterberg, T.W.: Development of a tracheal implant xenograft model to expose human bronchial epithelial cells to toxic gases. Toxicol. Pathol. 17:465-473,1989. Monticello, T.M., Morgan, K.T., Everitt, J.I., Popp, J.A.: Effects of formaldehyde gas on the respiratory tract of rhesus monkeys: Pathology and cell proliferation. Am. J. Pathol. 134:515-527. 1989. Bermudez, E., Everitt, J., Walker, C.: Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture. Exp. Cell Res. 190:91-98.1990. R&S147179 Restricted Distribution and Use -24- Everitt. Jeff Everitt, J.I., Hesterberg, T.W., Boreiko, C.J.: Uses of tracheal implants in toxicology and carcinogenesis studies. Toxicology 60:27 - 40,1990. Everitt, J.I., Richter, C.B.: Infectious diseases of the upper respiratory tract: implications for toxicology studies. Env. Health Persp. 85:239-247, 1990. Mangum, J.B., Everitt, J.I., Bonner, J.C., Moore, L.R., Brody, A.R.: Co-culture of primary pulmonary cells to model alveolar injury and translocation of proteins. In Vitro Cell. Dev. Biol. 26:1135-1143,1990. Casanova, M., Morgan, K.T., Steinhagen, W.H., Everitt, J.I., Popp, J.A., Heck, H.A.: Covalent binding of inhaled formaldehyde to DNA in the respiratory tract of rhesus monkeys: pharmacokinetics, rat-to-monkey interspecies scaling and extrapolation to man. Fundam. Appl. Tox. 17:409-428, 1991. Funaki, K., Everitt, J., Oshimura, M., Freed, J.J., Knudson, Jr., A.G., and Walker, C.: Hereditary renal cell carcinoma in the rat associated with nonrandom loss of chromosomes 5 and 6. Cancer Res. 51:4415-4422,1991. Funaki, K., Everitt, J., Bermudez, E., Walker, C.: Trisomy of rat chromosome 1 associated with mesothelial cell transformation. Cancer Res. 51:4059-4066,1991. Kinnula, V.L., Everitt, J.I., Whorton, A.R., Crapo, J.D.: Hydrogen peroxide production by freshly isolated alveolar type II cells, alveolar macrophages and cultured endothelial cells. Am. J. Physiol. 261 84-91. 1991. Walker, C., Funaki, K., Knudson, A.G., and Everitt, J.: The Eker rat: A model for hereditary renal cell carcinoma. In, Advances in Gene Technology: The Molecular Biology of Human Genetic Disease. Vol. 1, F. Ahmed, H. Bialy, S. Black, R. Howell, et al., Miami Bio/Technology Winter Symposia, 1990,103,1991. Walker, C., Everitt, J., Freed, J.J., Knudson, Jr., A.G., Whiteley, L.O.: Altered expression of rat TGF-alpha in hereditary renal cell carcinoma. Cancer Res. 51:2973-2978,1991. Walker, C., Bermudez, E., and Everitt, J.: Growth factor and receptor expression by mesothelial cells: A comparison between rodents and humans. In, Cellular and Molecular Aspects of Fiber Carcinogenesis. C.C. Harris, J.F. Lechner, B.R. Brinkley, eds., Cold Spring Harbor Laboratory Press, NY, 149-158,1991. Kinnula, V.L., Chang, L.Y., Everitt, J.I., and Crapo, J.D.: Oxidant and antioxidant characteristics in alveolar-epithelial type 11 cells: Immunocytochemical and biochemical comparisons between in situ, freshly isolated and cultured cells. Am. J. Physiol. 262 (Lung Cell. Mol. Physiol. ), L69-L77, 1992. Walker, C., Everitt, J., and Barrett, J.C.: Possible cellular and molecular mechanisms for asbestos carcinogenicity. Am. J. Indus. Med. 21:253-273,1992. Walker, C., Bermudez, E., Stewart, W., Bonner, J., Molloy, C.J., and Everitt, J.: Characterization of platelet-derived growth factor and platelet-derived growth factor receptor expression in asbestos-induced rat mesothelioma. Cancer Res. 52:301-306.1992. R&S147180 Restricted Distribution and Use -25- Everitt. Jeff Walker, C., Goldsworthy, T.L., Wolf, D., and Everitt, J.: Predisposition to carcinogen-induced renal cell carcinoma due to alteration of a cancer susceptibility gene. Science 255:1693-1695, 1992. Everitt, J.I., Goldsworthy, T.L., Wolf, D.C., and Walker, C.L.: Hereditary renal cell carcinoma in the Eker rat: A rodent familial cancer syndrome. J. Urol. 148:1932-1936.1992. Kinnula, V.L., Everitt, J.I., Mangum, J., Chang, L.Y., and Crapo, J.D.: Antioxidant defense mechanisms in cultured pleural mesothelial cells. Am. Rev. Respir. Dis. 7:95-103,1992. Lacy, S.A., Mangum, J.B., and Everitt, J.I.: Cytochrome P450- and glutathione-associated enzyme activities in freshly-isolated enriched lung cell fractions from B-napthoflavone-treated male F-344 rats. Toxicology Z147-160,1992. Walker, C., Recio, L., Funaki, F., and Everitt, J.: Cytogenetic and molecular correlates between rodent and human renal cell carcinoma. Comparative Molecular Carcinogenesis. A.J.P. KleinSzanto and T.J. Slaga, eds., Wiley-Liss, Inc., NY, 289-302,1992. Walker, C., and Everitt, J.: Molecular approaches to understanding mechanisms of mesothelioma development. Contemporary Issues in Fiber Toxicology. D. Warheit, ed., Academic Press, NY, 195-204, 1993. Walker, C., Bermudez, E., Bonner, J., and Everitt, J.: Species-specific PDGF expression in mesothelioma. Eur. Resp. Rev. 3(111:153-155.1993. Satoh, H., Lamb, P.W., Dong, J.T., Everitt, J., Boreiko, C., Oshimura, M., and Barrett, J.C.: Suppression of tumorigenicity of A549 lung adenocarcinoma cells by normal human chromosomes: 3 and 11 introduced via microcell-mediated chromosome transfer. Molec. Care. Z:157-164,1993. Farris, G.M., Everitt, J.I., Irons, R.D., Popp, J.A.: Carcinogenicity of inhaled benzene in CBA mice. Fundam. Appl. Toxicol. 20:503-507,1993. Cattley, R.C., Everitt, J.I., Gross, E.A., Moss, O.R., Hamm, T.E., Jr., and Popp, J.A.: Carcinogenicity and toxicity of inhaled nitrobenzene in B6C3F1 mice and F344 and CD rats. Fundam. Appl. Toxicol. 22:328-340,1994. Walker, C., Rutten, F., Yuan, C., Pass, H., Mew, D.M., and Everitt, J.: Wilms' tumor suppressor gene expression in rat and human mesothelioma. Cancer Res. 54:3101-3106.1994. Everitt, J.I., Bermudez, E., Mangum, J.B., Wong, B., Moss, O.R., Janszen, D., and Rutten, A.A.J.L.: Pleural lesions in Syrian hamsters and Fischer-344 rats following intrapleural instillation of man-made fibers. Toxicol. Pathol. 22(31:229-236.1994. Rutten, A.A.J.J.L., Bermudez, E., Mangum, J.B., Wong, B., Moss, O.R., and Everitt, J.I.: Mesothelial cell proliferation induced by intrapleural instillation of man-made fibers in rats and hamsters. Fundam. Appl. Toxicol. 23:107-116,1994. Hard, G.C., Long, P.H., Crissman, J.W., Everitt, J.I., Yano, B.L., and Bertram, T.A.: Atypical tubule hyperplasia and renal tubule tumors in conventional rats on 90-day toxicity studies. Toxicol. Pathol, (in press). R&S147181 Restricted Distribution and Use -26- Everitt- Jeff Horesovsky, G., Ginsler, J., Everitt, J., and Walker, C.: Increased susceptibility to in vitro transformation of cells carrying the Eker susceptibility mutation. Carcinogenesis (in press). R&S147182 Restricted Distribution and Use -27- PATRICIA O'BRIEN POMERLEAU Manager, Quality Assurance, Chemical Industry Institute of Toxicology EDUCATION: Bachelor of Science, Biology, Marymount College, Tarrytown, NY, 1964. Master of Science, Cellular Biology, Magna Cum Laude, Fairleigh Dickinson University, Teaneck, NJ, 1967. EXPERIENCE: 1990-present 1986-1990 1971-1986 1983-1986 1979-1983 1974-1979 1971-1974 1970-1971 1968-1970 1964-1968 Quality Assurance Manager, Chemical Industry Institute of Toxicology, Research Triangle Park, NC Manager, Quality Assurance, Rhone-Poulenc Rorer Pharmaceuticals Inc., Rh6ne-Poulenc Rorer Central Research, Horsham, PA Revlon Health Care Group (acquired by Rorer Pharmaceuticals, Inc. in 1985), USV Laboratories, Tuckahoe, NY Manager, Quality Assurance Unit, [FDA Good Laboratory Practice (GLP) regulations] Head, Quality Assurance Unit, [FDA Good Laboratory Practice (GLP) regulations] Senior Biochemist and Assistant Radiation Safety Officer Biochemist and Assistant Radiation Safety Officer Chemical Technician in Cancer Research, Farbenfabriken Bayer Research Center, Wuppertal, Germany Research Associate in Cancer Research, Yale Medical School, Department of Pharmacology and Medicine, New Haven, CT- Research Assistant in Viral Oncology, Charles Pfizer and Company, Inc., The John L. Smith Memorial for Cancer Research, Maywood, NJ ADVISORY APPOINTMENTS: Member of Scientific Review Panel for Proposals submitted to the National Institute of Health, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC. Reviewed (8/94) proposals submitted to NIEHS for conduct of studies of the toxic and carcinogenic potential of selected chemicals in laboratory animals. Member of Scientific Review Panel for Proposals submitted to the National Institute of Health, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC. Reviewed (4/94) proposal submitted to NIEHS for the Archives for the National Toxicology Program (NTP). Member of Scientific Review Panel for Proposals submitted to the National Institute of Health, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC. Reviewed proposals (5/92) submitted to NIEHS for conduct of studies of the toxic and carcinogenic potential of selected chemicals in laboratory animals. Member of Scientific Review Group for National Toxicology Program Proposals submitted to the National Institute of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC. Reviewed proposals (8/86) for scientific and technical merit in response to "Good Laboratory Practice Compliance and Data Auditing Support Resource" program. R&S147183 Restricted Distribution and Use -28- Pomerieau. Patricia EDITORIAL APPOINTMENTS: Member, Board of Publications, Society of Quality Assurance (1990-1993) Society of Quality Assurance Newsletter, Editor-in-Chief (1992-1993) PROFESSIONAL AFFILIATIONS: t North Carolina Society of Toxicology (1994-present) North Carolina Quality Assurance Discussion Group (NCQADG) Past President (1994) President (1991 - 1993) QA in Basic Research Committee (1991 - present) Society of Quality Assurance (SQA) President (1994-1995) Vice President (1993-1994) and Chairperson 1994 SQA Annual Meeting Planning Committee Board of Publications, Chairperson (1993, appointed; member, 1990-1993) Regulatory Review Committee (1992 - present) Total Quality Specialty Section (1993 - present) Historical Committee (1991 - present) Articles of Incorporation and By-Laws Committee (1989 - 1991) Education Committee (1989 -1990) Nominating Committee (1988) Ethics and Membership Committee (1984 -1986) Planning Committee (1983) Carolina Society of Environmental Toxicology and Chemistry (SETAC) (1992 - present) American Society for Quality Control (1986 - present) Drug Information Association (1986 - present) Pharmaceutical Manufacturer's Association, Bioresearch Monitoring Subcommittee (1988 -1991) AREAS OF INTEREST Research interests include the application of Quality Assurance (QA) principles in the research environment. Ms. O'Brien Pomerieau has major expertise in Quality Assurance (QA) and Good Laboratory Practice (GLP) regulations and has planned, coordinated, and managed a QA group for auditing preclinical studies performed under the GLP regulations. Interest also includes Total Quality Management (TQM) principles, toxicology research, analytical methodology in biochemistry and drug metabolism of pharmaceuticals and their metabolites, radiation safety, cancer research, with focus on chemotherapeutical agents, and tissue culture including Rauscher and Moloney viruses and Burkett's lymphoma cells. PUBLICATIONS: O'Brien Pomerieau, P.: Performing Good Laboratory Practice Regulation Studies in a Traditionally Non-GLP Facility: Quality Assurance: Good Pract. Regulation Law 3(2): 149-155,1994. O'Brien Pomerieau, P. and Benson, B.: Looking Back - A History of Progress, Society of Quality Assurance, Qual. Assurance: Good Pract. Regulat. Law 3(1): 110-116,1994. O'Brien Pomerieau, P.: Total Quality Crossword Puzzle Answers, Society of QA Newsletter, QA Classifieds 4(3): 2,1993. R&S147184 Restricted Distribution and Use -29- Fomerleau, Patricia O'Brien Pomerleau, P.: Quality Assurance (QA) Perspective on Compliance Education through Participationa! QA Programs, Qual. Assur.: Good Pract. Regulat. Law 2(2): 197-205,1993. O'Brien Pomerleau, P.: Total Quality Crossword Puzzle, Society of QA Newsletter 8(2): 6-7, 1993. O'Brien Pomerleau, P., McClellan, R.O., Popp, J.: Quality Assurance at CUT, CUT Activities 12(2): 1-5, 1992. O'Brien Pomerleau, P.: Who Are the Players and What Do They Bring to the Science and Compliance Teams? (American College of Toxicology and Society of Quality Assurance Joint Symposium - Science and Compliance: Study Management Through Total Quality), J. Am. Coll. Toxicol. 10(3): 377,1991. O'Brien Pomerleau, P.: GLP Crossword Puzzle, Society of QA Newsletter 6(2): 9,1991. Grebow, P., Feeney, W., Johnston, M., Lettieri, J., Li, H., Magnien, E., O'Brien, P., Swillo, R., Weinryb, I., Wolf, P., Marsiglia, J.: The Pharmacodynamics of Bucanide (RHC G-233): Pharmacokinetic Parameters and Relationship Between Plasma Levels and the Effect on the Electrocardiogram in the Dog, Research Communications in Chemical Pathology and Pharmacology 32(3): 407,1981. Grebow, P., O'Brien, P., Weinryb, I.: Stability of Tryptophan in Human Gastric Fluid, Proceedings of the Second International Meeting on Tryptophan Metabolism: Biochemistry, Pathology, and Regulation, 1977. Bertino, J., Q'Brien, P., McCullough, J.: Inhibition of Growth of Leukemia Cells by Enzymic Folate Depletion, Science 172: 161,1971. Nixon, P., Levitt, M., Kirschner, E., O'Brien, P., Bertino, J.: The Metabolism of 5Methyltetrahydrofolate in Patients with Pernicious Anemia, Journal of Clinical Investigations 46: 60a, 1969. Wright, B., O'Brien, P., Stephens, R., Bielewicz, H., Shibley, G.: Growth Curves of Rauscher and Friend Murine Leukemia Viruses in JLS-V9 Tissue Culture, Cancer Research 28: 1265,1968. Wright, B., O'Brien, P., Shibley, G., Mayyasi, S., Lasfargues, J.: Infection of an Established Mouse Bone Marrow Cell Line (JLS-V9) with Rauscher and Moloney Murine Leukemia Viruses, Cancer Research 27: 1672,1967. ABSTRACTS: O'Brien Pomerleau, P.: Compliance Education: Quality Assurance Perspective, QA. Good Pract. Reg. & Law 1(2): 150-151,1992. PRESENTATIONS Ms. Pomerleau is a frequent speaker at meetings of professional societies and in workshops concerned with Quality Assurance. R&S147185 Restricted Distribution and Use -30- Restricted Distribution and Use Organizational Structure of the Center for Lite Sciences and Toxicology -vj CO 3 S' 3 w o B(3U NU o' 3 O 3saa" 33 SOCW6 90u>lSfy 7.4 Biographical Sketches RTI Detailed curricula vitae can be found in Appendix #2. R&S 147187 Restricted Distribution and Use -32- 8.0 CORPORATE QUALIFICATIONS 8.1. Organization Chart CUT CHEMICAL INDUSTRY INSTITUTE OF TOXICOLOGY Board of Directors Chairman - Bell Vice Chairman - Capaldi President - McClellan Senior Advisor Preston Quality Assurance O'Brien Pomerleau Chemical Carcinogenesis Program _ Program Manager - Bond Associate Program Manager - Cattley Non-Cancer Programs Program Manager - Miller Respiratory Toxicology (Miller) Endocrine Toxicology (Conolly) Developmental Toxicology (Welsch) Research Infrastructure Inhalation Toxicology (Moss)** Animal Care (Everitt)** Analytical Services (Turner)*** Biostatistics (Janszen)** Computer Operations (Gerard)** Hematology/Flow Cytometry (Farris)* Clinical Chemistry (Cattley)*** Electron Microscopy (Wolf)*** Necropsy/Histopathology (Morgan)** 'reports to McClellan "reports to Miller "reports to Bond Administrative Support Financial (Althaus)* Accounting Purchasing Human Resources (Althaus, Acting Human Resources Manager)* Information Services (Griffin)* Editorial Library Word Processing/Graphics Facilities, Health & Safety (Cook)* Maintenance (Pittman) Facilities Services (Howard) Health & Safety (Crouse) Restricted Distribution and Use -33- 8.2. Organization Chart RTI Restricted Distribution and Use Raaaarch TrtangU InaUtuta - Raaaach Organization Laat Update January 11, ini 68 IZ'b't- S'Std 8.3 Statement of CUT Liability Insurance Coverage The Chemical Industry Institute of Toxicology is insured against general liability claims by the Hartford Insurance Companies up to a limit of $1,000,000 per each occurrence. Additional "Umbrella" coverage is in force, also provided by the Hartford, which raises the coverge an additional $4,000,000. 8.4 Research Facilities at CUT General Facility CUT is housed in a modern 94,000 square feet laboratory and office facility that includes a molecular biology core facility, neurotoxicology laboratory, and specifically equipped facilities for electron microscopy, nuclear magnetic resonance spectroscopy, mass spectrometry, liquid and gas chromatography, radioisotope analysis, histology, necropsy, animal housing (including primates), and inhalation toxicology. An active animal care and use program supports acute and chronic studies. Complete computer capabilities including both VAX mainframe, and personal computers are available. The Institute's library provides access to multiple computerbased literature research systems. Animal Facilities The AAALAC accredited animal facility at CUT is supervised by a veterinarian board certified in laboratory animal medicine. The facility is a centralized barrier facility with an average daily census of several thousand rodents and a few nonhuman primates. The facility has specialized equipment and standard operating procedures which permits animal exposures to hazardous chemical agents and maintains the animals in controlled monitored environments under disease free conditions. The rodent area contains nine mass air displacement rooms (Hazleton Bioclean); 20 conventional rooms containing inhalation chambers; a metabolism room; a chemical procedures room with three chemical containment hoods; a diet preparation room with twin steel blenders with hood and glovebox containment; and typical support areas such as clean and dirty cage wash areas with two rack and one tunnel washer (Girton). There is complete redundancy in the HVAC equipment and a fully automated and computerized environmental monitoring system (Andover Infiniti System). CUT procures rodents from specialized vendor areas and maintains one of the most extensive surveillance programs in the laboratory animal field. All animal clinical observations are conducted by a fully certified and experienced cadre of animal care technicians. The CUT animal care unit has experience in the conduct of acute subchronic, and long-term bioassays using a variety of stocks and strains of laboratory rodents. All clinical observations and body weights are computer recorded using PATH-TOX software (Xybion Corporation). The CUT animal facility is a seven day/week operation. Restricted Distribution and Use -35- R&S14719G Inhalation Exposure Facilities CUT'S inhalation exposure facilities contain equipment capable of handling a wide variety of animal inhalation studies. These range from long-term whole body exposures to brief nose-only exposures to radioactive materials. A staff of five attends the daily operations of the facility with oversight from three doctoral-degreed scientists. Major equipment includes 20 stainless steel 8 m3 inhalation chambers with a capacity of up to 300 rats, several smaller 1 m3 exposure chambers (e.g., Lab Products H-1000 inhalation chambers with up to 96 rat capacity), multiple nose-only towers, and a variety of other specialty inhalation chambers. Environmental parameters (e.g., temperature, relative humidity, airflow, and static pressure) inside the large chambers are automatically controlled, and the data logged and reported by a building management system. Whole body exposures may be automated for increased efficiency. The staff is fully trained in the use of a variety of analytical techniques such as gas chromatography and infrared spectrometry to monitor exposures. R&S147191 Restricted Distribution and Use -36- Schematic of CUT Facility 1. Animal Acclimation 2. Inhalation Exposure Chambers H&S147192 Restricted Distribution and Use -37- 8.5. General Facilities at RTI The facilities of the Reproductive and Developmental Toxicology Wing at RTI are described in Appendix #4. 8.6 Background and Related Research Capabilities 8.6.1 Quality Assurance at CUT It is the policy of the Chemical Industry Institute of Toxicology (CUT) and the Research Triangle Institute (RTI) to use quality assurance procedures to assure that all data generated in research is of known, documented high quality. The on-site CUT Quality Assurance office and archive are composed of modem office spaces equipped with two Macintosh personal computers for word processing and database capture, filing cabinets, as well as a Space Saver high-density mobile storage system and slide drawers. This space is secured through a CUT card-access building control as well as locked authorization access into the Quality Assurance/archive area. CIlTs on-site facility is complemented by a secure off-site location for archiving. The on-site RTI Quality Assurance office is composed of modern office spaces equipped with three Macintosh personal computers for word processing and database capture, as well as locked controlled access filing cabinets. The building at RTI has locked authorization access during non-business hours. Specific aspects of the quality assurance and archival areas that relate to the proposed studies include the following capabilities. Full-time on-site Quality Assurance at CUT and RTI will provide support for the proposed studies through protocol reviews, critical phase inspections, as well as study data and report audits. The results of Quality Assurance inspections and audits will be reported to the Study Director and to Management to assure appropriate follow-up action, if applicable. CUT'S controlled, secure archive capabilities will be available for the proposed study materials either as the studies are on-going or at the close of the proposed studies. Built into the process of quality data generation is the standard practice of including quality control procedures into the data collection process. The quality criteria used include reproducibility, accuracy, appropriate sampling, and standardization of data collection. Wellwritten SOPs, which augment the study protocol, are used to document routine, critical procedures. Data audits are performed to evaluate and report to the study director any inconsistencies between the data collection or study conduct and the required study methods as described in the protocol, SOPs, and GLPs. The report audit evaluates the completeness and consistency of the final report and the raw data. A quality assurance review of study records is augmented by peer review processes that are part of the CUT research program (e.g., extensive internal peer review of protocols, SOPs, abstracts, manuscripts, and presentations). All scientific information disseminated from CUT is extensively reviewed internally before release. Restricted Distribution and Use -38- R&S147193 8.6.2 Related Research Activities The Chemical Industry Institute of Toxicology (CUT) was founded in 1974 by a core group of 11 chemical companies to provide the scientific data necessary for making decisions about the safe use of chemicals. Since its inception, CUT has established itself as a premier institute for the study of toxicologic disease and has gained an international reputation in the field of toxicology. CIIT's mission is to provide an improved scientific basis for understanding and assessing the potential adverse effects of chemicals, pharmaceuticals, and consumer products on human health. The Institute has over 30 full-time doctoral level staff scientists at CUT with diverse expertise in toxicology, neurotoxicology, biochemistry, experimental pathology, molecular biology, inhalation toxicology, developmental toxicology, chemical engineering, extrapolation modeling, and biostatistics. The Institute's professional staff is complemented by over 25 postdoctoral fellows and a technical and support staff in excess of 100 individuals. Approximately 60% of the Institute's resources are used to study chemical carcinogenesis. CUT is developing methods for assessing the cancer-causing potential of chemicals through the in-depth study of key mechanisms of carcinogenicity. The Institute also has a strong program in respiratory toxicology, which seeks to understand species similarities and differences in mechanisms linking exposure, dose, and response for airborne substances. Small but productive programs in neurotoxicology, developmental toxicology, and immunotoxicology round out the Institute's research efforts. The scientific data generated reduce the uncertainties in chemical-specific risk assessments and make possible the use of risk assessment models that can be generalized across classes of compounds. CUT has a substantial research program that is investigating the toxicity of various fuels and fuel additives (e.g., methanol, MTBE, ETBE). Included in these studies are efforts to develop improved approaches to human risk assessment by extrapolating animal developmental toxicity data including mode of action information via physiologically based pharmacokinetic models of rodent gestation. R&S147194 Restricted Distribution and Use -39- Appendix 1 Letter from Dr. Tyl, December 4, 1995 R&S147195 R&S147196 RESEARCH TRIANGLE INSTITUTE Chemistry and Life Sciences Center for Life Sciences and Toxicology Decembers 1995 /RTI Dr. James A. Bond Chemical Industry Institute of Toxicology P. O. Box 12137 6 Davis Drive Research Triangle Park, NC 27709 Dear Dr. Bond: RE: RTI B&P No.: P606-025 In response to our discussions oonceming the collaboration of Research Triangle Institute (RTI) with CUT in a submission to Dr. H. Shah of the Chemical Manufacturers Association for reproductive and developmental toxicity studies of inhaled vinyl chloride, RTI and I are pleased to submit the enclosed cost estimates for performing a definitive developmental toxicity study of inhaled vinyl chloride in CD (SpragueDawley) rats, and a definitive reproductive toxicity study of inhaled vinyl chloride in CD (Sprague-Dawley) rats. Detailed descriptions of the proposed study designs are presented below, based on the Dow protocol provided by Dr. Shah and the most recent OPPTS Testing guidelines (see below). The cost estimates are presented in the attached letter from Ms. C. S. Parker, RTI Senior Contracts Administrator, and include costs for RTI's portions of the two studies following the study designs detailed below. The studies would be performed under U.S. EPA (TSCA) GLPs (Good Laboratory Practice regulations) and the most recent draft OPPTS Health Effects Test Guidelines for Prenatal Developmental Toxicity Study (OPPTS 870.3700, August 11,1995) and for Reproduction and Fertility Effects (OPPTS 870.3800, August 11,1995). As we have discussed, I would be Co-Study Director for both studies and the RTI Quality Assurance Unit (along with the CUT QAU) would oversee protocols, performance of studies and reports. The proposed study designs are as follows: A. Proposed Study Designs 1. Definitive Developmental Toxicity Study in Rats A total of 170 virgin female rats will be purchased and mated 1:1 to the males in the CUT breeding colony. The date of insemination (dropped copulation plug, vaginal sperm or vaginal copulation plug) will be designated gestational day (gd) 0. A total of 100 sperm-positive female rats ("dams") will be employed in four groups (three chemical and one vehicle control groups), 25 dams per group. The rats will be exposed to vinyl chloride by inhalation six hours per day, on gd 6 through 19 at exposure concentrations of 0,10,100 and 1100 ppm (as provided in Dow's protocol). These exposures will occur during the first prebreed exposure period of F0 animals in the two-generation study. Clinical observations will be documented daily (twice daily during the exposure period), and dams will be weighed on gd 0, 6, 9,12,15,18,19 and 20. Feed consumption will be documented on individually housed dams on a schedule corresponding to times of maternal body weight collection. At scheduled sacrifice on gd 20 at RTI, dams will be weighed and maternal liver and gravid uterine weights will be recorded. Maternal gross lesions will be retained in fixative. Ovarian corpora lutea will be counted and the status of uterine implantation sites will be recorded (live fetuses, dead fetuses, early and late resorptions). Any apparently nonpregnant uteri or uteri with apparent single horn pregnancies will be stained with ammonium sulfide to confirm pregnancy status and identify any early postimplantation pregnancy losses. All live fetuses will be counted, sexed, weighed and examined externally for malformations (including cleft palate) and variations: approximately 50% of the fetuses in each litter will be examined for visceral alterations, and decapitated and the heads fixed and decalcified for soft tissue 3040 Cornwallis Road Post Office Box 12194 Research Triangle Park, North Carolina 27709-2194 USA Telephone 919 541-5972 Fax 919 541-7237 lnternetrwt@rti.org R&S147197 Dr. J. A. Bond December 4,1995 Page 2 craniofacial examinations (including the fetal brain). All fetuses will be eviscerated, cleared and stained with alizarin red S (for ossified bone) and alcian blue (for cartilaginous bone); intact fetuses (50% per litter) will be examined for skeletal malformations and variations. Placental weights will be recorded. A draft report will be submitted within four months of the last sacrifice date. 2. Definitive Reproductive Toxicity Study This study is designed to conform to new draft OPPTS Testing Guidelines as requested. Route of administration will be inhalation exposure, six hours/day, five days/week during the FO and FI 10-week prebreed exposure periods, and seven days/week during mating, gestation and lactation of FO and FI parental animals; exposure may also occur to FI and F2 offspring during gestation via transplacental processes and/or during lactation by translactational transfer. One hundred forty (140) weanling (4-5 week old) CD (Sprague-Dawley) male and female rats will be ordered. During the two-week quarantine, 5/sex will be evaluated for serum viral antibody titers and parasites; all will be examined by the CUT veterinarian. At study start, 120 rats per sex, designated the FO generation, will be distributed by randomization procedures stratified by body weight into four groups, 30 animals/sex/group (with exposure concentrations of 0,10,100 and 1100 ppm as specified in the Dow protocol). Animals will be exposed by inhalation, six hours per day, five days/week for 10 weeks. The 10 weeks (70 days) corresponds to one complete spermatogenic cycle and allows for any bioaccumulation. Animals will be weighed weekly. Feed consumption will also be measured weekly; clinical observations will be recorded twice daily, morning and afternoon. Seven weeks into the 10-week F0 prebreed exposure period, the F0 females will be subjected to daily vaginal lavages for three weeks to determine estrous cyclicity. The three weeks correspond to at least three complete estrous cycles (which last 4-5 days in rats). They will be weighed, and feed consumption and clinical observations documented as described above for males. At the end of the 10 week F0 prebreed exposure period, animals will be cohabited 1:1 (one male:one female) within groups for two weeks (as specified by OPPTS; re-pairing unsuccessful animals within groups after one week of cohabitation will not be done.) Exposures for both sexes will continue now at seven days/week; body weights will be taken weekly in males and weekly until insemination occurs in females. Feed consumption will not be recorded during cohabitation. Females will be checked daily for dropped or vaginal copulation plug and/or vaginal sperm by lavage and for estrous cyclicity during the two-week mating period or until evidence of insemination. The date of evidence of copulation will be designated gd 0. F0 males will be necropsied at the end of the gestation period with reproductive organs, liver, kidneys (2), spleen, thymus, adrenal glands (2), brain, and pituitary weighed and retained (one testis per male will be frozen for spermatid head counts, one testis will be fixed for histopathologic examination), and any gross lesions retained in fixative. Sperm assessments (number, morphology and motility) will be done from the cauda epididymis and homogenization-resistant testicular sperm will be evaluated from the testis from all F0 males at necropsy. Presumed pregnant females (dams) will be weighed and feed consumption measured on gd 0, 7,14, and 20. Dams usually litter on gd 22 or 23; the date of parturition will be designated as postnatal day (pnd) 0. Offspring of F0 parents will be designated the FI generation. Pregnant females will not be exposed on gd 20 through pnd 4, with exposure to the dams resuming on pnd 5. Dams and their litters will be weighed and feed consumption measured on pnd 0.4,7,14, and 21. Pups will be counted, sexed, weighed individually and examined externally also on pnd 0,4,7,14 and 21. Anogenital distance will be recorded for all pups on pnd 0. On pnd 4, litters will be randomly culled to eight pups with as equal a sex ratio as possible; natural litters of eight or less pups will not be culled. On pnd 21, each litter will be weaned; the F0 dams will then be necropsied (with stage of estrus at sacrifice documented) with reproductive tract, liver, kidneys (2), spleen, thymus, adrenal glands (2), brain, and pituitary weighed and retained, and any gross lesions retained in fixative. A total of 30 FI weanlings per sex per group will be randomly selected from the maximum number of litters as FI parents for the next generation. i R&S 147198 Dr. J. A. Bond December 4,1995 Page 3 They will be exposed to vinyl chloride by inhalation, five days/week, beginning on pnd 22 (the day after weaning); when the last litter is weaned, the formal 10-week prebreed exposure period for the FI animals will begin (the youngest pups will be 13 weeks old at the end of this exposure period). In addition, three FI weanlings/sex/litter will be necropsied with reproductive organs, liver, kidneys (2), spleen, thymus, adrenal glands (2), brain, and pituitary weighed and retained, and any gross lesions retained in fixative. Remaining non-selected FI weanlings will be examined externally and euthanized with the concurrence of the Sponsor. The date of acquisition of vaginal patency in females (pnd 28-45) and of preputial separation (pnd 35-50) in males will be recorded in the FI pups selected as parents until all available pups have reached criterion. At the end of the FI 10-week prebreed exposure period (with a three-week evaluation of FI females for estrous cyclicity), mating, gestation and lactation (with pairing of non-sibling animals within groups) will be performed as described above for FO animals. Necropsy of FI parental animals will occur as described above for F0 parents. Offspring of FI parents will be designated the F2 generation. At weaning of F2 litters, three F2 weanlings/sex/litter will be necropsied as described above for FI weanlings; remaining unselected F2 weanlings will be examined externally and euthanized with concurrence of the Sponsor. Organs of FO and FI parental animals to be weighed (all groups) include ovaries (2), uterus, testes (2), epididymides (2), seminal vesicles (2) with coagulating glands, prostate, spleen, kidneys (2), liver, adrenal glands (2), thymus, brain and pituitary. Organs of these animals to be retained in fixative include the above (one testis per male will be frozen for homogenization-resistant spermatid head count), plus cervix and vagina in females. Organs of the top dose and control group parental animals, plus any animals in mid and low dose groups which die on study or were not reproductively successful, will be examined histologically. Ovaries from FO and FI parental females (high dose and control) will have five (5) sections taken at least 100 pm apart from the inner third of each ovary with enumeration of the total number of primordial follicles from these 10 sections per female. FO and FI parental males (all doses) will have sperm assessments (number, morphology, motility) performed from the cauda epididymis and homogenization-resistant spermatid head counts performed from the testis. Organs of FI and F2 weanlings will be retained in fixative for possible subsequent histopathologic assessment if gross examination and/or organ weights indicate possible treatment-related effects. A draft final report will be submitted within five months of the last necropsy date. B. Proposed Time Line 1- Two-Generation Study EVENT TENTATIVE DURATION DATE(S) PreStudy Submission of Bid Award of Bid by CMA Contract, acquisition of test material (with analysis?) Acceptable protocol Deliverables: Protocol (fully signed) Pre-Study Inhalation work (generation and analysis of test atmospheres, etc.), order animals, study-specific equipment/supplies 3 months 2 months Dec. 8,1995 Jan. 15,1996 (?) April 15,1996 April 30,1996 June 30,1996 R&S147199 Dr. J. A. Bond December 4,1995 Page 5 EVENTDURATIONTENTATIVE DATE(S) Study Animals arrive for developmental toxicity Aug. 5,1996 (breeding males and study females) Quarantine 2 weeks Aug. 5-19,1996 Mating (100 sperm-positive females) 4-5 days (gd 0) Aug. 20-25,1996 `Exposures (gd 6-19) 19 days (14 days/animal Aug. 26 (first gd 6) - Sept. with 5 breeding days 13,1996 (last gd 19) Scheduled Sacrifice (gd 20) 4-5 days Sept. 9-17,1996 Deliverables: Draft Report submitted 4 months Jan. 17,1997 Final Report submitted within 30 days of receipt of Sponsor's comments March, 1997 (?) * NOTE: Exposure for dams in developmental toxicity study will occur in same chambers at same time as F0 animals are in the prebreed exposure period for the two-generation study. C. Information on Proposed RTi Staff and Facilities 1. Resumes of Key RTI Personnel RTI Quality Assurance Unit: Ms. S. M. Taulbee, Manager Reproductive/Deveiopmental Toxicology: Dr. R. W. Tyi, Co-Study Director for both studies Ms. M. C. Marr, Laboratory Supervisor and Developmental Toxicity Study Supervisor Ms. C. B. Myers, Data Specialist and Reproductive Toxicity Study Supervisor Sperm Assessments: Dr. P. A. Fail, Reproductive Endocrinologist Histopathology: Ms. Tsai-Ying Chang, BS, HT-ASCP Dr. John C. Seely, DVM, ACVP, PATHCO Inc. 2. RTI Standard Operating Procedures fSOPst For Use in These Studies The Tables of Contents for the Reproductive and Developmental Toxicology Group, the Endocrinology Group and the Histology Group are attached. 3. Boor Plan of Proposed RTI Suite for Necropsies and_Fetal_EvaluatLojis The floor plan of the Reproductive and Developmental Toxicology Wing in the Hermann Building is attached. D. Comments on Study Designs. Deviations from the Dow-Protocol and Current OPPTS Draft Guidelines Developmental Toxicity Study 1. The rats will be exposed according to the new draft guidelines, from gd 6 to the day before scheduled sacrifice for six hours per day for the definitive study. I have specified exposure gd 6 through 19 and sacrifice on gd 20 since this is the procedure we follow at RTI (and our historical control database is also based on a gd 20 sacrifice date). The Dow protocol exposes through gd 20 with scheduled sacrifice on gd 21. This difference should have no effect on study design, performance or interpretation. -q % J* roo f Dr. J. A. Bond December 4, 1995 Page 6 2. The Dow protocol specifies staining of fetal preparations with alizarin red S (ossified bone) prior to skeletal evaluation. The current draft guidelines specify examination of both ossified and cartilaginous components of the skeletal system. We routinely use (and I have bid) staining with alizarin red S (for ossified bone) and with alcian blue (for cartilaginous bone) prior to skeletal evaluation, in conformance with the draft guidelines. 3. I've included placental weights in the definitive study since new harmonization guidelines are calling for more placental information, at least weight (we can retain them in fixative for possible subsequent histopathology if we see something at gross examination or in data analysis). Reproductive Toxicity Studies 1. Proposed guidelines call for a two-week mating period (with no mention of a change in unsuccessful partners within groups and after one week) and this is included in the bid. 2. Evaluation of sperm number, motility and morphology (from the cauda epididymis), and enumeration of homogenization-resistant spermatids (from one testis) are specified in the draft guidelines for all FO and FI parental males, and this is included in the bid (labor intensive). The Dow protocol specifies the first 15 FO and FI males; this does not follow the guidelines. 3. Vaginal cytology for estrous cyclicity, as specified in the draft guidelines, is included for three weeks prior to mating, and during the two-week mating period until insemination occurs, and at sacrifice for all FO and FI parental females (labor intensive). The Dow protocol specifies estrous cyclicity for the first 15 FO and Fl females; this does not follow the guideline. 4. The current draft guidelines specify rebreeding parental animals if there is evidence of reproductive problems. Therefore, I am proposing that we necropsy the FO and Fl males after the gestation periods of their respective litters, just in case we have to rebreed them. FO and Fl females will be necropsied after the weaning of their respective litters. The Dow protocol calls for sacrifice of both parents after the litter is weaned; this is unnecessary for parental males. 5. The current draft guidelines require that we identify the stage of the estrous cycle at necropsy of the FO and Fl adult females, and I have included that in the bid. The Dow protocol specifies necropsy of FO and Fl females at the same time in the estrous cycle; this is unnecessary. 6. Draft guidelines specify necropsy of 3 pups/sex/litter from Fl and F2 litters with organ weights and retention of selected organs. This is included in the bid. The draft guidelines indicate histopathology of weanling organs only if gross necropsy or organ weight data indicates possible treatment-related effects, so I have not bid histopathology of weanling tissues. The Dow protocol specifies necropsy and organ weights of first 15 Fl and F2 weanlings (one/sex/litter); this does not follow the guidelines. 7. The draft guidelines specify a large number of organ weights for parental and selected weanling animals at necropsy; these were included in the bid (labor intensive). 8. Draft guidelines specify evaluation of a minimum of five (5) sections taken at least 100 pm apart from the inner third of each ovary per parental female (FO and Fl) from high dose and control groups with enumeration of the total number of primordial follicles from these 10 sections per female (labor intensive). This is included in the bid. The Dow protocol specifies processing only the right ovary (left ovary retained), with a minimum of 10 sections, randomly selected, examined from one completely sectioned ovary per female. This does not follow the guidelines. 9. New draft guidelines specify examination for vaginal patency and preputial separation for Fl pups selected for mating. Therefore, I've bid evaluation of Fl pups for vaginal patency in females and preputial separation in males (F2 pups are terminated at weaning prior to acquisition of either of these R&S 147202 Dr. J. A. Bond December 4,1995 Page 7 hormonally-controlled landmarks) as time to criterion, with daily examination starting on pnd 28 for females and on pnd 35 for males based on our historical control data and experience (labor intensive). 10. Anogenital distance is incorporated for FI and F2 offspring at birth. Draft guidelines specify this assessment only for F2 pups rf there are effects on FI sexual maturation, but the bottom line on FI sexual maturation is, in fact, production of F2 offspring so we will not know if there are effects until after all F2 litters are bom (or are not bom). Therefore, I bid the parameter for both generations up front (labor intensive). 11. The Dow protocol specifies ophthalmologic examination of parental F0 and FI animals at necropsy. In addition, the Dow protocol also specifies fasting the parental F0 and FI males and females overnight prior to scheduled sacrifice. Neither of these activities is included in the guidelines, and these activities are therefore ugl included in the study design or the bid. E. Project Bid The costs for performing these studies are presented in the accompanying letter from Ms. C. S. Parker, RTI Senior Contracts Administrator. If you have any further questions, please do not hesitate to call me for technical aspects at (919) 541-5972, or Ms. Parker for contractual matters at (919) 541-6184. Thank you for the opportunity to assist CUT in its toxicologic testing needs. Sincerely, RWT.ng Attachments cc: LETTER ONLY: Dr. A. M. Cruze, EVP, RTI Dr. F. I. Carroll, Acting VP, CLS Dr. P. A. Fail Dr. S. E. Lewis Dr. J. C. Seely, PATHCO Ms. M. C. ManMs. C. B. Myers Ms. T. Y. Chang Ms. S. M. Taulbee, QAU Ms. C. S. Parker, Contracts Rochelle W. Tyl, Ph.D., DABT Research Director Center for Life Sciences and Toxicology R&S147203 R&S147204 Appendix 2 Detailed CVs of RTI Personnel R&S147206 ROCHELLE W. TYL, Research Director, Center for Life Sciences and Toxicology Professional Experience Center for Life Sciences and Toxicology, Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC. 7/15/93 - present. Research Director, Center for Life Sciences and Toxicology. Establish and implement Center goals and objectives consistent with RTI's overall financial and research strategic planning; recommend, interpret and implement RTI policies and procedures; establish guidelines and procedures for and manage allocation and utilization of Center facilities, equipment and funding; supervise senior staff of Center; initiate, plan and implement operational plans and strategies for Center direction(s) and development, and staff professional development; play a major role in establishing and implementing marketing goals and activities for the Center; maintain high level of involvement in technical efforts of the Center, including establishment and implementation of objectives, goals and procedures of projects, coordination and cooperation among senior staff in complex projects; contribute to and direct preparation and presentation of research reports to clients and the professional community. 5/1/91 -7/14/93. Assistant Research Director, Mammalian Toxicology Program; Program Manager, Reproductive and Developmental Toxicology. Duties as described below. 5/1/90 - 4/30/91. Senior Program Director, Mammalian Toxicology Program; Program Manager, Reproductive and Developmental Toxicology. Duties as described below. In addition, supervise senior staff in general toxicology and adult and developmental neurotoxicoiogy testing, work with higher management in policy and program development and implementation, building and renovation program for CLS. 6/15/89 - 4/30/90. Program Manager, Reproductive and Developmental Toxicology. Supervision of the staff of Developmental Toxicology, Developmental Neurotoxicoiogy, Reproductive Toxicology and Reproductive Endocrinology. Solicit and perform reproductive and developmental toxicity evaluations for governmental, industrial and commercial clients according to appropriate governmental guidelines, FDA, EPA (FIFRA or TSCA), OECD, EPA Test Rules or FIFRA Data "Call-Ins," under Good Laboratory Practice regulations; design and implement research protocols in reproductive and developmental toxicology for various clients; plan, coordinate and direct activities in program; prepare bids, protocols, final reports and manuscripts for refereed journals; evaluate personnel performance; direct supervision of four Ph.D. staff, two senior technical supervisory staff and an Administrative Assistant. Program includes seven doctoral level staff, six supervisory staff and approximately 15 technical staff. Member of RTI Institutional Animal Care and Use Committee (IACUC), 1990 present. 9/1/87 - 6/89. Assistant Director, Reproductive and Developmental Toxicology, Bushy Run Research Center (BRRC), Export, PA: Work with the Director and Associate Directors in planning, coordinating and directing work activities at BRRC. Prepare R&S 147207 Dr. Rochelle W. Tyl Page 2 equipment and personnel budgets and evaluate personnel performance. Supervise a Postdoctoral Scientist. Additional responsibilities as below. 7/1/83 - 8/31/87. Manager, Reproductive and Developmental Toxicology Section, Bushy Run Research Center (BRRC), Export, PA: Testing for developmental and reproductive toxicity of industrial chemicals by all routes of exposure in rats, rabbits and mice for Union Carbide and other industrial clients. Supervise ten staff members, responsible for protocol development, contact with clients, writing SOPs, writing study reports and manuscripts for refereed journals, staff training, sponsor liaison for UCC teratology studies done elsewhere, work under GLPs, FDA, EPA (TSCA), EPA (FIFRA), OECD guidelines, presentation of data to various professional groups. 5/83 - 6/30/83. Manager, Teratology Section and Senior Research Teratologist I, Research Triangle Institute, Research Triangle Park, NC: Research and testing in teratogenicity and reproductive toxicity of food additives, drugs, industrial chemicals, environmental pollutants, etc., in rats, mice and rabbits for governmental and industrial clients. Supervise eight people, responsible for all facets of studies, client contact, protocol development, SOPs, writing reports and manuscripts for refereed journals, Institute and community service by lectures to professional and academic groups, work under GLPs, EPA, FDA guidelines. 7/81 - 5/83. Supervisor, Teratology Section and Senior Research Teratologist I, Research Triangle Institute, Research Triangle Park, NC: Research and testing in teratogenicity and reproductive toxicity of food additives, drugs, industrial chemicals, environmental pollutants, etc., in rats, mice and rabbits for government and industrial clients. Supervise eight people, responsible for all facets of studies, client contact, protocol development, SOPs, writing reports and manuscripts for refereed journals, Institute and community service by lectures to professional and academic groups, work under GLPs, EPA, FDA guidelines. 7/78 - 7/81. Head, Teratology Section, Chemical Industry Institute of Toxicology (CUT), Research Triangle Park, NC: Research and testing in teratogenicity and reproductive toxicity of priority commodity chemicals, toxicokinetics and metabolism of commodity chemicals in pregnant animals, development of test battery for postnatal sequelae of in utero exposures. 9/68 - 6/78. Assistant Professor (1968-1973), Associate Professor (1973-1978), University of Connecticut, Southeastern Campus, Groton, CT: Teaching undergraduate courses in Biological Sciences, Genetics, Embryology, advising independent research students (undergraduate) and Master's thesis research students, direct own research, pre-medical student counseling, university committee memberships (tenured, 1974). Education A.B. cum laude, Biological Science, University of Connecticut, Storrs, CT, 1963. Ph.D., Developmental Genetics, University of Connecticut, Storrs, CT, 1968. Professional Societies Teratology Society Neurobehavioral Teratology Society Society of Toxicology (SOT) Active Member R&S 147208 Dr. Rochelle W. Tyl Page 3 SOT, Reproductive and Developmental Toxicology Subsection Member Middle Atlantic Reproduction and Teratology Association (MARTA) North Carolina Chapter of SOT Genotoxicity and Environmental Mutagenesis Society (GEMS, NC) Allegheny-Erie Regional Chapter of SOT (1983-1989) Honors Phi Beta Kappa Phi Kappa Phi Sigma Xi Gamma Sigma Delta Certification Diplomate, American Board of Toxicology (ABT), 1983; recertified 1988 and 1993. Outside Current Affiliations IRLG Workshop on Reproductive Toxicity Risk Assessment, 1981; by invitation. Consensus Workshop on Formaldehyde, 1983. NIOSH Symposium on "Toxic Effects of Glycol Ethers," 1983. American Industrial Health Council (AIHC), Reproductive Effects Subcommittee, 1984-1989. Chemical Manufacturers Association (CMA) Health Standards Task Group - Work Group on Neurobehavioral Issues, 1984-1989. Environmental Protection Agency (EPA), "Consensus Workshop on the Evaluation of Maternal and Developmental Toxicity," May 12-14,1986; co-chair Workshop III Modeling and Applications; by invitation. Adjunct Assistant Professor of Human Genetics in the Graduate School of Public Health, Department of Biostatistics, University of Pittsburgh, PA, 1986-1989. Mid-America Toxicology Course, Kansas City, MO, April 27,1987, April 18,1988, April 24, 1989, and April 23,1990, Lecturer on "Teratology"; by invitation. Editorial Board Member for Fundamental and Applied Toxicology, 1987 to present. Manuscript Reviewer for Toxicology and Applied Pharmacology (since 1983), for Teratology (since 1984), for Laboratory Animal Science (since 1984), and for Teratogenesis, Carcinogenesis and Mutagenesis (since 1989). Environmental Protection Agency (EPA), "Workshop on the Acceptability and Interpretation of Dermal Developmental Toxicity Studies," April 13-14,1988; by invitation. Environmental Protection Agency (EPA), "Workshop in Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity," April 11-13,1989; co-chair Work Group III "Weight-of-Evidence and Quantitative Evaluation of Data from Developmental Neurotoxicity Studies"; by invitation. Lecturer in Refresher Course entitled "Foundations of Abnormal Development," Topic: NOEL, LOEL, and Dose-Response Relationships, 1989 Annual Meeting of Teratology Society, June 3-4,1989; by invitation. Lecturer and Discussant in workshop entitled "Risk Assessment Issues in Reproductive and Developmental Toxicology," Topic: Developmental Toxicity: Animal Endpoints (Sponsored by ILSI and EPA), Berkeley, CA, September 18-19, 1989; by invitation. Participant, Alternative Fuels Research Strategy Peer Review (sponsored by U.S.EPA), Developmental/Reproductive Toxicology Public Health Concerns, Durham, NC, December 6-8, 1989; by invitation. R&S147209 Dr. Rochelle W. Tyl Page 4 > Environmental Protection Agency (EPA)/National Institute of Environmental Health Sciences (NIEHS), Manganese/MMT Conference, Health Effects Workgroup; Reproduction and Developmental Issues Specialty Section, March 12-15,1991; by invitation. Speaker at Allegheny-Erie Regional Chapter of SOT, Spring Meeting, Pittsburgh, PA, May 10,1991, Symposium entitled: "Toxicology of the Next Generation: Reproductive and Developmental Hazards," Topic: The Developing Fetus and Possible Effects Due to Chemical Exposures; by invitation. Lecturer in course entitled "Fundamentals of Environmental Toxicology," Topic: Toxic Responses of the Reproductive Systems, at Georgia Tech Research Institute, Georgia Institute of Technology, June 17-21,1991; by invitation. Lecturer in Continuing Education Course "Collection and Interpretation of Data for Developmental Toxicity (Teratology) Studies - 'State of the Art' Scientific Review and the Realities of the Regulatory Submission Process" sponsored by the International Federation of Teratology Societies (IFTS), Topic: Collection and Evaluation of Maternal Toxicity Data, June 25,1991 (at the Teratology Society Annual Meeting, Boca Raton, FL); by invitation. Speaker at American Industrial Hygienists Association Sixth Annual Toxicology Symposium, Topic: "Issues in Reproductive and Developmental Toxicology," San Diego, CA, August 12-16,1991; by invitation. Invited Participant and Presenter, Toxicology Round Table, Ocean Place, NJ, October, 1991. Councilor, Reproductive and Developmental Toxicity Specialty Subsection SOT, elected 1992-1994. Member of Council, Teratology Society, elected 1992-1995. Speaker at American Industrial Hygienists Association Seventh Annual Toxicology Symposium, Topic: "The Principles of Risk Assessment for Developmental Effects," San Diego, CA. August 13-16,1992; by invitation. Invited Participant and Presenter, Toxicology Round Table, Hidden Valley, PA, October, 1992. Speaker in American College of Toxicology Annual Meeting Symposium entitled, "Current Topics in Cholinesterase Risk Assessment," Topic: Cholinesterase Determinations in Reproductive and Developmental Toxicity Studies: Implications for Risk Assessment, San Francisco, CA, October 22-24,1992; by invitation. Member of IEHR (Institute for Evaluating Health Risks) Expert Committee on Reproductive and Developmental Toxicity, Williamsburg, VA, January 17-21,1993; by invitation. Lecturer in Continuing Education Course "Embryology forTeratologists," Topic: "Through the Looking Glass: Possible Embryologic Models or Mechanisms of Fetal Malformations," Teratology Society Annual Meeting, Tucson, A2, June 26-27, 1993; by invitation. Speaker at American Industrial Hygienists Association Eighth Annual Toxicology Symposium, Topic: "Reproductive/Developmental Toxicology," Asheville, NC, August .35,1993; by invitation. Lecturer in UNC-CH Toxicology 207: Advanced Toxicology, Topic: "Regulatory Issues in Reproductive and Developmental Toxicology," UNC-CH, September 29,1993; by invitation. Speaker at American Industrial Hygienists Association Ninth Annual Toxicology Symposium, Topic: "Genetic Toxicology, Reproductive and Developmental Toxicology," Baltimore, MD, August 15-16, 1994; by invitation. R&S147210 + " Dr. Rochelle W. Tyl Page 5 Lecturer in UNC-CH Toxicology 207: Advanced Toxicology, Topic: "Regulatory Issues in Reproductive and Developmental Toxicology," UNC-CH, September 14,1994 and September 13,1995; by invitation. Speaker at American Industrial Hygienists Association Tenth Annual Toxicology Symposium, Topic: Reproductive Toxicology: Boston, MA, August 15-16,1995; by invitation. Current Research Interests Toxicokinetics and metabolism of xenobiotics in pregnant and lactating test animals; research and testing for developmental and reproductive toxicity in animal models; developmental neurotoxicology. Publications Effect of Actinomycin D on Early Axial Development in Chick Embryos, R. M. Wolkowski, TeratologyQ, 389-398, 1970. Differential Cadmium-Induced Embryotoxicity in Two In-Bred Mouse Strains. I. Analysis of Inheritance of the Response to Cadmium and of the Presence of Cadmium in Fetal and Placental Tissues, R. M. Wolkowski, Teratology IQ, 243-262, 1974. The Interaction of Cadmium-binding Proteins (Cd-bp) and Progesterone in CadmiumInduced Tissue and Embryo Toxicity, R. M. Wolkowski-Tyl and S. F. Preston, Teratology 2Q, 341-352,1979. Perinatal Toxicity and Metabolism of n-Hexane in Fischer-344 Rats after Inhalation Exposure During Gestation. J. S. Bus, E. L. White, R. W. Tyl and C. S. Barrow, Toxicol. Appl. Pharmacol. 1, 295-302,1979. Chemical Urolithiasis. 1. Characteristics of Bladder Stone Induction by Terephthalic Acid and Dimethyl Terephthalate in Weanling Fischer-344 Rats, T. Y. Chin, R. W. Tyl, J. A. Popp and H. d'A. Heck, Toxicol. Appl. Pharmacol. 5g, 307-321,1981. Animal Model of Human Disease: Urolithiasis, R. Wolkowski-Tyl, T. Y. Chin, J. A. Popp and H. d'A. Heck, Amer. J. Pathology 107. 419-421, 1982. Urolithiasis, Model No. 256, R. Wolkowski-Tyl, T. Y. Chin, J. A. Popp, and H. d'A. Heck, In: Handbook: Animal Models of Human Disease. Fasc. 11, Edited by C. C. Capen, D. B. Hackel, T. C. Jones and G. Migaki, Registry of Comparative Pathology, Armed Forces Institute of Pathology, Washington, DC, 1982, 3 pages. Chemical Urolithiasis. 3. Pharmacokinetics and Transplacental Transport of Terephthalic Acid in Fischer-344 Rats, R. Wolkowski-Tyl, T. Y. Chin and H. d'A. Heck, Drug Metab. Disp.XQ, 486-490, 1982. Histopathology of Acute Toxic Response in Rats and Mice Exposed to Methyl Chloride by Inhalation, K. T. Morgan, J. A. Swenberg, T. E. Hamm, Jr., R. Wolkowski-Tyl and M. Phelps, Fundam. Appl. Toxicol. 2, 293-299, 1982. R&S14721 Dr. Rochelle W. Tyl Page 6 Structural Teratogenicity Evaluation of Methyl Chloride in Rats and Mice after Inhalation Exposure, R. Wolkowski-Tyl, M. Phelps and J. K. Davis, Teratology 27,181-195,1983. Evaluation of Heart Malformations in BgCgF. Mouse Fetuses Induced by In Utero Exposure to Methyl Chloride, R. WoUtowski-Tyl, A. D. Lawton, M. Phelps and T. E. Hamm, Jr., Teratology 27,197-206,1983. Effects of Selected Therapeutic Agents on Urolithiasis Induced by Terephthalic Acid in the Male Weanling Fischer 344 Rat, R. Wolkowski-Tyl and T. Y. Chin, Fundam. Appl. Toxicol. 21B, 552-558,1983. A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure, R. W. Tyl, G. Millicovsky, D. E. Dodd, I. M. Pritts, K. A. France and L. C. Fisher, Environmental Health Perspectives 57. 47-68, 1984. Teratologic and Postnatal Evaluation of Aniline Hydrochloride in the Fischer 344 Rat, C. J. Price, R. W. Tyl, T. A. Marks, L. L. Paschke, T. A. Ledoux, and J. R. Reel, Toxicol. Appl. Pharmacol. ZL 465-478,1985. Reproduction in Fischer-344 Rats Exposed to Methyl Chloride by Inhalation for Two Generations, T. E. Hamm, Jr., T. H. Raynor, M. C. Phelps, C. D. Auman, W. T. Adams, J. E. Proctor and R. Wolkowski-Tyl, Fundam. Appl. Toxicol. 5, 568-577,1985. Evaluation of a New Reproductive Toxicology Protocol using Diethylstilbestrol (DES) as a Positive Control Compound, J. R. Reel, A. D. Lawton, R. Wolkowski-Tyl, G. W. Davis and J. C. Lamb IV, J. Amer. College of Toxicol. 4(2), 147-162,1985. The Developmental Toxicity of Ethylene Glycol In Rats and Mice, C. J. Price, C. A. Kimmel, R. W. Tyl and M. C. Marr, Toxicol. Appl. Pharmacol. 8im. 113-127,1985. Teratologic Evaluation of Dinitrotoluene in the Fischer 344 Rat, C. J. Price, R. W. Tyl, T. A. Marks, L. L. Paschke, T. A. Ledoux and J. R. Reel, Fundam. Appl. Tox. f>, 948-961, 1985. Letter to the Editor: Heart Malformations in BfiCqF1 Mouse Fetuses Induced by Methyl Chloride-Continuing Efforts to Understand me ttiology and Interpretation of an Unusual Lesion: Response to Ms. John-Green, Dr. Welsh and Dr. Bus; R. W. Tyl, Teratology 32, 489-492, 1985. Evaluation of the Teratogenicity of Bis(2-Dimethylaminoethyl)Ether After Dermal Application in New Zealand White Rabbits, R. W. Tyl, L. C. Fisher, K. A. France, R. H. Garman and B. Ballantyne, J. of Toxicology - Cutaneous and Ocular Toxicology 5(4). 263-284, 1986. The Developmental Toxicity of Orally Administered Oxytetracycline in Rats and Mice, R. E. Morrissey, R. W. Tyl, C. J. Price, T. A. Ledoux, J. R. Reel, L. L. Paschke, M. C. Marr and C. A. Kimmel, Fundam. Appl. Toxicol. 7(3), 434-443, 1986. R&S147212 ' Dr. Rochelle W. Tyl Page 7 Letter to the Editor: Response to Dr. E. M. Johnson; by C. A. Kimmel, C. J. Price, M. C. Mart and R. W. Tyl, Toxicol. Appl. Pharmacol. M, 196-198,1986. Developmental Toxicity Evaluation of Inhaled Nitrobenzene in CD Rats, R. W. Tyl, K. A. France, L C. Fisher, D. E. Dodd, I. M. Pritts, J. P. Lyon, F. O. O'Neal and G. Kimmerle, Fundam. Appl. Toxicol. 8(41. 482-492,1987. Reproduction and Fertility Evaluations in CD Rats Following Nitrobenzene Inhalation, D. E. Dodd, E. H. Fowler, W. M. Snellings, I. M. Pritts, R. W. Tyl, J. P. Lyon, F. O. O'Neal and G. Kimmerle, Fundam. Appl. Toxicol. 8(4). 493-505,1987. Developmental Toxicity Evaluation of Inhaled Methyl Isobutyl Ketone in Fischer 344 Rats and CD-1 Mice, R. W. Tyl, K. A. France, L. C. Fisher, I. M. Pritts, T. R. Tyler, R. D. Phillips and E. J. Moran, Fundam. Appl. Toxicol. 8(3). 310-327,1987. The Developmental Toxicity of Bisphenol A in Rats and Mice, R. E. Morrissey, J. D. George, C. J. Price, R. W. Tyl, M. C. Marr, and C. A. Kimmel, Fundam. Appl. Toxicol. 8(41. 571-582, 1987. Consensus Workshop on the Evaluation of Maternal and Developmental Toxicity Work Group III Report: Low Dose Extrapolation and Other Considerations for Risk Assessment - Models and Applications, B. A. Schwetz and R. W. Tyl, Teratogenesis Carcinog. Mutagen. 7(3). 321-327,1987. Developmental Toxicity Evaluation of Inhaled 2-Ethoxyethanol Acetate in Fischer 344 Rats and New Zealand White Rabbits, R. W. Tyl, I. M. Pritts, K. A. France, L. C. Fisher and T. R. Tyler, Fundam. Appl. Toxicol. 10(11.20-39,1988. Developmental Toxicity Evaluation of Bendectin in CD Rats, R. W. Tyl, C. J. Price, M. C. Marr and C. A. Kimmel, Teratology 37(6). 539-552,1988. Developmental Toxicity Evaluation of Dietary Di(2-Ethylhexyl) Phthalate in Fischer 344 Rats and CD-1 Mice, R. W. Tyl, C. J. Price, M. C. Marr and C. A. Kimmel, Fundam. Appl. Toxicol. 10(31. 395-412,1988. Developmental Toxicity Evaluation of Beta(3-Epoxycyclohexyl) Ethyltrimethoxysilane in Fischer 344 Rats and New Zealand White Rabbits, R. W. Tyl, K. A. France, L. C. Fisher and B. Ballantyne, Fundam. Appl. Toxicol. 10(31. 439-452,1988. Evaluation of the Developmental Toxicity of Ethylene Glycol Monohexyl Ether Vapor in Fischer 344 Rats and New Zealand White Rabbits, R. W. Tyl, B. Ballantyne, K. A. France, L. C. Fisher, D. R. Klonne, and I. M. Pritts, Fundam. Appl. Toxicol. 12(2). 269-280, 1989. Dominant Lethal Assay of 2,4-Pentanedione Vapor in Fischer 344 Rats, R. W. Tyl, B. Ballantyne, L. C. Fisher, D. J. Tarasi, and D. E. Dodd, Toxicol. Ind. Health 5(3). 463-477, 1989. R&S147213 Dr. Rochelle W. Tyl Page 8 An Evaluation of the Developmental Toxicity of 2,4-Pentanedione in the Fischer 344 Rat by Vapour Exposure, R. W. Tyl, B. Ballantyne, I. M. Pritts, R. H. Ganman, L C. Fisher, K. A. France and D. J. McNeil, Toxicol. Ind. Health , 461-474, 1990. Proceedings of the Workshop on The Acceptability and Interpretation of Dermal Developmental Toxicity Studies. C. A. Kimmel and E. Z. Francis (R. W. Tyl, Invited Participant). Fundam. Appl. Toxicol. 14, 386-398,1990. Workshop on the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity, Workgroup III Report: Weight of Evidence and Quantitative Evaluation of Developmental Neurotoxicity Data, R. W. Tyl and William F. Sette, Neurotoxicology and Teratology 12(3). 275-280,1990. Reproductive Toxicity of Sulfamethazine in Swiss CD-I Mice During Continuous Breeding, J. R. Reel, R. W. Tyl, A. D. Lawton and J. C. Lamb, IV, Fundam. Appl. Toxicol., 18(41. 609-615, 1992. The Developmental Toxicity of 2-Ethylhexanol (2-EH) Applied Dermally to Pregnant Fischer 344 Rats, R. W. Tyl, L. C. Fisher, M. F. Kubena, M. A. Vrbanic, R. Gingell, D. Guest, J. A. Hodgson, S. R. Murphy, T. R. Tyler and B. D. Astill, Fundam. Appl. Toxicol., 19(2). 176-185, 1992. Developmental Toxicity Evaluation of Ethylene Glycol by Gavage in New Zealand White Rabbits, R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. C. Seely, J. J. Heindel and B. A. Schwetz, Fundam. Appl. Toxicol., 20(4). 402-412,1993. Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits, A. G. Hendrickx, P. E. Peterson, R. W. Tyl, L. C. Fisher, L. J. Fosnight, M. F. Kubena, M. A. Vrbanic and G. Katz, Fundam. Appl. Toxicol., 2Q. 199-209,1993. Developmental Toxicity Evaluation of Isopropanol by Gavage in Rats and Rabbits, R. W. Tyl, L. W. Masten, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. E. Strother, R. H. McKee and T. R. Tyler, Fundam. Appl. Toxicol., 22,139-151,1994. Evaluation of Exposure to Water Aerosol or Air by Nose-Only or Whole-body Inhalation Procedures for CD-I Mice in Developmental Toxicity Studies, R. W. Tyl, B. Ballantyne, L. C. Fisher, D. L. Fait, T. A. Savine, I. M. Pritts and D. E. Dodd, Fundam. Appl. Toxicol., 23(2). 251-260, 1994. Evaluation of the Developmental Toxicity of Ethylene Glycol Aerosol in the CD Rat and CD-I Mouse by Whole-Body Exposure, R. W. Tyl, B. Ballantyne, L. C. Fisher, D. L. Fait, T. A. Savine, D. E. Dodd, D. R. Klonne, and I. M. Pritts, Fundam. Appl. Toxicol., 24, 5775,1995. The evaluation of the Developmental Toxicity of Hydrochlorothiazide in Mice and Rats, J. D. George, C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, Fundam. Appl. Toxicol., 2, 174-180, 1995. R&S147214 ' Dr. Rochelle W. Tyl Page 9 Evaluation of the Developmental Toxicity of Ethylene Glycol Aerosol in CD-I Mice by Nose-Only Exposure, R. W. Tyl, B. Ballantyne, L C. Fisher, D. L. Fait, D. E. Dodd, D. R. Klonne, I. M. Pritts, and P. E. Losco, Fundam. Appl. Toxicol., 27 (1). 49-62,1995. Assessment of the Developmental Toxicity of Ethylene Glycol Applied Cutaneously to CD-I Mice, R. W. Tyl, L. C. Fisher, M. F. Kubena, M. A. Vrbanic, and P. E. Losco, Fundam. Appl. Toxicol., 27 (2). 155-166,1995. Determination of a No-Observed-Effect-Level (NOEL) for Developmental Toxicity of Ethylene Glycol Administered by Gavage to CD Rats and CD-I`Mice, T. L. Neeper-Bradey, R. W. Tyl, L. C. Fisher, M. F. Kubena, M. A. Vrbanic, and P. E. Losco, Fundam. Appl. Toxicol., 27 (If. 121-130, 1995. Developmental Toxicity Evaluation of Methyl Tertiary-Butyl Ether (MTBE) by Inhalation in Mice and Rabbits, C. Bevan, R. W. Tyl, T. L. Neeper-Bradley, L. C. Fisher, R. D. Panson, J. F. Douglas and L. S. Andrews, J. of Appl. Toxicol., in press, 1995. Two-Generation Reproductive Toxicity Study of Methyl Tertiary-Butyl Ether (MTBE) in Rats, C. Bevan, T. L. Neeper-Bradley, R. W. Tyl, L. C. Fisher, R. D. Panson, J. J. Kneiss and L. S. Andrews. J. ofAppl. Toxicol., in press, 1995. Reproductive Toxicity Assessment of Methylethyl Ketoxime by Gavage in CD Rats, R. W. Tyl, J. M. Gerhart, C. B. Myers, M. C. Marr, D. R. Brine, A. F. Gilliam, J. C. Seely, M. J. Derelanko, and W. E. Rinehart. Fundam. Appl. Toxicol., in press, 1995. Evaluation of the Reproductive Toxicity of Dietary Tributyl Phosphate in CD Rats, R. W. Tyl, J. M. Gerhart, C. B. Myers, M. C. Marr, D. R. Brine, and J. C. Seely, to be submitted to Fundam. Appl. Toxicol., 1995. Developmental Toxicity Evaluation of Triethylenetetramine by Occluded Cutaneous Application in New Zealand White Rabbits, R. W. Tyl, L. C. Fisher, C. M. Troup, T. A. Rebick, M. A. Vrbanic, H-W. Leung and T. R. Tyler, to be submitted to Fundam. Appl. Toxicol., 1995. Developmental Toxicity Evaluation of Aminotriazole Technical Administered by Gavage to CD`(Sprague-Dawley) Rats and New Zealand White Rabbits, R. W. Tyl, L. C. Fisher, D. L. Fait, T. A. Savine, and J. M. Charles, to be submitted to Fundam. Appl. Toxicol., 1995. Book Chapters and Monographs Strain and Tissue Differences in Cadmium-Binding Protein (Cd-bp) in Cd-Treated Mice, R. M. Wolkowski-Tyl, Department of Energy Symposium Series 47, 568-585, 1978. Reproductive and Teratogenic Effects: No More Thalidomides?, R. M. Wolkowski-Tyl, ACS Symposium Series: The Pesticide Chemist and Modern Toxicology 160.115-155, 1981. i R&S147215 Dr. Rochelle W. Tyl Page 10 The Induction of Bladder Stones by Terephthalic Acid, Dimethyl Terephthalate and Melamine (2,4,6-Triamino-s-triazine) and Its Relevance to Risk Assessment, H. d'A. Heck and R. W. Tyl, Regulatory Toxicology and Pharmacology 5, 294-313,1985. Chapter 8. Developmental Toxicity in Toxicology Research and Testing, R. W. Tyl, in: Perspectives in Basic and Applied Toxicology. (B. Ballantyne, Editor), John Wright and Sons, Year Book Publishers, pp. 203-238,1987. Chapter 25. Developmental and Reproductive Toxicity of Anticholinesterases, R. W. Tyl, in: Basic and Clinical Toxicology of Orpanophosphates and Carbamates. (B. Ballantyne and T. C. Marrs, Editors), John Wright and Sons, Year Book Publishers, pp. 241-257, 1992. Chapter 16. Reproductive and Developmental Toxicity Studies by Cutaneous Administration, R. W. Tyl, R. G. York and J. L. Schardein, in: Health Risk Assessment: Dermal and Inhalation Exposure and Absorption of Toxicants. (R. G. Wang, J. B. Knaak and H. I. Maibach, Editors), CRC Press, Inc., pp. 229-261,1993. Chapter 44. Developmental Toxicology, R. W. Tyl, in: Textbook of General and Applied Toxicology. Vol. 2 (B. Ballantyne, T. Marrs, P. Turner, Editors), The MacMillan Press, Ltd., 1993,1021-1046. Chapter 7. Developmental Toxicity Testing--Methodology, R. W. Tyl and M. C. Marr, in: Handbook of Developmental Toxicology (R. D. Hood, Editor), CRC Press, Inc., in press, 1995. Published Abstracts Specific Regional Responses of the Chick Embryo to Chemical Teratogens: Actinomycin D and Puromycin, R. M. Wolkowski, L. J. Pierro and N. W. Klein, Amer. Zool. 4, 396,1964. Effects of Deoxyguanosine on Axial Development in the Chick Embryo, L. J. Pierro, J. E. Coghill and R. M. Wolkowski, Amer, Zool. 7, 198,1967. Effects of Actinomycin D on Axial Development in the Chick Embryo, R. M. Wolkowski and L. J. Pierro, Amer. Zool. 7, 198,1967. Perinatal Toxicity of n-Hexane in Fischer 344 Rats, J. S. Bus and R. Wolkowski-Tyl, Teratology 19. 22A, 1979. A Comprehensive Teratological Examination Involving Metric, Morphologic, and Physiologic Parameters, Developmental Landmarks and Hematology in the Pre- and Postnatal F-344 Rat, R. Wolkowski-Tyl and D. McCauley, The Journal of Elisha Mitchell Scientific Society 9, 120, 1979. Terephthalic Acid-Induced Urolithiasis and Hypercalciuria in Adult and Preadolescent F-344 Rats, T. Y. Chin, R. W. Tyl, and H. d'A. Heck, The Pharmacologist 21_, 186, 1979. R&S147216 Dr. Rochelle W. Tyl Page 11 Toxicokinetics of Terephthalic Acid (TPA) in Adult F-344 Rats and Distribution of 14C-TPA in Maternal and Fetal Tissues, T. Y. Chin, R. W. Tyl and H. d'A. Heck, Toxicol. Appl. Pharmacol. Supplement, 1980. Distribution of 14C-Aniline HCI (ANI) in Dams and Fetuses of Fischer-344 Rats after Single or Multiple Dosing, R. Wolkowski-Tyl and J. R. Bus, Teratology 21.76A, 1980. Alterations in Maternal and Fetal Non-Protein Sulfhydryl (NPSH) Concentrations in Pregnant Fischer-344 Rats after Acute Inhalation Exposure to Methyl Chloride, J. S. Bus, R. Wolkowski-Tyl and C. Barrow, Teratology21, 32A, 1980. Urinary Excretion and Tissue Distribution of 14C-2,4-Dinitrotoluene in 20-Day Pregnant Fischer-344 Rats, D. E. Rickert, R. M. Long and R. W. Tyl, The Pharmacologist 22. 246, 1980. Urinary Saturation, Calculus Formation and Bladder Hyperplasia in Rats Ingesting Terephthalic Acid (TPA) or Dimethyl Terephthalate (DMT), H. Heck, T. Y. Chin, R. W. Tyl and J. A. Popp, The Toxicologist 1, 42,1981. Teratogenicity Evaluation of Technical Grade Dinitrotoluene in the Fischer-344 Rat, R. Wolkowski-Tyl, C. Jones-Price, T. A. Ledoux, T. A. Marks and L. Langhoff-Paschke, Teratology 2&, 70A, 1981. Teratogenicity Evaluation of Aniline HCI in the Fischer-344 Rat, R. Wolkowski-Tyl, C. Jones-Price, T. A. Ledoux, T. A. Marks and L. Langhoff-Paschke, Teratology22, 70A, 1981. The Effects of Daily Separation from the Dam on Postnatal Development in the Fischer-344 Rat, R. Wolkowski-Tyl and J. K. Davis, The Journal of the Elisha Mitchell Scientific Society 97(A). 268,1981 (Abstract No. 71). Heart Malformations in BgCsF, Mouse Fetuses Induced by In Utero Exposure to Methyl Chloride, R. Wolkowski-Tyl, A. D. Lawton, M. Phelps and T. E. Hamm, Jr., Teratology 25, 82A, 1982. Teratologic Evaluation of Sulfamethazine in CD Rats, R. Wolkowski-Tyl, C. Jones-Price, C. A. Kimmel, T. Ledoux, J. R. Reel and L. Langhoff-Paschke, Teratology 25, 81-82A, 1982. Melamine Urinary Bladder Stone Formation in Male Weanling Fischer 344 Rats, R. W. Mast, R. W. Tyl, C. H. Frith and M. A. Friedman, American College of Toxicology Abstracts, 1982. Effects on Reproduction in Fischer-344 Rats Exposed to Methyl Chloride by Inhalation, T. E. Hamm, Jr., T. Raynor, D. Auman, T. Adams, S. J. Proctor and R. Wolkowski-Tyl, The Toxicologists, 30, 1983. Teratologic Evaluation of Diethylhexyl Phthalate (DEHP) in CD-I Mice, R. Wolkowski-Tyl, C. Jones-Price, M. C. Marrand C. A. Kimmel, Teratology 27, 84-85A, 1983. R&S147217 Dr. Rochelle W. Tyl Page 12 Teratologic Evaluation of Diethylhexyl Phthalate (DEHP) in Fischer 344 Rats, R. Wolkowski-Tyl, C. Jones-Price, M. C. Marrand C. A. Kimmel, Teratology2Z, 85A, 1983. Teratologic Evaluation of L-5-Hydroxytryptophan (HTP) in CD Rats, R. Wolkowski-Tyl, C. Jones-Price, M. C. Marrand C. A. Kimmel, Teratology27, 85A, 1983. Teratologic Evaluation of Ethylene Glycol (EG) in CD Rats and CD-I Mice, C. J. Price, R. W. Tyl, M. C. Marrand C. A. Kimmel, Teratology29(2). 52A, 1984. Teratologic Evaluation of Bendectin in CD Rats, C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, Teratology 29(2). 52A, 1984. Developmental Toxicity of Carbon Disulfide in Rabbits and Rats, C. J. Price, R. W. Tyl, M. C. Marr, J. D. George and C. A. Kimmel, The Toxicologist A, 86,1984. Validation of a New Reproductive Toxicology Protocol using Diethylstilbestrol (DES) as a model compound, J. R. Reel, A. D. Lawton, R. Wolkowski-Tyl, and J. C. Lamb, IV, The Toxicologists, 136, 1984. Teratologic Evaluation of Inhaled Methyl Isobutyl Ketone (MIBK) in Fischer 344 Rats and CD-I Mice, R. W. Tyl, K. A. France, L. C. Fisher, T. R. Tyler, R. D. Phillips and E. J. Moran, The Toxicologists, 120,1985. Reproductive Toxicity of Dietary Diethylhexyl Phthalate (DEHP) in Mouse Breeding Pairs, J. R. Reel, A. D. Lawton, R. W, Tyl and J. C. Lamb, IV, The Toxicologists, 117,1985. Developmental Toxicity Evaluation of Bisphenol A (BPA) in Rats and Mice, J. D. George, C. J. Price, R. W. Tyl, M. C. Marrand C. A. Kimmel, The Toxicologists, 186,1985. Comparison of Distilled Water (DW) and Com Oil (CO) Vehicle Controls From Historical Teratology Study Data, C. A. Kimmel, C. J. Price, B. M. Sadler, R. W. Tyl and F. S. Gerling, The Toxicologists, 185,1985. Developmental Toxicity Evaluation of Inhaled 2-Ethoxyethanol Acetate (EEA) in Rats and Rabbits, R. W. Tyl, I. M. Pritts, K. A. France, L. C. Fisher and T. R. Tyler, Teratology 31 (3L 59A, 1985 (Abstract P63). Developmental Toxicity Evaluation of Inhaled Nitrobenzene (NB) in CD Rats, R. W. Tyl, K. A. France, L. C. Fisher, D. E. Dodd, I. M. Pritts, J. P. Lyon, F. O. O'Neal and G. Kimmerle, The Toxicologists, 90,1986. Teratogenicity Evaluation of Bis(2-Dimethylaminoethyl)Ether After Dermal Application in New Zealand White Rabbits, L. C. Fisher, R. W. Tyl, K. A. France, R. H. Garman and B. Ballantyne, The Toxicologists, 93,1986. Teratologic Evaluation of Chlorpromazine (CPZ) in CD-I Mice and F-344 Rats, C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, The Toxicologists, 91, 1986. Developmental Toxicity of Hydrochlorothiazide (HCTZ) in Rats and Mice. J. D. George, C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, The Toxicologists, 90, 1986. i R&S147218 Dr. Rochelle W. Tyl Page 13 Reproduction and Fertility Evaluations in Rats Following Nitrobenzene (NB) Inhalation, D. E. Dodd, E. H. Fowler, W. M. Snellings, I. M. Pritts, R. W. Tyl, J. P. Lyon, F. O. O'Neal, and G. Kimmerle, The Toxicologist 33,1986. Teratologic Evaluation of Oxytetracycline-HCl (OXT) in CD-I Mice and CD Rats, R. E. Morrissey, R. W. Tyl, C. J. Price, T. A. Ledoux, J. R. Reel, L. L. Paschke, M. C. Marr and C. A. Kimmel, The Toxicologist Q, 91,1986. Developmental Toxicity of Gentian Violet (GV) in Rats and Rabbits, C. A. Kimmel, C. J. Price, R. W. Tyl, T. A. Ledoux, J. R. Reel and M. C. Marr, Teratology, 33(31. 64-65C, 1986. Developmental Toxicity Evaluation of Inhaled N,N-Dimethylethanolamine (DMEA) in Fischer 344 Rats, R. W. Tyl, E. R. Homan, D. R. Klonne, I. M. Pritts, E. H. Fowler, L. C. Fisher, K. A. France, T. A. Rebick, J. L. Beskitt and B. Ballantyne, The Toxicologist 7, 173, 1987. Teratologic Evaluation of Beta (3,4-Epoxycyclohexyl) Ethyltrimethoxysilane (ECEMS) in Rats and Rabbits, R. W. Tyl, B. Ballantyne, K. A. France, L. C. Fisher, T. A. Savine and D. L. Fait, The Toxicologist 1,179,1987. The Teratogenic Potential of 2,4-Pentanedione Vapor in Fischer 344 Rats, R. W. Tyl, B. Ballantyne, I. M. Pritts, K. A. France, L. C. Fisher and D. J. McNeil, J. Amer. Coll. Toxicol. 5, 600,1986. Postnatal Development and Reproductive Performance of Fischer 344 Rats following Maternal Exposure to Diethylhexylphthalate (DEHP), C. J. Price, R. W. Tyl, M. C. Marr, B. M. Sadler, C. A. Kimmel and R. E. Morrissey, The Toxicologist2,145,1987. Developmental Toxicity Evaluation of Inhaled Ethylene Glycol Monohexyl Ether (EGHE) in Rats and Rabbits, R. W. Tyl, B. Ballantyne, I. M. Pritts, D. R. Klonne, L. C. Fisher, T. A. Savine, D. J. McNeil and M. F. Kubena, Teratology 35(21. 53-54A, 1987. Teratogenicity Evaluation of Water Aerosol (AER) versus air (AIR) in CD<SM Mice by Whole Body (WB) or Nose-Only (NO) Exposure, R. W. Tyl, B. Ballantyne, D. L. Fait, L. C. Fisher, T. A. Savine, I. M. Pritts, and D. E. Dodd, Teratology35(2), 39A, 1987. Developmental Toxicity Evaluation of 3-Chlorophenoxypropionic Acid (CPA) by Gavage to NZW Rabbits, L. C. Fisher, R. W. Tyl, T. A. Savine, and J. M. Charles, The Toxicologist 8(11. 244, 1988. Developmental Toxicity Evaluation of Ethylene Glycol (EG) Aerosol by Nose-Only (NO) or Whole-Body (WB) Exposure in CD-1 Mice, R. W. Tyl, B. Ballantyne, L. C. Fisher, D. L. Fait, D. R. Klonne, I. M. Pritts, and D. E. Dodd, The Toxicologist 8(11. 242, 1988. Developmental Toxicity Evaluation of Ethylene Glycol (EG) Applied Cutaneously to CD-1 Mice, R. W. Tyl, L. C. Fisher, M. F. Kubena, M. A. Vrbanic, and P. E. Losco, Teratology MSI, 498, 1988. R&S147219 Dr. Rochelle W. Tyl Page 14 Developmental Toxicity of 2-Ethylhexanoic Acid (2-EHA) by Gavage in Fischer 344 Rats and New Zealand White Rabbits, L. C. Fisher, R. W. Tyl, L. J. Fosnight, M. F. Kubena, and M. A. Vrbanic, The Toxicologist 9(11. 269,1989. Developmental Toxicity of Ethylene Glycol (EG) Aerosol by Whole-Body Exposure in CD Rats and CD-I Mice, R. W. Tyl, B. Ballantyne, L. C. Fisher, D. L. Fait, T. A. Savine, D. R. Klonne, I. M. Pritts, and D. E. Dodd, The Toxicologist 9(11. 270,1989. Cutaneous Developmental Toxicity Study of 2-Ethylhexanol (2-EH) in Fischer 344 Rats, L. C. Fisher, R. W. Tyl, and M. F. Kubena, Teratologym.51. 452, 1989 (P83). Determination of a Developmental Toxicity "No Observable Effect Level" (NOEL) for Ethylene Glycol (EG) by Gavage in CD-I Mice, R. W. Tyl, L. C. Fisher, M. F. Kubena, P. E. Losco, and M. A. Vrbanic, Teratology 39(5). 487,1989 (P75). Reproductive Toxicity Study of Inhaled Paradichlorobenzene (PDCB) Vapor in CD Rats, T. L. Neeper-Bradley, R. W. Tyl, L. C. Fisher, D. L. Fait, D. E. Dodd, I. M. Pritts, R. H. Garman, and J. A. Barter, Teratology 39(5). 470,1989 (P59). Developmental Toxicity Study of Inhaled Methyl Tertiary Butyl Ether (MTBE) in New Zealand White Rabbits and CD-I Mice, T. L. Neeper-Bradley, R. W. Tyl, L. C. Fisher, D. J. Tarasi, D. L. Fait, D. E. Dodd, I. M. Pritts, R. S. Panson and S. A, Ridlon, The Toxicologist 10(1). 41,1990 (Abstract 162). Developmental Toxicity Evaluation of 1,2,4,5-Tetrachlorobenzene (TCB) Administered by Gavage to Fischer 344 (F-344) Rats and New Zealand White (NZW) Rabbits, L. C. Fisher, R. W. Tyl, B. L. Butler, M. A. Vrbanic, J. P. Van Miller and C. R. Stack, Teratology 41 (5). 556,1990 (Abstract PI 53). Reproductive Toxicity Study of 1,2,4,5-Tetrachlorobenzene (TCB) in the Diet of CD Rats, T. L. Neeper-Bradley, R. W. Tyl, L. C. Fisher, D. L. Fait, M. A. Vrbanic, J. P. Van Miller, P. E. Losco and C. R. Stack, Teratology 41 (5). 580,1990 (Abstract P52). Developmental Toxicity Evaluation of Ethylene Glycol (EG) by Gavage in New Zealand White (NZW) Rabbits, R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, The Toxicologist 11(11. 341,1991 (Abstract 1337). Developmental Toxicity Evaluation of DEHP Metabolites in Swiss Mice, C. J. Price, R. W. Tyl, M. C. Marr, C. B. Myers, R. E. Morrissey, J. J. Heindel and B. A. Schwetz, Teratology, 43(51 457,1991 (Abstract PI32). Developmental Toxicity Evaluation of Isopropanol (IPA) by Gavage in New Zealand White (NZW) Rabbits, L. W. Masten, R. W. Tyl, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. J. Marino, R. H. McKee, and T. R. Tyler, The Toxicologist 12(1}, 232,1992 (No. 864). Developmental Toxicity Evaluation of Isopropanol (IPA) by Gavage in CD (Sprague-Dawley) Rats, R. W. Tyl, L. W. Masten, M. C. Marr, C. B. Myers, R. W. Slauter, T. H, Gardiner, D. J. Marino, R. H. McKee, and T. R. Tyler, The Toxicologist 12(1). 231, 1992 (No. 860). R&S 147220 Dr. Rochelle W. Tyl Page 15 Reproductive Toxicity Study of Methylethyl Ketoxime (MEKO) by Gavage in CD Rats, R. W. Tyl, J. M. Gerhart, C. B. Myers, M. C. Marr, D. R. Brine, A. F. Gilliam, J. C. Seely, and M. J. Derelanko, The Toxicologist, 13(1). 76,1993. Two Generation Study of Dietary Tributyl Phosphate (TBP) in CD Rats, J. M. Gerhart, R. W. Tyl, C. B. Myers, M. C. Marr, D. R. Brine, and J. C. Seely, The Toxicologist, 13(1). 76,1993. Reproductive Toxicity of Methoxychlor in Corn Oil to Male and Female Long-Evans Hooded Rats Using the Alternative Reproduction Test Protocol (ART). Anderson, S. A., P. A. Fail, B. T. McTaggart, R. W. Tyl, and L. E. Gray, Jr. Biology of Reproduction, 5Q, Suppl. 1, p. 101 (Abstract 186), 1994. Validation of the Alternative Reproductive Test (ART) to Assess Toxicity of Methoxychlor in Rats. Anderson, S. A., S. W. Pearce, P. A. Fail, B. T. McTaggert, R. W. Tyl, and L. E. Gray, Jr. The Toxicologist 15,164 (Abstract 871), 1995. Endocrine and Reproductive Toxicity of Vinclozolin (Vin) in Male Long-Evans Hooded Rats. Fail, P. A., S. A. Anderson, R. W. Tyl, L. E. Gray, Jr. The Toxicologist IS, 293 (Abstract 1570), 1995. Study Reports (Reports available through the National Technical Information Services [NTIS]f Port Royal Road, Springfield, VA 22161) Teratologic Evaluation of Gentian Violet (CAS No. 548-62-9) in CD Rats, R. Wolkowski-Tyi, C. A. Kimmel, C. Jones-Price, J. R. Reel, T. A. Ledoux, M. C. Marr and L. Langhoff-Paschke. Final Study Report, NCTR Contract No. 222-80-2031 (C), May 31, 1982, National Technical Information Services (NTIS) Accession No. PB83-155754. Teratologic Evaluation of Oxytetracycline Hydrochloride (CAS No. 2058-46-0) in CD-I Mice, R. Wolkowski-Tyl, C. A. Kimmel, T. A. Ledoux, J. R. Reel, C. Jones-Price and L. Langhoff- Paschke. Final Study Report, NCTR Contract No. 222-80-2031 (C), July 5, 1982, National Technical Information Services (NTIS) Accession No. PB83-151027. Teratologic Evaluation of Sulfamethazine (CAS No. 57-68-1) in CD Rats, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, J. R. Reel, T. A. Ledoux, and L. Langhoff-Paschke. Final Study Report NCTR Contract No. 222-80-2031 (C), July 6,1982, National Technical Information Services (NTIS) Accession No. PB83-151035. Teratologic Evaluation of Isoproterenol Hydrochloride (CAS No. 51-30-9) in CD Rats, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, T. A. Ledoux, J. R. Reel, L. Langhoff-Paschke. Final Study Report, NCTR Contract N01-ES-6-2127, December 3, 1982, National Technical Information Services (NTIS) Accession No. PB83-153007. Teratologic Evaluation of Oxytetracycline Hydrochloride (CAS No. 2058-46-0) in CD Rats, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, T. A. Ledoux, J. R. Reel, L. Langhoff-Paschke and M. Marr. Final Study Report, NCTR Contract No. I.ZZIHS'SH Dr. Rochelle W. Tyl Page 16 222-80-2031(0), March 1,1983, National Technical Information Services (NTIS) Accession No. PB83-182469. Teratologic Evaluation of Chlorpromazine Hydrochloride (CAS No. 69-09-0) Administered to CD-I Mice on Gestational Days 6 through 15, C. Jones-Price, C. A. Kimmel, R. Wolkowski-Tyl and M. Marr, Final Study Report, NCTR Contract No. 222-80-2031 (C), March 7,1983, National Technical Information Services (NTIS) Accession No. PB83-179846. Teratologic Evaluation of Chlorpromazine Hydrochloride (CAS No. 69*09-0) Administered to Fischer 344 Rats on Gestational Days 6 through 15, C. Jones-Price, 6. A. Kimmel, R. Wolkowski-Tyl and M. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), March 7,1983, National Technical Information Sen/ices (NTIS) Accession No. PB83-191080. Teratologic Evaluation of Gentian Violet (CAS No. 548-62-9) in New Zealand White Rabbits, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, J. R. Reel, M. Marr and L. Langhoff-Paschke. Final Study Report, NCTR Contract No. 222-80-2031 (C), March 15, 1983, National Technical Information Services (NTIS) Accession No. PB83-182519. Toxicologic Evaluation of Isoproterenol Hydrochloride (CAS No. 51-30-9) Administered Subcutaneously to CD Rats, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, and M. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), April 1,1983, National Technical Information Services (NTIS) Accession No. PB83-211466. Teratologic Evaluation of L-5-Hydroxytryptophan (CAS No. 56-69-9) in CD Rats, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), June 17,1983, National Technical Information Services (NTIS) Accession No. PB83-231332. Teratologic Evaluation of L-5-Hydroxytryptophan (CAS No. 56-69-9) in CD-I Mice, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, and M. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), June 17,1983, National Technical Information Services (NTIS) Accession No. PB83-231670. Teratologic Evaluation of Diethylhexyl Phthalate (CAS No. 117-81-7) in Fischer 344 Rats, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, and M. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), July 20,1983, National Technical Information Services (NTIS) Accession No. PB85-105658. Teratologic Evaluation of Diethylhexyl Phthalate (CAS No. 117-81-7) in CD-I Mice, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), July 20,1983, National Technical Information Services (NTIS) Accession No. PB85-105674. Diethylstilbestrol (DES): Reproduction and Fertility Assessment in CD-I Mice When Administered in the Feed, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. NO1-ES-2-5014, November 4, 1983, National Technical Information Services (NTIS) Accession No. PB84-136746. n&S\4/22?_ Dr. Rochelle W. Tyl Page 17 Bisphenol A: Reproduction and Fertility Assessment in CD-I Mice When Administered Via Subcutaneous Silastic Implants, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. N01-ES-2-5014, January 20,1984, National Technical Information Services (NTIS) Accession No. PB84-155308. Teratologic Evaluation of Carbon Disulfide (CAS No. 75-15-0) Administered to CD Rats on Gestational Days 6 through 15. C. Jones-Price, C. A. Kimmel, R. Wolkowski-Tyl and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), February 24,1984, National Technical Information Services (NTIS) Accession No. PB84-192343. Teratologic Evaluation of Carbon Disulfide (CAS No. 75-15-0) Administered in New Zealand White Rabbits on Gestational Days 6 through 19, C. Jones-Price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031(6), February24,1984 National Technical Information Services (NTIS) Accession No. PB84-192350. Teratologic Evaluation of Bendectin (CAS No. 8064-77-5) in CD Rats, R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), February 28,1984, National Technical Information Services (NTIS) Accession No. PB84-193879. Diethylhexyl Phthalate (DEHP): Reproduction and Fertility Assessment in CD-I Mice When Administered in the Feed, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. NO1-ES-2-5014, April 12,1984, National Technical Information Services (NTIS) Accession No. PB84-181734. Sulfamethazine: Reproductive and Fertility Assessment in CD-I Mice When Administered via the Diet, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. NO1-ES-2-5014, April 25,1984, National Technical Information Services (NTIS) Accession No. PB84-192160. Teratologic Evaluation of Sulfamethazine (CAS No. 57-68-1) in New Zealand White Rabbits, R. Wolkowski-Tyl, C. Jones-Price, M. Marr and 6. A. Kimmel. Final Study Report, NCTR Contract 222-80-2031 (C), May 7,1984, National Technical Information Services (NTIS) Accession No. PB85-172047/AS. Teratologic Evaluation of Hydrochlorothiazide (CAS No. 58-93-5) Administered to CD-I Mice on Gestational Days 6 through 15, J. D. George, R. Wolkowski-Tyl, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), May 9, 1984, National Technical Information Services (NTIS) Accession No. PB85-103570. Teratologic Evaluation of Hydrochlorothiazide (CAS No. 58-93-5) Administered to CD Rats on Gestational Days 6 through 15, J. D. George, R. Wolkowski-Tyl, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), May 25, 1984, National Technical Information Services (NTIS) Accession No. PB85-103588. R&S147223 Dr. Rochelle W. Tyl Page 18 Lead Acetate (PbAc): Reproduction and Fertility Assessment in CD-I Mice When Administered in the Drinking Water, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. NO1-ES-2-5014, May 29,1984, National Technical Information Services (NTIS) Accession No. PB84-208016. Teratologic Evaluation of Ethylene Glycol (CAS No. 107*21-1) Administered to CD Rats on Gestational Days 6 through 15, C. J. Price, R. Wolkowski-Tyl, C. A. Kimmel, and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), May 31,1984, National Technical Information Services (NTIS) Accession No. PB85-104594. Teratologic Evaluation of Ethylene Glycol (CAS No. 107-21-1) Administered to CD-I Mice on Gestational Days 6 through 15, C. J. Price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), May 31, 1984, National Technical Information Services (NTIS) Accession No. PB85-105385. Methyl Salicylate: Reproduction and Fertility Assessment in CD-I Mice When Administered by Gavage, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. NO1-ES-2-5014, August 10,1984, National Technical Information Services (NTIS) Accession No. PB84-241140. Caffeine: Reproduction and Fertility Assessment in CD-I Mice When Administered in the Drinking Water, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. NO1-ES-2-5014, August 29, 1984, National Technical Information Services (NTIS) Accession No. PB85-101202. Dibromochloropropane: Reproduction and Fertility Assessment in CD-I Mice When Administered by Gavage, J. R. Reel, R. Wolkowski-Tyl, A. D. Lawton and J. C. Lamb, IV. Final Study Report, National Toxicology Program Contract No. NO1-ES-2-5014, September 11,1984, National Technical Information Services (NTIS) Accession No. PB85-118644. Teratologic Evaluation of Bisphenol A (CAS No. 80-05-7) Administered to CD-I Mice on Gestational Days 6 through 15, J. D. George, C. J. price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), February 15,1985, National Technical Information Sen/ices (NTIS) Accession No. PB85-205102/AS. Teratologic Evaluation of Bisphenol A (CAS No. 80-05-7) Administered to CD Rats on Gestational Days 6 through 15, J. D. George, C. J. Price, R. Wolkowski-Tyl, M. C. Marr and C. A. Kimmel. Final Study Report, NCTR Contract 222-80-2031 (C), February 15, 1985, National Technical Information Services (NTIS) Accession No. PB85-205110/AS. Reproduction and Fertility Evaluation of Diethylhexy! Phthalate (CAS No. 117-81-7) in Fischer 344 Rats Exposed During Gestation, C. J. Price, R. W. Tyl, M. C. Marr, B. M. Sadler, and C. A. Kimmel, Final Study Report, NCTR/NTP Contract No. 222-80-2031 (C), September 12,1986, National Technical Information Services (NTIS) Accession No. PB87-119046/AS. R&S147224 ' Dr. Rochelle W. Tyl Page 19 Reproduction and Fertility Evaluation of Diethylhexyl Phthalate (CAS No. 117-81-7) in CD-I Mice Exposed During Gestation, C. J. Price, R. W. Tyl, M. C. Marr, B. M. Sadler and C. A. Kimmel, Final Study Report, NCTR/NTP Contract No. 222-80-2031 (C), January 26, 1988, National Technical Information Services (NTIS) Accession No. PB88-204300/AS. Developmental Toxicity Evaluation of Microencapsulated 2-Ethylhexanol (CAS No. 104-76-7) Administered to Swiss (CD-I) Mice in the Feed on Gestational Days 0 through 17, R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, March 11, 1991, National Technical Information Services (NTIS) Accession No. PB91-185900. Developmental Toxicity Evaluation of Ethylene Glycol (CAS No. 107-21 -1) Administered to New Zealand White Rabbits by Gavage on Gestational Days 6 through 19, R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, March 15, 1991, National Technical Information Services (NTIS) Accession No. PB91-211219. October, 1995 R&S147226 PATRICIA ANN FAIL (NODEN), Reproductive Biologist PROFESSIONAL EXPERIENCE November 1990 to date. Manager, Department of Reproductive Biology, Center for Life Sciences and Toxicology, Chemistry and Life Sciences, Research Triangle Institute, Post Office Box 12194, Research Triangle Park, NC 27709. Additional responsibilities beyond that listed below include coordination of group activities, administrative reporting, and decisions on group direction. January 1986 to November 1990. Senior Reproductive Biologist/Toxicologist, Center for Life Sciences and Toxicology, Chemistry and Life Sciences, Research Triangle Institute, Post Office Pox 12194, Research Triangle Park, NC 27709. Contract research and testing in reproductive toxicology and endocrinology for industrial, governmental, and university clients, which include: endocrinopathy after drug treatment (Principal Investigator); performing reproductive assessment by Continuous Breeding Protocol in rodents exposed to potential toxicants (Co-Principal Investigator); development of male contraceptive agents (Co-Investigator); basic research on control of sexual maturation in male deer mice; and genetic models of infertility and receptor binding and bioassay of antiprogestational activity. Collaborative research on social stimulation of testicular function in ring doves and endocrinology of reproductive function in prosimian primates. Responsible for contract administration, proposal development, protocol design, writing of Standard Operating Procedures, literature summaries, interim and final reports, and manuscripts for refereed journals, training and supervision of personnel, and supervision of chemical handling and dosage formulation. Studies conform to FDA and EPA guidelines and adhere to Good Laboratory Practices (GLP) regulations. 1987 to date. Visiting professor for minority institutions, sponsored by FASEB. Once or twice yearly, perform workshops and seminars on some aspect of reproduction or toxicology. 1984 to 1989. Research Associate, Department of Psychology, Duke University, Durham, NC. Research Consultant on reproductive endocrinology to study social stimulation of testicular function in ring doves and pubertal development of prosimian primates. 1980 to 1985. Assistant Professor of Physiology and Zoology, North Carolina State University, Raleigh, NC. Taught Veterinary Physiology, Special Topics in Physiology of Pregnancy, Histology, Comparative Physiology, and Vertebrate Physiology. Developed a research program on environmental and pituitary control of pubertal development of male rodents, hormonal regulation of prostaglandin synthesis at parturition; graduate training and undergraduate research. 1978 to 1980. Research Associate, Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, MI. Planned, organized, and directed research projects in lipid metabolism in perinates of mothers with diabetes, prostaglandin-forming cyclooxygenase formation by tissues of gestation in rabbits; planned and developed blood chemistry and endocrine laboratory. R&S147227 Patricia A. Fail Page 2 1975: 1977 to 1978. Assistant Professor and Instructor, Science Department, Lansing Community College, Lansing, MI. Taught Human Anatomy, Human Physiology, and Human Sexuality. Coordinated seven sections of Human Anatomy. 1976 to 1977. Research Associate, Kliniek Verloskunde, Gynaekologie en KI (Clinic of Veterinary Obstetrics, Gynecology and Artificial Insemination), Rijksuniversiteit te Utrecht, The Netherlands. Research on steriodogenesis in in vitro follicle cultures, purification of equine pituitary hormones, and induction of abortion in horses. 1970 to 1975. Research and Teaching Assistant, Department of Dairy Science and Physiology, Michigan State University, East Lansing, MI. Taught Dairy Science, Animal Reproduction, Human Physiology, and Biological Sciences Laboratories. Conducted research on ovulation control and reproductive endocrinology of horses, influence of vasoligation on sperm production in rats, radioimmunoassay development, and in vitro pituitary monolayer response to releasing hormones. 1966 to 1970. High School Teacher, Science Department, Sanger High School, Sanger, CA. Taught Biology, General Science, and General Mathematics. 1965 to 1966. Histological Research Technician. Experimental pathology. National Aeronautics and Space Administration, Moffett Field, CA. Performed histologic techniques (both routine and developmental) on nerve and brain tissue. 1963 to 1965. Research Assistant and Histological Technician, Zoology Department, Kansas State University, Manhattan, KS. Assisted in Human Anatomy and Embryology Laboratories; MS research on embryology of bovine heart; fixed, sectioned, and stained reproductive tissues; serial sectioned bovine and canine embryos. EDUCATION B.S., Kansas State University, Zoology (Embryology), 1964 M.S., Kansas State University, Zoology (Embryology), 1966 -- Fresno State University, Psychology and Biology, 1968 (teaching certificate) Ph.D., Michigan State University, Physiology and Dairy Science, 1975 HONORS Mary Barnes Scholarship, 1960-1962 Friedline Scholarship, 1962-1964 Kansas Heart Association Grant-in-Aid, 1964-1965 Phi Delta Gamma (Graduate Honorary), 1965 Graduate Office Scholarship Award, 1973 Excellence in Teaching Award Nominee, 1974 R & S 147228 . Patricia A. Fail Page 3 PROFESSIONAL SOCIETIES American Physiological Society American Society of Andrology Association for Study of Animal Science North Carolina Society of Toxicology Sigma Xi Society for Study of Reproduction DISSERTATIONS P. A. Noden, Cardiogenesis in the Bovine to 35 Somites, Masters Thesis, Kansas State University, 1965. P. A. Noden, Estrus, Ovulation and Changes in Some Hormones During the Estrus Cycle of Mares and After Prostaglandin F2a Ph.D. Dissertation, Michigan State University, 1975. PUBLICATIONS Ibrahim, M.Z.M., N. Call, and P. Noden (1968). Modifications of the Hortega silver carbonate method adapated for celloidin-embedded and frozen sections, Ada Neuropath., 10,258-260. Haymaker, W., M.Z.M. Ibrahim, J. Miquel, N. Call, P. Noden, W. Ashly, E.R. Ballinger, J. Ghidoni, I.R. Lindsay, A.J. Behar, and G. Baker (1972). Acute changes in the central nervous system of monkeys exposed to protons, J. Neuropath. Exp. Neurol., 31,72-101. Hafs, H.D., T.M. Louis, P.A. Noden, and W.D. Oxender (1974). Control of the estrous cycle with prostaglandin F2a in cattle and horses, J. Anim. Sci., 38, Suppl. 1,10-21. Hafs, H.D., W.D. Oxender, P.A. Noden, and R.P. Amann (1974). Testicular function in bulls 10 weeks after unilateral vasectomy,/. Anim. Sci., 38,117-120. Noden, P.A., W.D. Oxender, and H.D. Hafs (1974). Estrus, ovulation, progesterone, and lutenizing hormone after prostaglandin F2a in mares, Proc. Soc. Exp. Biol. Med., 145, 145-105. Oxender, W.D., P.A. Noden, T.M. Louis, and H.D. Hafs (1974). A review of prostaglandin F2a for ovulation control in cows and mares, Amer. J. Vet. Res., 35, 997-1001. Lin, Y.C., P.A. Noden, W.D. Oxender, and H.D. Hafs (1975). Androgens in the bovine fetus and dam, K. Mongkonpunya, Proc. Soc. Exp. Biol. Med., 148,489-493. Noden, P.A., W.D. Oxender, and H.D. Hafs (1975). The cycle of oestrus, ovulation and plasma levels of hormones in the mare, J. Reprod. Fertil., 23,189-192. R&SI47229 Patricia A. Fail Page 4 Oxender, W.D., P.A. Noden, D.L. Bolenbaugh, and H.D. Hafs (1975). Control of estrus with prostaglandin F2a in mares: minimal effective dose and stage of estrous cycle. Am. J. Vet. Res., 36,1145-1147. Oxender, W.D., P.A. Noden, and H.D. Hafs (1975). Oestrus, ovulation and plasma hormones after prostaglandin F2a in mares, J. Reprod. Fertil., 23,251-255. Oxender, W.D., and P.A. Noden (1976). Can artificial lights be used to initiate estrus and ovulation in mares? Quarter Horse Journal, 28,34-38. Oxender, W.D., and P.A. Noden (1976). Photoperiod initiation of estrus and ovulation in seasonally anestrous mares, Proc. VIII International Congress on Animal Reproduction and Artificial Insemination, Cracow, Poland, Vol. Ill, 160-164. Oxender, W.D., P.A. Noden, and H.D. Hafs (1977). Prostaglandins for horses. Quarter Horse Journal, 29,116*117. Britt, J.H., P.A. Noden, and R.S. Emery (1977). Teaching dairy science to a heterogeneous group of students at Michigan State University, J. Dairy Sci., 60,832-835. Oxender, W.D., P.A. Noden, and H.D. Hafs (1977). Estrus, ovulation and serum progesterone, estradiol and LH concentrations in mares after an increased photoperiod during winter. Am. J. Vet. Res., 38,203-207. Oxender, W.D., P.A. Noden, and M.C. Pratt (1977). Serum lutenizing hormone, estrus and ovulation in mares following treatment with prostaglandin F2a and gonadotropinreleasing hormone. Am. J. Vet. Res., 38,649-653. Oxender, W.D., and P.A. Noden (1978). Can hormones be used to cause ovulation in mares? Quarter Horse Journal, 30,36-37. Noden, P.A., W.D. Oxender, and H.F. Hafs (1978). Early changes in serum progesterone, estradiol and LH during prostaglandin F2a-induced luteolysis in mares, J. Anim. Sci., 47,666-671. Noden, P.A., W.D. Oxender, and H.D. Hafs (1978). Plasma lutenizing hormone, progestogens and estrogens in mares during gestation, parturition and first postpartum estrus (foal estrus). Am. J. Vet. Res., 39,1964-1967. Noden, P.A., W.L. Smith, D.L. DeWitt, and J.F. Roux (1981). Prostaglandin forming cyclooxygenase activity in rabbit amnion, yolksac splachnopleure, placenta, decidua and uterus at 20 to 30 days gestation, Biol. Reprod., 24,1042-1047. van Leeuwen, W., P.A. Noden, and S.J. Dieleman (1983). Induced abortion with two prostaglandin F2a analogues in mares: plasma progesterone changes. Veterinary Quarterly, 5,97-100. R&S147230 . Patricia A. Fail Page 5 Lepri, J.J., and P.F. Noden (1984). Reproductive function is independent of photoperiod in adult male Microtus pinetorum, J. Mammology, 65,696-697. Whitsett, J.M., P.F. Noden, J. Cherry, and A.D. Lawton (1984). Effect of transitional photoperiods on testicular development and puberty in male deer mice (JPeromyscus maniculatus), J. Reprod. Fertil., 72,277-286. Stroud, C.M., P.F. Noden, and J.M. Whitsett (1985). Bromoergocryptine decreases serum prolactin and delays sexual maturation in male golden hamsters, Biol. Reprod., 32,1191-1199. Kunze, D.J., and P.F. Noden (1986). The effect of flunixin meglumine on levels of prostaglandins E2 and F in the pony following endotoxin administration, J.N. Moore, N.A. White, and J.L. Becht (eds.). IN: Proceedings of the Second Colic Symposium, Vol. 2, Veterinary Learning Systems, Lawrenceville, NJ, pp. 233-234. Fail, P.A., and R.P. Reynolds (1987). Influence of cortisol on prostaglandin synthesis by fetal membranes, placenta and uterus of pregnant rabbits, Biol. Reprod., 37,47-54. Fail, P.A., and J. Whitsett (1988). Influence of photoperiod, ambient temperature and melatonin on testosterone synthesis and release during reproductive maturation in male deer mice, J. Andrology, 9,21-30. Izard, M.K., and P.A. Fail (1988). Progesterone levels during pregnancy in the greater thick-tailed galago (Galago crassicandatus), J. Med. Primatology, 17(3), 125-133. Fail, P.A., J.D. George, H.R. Sauls, S.W. Dennis, and J.C. Seely (1989). Effect of boric add on reproduction and fertility of rodents, Adv. Contra. Deliv. Syst., 5(3/4), 323-333. Fail, P.A., J.D. George, J.C Seely, T.B. Grizzle, and J.J. Heindel (1991). Reproductive toxitity of boric add in Swiss (CD-I) mice: assessment using the continuous breeding protocol. Fund. Appl. Tox., 17,225-239. Perry, J.M., M.K. Izard, and P.A. Fail (1991). Observations in reproductive hormones, copulatory behavior, and neonatal mortality in captive Lemur mongoz (mongoose Lemur), Zoo. Biol., 11,81-97. Cook, C.E., M.C. Wani, Y.W. Lee, P.A. Fail, and V. Petrow (1992). A striking reversal of activity profile: analogs of RU 486 with strong progestational (agonist) activity. Life Sciences, 52,155-162. Chapin, R.E., D.K. Gulati, P.A. Fail, E, Hope, S.R. Russell, J.J. Heindel, J.D. George, T.B. Grizzle, and J.L. Teague (1993). The effects of feed restriction on reproductive function in Swiss CD-I mice. Fund. Appl. Tox., 20,15-22. Grizzle, T.B., J.D. George, P.A. Fail, J.C. Seely, and J.J. Heindel (1994). Reproductive effects of 4-vinylcyclohexene in Swiss CD-I mice assessed by a continuous breeding protocol. Fund. Appl. Tox., 22,122-129. Patricia A. Fail Page 6 Cook, C.E., Y.-W. Lee, M.C. Wani, P.A. Fail, and V. Petrow (1994). Effects of D-ring substituents on antiprogestational (antagonist) and progestational (agonist) activity of llp-aryl steroids. IN: Progesterotte Antagonists in Reproductive Medicine and Oncology, H.M. Beier and I.M. Spitz (eds.). Human Reproduction Volume 9, Supplement 1, June 1994, Oxford University Press, pp. 32-39. Heindel, J.J., R.E. Chapin, D.IC Gulati, J.D. George, L.H. Barnes, P.A. Fail, and R.S.H. Yang (1994). Assessment of the reproductive toxicity of pestidde/fertilizer mixture in mice based on confirmed pestidde contamination in California and Iowa groundwater. Fund. Appl. Tox., 22,605-621. Grizzle, T.B., J.D. George, P.A. Fail, and J.J. Heindel (1995), Carisoprodol: reproductive assessment by continuous breeding in Swiss mice. Fund. Appl. Tox., 24,132-139. Fail, P.A., S.A. Anderson, S.W. Pearce, H.R. Sauls, and R.P. Reynolds (submitted). Endocrine toxidty of nickel: effects on prolactin, thyroxin, and progesterone in rodents after subchronic exposure to nickel chloride in drinking water, Toxicol. Appl. Pharm. Cook, C.E., M.C. Wani, J.M. Jump, Y.-W. Lee, P.A. Fail, S.A. Anderson, Y.-Q. Qu, and V. Petrow (1995). Structure-activity studies of 2,3,4,4a,5,9b-hexahydroindeo[l,2-c] pyridines as antispermatogenic agents for male contraception, J. Med. Chem. (in press). Fail, P.A., H.R. Sauls, and S.A. Anderson fin preparation). Testicular response to gondatropin after boric add treatment in rodents. Fund. Appl. Tox. George, J.D., P.A. Fail, T.B. Grizzle, and J.J. Heindel (in preparation). Nitrofurazone: reproductive assessment by continuous breeding in Swiss mice. Fund. Appl. Tox. Fail, P.A., J.D. George, T.B. Grizzle, and J.J. Heindel (in preparation). Formamide and dimethylformamide: reproductive assessment by continuous breeding in Swiss mice. Fund. Appl. Tox. ABSTRACTS Noden, P.A., H.D. Hafs, and W.D. Oxender (1973). Progesterone, estrus and ovulation after prostaglandin F2a in horses, Abst. Fed. Proc., 32: 229. Noden, P.A., W.D. Oxender, and H.D. Hafs (1973). LH after PGF?,, in mares, J. Anim. Sci., 37: 323. Noden, P.A., W.D. Oxender, and H.D. Hafs (1975). Estradiol, estrone and androstenedione after prostaglandin F2tx (PGF2a) in mares, Abst. Fed. Proc., 34:316. Noden, P.A., W.D. Oxender, and H.D. Hafs (1975). Mare LH and progesterone during gestation/foaling, /. Anim. Sci., 41:372. R&S147232 Patricia A. Fail Page 7 Oxender, W.D., and P.A. Noden (1976). Photoperiod induced estrus in anestrous mares, J. Anim. Sd., 42:1359. Noden, P.A., and W.D. Oxender (1976). LH and ovulation after GnRH in mares, J. Anim. Sd., 42:1360. Oxender, W.D., and P.A. Noden (1976). Photoperiod initiation of estrus and ovulation in seasonally anestrous mares, Proc. VIII International Congress on Animal Reproduction and Artificial Insemination, Cracow, Poland, Vol. 1:190. Oxender, W.D., P.A. Noden, and H.D. Hafs (1977). Estrous, ovulation and serum hormone concentration in seasonally anestrous mares exposed to 16 hours of light each day for 120 days, J. Am. Vet. Med. Assoc., 170:149. Noden, P.A., W.D. Oxender, and H.D. Hafs (1977). Acute changes in progesterone, estradiol and LH after PGF2a in mares, Am. Soc. Anim. Sd. Absts., July: 192. Noden, P.A., and J.F. Roux (1980). Glucose, cholesterol, triglycerides in the cord blood of infants from high risk pregnancies. Society for Gynecological Investigation, Denver, CO, March: 117. Noden, P.A., and J.F. Roux (1981). Prostaglandin-forming cyclooxygenase in rabbit amnion, yolksac splanchnopleure, placenta, decidua and uterus at 20 to 30 days gestation. Societyfor Gynecological Investigation, St. Louis, MO, March: 89. Reynolds, R.P., P.F. Noden, and M.E. Greene (1983). Cortisol-induced abortion in rabbits: maternal serum progesterone and cyclooxygenase activity in the gestational tissues, Biol. Reprod., 28: Suppl. 1:112. Stroud, C., J.M. Whitsett, and P.F. Noden (1984). 2-bromo-a-ergocryptine decreases serum prolactin, flank gland diameter, total accessory sex gland weight, serum testosterone, and testicular weight in prepubertal male golden hamsters, Biol. Reprod., 30: Suppl. 1:171. Stroud, C., J.M. Whitsett, and P.F. Noden (1984). 2-bromo-a-ergocyrptine (CB154) decreased serum prolactin and testosterone, flank gland diameter, total accessory sex gland and testicular weight in prepubertal male golden hamsters. Physiologist, 27: 228. Noden, P., M. Grizzle, M. Greene, and J. Whitsett (1984). Short photoperiod depressed serum testosterone, testes and accessory organ weight during sexual maturation in prairie deer mice, Physiobgist, 27: 228. van Leeuwen, W., P.A. Noden, and S.J. Dieleman (1984). Induced abortion with two prostaglandin F2a analogues in mares; plasma progesterone changes, Amer. Assoc. Equine Prac. Newsletter, 3:159 (Abstract 339). Noden, P., and M. Lancaster (1985). Response of testis to HCG in juvenile deer mice: effect of photoperiod, temperature, and melatonin, Biol. Reprod., 32 (Suppl. 1): 178. R&S147233 Patricia A. Fail Page 8 Fail, P.A. (1987). Response of testis to HCG in young deer mice: effect of photoperiod, temperature, and melatonin. National Research Council Symposium on Role of Biomarkers in Reproductive and Developmental Toocicology, January 12-13, Washington, DC. Fail, P.A. (1987). Influence of 35C and melatonin (MEL) on testosterone (T), testis, and accessory sex organs (ASO) after HCG in Juvenile deer mice, J. Andrology, 8: P23 (Abstract 26). Izard, M.K., and P.A. Fail (1987). Progesterone levels during pregnancy in Galago crassecaudatus, Am.}. PrimatoL, 12:350-351. Fail, P.A., J.D. George, J.C. Seely, T.B. Grizzle, and J.J. Heindel (1989). Reproductive toxicity of boric acid (BORA) in male mice, J. Andrology, 10: P-45. Fail, P.A., J.D. George, T.B. Grizzle, and J.J. Heindel (1989). Reproductive toxicity of boric add (BORA) in mice as evaluated by the continuous breeding protocol. The Toxicologist, 9 (1): 266 (Abstract 1066). Grizzle, T.B., H.R. Sauls, S.W. Dennis, and P.A. Fail (1989). Response of testis to HCG in Swiss mice (CD-I) following chronic exposure to boric add (BORA), Biol. Reprod. 40 (1): 153 (Abstract 316). Izard, M., J. Peny, and P. Fail (1989). Reproductive Biology of Captive Lemur mongoz.,, Am. J. PrimatoL, 18:149. Reynolds, R.P., and P.A. Fail (1990). Nickel chloride (Ni++)-induced perinatal toxidty in CD-I mice may be due to decreased prolactin secretion. The Toxicologist 10(1): 224 (Abstract 894). Izard, M.K., P.A. Fail, and R. Ange (1990). Correlates of puberty in the greater galago, Am. J. PrimatoL, 20:201. Fail, P.A., H.R. Sauls, and S.W. Dennis (1991). Reproductive toxidty of boric acid (BORA) in male deer mice, }. Andrology, 12, Suppl. P62 (Abstract 151). Fail, P.A., and C.S. Stroud (1991). Testicular development in golden hamsters <'Mesocricetus auratus) is influenced by prolactin. In: The Male Germ Cell: Spermatogonium to Fertilization, McGill University, (Abstract 65), p. 90. Izard, K., S. Anderson, H. Sauls, and P. Fail (1991). The use of chronic cannulation in longitudinal endocrinological studies: factors influencing longevity of patency. Triangle Consortium for Reproductive Biology Conference: Frontiers of Biotechnology: Molecular Approaches to Reproductive Biology, Research Triangle Park, NC, January. Fail, P.A., J.D. George, T.B. Grizzle, J.C. Seely, and J.J. Heindel (1991). Reproductive toxidty of 4-Vinylcyclohexene (VCH) in mice as evaluated by the continuous breeding protocol. The Toxicologist, 11 (1): 113 (Abstract 368). R&S 147234 * Patricia A. Fail Page 9 Fail, P.A., S.A. Anderson, M.C. Wani, D. Lee, and C.E. Cook (1991). Response of mouse testis to Sandoz 20-438 (S20438), Biol. Reprod., 42 (1): 175 (Abstract 490). Bishop, J.B., R.E. Chapin, F.A. Fail, J.D. George, T.B. Grizzle, B.M. Sadler, and J.J. Heindel (1991). Acrylamide-induced dominant lethality in mice following low dose chronic administration in drinking water. Environ. Molecular Mutagen., 17 (19): 11. Izard, M.K., P.A. Fail, and R. Ange (1992). Cytological and hormonal responses to follicle stimulating hormone (FSH) and human chorionic gonadotropin (HCG) in the greater galago (Galago crassicaudatus), Am. J. Primatol., 27:34. Fail, P.A., H.R. Sauls, S.W. Pearce, S.A. Anderson, and M.K. Izard (1992). Measures of pituitary and testicular function evaluated with an endocrine challenge test (ECT) in cannulated male rats. The Toxicologist, 12 (1): 436 (Abstract 1725). Izard, M.K., P.A. Fail, J.D. George, T.B. Grizzle, and J.J. Heindel (1992). Reproductive toxicity of cresol isomers administered in feed to mouse breeding pairs, The Toxicologist, 12 (1): 198 (Abstract 725). George, J.D., P.A. Fail, T.B. Grizzle, and J.J. Heindel (1992). Reproductive toxicity of nitrofurazone (NTFZ) administered in the feed to mouse breeding pairs. The Toxicologist, 12 (1): 199. Grizzle, T.B., J.D. George, P.A. Fail, and J.J. Heindel (1992). Reproductive toxicity of carisoprodol (CARD as evaluated by the continuous breeding protocol. The Toxicologist, 12(1): 197 (Abstract 723). Anderson, S.A., H.R. Sauls, S.W. Pearce, M.K. Izard, and P.A. Fail (1992). Measures of pituitary and testicular function evaluated with an endocrine challenge test in cannulated male rats, presented at Triangle Conference on Reproductive Biology, Sheraton Imperial Center, RTP, NC, January 11, Grizzle, T.B., P.A. Fail, J.D. George, R.D. Austin, R.E. Chapin, and J.J. Heindel (1992). Reproductive effects of feed restriction in Swiss (CD-I) mice, presented at Triangle Conference on Reproductive Biology, Sheraton Imperial Center, RTP, NC, January 11. Izard, M.K., P.A. Fail, J.D. George, T.B. Grizzle, and J.J. Heindel (1992). Reproductive toxicity of cresol isomers administered in feed to mouse breeding pairs, presented at Triangle Conference on Reproductive Biology, Sheraton Imperial Center, RTP, NC, January 11. Sauls, H.R., S.W. Dennis, S.W. Pearce, S.A. Anderson, and P.A. Fail (1992). Endocrine responses during boric acid (BORA) exposure for eight weeks in male Swiss CD-I mice, presented at Triangle Conference on Reproductive Biology, Sheraton Imperial Center, RTP, NC, January 11. R&S147235 Patricia A. Fail Page 10 Grizzle, T.B., J.D. George, P.A. Fail, and J.J. Heindel (1992). Reproductive toxidty of carisoprodol in Swiss mice, presented at Annual Meeting of North Carolina Society of Toxicology. Fail, P.A., T.B. Grizzle, J.D. George, R.D. Austin, R.E. Chapin, and J.J. Heindel (1992). Effect of restricted body weight gain on reproduction in Swiss mice, presented at the 1992 Annual Meeting of North Carolina Society of Toxicology. Anderson, S.A., H.R. Sauls, S.W. Pearce, M.K. Izard, and P.A. Fail (1992). Measures of pituitary and testicular function evaluated with an endocrine challenge test in cannulated male rats, presented at Annual Meeting of North Carolina Society of Toxicology. Sauls, H.R., S.W. Dennis, S.W. Pearce, and S.A. Anderson (1992). Luteinizing hormone, follicle stimulating hormone, and testosterone during boric add treatment for eight weeks in CD-I Swiss mice. Biology of Reproduction, 46(1): 170 (Abstrad 479). Anderson, S.A., H.R. Sauls, S.W. Pearce, and P.A. Fail (1992). Endocrine responses after boric add exposure for 2, 9, or 14 days in cannulated male CD rats. Biology of Reproduction, 46(1): 124 (Abstrad 293). Grizzle, T.B., P.A. Fail, J.D. George, R.E. Chapin, and J.J. Heindel (1992). Feed restriction affects the reproductive competence of Swiss (CD-I) mice. Biology of Reproduction, 46(1): 170 (Abstract 478). Cook, C.E., Y.W. Lee, M.C. Wani, P.A. Fail, and V. Petrow (1992). Synthesis and antagonist/agonist activity of lip-ARYL-19-Norpregnadienediones. Mohawk Mountain Conference, Terra Symposia III, May 25-29,1992. Fail, P.A., J.D. George, T.B. Grizzle, and J.J. Heindel (1993). Potential reproductive toxidty of formamide (FORM) as evaluated by the continuous breeding protocol. The Toxicologist, 13: 76. George, J.D., P.A. Fail, T.B. Grizzle, R.S. Yang, and J.J. Heindel (1993). Reproductive toxidty evaluation of a pestidde/fertilizer mixture administered in the drinking water to Mice, The Toxicologist, 13: 77. Fail, P.A., J.D. George, T.B. Grizzle, and J.J. Heindel (1993). Potential reproductive toxidty of formamide (FORM) as evaluated by the continuous breeding protocol. Triangle Conference on Reproductive Biology, January. Anderson, S.A., H.R. Sauls, S.W. Pearce, and P.A. Fail (1993). Endocrine responses after boric acid exposure for 2,9, or 14 days in cannulated male CD rats, Triangle Conference on Reproductive Biology, January. Fail, P.A., J.D. George, T.B. Grizzle, J. Bishop, and J.J. Heindel (1993). Dominant lethality of acrylamide and three of its congeners after chronic exposure in Swiss mice. Environmental Mutagen Society Annual Meeting, April. R&S147236  Patricia A. Fail Page 11 Fail, P.A., S.A. Anderson, S.W. Pearce, H.R. Sauls, and R.P. Reynolds (1994). Endocrine toxicity of nickel: effects on prolactin, thyroxine, and progesterone in rodents after subchronic exposure to nickel chloride in drinking water. Presented at Triangle Conference on Reproductive Biology, January 1994. Fail, P.A., S.W. Pearce, S.A. Anderson, and L.E. Gray (1994). Methoxychlor alters testosterone and LH response to human chorionic gonadotropin or gonadotropin releasing hormone in male Long-Evans hooded rats. Biology of Reproduction, 50, Suppl. l,p. 102 (Abstract 206). Anderson, S.A., P.A. Fail, B.T. McTaggart, R.W. Tyl, and L.E. Gray (1994). Reproductive toxicity of methoxychlor in com oil to male and female Long-Evans hooded rats using the alternative reproduction test protocol (ART). Biology of Reproduction, 50, Suppl. 1, p. 101 (Abstract 186). Fail, P.A., S.W. Pearce, S.A. Anderson, R.W. Tyl, and L.E. Gray, Jr. (1995). Endocrine and reproductive toxicity of vinclozolin (VIN) in male Long-Evans hooded rats. The Toxicologist, 15, Suppl. 1, p. 293 (Abstract 1570). Anderson, S.A., S.W. Pearce, P.A. Fail, B.T. McTaggart, R.W. Tyl, and L.E. Gray, Jr. (1995). Validation of the alternative reproductive test protocol (ART) to assess toxidty of methoxychlor in rats. The Toxicologist, 15, SuppL 1, p. 164 (Abstract 871). Fail, P.A., S.A. Anderson, C.E. Cook, LK. Jost, and D.P. Evenson (1995) Testicular target of indenopyridine analog contraceptive in male mice, presented at XIII Testes Workshop Serono Symposium, Raleigh, NC, March 1995. Cook, C.E., M.C. Wani, J.M. Jump, Y.-W. Lee, P.A. Fail, S.A. Anderson, and V. Petrow (1995) Structure-activity studies toward the development of potential antispermatogenic agents for male contraception, presented at XIII Testes Workshop Serono Symposium, Raleigh, NC, March 1995. Anderson, S.A., P.A. Fail, S.W. Pearce, R.W. Tyl, and L.E. Gray, Jr. (1995). Testicular and adrenal response in adult male Long-Evans hooded rats after antiandrogen vinclozolin exposure. Journal of Andrology, 15, Suppl. 1, p. P-43 (Abstract 78) Fail, P.A., S.A. Anderson, M.C. Wani, Y.W. Lee, J.M. Jump, and C.E. Cook (1995). Contraceptive potency of two indenopyridine analogs of sandoz 20-438 tested in swiss mice. Journal of Andrology, 15, Suppl. 1, p. P-48 (Abstract 99) R&S147237 Patricia A. Fail Page 12 STUDY REPORTS - COMMERCIAL CLIENT Custom-designed endocrine experiments are performed according to Good Laboratory Practices and governmental guidelines for FDA, OECD, or EPA (FIFRA/TSCA). These report titles are not available due to confidential nature of the study. STUDY REPORTS - GOVERNMENT CLIENT Boric Acid (BORA): Reproduction and Fertility Assessment in Swiss (CD-I) Mice When Administered in the Feed. P.A. Fail, J.D. George, T.B. Grizzle, R.E. Chapin, and J.J. Heindel, Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB90253808, April 13,1990. Mixed Chemicals (MIX): Reproduction and Fertility Assessment in Swiss (CD-I) Mice When Administered in the Drinking Water. J.D. George, P.A. Fail, T.B. Grizzle, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB91158444, November 1,1990. 4-Vinylcyclohexene (VCH): Reproduction and Fertility Assessment in CD-I Mice When Administered by Gavage in Com Oil. J.D. George, P.A. Fail, T.B. Grizzle, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB91211250, May 14,1991. Carisoprodol (CARI): Reproduction and Fertility Assessment in CD-I Mice When Administered by Gavage in Com Oil. J.D. George, P.A. Fail, T.B. Grizzle, J.J. Heindel, and R.E. Chapin. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB92128404, September 10,1991. Influence of Restricted Feeding on Reproduction and Fertility Assessment in CD-I Mice. P.A. Fail, J.D. George, T.B. Grizzle, J.J. Heindel, and R.E. Chapin, final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB92174259, February 21, 1992. Ortho-Cresol (OCRE): Reproduction and Fertility in CD-I Mice When Administered in the Feed, J.D. George, P.A. Fail, M.K. Izard, T.B. Grizzle, J.J. Heindel, and R.E. Chapin. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB92176890, March 13,1992. Meta-/Para-Cresol (MPCRE): Reproduction and Fertility Assessment in CD-I Mice When Administered in the Feed, M.K. Izard, J.D. George, P.A. Fail, T.B. Grizzle, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB92191741, May 1,1992. Nitrofurazone (NTFZ): Reproduction and Fertility Assessment in CD-I Mice When Administered in the Feed, J.D. George, P.A. Fail, T.B. Grizzle, J.J. Heindel, and R.E. Chapin. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB92217694, July 15,1992. R&S147238 * Patricia A. Fail Page 13 Iowa Pesticide/Fertilizer Mixture (IWA): Reproduction and Fertility Assessment in CD-I Mice When Administered in Drinking Water, J.D. George, P.A. Fail, T.B. Grizzle, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB93109270/AS, July 31,1992. Formamide (FORM): Reproduction and Fertility Assessment in CD-I Mice When Administered in Drinking Water, J.D. George, P.A. Fail, T.B. Grizzle, R.E Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB93109213, July 31,1992. N,N-Dimethylformamide (DMF): Reproduction and Fertility Assessment in CD-I Mice When Administered in Drinking Water. J.D. George, P.A. Fail, T.B. Grizzle, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB92123842, September 24,1992. Methacrylamide (MACR): Reproduction and Fertility Assessment in CD-I Mice When Administered in Drinking Water, P.A. Fail, J.D. George, M.K. Izard, T.B. Grizzle, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB93149284, November 10,1992. Acrylamide (ACRL): Reproduction and Fertility Assessment in CD-I Mice When Administered in Drinking Water. P.A. Fail, J.D. George, T.B. Grizzle, M.K. Izard, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB93158285, December 18,1992. N,N'-Methylenebisaaylamide (BACR): Reproduction and Fertility Assessment in CD-I Mice When Administered in Drinking Water, P.A. Fail, J.D. George, M.K. Izard, T.B. Grizzle, R.E Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB93160976, December 18,1992. NTHydroxymethyD-Acrylamide (HACR): Reproduction and Fertility Assessment in CD-I Mice When Administered in Drinking Water. P.A. Fail, J.D. George, M.K. Izard, T.B. Grizzle, R.E. Chapin, and J.J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-65141, NTIS No. PB93151561, December 18,1992. Development and Testing of Nonsteroidal Male Contraceptive Agents. C.E. Cook, Y.W. Lee, P.A. Fail, M.C. Wani, November 2, 1990, Fourth Quarterly Report, Project No. 311U-4587/00/06Q, July 1,1990 - September 30,1990. Development and Testing of Nonsteroidal Male Contraceptive Agents. C.E. Cook, Y.W. Lee, P.A. Fail, M.C. Wani, February 6, 1991, Fifth Quarterly Report, Project No. 311U-4587/00/06Q, October 1,1990 - December 31,1991. Development and Testing of Nonsteroidal Male Contraceptive Agents. C.E. Cook, Y.W. Lee, P.A. Fail, M.C. Wani, May 8, 1991, Sixth Quarterly Report, Project No. 311U-4587/00/06Q, January 1,1991 - March 31,1991. i R&S147239 Patricia A, Fail Page 14 Development and Testing of Nonsteroidal Male Contraceptive Agents. C.E. Cook, Y.W. Lee, P.A. Fail, M.C. Wani, September 19,1991, Seventh Quarterly Report, Project No. 311U-4587/00/06Q, April 1,1991 - June 30,1991. Development and Testing of Nonsteroidal Male Contraceptive Agents. C.E. Cook, Y.W. Lee, P.A. Fail, M.C. Wani, January 3, 1992, Eighth Quarterly Report, Project No. 311U-4587/00/06Q, July 1,1991 - September 30,1991. Development and Testing of Nonsteroidal Male Contraceptive Agents. C.E. Cook, Y.W. Lee, P.A. Fail, M.C. Wani, September 10, 1992, Ninth Quarterly Report, Project 311U4587/00/09Q. 28-Day Toxicology Screen: Indenopyridine RTI 4587-056 in Male Sprague-Dawley (CD) Rats. P.A. Fail, S.A. Anderson, H.R. Sauls, and C.E. Cook, January 13, 1993, Project 311U-4587-004. Synthesis and Testing of Male Contraceptive Agents. C.E. Cook, J.M. Jump, P.A. Fail, and S.A. Anderson, July 1,1994, Fourth Quarterly Report, Project 60U-5539/4Q. Two-generation study of methoxychlor administered in com oil to Long-Evans hooded rats using the alternative reproductive test protocol. Fail, P.A., S.W. Pearce, S.A. Anderson, A Final Report issued to US EPA CR820335-01-0.1995. (Submitted May 1994) Two-generation study of vinclozolin administered in com oil to Long-Evans hooded rats using the alternative reproductive test protocol. Fail, P.A., S.W. Pearce, S.A. Anderson, A Final Report issued to US EPA CR820335-01-0.1995. (In preparation) CONFIDENTIAL STUDY REPORTS Mechanistic Studies: Serum Hormone Concentrations after XXXXXX has been Administered in the Feed or by Gavage to Adult Female CD Rats, Experiment 1 and 2. P.A. Fail and M.K. Izard, 1991, Project No. 311C-4556-10, Submitted August 8, 1991, Confidential Client. Chronic Intra-atrial Cannulation and Microassay for Hormones Allows Longitudinal Study Design to Assess Endocrine Changes in Adult Female CD Rats Exposed to Dietary XXXXXX, Project B. M.K. Izard and P.A. Fail, 1990, Project No. 311C-4556-10, Submitted September 17,1990, Confidential Client. May 1995 R & S 147240 JOHN CURTIS SEELY Education: Residency in Comparative Pathology (1975-1980), Walter Reed Army Institute of Research. D.V.M., University of Missouri, 1975. A.B., Zoology, University of Missouri, 1971. Certification: Diplomate, American College of Veterinary Pathologists, 1981. Experience: 1985 - Present: Veterinary Pathologist, PATHCO, Inc. Duties Include: Co-Principal Investigator of a pathology support contract to the National Toxicology Program: this work includes primary histopathology, quality assessment histopathology, necropsy supervision, serving as Chairperson on PWGs, site visits, wet tissue audits and special projects as assigned. Serves additionally as a pathology consultant to the Research Triangle Institute, the Environmental Protection Agency, and to several other commercial clients. Utilizes the LABCAT histopathology computer program to generate histopathology data. Supports training efforts at both the professional and technical level in Pathology and Laboratory Animal Science. 1984 - 1985 Director of Pathology, Tegeris Laboratories, Inc., Laurel, Maryland (formerly Pharmacopathics Research Laboratories, Inc., and Borriston Laboratories, Inc.). 1980 - 1984 Veterinary Pathologist/Study Director, Tegeris Laboratories, Inc. Duties included: direct supervision of all gross necropsies and the subsequent tissue blocking and slide preparation; Study Director for dog studies; histopathological interpretation of tissues and consultation with the Study Director on the gross and histopathological data; writing pathology reports for in-house acute, subchronic, and chronic studies; supervisor for histology, clinical chemistry, and hematology departments; contribution to TL's Standard Operating Procedures; involvement in the study design and John Curtis Seely strict adherence of the SOPs regarding that portion of the study pertaining to gross and histopathology; entering of the gross and histopathology findings into the computerized LABCAT format and preparation of the pathology reports; and maintaining an active role in the continuing education of the laboratory personnel. 1975 - 1980 staff Pathologist, (Captain, U.S. Army), Walter Reed Army Institute of Research, Washington, D.C., Department of Comparative Pathology, Division of Pathology. Duties included: Comparative Pathology residency training; grqss and microscopic pathology diagnostic support involving a wide variety of laboratory animals including non-human primates. Electron microscopic support of both diagnostic cases and collaborative research projects. Active participation in training programs at WRAIR and the AFIP. 1977 - 1979 Instructor in Anatomy (1977 - 1978), Adjunct Assistant Professor (1978 - 1979) Department of Anatomy (Histology), Uniformed Services University of the Health Sciences, Bethesda, Maryland. Duties included: Primary lab instructor for the first year medical school histology course. This included weekly presentations of each organ system at both the light and ultrastructural level, test preparation and student evaluation. Awards s U.S. Army Health Professions Scholarship Phi Zeta Honor Society of Veterinary Medicine Memberships/Societies: American Veterinary Medical Association American College of Veterinary Pathologists Society of Toxicologic Pathologists American Association for Laboratory Animal science International Academy of Pathology Japanese Society of Toxicologic Pathology R&S 147242 2 John Curtis Seely Gonimittees And Professional Activities; Chairman, Special Presentations Group, 3rd International Symposium of the Society of Toxicologic Pathologists, May 14-16, 1984. Local Arrangements, Society of Toxicologic Pathologists, 1985 Annual Meeting. Ad Hoc Committee on Commercial Exhibits, American College of Veterinary Pathologists. Editorial Advisory Board (Pathology) LAB ANIMAL. Nature Publishing Co. Renal Specialty Group (Co-Chairperson), American College of Veterinary Pathologists, 1991 Annual Meeting. Renal Specialty Group (Chairperson), American College of Veterinary Pathologists, 1992 Annual Meeting. Abstract Review Committee, 1994 National AALAS meeting. Publications: Cox, V.S. and Seely, J.C.: A Simplified Resectioning Technique. Stain Tech. 40:329-333, 1974. Seely, J.C., Cosenza, S.P., Montgomery, C.: Leiomyosarcoma of the Urinary Bladder in a Dog, with Metastases, JAVMA 172:1427-1429, 1978. Jacobson, E.R., Seely, J.C., Novilla, M. N. and Davidson, J.: Heart Failure Associated with Unusual Hepatic Inclusions in a Deckert's Rat Snake, . of Wildlife Pis. 15:75-81, 1979. Jacobson, E.R., Seely, J.C., and Novilla, M. N.: Lymphosarcoma Associated with Viruslike Intranuclear Inclusions in a California King Snake (Columbr-iriae lamproneltis) . JNCI 65:577-582, 1980. Jessup, D.A. and Seely, J.C.: Zygomycete Fungus Infection in Two Captive Snakes: Gopher snake fPituophis melanoleucus) and Copperhead (Acrkistrondon controtrixl. J. Zoo. An. Med. 12:54-59, 1981. Sobel, D.A., Marguet, E. and Seely, J.C.: A Case for the Panel: Viruslike Particles in Hamster Liver. Ultrastruct. Path. 5:257258, 1983. Seely, J.C.: Zymbal Glands in the Rat. Lab Animal 15:25-31, 1986. Cosenza, S.F. and Seely, J.C.: Generalized Nodular Dermatofibrosis and Renal Cystadenocarcinomas in a German Shepherd Dog. JAVMA 189: 1587-1590, 1986. 3 R&S147243 John Curtis Seely Seely, J.C.: The Harderian Gland, Lab Animal 16:33-39, 1987. Mayes, M.E., Held, G.A., Seely, J.C., Roe, R.M., Dauterman, W.C. and Kawanishi, C.Y.: Characterization of the Mammalian Toxicity of the Crystal Polypeptides of Bacillus thurinoiensis subsp. israelensis. Fund. Appl. Toxicol. 13:310-322, 1989. Fail, P.A., George, J.D., Sauls, H.R., Dennis, S.W., and Seely, J.C.: Effect of Boric Acid on Reproduction and Fertility of Rodents, ftdv. Contra. Deliv. Svst. 5:323-333, 1989. Bucher, J.R., Uraih, L.C., Hildebrandt, P.K., Sauer, R.M., and Seely, J.C.: Carcinogenicity and Pulmonary Pathology Associated with a Single 2-Hour Inhalation Exposure of Laboratory Rodents to Methyl Isocyanate. JNCI 81:1586-1587, 1989. Allis, J.W., Ward, T.R., Seely, J.C., and Simmons, J.E.: Assessment of Hepatic Indicators of Subchronic Carbon Tetrachloride Injury and Recovery in Rats. Fund. AppI. Toxicol. 15:558-570, 1990. Dubey, J.P., Cosenza, S.F., Lipscomb, T.P., Topper, M.J., Speer, C.A., Hoban, L.D., Davis, S.W., Kincaid, A.L., Seely, J.C., Marrs, G.E.: Acute Sarcocystosis-Like Disease in a Dog. JAVMA 198:439443, 1991. Simmons, J.E., Allis, J.W., Grose, E.C., Seely, J.C., Robinson, B.L., and Berman, E.: Assessment of the Hepatotoxicity of Acute and Short-Term Exposure to Inhaled p-Xylene in F344 Rats. J. Toxic. Environ. Health 32:295-306, 1991. Fail, P.A., George, J.D., Seely, J.C., Grizzle, T.B., and Heindel, J.J.: Reproductive Toxicity of Boric Acid in Swiss (CD-I) Mice: Assessment Using the Continuous Breeding Protocol. Fund. AppI. Toxicol. 17:225-239, 1991. Seely, J.C.: Adenoma of the Auditory Sebaceous Glands, Rat. Eve and Ear. ILSI Monograph on Pathology of Laboratory Animals. T.C. Jones, U. Mohr, R.D. Hunt (Eds.) Springer-Verlag, Berlin, 1991; pp. 143-145. Seely, J.C.: Carcinoma of the Auditory Sebaceous Glands, Rat. Eye and Ear. ILSI Monograph on Pathology of Laboratory Animals. T.C. Jones, U. Mohr, R.D. Hunt (Eds.) Springer-Verlag, Berlin, 1991; pp. 145-149. 4 R&S147244 John Curtis Seely House, D.E., Berman, E., Seely, J.C., and Simmons, J.E. Comparison of Open and Blind Histopathologic Evaluation of Hepatic Lesions. Toxicology Letters, 63:127-133, 1992. Tyl, R.W., Price, C.J., Marr, M.C., Myers, C.B., Seely, J.C., Heindel, J.J., and Schwartz, B.A. Developmental Toxicity Evaluation of Ethylene Glycol By Gavage In New Zealand White Rabbit. Fund. Appl. Toxicol. 20:402-412, 1993. Grizzle, T.B., George, J.D., Fail, P.A., Seely, J.C., and Heindel, J.J. Reproductive Effects of 4-Vinylcyclohexene in Swiss CD-I Mice Assessed by A Continuous Breeding Protocol. Fund. Appl. Toxicol. 22:122-129, 1994. Robinson, B.L., Guinnup, D.E., Andrews, J.E., Allis, J.W., McDonald, A., Seely, J.C., Mohin, T.J., and Simmons, J.E. Hepatic and Renal Assessment of Acute Exposure to Inhaled Epichlorohydrin: Toxicological Assessment and Exposure Modeling. (Submitted for Publ.) Simmons, J.E., Yang, R.S.H., Svendsgaard, D.J., Thompson, M.B., Seely, J.C., McDonald, A. Toxicology Studies of a Chemical Mixture of 25 Groundwater Contaminants: Hepatic and Renal Assessment, Response to Carbon Tetrachloride Challenge and Influence of Treatment-Induced Water Restriction. (In Press) Thornton-Manning, J.R., Seely, J.C., and Pegram, R.H. Toxicology of Bromodichloromethane in Female Rats and Mice After Repeated Oral Dosing. (In Press) Price, C.J., Marr, M.C., Myers, C.B., Seely, J.C., Heindel, J.J., and Schwetz, B.A. The Developmental Toxicity of Boric Acid in Rabbits. (In Preparation) Price, C.J., Field, E.A., Marr, M.C., Myers, C.B., Seely, J.C., Morrissey, R.E., Heindel, J.J. and Schwetz, B.A. The Developmental Toxicity of Butyl Benzyl Fhthalate in Rats and Mice. (In Preparation) Simmons, J.E., McDonald, A., Seely, J.C., Sey, Y.M. Potentiation of Carbon Tetrachloride Hepatotoxicity by Inhaled Methanol: TimeCourse of Injury and Recovery. (In Preparation) Boolcs/Boofc Chapters Feldman, D.B. and Seely, J.C.: Necropsy Guide: Rodents and the Rabbit. CRC Press, Inc., Boca Raton, FL., 1988. 5 R&S147245 John Curtis Seely Yang, R.S.H., Huff, J., Germolec, D.R., Luster, M.I., Simmons, J.E., and Seely, J.c. Carcinogenicity and Pesticides: Biological Issues In Extrapolation. In: Carcinogenicity and Pesticides: Principles. Issues, and Relationships (N.N. Ragsdale, R.E. Menzer; eds.) ACS Symposium Series No. 414, Chapter 9, 1989. Seely, J.c. and Hildebrandt, P.K.: Parathyroid Gland. In: Pathology of the Fischer Rat. Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery, C.A., and MacKenzie, W.F. (eds.) Academic Press, Orlando, 1990, pp. 537-543. Montgomery, C.A. and Seely, J.C.: Kidney. In: Pathology of the Fischer Rat. Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery, C.A., and MacKenzie, W.F. (eds.) Academic Press, Orlando, 1990, pp. 127-153. Seely, J.C. Auditory Sebaceous Glands (Zymbal's Glands). In: Integumentary System. ILSI Monographs on the Pathology of Aging Animals, u. Mohr, D.L. Dungworth, C.C. Capen, ILSI Press, Wash. D.C., 1994, pp. 423-433. Seely, J.C., Eustis, S.L. and Boorman, G.A.: Mammary Gland. Pathology of the B6C3F1 Mouse. Boorman, G.A., Eustis, S.L., Elwell, M.R. (eds.). Academic Press. (In Preparation) In: Hailey, J.R. and Seely, J.C.: Kidney, Ureter, Urinary Bladder. In: Pathology of the B6C3F1 Mouse. Boorman, G.A., Eustis, S.L., Elwell, M.R. (eds.). Academic Press. (In Preparation) Study Sets Goodman, D.G., Anver, M.R., Sauer, R.M., Seely, J.C., strandberg, J.D., Hildebrandt, P.K., Vonderfecht, S.L., Imes, G.D., Ward, J.M., Parker, G.A., Boorman, G.A., and Uraih, L.: Experimentally Induced and Other Proliferative and Neoplastic Lesions in Mice. Registry of Veterinary Pathology, Armed Forces Institute of Pathology, Washington, D.C., 1989. Presentations: Cerebellar Hypoplasia in the Cat: An Ultrastructural Study. Presented at the Central States Electron Microscopic Society, March 1974, Columbia, Missouri. Experimental Trypanosomiasis in Mice: Morphologic Pathology. Presented at the ACVP Veterinary Neuropathology Interest Group, December, 1976, Miami Beach, Florida. R&S147246 6 John Curtis Seely Diagnostic Electron Microscopic Pathology. Presented at the Pathology of Lab Animals Course, AFIP, 1977, 1978, 1979, 1980, Washington, D.C. Electron Microscopy as a Technique for Diagnosis. Presented at .the Wildlife Disease Meeting, August, 1978, Ft. Collins, Colorado. Diagnostic E.M. in Veterinary Pathology. Presented at the Ultrastructural Pathology Course, NIH, October, 1977, 1978, Bethesda, Maryland. Reptile Histology and Selected Diseases. Presented at the North Carolina Society of Histopathology Technologists Annual Meeting, May, 1986, Burlington, N.C. Abdominal Swelling in Female Mice. Presented at the District 4 Meeting - AALAS, March 1987, Raleigh, N.C. Diseases of the Kidney. Presented at the American Association for Laboratory Animal Science Annual Meeting, November 1987, Denver, Colorado. Miscellaneous Skin Diseases of Laboratory Animals. Presented at the American Association for Laboratory Animal Science Annual Meeting, October 1988, Detroit, Michigan. Diseases of the Kidney. Presented at the CUT Pathology Minicourse, June 1990, Research Triangle Park, North Carolina. Toxicologic Pathology of the Kidney. Presented at the College of Veterinary Medicine, NCSU as part of a graduate level course on Toxicologic Pathology, 1990, 1992, Raleigh, North Carolina. Histopathology of the Kidney. Presented at the College of Veterinary Medicine, NCSU as part of a graduate level course on Histopathology, 1993, Raleigh, North Carolina. Toxicologic Pathology of the Kidney and Diseases of Reptiles. Presented at the College of Veterinary Medicine, Kagoshima University, Kagoshima, Japan and at the Institute of Environmental Toxicology, Ibaraki, Japan. Nov., 1993. Abstracts/Posters: Avoiding Pitfalls in Necropsy and Histology Procedures - QA Considerations; Society of Quality Assurance, Chicago 1986. J.C. Seely, and P.K. Hildebrandt. 7 R&S147247 John Curtis Seely Influence of Diet and Route of Administration on Vitamin E. Toxicity in Male F-344 Rats. Federation of American Societies for Experimental Biology, Las Vegas, 1988. K.M. Abdo, M. Thompson, J. Bucher, C.W. Jameson, J.C. Seely, S. Seilkop and B. Prillman. FASEB Journal, 2:Abst. 4655 (1988). Enhancement of Carbon Tetrachloride (CCL4) Hepatotoxicity by Prior Exposure to a Mixture of 25 Groundwater Contaminants. Society of Toxicology, Atlanta, 1989. J.E. Simmons, R.S.H. Yang, J.C. Seely, D. Svendsgaard, and A. McDonald. The Toxicologist, 9:58 (1989). Reproductive Toxicity of Boric Acid (BORA) in Male Mice. Society of Andrology, New Orleans, 1989. P.A. Fail, J.D. J.C. Seely, T.B. Grizzle, and J.J.Heindel. J. Andrology, (1989). American George, 10:45 Inhaled Methanol Enhances the Hepatotoxicity of Orally Administered Carbon Tetrachloride. Society of Toxicology, Miami Beach, 1990. J.E. Simmons, J.W. Allis, A. McDonald, J.C. Seely, and B.L. Robinson. The Toxicologist, 10:85 (1990). Effects of a Mixture of 25 Groundwater Contaminants on Carbon Tetrachloride (CCL4) Hepatotoxicity. 4th International Conference on Combined Effects of Environmental Factors, Baltimore, 1990. J.E. Simmons, R.S.H. Yang, B. Svendsgaard, J.C. Seely, M.B. Thompson, and A. McDonald. Reproductive Toxicity of 4-Vinylcyclohexene (VCH) in Mice as Evaluated by the Continuous Breeding Protocol. Society of Toxicology, Dallas, 1991. P.A. Fail, J.D. George, T.B. Grizzle, J.C. Seely, and J.J. Heindel. The Toxicologist 11:113 (1991). Methanol (MEOH) Potentiation of Carbon Tetrachloride (CCL4) Hepatotoxicity Depends on MEOH Concentration. Society of Toxicology, Dallas, 1991. J.E. Simmon, J.W. Allis, A. McDonald, D. Svendsgaard, J.C. Seely. The Toxicologist 11:219 (1991). Effects of a Mixture of 25 Groundwater Contaminants on Carbon Tetrachloride (CCL4) Hepatotoxicity. society of Toxicology, Dallas, 1991. D. Svendsgaard, R.S.H. Yang, J.C. Seely, M.B. Thompson, A. McDonald, J.E. Simmons. The Toxicologist 11:219 (1991). Hepatic and Renal Effects of Concurrent Exposure to Trichloroethylene and Carbon Tetrachloride. North CarolinaSociety of Toxicology, RTP, 1991. A. McDonald, Y.M. Sey, J.C. Seely, D.J. Svendsgaard, M.B. Thompson, and J.E. Simmons. R&S147248 8 John Curtis Seely Hepatic and Renal Toxicity Following Concurrent Oral Exposure to Trichloroethylene (TCE) and Carbon Tetrachloride (CCL4). Society of Toxicology, Seattle, 1992. J.E. Simmons, Y.M. Sey, J.C. Seely, M.B. Thompson, D.J. Svendsgaard. The Toxicologist 12:892 (1992). Reproductive Toxicity Study of Methylethyl Ketoxime (MEKO) by Gavage in CD Rats. R.W. Tyl, J.M, Gerhart, C.B. Myers, M.C. Marr, D.R. Brine, A.F. Gilliam, J.C. Seely, M.J. Derelanko. The Toxicologist 13:196 (1993). Two Generation Study of Dietary Tributyl Phosphate (TBP) in CD Rats. J.M. Gerhart, R.W. Tyl, C.B. Myers, M.C. Marr, D.R. Brine, J.C. Seely. The Toxicologist 13:199 (1993). Alterations In Ovarian Histology and Reproductive Patterns of Female Mice Exposed to Xenobiotics. J.B. Bishop, J.C. Seely, K.T. Cain, and W.M. Generoso. Environmental and Molecular Mutagenesis 21: Supp. 21:6 (1993). Renal and Hepatic Toxicity of Inhaled Chloroform in Male F-344 Rats. A. McDonald, Y.M. Sey, J.C. Seely, T.A. Grantham and J.E. Simmons. The Toxicologist 14:178 (1994). 9 R&S147249 P John Curtis Seely HTP Chemicals Reviewed In Pathology Working Group Evaluations National Toxicology Program/Technical Report Series htp te m335 338 341 343 344 357 368 369 367 375 378 371 382 399 CHEMICAL c. X. Acid Orange 3, Dec., 1988 Erythromycin Stearate, Dec., 1988 Nitrofurantoin, Sept., 1989 Benzyl Alcohol, June, 1989 Tetracycline Hydrochloride, Aug., 1989 Hydrochlorothiazide, July, 1989 Nalidixic Acid, Oct., 1989 a - Methylbenzyl Alcohol, Jan., 1990 Phenylbutazone, March, 1990 Vinyl Toluene (mixed isomers), March, 1990 Benzaldehyde, March, 1990 Toluene, Feb., 1990 Furfural, March, 1990 Titanocene Dichloride, 1991 10 Pi'SS 147250 John Curtis Seely NTP Chemicals Reviewed In Pathology Working Group Evaluations National Toxicology Program/Technical Report Series NTP TR NO. 406 411 402 413 414 417 427 398 CHEMICAL Butyrolactone (Gamma), March, 1992 C.I. Pigment Red 23, Nov., 1992 Furan, Jan., 1993 Ethylene Glycol, Feb., 1993 Pentachloroanisole, Apr., 1993 p-Nitrophenol, Apr., 1993 Turmeric Oleoresin, Aug., 1993 Polybrominated Biphenyls, Aug., 1993 R&S147251 11 R&S147252 John Curtis Seely, D.V.M. Diplomats, American College of Veterinary Pathologists Summary of Experience in Carcinogenic and Toxicologic Pathology Dr. Seely has more than 19 years of experience in veterinary pathology. Since 1980, he has been active in toxicologic pathology. He has been responsible for all aspects of pathology including supervising histology and clinical pathology at a toxicology testing laboratory. In various capacities, he has provided pathology support to private clients and to various government scientific advisory and regulatory agencies including the National Toxicology Program (NTP) of the National Institute of Environmental Health Sciences (NIEHS), and the Environmental Protection Agency (EPA). include: Examples of pathology support provided to these clients . Chairing conduct of more than 85 Pathology Working Groups (PWGs) on both subacute and chronic toxicology/carcinogenicity studies conducted by NTP Participating in PWGs at NTP . Conducting wet tissue and pathology data audits for NTP . Supervising and performing gross necropsies for toxicity/carcinogenicity studies . Conducting independent reviews of selected lesions/target organs for both private and government clients . Electron microscopy consultation R&S147253 Page 2 John Curtis Seely, D.V.M., ACVP Consulting on design of study protocols for subchronic and chronic studies Performing histopathologic evaluations of microslides from numerous toxicity/carcinogenicity studies involving dogs, rats and mice for both private and government clients R&S147254 MELISSA C. MARR, Research Biologist II Professional Experience Research Triangle Institute, Center for Life Sciences and Toxicology, Chemistry and Life Sciences, Research Triangle Park, NC 27709. June 1981 to date. Reproductive and Developmental Toxicology Laboratory Supervisor. Responsibilities include scheduling timetables for completion of all phases of studies involving mice, rats, hamsters and rabbits; direct supervision of up to nine other laboratory personnel including assignment of tasks, training and quality control, coordination of support analytical and clinical chemistry, expertise in all phases of postnatal studies including multigenerational reproductive toxicity and behavioral landmarks; development of SOPs, protocols, and preparation of study reports; design and implementation of and training of staff in procedures for research protocols in pharmacokinetics and metabolism of test agents in pregnant and lactating animals (and their offspring), and transplacental and translactational transport of test agents and/or metabolites in animal models. 1979 to 1981. Biologist I in Teratology. Teratological evaluation of compounds in laboratory animals (rats, mice, rabbits); expertise in all RTI SOPs for conventional teratology. University of North Carolina School of Medicine, Department of Radiology, Chapel Hill, North Carolina. 1977 to 1979. Research Technician II. Used microradiofogical techniques to study the effects of vascular disease of the kidney in human and laboratory animals. Bowman Gray School of Medicine, Department of Physiology, Winston-Salem, North Carolina. 1976 to 1977. Laboratory Technician II. Studied the effects of hypertension on vascular size in humans and laboratory animals. Education B.A., Biology (Psychology Minor), University of North Carolina at Greensboro, North Carolina, 1975. Developmental Toxicology and Teratology, K. K. Sulik, course director, University of North Carolina at Chapel Hill (Spring, 1990). American Association of Laboratory Animal Science--Laboratory Animal Technologist Certification course (EPA, Fall 1991) Certification Laboratory Animal Technologist (LATG), AALAS Certification (1992). Professional Organizations Society of Toxicology, NC Chapter Teratology Society North Carolina Association for Biomedical Research North Carolina Quality Assurance Discussion Group R&S147255 Melissa C. Marr Page 2 Publications Arteriolar Rarefaction in the Conjunctiva of Human Essential Hypertensives. R. N. Harper, M. A. Moore, M. C. Mam, L. E. Watts and P. M. Hutchins, Microvascular Research 16, 369,1978. Experimental Renal Papillary Necrosis in Rats: Microangiographic and Tubular Micropuncture Injection Studies. J. T. Cuttino, Jr., Fred V. Goss, Richard L Clark, and Melissa C. Marr, Investigative Radiology, 16,2,1981. Microangiographic Studies of Experimental Erosive Synovitis in Rats. Richard L. Clark, Melissa C. Marr, John H. Schwabb and William J. Chromartie, Investigative Radiology, 18, 2, 1983. The Developmental Toxicity of Ethylene Glycol in Rats and Mice. C. J. Price, C. A. Kimmel, R. W. Tyl and M. C. Marr, Toxicology and Applied Pharmacology fil, 113-127,1985. The Developmental Toxicity of Orally Administered Oxytetracycline in Rats and Mice. R. E. Morrissey, R. W. Tyl, C. J. Price, T. A. Ledoux, J. R. Reel, L. L. Paschke, M. C. Marr and C. A. Kimmel, Fundamental and Applied Toxicology 7, 434-443,1986. The Developmental Toxicity of Diethyiene Glycol Dimethyl Ether in Mice. C. J. Price, C. A. Kimmel, J. D. George and M. C. Marr, Fundamental and Applied Toxicology fi, 115-126, 1987. The Developmental Toxicity of Bisphenol A in Rats and Mice. R. E. Morrissey, J. D. George, C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, Fundamental and Applied Toxicology 8, 571-582,1987. The Developmental Toxicity of Triethylene Glycol Dimethyl Ether in Mice. J. D. George, C. J. Price, C. A. Kimmel and M. C. Marr, Fundamental and Applied Toxicology 8,173-181,1987. Developmental Toxicity Evaluation of Bendectin in CD Rats. R. W. Tyl, C. J. Price, M. C. Marr and C. A. Kimmel, Teratology 2Z, 539-552,1988. Developmental Toxicity Evaluation for Dietary Di(2-ethylhexyl)-phthalate in Fischer 344 Rats and CD-I Mice. R. W. Tyl, C. J. Price, M. C. Marr and C. A. Kimmel, Fundamental and Applied Toxicology 16, 395-412,1988. Developmental Toxicity of 1,1,1-Trichloroethane in CD Rats. J. D. George, C. J. Price, M. C. Marr, B. M. Sadler, B. A. Schwetz, L. S. Bimbaum and R. E. Morrissey, Fundamental and Applied Toxicology 18, 641-671,1989. The Developmental Toxicity of Orally Administered Thiophylline in Rats and Mice. P. Lindstrem, R. E. Morrissey, J. D. George, C. J. Price, M. C. Marr, C. A. Kimmel and B. A. Schwetz, Fundamental and Applied Toxicology 14,167-178,1990. Developmental Toxicity Evaluation of Acrylamide in Rats and Mice. E. A. Field, C. J. Price, R. B. Sleet, M. C. Marr, B. A. Schwetz and R. E. Morrissey, Fundamental and Applied Toxicology 14, 502-512, 1990. R&S147256 Melissa C. ManPage 3 Codeine: Developmental Toxicity in Hamsters and Mice. J. Williams, C. J. Price, R. B. Sleet, J. D. George, M. C. Marr, C. A. Kimmei and R. E. Morrissey, Fundamental and Applied Toxicology 12, 401-413,1991. The Developmental Toxicity of Ethylene Glycol Diethyl Ether in Mice and Rabbits. J. D. George, C. J. Price, M. C. Marr, C. A. Kimmei, B. A. Schwetz and R. E. Morrissey, Fundamental and Applied Toxicology 19.15-25,1992. Developmental Stages of the CD (Sprague-Dawiey) Rat Skeleton After Maternal Exposure to Ethylene Glycol. M. C. Marr, C. J. Price, C. B. Myers and R. E. Morrissey, Teratology 4j[2), 169-181,1992. Developmental Toxicity of Diethylene and Triethylene Glycol Dimethyl Ethers in Rabbits. B. A. Schwetz, C. J. Price, J. D. George, C. A. Kimmei, R. E. Morrissey, and M. C. Marr, Fundamental and Applied Toxicology 13,238-245,1992. Developmental Toxicity Evaluation of Ethylene Glycol by Gavage in New Zealand White Rabbits. R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. C. Seely, J. J. Heindel, and B. A. Schwetz, Fundamental and Applied Toxicology 2Q. 402-412,1993. Developmental Toxicity Evaluation of Diethyl and Dimethyl Phthalate in Rats. E. A. Field, C. J. Price, R. B. Sleet, J. D. George, M. C. Marr, C. B. Myers, B. A. Schwetz, and R. E. Morrissey, Teratology, 42, 33-44,1993. Reproductive Toxicity Study of Methylethyl Detoxime (MEKO) by Gavage in CD Rats. R. W. Tyl, J. M. Gerhart, C. B. Myers, M. C. Marr, D. R. Brine, A. F. Gilliam, J. C. Seely, and M. J. Derelanko, The Toxicologist, 12.1,1993. Two Generation Study of Dietary Tributyl Phosphate (TBP) in CD Rats. J. M. Gerhart, R. W. Tyl, C. B. Myers, M. C. Marr, D. R. Brine and J. C. Seely, The Toxicologist, 12,1,1993. Developmental Toxicity Evaluation of Isopropanol by Gavage in Rats and Rabbits. R. W. Tyl, L. W. Masten, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. E. Strother, R. H. McKee and T. R. Tyler, Fundamental and Applied Toxicology 22,139-151,1994. Assessment of the Reproductive and Developmental Toxicity of Pesticide/Fertilizer Mixtures Based on Confirmed Pesticide Contamination in California and Iowa Ground Water. J. J. Heindel, R. E. Chapin, D. K. Gulati, J. D. George, C. J. Price, M. C. Marr, C. B. Myers, L. H. Barnes, P. A. Fail, T. A. Grizzle, B. A. Schwetz and R. S. H. Yang, Fundamental and Applied Toxicology 22, 605-621,1994. Presentations and Published Abstracts A Longitudinal Study of the Arteriolar Microcirculation in the Spontaneously Hypertensive Rat by Latex Injection and In Vivo Microscopy. P. Hutchins, M. C. Marr, J. Dusseau, Federation Proceedings, 32, 451, 1977. Teratologic Evaluation of Diethylhexyl Phthalate (DEHP) in CD-I Mice. R. Wolkowski-Tyl, C. Jones-Price, M. C. Marr and C. A. Kimmei, Teratology 27, 85A, 1983. R&S147257 Melissa C. ManPage 4 Teratologic Evaluation of Diethylhexyl Phthalate (DEHP) in Fischer 344 Rats. R. Wolkowski-Tyi, C. Jones-Price, M. C. Marr and C. A. Kimmel, Teratology, 21, 85A, 1983. Teratologic Evaluation of L-5-Hydroxytryptophan (HTP) in CD Rats. R. Wolkowski-Tyl, C. Jones-Price, M. C. Marr and C. A. Kimmel, Teratology 21, 85A, 1983. Teratologic Evaluation of Diphenhydramine Hydrochloride (DPH) in CD-I Mice. C. Jones-Price, C. A. Kimmel, T. A. Ledoux, J. R. Reel, L. Langhoff-Paschke and M. C. Marr, Teratology 27. 53A, 1983. Developmental Toxicity of Carton Disulfide in Rabbits and Rats. C. J. Price, R. W. Tyl, M. C. Marr, J. D. George and C. A. Kimmel, The Toxicologist 4,1984. Teratologic Evaluation of Bendectin in CD Rats. C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, Teratology 22, 52A, 1984. Teratologic Evaluation of Ethylene Glycol in CD Rats and CD-I Mice. C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, Teratology 22, 52A, 1984. Developmental Toxicity Evaluation of Bisphenol A (BPA) in Rats and Mice. J. D. George, C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, The Toxicologists, 186,1985. Teratogenicity of Diethylene Glycol Dimethyl Ether (DYME) in Mice. C. J. Price, J. D. George, M. C. Marr and C. A. Kimmel, Teratology 31,57A, 1985. Teratogenicity of Triethylene Glycol Dimethyl Ether (TGDM) in Mice. J. D. George, C. J. Price, M. C. Marr and C. A. Kimmel, Teratology 31,53A, 1985. Teratologic Evaluation of Oxytetracycline-HCI (OXT) in CD-I Mice and CD Rats. R. E. Morrissey, R. W. Tyl, C. J. Price, T. A. Ledoux, J. R. Reel, L. L. Paschke, M. C. Marr and C. A. Kimmel, Society of Toxicology Annual Meeting, March, 1986, The Toxicologists, 91,1986. Teratologic Evaluation of Chlorpromazine (CPZ) in CD-I Mice and F344 Rats. C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, Society of Toxicology Annual Meeting, March, 1986, The Toxicologist 3, 91,1986. Developmental Toxicity of Hydrochlorothiazide (HCTZ) in Rats and Mice. J. D. George, C. J. Price, R. W. Tyl, M. C. Marr and C. A. Kimmel, Society of Toxicology Annual Meeting, March, 1986, The Toxicologists, 91,1986. Teratologic Evaluation of Phenol in Rats and Mice. C. J. Price, T. A. Ledoux, J. R. Reel, P. W. Fisher, L. L. Paschke, M. C. Marr and C. A. Kimmel, Teratology Society 26th Annual Meeting, Boston, MA, July 1986, Teratology 32, 92C, 1986. Teratogenicity of Theophylline (THEO) in Mice and Rats. J. D. George, C. J. Price, M. C. Marr and C. A. Kimmel, Teratology Society 26th Annual Meeting, Boston, MA, July, 1986, Teratology 33, 70C, 1986. R&S147258 Melissa C. ManPage 5 Developmental Toxicity of Gentian Violet (GV) in Rats and Rabbits. C. A. Kimmel, C. J. Price, R. W. Tyl and M. C. Mart, Teratology Society 26th Annual Meeting, Boston, MA, July, 1986, Teratology 33, 64C, 1986. Developmental Toxicity of 1,1,1-Trichloroethane (TCEN) in CD Rats. J. D. George, C. J. Price, M. C. Man, B. A. Schwetzand R. E. Morrissey, The Toxicologist 2,175,1987. Teratologic Evaluation of Nitrofurazone (NF) in CD-I Mice. C. J. Price, J. D. George, M. C. Mam and C. A. Kimmel, The Toxicologist Z, 179,1987. Postnatal Developmental and Reproductive Performance of Fischer 344 Rats Following Maternal Exposure to Diethylhexyl Phthalate (DEHP). C. J. Price, R. W. Tyl, M. C. Man, B. M. Sadler, C. A. Kimmel and R. E. Morrissey, The Toxicologist Z, 145,1987. Conceptus Development in Mice and Rats Exposed to Alpha-Methyldopa. R. B. Sleet, J. D. George, C. J. Price, M. C. Marr, C. A. Kimmel and B. A. Schwetz, The Toxicologist Z. 1, 1987. Developmental Phase Specific Effects of Methoxyacetic Acid (MAA) in Fischer-344 Rats. R. B. Sleet, C. B. Myers and M. C. Marr, The Toxicologists, 242,1988. Developmental Effects of Codeine in LVG Hamsters and CD-I Mice. C. A. Kimmel, C. J. Price, R. B. Sleet, J. D. George, M. C. Man, R. E. Morrissey and B. A. Schwetz, The Toxicologists, 240,1988. Developmental Toxicity Evaluation of Nitrofurazone (NF) in Rabbits. C. J. Price, J. D. George, M. C. Man, C. A. Kimmel, R. E. Morrissey and B. A. Schwetz, The Toxicologists, 1988. Developmental Toxicity of Ethylene Glycol Diethyl Ether (EGDE) in CD-I Mice and New Zealand White Rabbits. J. D. George, C. J. Price, M. C. Man, C. A. Kimmel, R. E. Morrissey and B. A. Schwetz, Teratology 3Z, 460,1988. Developmental Toxicity of Diethylene Glycol Diethylene Glycol Dimethyl Ether (diEGdiME) in New Zealand White Rabbits. C. J. Price, J. D. George, M. C. Man, R. E. Morrissey, B. A. Schwetz and C. A. Kimmel, Teratology 3Z, 483,1988. Embryo/fetal Development in CD-I Mice and New Zealand White Rabbits Exposed to Diethylene Glycol Diethyl Ether (DGDE). R. B. Sleet, J. D. George, C. J. Price, M. C. Marr, C. A. Kimmel, B. A. Schwetz and R. E. Monissey, Teratology 3Z, 494,1988. A Comparison of Developmental Toxicity in Fischer-344 (F-344) and CD Rats Exposed to Ethylene Glycol (EG). C. B. Myers, M. C. Man, R. B. Sleet, Teratology 3Z, No. 5, 479,1988. Comparison of Single and Double Staining for Evaluation of Skeletal Development; The Effects of Ethylene Glycol (EG) in CD Rats. M. C. Man, C. B. Myers, J. D. George, C. J. Price, Teratology 3Z, No. 5, 476, 1988. Developmental Toxicity of Scopolamine Hydrobromide (SCOP) in Rats and Mice. J. D. George, C. J. Price, M. C. Marr, C. A. Kimmel, R. E. Morrissey and B. A. Schwetz, The Toxicologist 3 (1), 241, 1988. R&S147259 Melissa C. ManPage 6 Teratologic Evaluation of Com Oil (CO) or Distilled Water (DW) in CD-I Mice and CD Rats. C. J. Price, J. D. George, B. M. Sadler, M. C. Marr, C. A. Kimmel, B. A. Schwetz, and R. E. Morrissey. The Toxicologists, 269,1989. Teratologic Evaluation of Acrylamide (ACRL) in CD-I Mice and CD Rats. E. A. Field, C. J. Price, R. B. Sleet, M. C. Marr, R. E. Morrissey, and B. A. Schwetz. The Toxicologists, 273,1989. Developmental Toxicity Evaluation of Diethyl Phthalate (DEP) in CD Rats. C. J. Price, R. B. Sleet, J. D. George, M. C. Marr, B. A. Schwetz, and R. E. Morrissey. Teratology 33, 473, 1989. Developmental Toxicity Evaluation of Dimethyl Phthalate (DMP) in CD Rats. E. A. Field, R. B. Sleet, C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey, and B. A. Schwetz. Teratology S3, 452,1989. Developmental Stages of the CD Rat Skeleton. M. C. Marr, C. B. Myers, C. J. Price, R. E. Morrissey, and B. A. Schwetz. Teratology 33, 468,1989. Developmental Toxicity of Boric Acid (BORA) in Mice and Rats. C. J. Price, E. A. Field, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. The Toxicologist 13, 39,1990. Postnatal Effects of In Utero Exposure to Ethylene Glycol (EG) in the CD Rat. H. K. Bates, C. J. Price, J. D. George, M. C. Marr, C. A. Kimmel, R. E. Morrissey and B. A. Schwetz. The Toxicologist IQ, 38,1990. Developmental Toxicity of Butyl Benzyl Phthalate (BBP) in Mice and Rats. C. J. Price, E. A. Field, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Teratology 41.586,1990. Developmental Toxicity of Triethylene Glycol Dimethyl Ether (TGDM) in New Zealand White Rabbits. J. D. George, C. J. Price, M. C. Marr, R. E. Morrissey and B. A. Schwetz. Teratology 41,560,1990. Developmental Stages of the CD Rat Skeleton after Maternal Exposure to Ethylene Glycol (EG). M. C. Marr, C. J. Price, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Teratology 41, 576, 1990. Developmental Toxicity of Diethylene Glycol (DEG) in CD-I Mice. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. The Toxicologist 11, 340,1991. Developmental Toxicity of Methacrylamide (MAC) in Mice, J. D. George. C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. The Toxicologist 11. 343,1991. Developmental Toxicity Evaluation of Ethylene Glycol (EG) by Gavage in New Zealand White (NZW) Rabbits. R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. The Toxicologist 11, 341,1991. Developmental Toxicity of N,N'-methylenebisacrylamide (BAC) in Mice. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Teratology 43, 457, 1991. R&S147260 ! Melissa C. Man Page 7 Developmental Toxicity Evaluation of DEHP Metabolites in Swiss Mice. C. J. Price, R. W. Tyl, M. C. Marr, C. B. Myers, R. E. Morrissey, J. J. Heindel and B. A. Schwetz. Teratology 43,457, 1991. Cardiovascular Development (CVD) in F-344 Rats Following Phase-Specific Exposure to 2-Butoxyethanol (BE). R. B. Sleet, C. J. Price, M. C. Marr, R. M. Morrissey and B. A. Schwetz. Teratology 43,466,1991. Developmental Toxicity of Boric Acid (BORA) in New Zealand White Rabbits. C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, The Toxicologist 12,103,1992. Developmental Toxicity Evaluation of Isopropanol (IPA) by Gavage in New Zealand White (NZW) Rabbits. L. W. Masten, R. W. Tyl, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. J. Marino, R. H. McKee, and T. R. Tyler, The Toxicologist 12m. 232,1992 (No. 864). Developmental Toxicity Evaluation of Isopropanol (IPA) by Gavage in CD (Sprague-Dawley) Rats. R. W. Tyl, L. W. Masten, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. J. Marino, R. H. McKee, and T. R. Tyler, The Toxicologist 12(1), 231,1992 (No. 860). Developmental Toxicity Evaluation of Naphthalene in Rats. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, Teratology, 45,475,1992. Phase Specificity (PS) and Dose Response Relationship (DR) for the Developmental Toxicity of 2-Methoxyethanol (2-ME) in Rats. M. C. Marr, C. B. Myers, F. Welsch, R. B. Sleet, Teratology 45,482,1992. Developmental Toxicity Evaluation in Rats of a Pesticide/Fertilizer Mixture Selected to Mimic i! Environmental Exposure. J. J. Heindel, C. J. Price, J. D. George, M. C. Marr, C. B. Myers, B. A. Schwetz and R. S. H. Yang, Teratology, 45,500,1992. Reproductive Toxicity Study of Methylethy! Detoxime (MEKO) by Gavage in CD Rats. R. W. Tyl, J. M. Gerhart, C. B. Myers, M. C. Marr, D. R. Brine, A. F. Gilliam, J. C. Seely, and M. J. Derelanko, The Toxicologist, 13,1,1993. Two Generation Study of Dietary Tributyl Phosphate (TBP) in CD Rats. J. M. Gerhart, R. W. Tyl, C. B. Myers, M. C. Marr, D. R. Brine and J. C. Seely, The Toxicologist, 13,1,1993. Developmental Toxicity Evaluation of 1,4-Butanediol (BUTE) in Swiss Mice. C. J. Price., M. C. Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz, Teratology, 4Z, 433,1993 Developmental Toxicity Evaluation of Ethylenediamine (EDA) in New Zealand White (NZW) Rabbits. C. J. Price, J. D. George, M. C. Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz, Teratology, 47, 432,1993. Comparison of Developmental Toxicity Databases for Vendor-Supplied Naturally Mated and Inhouse Artificially Inseminated New Zealand White Rabbits. M. C. Marr, C. B. Myers, and R. W. Tyl, Teratology 42, 416,1994. R&S 147261 Melissa C. Marr Page 8 Study Reports Study Reports for Developmental Toxicity Evaluations of Test Compounds Conducted Under Good Laboratory Practice Regulations (FDA, 1978) and supported by The National Toxicology Program. Reports available through the National Technical Information Service, Port Royal Road, Springfield, VA 22161. Teratologic Evaluation of Chlorpromazine Hydrochloride (CAS No. 69-09-0) Administered to Fischer 344 Rats on Gestational Days 6 Through 15. C. Jones-Price, C. A. Kimmel, R. Wolkowski-Tyl and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No., PB83-191080, March 7,1981. Teratologic Evaluation of Gentian Violet (CAS No. 548-62-9) in CD Rats. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, J. R. Reel, T. A. Ledoux, M. C. Marr and L. Langhoff-Paschke. Final Study Report, NCTR Contract No. 222-80-2031(6), National Technical Information Service (NTIS) Accession No. PB83-155754, May 31,1982. Teratologic Evaluation of Diphenhydramine Hydrochloride (CAS No. 147-24-0) Administered to CD-I Mice on Gestational Days 11 Through 14. C. Jones-Price, C. A. Kimmel, T. A. Ledoux, J. R. Reel, L. Langhoff-Paschke and M. C. Marr, Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB83-148684, July 23,1982. Teratologic Evaluation of Oxytetracycline Hydrochloride (CAS No. 2058-46-0) in CD Rats. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, T. A. Ledoux, J. R. Reel, L. Langhoff-Paschke and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB83-182469, March 1,1983. Teratologic Evaluation of Chlorpromazine Hydrochloride (CAS No. 69-09-0) Administered to CD-I Mice on Gestational Days 6 Through 15. C. Jones-Price, C. A. Kimmel, R. Wolkowski-Tyl and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB83-179846, March 7, 1983. Teratologic Evaluation of Gentian Violet (CAS No. 548-62-9) in New Zealand White Rabbits. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price, J. R. Reel, M. C. Marr and L. Langhoff-Paschke. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB83-182519, March 15,1983. Toxicologic Evaluation of Isoproterenol Hydrochloride (CAS No. 51-30-9) Administered Subcutaneously to CD Rats. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. C. Marr. Final Study Report NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB83-211466, April 1,1983. Teratologic Evaluation of Ethylene Oxide (CAS No. 75-21-8) in New Zealand White Rabbits. C. Jones-Price, C. A. Kimmel, T. A. Marks, T. A. Ledoux, J. R. Reel, P. W. Fisher, L. Langhoff-Paschke and M. C. Marr. Final Study Report, NIEHS Contract No. N01-ES-6-2127, National Technical Information Service (NTIS) Accession No. PB83-242016, April 18, 1983. R&S147262 Melissa C. ManPage 9 Teratologic Evaluation of L-5-Hydroxytryptophan (CAS No. 59-69-9) in CD Rats. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. C. Marr, Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB83-231332, June 17,1983. Teratologic Evaluation of L-5-Hydroxytryptophan (CAS No. 56-69-9) in CD-I Mice. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB83-231670, June 17,1983. Teratologic Evaluation of Diethylhexyl Phthalate (CAS No. 117-81-7) in Fischer 344 Rats. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB85-105658, July 20, 1983. Teratologic Evaluation of Diethylhexyl Phthalate (CAS No. 117-81-7) in CD-I Mice. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB85-105674, July 20,1983. Teratologic Evaluation of Phenol (CAS No. 108-95-2) in CD Rats. C. Jones-Price, C. A. Kimmel, T. A. Ledoux, J. R. Reel, P. W. Fisher, L. Langhoff-Paschke and M. C. Marr. Final Study Report, NIEHS Contract No. N01-ES-6-2127, National Technical Information Service (NTIS) Accession No. PB83-247726, July 29,1983. Teratologic Evaluation of Phenol (CAS No. 108-95-2) in CD-I Mice. C. Jones-Price, C. A. Kimmel, T. A. Ledoux, J. R. Reel, L. Langhoff-Paschke, and M. C. Marr. Final Study Report, NIEHS Contract No. N01-ES-6-2127, National Technical Information Service (NTIS) Accession No. PB85-104461, July 29,1983. Teratologic Evaluation of Ethylene Chlorohydrin (CAS No. 107-07-3) in New Zealand White Rabbits. C. Jones-Price, C. A. Kimmel, T. A. Marks, T. A. Ledoux, J. R. Reel, P. W. Fisher, L. Langhoff-Paschke and M. C. Mam Final Study Report, Contract No. NIEHS N01-ES-6-2127, National Technical Information Service (NTIS) Accession No. PB85-170959/AS, August 31,1983. Teratologic Evaluation of Ethylene Chlorohydrin (CAS No. 107-07-3) in CD-I Mice. C. Jones-Price, C. A. Kimmel, T. A. Marks, T. A. Ledoux, J. R. Reel, P. W. Fisher, L. Langhoff-Paschke and M. C. Mam Final Study Report, NIEHS Contract No. N01-ES-6-2127, National Technical Information Service (NTIS) Accession No. PB85-172104/AS, August 31,1983. Teratologic Evaluation of Carbon Disulfide (CAS No. 75-15-0) Administered to New Zealand White Rabbits on Gestational Days 6 Through 19. C. Jones-Price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB84-192350, February 24, 1984. R&S147263 Melissa C. ManPage 10 Teratologic Evaluation of Carbon Disulfide (CAS No. 75-15-0) Administered to CD Rats on Gestational Days 6 Through 15. C. Jones-Price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C) National Technical Information Service (NTIS) Accession No. PB84-192343, February, 1984. Teratologic Evaluation Carbon Disulfide (CAS No. 75-15-0) Administered to New Zealand White Rabbits on Gestational Days 6 through 19. C. Jones-Price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB84-192350, February 24,1984. Teratologic Evaluation of Bendectin (CAS No. 8064-77-5) in CD Rats. R. Wolkowski-Tyl, C. A. Kimmel, C. Jones-Price and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB84-193879, February 28,1984. Teratologic Evaluation of Sulfamethazine (CAS No. 57-68-1) in New Zealand White Rabbits. R. Wolkowski-Tyl, C. Jones-Price, M. C. Marr and C. A. Kimmel. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB85-172047/AS, May 7, 1984. Teratologic Evaluation of Hydrochlorothiazide (CAS No. 58-93-5) Administered to CD-I Mice on Gestational Days 6 Through 15. J. D. George, R. Wolkowski-Tyl, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB85-103570, May 9,1984. Teratologic Evaluation of Hydrochlorothiazide (CAS No. 58-93-5) Administered to CD Rats on Gestational Days 6 Through 15. J. D. George, R. Wolkowski-Tyl, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB85-103588, May 25,1984. Teratologic Evaluation of Ethylene Glycol (CAS No. 107-21-1) in CD Rats. C. J. Price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031(C), National Technical Information Service (NTIS) Accession No. PB85-104594/GAR, May 31,1984. Teratologic Evaluation of Ethylene Glycol (CAS No. 107-21-1) in CD-I Mice. C. J. Price, R. Wolkowski-Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR Contract No. 222-80-2031(C), National Technical Information Service (NTIS) Accession No. PB85-105385/GAR, May 31, 1984. Teratologic Evaluation of Bisphenol A (CAS No. 80-05-7) Administered to CD Rats on Gestational Days 6 through 15. J. D. George, C. J. Price, R. W. Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR/NTP Contract No. 222-80-2031 (C), National Technical Information Service (NTIS) Accession No. PB85-205110/AS, February 15,1985. Teratologic Evaluation of Bisphenol A (CAS NO. 80-05-7) Administered to CD-I Mice on Gestational Days 6 through 15. J. D. George, C. J. Price, R. W. Tyl, C. A. Kimmel and M. C. Marr. Final Study Report, NCTR/NTP Contract No. 222-80-2031(6), National Technical Information Service (NTIS) Accession No. PB85-205102/AS, February 15, 1985. R&S147264 Melissa C. ManPage 11 Teratologic Evaluation of Theophylline (CAS No. 58-55-9) Administered to CD-I Mice on Gestational Days 6 through 15. J. D. George, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, National Technical Information Service (NTIS) Accession No. PB86-103223, May 15,1985. Teratologic Evaluation of Theophylline (CAS No. 58-55-9) Administered to CD Rats on Gestational Days 6 through 15. J. D. George, C. J. Price, M. C. Marr and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NO1-ES-55086, National Technical Information Service (NTIS) Accession No. PB86-108172, May 15,1985. Teratologic Evaluation of Diethylene Glycol Dimethyl Ether (CAS No. 111-96-6) Administered to CD-I Mice on Gestational Days 6 Through 15. C. J. Price, J. D. George and M. C. Marr. Final Study Report, NTP/NIEHS Contract No. NOI -ES-55080, National Technical Information Service (NTIS) Accession No. PB86-135233/AS, August 30,1985. Teratologic Evaluation of Triethylene Glycol Dimethyl Ether (CAS No. 112-49-2) Administered to CD-I Mice on Gestational Days 6 through 15. J. D. George, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB86-103215, August, 1985. Teratologic Evaluation of Nitrofurazone (CAS No. 59-87-0) Administered to CD-I Mice on Gestational Days 6 through 15. C. J. Price, J. D. George, M. C. Marr and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB86-145844/AS, October 31,1985. Teratologic Evaluation of a-Methyldopa (CAS No. 555-30-6) Administered to CD Rats on Gestational Days 6 through 20. J. D. George, C. J. Price, M. C. Marr and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB86-245321/AS, April 1,1986. Teratologic Evaluation of Triethylene Glycol Dimethyl Ether (CAS No. 112-49-2) Administered to New Zealand White Rabbits on Gestational Days 6 through 19. J. D. George, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) No. PB87-181657/AS, January 9,1987. Teratologic Evaluation of a-Methyldopa (CAS No. 555-30-6) Administered to CD-I Mice on Gestational Days 6 through 17. J. D. George, C. J. Price, C. A. Kimmel and M. C. Marr. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) No. PB87-172607/AS, January 9, 1987. Teratologic Evaluation of Scopolamine Hydrobromide (CAS No. 114-49-8) Administered to CD Rats on Gestational Days 6 through 15. J. D. George, C. J. Price, M. C. Marr R. E. Morrissey, B. A. Schwetz and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB87-235412/AS, April 6, 1987. R&S147265 Melissa C. Marr Page 12 Teratologic Evaluation of Scopolamine Hydrobromide (CAS No. 114-49-8) Administered to CD-I Mice on Gestational Days 6 through 15. J. D. George, C. J. Price, M. C. Marr, R. E. Morrissey, B. A. Schwetz and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI -ES-55080, National Technical Information Service (NTIS) Accession No. PB87-209516/AS, April 6,1987. Developmental Toxicity Evaluation of 1,1,1 -Trichloroethane (CAS No. 71-55-6) Administered to CD Rats (Parts I and II). J. D. George, C. J. Price, M. C. Marr, R. E. Morrissey and B. A. Schwetz. Final Study Reports, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-131321/AS and PB88-134101, August 28, 1987 (Part I) and September 23,1987 (Part II). Teratologic Evaluation of Njtrofurazone (CAS No. 59-87-0) Administered to New Zealand White Rabbits on Gestational Days 6 through 19. C. J. Price, J. D. George, M. C. Marr and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-130984/AS, August 18,1987. Teratologic Evaluation of Codeine (CAS No. 76-57-3) Administered to CD-I Mice on Gestational Days 6 through 15. C. J. Price, J. D. George, M. C. Marr, R. E. Morrissey, B. A. Schwetz and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB87-209524/AS, April 7,1987. Teratologic Evaluation of Codeine (CAS No. 76-57-3) Administered to LVG Hamsters on Gestational Days 5 through 13. R. B. Sleet, C. J. Price, J. D. George, C. A. Kimmel and M. C. Marr. Final,Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-131040/AS, September 15,1987. Teratologic Evaluation of Ethylene Glycol Diethyl Ether (CAS No. 629-14-1) Administered to New Zealand White Rabbits on Gestational Days 6 through 19. J. D. George, C. J. Price, M. C. Marr, R. E. Morrissey, B. A. Schwetz and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-168257/AS, October 16,1987. Teratologic Evaluation of Ethylene Glycol Diethyl Ether (CAS No. 629-14-1) Administered to CD-I Mice on Gestational Days 6 through 15. J. D. George, C. J. Price, M. C. Marr, R. E. Morrissey, B. A. Schwetz and C. A. Kimmel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-134093, August 25, 1987. Teratologic Evaluation of Diethylene Glycol Diethyl Ether (CAS No. 112-36-7) Administered to CD-I Mice on Gestational Days 6 through 15. R. B. Sleet, J. D. George, C. J. Price, M. C. Marr, C. A. Kimmel, B. A. Schwetz and R. E. Morrissey. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-168257/AS, November 6, 1987. Teratologic Evaluation of Diethylene Glycol Diethyl Ether (CAS No. 112-36-7) Administered to New Zealand White Rabbits on Gestational Days 6 through 19. R. B. Sleet, J. D. George, C. J. Price, M. C. Marr, C. A. Kimmel, B. A. Schwetz and R. E. Morrissey. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-168497/AS, December 7,1987. R&S147266 Melissa C. Marr Page 13 Developmental Toxicity Evaluation of Ethylene Glycol (CAS No. 107-21-1) in CD Rats. C. J. Price, J. D. George, M. C. Marr, C. A. Kimmel, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, National Technical Information Service (NTIS) Accession No. PB88-204326/AS, March 2,1988. Teratologic Evaluation of Com Oil or Distilled Water Administered by Gavage to CD-I Mice on Gestational Days 6 through 15. J. D. George, C. J. Price, M. C. Marr, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, National Technical Information Service (NTIS) Accession No. PB89-122246/AS, September?, 1988. Teratologic Evaluation of Acrylamide (CAS NO. 79-06-1) Administered to CD-I Mice on Gestational Days 6 through 17. C. J. Price, R. B. Sleet, E. A. Field, M. C. Marr, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB89-140008/AS, October 7, 1988. Teratologic Evaluation of Acrylamide (CAS NO. 79-06-1) Administered to Sprague-Dawley (CD) Rats on Gestational Days 6 through 20. R. B. Sleet, E. A. Field. C. J. Price, M. C. Marr, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, National Technical Information Service (NTIS) Accession No. PB89-164669/AS, November 28, 1988. Developmental Toxicity Evaluation of Dimethyl Phthalate (CAS NO. 131-11-3) Administered to CD Rats on Gestational Days 6 through 15. E. A. Field, R. B. Sleet, C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, National Technical Information Service (NTIS) Accession No. PB89-164826/AS, January 9,1989. Teratologic Evaluation of Com Oil or Distilled Water Administered to CD Rats on Gestational Days 6 through 15. C. J. Price, J. D. George, M. C. Marr, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, National Technical Information Service (NTIS) Accession No. PB89-165401/AS, January 25,1989. Teratologic Evaluation of Ethylene Glycol Monobutyl Ether (CAS No. 111-76-2) Administered to Fischer-344 Rats on Either Gestational Days 9 through 11 or Days 11 through 13. R. B. Sieet, C. J. Price, M. C. Marr, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, National Technical Information Service (NTIS) Accession No. PB89-165549/AS January 25,1989. Developmental Stages of the CD Rat Skeleton: Part I: Normal Development. M. C. Marr, C. J. Price, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-55080, February 10,1989. Developmental Toxicity Evaluation of Butyl Benzyl Phthalate (CAS No. 85-68-7) Administered in Feed to CD Rats on Gestational Days 6 to 15. E. A. Field, C. J. Price, M. C. Marr, C. B, Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Service (NTIS) Accession No. PB90-115346/AS, August 4, 1989. K /2 6 7 Melissa C. ManPage 14 Developmental Toxicity Evaluation of Boric Acid (CAS No. 10043-35-3) Administered in Feed to CD-I Mice on Gestational Days 0 to 17. E. A. Field, C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI -ES-95255, National Technical Information Service (NTIS) Accession No. PB91 -132332, August 11,1989. Developmental Stages of the CD Rat Skeleton: Part II: Development after Maternal Exposure to Ethylene Glycol (EG). M. C. Marr, C. J. Price, C. B. Myers, R. E. Morrissey, B. A. Schwetz and J. J. Heindel. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255. Developmental Toxicity Evaluation of Boric Acid (CAS No. 10043-35-3) Administered in Feed to CD Rats on Gestational Days 0 to 20 or 6 to 15. C. J. Price, E. A. Field, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Service (NTIS) Accession No. PB91137588/AS, December 20,1989. Developmental Toxicity Evaluation of Diethylene Glycol (CAS No. 111-46-6) Administered to Swiss (CD-I) Mice on Gestational Days 6 through 15. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Service (NTIS) Accession No. PB91 -159327, Decembers, 1990. Developmental Toxicity Evaluation of Mono(2-ethylhexyl) Phthalate (CAS No. 4376-20-9) Administered in Feed to Swiss (CD-I) Mice on Gestational Days 0 to 17. C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey, J. J. Heindel, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-95255, National Technical Information Service (NTIS) Accession No. PB91 -185926, December 17,1990. Developmental Toxicity Evaluation of Microencapsulated 2-Ethylhexanol (CAS No. 104-76-7) Administered to Swiss (CD-I) Mice in the Feed on Gestational Days 0 to 17. R. W. Tyl, C. J. Price, M. M. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB91185900, March 11,1991. Developmental Toxicity Evaluation of Ethylene Glycol (CAS No. 107-21-1) Administered to New Zealand White Rabbits by Gavage on Gestational Days 6 through 19. R W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB91211219, March 15,1991. Developmental Toxicity Evaluation of Methacrylamide (CAS No. 79-39-0) Administered by Gavage to CD-I Mice on Gestational Days 6 through 17. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB91208678, April 10, 1991. R & S 147268 Melissa C. ManPage 15 Developmental Toxicity Evaluation of Boric Acid (CAS No. 10043-35-3) Administered to New Zealand White Rabbits by Gavage on Gestational Days 6 through 19. C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB921295Q/AS, October 30,1991. Developmental Toxicity Evaluation of Naphthalene (CAS No. 91-20-3) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 through 15. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB92135623, Decembers, 1991. Developmental Toxicity Evaluation of California Pesticide/Fertilizer Mixture Administered in the Drinking Water to Sprague-Dawley (CD) Rats on Gestational Days 6 to 20. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB92170406, February 24,1992. Developmental Toxicity Evaluation of d-Camphor (CAS No. 464-49-3) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 Through 15. H. A. Navarro, C. J. Price, M. C. Marr, and C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB92170406, March 5,1992. Developmental Toxicity Evaluation of N.N'-Methylenebisacrylamide (CAS No. 110-26-9) Administered by Gavage to Swiss (CD-I) Mice on Gestational Days 6 Through 17. J. D. George, C. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB92177781, March 26,1992. Developmental Toxicity Evaluation of Dipropylene Glycol (CAS No. 25265-71-8) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 Through Gestation Day 15. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-ES95255, National Technical Information Services (NTIS) Accession No. PB92196179, May 26, 1992. Developmental Toxicity Evaluation of 8-Methoxypsoralen (CAS No. 298-81-7) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 Through 15. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-ES95255, National Technical Information Services (NTIS) Accession No. PB92219666, June 22, 1992. Developmental Toxicity Evaluation of Naphthalene (CAS No. 91-20-3) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 Through 19. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-ES95255, National Technical Information Services (NTIS) Accession No. PB92219831, July 13, 1992. R&S147269 M?I: Melissa C. ManPage 16 Developmental Toxicity Evaluation of Iowa Pesticide/Fertilizer Mixture Administered in the Drinking Water to Sprague-Dawley (CD) Rats on Gestational Day 6 to 20. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, B. A. Schwetz. Final Study Report NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-109296, August 24,1992. Developmental Toxicity Evaluation of Dipropylene Glycol (CAS No. 25265-71-8) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestation Day 6 through Gestation Day 19. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS, Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB92-238294, August 28,1992. Developmental Toxicity Evaluation of d -Camphor (CAS No. 464-49-3) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 through 15. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS, Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-123784, October 9,1992. Developmental Toxicity Evaluation of Polyoxyethylene Sorbitan Monolaurate (CAS No. 9005-645) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 through 15. C. J. Price, J. D. George, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS, Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-123800, October 14,1992. Developmental Toxicity Evaluation of Polyoxyethylene Sorbitan Monooleate (CAS No. 9005-656) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 through 15. C. J. Price, J. C. George, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS, Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-123826, October 14,1992. Developmental Toxicity Evaluation of Ethylenediamine (CAS No. 107-15-3) Administered by Gavage to New Zealand White Rabbits on Gestational Days 6 through 19. C. J. Price, J. D. George, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter and B. A. Schwetz. Final Study Report, NTP/NIEHS, Contract No' N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-190056, March 12,1993. Developmental Toxicity Evaluation of Methacrylonitrile (CAS No. 126-98-7) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 through Gestation Day 15 by Gavage. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, B. A. Schwetz. Final Study Report, NTP/NIEHS, Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-190072, April 7,1993. Developmental Toxicity Evaluation of Methacrylonitrile (CAS No. 126-98-7) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestational Day 6 through 19. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter and B. A. Schwetz. Final Study Report, NTP/NIEHS, Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-196061, April 22,1993. R&S147270 ! Melissa C. Mart Page 17 Developmental Toxicity Evaluation of Methylene Blue Trihydrate (CAS No. 7220-79-3) Administered by Gavage to Sprague-Dawley (CD) Rats from Gestational Days 6 through 15. H. A. Navarro, C. J. Price, M. C. Man, 6. B. Myers, J. J. Heindel, E. S. Hunter, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB93-219574, June 14,1993. Developmental Toxicity Evaluation of Glyoxal Trimeric Dihydrate (CAS No. 4405-13-4) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestational Days 6 through 19. J. D. George, C. J. Price, M. C. Man, C. B. Myers, J. J. Heindel, E. S. Hunter, B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, NTIS Accession No. PB94-104064, Final Report; National Technical Information Services (NTIS) Accession No. PB94-104072, Laboratory Supplement, August 18,1993. Developmental Toxicity Evaluation of Sodium Fluoride (CAS NO. 7681-49-4) Administered to New Zealand White (NZW) Rabbits from Gestational Day 6 through Gestational Day 19 in Drinking Water. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, M. D. Shelby and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES95255, National Technical Information Sen/ices (NTIS) Accession No. PB94-142684, Final Report; National Technical Information Services (NTIS) Accession No. PB94-142809, Laboratory Supplement, December 15,1993. Developmental Toxicity Evaluation of a-Cyclodextrin (CAS NO. 10016-20-3) Administered in the Feed to Sprague-Dawley (CD) Rats on Gestational Days 6 to 16. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, M. D. Shelby and B. A. Schwetz. Final Study Report NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB94-13995, Final Report; National Technical Information Services (NTIS) Accession No. PB94-141926, Laboratory Supplement, January 10,1994. Developmental Toxicity Evaluation of Glyoxal Trimeric Dihydrate (CAS NO. 4405-13-4) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 through Gestation Day 15 by Gavage. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, M. B. Shelby and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES95255, National Technical Information Services (NTIS) Accession No. PB94-151974, Final Report; National Technical Information Services (NTIS) Accession No. PB94-152113, Laboratory Supplement, February 3,1994. Developmental Toxicity Evaluation of Thiophenol (CAS No. 108-98-5) Administered to SpragueDawley (CD) Rats from Gestation Day 6 through Gestation Day 15 by Gavage. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, M. D. Shelby, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB94-155009; National Technical Information Services (NTIS) Accession No. PB94-154853, Laboratory Supplement, February 28, 1994. Developmental Toxicity Evaluation of ot-Cyclodextrin (CAS NO. 10016-20-3) Administered in the Feed to Swiss (CD-I) Mice on Gestational Days 6 to 16. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, M. B. Shelby, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, May 9,1994. G* V X IV 'J Melissa C. Man Page 18 Developmental Toxicity Evaluation of 8-Methoxypsoralen (CAS NO. 298-81-7) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestational Days 6 through 19. C. J. Price, H. A. Navarro, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, M. D. Shelby and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, May 9, 1994. Developmental Toxicity Evaluation of Thiophenol (CAS No. 108-98-5) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 through 19, H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), July 29, 1994. Developmental Toxicity Evaluation of Methylene Blue Trihydrate (CAS No. 7220-79-3) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 through 19, H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J, Heindel, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), August 8,1994. Developmental Toxicity Evaluation of Methylene Blue Trihydrate (CAS No. 7220-79-3) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 through 19, H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), August 8,1994. Developmental Toxicity Evaluation of Sodium Fluoride (CAS No. 7681-49-4) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 through Gestation Day 15 in Drinking Water, H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), Septembers, 1994. Developmental Toxicity Evaluation of Diethylstilbestrol (CAS No. 56-53-1) Administered Subcutaneously to Swiss (CD-I) Mice on Gestational Days 9 through 16, H. A. Navarro, J. D. George, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), Octobers, 1994. March, 1995 R&S147272 CHRISTINA B. MYERS, Research Biologist II Professional Experience Center for Life Sciences and Toxicology, Chemistry and Life Sciences Unit, Research Triangle Institute, Post Office Box 12194, Research Triangle Park, North Carolina 27709. August 1987 to present. Data Specialist, Teratology Laboratory. Responsible for overseeing ail data entry, statistical analysis of data for reports, SAS programming, EasyEntry Program ming, dBase programming, 20/20 programming, report preparation and review. Proficiency in teratology laboratory SOPs for mice, rats and rabbits, and clinical chemistry; involved in the development of SOPs, protocols, and preparation of study reports. Appointed Supervisor of Reproductive Toxicology Studies for commercial clients, March, 1990. August 1984 to July 1987. Supervisor of Fertility Assessment by Continuous Breeding. Responsibilities included scheduling studies, dose preparation of test chemicals, microcomputer operation for the collection and analysis of data and necropsy procedures. January 1984 to July 1984. Biologist I. Fertility Assessment by Continuous Breeding. Responsibilities included dosing of animals, vaginal smear analysis, sperm analysis and collection of litter data. January 1983 to December 1983. Biologist I. Conducted metabolic studies in rats using radiolabeled xenobiotics with analysis of the biological fluids by HPLC and oxidation of the animal tissue for radioactivity determinations, jo vitro xenobiotic metabolism, isolation of metabolites from biological fluids using reverse and normal phase HPLC. October 1982 to December 1982. Biologist. Performed enzyme purification from various mouse tissues and Drosophila using affinity chromatography and isoelectric focusing. June 1981jQ_September 1982. Biologist. Development of radioimmunoassays of cannabinoids. November 1980 to May 1981. Biologist. Use of alkaline elution assay for determination of DNA damage, closing efficiency assays of mammalian tissue culture cells, isolation of rat alveolar macrophages and their use in cytotoxicity screening, general tissue culture techniques and Ames assay for mutagenicity. Education B.A., Biology, West Virginia University, Morgantown, WV, 1978. M.S., Biochemistry, West Virginia University, Morgantown, WV, 1980. Computer Programming Courses SAS Program for New Computer Users SAS Basics SAS Processing R&S147273 Christina B. Myers Page 2 SAS Introduction to Statistic SAS Regression and ANOVA SAS Making the Transition to Release 6.06 of the SAS System SAS Macro Language SAS Report Writing Introduction to 20/20 for VAX/VMS Professional Societies North Carolina Chapter of the Society of Toxicology Teratology Society, Regular Member Abstracts and Publications Characterization and Subcellular Location of Soluble Proteins which Stimulated DNA Replication and Repair in Lysolecithin Permeabilized Animal Cells. Christina B. Myers, Pragna I. Patel and Michael R. Miller, Fed. Proc. 22 (Abstract), 1959,1980. In Vitro Applied Toxicology: A Reproducible, Dose-Dependent Semi-Micro Method for Quantifying Cytotoxicity to Cultured Rat Alveolar Macrophages. Christina B. Myers, Robert S. DeWoskin and Alan R. Kolber, Presented at the First Annual Meeting of the North Carolina Chapter of the Society of Toxicology, 1981. Subcellular Location of a Soluble Factor that Stimulates DNA Replication in Permeable Animal Cells. Christina B. Myers, Pragna I. Patel and Michael R. Miller, Exp. Cell Res. 145. 227.1983. Identification of Mammalian DNA Repair Factors Using a Reconstituted Subcellular System. 1 Partial Characterization and Subcellular Location of a DNA Repair Stimulating Protein in Hamster Cells. Pragna I. Patel, Christina B. Myers and Michael R. Miller, Exp. Cell Res. 149. 347.1983. Comparative Genetoxicity of Sidestream and Mainstream Cigarette Smoke. L. G. Monteith, D. M. Simmons, C. B. Myers, T. J. Hughes and L D. Claxton, Environmental Mutagenesis 2 Supp. 8, 75, 1987. Developmental Phase Specificity Effects of Methoxyacetic Acid (MAA) in Fischer 344 Rats. R. B. Sleet, C. B. Myers, and M. C. Marr, The Toxicologist 2, 242,1988. Comparison of Single and Double Staining for Evaluation of Skeletal Development: The Effects of Ethylene Glycol (EG) in CD Rats. M. C. Marr, C. B. Myers, J. D. George and C. J. Price, Teratology 37(5). 476,1988. A Comparison of Developmental Toxicity in Fischer-344 (F-344) and CD Rats Exposed to Ethylene Glycol (EG). C. B. Myers, M. C. Marr, R. B. Sleet, Teratology 2Z, No. 5, 479 (1988). Developmental Toxicity Evaluation of Dimethyl Phthalate (DMP) in CD Rats. E. A. Field, R. B. Sleet, C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey, and B. A. Schwetz, Teratology 32, 452, 1989. Christina B. Myers . Page 3 Developmental Stages of the CD Rat Skeleton. M. C. Man, C. B. Myers, C. J. Price, R. E. Morrissey, and B. A. Schwetz, Teratology S3,468,1989. Developmental Toxicity of Boric Add (BORA) in Mice and Rats. C. J. Price, E. A. Reid, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz, The Toxicologist 10.39,1990. Developmental Toxidty of Butyl Benzyl Phthalate (BBP) in Mice and Rats. C. J. Price, E. A. Field, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Teratology 41,586, 1990. Reproductive Toxidty of Trichloroethylene (TCE) in Mouse and Rat Breeding Pairs. J. D. George, J. R. Reel, C. B. Myers, J. C. Lamb, IV, and J. J. Heindel, The Toxicologist 10,209, 1990. Developmental Stages of the CD Rat Skeleton after Maternal Exposure to Ethylene Glycol (EG). M. C. Marr, C. J. Price, C. B. Myers, R. E. Morrissey and B. A. Schwetz, Teratology 41, 576,1990. Developmental Toxicity of Diethylene Glycol (DEG) in CD-I Mice. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, The Toxicologist 11, 340,1991. Developmental Toxicity of Methacrylamide (MAC) in Mice. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, The Toxicologist H, 343,1991. Developmental Toxicity Evaluation of Ethylene Glycol (EG) by Gavage in New Zealand White (NZW) Rabbits. R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, The Toxicologist H, 341,1991. Developmental Toxicity of N.N'-methylenebisacrylamide (BAG) in Mice. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, Teratology 43.457,1991. Developmental Toxicity Evaluation of DEHP Metabolites in Swiss Mice. C. J. Price, R. W. Tyl, M. C. Marr, C. B. Myers, R. E. Morrissey, J. J. Heindel and B. A. Schwetz, Teratology 43, 457,1991. Developmental Toxicity of Boric Acid (BORA) in New Zealand White Rabbits. C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, The Toxicologist 12,103,1992. Developmental Toxicity Evaluation of Isopropanol (IPA) by Gavage in New Zealand White (NZW) Rabbits. L. W. Masten, R. W. Tyl, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. J. Marino, R. H. McKee, and T. R. Tyler, The Toxicologist 12(1). 232, 1992 (No. 864). Developmental Toxicity Evaluation of Isopropanol (IPA) by Gavage in CD (Sprague-Dawley) Rats. R. W. Tyl, L. W. Masten, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. J. Marino, R. H. McKee, and T. R. Tyler, The Toxicologist 12(11. 231,1992 (No. 860). Developmental Toxicity Evaluation of Naphthalene in Rats. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz, Teratology, 45, 475,1992. R&S147275 Christina B. Myers Page 4 Phase Specificity (PS) and Dose Response Relationship (DR) for the Developmental Toxicity of 2-Methoxyethanoi (2-ME) In Rats. M. C. Marr, C. B. Myers, F. Welsch, R. B. Sleet, Teratology 45,482,1992. Developmental Toxicity Evaluation in Rats of a Pesticide/Fertilizer Mixture Selected to Mimic Environmental Exposure. J. J. Heindel, C. J. Price, J. D. George, M. C. Marr, C. B. Myers, B. A. Schwetz and R. S. H. Yang, Teratology, 45,500,1992. Developmental Stages of the CD (Sprague-Dawley) Rat Skeleton after Maternal Exposure to Ethylene Glycol. M. C. Marr, C. J. Price, C. B. Myers, and R. E. Morrissey, Teratology, 46(21.169-181,1992. Developmental Toxicity Evaluation of Ethylene Glycol by Gavage in New Zealand White Rabbits. R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. C. Seely, J. J. Heindel, and B. A. Schwetz, Fundamental and Applied Toxicology 20,402-412,1993. Reproductive Toxicity Study of Methyiethyl Detoxime (MEKO) by Gavage in CD Rats. R. W. Tyl, J. M. Gerhart, C. B. Myers, M. C. Marr, D. R. Brine, A. F. Gilliam, J. C. Seely, and M. J. Derelanko, The Toxicologist, ik 1,1993. Two Generation Study of Dietary Tributyl Phosphate (TBP) in CD Rats. J. M. Gerhart, R. W. Tyi, C. B. Myers, M. C. Marr, D. R. Brine and J. C. Seely, The Toxicologist, 13,1,1993. Developmental Toxicity Evaluation of Ethylene Glycol by Gavage in New Zealand White Rabbits. R. W. Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. C. Seely, J. J. Heindel, and B. A. Schwetz, Fundamental and Applied Toxicology 2Q. 402-412,1993. 4 Developmental Toxicity Evaluation of Diethyl and Dimethyl Phthalate in Rats. E. A. Field, C. J. Price, R. B. Sleet, J. D. George, M. C. Marr, C. B. Myers, B. A. Schwetz, and R. E. Morrissey, Teratology, 4B, 33-44,1993. Developmental Toxicity Evaluation of Isopropanol by Gavage in Rats and Rabbits. R. W. Tyl, L. W. Masten, M. C. Marr, C. B. Myers, R. W. Slauter, T. H. Gardiner, D. E. Strother, R. H. McKee and T. R. Tyler, Fundamental and Applied Toxicology 22,139-151,1994. Assessment of the Reproductive and Developmental Toxicity of Pesticide/Fertilizer Mixtures Based on Confirmed Pesticide Contamination in California and Iowa Ground Water. J. J. Heindel, R. E. Chapin, D. K. Gulati, J. D. George, C. J. Price, M. C. Marr, C. B. Myers, L H. Barnes, P. A. Fail, T. A. Grizzle, B. A. Schwetz and R. S. H. Yang, Fundamental and Applied Toxicology 22, 605-621,1994. Developmental Toxicity Evaluation of 1,4-Butanediol (BUTE) in Swiss Mice. C. J. Price, M. C^Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz, Teratology, 4Z, 433, 1993 Developmental Toxicity Evaluation of Ethylenediamine (EDA) in New Zealand White (NZW) Rabbits. C. J. Price, J. D. George, M. C. Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz, Teratology, 4Z, 432,1993. Comparison of Developmental Toxicity Databases for Vendor-Supplied Naturally Mated and In-house Artificially Inseminated New Zealand White Rabbits. M. C. Marr, C. B. Myers, and R. W. Tyl, Teratology 49, 416,1994. R&S 147276 Christina B. Myers * Page 5 Study Rep rts Study Reports for Fertility Assessment by Continuous Breeding and Developmental Toxicity Evaluations of Test Compounds conducted under Good Laboratory Practice Regulations (FDA, 1978) and supported by the National Toxicology Program. Reports available through the National Technical Information Service, Port Royal Road, Springfield, VA 22161. Bisphenol A: Reproduction and Fertility Assessment in CD-I Mice When Administered in the Feed. J. R. Reel, J. D. George, C. B. Myers, A. D. Lawton and J. C. Lamb IV. Final Study Report, NTP/NIEHS Contract No. NO1-ES-2-5014, National Technical Information Service (NTIS) Accession No. PB86103207, May 31,1985. Tricresyl Phosphate: Reproduction and Fertility Assessment in CD-I Mice When Adminis tered in the Feed. J. D. George, J. R. Reel, C. B. Myers, A. D. Lawton and J. C. Lamb IV. Final Study Report NTP/NIEHS Contract No. NO1-ES-2-5014, National Technical Information Service (NTIS) Accession No. PB86167277/AS, October 16,1985. Ethanol: Reproduction and Fertility Assessment in CD-I Mice When Administered in the Drinking Water. J. D. George, J. R. Reel, C. B. Myers, A. D. Lawton and J. C. Lamb IV. Final Study Report, NTP/NIEHS Contract No. NO1-ES-2-5014, National Technical Information Service (NTIS) Accession No. PB86144979/AS, November 4,1985. Trichloroethylene: Reproduction and Fertility Assessment in CD-I Mice When Administered in the Feed. J. D. George, J. R. Reel, C. B. Myers, A. D. Lawton and J. C. Lamb IV. Final Study Report, NTP/NIEHS Contract No. NO1-ES-2-5014, National Technical Information Service (NTIS) Accession No. PB86173150/AS, January 13,1986. Triethylene Glycol Diacetate: Reproduction and Fertility Assessment in CD-I Mice When Administered in the Drinking Water. J. D. George, J. R. Reel, C. B. Myers, A. D. Lawton and J. C. Lamb IV. Final Study Report, NTP/NIEHS Contract No. NO1-ES-2-5014, National Technical Information Service (NTIS) Accession No. PB86161999/AS, January 13,1986. Methoxyacetic Acid: Reproduction and Fertility Assessment in CD-I Mice When Administered in the Drinking Water. J. D. George, J. R. Reel, C. B. Myers, A. D. Lawton and J. C. Lamb IV. Final Study Report, NTP/NIEHS Contract No. NO1-ES-2-5014, National Technical Information Service (NTIS) Accession No. PB86164274/AS, January 17,1986. Trichloroethylene: Reproduction and Fertility Assessment in F-344 Rats When Administered in the Feed. J. D. George, J. R. Reel, C. B. Myers, A. D. Lawton and J. C. Lamb IV. Final Study Report, NTP/NIEHS Contract No. NO1-ES-2-5014, National Technical Information Service (NTIS) Accession No. PB86190782/AS, January 13,1986. Final Contract Report: Fertility Assessment by Continuous Breeding. J. D. George, C. B. Myers and J. C. Lamb IV, NTP/NIEHS Contract No. NO1-ES-2-5014, September 8, 1986. R&S147277 Christina B. Myers Page 6 Reproduction and Fertility Evaluation of Diethylhexyl Phthalate (CAS No. 117-81-7) in CD-i Mice Exposed During Gestation. C. J. Price, R. W. Tyl, M. C. Marr, C. B. Myers, B. M. Sadler and C. A. Kimmel. Final Study Report, NCTR/NTP Contract No. 222-80-2031 (c), National Technical Information Servidte (NTIS) Accession No. PB88-20430Q/ AS, April 15,1988. Developmental Toxicity Evaluation of Dimethyl Phthalate (CAS No. 131-11-3) Administered to CD Rats on Gestational Days 6 through 15. E. A. Reid, R. B. Sleet, C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, National Technical Information Service (NTIS) Accession No. PB89-164826/AS, January, 9,1989. Developmental Stages of the CD Rat Skeleton: Part I: Normal Development. M. C. Marr, C. J. Price, C. B. Myers, R. E. Morrissey, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-55080, February 10,1989. Developmental Toxicity Evaluation of Butyl Benzyl Phthalate (CAS No. 85-68-7) Administered in Feed to CD Rats on Gestational Days 6 to 15. E. A. Field, C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Service (NTIS) Accession No. PB90-115346AS, August 4,1989. Developmental Toxicity Evaluation of Boric Acid (CAS No. 10043-35-2) Administered in Feed to CD-I Mice on Gestational Days 0 to 17. E. A. Field, C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, August 11,1989. Developmental Toxicity Evaluation of Boric Acid (CAS No. 10043-35-3) Administered in Feed to CD Rats on Gestational Days 0 to 20 or 6 to 15. C. J. Price, E. A. Reid, M. C. Marr, C. B. Myers, R. E. Morrissey and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract N01-ES-95255, December 20,1989. Developmental Stages of the CD Rat Skeleton: Part II: Development After Maternal Exposure to Ethylene Glycol (EG). M. C. Marr, C. J. Price, C. B. Myers, R. E. Morrissey, B. A. Schwetz, and J. J. Heindel. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, January 5,1990. Developmental Toxicity Evaluation of Diethylene Glycol (CAS No. 111-46-6) Administered to Swiss (CD-I) Mice on Gestational Days 6 through 15. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, December 5,1990. Developmental Toxicity Evaluation of Mono(2-ethylhexyl) Phthalate (CAS No. 4376-20-9) Administered in Feed to Swiss (CD-I) Mice on Gestational Days 0 to 17. C. J. Price, M. C. Marr, C. B. Myers, R. E. Morrissey, J. J. Heindel, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-95255, December 17,1990. Developmental Toxicity Evaluation of Microencapsulated 2-Ethylhexanol (CAS No. 104-76-7) Administered to Swiss (CD-I) Mice in the Feed on Gestational Days 0 to 17. R. W. Tyl, C. J. Price, M. M. Marr, C. B, Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Services (NTIS) Accession No. PB91185900, March 11, 1991. R&S147278 Christina B. Myers Page 7 Developmental Toxicity Evaluation of Ethylene Glycol (CAS No. 107-21-1) Administered to New Zealand White Rabbits by Gavage on Gestational Days 6 through 19. R. W, Tyl, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Services (NTIS) Accession No. PB91211219, March 15,1991. Developmental Toxicity Evaluation of Methacrylamide (CAS No. 79-39-0) Administered by Gavage to CD-I Mice on Gestational Days 6 through 17. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, NTIS Accession No. PB91208678, April 10,1991. Developmental Toxicity Evaluation of Boric Acid (CAS No. 10043-35-3) Administered to New Zealand White Rabbits by Gavage on Gestational Days 6 through 19. C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-95255, NTIS Accession No. PB9212950/AS, October 30,1991., Developmental Toxicity Evaluation of Napthaiene (CAS No. 91-20-3) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 through 15. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-95255, National Technical Information Service (NTIS) Accession No. PB92135623, December 12,1991. Developmental Toxicity Evaluation of California Pesticide/Fertilizer Mixture Administered in the Drinking Water to Sprague-Dawley (CD) Rats on Gestational Days 6 to 20. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-95255, National Technical Information Service (NTIS) Accession No. PB92170406, February 24,1992. Developmental Toxicity Evaluation of d-Camphor (CAS No. 464-49-3) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 Through 15. H. A. Navarro, C. J. Price, M. C. Marr, and C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI95255, National Technical Information Service (NTIS) Accession No. PB92170406, March 5, 1992. Developmental Toxicity Evaluation of N.N'-Methylenebisacrylamide (CAS No. 110-26-9) Administered by Gavage to Swiss (CD-I) Mice on Gestational Days 6 Through 17. J. D. George, C. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-95255, National Technical Information Service (NTIS) Accession No. PB92177781, March 26, 1992. Developmental Toxicity Evaluation of Dipropylene Glycol (CAS No. 25265-71-8) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 Through Gestation Day 15. H. K. Bates, 6. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-95255, National Technical Information Service (NTIS) Accession No. PB92196179, May 26,1992. R & S 147279 Christina B. Myers Page 8 Developmental Toxicity Evaluation of 8-Methoxypsoralen (CAS No. 298-81-7) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 Through 15. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-95255, National Technical Information Service (NTIS) Accession No. PB92219666, June 22,1992. Developmental Toxicity Evaluation of Naphthalene (CAS No. 91-20-3) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 Through 19. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers. Final Study Report, NTP/NIEHS Contract No. NOI-95255, National Technical Information Service (NTIS) Accession No. PB92219831, July 13, 1992. Developmental Toxicity Evaluation of Iowa Pesticide/Fertilizer Mixture Administered in the Drinking Water to Sprague-Dawley (CD) Rats on Gestational Day 6 to 20. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, B. A. Schwetz. Final Study Report NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-109296, August 24,1992. Developmental Toxicity Evaluation of Dipropylene Glycol (CAS No. 25265-71-8) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestation Day 6 through Gestation Day 19. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Service (NTIS) Accession No. PB92-238294, August 28,1992. Developmental Toxicity Evaluation of d -Camphor (CAS No. 464-49-3) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 through 15. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-123784. Developmental Toxicity Evaluation of Polyoxyethylene Sorbitan Monolaurate (CAS No. 900564- 5) Administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 through 15. C. J. Price, J. D. George, M. C. Man, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-123800, October 14,1992. Developmental Toxicity Evaluation of Polyoxyethylene Sorbitan Monooleate (CAS No. 900565- 6) administered by Gavage to Sprague-Dawley (CD) Rats on Gestational Days 6 through 15. C. J. Price, J. C. George, M. C. Man, C. B. Myers, J. J. Heindel and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-123826, October 14,1992. Developmental Toxicity Evaluation of Ethylenediamine (CAS No. 107-15-3) Administered by Gavage to New Zealand White Rabbits on Gestational Days 6 through 19. C. J. Price, J. D. George, M. C. Man, C. B. Myers, J. J. Heindel, E. S. Hunter and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-190056, March 12, 1993. R&S147280 Christina B. Myers Page 9 Developmental Toxicity Evaluation of Methacryionitrile (CAS No. 126-98-7) Administered to Sprague-Dawtey (CD) Rats from Gestation Day 6 through Gestation Day 15 by Gavage. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindei, E. S. Hunter, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-190072, April 7,1993. Developmental Toxicity Evaluation of Methacryionitrile (CAS No. 126-98-7) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestational Day 6 through 19. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-196061, April 22,1993. Developmental Toxicity Evaluation of Methylene Blue Trihydrate (CAS No. 7220-79-3) Administered by Gavage to Sprague-Dawley (CD) Rats from Gestational Days 6 through 15. H. A. Navarro, C. J. Price, M. C. Marr, 6. B. Myers, J. J. Heindei, E. S. Hunter, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Service (NTIS) Accession No. PB93-219574, June 14,1993. Developmental Toxicity Evaluation of Glyoxal Trimeric Dihydrate (CAS No. 4405-13-4) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestational Days 6 through 19. J. D. George. C. J, Price, M. C. Marr, C. B. Myers, J. J. Heindei, E. S. Hunter, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, National Technical Information Service (NTIS) Accession No. PB94-104064, Final Report; National Technical Information Service (NTIS) Accession No. PB94-104072, Laboratory Supplement, August 18,1993. Developmental Toxicity Evaluation of Sodium Fluoride (CAS NO. 7681-49-4) Administered to New Zealand White (NZW) Rabbits from Gestational Day 6 through Gestational Day 19 in Drinking Water. H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindei, E. S. Hunter, M. D. Shelby and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. NOI-ES95255, December 15,1993. Developmental Toxicity Evaluation of a-Cyclodextrin (CAS NO. 10016-20-3) Administered in the Feed to Sprague-Dawley (CD) Rats on Gestational Days 6 to 16. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, M. D. Shelby and B. A. Schwetz. Final Study Report NTP/NIEHS Contract No. N01-ES-95255, January 10,1994. Developmental Toxicity Evaluation of Glyoxal Trimeric Dihydrate (CAS NO. 4405-13-4) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 through Gestation Day 15 by Gavage. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindei, E. S. Hunter, M. B. Shelby and B. A. Schwetz. Final Study Report NTP/NIEHS Contract No. NOIES-95255, February 3,1994. Developmental Toxicity Evaluation of Thiophenol (CAS No. 108-98-5) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 through Gestation Day 15 by Gavage. J. D. George, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, M. D. Shelby, and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, February 28, 1994. RS.SU7281 Christina B. Myers Page 10 Developmental Toxicity Evaluation of a-Cyciodextrin (CAS NO. 10016-20-3) Administered in the Feed to Swiss (CD-I) Mice on Gestational Days 6 to 16. H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, E, S. Hunter, M. B. Shelby, and B. A. Schwetz. Pinal Study Report, NTP/NIEHS Contract No. N01-ES-95265, May 9,1994. Developmental Toxicity Evaluation of 8-Methoxypsoralen (CAS NO. 298-81-7) Administered by Gavage to New Zealand White (NZW) Rabbits from Gestational Days 6 through 19. C. J. Price, H. A. Navarro, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, M. D. Shelby and B. A. Schwetz. Final Study Report, NTP/NIEHS Contract No. N01-ES-95255, May 9,1994. Developmental Toxicity Evaluation of Thiophenol (CAS No. 108-98-5) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 through 19, H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), July 29,1994. Developmental Toxicity Evaluation of Methylene Blue Trihydrate (CAS No. 7220-79-3) Administered by Gavage to New Zealand White (NZW) Rabbits on Gestational Days 6 through 19, H. A. Navarro, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), August 8,1994. Developmental Toxicity Evaluation of Sodium Fluoride (CAS No. 7681-49-4) Administered to Sprague-Dawley (CD) Rats from Gestation Day 6 through Gestation Day 15 in Drinking Water, H. K. Bates, C. J. Price, M. C. Marr, C. B. Myers, J. J. Heindel, E. S. Hunter, III, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), Septembers, 1994. Developmental Toxicity Evaluation of Diethylstilbestrol (CAS No. 56-53-1) Administered Subcutaneously to Swiss (CD-I) Mice on Gestational Days 9 through 16, H. A. Navarro, J. D. George, C. J. Price, M. C. Marr, C. B. Myers, E. S. Hunter, ill, M. D. Shelby, and B. A. Schwetz. NTP/NIEHS Contract N01-ES-95255, NTIS Nos. (to be assigned), October 5, 1994. March, 1995 TSAI-YING YU CHANG, Research Histotechnologist 1 PROFESSIONAL EXPERIENCE May 1992 to date. Research Histotechnologist 1, Center for Life Sciences and Toxicology, Chemistry and Life Sciences, Research Triangle Institute, Post Office Box 12194, Research Triangle Park, NC 27709. Perform all facets of work in histology laboratory, including gross trimming, embedding, cutting, staining, inventory, quality control, operating and maintenance of equipment, developing new Standard Operating Procedures (SOPs) as needed and updating existing SOPs, and performing special techniques of dissecting nervous tissue for paraffin and plastic sections. Participate in necropsies, wet tissue audits on special projects, and assist other laboratories as needed. Train and supervise laboratory personnel, communicate with project leaders and subcontractors, and provide cost estimates for proposals. November 1990 to April 1992. Histotechnologist 2 August 1986 to October 1990. Pathologist Assistant, Roche Biomedical Laboratory, Inc., 1447 York Court, Burlington, NC 27215. Performed gross description and trimming of surgical specimens and summarized patient clinical histories. August 198Q to July 1986. Histology Supervisor, Tegeris Research Laboratories, Inc., 9705 N. Washington Boulevard, Laurel, MD 20854. Trained and supervised histology and necropsy technicians. Performed gross trimming, processing, embedding, cutting, and staining of tissues. August 1973 to April 1980. Histology Technician, Gillette Medical Evaluation Laboratory, 1413 Research Boulevard, Rockville, MD 20850. Supervised and trained histology technicians. Performed gross trimming, processing, embedding, cutting, and staining of tissues. April 1972 to July 1973. Histology Technician, Columbia Hospital for Women, 24th Street, N.W., Washington, DC 20037. Performed routine histology laboratory studies.(tissues, sputum, CSF). April 1969 to August 1971. Laboratory Technician, Smithsonian Institute, 12441 Parklawn Drive, Rockville, MD 20852. Performed culture of plant materials, scoring of chromosomal aberrations, and statistical analysis of data. EDUCATION BS, Entomo-Phyto Pathology, Chung-Hsin University, Taichung, Taiwan, 1954 Certified Histotechnologist (HT-ASCP, #HT008134), Washington, DC, 1976. PROFESSIONAL SOCIETIES American Society of Clinical Pathology for Medical Technology National Society for Histotechnologists R&S147283 Tsai-Ying Yu Chang Page 2 THESIS Studies on Two Strains of Brown Strip Disease Pathogens (Helminthosporum stenospilus) of Sugarcane (BS Thesis, 1970) PUBLICATIONS Ma, T.-H., A. J. Snope, and T.-Y. Chang (1970). Far-red light effect of ultraviolet light induced chromatid aberrations in pollen tubes of Tradescantia. Radiation Botany 11: 39-43. Chang, T.-Y., and R. Blakeney (1984). Precision positioning of small tissues with agar. Laboratory Medicine. Chang, T.-Y., and J.L. Murdock (1985). A modified oil Red 0 technique. The Maryland Micron, Official Newsletter of the Maryland Society of Histotechnologists, July 5-6. March 1995 STEPHANIE M. TAULBEE, Manager, Quality Assurance Unit Professional Experience 1988 to date. Research Triangle Institute, Research Triangle Park, NC 1991 to date: Manager, Quality Assurance Unit, Research Triangle Institute, Research Triangle Park, NC 27709. Managed the Quality Assurance Unit which is responsible for assuring the compliance of ongoing nonclinical studies with 25 study directors and task leaders for the FDA, EPA and International Good Laboratory Practice (GLP) Regulations. Hosted site visitors and QA auditors from commercial and governmental sponsors. Provided training in the GLPs for study directors, laboratory personnel, and members of the QA Unit Conducted off-site audits for private contractors and inspected laboratory subcontractors. Consulted with contractors concerning implementation of GLPs. Assisted in the development of governmental guidelines, finalization ofEPA's Good Automated Laboaratory Practices. Performed quality and consistency audits on Toxicological Profiles prepared by RH staff. 1988 to 1991: Quality Assurance Specialist, Quality Assurance Unit, Research Triangle Institute, Research Triangle Park, NC 27709. Responsible for reviewing protocols, scheduling inspections of critical phases, and auditing reports and study records for the Developmental and Neurobehavioral Toxicology Laboratories to assure compliance with the FDA and EPA Good Laboratory Practice Regulations. Hosted governmental and commercial clients during site visits and their respective auditors during data and report audits. Responsible for receiving of data and specimens into the archives and maintaining the archive data base. Developed and conducts three part training seminar for study directors and laboratory staff in GLPs. 1985 to 1988: Histology Technician, Pathology Associates, Inc., Research Triangle Park, NC 27709. Conducted Quality Assurance audits for over 100 studies on NTP Retrospective Audit contract in conjunction with Argus Research Laboratories including slide/block evaluation, wet tissue review, and data auditing. Performed histological procedures including necropsy, tissue processing, embedding, cutting, staining, etc. Quality Assurance inspections and report auditing for Electron Microscopy Laboratory at Pathology Associates, Inc. 1985 to 1986. Lab Aide, Cytology Department, Wake County Medical Center, Raleigh, NC. Received, logged and numbered cytology specimens. 1979. Pathology Assistant, Carteret General Hospital, Morehead City, NC. Assisted Pathologist and Histotechnician in procedures including tissue examination and sectioning, tissue processing and embedding, staining and other special procedures. 1976 to 1978. Parapathology Supervisor, Toxic Hazards Research Unit, Dayton, OH. Duties included necropsy, description of lesions, anesthesia, euthanasia, tissue processing and embedding, stain techniques, and many special procedures relating to oncogenic studies on Rhesus monkeys, dogs, rabbits, rats, mice, hamsters, and guinea pigs. Supervised 7 lab assistants, development of new quality control procedures, writing of Standard Operating Procedure Manual, and training new technicians. 1975. Veterinary Assistant, Old Troy Pike Veterinary Clinic, Dayton, OH. Animal handling and care, assisted in clinical and operating room procedures, lab work including stool exam, urine tests, and blood tests, anesthesia, X-ray, administration of medication including injections and IV. R&S147285 Stephanie M. Taulbee Page 2 1974 to 1975. Media Preparation Technician, Hill Top Research, Inc., Miamiville, OH. Preparation of microbiological media and reagents, stock and inventory, assisted in testing procedures in food and product testing lab, supervised part-time assistants. 1973 to 1974. Hematology Technician, Eastern Hill/Central Laboratories, Cincinnati, OH. C.B.C or autohemolyzer, sedimentation rates, prothrombin times, pregnancy tests, type and RH factors, and urinalysis. Education M.S.P.H., Environmental Science and Engineering, University of North Carolina at Chapel Hill, expected completion 1995. B.S. Health Occupations Education(Summa Cum Laude), North Carolina State University, Raleigh, NC, 1991. Attended University of Cincinnati, Cincinnati, OH, Biology, 1972. Attended Marshall University, Huntington, WV, Zoology, 1968-1971. Special Training Quality Assurance Basic Training Seminar, Society of Quality Assurance Annual Meeting, 1988. University of California, Irvine, Wright Patterson Air Force Base, Dayton, OH. Six month training program including three months of classroom training in comparative anatomy, pathology, and laboratory procedures and three months ofpractical training. Carteret Technical College, Morehead City, NC. Two classes in basic computer programming. Professional Affiliations The Honor Society of Phi Kappa Phi American Society of Clinical Pathologists Society of Quality Assurance North Carolina Quality Assurance Discussion Group, Chairperson of committee , 1991-1993. Training Sub Professional Certification HT, American Society of Clinical Pathologists Seminars Presented Archive Verification, Basic Training Seminar, Society of Quality Assurance Annual Meeting, Kansas City, MO, 1991. Walk Through the GLPs, Research Triangle Institute. Walk through the GLPs, North Carolina Quality Assurance Discussion Group, April 1993 R & S 147286 Stephanie M. Taulbee Page 3 The Importance of Scientific Accuracy: Issues of Ethics and Integrity, February 1994, Served as Chairman of Seminar Committee and presented the Concluding Remarks. Publications The Good Laboratory Practices in Parallel (compiled by S, M. Taulbee), Research Triangle Institute, 1991. International GLPs, R.S. DeWoskin and S.M. Taulbee, Interpharm Press, 1993 Taulbee's Pocket Companion: US FDA and EPA GLPs in Parallel, edited by S.M. Taulbee and R.S. DeWoskin, Interpharm Press, 1993 Taulbee's International Pocket Companion, International GLPs in Parallel, edited by S.M. Taulbee and R.S. DeWoskin, Interpharm Press, 1994 Implementation of Current Good Manufacturing Practices in a Small Research Laboratory Setting: Celia D. Keller and Stephanie M. Taulbee. Quality Assurance: Good Practice Regulation and Law 4(1). Abstract and Poster Presentations FDA-EPA: So, What's the Difference? S. M Taulbee, Society of Quality Assurance Annual Meeting, Kansas City, MO, October 1991. published in Quality Assurance: Good Practices, Regulations and Law, 1993. Getting Started with Regulatory Compliance: How the QA Professional Can Help: S.M. Taulbee, G.D. Digsby, D.L. Brodish, C.D. Keller, and P.D Hall. Poster presented at the Society of Quality Assurance Annual Meeting, San Francisco, CA. October 1993. Implementation of Current Good Manufacturing Practices in a Small Research Laboratory Setting: Celia D. Keller and Stephanie M. Taulbee. Poster presented at the Society of Quality Assurance Annual Meeting, New Orleans, LA, October 1994. September 1995 r &S147288 Appendix 3 SOP Listings from RTI including Quality Assurance R & S 147289 R&S147290 STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Contents Teratology SOPs Page 1 of 12 i SOE Number TERA-001 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS Subisgl Calibration of Analytical Balances and Verification of Routine Calibration Effective Date Review or Revision Date 1/28/87 11/29/95 TERA-003 Dose Formulation 1. Dose Formulation Preparation 2. Weighing of Compound 3. Preparation of a Solution 4. Preparation of a Suspension 5. Preparation of Dosed Feed 6. Preparation of Dosed Drinking Water 1/29/87 1/14/94 TERA-004 Formulation of Common Fixatives and Staining Solutions 1/29/87 1/7/94 TERA-005 Chemical Handling and Analysis RETIRED AS OF 11/27/95 1. Receipt of Chemical, Record Keeping and Initial Processing 2. Purity and Identify of Bulk Chemical 3. Dosage Formulation and Analysis 4. Chemical-Vehicle Referee Analysis Program 5. Bulk Chemical Reanalysis 1/28/87 10/26/93 TERA-006 Peroxide Analysis RETIRED AS OF 11/27/95 1/28/87 10/26/93 TERA-007 Weighing Granular or Pelletized Food for Determining Food Consumption 1/28/87 for Rodents 1/7/94 TERA-008 Weighing Water for Determining Water Consumption 1/28/87 11/29/95 TERA-009 Blood Collection from Fetal or Neonatal Rodents 1/28/87 11/30/95 TERA-010 Blood Collection from Adult Rodents 1/28/87 1/20/94 TERA-011 Plasma Collection 1/28/87 10/26/93 TERA-012 Serum Collection 1/28/87 10/26/93 TERA-013 Necropsy Procedures for Unscheduled Deaths 1/28/87 10/26/93 TERA-014 Necropsy of Neonatal, Postweaning and Adult Rodents - Defined Ages 1/28/87 11/30/95 TERA-015 Necropsy - General Comments TERA-016 Necropsy of Neonatal Rodents TERA-017 Necropsy of Postweaning and Adult Rodents 1/28/87 1/28/87 6/15/89 11/30/95 10/26/93 9/21/95 38a1, I IS?/ Rev. 12/1/95 STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Cont nts Teratology SOPs Page 2 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) SQE Number Subject TERA-018 Weighing and Storage of Organs TERA-019 Collection of Urine and/or Uroliths from Rodents at Necropsy TERA-020 Identification of Animals TERA-021 Calibration and Use of Vapor Pressure Osmometer TERA-022 Blood Collection and Processing for Serodiagnostic Test Panel TERA-023 Preparing Specimens and Data to be Sent to the Research Triangle Institute Archives and the National Toxicology Program (NTP) Archives TERA-024 Staining Implantation Sites in Formalin-Fixed Uteri with Potassium Ferricyanide TERA-025 Skeletal Staining with the Sakura EBS-400B Teratology Processor TERA-026 Determination of Estrous Cyclicity and Cycle Length in Rodents TERA-027 External Determination of Fetal or Neonatal Sex in Rodents TERA-028 Collection of Amniotic Fluid TERA-029 Identification of Neonatal Rodents TERA-030 Evaluation of Postnatal Rodent Heads TERA-031 External Exam of Neonatal Rodents TERA-032 Necropsy of the Rodent Dominant Lethal Females TERA-033 Transferring Animals Into and Out of Inhalation Exposure Chambers TERA-034 Administration of Test Chemical by Cutaneous Application TERA-035 Descriptions of Findings During Teratological Evaluations (Glossary) TERA-036 Obtaining Random Numbers for Use in Reproductive Toxicity Studies TERA-037 Transfer of Live Study Rodents from Another Facility to RTI TERA-038 Measuring Anogenital Distance in Perinatal Rodents Review or Effective Revision Date Date 12/20/88 11/30/95 1/28/87 11/30/95 1/27/88 1/7/94 2/16/88 RETIRED 12/20/88 1/7/94 10/12/89 4/8/94 5/14/90 11/1/93 5/24/90 11/5/93 3/8/91 11/5/93 4/15/91 11/10/93 4/2/92 11/8/93 3/10/93 11/8/93 4/13/93 11/8/93 10/15/93 1/24/94 1/24/94 2/8/94 10/24/94 10/25/94 10/13/95 8/28/95 III \ tIIII II 02) C/) rrCooO Rev. 12/1/95 STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Cont nts Teratology SOPs Page 3 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) SOE Number Subject Effective Date Review or Revision Date TERA-039 Unscheduled Deaths When the In-Life Portions of a Study are Conducted at Another Facility 10/16/95 TERA-040 Calibration of Liquid in Glass Laboratory Thermometers 11/16/95 Rev. 12/1/95 t I II XI in <-hnDo| CO STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Tabl f Contents Teratology SOPs Page 4 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) SPECIES-SPECIFIC STANDARD OPERATING PROCEDURES RAT: TERA-100 SERIES SOP Number TERA-100 Subject Teratological Evaluation in Rats TERA-101 TERA-102 Weighing Rats 1. Weighing Mature Rats 2. Weighing Neonatal Rats Breeding Rats TERA-103 Examination of Vaginal Cytology in Rats TERA-104 Vaginal Smears: Detection of Sperm - Positive Females TERA-105 Assignment of Female Rats to Dose Groups Using Stratified Randomization Procedures TERA-106 Compound Administration 1. General Remarks 2. Intravenous Injection (iv) 3. Intraperitoneal Injection (ip) 4. Subcutaneous Injection (sc) 5. Gavage(po) 6. Administration of Test Chemical by Drinking Water 7. Administration of Test Chemical by Feed 8. Clinical Signs TERA-109 Teratological Evaluation 1. Station I 2. Station II 3. Station III 4. Station IV TERA-110 Determining Fetal Crown-Rump Length TERA-111 Detailed Examination of Diaphragm and Removal of Diaphragm and Heart from Rodent Fetuses TERA-112 Examination and Storage of Fetal Rat Heads TERA-113 Staining the Rat Skeleton with Alizarin Red S TERA-114 Examination of Alizarin Red S Stained Skeletons Review or Effective Revision Date Date 1/29/87 1/30/87 7/26/93 1/29/87 1/30/87 1/29/87 1/29/87 8/1/95 8/1/95 8/1/95 9/18/95 1/30/87 2/28/95 i 1/30/87 8/1/95 t 1/29/87 1/29/87 8/2/95 8/1/95 1/30/87 1/29/87 1/30/87 8/1/95 10/22/95 10/22/93 C 4 cr 4- Rev, 12/1/95 STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of C ntents Teratology SOPs Page 5 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) RAT: TERA-100 SERIES SOP Number Subject TERA-115 Staining the Rat Skeleton with Alcian Blue/Alizarin Red S TERA-116 Examination of Alcian Blue/Alizarin Red S Stained Rat Skeletons TERA-117 Preparation of Rat Skeletons for Storage TERA-118 Milk Collection from Lactating Rats TERA-119 Pup Fluid Deprivation RETIRED 10/21/93 TERA-120 Culling Postnatal Litters TERA-121 Orbital Bleeding of Rodents TERA-122 Selection of Fetuses for External, Visceral, Craniofacial and Skeletal Examinations During a Definitive Developmental Toxicity Study TERA-123 Documentation of Postnatal Day 0, of Culling of Litters, of Pup Body Weights, and of Pup Selections for Multigeneration Studies TERA-124 Administering Dosing Formulations by Gavage or Parenteral Routes to Females During Delivery of their Litters Effective Date Review or Revision Date 1/30/87 11/20/95 1/30/87 12/1/95 1/29/87 11/20/95 2/16/88 11/20/95 2/16/88 i 3/16/89 11/20/95 7/19/89 11/20/95 10/17/89 10/22/93 6/5/90 11/20/95 9/19/90 11/20/95 ii Rev. 12/1/95 3G3 C/3 5rcoo CJi STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Cont nts Teratology SOPs Page 6 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) MOUSE: TERA-200 SERIES SQE Number Subject TERA-200 Teratological Evaluation in Mice TERA-201 Weighing Mice 1. Weighing Mature Mice 2. Weighing Neonatal Mice TERA-202 Breeding Mice TERA-203 Copulation Plugs in Mice TERA-204 Assignment of Female Mice to Dose Groups Using Stratified Randomization Procedures TERA-205 Compound Administration to Mice 1. General Remarks 2. Intravenous Injection (iv) 3. Intraperitoneal Injection (ip) 4. Subcutaneous Injection (sc) 5. Gavage(po) 6. Administration of Test Chemical in Drinking Water 7. Administration of Test Chemical by Feed 8. Clinical Signs TERA-209 Teratological Evaluation 1. Station 1 2. Station II 3. Station III 4. Station IV TERA-210 Examination and Storage of Fetal Mouse Heads TERA-211 Staining the Mouse Skeleton with Alizarin Red S TERA-212 Examination of Alizarin Red S Stained Skeletons TERA-213 Staining the Mouse Skeleton with Alcian Blue/Alizarin Red S TERA-214 Examination of Alcian Blue/Alizarin Red S Stained Mouse Skeletons TERA-215 Preparation of the Mouse Skeleton for Storage TERA-216 Selection of Fetuses for External, Visceral, Craniofacial and Skeletal Examinations During a Definitive Developmental Toxicity Study Review or Effective. Revision Date Date 1/28/87 7/13/95 1/28/87 9/6/96 1/29/87 1/28/87 1/28/87 9/6/96 9/6/96 9/6/96 1/28/87 9/6/96 1/30/87 10/3/95 1/30/87 9/6/96 1/28/87 7/18/90 1/30/87 7/18/90 1/28/87 10/3/95 2/2/87 7/13/93 1/28/87 7/13/93 10/17/89 9/6/96 Rev. 12/1/95 STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Tabl of Contents T ratology SOPs Page 7 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) RABBIT: TERA-300 SERIES SOP Number Subject TERA-300 Teratological Evaluation in Rabbits TERA-301 Weighing Rabbits 1. Weighing Mature Rabbits 2. Weighing Neonatal Rabbits TERA-302 Artificial Insemination of the Rabbit TERA-303 Assignment of Female Rabbits to Dose Groups Using Stratified Randomization Procedures TERA-304 Compound Administration in Rabbits 1. General Remarks 2. Intravenous Injection (iv) 3. Subcutaneous Injection (sc) 4. Gavage(po) 5. Clinical Signs TERA-305 Necropsy of Rabbits TERA-307 Teratological Evaluation of Rabbit Conceptus 1. Station 1 2. Station II 3. Station III 4. Station IV TERA-308 Examination and Storage of Fetal Rabbit Heads TERA-309 Staining the Rabbit Skeleton with Alizarin Red S TERA-310 Examination of Alizarin Red S Stained Rabbit Fetal Skeletons TERA-311 Staining the Rabbit Skeleton with Alcian Blue/Alizarin Red S TERA-312 Examination of Alcian Blue/Alizarin Red S Stained Rabbit Skeletons TERA-313 Preparation of Rabbit Skeletons for Storage TERA-314 Arterial Blood Collection from the Central Artery of the Rabbit Ear TERA-315 Selection of Fetuses for External, Visceral, Craniofacial and Skeletal Examinations During a Definitive Developmental Toxicity Study Rev. 12/1/95 Review or Effective Revision Date Date 1/29/87 _ 1/29/87 5/19/95 1/28/88 1/29/87 5/19/95 5/22/95 1/29/87 5/19/95 7/20/89 1/30/87 5/19/95 7/31/95 1/30/87 1/29/87 1/30/87 1/29/87 1/30/87 1/29/87 9/6/89 7/31/95 7/31/95 7/31/95 7/31/95 7/31/95 7/31/95 7/31/95 RETIRED 3/93 zi CO ro 'h! STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Cont nts Teratology SOPs Page 8 f 12 SQE Number Subject STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) RABBIT: TERA-300 SERIES Review or Effective Revision Date Date TERA-316 Weighing Pelletized Feed for Determining Food Consumption for Rabbits 9/26/90 7/31/95 TERA-317 Determining Fetal Crown Rump Length in Rabbits 7/14/92 3/8/95 TERA-318 Collection of Blood from the Rabbit for Coagulation Assays 11/10/92 7/31/95 TERA-319 Ordering, Receipt, Housing, Quarantine and Initial Feeding for VendorMated Rabbits 11/19/93 8/14/94 TERA-320 Administration of a Test Article by Application to the Dorsal Skin of Rabbits 2/8/94 TERA-321 Collection of Urine in Female Rabbits 1/19/95 TERA-322 Identification of Rabbits by Microchip 3/13/95 Rev. 12/1/95 II tII ID cn ro CD CO STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Tabl ofCont nts Teratology SOPs Page 9 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) HAMSTER: TERA-400 SERIES (TERA-400 SERIES IS NOT CURRENTLY IN USE AND IS IN THE PROCESS OF BEING REVISED) SQE Number Subject TERA-400 Teratological Evaluation in Hamsters TERA-401 Weighing Hamsters 1. Weighing Mature Hamsters 2. Weighing Neonatal Hamsters TERA-402 Breeding Hamsters TERA-403 Assignment of Female Hamsters to Dose Groups Using Stratified Randomization Procedures TERA-404 Compound Administration 1. General Remarks 2. Intraperitoneal Injection (ip) 3. Subcutaneous Injection (sc) 4. Gavage (po) 5. Administration of Test Chemical by Drinking Water 6. Administration of Test Chemical by Feed 7. Clinical Signs TERA-407 Teratological Evaluation of Hamster Conceptus 1. Station I 2. Station II 3. Station III 4. Station IV TERA-408 Examination and Storage of Fetal Heads TERA-409 Staining the Hamster Skeleton with Alizarin Red S TERA-410 Examination of Alizarin Red S Stained Skeletons TERA-412 Examination of Alcian Blue/Alizarin Red S Stained Hamster Skeletons TERA-413 Preparation of the Hamster Skeleton for Storage Effective Revision Date Date 3CeDD -b ro ttoo Rev. 12/1/95 STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Contents Teratology SOPs Page 10 of 12 SQE Number TERA-500 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) DATA ENTRY AND STATISTICS TERA-500 SERIES Subject Data Entry and Statistical Processing RETIRED 8/9/95 Review or Effective Revision Date Date 1/29/87 TERA-502 Preparation of Data for Computer Entry 1/29/87 8/9/95 TERA-504 Overview of the VAX Accounts 5/2/91 8/9/95 TERA-509 Helpful Information for Using the VAX and Submitting SAS Jobs 6/11/91 8/9/95 TERA-511 Entering Preliminary Toxicity Data and Teratology Study Data Using Easy Entry on the VAX 5/7/91 8/9/95 TERA-526 Computer Software Program Calculation of Percentage of Fetuses Affected with Malformations or Variations 7/5/90 8/9/95 TERA-527 Collecting, Collating and Summarizing Clinical Observations 12/12/90 8/9/95 TERA-528 Logging Onto the VAX Using the VT 320 or VT 420 5/7/91 8/9/95 TERA-529 Generation of Study-Specific Codebook TERA-530 Creating SAS Files from Raw Teratology Data TERA-531 Bartlett Test 5/2/91 mm mm 8/9/95 8/9/95 8/9/95 TERA-532 Analysis of Variance - ANOVA 6/4/91 8/9/95 TERA-533 Dunnett's Test 5/31/91 8/9/95 TERA-534 Williams' Test 6/11/91 8/9/95 TERA-535 Linear Trends Test 6/4/91 8/9/95 TERA-536 Chi-Square Test 5/31/91 8/9/95 TERA-537 Fisher's Exact Test 6/4/91 8/9/95 TERA-538 Linear Trend on Proportions 5/31/91 8/9/95 TERA-539 Repeated Measures ANOVA 6/12/91 8/9/95 TERA-540 Kruskal-Wallis Test 6/11/92 8/9/95 R&S147300 Rev. 12/1/95 STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Contents Teratology SOPs Page 11 of 12 BQE . Number TERA-541 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) DATA ENTRY AND STATISTICS: TERA-500 SERIES Subject Mann-Whitney U Test Effective Date Review or Revision Date 6/11/91 S/9/95 TERA-542 Jonckheere's Test 6/11/91 8/9/95 TERA-543 Generating a Table of Defects 6/12/91 8/9/95 TERA-544 Generating the Embryo/Fetal Table 6/11/91 8/9/95 TERA-545 Generating Individual Data Tables 6/11/91 8/9/95 TERA-546 Generating Summary Data Tables 6/11/91 8/9/95 TERA-547 Entry of Non-Standard Teratology Data and Generation of SAS Datasets 6/11/91 8/9/95 TERA-548 Validation of Statistical Analysis Programs 6/11/91 9/27/95 TERA-549 Determination of Data Outliers 6/11/91 8/9/95 TERA-550 Summarizing Clinical Observations for Report Tables 6/12/92 8/9/95 TERA-551 Cochran-Armitage Test 10/26/92 8/9/95 TERA-552 Weighted Analysis of Covariance 10/26/92 8/9/95 TERA-553 Multiplicity-Adjusted Fisher Test 10/26/92 8/9/95 TERA-554 Normality Test 10/26/92 8/9/95 TERA-555 Weighted ANOVA 10/26/92 8/9/95 Rev. 12/1/95 nec)o $w o STANDARD OPERATING PROCEDURE RESEARCH TRIANGLE INSTITUTE POST OFFICE BOX 12194 RESEARCH TRIANGLE PARK, NC 27709 Table of Contents T ratology SOPs Page 12 of 12 STANDARD OPERATING PROCEDURES TABLE OF CONTENTS (continued) ADMINISTRATIVE: TERA-600 SERIES SQE Number Subject Effective Date Review or Revision Date TERA-601 Role and Responsibilities of a Study Director for Nongovernmental Clients 10/26/93 TERA-602 Recording Handwritten Raw Data 10/26/93 TERA-603 Archiving Study Records 3/23/94 TERA-604 Preparation and Revision of a Standard OperatingProcedure 3/11/94 TERA-605 Disposition and Fate of Animals for Data Summarization and Analyses in Preparation for Final Reports for Developmental and Reproductive Toxicity Studies 10/24/94 TERA-606 Assignment of 5-Digit Rx Code and Color Code For Dose Groups Within a Study 4/20/95 TERA-607 Training Reproductive and Developmental Toxicology Staff 5/23/95 Rev. 12/1/95 DD in w-si oro SOP NO. LORET-OOl LORET-002 LORET-003 LORET-004 - 009 LORET-010 LORET-011 LORET-012 - 019 LORET-020 LORET-021 LORET-022 LORET-023 LORET-024 LORET-025 LORET-026 LORET-027 LORET-028 LORET-029 LORET-030 LORET-031 LORET-032 LORET-033 LORET-034 LORET-035 TABLE OF CONTENTS LORET STANDARD OPERATING PROCEDURES KEY WORD TITLE Chemicals Chemicals Chemicals Chemicals Formulation Formulation Receipt, Storage, and Disposal of Bulk Test Chemical Handling, Storage, and Disposal of the Test Chemical Formulations Preparation of Methyl Cellulose as Vehicle for Gavage Studies RESERVED Preparation of Test Chemical by Gavage RETIRED Formulation Animals Animals Animals Animals Animals Animals Animals Animals Animals Animals Animals Animals Animals Animals Animals Animals RESERVED Purchasing, Receipt, and Quarantine of Animals Eartagging Randomization Procedures for Assignment of Rodents to Groups Weighing Rodents Weighing Granular or Pelletized Feed for Determining Feed Consumption for Rodents Weighing Water for Determining Water Consumption Collection, Preparation, and Examination of Vaginal Cytology in Rodents Examination of Animals Having Unscheduled Deaths Necropsy of Rodents Intra-atrial Cannulation and Blood Collection of Rats Pair Feeding - Group Average Method Sacrifice of Animals to Minimize Release of Stress Hormone Breeding Rats Vaginal Smears: Detection of Sperm/Plug-Positive Females Culling Postnatal Litters Castration of the Rat R&S147303 STANDARD OPERATING PROCEDURES (Continued) SOP NO. KEYWORD TITLE LORET-036 Animals Measuring Anogenital Distance in Prepubertal Rodents LORET-037 Animals Counting Nipples on Rodents LORET-038 Animals Oral and Parenteral Dosing of Rodents LORET-039 Animals Observation of Clinical Signs LORET-040 Animals Disposition and Fate of Animals for Data Summarization and Analyses in Preparation for Final Reports of Reproductive and Endocrine Toxicity Studies LORET-041 -049 Animals RESERVED LORET-050 Andrology Estimating Speim Motility With a Microscope LORET-051 Andrology Performing Epididymal Sperm Analyses - Rats LORET-052 Andrology Sperm Head Counts in Rats LORET-053 Andrology Obtaining Ejaculated Sperm Counts in Rats LORET-054 Andrology Evaluation of Spermatogenic Potency Using the Spermatogenic Index LORET-055 Andrology Staging of the Spermatogenic Cycle in Rodents LORET-056 Andrology Intratesticular Hormone Assay: Sample Homogenization, Storage, and Preparation LORET-057 - 059 Andrology RESERVED LORET-060 Gynecology Conducting Oocyte Counts in Ovarian Sections From Rodents or Rabbits LORET-061 - 079 Gynecology RESERVED LORET-080 In Vitro Culture Testicular In Vitro Incubation LORET-081 -100 In Vitro Culture RESERVED LORET-101 Endocrinology Mouse Prolactin Radioimmunoassay LORE-102 Endocrinology Rat Prolactin Radioimmunoassay LORET-103 - 200 Endocrinology RESERVED LORET-201 Endocrinology RETIRED LORET-202 Endocrinology RETIRED R&S147304 STANDARD OPERATING PROCEDURES (Continued) SOP NO. LORET-203 LORET-204 LORET-205 - 300 LORET-301 LORET-302 LORET-303 LORE-304 LORET-305 - 399 LORET-400 LORET-401 LORET-402 LORET-402R LORET-403 LORET-404 LORET-405 LORE-406 LORE-407 LORE-408 LORE-409 LORE-410 LORE-411 LORE-412 LORE-413 LORET-414 LORET^15-449 KEY WORD TITLE Endocrinology Endocrinology RETIRED Rat Luteinizing Hormone Mini-Radioimmunoassay Endocrinology RESERVED Endocrinology RETIRED Endocrinology RETIRED Endocrinology RETIRED Endocrinology Rat Follicle Stimulating Hormone Mini-Radioimmunoassay Endocrinology RESERVED Endocrinology Validation of Immunoassays Endocrinology RETIRED Endocrinology RETIRED Endocrinology RETIRED Endocrinology Estradiol Radioimmunoassay Endocrinology RETIRED Endocrinology Testosterone Coat-A-Count Assay Endocrinology Total Thyroxine Coat-A-Count Assay Endocrinology Endocrinology Endocrinology Endocrinology Progesterone Coat-A-Count Assay Rat Growth Hormone Mini-Radioimmunoassay Estradiol Double Antibody Radioimmunoassay Rat Corticosterone Coat-A-Count Assay Endocrinology Endocrinology ACTH Double Antibody Radioimmunoassay Rat Thyroid Stimulating Hormone Mini-Radioimmunoassay Endocrinology Endocrinology Triiodothyronine Coat-A-Count Assay Aldosterone Coated-Tube Assay Endocrinology RESERVED R&S147305 STANDARD OPERATING PROCEDURES (Continued) SOP NO. KEYWORD TITLE LORET-450 LORET-451 - 500 Endocrinology Protein Hormone lodination Endocrinology RESERVED LORET-501 Endocrinology Enzyme Immunoassay for Progesterone LORET-502 Endocrinology Enzyme Immunoassay for Estradiol LORET-503 - 549 Endocrinology RESERVED LORET-550 Receptors Androgen Receptor Competitive Binding Assay and Androgen Scatchard Analysis LORET-551 -600 Receptors RESERVED LORET-601 Challenge Test Hormone Challenge Tests LORET-602 - 649 Challenge Test RESERVED LORE-650 Hormone Assessments Summarizing Hormone Secretory Patterns LORET-651 -699 Hormone Assessments RESERVED LORET-700 Miscellaneous Other Related SOPs Used by LORET LORET-701-799 Miscellaneous RESERVED LORET-800 Statistics Logging on and off VAX using the VT220, VT320, or VT420 LORET-801 Statistics Organization of VAX Accounts and Subdirectories LORET-802 Statistics Submitting SAS Jobs on the VAX LORET-803 Statistics Entering Data on the VAX Using EasyEntry LORET-804 Statistics Putting Isodata Files From Diskette into Microsoft Word LORET-805 - 899 Statistics RESERVED LORE-900 Equipment Operation of TJ-6 Centrifuge LORET-901 Equipment RETIRED LORET-902 Equipment Operation of Toploading Balance LORET-903 Equipment Calibration of Toploading Electronic Balances R&S 147306 SOP NO. LORET-904 LORET-905 LORET-906 LORET-907 LORET-908 LORET-909 LORET-910 LORET-911 LORET-912 LORET-913 LORET-914 STANDARD OPERATING PROCEDURES (Continued) KEY WORD TITLE Equipment Equipment Equipment Equipment Equipment Equipment Equipment Equipment Equipment Equipment Equipment RETIRED Operation of Beta Sdntillation Counter RETIRED Maintenance of Refrigerator and Freezer Units Verification of Pipetman Calibration (Gravimetric Method) Use and Calibration of ICN Apex 10/600 Gamma Counter Use of Isodata Software Operation and Maintenance of the CADD-1 Computerized Ambulatory Infusion Pump Operation of Coming 340 pH Meter Operating and Cleaning Microscope (Zeiss or Other) Operation and Maintenance of the Water-Jacketed C02 Incubator R&S147307 HISTOLOGY STANDARD OPERATING PROCEDURES TABLE OF CONTENTS SOP No. TITLE HIST-001 Receiving Wet Tissues and Logging in Specimens HIST-002 Tissue Trimming HIST-003 Tissue Processing HIST-004 Tissue Embedding HIST-005 Microtomy HIST-006 Staining: Hematoxylin and Eosin HIST-007 Coverslipping and Labeling Slides HIST-008 Tissue/Slide/Block Checkout-Quality Control HIST-009 Bagging of Trimmed Tissue HIST-010 Delivery and Storage HIST-011 Equipment Maintenance HIST-012 Balance Calibration HIST-013 Laboratory Safety HIST-014 Personnel Training File HIST-015 Necropsy HIST-016 Decalcification HIST-017 Processing the Eye HIST-018 Fine Dissection of Central and Peripheral Nervous System HIST-019 Special Stains HIST-020 Glycol Methacrylate Procedure (GMA) EFFECTIVE DATE October 8,1992 October 21,1992 October 8,1992 October 21,1992 October 21,1992 October 21,1992 October 8,1992 October 21,1992 October 8,1992 October 21,1992 October 21,1992 October 21,1992 October 8,1992 October 20,1992 October 8,1992 October 21,1992 October 20,1992 October 21,1992 October 21,1992 November 30,1994 R&S147308 Appendix 4 RTI Reproductive and Developmental Toxicology Wing * Appendix 5 CUT Experimental Design Figure and CIIT/RTI Task Sharing Tables R&S147313 Figure 1 Reproduction/Fertility with Added on Developmental Toxicity Study in Rats The study takes ~ 18 months to completion 11/97 7/9641 weeks_____________ 17-22 weeks Final Report 2 wk* Exposures over 2 generations Complete analyses to CMA Qu' Interim analyses Draft report Place the Developmental Toxicity Study into the first prebreeding period F, cull PND4 to 8/L F2 F 1 6-9 wk ' M/F 120/120 2 wk., 10 wk. Fn0 I Qu. ' Prebreed 1 \ EXP. r Developmental Toxicity Study 2 wk. 3 wk. Pause Mate Gest. GD20 EXP. EXP. to } PND4 F0 M complete nec. + sperm 3 wk. , Lactat.i EXP./ 10 wk. F1( 2 wk. 3 wk., 3 wk. P rebreed.* Mate GestJ Lactat. EXP. EXP. EXP. EXP. f2 Wean (exam) /T * /F0F / complete nec. + / histology T F iM complete nec. + sperm r FiF complete histology 36 weeks continuous exposure 4 exposure groups (30 F/30 M each) throughout in Repro./Fert. Study V X 1 F,,/sex/L nec. 4 exposure groups (25 pregnant F each) with daily exposure throughout pregnancy in the Developmental Toxicity Study StC/nSStl Table 1 Definitive Developmental Toxicity Study in Rats Task SharingRTI Purchase Receipt Quarantine Mating V Group Assignment V Exposure V Daily observation Food consumption/body weight V Remove for necropsy Complete necropsy3 Fetal evaluation V V V Report Preparation - Draft - Final V V Quality Assurance V CUT V V V V V V V V V V aThe sequence of task sharing for the range finding study in rats and mice is the same up to this task. it jO 9to t'soi 05 I*' Table 2 Definitive Reproduction/Fertility Study in Rats _________________________Task Sharing____________________ Purchase Receipt Quarantine Assign to Study (6-9 wks only) Pre Breed, exposure (10 weeks) Daily observation Vaginal cyclicity (last 3 weeks) 2 week mating Vaginal smears/vaginal cyclicity Sperm detection GD 0 Fo male removal; necropsy; sperm analysis; retain tissues Gestation 3 weeks Food consumption to GD 19 Exposure stop GD20 through PND 4 PND 0 -anogenital distance Cull to 8 pups on PND 4 Dams back into chambers on PND 5 Exposure during lactation 3 weeks Wean PND 21 Fo females; 3 wk postweaning vaginal cyclicity F0 females removed; necropsy; retain tissues Necropsy of selected Fi offspring; one/sex/litter F-| Pre Breed, exposure (10 weeks) Vaginal cyclicity (last 3 weeks) 2 week mating Ft male removal; necropsy; sperm analysis Gestation 3 weeks Food consumption to GD 19 Exposure stop GD 20 to PND 4 Gestation, litter GD 22 F2 offspring PND 0 -anogenital distance Cull to 8 pups on PND 4 Dams back into chambers PND 5 Exposure during 3 weeks of lactation Wean PND 21 Fi females 3 weeks postweaning vaginal cyclicity F-) females removed; necropsy; retain tissues Necropsy of selected F2 weanlings (one/sex/litter) Histology -Fo -Fi RTI CUT --------- T~ V V V V V V V V V V V V V V V VV V V V V V V V V V V V V V V V VV V V V V V v R&S147317 ~Z Data analysis Report -Draft -Final Quality Assurance Table 2 (cont'd) Definitive Reproduction/Fertility Study in Rats Task Sharing -- ------------------------------------- RTI CUT 1------------ VV VV VV VV 30 CO fi a CD