Immotoxicology and Immotoxicology Sponsored Session

Sunday March 16, 2008 8:15 AM CE Session - AM03 Session Title: Stem Cells and Their Multipotential Uses and Potential Dangers PO/PL Chairperson: David Lawrence PO/PL Co-Chair: Marc Pallardy Location: Room 605 (Convention Center)

Stem cells can theoretically divide without limit to replenish cells and each daughter cell has the potential to remain a stem cell or develop into a fully functional differentiated cell. Therefore, stem cells have the potential to develop into many cell types that could benefit the health status of many individuals but the types of cells that could differentiate from stem cells must be considered in that certain growth and differentiation factors could give rise to conditions that could be harmful including development of a cancer stem cell. Additionally, environmental factors can skew the developmental patterns of stem cells leading to harmful deficiencies or expansions of certain types of progenitors. This course is designed as a basic level course to provide an overview of the field of stem cell biology, touch upon the differences of adult versus embryonic stem cells and provide a foundation for understanding the implications of the use of stem cells in toxicological research. Presentations will cover in vitro and in vivo proliferation and differentiation of stem cells and the influences of toxicants on these processes. Quantification of normal and aberrant immunophenotypic changes with development, mechanisms that influence proliferation, differentiation, and functional changes, and in vivo control of progenitors in their developmental niche will be discussed. The effect of environmental toxicants on a single molecular pathway controlling cell signaling and development of the CNS will be presented. Finally, the challenges in pharmacologically regulated cell therapy including the ability to regulate the fate of engineered cells will be deliberated.

• Analysis and Use of CD34+ Stem Cells from Human Cord Blood. David Lawrence

• Human Dendritic Cells Derived from Hematopoietic Progenitors for Detecting Sensitizing Molecules. Marc J. Pallardy

• Pharmacologically Regulated Cell Therapy. Anthony C. Blau

• The Critical Interaction Between Hematopoietic Progenitor Cells (hPC) and the Bone Marrow Microenvironment in Normal Hematopoiesis and Hematopoietic Toxicology. David W. Pyatt

• Redox Modulation of Neural Progenitor Cell Function by Environmental Toxicants. Mark Noble Monday March 17, 2008 9:30 AM Workshop Session Session Title: LLNA: False Positives, False Negatives, and Alternative Endpoints PO/PL Chairperson: David Basketter PO/PL Co-Chair: Ian Kimber Location: Room 608 (Convention Center)

9:30 - 9:45 AM #41 The LLNA, false positives, false negatives, and alternative endpoints. D. Basketter

9:45 – 10:15 AM 42 The local lymph node assay: Introduction, conduct, and performance. I. Kimber

10:15 – 10:45 AM #43 Alternative methods and endpoints in “enhanced” local lymph node assays and the photo- LLNA. G. L. DeGeorge

10:45 – 11:15 AM #44 Use of the local lymph node assay for sensitization hazard identification: A five-years experience from a regulator’s point of view. A. Oberemm; H. B. Richter-Reichhelm; U. Gundert- Remy

11:15 – 11:45 AM #45 Discordant results between the LLNA and guinea pig tests: Specificity vs. selectivity. A. Mehling; N. Ball1; H. Certa; D. Eigler; H. Esch; C. Haux; R. Kreiling; K. Skirda; G. Veenstra

11:45 AM – 12:15 PM #46 Where are we now? True and false positives and negatives. D. A. Basketter. Monday March 17, 2008 9:30 AM Poster Session Session Title: Immunotoxicology PO/PL Chairperson: Timothy Pastoor PO/PL Co-Chair: Courtney Sulentic Location: Exhibit Hall (Convention Center)

#163 Poster Board 301. 2,3,7,8-Tetrachlorodibenzp-p-dioxin-mediated impairment of B-cell differentiation through deregulation of paired box gene 5 (PAX5). M. A. Manzan; D. Schneider; N. E. Kaminski #164 Poster Board 302. A COX-2 metabolite of 2-arachidonyl glycerol is involved in the suppression of IL-2 secretion in activated Jurkat T-cells. P. Raman; C. E. Rockwell; B. L. Kaplan; N. E. Kaminski #165 Poster Board 303. Role of NF-κB/Rel proteins in mediating the repressive effects of TCDD on 3’IgHRR activation. R. Salisbury; E. J. Romer; C. E. Sulentic #166 Poster Board 304. 3,4-dichloropropananilide alters T-cell activation by inhibiting the Ca2+ influx pathway. T. L. Lewis; K. M. Brundage; R. Brundage; J. B. Barnett #167 Poster Board 305. TCDD-induced modulation of the human polymorphic hs1,2 enhancer within the 3’IgH regulatory region. T. Fernando; R. Fecher; C. E. Sulentic #168 Poster Board 306. Effect of TCDD on the transcriptional activity of the 3’IgHRR enhancer elements hs3A and hs1 2. T. Fernando; C. E. Sulentic #169 Poster Board 307. Evaluation of possible modes of action for PFOS-induced humoral immunosuppression. M. Peden-Adams; M. Mollenhauer; E. Driscoll; S. G. Bradshaw; J. Berger; P. A. Fair; D. E. Keil #170 Poster Board 308. Drug metabolism and immune response crosstalk: The role of pregnane X receptor in MHC-II transcriptional regulation. E. Fuentes-Mattei; B. D. Jimenez #171 Poster Board 309. Metallothionein gene dose influences cytokine secretion profile. X. Yin; D. W. Unfricht; G. Jin; K. Zaffuto; M. Lynes #172 Poster Board 310. Mechanisms of dithiocarbamate immunomodulation: Altered cellular red-ox status. S. B. Pruett; R. Fan; B. Cheng #173 Poster Board 311. Alterations in poly I:C-induced cytokine production by acute ethanol administration: Role of neuroendocrine mediators. M. Glover; S. B. Pruett #174 Poster Board 312. Immune function in intact and PPARα knockout mice exposed to PFOA. J. DeWitt; C. B. Copeland; R. W. Luebke #175 Poster Board 313. Histologic features of the developing immune system of rats G. A. Parker; C. A. Picut; K. L. Scully; D. J. Veney #176 Poster Board 314. Effects of glutathione depletion on pulmonary and splenic inflammatory cells following exposure to diesel exhaust. H. Neff-LaFord; L. M. Corey; C. C. White; J. Stewart; J. D. Kaufman; M. E. Rosenfeld; T. J. Kavanagh #177 Poster Board 315. Immunologic effects after utero and lactational exposure to endoslfan in lymph nodes, spleen, and thymus of immature rats. A. Lafuente; T. Cabaleiro; A. Caride; A. Romero; A. Anadon #178 Poster Board 316. Metallothionein expression affects the innate immune response to infection. G. Marusov; X. Yin; R. Emeny; D. A. Lawrence; M. Lynes #179 Poster Board 317. Exposure to environmental bacteria is associated with TNFand IL-6 producing capacity in infancy. M. H. Lappalainen; M. Roponen; A. Hyvärinen; A. Nevalainen; O. Laine; J. Pekkanen; M. Hirvonen #180 Poster Board 318. Dichlorvos significantly decreases the expression of granzyme B and granzyme 3/K in human NK cells. Q. Li; M. Kobayashi; T. Kawada #181 Poster Board 319. Prenatal exposure to cigarette smoke suppresses cytotoxic T- lymphocyte (CTL) activity in the offspring possibly via increased numbers of T-regulatory cells. S. P. Ng; A. E. Silverstone; Z. Lai; J. T. Zelikoff #182 Poster Board 320. Comparison of 28S rRNA cleavage by ricin and trichothecene deoxynivalenol in RAW 264.7 macrophages. M. Li; J. Pestka #183 Poster Board 321. Toxicological effects of naphthalene on innate immunity of fish (Centropomus parallelus). Evaluation by flow cytometry. L. C. Sá-Rocha; V. M. Sá-Rocha; D. Kinoshita; S. F. Affonso #184 Poster Board 322. Early toxicity of T-2 toxin: Effects on human monocyte, macrophage and dendritic cell D. Parent-Massin; N. Hymery; Y. Sibiril #185 Poster Board 323. Lessons from the Immunotoxicology bench: A multi-platform approach to innate immune evaluation of potential immunotoxicities. W. J. Freebern; T. J. Bigwarfe; K. A. Bello; K. D. Price; T. P. Reilly; H. G. Haggerty #186 Poster Board 324. Arsenite exposure decreases functional activation response and bactericidal capability of LPS-stimulated J774A.1 murine macrophages. L. C. Acosta-Saavedra; P. C. Conde; I. Estrada; E. S. Calderon-Aranda #187 Poster Board 325. IMMUNOTOXIBASE: A free-access database on the immunotoxicity of drugs and chemicals. J. Descotes #188 Poster Board 326. Exposure to carbon black nanoparticles activates antigen-presenting cells in vivo and in vitro. E. Koike; H. Takano; K. Inoue; R. Yanagisawa; M. Sakurai; T. Kobayashi #189 Poster Board 327. Suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p- dioxin. J. E. Suárez; N. E. Kaminski #190 Poster Board 328. Subcellular localization of the amide class herbicide 3,4-dichloropropi- onanilide (DCPA) in T-cells. M. L. Hanson; C. J. Peer; K. M. Brundage; R. Schafer; S. A. Eremin; J. B. Barnett #191 Poster Board 329. Evaluation of viral reactivation by murine IFNβ and an α4 integrin monoclonal antibody in a MCMV host resistance model. N. G. Wehner; G. Burleson; J. Clarke; C. Hurst #192 Poster Board 330. Augmentation of inflammatory mediators in aqueous humor and differential remodeling of the corneal stroma in response to sulfur mustard exposure. D. Milhorn; M. R. Nelson; K. A. Whitten; T. A. Hamilton #193 Poster Board 331. Effect of targeted anti-inflammatory agents in a rat streptococcal host resistance model: IL-1Ra, anti-TNF, or combined IL-1Ra and anti-TNF. W. J. Komocsar; F. G. Burleson; P. S. Struve; D. Wierda #194 Poster Board 332. In vitro immunotoxic effects of mercury depend on activation of human PBMCs. R. M. Gardner; J. F. Nyland; S. Evans; S. Wang; K. M. Doyle; D. M. Ansari; E. K. Silbergeld #195 Poster Board 333. Development of tolerance to Δ9-THC-induced suppression of in vivo and in vitro humoral immune responses. C. M. Sheth; K. L. White #196 Poster Board 334. A constitutively-active AHR expressed in T-cells increases percentage of CD25+CD4+ T-cells but does not suppress antibody production upon OVA immunization of mice. K. Nohara; K. Ao; Y. Miyamoto; K. Inouye; X. Pan; H. Motohashi; M. Yamamoto; C. Tohyama #197 Poster Board 335. Enhance host resistance to Listeria monocytogenes (LM) following exposure to the potent immunosuppressive compounds benzo(a)pyrene and diben(a,h)anthracene in female B6C3F1 mice. W. Auttachoat; D. Roesh; R. D. Brown; K. L. White #198 Poster Board 336. The effects of perfluorooctane sulfonate exposure on inflammation in B6C3F1 mice. M. Mollenhauer; J. A. Cook; P. A. Fair; M. Peden-Adams #199 Poster Board 337. HPLC/DAD study on covalent bindings of sensitizing chemical substances to serum albumin. T. Isse; O. Tsunehiro; T. Pham; T. Kawamoto #200 Poster Board 338. An electrophoretic study on covalent bindings of sensitizing chemical substances to albumin. T. Kawamoto; T. Oyama; T. Isse; T. Pham Monday March 17, 2008 9:30 AM Platform Session Session Title: Developmental Immunotoxicology, Host Resistance and Genomics Session Chairperson: Kathleen Gilbert Session Co-Chair: Wimolnut Auttachoat Location: 6E (CC)

9:30 - 9:54 AM #64. Immunosuppression by TBTO revealed by gene expression profiling in vivo and in vitro. K. Baken; J. Pennings; H. van Steeg; H. van Loveren 9:54 - 10:18 AM #65. Overlapping gene expression profiles of immunotoxic model compounds. H. Van Loveren; K. Baken; J. Pennings; H. Van Steeg; T. Breit 10:18 - 10:42 AM #66. Combining transcriptomics and metabolomics to delineate immunotoxicity of trichloroethylene. K. Gilbert; B. Przybyla; J. Fuscoe; T. Han; L. Schnackenberg; N. Pumford; J. Doss; L. Macmillan-Crow; S. Blossom 10:42 - 11:06 AM #67. Juvenile developmental immunotoxicity (DIT) testing in SD rats: Effect of dexamethasone on influenza viral clearance, NK activity, CTL activity, and T-dependent viral-specific IgM and IgG antibody production (TDAR). G. R. Burleson; F. G. Burleson; R. R. Dietert 11:06 - 11:30 AM #68. Developmental and early life exposure to trichloroethylene promotes an autistic phenotype in MRL+/+ mice: Potential role of oxidative stress in neuroimmune dysfunction. S. Blossom; S. James; S. L. Jernigan; S. Melnyk 11:30 - 11:53 AM #69. Naphthoflavone causes an AhR-dependent inhibition of invasion and intracellular multiplication of Listeria monocytogenes in murine hepatocytes. L. Z. Shi; C. R. Jefcoate; C. J. Czuprynski 11:53 - 12:15 PM #70. A developmental immunotoxicity study in the juvenile rat with cyclosporin. P. Barrow; F. Horand; P. Fant; J. Briffaux; L. Allais

Monday March 17, 2008 1:30 PM Symposium Session Session Title: Oxidant Air Pollution and Childhood Asthma Session Chairperson: Laura Van Winkle Session Co-Chair: Jack Harkema Location: 6C (CC)

1:30 - 1:40 PM #568. Oxidant air pollution and childhood asthma. L. S. Van Winkle; J. R. Harkema 1:40 - 2:00 PM #569. Oxidant air pollution and childhood asthma: Gene, environment and gene-environment interaction. T. S. Islam; F. D. Gilliland 2:00 - 2:20 PM #570. Genetic mechanisms of susceptibility to ozone-induced lung injury: New insights. S. R. Kleeberger 2:20 - 2:40 PM #571. Effects of oxidant exposure on immune system development in early life. L. A. Miller 2:40 - 3:00 PM #572. Critical timepoints for postnatal development of inflammatory and epithelial defense mechanisms: Ozone and LPS exposure. C. J. Johnston; J. N. Finkelstein 3:00 - 3:30 PM #573. Ozone-induced injury in the immature/developing nasal airways of infants. J. R. Harkema; S. A. Carey; J. G. Wagner; E. M. Postlethwait 3:30 -- 3:50 PM #574. Ozone-induced changes in conducting airways in non-human primates. M. V. Fanucchi 3:50 - 4:10 PM #575. Structural and functional consequences of ozone inhalation on alveolar morphogenesis. D. M. Hyde; N. K. Tyler; L. F. Putney; M. V. Avdalovic 4:10 - 4:15 PM Panel Discussion: Key Points Regarding Ozone and Asthma Structural Changes Monday March 17, 2008 1:30 PM Platform Session Session Title: APC's, B-Cells, and Haematopoiesis PO/PL Chairperson: David M Shepherd Location: 602 (CC)

1:30 - 1:54 PM #604. Innate control of adaptive immunity: Dendritic cells and TCDD. J. Bankoti; B. Rase; D. M. Shepherd 1:54 - 2:18 PM #605. Mechanisms of ethanol-mediated suppression of macrophage activation. K. von Maltzan; S. B. Pruett 2:18 - 2:42 PM #606. AhR activation reduces dendritic cell function but not migration in influenza virus- infected mice. G. Jin; J. J. Neumiller; J. A. Cundiff; B. Lawrence 2:42 - 3:06 PM #607. Activation and trafficking of peritoneal B1a B-cells in response to asbestos. J. C. Pfau; K. M. Hurley; S. Li 3:06 - 3:30 PM #608. Effects of the heavy metals mercury and lead on IL-33-induced mast cell cytokine secretion. C. A. Hudson; P. T. Massa; D. Lawrence 3:30 - 3:53 PM #609. Contribution of p53 and Bcl-2 family members in prostaglandin and phthalate-induced pro/pre-B-cell apoptosis. J. Schlezinger; S. L. Bissonnette; J. E. Teague; D. H. Sherr 3:53 - 4:15 PM #610. Benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene differentially disrupt haematopoiesis in bone marrow and lymphoid organs. A. N'jai; L. Shi; M. Larsen; C. Jefcoate; C. Czuprynski Monday March 17, 2008 4:30 PM Roundtable Session Session Title: Immunotoxicity Testing: Should Elevated Antibody Responses Be Interpreted as an Indicator of Immunotoxicological Hazard? Session Chairperson: Robert Luebke Session Co-Chair: Michael Holsapple Location: Room 615 (CC)

4:30 - 4:35 PM #628a. Immunotoxicity testing: Should elevated antibody responses be interpreted as an indicator of immunotoxicological hazard? R. W. Luebke; M. P. Holsapple 4:35 - 4:40 PM #628b. The Background: Elevated antibody responses following exposure to pesticides. R. Shafer 4:40 - 4:45 PM #628c. The Issue, Part I: Elevated antibody responses alone can be interpreted as an indicator of immunotoxicological hazard. H. van Loveren 4:45 - 4:50 PM #628d. The Issue, Part II: Elevated antibody responses alone should not be interpreted as an indicator of immunotoxicological hazard. M. Selgrade 4:50 - 4:55 PM #628e. The Reaction: An industry perspective. M. Woolhiser 4:55 - 5:00 PM #628e. The Reaction: An EPA perspective. V. Dellarco 5:00 – 5:50 PM Panel Discussion Tuesday March 18, 2008 9:00 AM Workshop Session Session Title: The Allergic March: The Role of Chemicals in the Increasing Prevalence of Allergy and Asthma PO/PL Chairperson: Ian Kimber PO/PL Co-Chair: Ian Gilmour Location: Room 6A (Convention Center)

9:00 - 9:15 AM #652. The Allergic March: The role of chemicals in the increasing prevalence of allergy and asthma. I. Kimber; I. Gilmour 9:15 – 9:45 AM #653. Introduction: The changing face of allergy and asthma. J. Vanoirbeek 9:45 – 10:15 AM #654. The influence of particulate air pollutants on allergic sensitization in animal models. M. Gilmour 10:15 – 11:45 AM #655. The “Hygiene Hypothesis” and beyond. I. Kimber 10:45 – 11:15 AM #656. Particulates, allergy, and asthma. M. Lovik; T. Alberg; M. Samuelsen; J. S. Hansen; U. Nygaard; A.Nilsen 11:15 AM – 11:45 PM #657. Phthalates and atopic allergy: Is there an effect? R. J. Dearman Tuesday March 18, 2008 9:00 AM Poster Session Session Title: Particulate Matter and the Cardiovascular System PO/PL Chairperson: Michael Kleinman PO/PL Co-Chair: Urmila Kodavanti Location: Exhibit Hall (Convention Center)

#726 Poster Board 122. Atherogenic and pulmonary response of ApoE- and LDL receptor- deficient mice to cigarette smoke. S. Han; D. Howatt; A. Daugherty; C. Gairola #727 Poster Board 123. Exacerbation of atherosclerosis following exposure to various combustion source particles. H. S. Floyd; N. Haykal-Coates; K. L. Dreher #728 Poster Board 124. Inhaled nickel nanoparticles induce systemic inflammation and accelerate atherosclerotic plaque formation in apoprotein E (ApoE) knockout mice. G. Kang; P. Gillespie; Q. Li; M. Zhong; T. Gordon; L. Chen #729 Poster Board 125. Health effects of traffic related particulate matter. M. Gerlofs-Nijland; A. Campbell; M. Miller; K. Donaldson; F. Cassee #730 Poster Board 126. Will the gaseous diesel exhaust synergistically exacerbate concentrated ambient particles induced progression of atherosclerosis plaque in ApoE-/- mice? C. Quan; X. Jin; M. Zhong; M. Lippmann; L. Chen #731 Poster Board 127. Alteration of cardiac function by urban and rural concentrated ambient PM. Q. LI; X. Jin; M. Zhong; M. Lippmann; L. Chen #732 Poster Board 128. Fine particulate matter exposure exacerbates atherosclerosis in genetically-susceptible (ApoE knockout) mice. M. T. Kleinman; D. Meacher; G. Gookin; K. Salazar; P. Willett; X. Jin; Q. Li; L. Chen #733 Poster Board 129. Ultrafine PM affects CNS inflammatory processes and may act via MAP kinase signaling pathways. M. T. Kleinman; J. Araujo; A. Nel; C. Sioutas; P. Q. Cong; S. C. Bondy #734 Poster Board 130. Chronic exposure of apo-liprotein E knockout mice to fine particles induced heart rate changes but not changes in time domain measurements of heart rate variability. K. Salazar; D. Meacher; G. Gookin; P. Willett; M. Kleinman #735 Poster Board 131. Exposure to particulate matter potentiates insulin resistance associated with macrophage accumulation in adipose tissue. Q. Sun; C. N. Lumeng; A. Wang; X. Jin; Y. Cai; M. Zhong; M. Lippmann; A. R. Saltiel; L. Chen; S. Rajagopalan #736 Poster Board 132. Adverse cardiovascular effects with acute particulate matter and ozone exposures: The role of Toll-like receptor 4. A. Hamade; R. Rabold; C. G. Tankersley #737 Poster Board 133. Diesel exhaust exposure augments endothelin constrictor sensitivity and diminishes acetylcholine-mediated dilation in rat coronary arteries. T. Cherng; N. Kanagy; M. Campen; B. Walker #738 Poster Board 134. Inhaled complex combustion emissions up-regulate transcription and activity of systemic matrix metalloproteinase-9 (MMP9): Evidence in murine and human models. M. J. Campen; A. K. Lund; M. C. Madden; J. Lucero; S. Lucas; T. L. Knuckles; M. Doyle- Eisele; S. Allen; J. D. McDonald; M. D. Reed; J. Seagrave; J. L. Mauderly #739 Poster Board 135. Gasoline engine emissions exposure results in up-regulation of endothelin-1-mediated vascular matrix metalloproteinase activity. A. K. Lund; J. Lucero; S. Lucas; T. L. Knuckles; M. J. Campen #740 Poster Board 136. Carbon nanotube acute lung exposure induces plasminogen activator inhibitor 1. A. Erdely; T. Hulderman; R. Salmen; A. Liston; P. C. Zeidler-Erdely; P. Simeonova #741 Poster Board 137. The aorta, but not lung or heart, is the target of subchronic diesel- induced injury and inflammation. R. Thomas; M. C. Schladweiler; A. D. Ledbetter; J. Shannahan; J. Wallenborn; A. Nyska; D. Malarkey; J. H. Richards; R. Jaskot; U. P. Kodavanti #742 Poster Board 138. Changes in endothelial tube cell-cell borders in response to diesel exhaust particles. M. Chao; P. Po; J. Koslosky; D. R. Gerecke; R. Laumbach; M. K. Gordon #743 Poster Board 139. Exacerbation of atherosclerosis by urban and rural concentrated ambient PM. L. Chen; Q. Li; C. Prophete; X. Jin; M. Zhong; Q. Sun; S. Rajagopalan; M. Lippmann #744 Poster Board 140. Lipoic acid prevents vascular dysfunction and inflammation in particulate air pollution exposure. S. Rajagopalan; C. N. Lumeng; A. Wang; X. Jin; M. Zhong; Y. Cai; A. R. Saltiel; L. Chen; Q. Sun #745 Poster Board 201. Effects of freshly-generated low- and ultralow-sulfur fuel emission aerosols in insulin-resistant, obese rats. A. Elder; N. Corson; R. Gelein; P. Mercer; A. Rinderknecht; W. Watts; D. Kittelson; R. Phipps; M. Frampton; M. Utell; J. Finkelstein; G. Oberdörster #746 Poster Board 202. Repeated exposure effect of traffic-related air pollutants on thrombogenicity. E. Kilinc; H. Spronk; H. ten Cate; R. van Oerle; F. Cassee; M. Gerlofs-Nijland #747 Poster Board 203. Particle-induced release of cytokines in mono- and co-cultures of primary lung and heart cells. A. I. Totlandsdal; M. Refsnes; T. Skomedal; J. Osnes; P. E. Schwarze; M. Låg #748 Poster Board 204. Acute exposure to particulate matter (PM) in a rat model of heart failure. A. P. Carll; N. Haykal-Coates; D. W. Winsett; W. H. Rowan; A. D. Ledbetter; J. H. Richards; A. K. Farraj; D. L. Costa; W. P. Watkinson #749 Poster Board 205. Differential cardiac arrhythmia profiles in hypertensive and normal rats after emission source particulate exposure. A. K. Farraj; D. W. Winsett; N. Haykal-Coates; M. S. Hazari; A. P. Carll; A. D. Ledbetter; D. L. Costa #750 Poster Board 206. Dose-independent changes in heart rate and heart rate variability following inhalational exposure to diesel exhaust. L. M. Corey; C. Baker; J. Stewart; D. L. Luchtel; J. D. Kaufman; T. J. Kavanagh; M. E. Rosenfeld #751 Poster Board 207. Alterations of heart rate variability and cardiovascular risk factors in rats exposed to coarse and fine particulate matter. T. Cheng; C. Chang #752 Poster Board 208. Acute effects of tobacco, incense, and candle smoke on porcine blood gases and cardiovascular function. A. Al-Dissi; J. Marit; T. German; L. P. Weber #753 Poster Board 209. Changes in cardiac physiology after chronic exposure to concentrated ambient particles in aged rats. G. Gookin; K. Salazar; P. Willett; D. Meacher; M. T. Kleinman Tuesday March 18, 2008 1:00 PM Poster Session Session Title: Inhalation Toxicology PO/PL Chairperson: James Wagner PO/PL Co-Chair: Jon Hotchkiss Location: Exhibit Hall (Convention Center)

#1071 Poster Board 409. Comparative effects of subchronic inhalation exposure of rodents to diesel and gasoline engine emissions, hardwood smoke, and simulated downwind coal emissions. J. L. Mauderly; E. G. Barrett; M. J. Campen; A. P. Gigliotti; J. D. McDonald; J. Seagrave; M. D. Reed; S. K. Seilkop #1072 Poster Board 410. Subchronic episodic exposure of rats to diesel pluz ozone induces minimal cardiopulmonary effects. M. C. Schladweiler; A. D. Ledbetter; J. Shannahan; J. Wallenborn; A. Nyska; D. Malarkey; J. Richards; H. Tong; R. B. Devlin; U. P. Kodavanti #1073 Poster Board 411. Inhibition of tyrosine phosphatase activity initiates receptor signaling in airway epithelial cells exposed to diesel exhaust particles. T. Tal; P. A. Bromberg; R. Silbajoris; J. M. Samet #1074 Poster Board 412. Lung injury is induced by insoluble and total, but not soluble, particulate matter (PM) collected in Mexico City. A. De Vizcaya-Ruiz; A. Osornio-Vargas; M. C. Schladweiler; A. D. Ledbetter; J. H. Richards; J. McGee; R. H. Jaskot; U. P. Kodavanti #1075 Poster Board 413. Urban particulate matter activates calpain and triggers the unfolded protein response. T. L. Watterson; B. Hamilton; R. Martin; R. A. Coulombe #1076 Poster Board 414. 90-Day inhalation toxicity study with disk-shaped magnesium potassium titanate particles (Terracess PS) in rats. S. Sakai; K. Inada; A. K. Tanaka; D. P. Kelly; G. Sykes; K. P. Lee #1077 Poster Board 415. Classification of aerosolized mineral base oils under the globally harmonized system of classification and labeling of chemicals (GHS). W. Dalbey; F. Whitman; M. Amoruso #1078 Poster Board 416. In vivo evaluation of lung structure by magnetic resonance imaging (MRI) following elastase-induced emphesema in rats. R. E. Jacob; K. M. Gideon; K. R. Minard; C. Timchalk #1079 Poster Board 417. Progressive pulmonary and pleural effects of indium phosphide in B6C3F1 mice: Particulate-induced pleural fibrosis and proliferation. P. Kirby; C. Shines; G. Taylor; R. Bousquet; H. Price; J. Everitt; D. Morgan #1080 Poster Board 418. Toxicological characterization of inhaled custom peptides. K. McInally; A. S. Aslam; E. Devemy; O. Blaschuck #1081 Poster Board 419. Inhalation of stainless steel welding fume results in dissimilar inflammatory responses in the lungs of A/J and C57BL/6J mice. P. C. Zeidler-Erdely; S. Stone; M. Donlin; A. Moseley; J. Cumpston; B. T. Chen; D. G. Frazer; S. Young; J. M. Antonini #1082 Poster Board 420. Beryllium-induced densitization and granulomatous lung disease in murine models. L. M. Tarantino; A. F. Hubbs; M. D. Hoover; D. L. Delano; T. Wiltshire; T. Gordon #1083 Poster Board 421. Use of a mouse model to evaluate pulmonary inflammation caused by floor dust from a water-damaged building. S. Young; J. M. Cox-Ganser; M. Wolfarth; J. M. Antonini; V. Castranova; J. Park #1084 Poster Board 422. Refinement of traditional restrained whole-body plethysmography (WBP): Development of a modular restrained WBP chamber for nose-only inhalation exposure studies in mice. S. M. Krieger; T. J. Cawley; W. M. Snellings; M. J. Filary; S. G. Walker; J. A. Hotchkiss #1085 Poster Board 423. Differential physicochemical properties of particles from wood combustion and traffic determine pro-inflammatory potential. P. Schwarze; A. Kocbach; J. I. Herseth; T. Sandström #1086 Poster Board 424. The protective effect of the upper airways against water-soluble irritant gas exposure – A case study of acute ammonia exposure. J. Kind; P. Nony; D. Hewitt #1087 Poster Board 425. Lung response to coarse PM: Bioassay in mice. T. C. Wegesser; J. A. Last #1088 Poster Board 426. Ozone exposure exacerbates eosinophilic and epithelial cell responses in sinus and nasolacrimal duct airways in allergic rats. J. G. Wagner; M. E. Swinkey; J. R. Harkema; D. B. Peden #1089 Poster Board 427. Effects of in vitro exposure of human respiratory epithelial cells to formaldehyde. C. R. O'Lenick; K. G. Sexton; K. DeBruijne; S. Ebersviller; S. Casper; I. Jaspers; H. Jeffries #1090 Poster Board 428. Nasal uptake of diacetyl and butyric acid vapors. J. B. Morris; A. F. Hubbs #1091 Poster Board 429. Comparing the toxicity of fresh and aged diesel exhaust using separate particle and gaseous exposure systems. K. de Bruijne; S. Ebersviller; K. G. Sexton; C. Olenick; R. Woodside; S. Casper; I. Jaspers; H. Jeffries #1092 Poster Board 430. Nasal uptake of naphthalene in the F344 rat. B. Simmons; J. B. Morris; A. Buckpitt #1093 Poster Board 431. Ambient particulate matter suppresses alveolar macrophage cytokine response to lipopolysaccharide. K. Sawyer; M. C. Madden; A. J. Ghio #1094 Poster Board 432. The role of Sparc in asbestos-induced pulmonary fibrosis. A. M. Smartt; M. Brezinski; A. Brave Rock; E. A. Putnam #1095 Poster Board 433. Toxicologic effects of acute 1, 2-dichloroethane (ethylene dichloride; EDC) inhalation in F344 rats. J. A. Hotchkiss; K. A. Johnson; A. K. Andrus; S. M. Krieger; J. P. Maurissen #1096 Poster Board 434. Bioaerosol emissions from composting grounds induce cytotoxicity and inflammatory responses in RAW264.7 macrophages. M. Roponen; K. Huttunen; H. Rintala; P. Kaarakainen; A. Nevalainen; M. Hirvonen #1097 Poster Board 435. Comparison of lung injury for JP-8 versus S-8 jet fuels at threshold concentrations. M. McLaughlin; J. Vargas; R. Camponovo; S. S. Wong; K. Le; M. Witten #1098 Poster Board 436. Extrapulmonary tissue distribution of metals following repeated lung exposures to welding fumes with different elemental profiles. J. M. Antonini; J. R. Roberts; K. Sriram; S. A. Benkovic; J. P. O'Callaghan; D. B. Miller #1099 Poster Board 437. Design of an inhalation exposure system to study spot welding fume characteristics and biological effects. A. A. Afshari; J. M. Antonini; V. Castranova; R. Boylstein; R. Kanwal; D. G. Frazer #1100 Poster Board 438. A novel method for the chemical characterization of generated jet fuel vapor and aerosol for animal studies. R. T. Tremblay; S. A. Martin; L. D. Fechter; J. W. Fisher #1101 Poster Board 439. Selectivity of neuropeptide release from pulmonary capsaicin- sensitive afferents in relation to diesel exhaust exposure. S. S. Wong; N. N. Sun; I. Keith; C. Lantz; M. Witten #1102 Poster Board 440. Determination of cell proliferation, apoptosis, and cytokeratin expression in the epithelium of the dog larynx. A. Postoyalko; C. M. Bray Tuesday March 18, 2008 1:30 PM Platform Session Session Title: Mechanisms of Hypersensitivity PO/PL Chairperson: Rebecca Dearman PO/PL Co-Chair: Jean Regal Location: 6E (Convention Center)

1:30 - 1:54 PM #1310. The impact of glycosylation on IgE antibody responses. R. Almond; R. J. Dearman; B. F. Flanagan; I. Kimber 1:54 - 2:18 PM #1311. Limiting allergen exposure during development: Differential effect on asthma symptoms in a mouse model. J. F. Regal; A. L. Greene; M. S. Rutherford; R. R. Regal; M. Duan; V. Haynes; M. Mohrman 2:18 - 2:42 PM #1312. Local antibody class switching in the nasal mucosa of mice with TDI rhinitis. V. J. Johnson; K. Fluharty; J. S. Reynolds; M. I. Luster; B. Yucesoy 2:42 - 3:06 PM #1313. Evaluation of irritancy and the sensitization potential of metal working fluids and metal working fluid components. S. Anderson; K. Brown; L. Butterworth; A. Fedorowicz; D. Beezhold; A. E. Munson; B. J. Meade 3:06 - 3:30 PM #1314. Evaluation of a genomic approach to the local lymph node assay (LLNA). D. R. Boverhof; B. B. Gollapudi; J. A. Hotchkiss; M. R. Woolhiser 3:30 - 3:53 PM #1315. Heme-oxygenase 1 and NADPH quinone oxidoreductase 1: New target genes to predict the sensitizing potential of chemicals? M. Pallardy; N. Ade; L. Bochet; H. Assaf-Vandecasteele; S. Kerdine-Römer; J. Ourlin 3:53 - 4:15 PM #1316. Zinc diethyldithiocarbamate allergenicity: Potential haptenation mechanisms. I. Chipinda; J. M. Hettick; R. H. Simoyi; P. D. Siegel Wednesday March 19, 2008 9:00 AM Poster Session Session Title: Respiratory and Skin Hypersensitivity PO/PL Chairperson: Marc Pallardy PO/PL Co-Chair: Victor Johnson Location: Exhibit Hall (Convention Center)

#1434 Poster Board 128. Anti-inflammatory effect of saponins isolated from the roots ofPlatycodon grandiflorum in a mouse model of allergic lung inflammation. J. Choi; H. Jeong #1435 Poster Board 129. Saponins derived from roots of Platycodon grandiflorum inhibits inflammatory cytokine expression in rat mast cells. C. Youngchul; E. Han; H. Jeong #1436 Poster Board 130. Up-regulation of cyclooxygenase-2 expression by serine protease, subtilisin, in macrophages. J. Hyepark; E. H. Han; H. Jeong #1437 Poster Board 131. Alcalase-mediated gene expression profile change in human airway epithelial cell line A549 grown in an air/liquid interface. T. Hu; M. Baccam; T. Reichling; G. Carr; E. Roggen; K. Sarlo #1438 Poster Board 132. A draining lymph node assay (DLNA) as a potential first tier for assessing the sensitizing potential of proteins. M. R. Woolhiser; B. B. Gollapudi; J. A. Hotchkiss; D. R. Boverhof #1439 Poster Board 133. Immunoglobulin E in asthmatic human sera is reactive against mold extracts. Y. Chung; M. D. Ward; E. Svendsen; K. Yeatts; D. Peden; L. Neas; R. Devlin #1440 Poster Board 134. Immunologic skewedness toward type-2 response prone to respiratory allergy in public service facility employees. Y. Heo; H. Kim; S. Lee; S. Kim #1441 Poster Board 135. Mixed air pollution, allergy and inflammation. A. Nilsen; T. Alberg; J. S. Hansen; U. C. Nygaard; M. Lovik #1442 Poster Board 136. An animal model of platinum (Pt) hypersensitivity. E. H. Boykin; J. R. Lehmann; D. L. Doerfler; S. H. Gavett; M. K. Selgrade #1443 Poster Board 137. Identification of respiratory sensitizing chemicals of low molecular weight using bronchoalveolar lavage fluid cytokines and serum. IgE M. Ota; T. Mori; K. Nishioka; H. Kaneko #1444 Poster Board 138. Evaluation of respiratory chemical allergens in the peptide reactivity assay. H. Rothe; K. Sarlo; F. Gerberick; L. Foertsch; R. Dearman; I. Kimber #1445 Poster Board 139. Carbon nanotubes enhance allergic responses in mice. U. C. Nygaard; J. S. Hansen; M. Lovik #1446 Poster Board 140. Activity of chemical respiratory sensitizers in a non-standard local lymph node assay (LLNA). R. J. Dearman; D. A. Basketter; H. F. McGarry; I. Kimber #1447 Poster Board 201. Evaluation of the potential and strength of skin sensitization using in vitro skin sensitization test – human cell line activation test (h-CLAT). Y. Nukada; T. Ashikaga; N. Kosaka; S. Sono; H. Sakaguchi; H. Itagaki; N. Nishiyama #1448 Poster Board 202. Investigation of false-negative contact allergens in the in vitro skin sensitization test; human cell line activation test (h-CLAT). N. Kosaka; Y. Nukada; H. Sakaguchi; N. Nishiyama #1449 Poster Board 203. Examination of a human cell line activation test (h-CLAT) for predicting skin sensitization potential: Outcome of the Third Ring Trial. C. Ryan; H. Sakaguchi; T. Ashikaga; J. Ovigne; D. Eschrich #1450 Poster Board 204. Intra- and interlaboratory evaluation of the LLNA-DA method: A non- RI modified LLNA in which ATP content is used as the endpoint. K. Idehara; G. Yamagishi; K. Yamashita #1451 Poster Board 205. Inter-laboratory Validation of a Non-Radioisotope Version of the LLNA*. H. Kojima; M. Takeyoshi; T. Omori; T. Sozu; K. Arima; K. Idehara; Y. Ikarashi; Y. Kanazawa; E. Maki; N. Nakagiri; M. Tanaka; A. Yuasa; I. Yoshimura #1452 Poster Board 206. Testing water soluble allergens via the ear canal in the local lymph node assay. N. Berg; U. Festersen; C. Rasmussen; T. Kjaer; E. Roggen #1453 Poster Board 207. Sensitization potential of vetiveryl acetate evaluated using the local lymph node assay. L. Jones; R. Foxenberg; J. Lalko; C. Letizia; A. Api #1454 Poster Board 208. Impact of olive oil and DMSO as vehicles on murine local lymph node assay (LLNA) estimated by two sets of endpoints. W. Wang-Fan; E. Deparade; L. G. Ullmann #1455 Poster Board 209. Performance characteristics of the local lymph node assay (LLNA) limit dose procedure. W. Stokes; D. Allen; T. Burns; N. Choksi; J. Matheson; A. Jacobs; R. Tice #1456 Poster Board 210. The chemical allergen nickel sulfate triggers the production of the bioactive form of IL-12 by human dendritic cells. M. Pallardy; D. Antonios; S. Kerdine-Römer; N. Ade; A. Larangé #1457 Poster Board 211. The effects of ascorbate and glutathione deficiency on the toxicity and immunogenicity of sulfamethoxazole nitroso in guinea pigs. S. Bhusari; M. Padilla; M. Pinkerton; L. Trepanier Wednesday March 19, 2008 9:00 AM Symposium Session Session Title: Developmental Basis of Health and Disease: Persistent Effects of Tobacco Smoke Exposure Session Chairperson: Laura Van Winkle Session Co-Chair: Kent Pinkerton Location: 605 (Convention Center)

9:00 - 9:05 AM #1331. Developmental effects of health and disease: Persistent effects of tobacco smoke exposure. L. S. Van Winkle; K. E. Pinkerton 9:05 -9:30 AM #1332. Effects of Environmental Tobacco Smoke on the developing immune system of infant monkeys. K. E. Pinkerton; L. Wang; J. P. Joad 9:30 - 9:55 AM #1333. ETS and gender effects on allergic asthma. L. J. Gershwin; V. L. Mitchell; L. S. Van Winkle 9:55 - 10:20 AM #1334. Prenatal exposure to tobacco smoke induces asthma-related responses in non- sensitized female offspring later in life. J. T. Zelikoff; S. Doherty; C. Hoffman; E. Brush 10:20 - 10:45 AM #1335. Environmental Tobacco Smoke (ETS) as a risk factor in childhood behavioral disorders. M. Golub 10:45 - 11:10 AM #1336. Maternal smoking and fetal lung development. E. R. Spindel 11:10 - 11:35 AM #1337. Sex differences in adult susceptibility to toxic challenge: Role of neonatal ETS exposures. L. S. Van Winkle; K. Sutherland; P. Edwards; G. Baker; M. Shultz; D. Nguyen 11:35 - 11:45 AM Panel Discussion Wednesday March 19, 2008 9:00 AM Workshop Session Session Title: Natural Killer Cells as Targets of Drugs, Toxicants, and Biologicals Session Chairperson: Raj Krishnaraj Session Co-Chair: Stephen Pruett Location: 6B (Convention Center)

9:00 - 9:25 AM #1344. Natural killer cells as targets of drugs, toxicants, and biologicals. R. Krishnaraj 9:25 - 10:00 AM #1345. Environmental immunotoxicants on human NK cells. M. Whalen 10:00 - 10:35 AM #1346. Natural killer cells at the interphase of innate and adaptive immunity. C. Munz 10:35 - 11:10 AM #1347. Direct and indirect effects of ethanol on activation of NK cells through TLR3. S. B. Pruett 11:10 - 11:45 AM #1348. Subtype markers define the tissue-specific effects of chronic alcohol consumption on NK cells. G. G. Meadows; H. Zhang Wednesday March 19, 2008 1:00 PM Poster Session Session Title: Oxidative Injury and Redox Biology I: In Vivo PO/PL Chairperson: Terrance Kavanagh PO/PL Co-Chair: Debra Laskin Location: Exhibit Hall (Convention Center)

#1944 Poster Board 642. Acetaminophen-protein adducts are not sufficient for hepatocellular necrosis in mice: Modulation of toxicity by gender and glutamate cysteine ligase modifier Subunit. I. Mohar; C. C. White; T. J. Kavanagh #1945 Poster Board 643. Chronic ethanol administration results in down-regulation of peroxiredoxin 6 and oxidative stress. J. Roede; B. J. Stewart; D. R. Petersen #1946 Poster Board 644. The natural triterpenoid oleanolic acid and a synthetic derivative CDDO-Im protect the liver from hepatotoxicants and increase antioxidant genes through activation of Nrf2. S. A. Reisman; L. M. Aleksunes; D. B. Buckley; Y. Tanaka; C. D. Klaassen #1947 Poster Board 645. Glutathione depletion activates specific mitogen-activated protein kinase (MAPK) in mice. M. E. Gonsebatt; J. H. Limón Pacheco #1948 Poster Board 646. Increased sensitivity of glutathione S-transferase P-null mice to cyclophosphamide toxicity. D. J. Conklin; R. A. Prough; A. Bhatnagar #1949 Poster Board 647. Mice that do not express glutathione reductase are more susceptible than are wild-type mice to infection with Group B streptococcus. M. M. Ralston; K. D. Bongiovanni; A. L. Jones; C. V. Smith #1950 Poster Board 648. Expression and function of aldehydes dehydrogenase 3B1 S. A. Marchitti; D. J. Orlicky; V. Vasiliou #1951 Poster Board 649. ALDH7A1 is a novel ALDH that protects against oxidative damage. C. Brocker; M. Cantore; A. Pappa; N. Lassen; T. Estey; S. A. Marchitti; T. Chavakis; V. Vasiliou #1952 Poster Board 650. Oral administration of polaprezinc, an anti-ulcer drug, protects mice against endotoxin shock T. Matsura; C. Moriyama; A. Yamashita; H. Morikawa; T. Nishida; S. Ohata; C. Kusumoto; J. Nakada; K. Yamada #1953 Poster Board 651. The role of reactive oxygen species (ROS) in airway hyper- responsiveness: The effects of 2-cyano-3,12-dioxooleana -1,9(11)-diene-28-oic acid (CDDO). D. Hochman; D. Nanyes; S. Schultz; E. Brooks #1954 Poster Board 652. Distinct roles of reactive oxygen and nitrogen intermediates in acute lung injury induced by ozone and bleomycin. A. M. Groves; J. D. Laskin; A. J. Gow; C. Guo; D. L. Laskin #1955 Poster Board 653. Disruption of antioxidant defense and DNA repair systems during 2- acetylaminofluorene-induced hepatocarcinogenesis in rats. T. V. Bagnyukova; C. L. Powell; B. Montgomery; F. A. Beland; I. P. Pogribny #1956 Poster Board 654. 670 nm photobiomodulation normalizes antioxidant enzyme activities suppressed in streptozotocin-induced diabetic rat. J. Lim; R. A. Sanders; R. Wilson; A. C. Snyder; S. Gopalakrishnan; J. T. Eells; J. B. Watkins III; D. S. Henshel #1957 Poster Board 655. Subchronic toxicity of inhaled toluene in rats: Oxidative stress markers in brain. D. A. Moore-Smith; J. H. Richards; T. E. Samsam; P. Evansky; P. J. Bushnell; P. R. Kodavanti #1958 Poster Board 656. Suppression of DFP-induced oxidative injury and dendritic damage in rat brain. D. Milatovic; S. Zaja-Milatovic; R. C. Gupta; M. Aschner #1959 Poster Board 657. A biotin-hydroxylamine labeling method for the detection of oxidized proteins using Western blot analyses and mass spectrometry. W. Chung; C. L. Miranda; C. S. Maier #1960 Poster Board 658. A UPLC/MS/MS procedure for the determination of isoprostanes in human serum. A. R. Molinelli; T. J. Laha; M. J. Edenfield; S. M. Sadrzadeh #1961 Poster Board 659. Phospholipid peroxidation biomarkers of Alzheimer’s Disease in the brain: Selective oxidation of phosphatidylserine. V. A. Tyurin; Q. Zhao; A. Mnuskin; R. L. Hamilton; S. T. DeKosky; W. F. Reynolds; V. E. Kagan #1962 Poster Board 660. Evidence of oxidative stress in lung, liver, and heart from sheep exposed to chlorine (Cl2) gas. M. A. Dubick; A. I. Batchinsky; J. L. Barr; L. C. Cancio #1963 Poster Board 661. NRF2 plays a protective role in response to pro-oxidant exposure of zebrafish embryos (Danio rerio). L. Van Tiem; A. Timme-Laragy; R. Di Giulio #1964 Poster Board 662. Is oxidative stress a significant factor in the synergistic developmental toxicity of model PAHs in zebrafish? R. Di Giulio; A. R. Timme-Laragy; L. Van Tiem; D. Jung Wednesday March 19, 2008 1:30 PM Platform Session Session Title: Immunotoxicology: T-Cells PO/PL Chairperson: Barbara Kaplan PO/PL Co-Chair: Narendra Singh Location: Room 602 (Convention Center)

1:30 - 1:58 PM #2002. The mechanism by which cannabidiol, a plant-derived cannabinoid, suppresses immune function involves suppression of nuclear factor of activated T cells (NFAT) transcriptional activation, but not suppression of NFATc1 or NFATc2 mRNA expression. B. L. Kaplan; N. E. Kaminski 1:58 - 2:26 PM #2003. Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: Involvement of regulatory T-cells. V. L. Hegde; S. Hegde; M. Nagarkatti; P. S. Nagarkatti 2:26 - 2:54 PM #2004. c-FLIP plays important role in TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced apoptosis in primary T-cells and established T-cell line in vitro. N. P. Singh; M. Nagarkatti; P. Nagarkatti 2:54 - 3:21 PM #2005. Inorganic mercury modulates CD95/FAS dependent cross-regulation of T-cell antigen receptor signal transduction M. D. Laiosa; M. J. McCabe 3:21- 3:48 PM #2006. Ex-vivo characterization of T-regulatory type CD4+ T-cells in mice exposed to TCDD. N. B. Marshall; L. B. Steppan; W. R. Vorachek; D. V. Mourich; N. I. Kerkvliet 3:48 - 4:15 PM #2007. Suppression of T-cell co-stimulator ICOS by 9-tetrahydrocannabinol. H. Lu; B. L. Kaplan; N. E. Kaminski Wednesday March 19, 2008 4:30 PM Informational Session Session Title: Implementation of the ICH S8 Immunotoxicity Testing Guideline PO/PL Chairperson: Thomas Kawabata PO/PL Co-Chair: Pramila Singh Location: Room 615 (Convention Center) The ICH S8 Guideline, “Immunotoxicity Studies for Human Pharmaceuticals” provides recommendations for nonclinical safety testing of low molecular weight drugs for potential to induce harmful effects via suppression of the immune system. It applies to new drugs; existing drugs in which intended indication or label changes may result in unaddressed toxicological issues; and drugs in which signs of immunosuppression arise during clinical trials or following market approval. Preparation of the S8 guidance document progressed through the combined efforts of pharmaceutical industry representatives (PhRMA, JPMA, EFPIA) and members from tripartite government regulatory agencies (FDA, MHLW, CHMP) who recognized the need for globally harmonized regulatory guidance on immunotoxicological testing in drug development. Over the years leading up to the adoption of the S8 Guideline by regional regulatory agencies (2005-2006), there was significant debate and even some confusion over the compulsory versus voluntary nature of the testing recommendations and on how to apply the guidance in concert with pharmaceutical industry objectives. The purpose of this informational seminar is to provide a forum for the discussion of the practical implementation of the S8 Guideline including industry case examples and questions that remain unanswered. A panel consisting of members of the ICH S8 Expert Working Group responsible for creating the S8 Guideline and representing the U.S., Europe, and Japan will be available to answer questions from the audience. This session is intended to be an interactive forum with the expert panel, audience, and selected speakers from industry who have comments or questions on the scope and application of the S8 Guideline in current industry practice. The session will begin with a brief introduction followed by an overview of the development of the S8 Guideline and the rationale for the recommendations made. This will be followed by two individual oral presentations by industry professionals with key opinions to consider about the practical application of the Guideline, an open question and answer session, and concluding thoughts. 4:30 - 4:35 PM #2042a. Implementation of the ICH S8 Immunotoxicity Testing Guideline. P. Singh ;T. Kawabata 4:30 - 5:00 PM #2042b. Overview and history of the development of the ICH S8 Guideline. J. van der Laan 5:00 - 5:25 PM #2042c. Filling the gap: Immunotoxicity of biotechnology products. D. Wierda 5:25 - 5:30 PM #2042d. Guideline positions on additional immunological parameters. G. Burleson 5:30-5:50 PM #2042e. Concluding Remarks Thursday March 20, 2008 8:30 AM Poster Session Session Title: Method Development, Autoimmunity, and Disease Mechanisms in Immunotoxicology PO/PL Chairperson: Lin Mantell PO/PL Co-Chair: Tai Guo Location: Ballroom C&E (Convention Center)

#2123 Poster Board 221. Evidence of autoimmune-related effects of trichloroethylene in studies in mice and humans. G. S. Cooper; S. L. Makris; J. Jinot #2124 Poster Board 222. Enhanced inducible nitric oxide synthase expression and nitrotyrosine formation in trichloroethene-mediated autoimmune response. G. Wang; J. Wang; M. Khan #2125 Poster Board 223. Evidence for postnatal autoimmune disease following developmental exposure to TCDD in 24-wk-old C57BL/6 mice. S. D. Holladay; A. Mustafa; M. Goff; S. Witonsky; R. P. Kerr; C. D. Reilly; P. Sponenberg; R. M. Gogal #2126 Poster Board 224. Perinatal TCDD exposure modulates B-cell development in juvenile C57BL/6 mice. R. M. Gogal; H. Groch; A. Mustafa; S. D. Holladay #2127 Poster Board 225. Exacerbation of postnatal autoimmune disease in 24-wk-old SNF1 lupus nephritis mice prenatally exposed to TCDD. A. Mustafa; S. D. Holladay; M. Goff; S. Witonsky; R. P. Kerr; C. D. Reilly; P. Sponenberg; R. M. Gogal #2128 Poster Board 226. Effects of feed-borne Fusarium mycotoxins on intestine and immune response of birds infected with coccidia. G. N. Girgis; T. K. Smith; J. R. Barta; S. Sharif; H. J. Boermans #2129 Poster Board 227. TCDD prevents diabetes in non-obese diabetic (NOD) mice. D. G. Farrer; L. B. Steppan; S. Oda; W. R. Vorachek; D. Pham; D. V. Mourich; N. I. Kerkvliet #2130 Poster Board 228. Genistein protects female non-obese diabetic (NOD) mice from developing Type I diabetes. T. L. Guo; D. R. Germolec; W. Auttachoat; J. F. Zheng; K. L. White Jr. #2131 Poster Board 229. Effects of deoxynivalenol on the antibody formation against Parvo virus vaccination in male mice. S. Jeong; J. Cho; E. Kim; B. Choi; Y. Jean; D. Tark; H. Kang #2132 Poster Board 230. The role of HMGB1 in the pathogenesis of cystic fibrosis. T. Entezari- Zaher; D. Weiss; S. Gangisetti; K. J. Tracey; H. Wang; M. Caryl; L. Mantell #2133 Poster Board 231. Systemic and local immunomodulatory effects following a single intratracheal exposure of 1,2:5,6-dibenzanthracene (DBA) in adult female B6C3F1 mice. D. Smith; M. J. Smith; K. L. White #2134 Poster Board 232. Validation of an immunotoxicity screening method using tetanus toxoid (TT) in the Cynomolgus monkey. S. A. Kirk; S. R. Fraser; D. Gordon; A. Templeton #2135 Poster Board 233. Electrospun nano-fibrous tissue engineering scaffolds of polydioxanone blended with elastin: A study of in vitro immunomodulatory effects. M. J. Smith; D. C. Smith; K. L. White; G. L. Bowlin #2136 Poster Board 234. Immunological assessments in one-year intravenous toxicity study in monkeys with abatacept, a selective co-stimulation modulator. L. C. Phelps; M. Abbott; T. Bigwarfe; L. Phelps; D. DeVona; T. Testorf; H. Haggerty #2137 Poster Board 235. Characterization of the long-term proinflammatory effects of 2’MOE gapmer phosphorothioate. Oligonucleotides T. Machemer; S. Burel; H. Zhang; B. Perkins; G. Hung; S. Greenlee; S. Henry #2138 Poster Board 236. Immunotoxicity assessment of young and adult C57BL/6 mice fed tributyltin-contaminated fish in their diet. B. Badiwa Bizowe; M. Fortier; S. Pillet; M. Fournier; P. Brousseau #2139 Poster Board 237. Immunological alterations in IN B6C3F1 mice following oral exposure to a brominated flame retardant mixture: DE-71. P. A. Fair; H. Stavros; M. Mollenhauer; D. E. Keil; M. Peden-Adams #2140 Poster Board 238. Evaluation of the potential effects of atrazine and its metabolites on the immune system routine toxicity studies conducted in rat, mouse, and dog. T. Pastoor; C. Breckenridge; J. Stevens #2141 Poster Board 239. Characterization of immune and asthmatic responses in cynomolgus macaques following antagonism of IL-12/23 activity with Ustekinumab (CNTO 1275). C. Sachs; J. Benson; P. Smith; A. Schantz; E. Martin; D. Graden; Q. Jiao; J. Cornacoff; P. Martin; G. Treacy #2142 Poster Board 240. Immunotoxic effects of tributyltin on splenocytes in F1 rats after subacute administration. M. Tsunoda; M. Tsuji; Y. Zhang; S. Kimura; C. Sugaya; Y. Inoue; Y. Kudo; T. Satoh; M. Wakasa; T. Tashiro; Y. Sugita-Konishi; Y. Aizawa #2143 Poster Board 241. Simultaneous time course and dose response characterization of 2,3,7,8-tetrachlorodibenzo-p-dioxin effects on the in vivo LPS-activated primary IgM response in female C57BL6 mice. C. M. North; R. B. Crawford; H. Lu; N. E. Kaminski #2144 Poster Board 242. Evaluation of the effects of antisense oligonucleotides on influenza clearance and macrophage function in mouse. T. Kim; T. Zanardi; S. P. Henry; F. G. Burleson; G. R. Burleson #2145 Poster Board 243. Phenotypic characterization of lymphocyte subpopulations in the minipig. F. Horand; F. Condevaux; J. Briffaux; P. Phothirath #2146 Poster Board 244. Validation of method for determination of anti-DA-3803 antibodies in rat serum using enzyme-linked immunosorbent assay. W. Choi; C. Kim; K. Na; D. Kim; W. Koh #2147 Poster Board 245. Development of a solid phase in vitro cytokine release assay using a customized superagonist monoclonal antibody. C. J. Gross; J. Min; T. Kawabata #2148 Poster Board 246. Development of in vitro model to assess proinflammatory properties of 2’-MOE oligonucleotides. S. Greenlee; S. Burel; T. Machemer; C. Black; S. P. Henry #2149 Poster Board 247. T-Cell dependent antibody response in cynomolgus monkeys for immunotoxicity evaluation. T. Nakamura; H. Yamatoya; J. Hayashi; T. Fukuda; N. Matsuo; Y. Takahashi; H. Izumi; H. Tokado; R. Nagata #2150 Poster Board 248. Analytical validation of spleen, thymus, and mesenteric and mandibular lymph node immunophenotyping for Cynomolgus monkey. J. E. Arrington; J. Fishel; P. Joshi #2151 Poster Board 249. Evaluation of Circulating Immune Complexes (CIC) BioAssay™ ELISA kit to determine the safety profile of monoclonal antibodies in mice. M. Ko; A. John-Baptiste; Q. Zong; F. Sace; M. Manya #2152 Poster Board 250. Immunophenotyping of CD4 T-lymphocytes from whole blood of Cynomolgus monkeys by flow cytometry is improved by usage of Clone L200. G. Bannish; M. S. Russell; C. S. Page; D. Lanham; B. A. Litzenberger; M. Wing #2153 Poster Board 251. Optimization and kinetics of the primary and secondary T-cell- dependent antibody response model in Wistar rats. C. Dumont; S. Corneau; H. Khalil; N. Cristiano; C. Li; L. LeSauteur #2154 Poster Board 252. Immunophenotyping of rat whole blood using automated lysis and fixation leads to improved process efficiency and precision. C. S. Page; G. Bannish; M. S. Russell; D. Lanham; B. A. Litzenberger; M. Wing #2155 Poster Board 253. Partial phenotypic and functional characterization of leukocytes from RyR1 R163C MH mice. S. R. Goth; S. Tong; B. T. Yuen; P. D. Allen; I. N. Pessah Thursday March 20, 2008 8:30 AM Poster Session Session Title: AHR Mechanisms PO/PL Chairperson: Richard S Pollenz PO/PL Co-Chair: Wade Powell Location: Ballroom C&E (Convention Center)

#2156 Poster Board 254. Role of the Cullin 4b, E6AP and MdM2 ubiquitin E3 ligase enzymes in ligand-dependent and -independent degradation of the AH receptor. R. S. Pollenz #2157 Poster Board 255. Role of DNA binding and dimerization with ARNT in the ligand-induced degradation of the AH receptor. R. Buzzeo; E. J. Dougherty; R. S. Pollenz #2158 Poster Board 256. Hsp90 displacement during ligand-dependent transformation of the aryl hydrocarbon receptor. A. Soshilov; M. S. Denison #2159 Poster Board 257. Identification of murine AhR residues that may a play role in signal transduction through phosphorylation. D. P. Vorojeikina; S. k. Park; T. A. Gasiewicz #2160 Poster Board 258. Epidermal growth factor receptor pathway blocks aryl hydrocarbon receptor-mediated transcription and differentiation in epidermal keratinocytes. C. H. Sutter; H. Yin; Y. Li; M. S. Jennifer; T. R. Sutter #2161 Poster Board 259. Serine 395, a site important for transcriptional activity in the mouse aryl hydrocarbon receptor (AhR), is phosphorylated by protein kinase. A B. Kobielush; G. D. Minsavage; D. Vorojeikina; M. L. Easterling; A. Friedman; T. A. Gasiewicz #2162 Poster Board 260. In vivo leflunomide exposure mimics the effects of TCDD in an AHR- dependent manner. K. S. Saili; L. K. Mathew; S. Sengupta; N. I. Kerkvliet; S. K. Kolluri; R. L. Tanguay #2163 Poster Board 301. Ligand-dependent differences of DNA binding by AHR-ARNT complexes versus AHR-ARNT2 complexes in vitro. E. J. Dougherty; R. S. Pollenz #2164 Poster Board 302. Relative potencies of individual dioxin-like compounds for in vitro cytochrome P450 1A1 transactivation of aryl hydrocarbon receptor from Baikal seal. H. Iwata; E. Kim; T. Suda; S. Tanabe; E. A. Petrov #2165 Poster Board 303. Responsiveness of a Xenopus laevis cell line to the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole (FICZ). L. B. Laub; B. D. Jones; W. H. Powell #2166 Poster Board 304. Distinct regulation of the aryl hydrocarbon receptor activity by different ligands. S. Luecke; K. Gradin; L. Poellinger; A. Rannug; M. Backlund #2167 Poster Board 305. Ligand specificity in modulating aryl hydrocarbon receptor DNA binding. D. DeGroot; Y. Song; S. R. Rushing; M. S. Denison #2168 Poster Board 306. Newspapers and newspaper ink contain agonists for the Ah receptor B. Zhao; J. E. Bohonowych; G. He; M. S. Denison #2169 Poster Board 307. Aryl hydrocarbon receptor (AHR), aging, and immunity. L. B. Steppan; D. G. Farrer; D. Pham; N. I. Kerkvliet #2170 Poster Board 308. Aryl hydrocarbon receptor (AhR) represses acute phase response gene expression in a DNA-binding independent manner. R. D. Patel; A. Kusnadi; C. A. Flaveny; G. H. Perdew #2171 Poster Board 309. Combination of inflammatory signaling and an AhR ligand leads to synergistic induction of IL-6. B. DiNatale; B. Hollingshead; G. H. Perdew Thursday March 20, 2008 8:30 AM Poster Session Session Title: Cardiovascular System: Vascular Effects PO/PL Chairperson: Bo Jiang PO/PL Co-Chair: Judith Zelikoff Location: Ballroom C&E (Convention Center)

#2200 Poster Board 341. Vascular dilation and aneurysm detected by noninvasive high- frequency ultrasonography in apoE deficient mice injected with angiotensin II. E. Suzuki; N. Shimoji; S. Tomioka; H. Kameda; M. Kammueller; Y. Nagae #2201 Poster Board 342. Inflammatory protein and gene expression in monocytes and macrophages exposed to cholesterol secoaldehyde: Implications to atherosclerotic plaque development. A. C. Raghavamenon; X. Gao; O. D'Auvergne; K. G. Kousoulas; R. M. Uppu #2202 Poster Board 343. Effects of prenatal cigarette smoke exposure on lipid parameters associated with offspring cardiac risk: A study in mice J. T. Zelikoff; S. P. Ng; J. Lyon; D. D. Bolanowski; D. Conklin; A. Bhatnagar #2203 Poster Board 344. Mechanisms of inhibition of vascular calcification by phosphonoformic acid (FOSCARNET) in rat vascular smooth muscle cells. V. Sorribas; R. Villa-Bellosta; J. Ducha; R. Morales; V. Latorre; A. Anadon #2204 Poster Board 345. Aryl hydrocarbon receptor-dependent alterations in hepatic and vascular gene expression in adult zebrafish. B. Bugiak; L. P. Weber View #2205 Poster Board 346. Vascular smooth muscle dysfunction induced by ginsenoside Rg3, a bioactive component of ginseng. J. Lee; O. Bae; K. Lim; J. Noh; J. Chung #2206 Poster Board 347. Subchronic exposure of adult mice to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) increases blood pressure and alters vascular reactivity. P. G. Kopf; M. K. Walker #2207 Poster Board 348. Hypertensive heart disease in older aryl hydrocarbon receptor-null mice progresses to symptoms of heart failure. L. Agbor; P. G. Kopf; A. C. Aragon; M. T. Walsh; M. Goens; M. K. Walker #2208 Poster Board 349. Non-invasive blood pressure monitoring in the Cynomolgus monkey (Macaca fascicularis): High-definition oscillometry versus implanted telemetric devices. B. Schmelting; M. Niehoff; B. Egner; S. Korte; G. Weinbauer #2209 Poster Board 350. Effects of NO modulators on cardiovascular risk factors in mild hyperhomocysteinemic rat model. M. Sharma; S. Rai; R. Tiwari; M. Tiwari; R. Chandra #2210 Poster Board 351. 15-Deoxy-Δ12,14 prostaglandin J2 induces platelet formation in a human megakaryoblastic cell line. J. J. O'Brien; R. P. Phipps #2211 Poster Board 352. An investigation of paraoxonase-1 (PON1192) activities in the serum of Southerners as related to gender and race. K. A. Davis; H. Chambers; A. Crow; J. E. Chambers #2212 Poster Board 353. Characterization of endothelial dysfunction induced by nucleoside reverse transcriptase inhibitor analogues and their phosphorylated metabolites. V. Y. Hebert; B. Jiang; A. R. Khandelwal; T. R. Dugas #2213 Poster Board 354. Antiretrovirals induce endothelial dysfunction via an oxidant- dependent pathway and promote neointimal hyperplasia. B. Jiang; J. H. Zavecz; T. R. Dugas #2214 Poster Board 355. Manufactured nanoparticles induce endothelial cell inflammation. C. Deering; S. Cutler; J. Veranth; G. Yost #2215 Poster Board 356. Endothelial cell caveolae are involved in activation of aryl hydrocarbon receptor pathway by coplanar polychlorinated biphenyls. Z. Majkova; E. Lim; E. Smart; M. T. Tseng; M. Toborek; B. Hennig #2216 Poster Board 357. Environmental PCBs increase blood vessel formation by oxidant signaling. Q. Felty #2217 Poster Board 358. Arsenic signals through a Gαi-coupled pathway to induce angiogenic genes in human microvascular endothelial cells. L. R. Klei; A. Barchowsky #2218 Poster Board 359. Genotoxic effects of 1-nitropyrene in human endothelial cells. H. L. Andersson; E. Piras; B. Hellman; E. Brittebo #2219 Poster Board 360. A novel CXCR4 antagonist derived from human SDF-1, SDF-1P2G, stimulates angiogenesis in a murine model of acute hindlimb ischemia. Y. Tan; X. Li; L. Cai #2220 Poster Board 401. Benzo[a]pyrene-induced vascular endothelial adhesion molecule expression can be disrupted by selective flavonoid treatment. E. Oesterling; M. Toborek; B. Hennig Vi