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667 EVALUATION OF THE IMMUNOMODULATORY POTENTIAL OF DIETHYL PHTHALATE FOLLOWING DERMAL EXPOSURE IN A MURINE MODEL. J. L. Franko, E. Lukomska, B. J. Meade and S. E. Anderson. NIOSH, Morgantown, WV. Over the past 50 years the prevalence of asthma and allergy has increased throughout the US and other industrialized nations. During the same period there has been an increase in the production and use of phthalate compounds. Previous studies have suggested that certain phthalate compounds, including diethy-hexyl phthalate and butyl benzyl phthalate, have contributed to allergic disease by functioning as adjuvants, augmenting immunologic responses to other chemical and protein antigens without being allergenic themselves. Diethyl phthalate (DEP), another phthalate ester, used as a plasticizer in a variety of consumer products, has the potential for widespread exposure, both occupationally and in the general population. Although DEP is not an immune sensitizer, little is known about other immunological effects that may be associated with DEP exposure. The current study evaluated the immunotoxic potential of DEP. Dermal exposure to DEP concentrations as low as 50% were shown to be immunosuppressive, resulting in a modest reduction in thymus weights (%) and numbers of CD4+ and CD8+ thymocytes (30.7 and 37.6% respectively) in BALB/c mice. A dose responsive decrease in the primary IgM response to sheep red blood cells was observed following dermal exposure to DEP reaching 54% reduction at the highest concentration. Conversely, prior dermal exposure to 75% DEP enhanced airway hyperreactivity responses to aerosolized methacholine in mice sensitized to increasing concentrations of OVA, suggesting that despite its immunosuppressive properties, DEP may enhance airway responsiveness to environmental and occupationally relevant antigens and thereby contributing to the increased prevalence of allergic disease. These results warrant the need for additional investigation into the mechanisms underlying the immunotoxic effects associated with DEP exposure. 668 AFRICAN DUST ENDOTOXINS AND THEIR PRO- INFLAMMATORY ROLE IN HUMAN BRONCHIAL EPITHELIAL CELLS. M. G. Ortiz-Martínez 1, 3 , E. Rivera 4, 3 , L. B. Méndez 2 and B. D. Jiménez Vélez 1, 3 . 1 Biochemistry, University of Puerto Rico- Medical Sciences Campus, San Juan, 2 Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, 3 Center for Environmental and Toxicological Research, University of Puerto Rico, San Juan and 4 Department of Biology, University of Puerto Rico-Río Piedras, San Juan. African dust reaching the island of Puerto Rico is associated with increments in ambient particulate matter (PM). Among the PM components associated with adverse health effects are particle-bound endotoxins (ENX). Therefore, aqueous and organic extracts of PM 10 samples collected from specific African Dust Events (ADE) reaching Puerto Rico in March 2004 were characterized for their ENX content and evaluated for its cytotoxic and pro-inflammatory responses in the human bronchial epithelial cell line BEAS-2B. To accomplish these aims, we analyzed PM 10 extracts from samples collected at the Atlantic Ocean and two sites in Puerto Rico (e.g. rural vs. urban). The ENX content in the extracts, as determined by the LAL assay, was higher in the organic fraction of PM 10 and increased during ADE for all sites. Organic extracts of the ADE samples were highly cytotoxic even at low doses. The levels of IL-6 and IL-8 in cell culture supernatants were significantly higher in cells exposed for 24 hrs to ADE PM 10 aqueous extracts versus those exposed with non- ADE extracts. However, only IL-8 was induced with the ADE organic extracts. To evaluate the role of ENX in the induced cellular responses, the extracts were pretreated with the ENX inhibitor polymyxin B prior cell exposure and the induction of pro-inflammatory mediators in human lung cells was inhibited. Since inhibition of ENX reduced the pro-inflammatory responses of ADE PM 10 extracts current experiments are being performed to determine the expression of Toll-like receptor 4, which recognizes ENX, after exposure to PM extracts. The results obtained so far suggest that African dust reaching Puerto Rico increases the ENX content in ambient PM, which can induce inflammatory responses in the lung. Supported by MBRS-RISE Grant R25GM061838. 144 SOT 2011 ANNUAL MEETING 669 AFRICAN DUST PM 2.5 REACHING PUERTO RICO INDUCES OXIDATIVE STRESS AND PRO- INFLAMMATORY MEDIATORS IN HUMAN LUNG CELLS. R. I. Rodríguez 1, 3 , L. B. Méndez Torres 2 and B. D. Jiménez Vélez 1, 3 . 1 Biochemistry, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico, 2 Department of Microbiology and Molecular Genetics, University of California, Irvine, CA and 3 Center for Environmental and Toxicological Research, University of Puerto Rico, San Juan. African dust reaching the island of Puerto Rico is known to sporadically increase ambient particulate matter (PM). Particle-bound metals have been associated with adverse health effects. Organic extracts from PM 2.5 samples collected during African dust events (ADE) reaching Puerto Rico were characterized for its metal content and oxidant capacity. Extracts were also evaluated for its role in inducing oxidative stress and pro-inflammatory responses in the human bronchial epithelial cells (BEAS-2B). ADE and non-ADE PM 2.5 organic extracts exhibited similar oxidative capacity, using the DTT assay. However, metal compositions of organic extracts, determined by ICP-MS analysis revealed an increase in Cu and V concentrations in ADE vs. non-ADE extracts. This supports the hypothesis that differences in metal concentrations might be responsible for the immune responses observed between extracts. In-vitro experiments showed a reduction in the total antioxidant capacity and glutathione concentrations in lysates of organic extracts (50μg/ml). This reduction was greater in ADE organic extracts. Secretions of IL-6 and IL-8 were significantly higher in cells exposed (24hrs) to ADE vs. non-ADE extracts. However, the levels of MCP-1 were significantly reduced after exposure to either type of extract. The addition of metal chelators (deferoxamine and tetraethylenepentamine) increased antioxidant capacity and decreased the secretion of pro-inflammatory mediators in human lung cells exposed to organic extracts. These results demonstrate that the effects of organic extracts are produced by trace elements. This study suggests that African dust reaching Puerto Rico increases the concentrations of trace elements in ambient PM 2.5 , inducing oxidative stress and inflammatory responses in the lung. Supported by MBRS-RISE Grant R25GM061838 670 HEALTH EFFECTS DUE TO ACUTE EXPOSURE OF DUST SAMPLES COLLECTED FROM NELLIS DUNES RECREATIONAL AREA. S. Proper 1 , M. Peden-Adams 2 , N. Ayala 2 , J. Berger-Ritchie 2 , S. Labahn 2 , S. Young 2 , B. Buck 2 , D. Goossens 2, 3 , D. Soukup 4 , R. Sudowe 2 , Y. Teng 2 , D. Baron 2 , J. R. Harkema 1 and D. E. Keil 5, 2 . 1 Michigan State University, East Lansing, MI, 2 University of Nevada, Las Vegas, NV, 3 Katholieke Universiteit, Leuven, Belgium, 4 California State University, Bakersfield, CA and 5 University of Utah, Salt Lake City, UT. The Nellis Dunes Recreational Area (NDRA; Las Vegas, NV) is a popular natural site for recreational vehicle operators with over 300,000 visitors per year. Potential health effects caused by PM10 generation from ORV activity were examined. B6C3F1 mice were exposed to dust collected from 3 NDRA map unit sites (2.2, 3.1, or 3.2). Exposure was administered via oropharyngeal aspiration at doses of 0.1, 1, 100, and 1000 mg/kg/day for 3 days. The lowest adverse effect level (LOAEL) for map unit 2.2 was 0.1 mg/kg/day while the LOAEL was 1.0 mg/kg/day for map units 3.1 and 3.2. Each LOAEL was based on significant and dose-responsive decreases in specific IgM B-cell responses and CD4/CD8 splenic lymphocytic subpopulations. Pulmonary histopathology was evident in the 100 and 1000 mg/kg/day dose groups. Observations were primarily multifocal, centriacinar bronchiolitis with accumulation of dust-filled macrophages and interstitial fibrosis. Alveolar bronchiolarization and bronchiolitis obliterans were also common, characteristic of pneumoconiosis. Median particle diameter for map units 2.2, 3.1, and 3.2 was 4.3, 2.4, and 3.1 um, respectively. The predominant mineral was smectite while palygorskite was also common. ICP-MS measured >20 naturally-occurring metals to include: 23-143 ppm total As, 18-24 ppm Pb, 9-18 ppm Cr, 6600-9800 ppm Al, 106-183 ppm Sr, and 274-428 ppm Mn. Research is needed to determine the impact of dust exposure on respiratory health and disease resistance because of the likelihood of human exposure.
671 INFLAMMATION AND TISSUE DAMAGE IN THE MOUSE LUNG INDUCED BY WOOD SMOKE PARTICULATE MATTER FROM NEW AND OLD TECHNOLOGY HEATING APPLIANCES. O. Uski 1 , M. Happo 2 , P. Jalava 1, 2 , K. Joachim 3 , T. Brunner 3, 4, 5 , I. Obernberger 3, 4, 5 , M. Tapanainen 1 , J. Jokiniemi 2, 6 and M. Hirvonen 1, 2 . 1 National Institute for Health and Welfare, Kuopio, Finland, 2 University of Eastern Finland, Kuopio, Finland, 3 BIOENERGY 2020+ GmbH, Graz, Austria, 4 Graz University of Technology, Graz, Austria, 5 BIOS BIOENERGIESYSTEME GmbH, Graz, Austria and 6 VTT Technical Research Centre of Finland, Espoo, Finland. Sponsor: M. Viluksela. Particulate air pollution (PM) is a global problem, which is responsible for large variety of adverse health outcomes. EU has decided to increase the use of biomass energy to 20% on average from the total energy consumption by 2020. Since large proportion of PM emissions are derived from small scale combustion, it is important to reveal the effects of the combustion technology, user practice and fuel type or quality on these emissions. The effects of these factors on toxicological properties are still poorly known. In this study, we compared the adverse health effects induced by PM-samples collected from new (woodchip boiler) and old (logwood boiler) technology heating appliances. Particulate samples (Dp
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIODEGRADABLE MATERIALS FOR TISSU
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that genetic toxicology data are ge
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well-orchestrated lung inflammation
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scribed in the literature. We have
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years ago). We will illustrate how
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involved in the biodegradation proc
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stem cells but rather a treatment i
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additional compound showed agreemen
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82 COMPARISON OF 3H-THYMIDINE INCOR
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irritants. While in practice these
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alleles are especially vulnerable t
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109 CD4+ T CELL INTRINSIC TNF RECEP
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118 TO STUDY THE SIGNAL TRANSDUCTIO
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PAHs, such as dioxins, are prevalen
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containing substituents and/or hydr
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146 COMPUTATIONAL MODELING FOR QT P
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suggest that the combination of too
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164 TRANSLOCATOR PROTEIN (18 KDA) (
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function as a metal binding protein
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laboratory has demonstrated that NR
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known. The aim of this study was to
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from 5 to 28 days in duration) in e
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positive cells, caspase-3 activatio
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creased level in the 46 kDa preproe
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invasiveness at concentrations repr
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thracene (DMBA,50 μg in acetone, a
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247 CO-CARCINOGENESIS OF N, N- DIET
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sponds to the endosomal dsRNA that
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ODD in both WT (maximum 177% of con
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Lastly, using p53siRNA cells, p53 w
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its receptor Mpl to exert its funct
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294 LOW LEVEL OF LEAD CAN INDUCE PH
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lunar surface presented potential h
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lar about cellular export mechanism
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DNA in the kidney medulla, grandula
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5.00 and 7.50 mg/kg/day by oral gav
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events and carcinogenesis. Here we
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tinization of cells of the hair fol
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358 CHARACTERIZATION OF GENOME-WIDE
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RNAi were also performed to identif
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376 A FUNCTIONAL CROSSTALK BETWEEN
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UGT1A gene induction, while this re
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tivity, specifically peroxisome pro
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and cytotoxic effects; however, its
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histone deacetylase that is necessa
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ment. Paradoxically, buthionine sul
Page 97 and 98: drug leflunomide and its major (A77
Page 99 and 100: 442 GENE EXPRESSION AND MORPHOLOGIC
Page 101 and 102: 451 INHIBITION OF THE MITOCHONDRIAL
Page 103 and 104: 460 SULFORAPHANE PREVENTS ACETAMINO
Page 105 and 106: drophilic/lipophilic balance. Other
Page 107 and 108: pharmacokinetic and toxicological p
Page 109 and 110: 489 USE OF ‘OMICS DATA TO IMPROVE
Page 111 and 112: 498 APPLICATION OF AGE-SPECIFIC ADJ
Page 113 and 114: 507 A DOSE VOLUME TOLERABILITY STUD
Page 115 and 116: involved the use of an acute inflam
Page 117 and 118: sorption in the gastrointestinal (G
Page 119 and 120: (ABC) transporters actively transpo
Page 121 and 122: 545 BEHAVIORAL EFFECTS OF REPIN IN
Page 123 and 124: a blood pressure phenotype that res
Page 125 and 126: and inhalation exposure system that
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Page 129 and 130: position, on vascular reactivity an
Page 131 and 132: therefore more accurate and reprodu
Page 133 and 134: commercial chrysotile product that
Page 135 and 136: elative to their controls. ST-depre
Page 137 and 138: ats. The majority of the studies fo
Page 139 and 140: in the China Jintan Child Cohort St
Page 141 and 142: corneum thickness, cellular epiderm
Page 143 and 144: 645 EVALUATION OF THE IN VITRO EPIS
Page 145 and 146: 654 TCDD ADSORBED ONTO NATURAL AND
Page 147: tion revealed no test article-relat
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Page 153 and 154: 689 ENHANCED SUPPRESSIVE FUNCTION O
Page 155 and 156: NAC + LPS yielded different levels
Page 157 and 158: 707 LIFE-STAGE PBPK MODELS FOR MULT
Page 159 and 160: downstream of the apical endpoint o
Page 161 and 162: 726 UPDATED ALUMINUM PHARMACOKINETI
Page 163 and 164: global parameter sensitivity analys
Page 165 and 166: and renal inflammation induced by 2
Page 167 and 168: 754 PLASMA, URINE, AND TISSUE CONCE
Page 169 and 170: cently characterized transporter OA
Page 171 and 172: exposure system was developed from
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Page 175 and 176: practical alternatives to MC in non
Page 177 and 178: imals dosed with 167 mg/kg THU alon
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Page 181 and 182: yet is induced in most bladder and
Page 183 and 184: 830 RISK ASSESSMENT OF THE SPILL: C
Page 185 and 186: knowledgebase creation. Results are
Page 187 and 188: 852 UNDERSTANDING STRUCTURAL AND PH
Page 189 and 190: for integrating epidemiology and an
Page 191 and 192: motor activity, including age of th
Page 193 and 194: y partial purification of urine (fr
Page 195 and 196: pacity for self-renewal and may dif
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910 IMPLEMENTING CALIFORNIA’S GRE
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concentrations in six tissues and b
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934 THE FDA’S LIVER TOXICITY KNOW
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943 GENOME-WIDE DNA METHYLATION DIF
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membrane localization and subsequen
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trols, respectively. Subtoxic and t
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survival using both smoking regimes
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as non-, weak, moderate, or strong
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988 NNK-INDUCED CYTOKINE ALTERATION
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group (one-way ANOVA, p90 % viabili
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ered as an organ involved in xenobi
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Transport of CPZ across the Caco-2
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estrous cycle and sexual behavior d
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mRNA expression levels. Collectivel
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1043 THE EFFECTS OF ENDOCRINE DISRU
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1052 MONO-2-ETHYLHEXYL PHTHALATE IN
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Results: MC was variable within and
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UtSMCs. Phosphorylation of FoxO1 wa
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nonpregnant and pregnant diabetic m
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1089 PFOA-INDUCED LIVER EFFECTS IN
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events in the liver. AZD9056 was ev
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The peppermint oil caused a concent
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OA did not affect food consumption.
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1126 PERSISTENT DEVELOPMENTAL ARYLH
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1135 BACH2 BINDING TO Prdm1 AS A ME
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The purpose of this project was to
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one marrow. Since Chk1 is an attrac
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1163 THE MRNA AND MIRNA PROFILE OF
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have now compared the IC50 values b
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1181 ELUCIDATION OF FACTORS DETERMI
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enced by pre-exposure to cigarette
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if abnormal PF was associated with
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weight (P=0.016) and small for gest
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portant cause of death, compared to
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posure groups. However, the differe
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Naphthalene is routinely analyzed i
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1245 SEASONAL CHARACTERIZATION OF H
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1255 URINARY T, T MUCONIC ACID LEVE
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modating a reliable data evaluation
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enzoquinone generate ROS and arylat
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teins (e.g. C3, 4, and 5, APOB, VDB
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1293 TRANSFORMING GROWTH FACTOR BET
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mation was decreased to the same le
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1312 EVALUATION OF THE SENSITIVITY
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luted OFR and CRL. Culture media ex
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urinary TCPy levels, blood and brai
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activity. The dose-response curves
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mice, each with 4 dose groups. One
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exposure to both ATR and DACT has a
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third tetratricopeptide repeats (TP
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7d. 28d after TMT injury there was
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subunits. Each cell type was treate
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1394 COMPARATIVE EFFECTS OF METHYLM
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1403 GENOTOXICITY AND PRE-NEOPLASTI
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vated only in high-dose-treated ani
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1421 DOSE-RESPONSE OF NAPHTHALENE-I
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cisplatin; 1.2-, 1.9- and 2.9-fold
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Day 11 and started to recover on Da
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1448 DEVELOPMENT OF A METHOD FOR QU
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1457 GLOBAL GENE PROFILING REVEALS
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cluding mouse and human macrophage,
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model of lung inflammation and host
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1484 NANOTOXICOLOGY AND NANOHEALTH
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throughput in vitro approach was us
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1502 IMMUNOLOGICAL ASPECTS OF AN AN
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(CIA) and the Streptococcal cell wa
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sitizers were 100% concordant among
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1530 MINIMAL RISK LEVELS FOR STYREN
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ical groups in the field of regulat
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vitro with this potentially insect-
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their performance on toxicological
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need for a better understanding of
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1577 AN IN VITRO MODEL SYSTEM FOR A
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gene expression post-transcriptiona
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1595 GENE EXPRESSION PROFILE OF RAT
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to confirm a hepatotoxic property o
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1613 AN INVESTIGATION OF THE CLEARA
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its nuclear translocation was reduc
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were collected from TK animals at d
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egulated targets were selected for
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U/L after tetracycline. Minocycline
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peri-pubertal FasL-/- mice show a d
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showed similar levels of apoptosis
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1676 TWO BIOMARKERS FOR EVALUATION
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motifs selected. This system was ap
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1693 VOC SERUM LEVELS IN THE GENERA
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1702 DOES THE CLOCK MAKE THE POISON
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those with high nickel content are
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isk assessment. However, unique cha
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model of APAP metabolism and glutat
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logically & morphologically similar
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posure, blood chemistry was analyze
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elated to oxidative stress by measu
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ostasis), but work is needed to tra
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tokine products during carcinogenes
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ways as chemical stressors and, the
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toxicity of nanomaterials relates s
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1815 MEASURING COMPOUND SELECTIVITY
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1825 EFFECTS OF METABOLISM BY INTES
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cyanoacetic acid increased 2-3 fold
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1845 IS THE PROMISCUITY OF THE ARYL
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crorarray analysis. RT-PCR results
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are a family of phase-II biotransfo
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ous labs. As a result of positive s
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down the doses may produce more tox
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spectively. Below 100 mg/l of gemfi
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1900 GENERATION OF PRECISION CUT LI
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iomarkers or observation of lesions
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creased reticulocytes and lymphocyt
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statistically significant interacti
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monize sample preparation and analy
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NPC and sinonasal cancer in neighbo
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showed incidences of lung and nasal
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utylbenzenes, exhibited most simila
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1975 DIFFERENTIAL MODULATION OF CYP
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organic As to MMA(V) and a lower ca
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ole in invasion and metastasis of c
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3T3-L1 cells to low-levels of arsen
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2011 IDENTIFICATION OF A NOVEL VX M
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This work was supported by Cooperat
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2029 EFFICACY OF ENDOTRACHEAL ADMIN
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Diazepam injections and its combina
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2047 ESTERASE ACTIVITIES AND HEMOST
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nanoparticle-induced toxicity progr
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house, were iv infused into rats ov
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een explored. This study investigat
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croscopic analysis revealed that on
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egg yolk collected from turtles inh
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consistency of results in both expe
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2111 CYTOCHROME P450 3A5 GENOTYPE I
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esidues of organophosphates or thei
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manganism. Recent work from our lab
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Aβ1-40 in CSF and hippocampus in P
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2147 CATALASE MANIPULATIONS MODIFY
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ation based on real-world exposure
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NPs. Aggregation of citrate-stabili
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2175 THE ROLE OF SURFACE CHEMISTRY
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seen rapid uptake in biological ima
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effect on uterine weight or vaginal
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dicating widespread exposure. While
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components into the liver parenchym
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2223 ISOLATION AND DETECTION OF RIC
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stored (-20 celsius degree). The co
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2241 DDA, A BIOMARKER FOR ENVIRONME
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2249 INTERACTION BETWEEN DIETARY SE
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2258 PHARMACOKINETICS, EXCRETION BA
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2267 SENSITIVE AND SPECIFIC FLUORES
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2276 METABOLISM AND DISPOSITION OF
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ment of hypertension in companion a
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for the propyl series can be used f
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2304 IN VITRO EXPOSURE AND EVALUATI
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2313 THE SYNERGISTIC EFFECT OF SODI
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genes that play a crucial role in M
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2330 THE ROLE OF TRANSFORMING GROWT
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ined following up to 96 h continuou
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effect doses obtained with the rat
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diated transcriptional response of
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docrine disruptor activities of EDC
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individuals. Week 6 results were qu
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functionality of photosystem II and
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wild mice (Mus musculus) from areas
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2406 TOXICITY AND BIOACCUMULATION O
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Isocitric acid is the acid in the h
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2425 EFFECTS OF FUMONISINS IN ETHAN
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centration(μg/g) were: 5.1-95.3; 2
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2445 AUTOPHAGY IN DEVELOPMENT: A LI
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sures to inhaled Mn in dust. Nevert
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2466 CRITICAL EVALUATION OF ANIMAL
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elationships predict that resting r
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2489 COMPARATIVE TOXICITY OF BIODIE
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2497 TRANSCRIPTIONAL REGULATION OF
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2506 TOXICOLOGICAL CONSIDERATIONS O
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launched with the aim of developing
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forms mRNA expression levels were a
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2534 CUTANEOUS WOUND HEALING IN THE
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wells (0, 1, 5, 10, 25, 50, 100, an
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2553 AN ORGANOTYPIC MICROLIVER PLAT
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serum-free media. At 24 hrs, the gr
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2572 INCREASED ARSENIC BIOACCESSIBI
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nology to develop improved methods.
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tuna, swordfish, or mako shark (3.5
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nificantly reduce circulating thyro
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grouped into 9 observation periods
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histopathological or biochemical ev
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exhibited a hyperactive phenotype,
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the search of effective drugs for e
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2644 COVALENT BINDING OF 14 C 2-MET
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aries targeting all transcription f
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(p 9 weeks) and CSC phenotype acqui
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2673 IMMUNE-MEDIATED VASCULAR INJUR
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for risk identification and charact
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to control toxicant delivery in tob
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Author Index (Continued) The numera
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Keyword Index (Continued) Arsenite
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Keyword Index (Continued) Covalent
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Keyword Index (Continued) flow cyto
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Keyword Index (Continued) innate im
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Keyword Index (Continued) nanoparti
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Keyword Index (Continued) preservat
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Keyword Index (Continued) Thrombocy
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Toxicological Sciences The Official
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