The Toxicologist - Society of Toxicology

More documents

Recommendations

Info

1525 SAFETY ASSESSMENT OF FOOD AND FEED FROM BIOTECHNOLOGY-DERIVED CROPS WITH MODIFICATIONS THAT REGULATE ENDOGENOUS GENE EXPRESSION. J. S. Petrick 1 , W. Parrott 2 , B. Chassy 3 , J. Ligon 4 , L. Meyer 5 , J. Zhou 6 , R. Herman 7 , B. Delaney 8 and M. Levine 9 . 1 Product Safety Center, Monsanto Company, Saint Louis, MO, 2 Crop and Soil Sciences, University of Georgia, Athens, GA, 3 College of ACES, University of Illinois, Urbana, IL, 4 Bayer CropScience, Research Triangle Park, NC, 5 Syngenta Biotechnology, Inc., Research Triangle Park, NC, 6 Johnson & Johnson, Raritan, NJ, 7 Dow AgroSciences, Indianapolis, IN, 8 Pioneer, A DuPont Company, Johnston, IA and 9 International Life Sciences Institute, Washington, DC. Agricultural biotechnology traits in development include those using tools such as transcription factors and RNA interference (RNAi) to modulate endogenous plant gene expression for the improvement of yields, tolerance to biotic and abiotic stresses, and nutritional quality. Biotechnology-derived crops are presently evaluated for food and feed safety relative to a conventional comparator according to an internationally-accepted safety assessment paradigm. This robust and comprehensive approach incorporates basic concepts from food safety, toxicology, nutrition, molecular biology, and plant breeding and has been used effectively by scientists and regulatory agencies for nearly 15 years. The main aspects of the comparative safety assessment process are reviewed and recommendations are provided for scientifically sound principles to evaluate the safety of biotechnology-derived crops developed using biological approaches that modify endogenous plant gene expression. Key considerations for applicability of the existing safety assessment process include: 1) The history of safe consumption of RNAi- mediating small RNAs (e.g., miRNAs) and regulatory proteins such as transcription factors; 2) The growing scientific literature describing the central role that RNAi and transcription factors have played in plant domestication and conventional breeding; 3) Crops engineered using RNAi constructs are not expected to produce heterologous proteins; 4) Modulation of plant gene expression may result in quantitative differences in levels of endogenous plant components (but not de novo components) that can be assessed through compositional analysis. 1526 USE OF CLUSTER ANALYSIS IN PESTICIDE INERT INGREDIENT RISK ASSESSMENT. A. S. Duggan 1 , J. Johnston 2 , J. Messina 2 , K. Akkari 3 , D. Hillebold 4 , G. Lindner 5 and P. McCain 6 . 1 Health Practice Center for Toxicology and Mechanistic Biology, Exponent, Inc., Philadelphia, PA, 2 Health Practice Center for Chemical Regulation and Food Safety, Exponent, Inc., Washington, DC, 3 APD/RD, BASF Corp., Research Triangle Park, NC, 4 Surface Chemistry, Akzo Nobel, LLC, Chicago, IL, 5 Crop Care Applications, Croda, Inc., New Castle, DE and 6 Regulatory Affairs, Syngenta Crop Protection, Inc., Greensboro, NC. The poster illustrates the use of read-across methodology and dietary risk assessment for oleochemical surfactants that are used as inert ingredients in pesticide formulations. The August 9, 2006, revocation of 130 food tolerance exemptions resulted in unprecedented challenges for EPA and industry (pesticide registrants and surfactant manufacturers) to evaluate reproductive and developmental toxicity for more than 20 classes of inert ingredients within three years. Structurally similar compounds have similar physical, metabolic and toxicological properties. It is possible to bridge (read-across) results from one compound to others within a defined cluster of chemically-related compounds. EPA and the OECD applied cluster analysis in the High Production Volume (HPV) Programs to reduce the number of toxicity tests, laboratory animals and the time required to review the study data. The same methodology was successfully used to conduct OECD 422 Studies (Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Tests) data development plans. The OECD 422 test results were used in conjunction with the EPA screening-level dietary exposure model for inert ingredients (I-DEEM) to assess dietary exposure and risks for the US population, adults and children. The methodology was validated and resulted in the successful reassessment and retention of the food use tolerance exemptions of the inert ingredients. 1527 OPTIONS FOR INCREASED REGULATORY OVERSIGHT OF COSMETICS IN THE U.S. N. Beck 1 , K. Sullivan 1 and C. Willet 2 . 1 Physicians Committee for Responsible Medicine, Washington, DC and 2 People for the Ethical Treatment of Animals, Norfolk, VA. Cosmetics have recently become one of the focal points of efforts to strengthen chemical regulations in the US. Under the current law, cosmetics manufacturers are responsible for substantiating the safety of their products, but for most ingredients, 328 SOT 2011 ANNUAL MEETING specific toxicity testing is not required, nor is pre-market approval from the Food and Drug Administration (FDA). Concern over the long-term safety of cosmetics has prompted legislative efforts to increase oversight. Emerging regulatory models in the US were analyzed, namely the “FDA Globalization Act of 2009” and the “Safe Cosmetics Act of 2010.” Specifically, each bill’s approach to hazard and risk assessment, was examined, including their flexibility in information requirements and potential for incorporating evolving science. Then, current US cosmetics regulations were compared with international approaches, revealing broad agreement overall. Finally, the proposed US models were addressed in the context of the EU’s distinctive position on animal testing. EU law gradually phases out the use of animals for cosmetics testing, with a complete ban on the marketing of animal-tested products by 2013. The market ban presents significant implications for trade with the EU, which should be considered when drafting new legislation in the US. The testing and marketing prohibitions in the EU have also impacted the state of regulatory toxicology, with the impending ban serving as a tool to drive progress in the development of in vitro and in silico test methods. In order to efficiently assess cosmetic ingredients and advance international harmonization, proposals to reform US cosmetics regulations should seek to facilitate the development of modern, harmonized approaches to testing and assessment. 1528 THE SHE CELL TRANSFORMATION ASSAY—ITS USE IN HAZARD AND RISK ASSESSMENT FOR REACH. A. H. Poth. Genetic and Alternative Toxicology, Harlan Cytotest Cell Research GmbH, Rossdorf, Germany. The 2-year bioassay is the standard method for carcinogen detection which is time and resource intensive. Many short-term test, especially genotoxicity tests have been developed to aid in identification of potential carcinogens. However, the endpoint of theses systems is genotoxicity and their concordance between rodent bioassays is only about 60% and a battery of short-term genotoxicity tests can not improve the overall concordance. In vitro cell transformation tests using SHE- and Balb/c3T3-cells simulate the process of animal two-stage carcinogenesis. These tests are suited for the in vitro detection of a carcinogenic potential of test compounds in safety and risk assessment. Results from cell transformation assays can provide information, which in combination with data from other testing methods, are useful for identifying the carcinogenic potential of chemical compounds. The results of these assays in combination with other information such as genotoxicity data, structure activity analysis, in vivo toxicity data and pharmaco-/toxicokinetic information can facilitate a relatively comprehensive assessment of a carcinogenic potential of a chemical. For prediction of the carcinogenic potential of compound the SHE cell transformation assay is included in the endpoint specific guidance document for REACH. In the first phase of REACH (substances > 1000 tonnage per year), data of the SHE cell transformation were included in the hazard and risk assessment. Case studies are provided for heavy metal powders and alloys, where the SHE cell transformation data were used for mechanistic investigations beside other in vitro test systems. SHE cell transformation data are also provided of a chemical class (aromatic amines) where genotoxicity data do have only limited value and for a compound with an structural alert for carcinogenicity (pararosaniline derivatives), where SHE cell transformation data were used to demonstrate the similarities across a chemical category. 1529 DEVELOPMENT OF A HEALTH RISK-BASED SURFACE CONTAMINATION CLEAN-UP STANDARD FOR OCCUPATIONAL EXPOSURE TO BERYLLIUM. P. Damian. SCS Engineers, West Sacramento, CA. A health risk-based surface contamination cleanup standard (SCS) for beryllium (BE) was developed to facilitate the safe transfer of property (equipment and buildings) previously used in BE-related processes. Previous SCSs for BE were primarily based on Department of Energy (DOE) housekeeping criteria rather than health risks. Quantitative health risk assessment methods were used to develop an occupational SCS that explicitly considers the relevant exposure pathways and toxicity endpoints, including both cancer and non-cancer endpoints. For the cancer endpoint at the 1E-06 risk level, the analysis resulted in an SCS of 17 μg/100 cm 2 based on resuspension of settled dust and subsequent inhalation exposure only (BE is regulated as a carcinogen by the inhalation route only). For the non-cancer endpoint, the analysis resulted in an SCS of 0.07 μg/100 cm 2 based on dermal absorption, incidental ingestion following dermal contact, and inhalation. The non-cancer SCS was determined virtually entirely by the dermal absorption exposure pathway, with negligible contributions from the incidental ingestion and inhalation pathways. This analysis shows that application of the non-cancer SCS in BE monitoring and control programs will adequately protect workers from both the cancer and non-cancer health effects of BE when surface contamination is the primary source of BE exposure.
1530 MINIMAL RISK LEVELS FOR STYRENE. S. Chou 1 and L. Ingerman 2 . 1 Division Toxicology and Env.Med. ., ATSDR/CDC, Atlanta, GA and 2 SRC, Inc., Syracuse, NY. Sponsor: B. Fowler. Styrene is a high production chemical. Manufactured styrene is primarily used in the production of polystyrene plastics, resins and copolymers. In the general population, exposure to styrene occurs primarily by inhalation of contaminated indoor air and can be attributed to emissions from building materials, consumer products and tobacco smoke. The workplace or home office may have substantially higher levels of airborne styrene, due to emissions from laser printers and photocopiers. Exposure to styrene may also occur through ingestion of contaminated food or water. The inhalation and oral database provides evidence that the nervous system is the most sensitive target following acute and chronic duration exposures to styrene. After reviewing the literature, an MRL of 5 ppm was derived for acute-duration inhalation exposure to styrene based on no-observed-adverse-effect level (NOAEL) for alterations in tests of reaction time, memory, attention, color discrimination and olfactory threshold in humans (Ska et al. 2003) and an MRL of 0.2 ppm was derived for chronic-duration inhalation exposure based on lowest-observed-adverse-effect level (LOAEL) for neurological effects from a meta-analysis of occupational exposure studies (Benignus et al. 2005). In addition, an MRL of 0.1 mg/kg/day for styrene was derived for acute-duration oral exposure based on for impaired learning in rats (Husain et al. 1985). These MRLs are presented and discussed in the ATSDR toxicological profile for styrene released in September 2010. These substance-specific health guidance values are intended to serve as screening levels for use by health assessors and other responders to identify contaminants and potential health effects that may be of concern at hazardous waste sites. 1531 RISK ASSESSMENT FOR ETHYL TERTIARY-BUTYL ETHER (ETBE) TO DETERMINE ACCEPTABLE DRINKING WATER LEVELS. V. S. Bhat, G. L. Ball and C. J. McLellan. NSF International, Ann Arbor, MI. ETBE can be detected in the extract water of some cross-linked polyethylene pipes that convey potable water. Human oral data for ETBE were not identified. In the key study, chronic drinking water exposure was associated with increased kidney weights and exacerbated chronic progressive nephropathy (CPN) severity in male and female F344 rats. The rats appeared to compensate for the reduced palatability of ETBE, so the results were considered reliable for interpretation. Available data support that the liver effects after gavage or inhalation exposure are mediated by adaptive mechanisms to metabolizing high or bolus ETBE doses as they were not observed after drinking water exposure. There are insufficient data to establish a mode of action other than α-2μ-globulin nephropathy in male rats. Interim sacrifices were not included to allow for histological assessment of kidney tubules in a less marked CPN stage. Recognizing the challenge in interpreting chemical-specific renal toxicity in rats with advanced CPN and α-2μ-globulin nephropathy, the point of departure for the Reference Dose (RfD) was the BMDL 10 of 220 mg/kgday for exacerbated CPN severity in female rats. Exacerbated CPN severity was more amenable to benchmark dose modeling thus providing more confidence for risk assessment compared to kidney weight data. The dose metric was the received dose due to insufficient kinetic data to construct of model describing ETBE or its metabolites in blood, urine or target tissue for use as an internal dose metric. No tumor incidences were statistically increased in the key study and ETBE has low genotoxic potential. Using U.S. EPA (2005) guidelines, there is inadequate information to assess carcinogenic potential of ETBE due to the lack of chronic data in a second species. Gavage exposure during pregnancy was associated with maternal toxicity with no specific effects on reproduction or development. A 300-fold uncertainty factor was applied to the BMDL 10 to obtain a RfD of 0.7 mg/kg-day. This corresponds to a Total Allowable Concentration of 5 mg/L in drinking water assuming a 70 kg adult drinks 2 L/day. 1532 HEALTH RISK ASSESSMENT FOR HYDROGEN PEROXIDE TO DETERMINE ACCEPTABLE DRINKING WATER LEVELS. G. L. Ball, J. C. English and C. J. McLellan. NSF International, Ann Arbor, MI. Acceptable levels for hydrogen peroxide (H 2 O 2 ) in drinking water were determined due to its use as a drinking water disinfectant in combination with a small amount of silver. H 2 O 2 participates in the maintenance of cellular homeostasis at endogenous, physiologic levels, and low exposure concentrations can induce the adaptive up-regulation of antioxidant enzymes. At progressively higher levels, a pro-inflammatory response is provoked and oxidative stress ensues. Local irritation occurs with time and concentration dependence, and catalase, among other enzymes, participates in the removal of H 2 O 2 from tissue. The critical effects observed in laboratory animals included dose-dependent increases in glandular stomach erosion, duodenal hyperplasia, and duodenal carcinoma in mice given H 2 O 2 chronically in drinking water. The lesions correlated inversely with catalase activity and were attributed to chemical irritation. H 2 O 2 in vitro induced forward and reverse mutations, chromosomal aberrations, DNA damage/repair, and sister chromatid exchanges. The lack of genotoxicity in vivo is likely related to detoxifying enzyme activities and endogenous radical scavenging substances. Although H 2 O 2 produced duodenal carcinomas upon repeated administration in drinking water to catalasedeficient mice, these tumors failed to metastasize and hyperplasia readily resolved upon cessation of treatment. The data support the classification of suggestive evidence of carcinogenic potential, based on U.S. EPA (2005) guidelines for carcinogen risk assessment. The data additionally support a low-dose nonlinear mode of action and H 2 O 2 was evaluated accordingly. A 100-fold uncertainty factor was applied to the BMDL 05 of 49 mg/kg-day for duodenal hyperplasia from a subchronic drinking water study in catalase-deficient mice to obtain a Reference Dose (RfD) of 0.5 mg/kg-day. The RfD corresponds to a Total Allowable Concentration of 8 mg/L in drinking water assuming a 70 kg adult drinks 2 L/day, taking into account the fact that the major known non-drinking water sources of ingested H 2 O 2 constitute approximately 50% of the oral RfD. 1533 LEAD SOIL SCREENING LEVELS AND CLEAN-UP AT CALIFORNIA HAZARDOUS WASTE SITES. T. Behrsing 1 , J. Carlisle 2 , E. Sciullo 1 , J. Spearow 1 , B. Davis 1 , K. Day 1 and M. Wade 1 . 1 Department of Toxic Substances Control (DTSC), CalEPA, Sacramento, CA and 2 Office of Environmental Health Hazard Assessment (OEHHA), CalEPA, Sacramento, CA. In 2007, CalEPA developed a new toxicity evaluation of lead replacing the 10 μg/dL threshold blood lead concentration (PbB) with a source-specific “benchmark change” of 1 μg/dL (the estimated incremental increase in children’s PbB reducing IQ by 1 point). Here we show the resulting derivation of the revised California Human Health Screening Levels (CHHSLs) using the new PbB criterion and newer blood lead population data. The updated CHHSLs of 80 and 320 mg/kg lead in soil for residential and industrial/commercial land use scenarios, respectively, are lower than previous Cal-modified USEPA Region 9 Preliminary Remediation Goals of 150 and 800 mg/kg. To evaluate lead risk and cleanup options, DTSC recommends calculating the 95 percent upper confidence limit on the arithmetic mean (95%UCL) lead concentration. If individual samples exceed the CHHSL, the exposure area itself would not exceed the CHHSL as long as the 95%UCL is below the CHHSL (assuming no hot spots). If data are insufficient to calculate a 95%UCL, comparison of the maximum detected concentration to the CHHSLs is appropriate. In such cases, additional sampling or cleanup may be warranted. In our experience, the upper lead concentration associated with a 95%UCL of 80 mg/kg is about 150 mg/kg unless there are hot spots. At sites A and B (with maximum lead concentrations of 2078 and 4100 mg/kg) removing samples with lead above 144 and 180 mg/kg lead, respectively, results in predicted 95%UCLs of ~80 mg/kg. The actual maximum threshold for lead to achieve a specific 95%UCL for a given site depends on many factors such as contaminant distribution and confirmation sampling results. Depending on site-specific conditions, cleanup goals consistent with a 95%UCL equal to the revised residential CHHSL can be approached by excavating contaminated soils with lead concentrations above approximately twice the revised CHHSL. A 95%UCL should be calculated using remaining soil and confirmation sampling data following remediation. 1534 MYCOTOXINS: U.S., CANADIAN, EUROPEAN, AND JECFA REGULATORY STRATEGIES. S. H. Henry. Center for Food Safety and Applied Nutrition, U.S. FDA, Greenbelt, MD. U.S., Canadian, European, and JECFA (Joint World Health Organization/Food and Agriculture Organization Expert Committee on Food Additives) approaches to safety/risk assessment and regulatory guidance for mycotoxins of concern for human health, including aflatoxins and ochratoxin, will be summarized and compared. Aflatoxins are found in human and amimal foods, such as peanuts,corn and tree nuts as a result of fungal contamination during growth and after harvest. The U.S. Food and Drug Administration in its risk asesment of aflatoxin attempted to separate the risk of liver cancer attributed to aflatoxin from the risk from other factors, such as hepatitis B and C. This risk-based approach will be contrasted to an “as low as reasonably achievable” (ALARA) or European approach to aflatoxin standards. The conclusions of the JECFA regarding a safety/risk assessment of the potent liver carcinogen aflatoxin will be discussed with reference to the Codex Alimentarius Commission standards for aflatoxins in tree nuts (almonds, hazelnuts and pistachios) intended for further processing and ready-to-eat trade categories. SOT 2011 ANNUAL MEETING 329
Page 1 and 2:
The Toxicologist Supplement to Toxi
Page 3 and 4:
The Toxicologist Supplement to Toxi
Page 5 and 6:
1 BIODEGRADABLE MATERIALS FOR TISSU
Page 7 and 8:
that genetic toxicology data are ge
Page 9 and 10:
well-orchestrated lung inflammation
Page 11 and 12:
scribed in the literature. We have
Page 13 and 14:
years ago). We will illustrate how
Page 15 and 16:
involved in the biodegradation proc
Page 17 and 18:
stem cells but rather a treatment i
Page 19 and 20:
additional compound showed agreemen
Page 21 and 22:
82 COMPARISON OF 3H-THYMIDINE INCOR
Page 23 and 24:
irritants. While in practice these
Page 25 and 26:
alleles are especially vulnerable t
Page 27 and 28:
109 CD4+ T CELL INTRINSIC TNF RECEP
Page 29 and 30:
118 TO STUDY THE SIGNAL TRANSDUCTIO
Page 31 and 32:
PAHs, such as dioxins, are prevalen
Page 33 and 34:
containing substituents and/or hydr
Page 35 and 36:
146 COMPUTATIONAL MODELING FOR QT P
Page 37 and 38:
suggest that the combination of too
Page 39 and 40:
164 TRANSLOCATOR PROTEIN (18 KDA) (
Page 41 and 42:
function as a metal binding protein
Page 43 and 44:
laboratory has demonstrated that NR
Page 45 and 46:
known. The aim of this study was to
Page 47 and 48:
from 5 to 28 days in duration) in e
Page 49 and 50:
positive cells, caspase-3 activatio
Page 51 and 52:
creased level in the 46 kDa preproe
Page 53 and 54:
invasiveness at concentrations repr
Page 55 and 56:
thracene (DMBA,50 μg in acetone, a
Page 57 and 58:
247 CO-CARCINOGENESIS OF N, N- DIET
Page 59 and 60:
sponds to the endosomal dsRNA that
Page 61 and 62:
ODD in both WT (maximum 177% of con
Page 63 and 64:
Lastly, using p53siRNA cells, p53 w
Page 65 and 66:
its receptor Mpl to exert its funct
Page 67 and 68:
294 LOW LEVEL OF LEAD CAN INDUCE PH
Page 69 and 70:
lunar surface presented potential h
Page 71 and 72:
lar about cellular export mechanism
Page 73 and 74:
DNA in the kidney medulla, grandula
Page 75 and 76:
5.00 and 7.50 mg/kg/day by oral gav
Page 77 and 78:
events and carcinogenesis. Here we
Page 79 and 80:
tinization of cells of the hair fol
Page 81 and 82:
358 CHARACTERIZATION OF GENOME-WIDE
Page 83 and 84:
RNAi were also performed to identif
Page 85 and 86:
376 A FUNCTIONAL CROSSTALK BETWEEN
Page 87 and 88:
UGT1A gene induction, while this re
Page 89 and 90:
tivity, specifically peroxisome pro
Page 91 and 92:
and cytotoxic effects; however, its
Page 93 and 94:
histone deacetylase that is necessa
Page 95 and 96:
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
Page 127 and 128:
and lethality associated with these
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 and 148:
tion revealed no test article-relat
Page 149 and 150:
671 INFLAMMATION AND TISSUE DAMAGE
Page 151 and 152:
model, ethanol was found to inhibit
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
Page 173 and 174:
lood cell mass and decrease in urin
Page 175 and 176:
practical alternatives to MC in non
Page 177 and 178:
imals dosed with 167 mg/kg THU alon
Page 179 and 180:
and organ weights, clinical signs a
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
Page 197 and 198:
sue. The depth of our analysis led
Page 199 and 200:
910 IMPLEMENTING CALIFORNIA’S GRE
Page 201 and 202:
concentrations in six tissues and b
Page 203 and 204:
934 THE FDA’S LIVER TOXICITY KNOW
Page 205 and 206:
943 GENOME-WIDE DNA METHYLATION DIF
Page 207 and 208:
membrane localization and subsequen
Page 209 and 210:
trols, respectively. Subtoxic and t
Page 211 and 212:
survival using both smoking regimes
Page 213 and 214:
as non-, weak, moderate, or strong
Page 215 and 216:
988 NNK-INDUCED CYTOKINE ALTERATION
Page 217 and 218:
group (one-way ANOVA, p90 % viabili
Page 219 and 220:
ered as an organ involved in xenobi
Page 221 and 222:
Transport of CPZ across the Caco-2
Page 223 and 224:
estrous cycle and sexual behavior d
Page 225 and 226:
mRNA expression levels. Collectivel
Page 227 and 228:
1043 THE EFFECTS OF ENDOCRINE DISRU
Page 229 and 230:
1052 MONO-2-ETHYLHEXYL PHTHALATE IN
Page 231 and 232:
Results: MC was variable within and
Page 233 and 234:
UtSMCs. Phosphorylation of FoxO1 wa
Page 235 and 236:
nonpregnant and pregnant diabetic m
Page 237 and 238:
1089 PFOA-INDUCED LIVER EFFECTS IN
Page 239 and 240:
events in the liver. AZD9056 was ev
Page 241 and 242:
The peppermint oil caused a concent
Page 243 and 244:
OA did not affect food consumption.
Page 245 and 246:
1126 PERSISTENT DEVELOPMENTAL ARYLH
Page 247 and 248:
1135 BACH2 BINDING TO Prdm1 AS A ME
Page 249 and 250:
The purpose of this project was to
Page 251 and 252:
one marrow. Since Chk1 is an attrac
Page 253 and 254:
1163 THE MRNA AND MIRNA PROFILE OF
Page 255 and 256:
have now compared the IC50 values b
Page 257 and 258:
1181 ELUCIDATION OF FACTORS DETERMI
Page 259 and 260:
enced by pre-exposure to cigarette
Page 261 and 262:
if abnormal PF was associated with
Page 263 and 264:
weight (P=0.016) and small for gest
Page 265 and 266:
portant cause of death, compared to
Page 267 and 268:
posure groups. However, the differe
Page 269 and 270:
Naphthalene is routinely analyzed i
Page 271 and 272:
1245 SEASONAL CHARACTERIZATION OF H
Page 273 and 274:
1255 URINARY T, T MUCONIC ACID LEVE
Page 275 and 276:
modating a reliable data evaluation
Page 277 and 278:
enzoquinone generate ROS and arylat
Page 279 and 280:
teins (e.g. C3, 4, and 5, APOB, VDB
Page 281 and 282: 1293 TRANSFORMING GROWTH FACTOR BET
Page 283 and 284: mation was decreased to the same le
Page 285 and 286: 1312 EVALUATION OF THE SENSITIVITY
Page 287 and 288: luted OFR and CRL. Culture media ex
Page 289 and 290: urinary TCPy levels, blood and brai
Page 291 and 292: activity. The dose-response curves
Page 293 and 294: mice, each with 4 dose groups. One
Page 295 and 296: exposure to both ATR and DACT has a
Page 297 and 298: third tetratricopeptide repeats (TP
Page 299 and 300: 7d. 28d after TMT injury there was
Page 301 and 302: subunits. Each cell type was treate
Page 303 and 304: 1394 COMPARATIVE EFFECTS OF METHYLM
Page 305 and 306: 1403 GENOTOXICITY AND PRE-NEOPLASTI
Page 307 and 308: vated only in high-dose-treated ani
Page 309 and 310: 1421 DOSE-RESPONSE OF NAPHTHALENE-I
Page 311 and 312: cisplatin; 1.2-, 1.9- and 2.9-fold
Page 313 and 314: Day 11 and started to recover on Da
Page 315 and 316: 1448 DEVELOPMENT OF A METHOD FOR QU
Page 317 and 318: 1457 GLOBAL GENE PROFILING REVEALS
Page 319 and 320: cluding mouse and human macrophage,
Page 321 and 322: model of lung inflammation and host
Page 323 and 324: 1484 NANOTOXICOLOGY AND NANOHEALTH
Page 325 and 326: throughput in vitro approach was us
Page 327 and 328: 1502 IMMUNOLOGICAL ASPECTS OF AN AN
Page 329 and 330: (CIA) and the Streptococcal cell wa
Page 331: sitizers were 100% concordant among
Page 335 and 336: ical groups in the field of regulat
Page 337 and 338: vitro with this potentially insect-
Page 339 and 340: their performance on toxicological
Page 341 and 342: need for a better understanding of
Page 343 and 344: 1577 AN IN VITRO MODEL SYSTEM FOR A
Page 345 and 346: gene expression post-transcriptiona
Page 347 and 348: 1595 GENE EXPRESSION PROFILE OF RAT
Page 349 and 350: to confirm a hepatotoxic property o
Page 351 and 352: 1613 AN INVESTIGATION OF THE CLEARA
Page 353 and 354: its nuclear translocation was reduc
Page 355 and 356: were collected from TK animals at d
Page 357 and 358: egulated targets were selected for
Page 359 and 360: U/L after tetracycline. Minocycline
Page 361 and 362: peri-pubertal FasL-/- mice show a d
Page 363 and 364: showed similar levels of apoptosis
Page 365 and 366: 1676 TWO BIOMARKERS FOR EVALUATION
Page 367 and 368: motifs selected. This system was ap
Page 369 and 370: 1693 VOC SERUM LEVELS IN THE GENERA
Page 371 and 372: 1702 DOES THE CLOCK MAKE THE POISON
Page 373 and 374: those with high nickel content are
Page 375 and 376: isk assessment. However, unique cha
Page 377 and 378: model of APAP metabolism and glutat
Page 379 and 380: logically & morphologically similar
Page 381 and 382: posure, blood chemistry was analyze
Page 383 and 384:
elated to oxidative stress by measu
Page 385 and 386:
ostasis), but work is needed to tra
Page 387 and 388:
tokine products during carcinogenes
Page 389 and 390:
ways as chemical stressors and, the
Page 391 and 392:
toxicity of nanomaterials relates s
Page 393 and 394:
1815 MEASURING COMPOUND SELECTIVITY
Page 395 and 396:
1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398:
cyanoacetic acid increased 2-3 fold
Page 399 and 400:
1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402:
crorarray analysis. RT-PCR results
Page 403 and 404:
are a family of phase-II biotransfo
Page 405 and 406:
ous labs. As a result of positive s
Page 407 and 408:
down the doses may produce more tox
Page 409 and 410:
spectively. Below 100 mg/l of gemfi
Page 411 and 412:
1900 GENERATION OF PRECISION CUT LI
Page 413 and 414:
iomarkers or observation of lesions
Page 415 and 416:
creased reticulocytes and lymphocyt
Page 417 and 418:
statistically significant interacti
Page 419 and 420:
monize sample preparation and analy
Page 421 and 422:
NPC and sinonasal cancer in neighbo
Page 423 and 424:
showed incidences of lung and nasal
Page 425 and 426:
utylbenzenes, exhibited most simila
Page 427 and 428:
1975 DIFFERENTIAL MODULATION OF CYP
Page 429 and 430:
organic As to MMA(V) and a lower ca
Page 431 and 432:
ole in invasion and metastasis of c
Page 433 and 434:
3T3-L1 cells to low-levels of arsen
Page 435 and 436:
2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438:
This work was supported by Cooperat
Page 439 and 440:
2029 EFFICACY OF ENDOTRACHEAL ADMIN
Page 441 and 442:
Diazepam injections and its combina
Page 443 and 444:
2047 ESTERASE ACTIVITIES AND HEMOST
Page 445 and 446:
nanoparticle-induced toxicity progr
Page 447 and 448:
house, were iv infused into rats ov
Page 449 and 450:
een explored. This study investigat
Page 451 and 452:
croscopic analysis revealed that on
Page 453 and 454:
egg yolk collected from turtles inh
Page 455 and 456:
consistency of results in both expe
Page 457 and 458:
2111 CYTOCHROME P450 3A5 GENOTYPE I
Page 459 and 460:
esidues of organophosphates or thei
Page 461 and 462:
manganism. Recent work from our lab
Page 463 and 464:
Aβ1-40 in CSF and hippocampus in P
Page 465 and 466:
2147 CATALASE MANIPULATIONS MODIFY
Page 467 and 468:
ation based on real-world exposure
Page 469 and 470:
NPs. Aggregation of citrate-stabili
Page 471 and 472:
2175 THE ROLE OF SURFACE CHEMISTRY
Page 473 and 474:
seen rapid uptake in biological ima
Page 475 and 476:
effect on uterine weight or vaginal
Page 477 and 478:
dicating widespread exposure. While
Page 479 and 480:
components into the liver parenchym
Page 481 and 482:
2223 ISOLATION AND DETECTION OF RIC
Page 483 and 484:
stored (-20 celsius degree). The co
Page 485 and 486:
2241 DDA, A BIOMARKER FOR ENVIRONME
Page 487 and 488:
2249 INTERACTION BETWEEN DIETARY SE
Page 489 and 490:
2258 PHARMACOKINETICS, EXCRETION BA
Page 491 and 492:
2267 SENSITIVE AND SPECIFIC FLUORES
Page 493 and 494:
2276 METABOLISM AND DISPOSITION OF
Page 495 and 496:
ment of hypertension in companion a
Page 497 and 498:
for the propyl series can be used f
Page 499 and 500:
2304 IN VITRO EXPOSURE AND EVALUATI
Page 501 and 502:
2313 THE SYNERGISTIC EFFECT OF SODI
Page 503 and 504:
genes that play a crucial role in M
Page 505 and 506:
2330 THE ROLE OF TRANSFORMING GROWT
Page 507 and 508:
ined following up to 96 h continuou
Page 509 and 510:
effect doses obtained with the rat
Page 511 and 512:
diated transcriptional response of
Page 513 and 514:
docrine disruptor activities of EDC
Page 515 and 516:
individuals. Week 6 results were qu
Page 517 and 518:
functionality of photosystem II and
Page 519 and 520:
wild mice (Mus musculus) from areas
Page 521 and 522:
2406 TOXICITY AND BIOACCUMULATION O
Page 523 and 524:
Isocitric acid is the acid in the h
Page 525 and 526:
2425 EFFECTS OF FUMONISINS IN ETHAN
Page 527 and 528:
centration(μg/g) were: 5.1-95.3; 2
Page 529 and 530:
2445 AUTOPHAGY IN DEVELOPMENT: A LI
Page 531 and 532:
sures to inhaled Mn in dust. Nevert
Page 533 and 534:
2466 CRITICAL EVALUATION OF ANIMAL
Page 535 and 536:
elationships predict that resting r
Page 537 and 538:
2489 COMPARATIVE TOXICITY OF BIODIE
Page 539 and 540:
2497 TRANSCRIPTIONAL REGULATION OF
Page 541 and 542:
2506 TOXICOLOGICAL CONSIDERATIONS O
Page 543 and 544:
launched with the aim of developing
Page 545 and 546:
forms mRNA expression levels were a
Page 547 and 548:
2534 CUTANEOUS WOUND HEALING IN THE
Page 549 and 550:
wells (0, 1, 5, 10, 25, 50, 100, an
Page 551 and 552:
2553 AN ORGANOTYPIC MICROLIVER PLAT
Page 553 and 554:
serum-free media. At 24 hrs, the gr
Page 555 and 556:
2572 INCREASED ARSENIC BIOACCESSIBI
Page 557 and 558:
nology to develop improved methods.
Page 559 and 560:
tuna, swordfish, or mako shark (3.5
Page 561 and 562:
nificantly reduce circulating thyro
Page 563 and 564:
grouped into 9 observation periods
Page 565 and 566:
histopathological or biochemical ev
Page 567 and 568:
exhibited a hyperactive phenotype,
Page 569 and 570:
the search of effective drugs for e
Page 571 and 572:
2644 COVALENT BINDING OF 14 C 2-MET
Page 573 and 574:
aries targeting all transcription f
Page 575 and 576:
(p 9 weeks) and CSC phenotype acqui
Page 577 and 578:
2673 IMMUNE-MEDIATED VASCULAR INJUR
Page 579 and 580:
for risk identification and charact
Page 581 and 582:
to control toxicant delivery in tob
Page 583 and 584:
Author Index (Continued) The numera
Page 585 and 586:
Page 587 and 588:
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Page 607 and 608:
Page 609 and 610:
Page 611 and 612:
Keyword Index (Continued) Arsenite
Page 613 and 614:
Keyword Index (Continued) Covalent
Page 615 and 616:
Keyword Index (Continued) flow cyto
Page 617 and 618:
Keyword Index (Continued) innate im
Page 619 and 620:
Keyword Index (Continued) nanoparti
Page 621 and 622:
Keyword Index (Continued) preservat
Page 623 and 624:
Keyword Index (Continued) Thrombocy
Page 625 and 626:
Toxicological Sciences The Official
show all

The Toxicologist - Society of Toxicology

Create successful ePaper yourself

Delete template?

Save as template?