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889 APPLICATION OF TISSUE-TIME COURSE DATA TO ELUCIDATE MECHANISTIC DETAILS OF CARBON TETRACHLORIDE (CCL4) TRANSPORT USING AN UPDATED PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODEL IN RATS. M. V. Evans 1 , C. R. Eklund 1 , U. Y. Sanzgiri 2 , J. V. Bruckner 2 and J. E. Simmons 1 . 1 Pharmacokinetics, U.S. EPA, Research Triangle Park, NC and 2 Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA. CCl4 is a common environmental contaminant in water and superfund sites, and a model liver toxicant. One application of PBPK models used in risk assessment is simulation of internal dose for the metric involved with toxicity, particularly for different routes of exposure. Time-course pharmacokinetic data for different tissues (Sanzgiri et al., 1997) were used to evaluate a rat PBPK model employing previous metabolic estimates. The flow-limited PBPK model contained: fat, liver, brain, rapidly and slowly perfused compartments. Arterial concentration data measured for 100 or 1000 ppm constant inhalation exposure lasting 2 hours were used to evaluate the initial PBPK predictions. These simulations were able to describe the timecourse data well at both inhaled concentrations. However, a closer examination of tissue uptake data of 1000 ppm CCl4 revealed an inconsistency with the preliminary simulations. Upon further evaluation of tissue time-course results, the PBPK model underpredicted brain and fat tissue concentrations. Also, the peak arterial concentration was about twice that predicted by the initial calibration simulation. Further modeling is needed to incorporate physiological and structural details (i.e. diffusion) that may be taking place at higher exposure concentrations. Ongoing model refinement strategies will include: (1) addition of a blood brain barrier component (for brain tissue), and (2) a diffusion-limited compartment for fat, and (3) diffusion in the respiratory tract during the breathing cycle. Diffusion may help explain the difference between observed and predicted tissue concentrations. In summary, tissue time-course data are essential for the determination of mechanistic detail for different organs, and the accurate prediction of internal liver dose. (This abstract does not reflect EPA policy.) 890 ALTERNATIVE APPROACH TO MAXIMUM FLUX FOR TTC APPLIED TO SAFETY EVALUATION OF COSMETIC INGREDIENTS. A. Garrigues-Mazert, S. Grégoire and J. Meunier. Safety Research Department, L’Oréal, Aulnay sous Bois, France. Sponsor: G. Nohynek. Relevant and accurate prediction of dermal uptake/exposure of topically applied chemicals is essential for risk assessment. It could be obtained without recourse to an experimental measurement and avoids any problems with ethical issues, recruiting volunteers or housing animals. Typically, QSAR model predicting permeability coefficients (i.e. kp) are used. Many models were developed; all of them lead to the same conclusion: small lipophilic chemicals have greatest skin permeability. This analysis often rises to confusion. Dataset used to build up this relation concerns percutaneous transport from aqueous solution. Whereas, kp increases with log P, aqueous solubility decreases with lipophily. Resulting flux, and effective absorbed amount of chemical, is then balanced between two competitive factors (permeability and solubility). Concept of maximum flux means that a chemical cannot cross the skin higher than flux measured at steady state with a chemical applied on the surface in saturated solution (or in neat chemical form). It allows assessing the maximum absorbed dose. This concept was recently used in TTC approach for cosmetic ingredient. A classification of potential of cutaneous chemical absorption was proposed on the basis of their physico-chemical properties. Unfortunately, the proposed classification does not cover all range of molecular weight and log P. Moreover, the default proposed values greatly overestimate the absorption experimentally obtained. To overcome these limitations, a QSAR model recently developed by L’Oréal can be used. It estimates the cumulative mass of a chemical absorbed into and through the skin in typical ‘in-use’ cosmetic conditions. Applicability domain is clearly defined and covers a wide range of physico-chemical properties. Moreover, the model was build up with 101 data. More than 90% were well predicted (i.e. difference between predicted and experimental values less than a factor 5). At least, improvement was recently done to take into account property of volatile chemicals. 891 SKIN ABSORPTION STRATEGY: FROM IN SILICO TO EX VIVO. A. Garrigues, S. Grégoire, W. Wargniez, C. Patouillet, I. Durand, J. Becquet and J. Meunier. Safety Research, L’Oreal, Aulnay sous Bois, France. Sponsor: G. Nohynek. Skin is daily exposed to many chemicals that could represent a risk to human health. Thus, determination of cutaneous absorption is a key parameter to evaluate the exposure and assess the risk. Since animal experiments have to be avoided for ethical considerations and for scientific relevance, the bioavailability is typically achieved by conducting relevant in vitro permeation studies in accordance with accepted guidelines. Particularly the OECD guidelines 428 clearly have stated that excised Human skin, or alternatively pig skin, are the most suitable models to predict in vivo dermal absorption. However, limitations of this method are the variability between donors, the availability of skin explants and time consuming for sample preparation. To overcome these limitations and to reduce the number of ex vivo experiments, reliable and widely applicable in silico models and in vitro reconstructed Human epidermis models (RHE) can be used. On one hand, a new QSAR model was developed by L’Oréal Laboratories to estimate a cumulative dose absorbed into the skin with a concordance of more than 90% (I.e. the difference between predicted and experimental data was less than a factor 5). On the other hand, it has been proved that the RHE models Episkin are appropriate alternatives to human skin and useful for ranking chemicals according their skin permeation potential, despite their lower barrier function. To conclude, sequential testing strategy for cutaneous absorption provides information very quickly to prioritize the ex vivo experimental investigations, to predict the permeation of a new chemical entity (even before it synthesis) and to lead to an efficient screening of chemicals. 892 COMPARISON OF ESTIMATED PCB-153 CONCENTRATIONS IN HUMAN MILK USING VARIOUS PHARMACOKINETIC MODELS. D. G. Farrer 1 , M. Poulsen 2 , D. Davoli 3 , M. Bailey 3 , D. Moffett 4 , D. Fowler 4 , C. Welsh 4 , R. Yang 5 , P. Ayotte 6 , M. Verner 7 , G. Muckle 6 and S. Haddad 7 . 1 Oregon DHS, Portland, OR, 2 Oregon DEQ, Portland, OR, 3 U.S. EPA, Seattle, WA, 4 ATSDR, Atlanta, GA, 5 Ray Yang Consulting LLC, Ft. Collins, Co., 6 Centre Hospitalier Universitaire de Québec, Montréal, QC, Canada and 7 Department of Biological Sciences, Université du Québec, Montréal, QC, Canada. Risk to infants from consuming human milk contaminated with lipophilic chemicals is difficult to assess. Typically, risk assessors use measured chemical concentrations in media of concern. Human milk is often difficult to sample for chemical concentrations. Therefore, models that predict chemical levels in human milk and subsequent average daily dose to the nursing infant (ADDi) are desirable. We compared adaptations of three published models in an effort to help risk assessors and public health practitioners choose an appropriate method to estimate ADDi. Models chosen for comparison included a classic single-compartment model, a 3- compartment physiologically-based pharmacokinetic (PBPK) model, and an 8- compartment PBPK model. The models were compared by running two sets of simulations in each model using the polychlorinated biphenyl congener 153 (PCB- 153), a lipophilic environmental contaminant. The first set of simulations used back-calculated average maternal daily oral dose (ADDm) values as starting points. ADDm was calculated using the 8-compartment PBPK model based on PCB-153 blood concentrations measured in 8 human subjects. From derived ADDm values, the models simulated both the milk concentration and ADDi for each subject. Estimated milk concentrations were then compared to observed concentrations. The second set of simulations used an ADDm derived for PCB-153 assuming consumption of contaminated fish. All 3 model results were similar to within a factor of 2. The classic single compartment model consistently produced the highest estimates of PCB-153 concentration in human milk and ADDi. Our results indicate that the simplest model studied may be appropriate for risk assessors and public health practitioners to use for predicting the ADDi for lipophilic environmental contaminants. 190 SOT 2010 ANNUAL MEETING
893 UNVEILING ASSOCIATIONS BETWEEN LACTATIONAL EXPOSURE TO POLYCHLORINATED BIPHENYLS (PCBS ) AND INFANT NEURODEVELOPMENT: USE OF PBPK MODELING VS TRADITIONAL EXPOSURE METRICS. M. Verner 1 , P. Plusquellec 2 , G. Muckle 2 , P. Ayotte 2 , Dewailly 2 , S. W. Jacobson 3 , J. L. Jacobson 3 , M. Charbonneau 4 and S. Haddad 1 . 1 Université du Québec à Montréal, Montréal, QC, Canada, 2 Université Laval, Québec, QC, Canada, 3 Wayne State University School of Medicin, Detroit, MI and 4 INRS-Institut Armand-Frappier, Laval, QC, Canada. Traditional approaches to assess lactational exposure to PCBs in epidemiologic studies rely on levels measured in biologic specimens. Because of the multiple concurrent toxicokinetic processes involved in postnatal exposure, such metrics are unlikely to embody the complete infant internal exposure profile. We conducted this study to compare exposure estimates generated by different approaches and their sensitivity in screening for associations with neurodevelopmental outcomes in northern Québec Inuit infants. Postnatal exposure was calculated using published metrics based on samples of breast milk (1 month postpartum) and infant blood (at 6 months of age) and through PBPK modeling of mother-infant lactational transfer. PCB-153 was used as a proxy of exposure to a mixture of PCBs. As expected, breast milk levels were found to be more highly correlated with cord blood levels than with infant blood levels at 6 months and are, therefore, surrogates of prenatal exposure. When breast milk levels were multiplied by the duration of breast-feeding, estimates were highly correlated with infant blood levels (Pearson r = 0.78). However, PBPK-simulated concentrations were even better predictors of infant levels (Pearson r = 0.86). Using PBPK-simulated monthly area under the curve, associations were found between PCB-153 levels during specific periods and two neurodevelopmental outcomes (mean novelty preference at 6 months and non-elicited activity at 11 months). These associations fell short of significance with traditional exposure metrics. The results of this study provide evidence that complete toxicokinetic profiles estimated by PBPK modeling are better suited than point estimates to assess the neurodevelopmental effects of lactational exposure to PCBs. 895 USING IN VITRO PHARMACOKINETIC AND PHARMACODYNAMIC DATA TO REFINE THE PHARMACOKINETIC MODEL FOR CARBARYL IN THE RAT. M. Yoon 1 , G. Kedderis 2 , Y. Tan 1 and H. Clewell 1 . 1 The Hamner Institutes, Research Triangle Park, NC and 2 Consultant, Chapel Hill, NC. There is increasing interest in applying in vitro data and pharmacokinetic (PK) modeling to improve risk assessments of chemicals in humans. Carbaryl is a widely used anti-cholinesterase (ChE) insecticide with significant human exposure. In the present study, parameters for metabolism and ChE inhibition of carbaryl were determined in vitro to refine the previously developed rat physiologically based pharmacokinetic (PBPK) model. Metabolism was determined in freshly isolated hepatocytes from adult male Sprague Dawley rats. Carbaryl disappearance followed Michaelis-Menten kinetics with Vmax of 1.3 nmol/min/10 6 cells and apparent KM 50 - 80μM. Interactions between carbaryl and ChEs were determined in brain, red blood cells (RBCs), and plasma. Bimolecular inhibition rate constants (Ki) were 2 - 12μM -1 h -1 for acetylcholinesterase (AchE) suggesting differing degrees of sensitivity of AChEs in RBCs, brain, and plasma. The Ki for butyrylcholinesterase (BChE) in plasma was lower than AChE. The rates of regeneration of the carbamylated ChEs were 0.5 - 2h -1 indicating similar rates of recovery for AchE and BChE. These in vitro PK and pharmacodynamic data were extrapolated to whole animal to refine the description of the metabolism and ChE inhibition dynamics of carbaryl in the model. Predicted tissue carbaryl concentrations and ChE inhibition profiles in brain and blood were in better agreement with the observed data compared to the previous modeling, in which the metabolic and ChE inhibition parameters were all estimated from in vivo kinetic data. The refined rat model will be scaled up to a human model with data from in vitro studies using human tissues. The ultimate goal is to demonstrate a process for developing a human PBPK model for risk assessment based on an animal PBPK model augmented with in vitro to in vivo extrapolation approaches using human tissues. The resulting model will be used as a template for developing models for other N-methyl carbamates to support a cumulative risk assessment and interpret biomonitoring data on this class of pesticides. 894 A BBDR-HPT AXIS MODEL FOR THE LACTATING RAT AND NURSING PUP: EVALUATION OF IODIDE DEFICIENCY. S. Li 1 , M. Gilbert 2 , T. Zoeller 3 , K. Crofton 4 , E. McLanahan 5 , D. Mattie 6 , B. Blount 7 , L. Valentin-Blasini 7 , K. Kurunthachalam 8 , T. Kunisue 8 and J. W. Fisher 1 . 1 College of Public Health, University of Georgia, Athens GA, GA, 2 Toxicology Assessment Division, U.S. EPA, Research Triangle Park, NC, 3 Biology Department, University of Massachusetts, Amherst, MA, 4 Integrated Systems Toxicology Division, U.S. EPA, Research Triangle Park, NC, 5 National Center for Environmental Assessment, U.S. EPA, Research Triangle Park, NC, 6 RHPB, USAF/AFRL 711 HPW, Wright-Patterson AFB, OH, 7 CCEHIP/NCEH, CDC, Atlanta, GA and 8 Wadsworth Center, NYS Department of Health, Albany, NY. A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the lactating rat and pup quantify the compensatory mechanisms that govern the relationships between serum and brain thyroid hormone (TH) concentrations in the lactating dam and the nursing neonate, recognizing that these relationships may be affected by the mechanism of toxicity of different compounds. Initially, the model will be used to delineate perturbations in the HPT axis caused by inadequate dietary iodide (ID). Later, environmental toxicants that alter HPT axis homeostasis will be examined. The current model uses the McLanahan et al. (2009) BBDR-HPT axis model for the adult rat as a foundation, but includes several new features: 1) formation rates of THs, 2) negative feedback loop controlled by model-predicted brain concentrations of T3, 3) extrathyroidal metabolism of THs by deiodinase enzymes, 4) regulation of deiodinase II in the brain, 5) serum protein binding of THs, and 6) maternal excretion of TSH and iodide via the milk. Algebraic equations were developed to describe physiological changes for the dam and nursing pups. The model is calibrated to predict perturbations in the HPT axis caused by ID and to ascertain the pup HPT axis tolerance to maternal ID during the nursing period. (Support: U.S. EPA STAR Cooperative Agreement R832134 and AFRL through the Henry Jackson Foundation for the Advancement of Military Medicine Contract 185137. This abstract does not necessarily reflect EPA policy.) 896 LINKING REAL-WORLD PHYSIOLOGY AND EXPOSURES TO PHARMACODYNAMIC ENDPOINTS: A CASE STUDY USING CHLORPYRIFOS. P. M. Hinderliter 1 , P. S. Price 2 , K. D. Schnelle 3 , M. J. Bartels 2 , C. Timchalk 1 and T. S. Poet 1 . 1 Battelle, Pacific Northwest Division, Richland, WA, 2 The Dow Chemical Company, Midland, MI and 3 Dow AgroSciences, LLC, Indianapolis, IN. Physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models are important tools in risk assessment, allowing for the evaluation of the predicted effects of chemical exposures on humans that occur as the result of real world exposures. In a case study using the pesticide chlorpyrifos, dietary doses from two dietary exposure models (CARES and LifeLine) were linked to a PBPK/PD model that evaluates potential effects of chlorpyrifos exposure on brain cholinesterase. Sensitivity analysis identified the key model parameters that strongly impact predicted brain cholinesterase inhibition: cardiac output, liver blood flow, and blood and liver PON1 metabolism (which accounts for deactivation of the active moiety, chlorpyrifos-oxon). Variation in human physiology was characterized by modeling differences in organ size and perfusion based on demographic data of height and body weight in adults and children. Variation in metabolism was modeled based on published data on interindividual variation in P450 and PON1 levels in humans by extrapolating from measured variability of the same enzymes on similar substrates. The impact of variation in activity levels was characterized by varying cardiac output to reflect a range of activity levels from sedentary to active (0.9 to 1.4x base levels). These tools and approaches provide a means of refining interspecies and interindividual uncertainty factors typically used when extrapolating from animal models to humans and from typical (i.e., average or centric) to sensitive individuals. Brain cholinesterase inhibition was predicted from modeling 5 consecutive days of dietary exposure in 1000 adults and children. This analysis predicted no significant impact from these exposures (with inhibition
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIOLOGICAL PATHWAY ANALYSIS: AN I
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11 ICH INITIATIVES FOR CONDUCTING P
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models. Experimental approaches and
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30 SILICA AND ASBESTOS IMMUNOTOXICI
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40 NONCANCER TOXICITY POTENTIAL AT
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ased products for patient administr
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nase regulates Hsp27-induced reorga
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exposure resulted in splenomegaly.
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We investigated the effect of imati
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well plate prevented free cell move
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98 DERIVING SIGNATURES OF IN VIVO T
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sulfate, cinnamic aldehyde, 2,4-din
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The final product will be a system
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mercially available STP brands by m
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for six weeks, with 10 mg/kg azoxym
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eceived RES post-TCDD exposure when
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morigenesis. Knocking down of JARID
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163 MICROPET IMAGING OF [18F]-DFNSH
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These results are comparable to tha
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activity as assessed by lever press
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for measured physico-chemical param
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199 DEVELOPMENT OF A MULTIPARAMETER
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To cause PLD, a drug needs to enter
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In contrast to the parent PBDEs and
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transiently transfected HEK 293 cel
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TCDD exposure, 24 h prior to a 20 %
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244 NON-ADDITIVE EFFECTS OF PCB153
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253 COMPARISON OF MIXTURE TOXICITY
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two cerium oxide nanoparticles of v
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271 SIZE-DEPENDENT EFFECTS OF TUNGS
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adigms such as Tox 21 and Toxcast,
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QDs with emission maximum at 800nm
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Cleveland, while others were found
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without the need of animal testing.
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Conclusions: These results are cons
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ing oxime reactivation and organoph
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335 A NON-OXIME IMPROVES SURVIVAL I
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alties suffer from permanent lung i
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ies have established inflammatory b
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363 GENETIC VARIATION IN ISOGENIC M
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372 EVALUATING THE BIOLOGICAL INTER
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dose of 1/20 LD50 (400 mg/kg.bwt) f
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median CR-adjusted isoflavone conce
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data indicate that AhR deletion pro
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February 2006). The rabbit is one o
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tal neurotoxicity (DNT) test (OECD
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of selected microorganisms that are
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BVI. Histopathological analysis was
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446 MOLECULAR CLONING AND CHARACTER
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portant in predicting risk. CYPs 1A
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ats, which involves metabolic activ
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473 BOVINE CORNEAL OPACITY AND PERM
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482 TYPE III DEIODINASE (D3) IS PRO
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tancy evaluation and ranking of bat
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501 CHARACTERIZATION OF ESTERASE, G
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510 REDOX CYCLING BY ENDOGENOUS 2-
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prostate cancer cells. All 8 BEL de
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metallic nickel nanoparticles. Acti
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variety of more or less reactive ch
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550 QUALIFICATION STRATEGIES-GENOTO
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ferentiation, and 3) how mixtures o
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572 LOW-CHRONIC ARSENIC EXPOSURE: E
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582 IDENTIFICATION OF SENSITIVE URI
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duced by the genetic outcross of fe
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fects of new compounds are equally
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acterize the current state of the s
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620 CHARACTERIZATION OF POTENTIAL I
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ways. Moreover, both MAP kinase and
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641 POPS IN THE U.S. POPULATION AND
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zebrafish cells were first exposed
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utene-1,4-dial, which has been show
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groups, largely due to lower non-HD
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Exposure to gluten in individuals w
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contrast to VGSC activators such as
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1175 70% HYDROFLUORIC ACID (HF) CUT
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axis. An increase in hyaline drople
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1194 esiRNA AND siRNA HIGH-THROUGHP
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1203 ARYL HYDROCARBON RECEPTOR-DNA
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permeability (calcein), mitochondri
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olytic caspase activation, caspase-
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teristics of a human T-type voltage
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80% of the activity from the yellow
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1251 DEVELOPMENTAL EXPOSURE TO DELT
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1260 MANEB ENHANCES MPP + -INDUCED
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demonstrated by knockdown of beclin
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1278 PINK1 AND MITOCHONDRIAL DYNAMI
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treatment for number of live worms.
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1297 INVESTIGATION OF THE NEUROTOXI
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1306 DEVELOPMENT OF AN IN VITRO ASS
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1315 EVALUATION OF 3- AND 1-METHYLH
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prior to kainic acid-induced seizur
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1334 AFFECT OF GENETIC VARIATION ON
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1346 THE OTHER WORLD OF THE TRANSCR
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strate, leading to excess microvesi
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1368 OVERVIEW OF THERAPEUTIC VACCIN
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to a bovine adrenal cortical epithe
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DOTC had no effects. These results
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1398 PULMONARY TOXICITY OF CERIUM D
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PPARα, LXR, ER, AR and AhR activit
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1417 MECHANISM OF GENDER-DIVERGENT
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els, they disrupt homeostatic contr
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were to characterize exposure of th
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1448 ADVERSE OUTCOME PATHWAYS AND E
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the level in urine was 25% of the m
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1;akt-2 double mutant and pdk-1 mut
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jury effects when compared to contr
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tude than equivalent oral doses. Af
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cells; and increased iNOS and MCP-1
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B6.Cg-Kit W-sh mice. These findings
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1511 STATIN-TREATMENT EFFECTIVELY R
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1520 EFFECT OF INHALATION EXPOSURE
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numbers of IFN-γ producing cells w
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These data indicate that TCDD treat
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esponse to allogenic cells, where P
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larly suppressed LPS-induced TNF-α
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1565 INFLUENCE OF EXPOSURE ROUTE AN
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veloping animals to adverse effects
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the observed CL values were 0.07 L/
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which is most relevant for potentia
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tive impairment, suggesting that ox
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1611 AN IN VITRO METABOLOMICS APPRO
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Expression of the β6 integrin (Itg
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ats (10 μg/kg TCDD). Here we repor
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at liver slices and how the metabon
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with gender differences in AUC and
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oxetine (30 mg/kg reduced to 15 mg/
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eleased from necrotic cells where i
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plants, they are present in surface
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ferentiation (quantitative in-cell
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control for macrophage activation).
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to 0.5μg/ml. Minimal inhibitory co
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lines tested. Given that dex and AT
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tion in the absence of an immune re
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treated rats had lower calcium load
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1740 PROFILING COMPOUNDS WITH CARDI
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dothelial cells confirmed caveolin-
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1758 GINKGO BILOBA EXTRACT INDUCES
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arin-induced suppression of MDR1 ex
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1780 ANTIANDROGENIC AND ANTIPROLIFE
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included in the evaluation, most of
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1799 GUIDANCE ON THE APPLICATION OF
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However, substances with EC3 values
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1816 CD-INDUCED EGFR TRANSACTIVATIO
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1826 KERATIN 7 EXPRESSION IN INDEPE
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centa were collected at the time of
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1845 SYSTEMATIC SCREENING OF YEAST
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underlying the development of co-mo
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eing measured in experimental roden
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ufactured in the US for more than 3
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nine (N7-THB-Gua) and N7-hydroxyphe
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1892 EFFECT OF LAMBDA-CYHALOTHRIN O
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22 in Phase I. Antimicrobial pestic
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kinetic and dynamic differences, an
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iphenyl, saccharin and melamine was
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1930 DEVELOPMENT OF A RELATIVE SOUR
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1939 MODE OF ACTION FOR THE CANCER
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human was about 1.5-fold lower (60
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Disruption of BDEC integrity in alp
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1968 A HUMAN HEPG2 LUCIFERASE ASSAY
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in the offspring during tumor devel
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een developed to investigate perfus
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to 131.73 μg/mL for KLH-specific I
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cell lines (ATCC) were cultured in
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flammation and xenobiotic metabolis
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vide many contributions: with its g
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to-metal joint replacement. For exa
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to be addressed or negotiated. Deci
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especially with anti-TNF therapies.
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genic line Tg(are:eGFP) was created
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2074 COMPUTATIONAL ASSESSMENT OF TH
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2084 INHIBITION OF 11β-HSD1 DECREA
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(T) and express several enzymes inv
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2101 GENISTEIN MODULATION OF BLOOD
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males per group were dosed orally o
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ate the feasibility of assessing re
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changed. Hepatic protein carbonyl l
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sought to examine alterations in he
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2147 A SINGLE AMINO ACID CONTROLS T
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Gstm7) was independent of both CAR
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ility of tungsten trioxide (WO3), t
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ured by real-time PCR array and rel
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glucose, and creatinine levels, and
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Several studies have reported suppr
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exposure between TCDD-exposed labor
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Furthermore, with increasing number
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Society of Toxicology 2010 Author I
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Society of Toxicology 2010 Abstract
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49 th Annual Meeting and ToxExpo A
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The Official Journal of the Society
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The Toxicologist - Society of Toxicology

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