U.S. flag

An official website of the United States government

Dot gov

The .gov means it's official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.


ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Journal Articles

Alberga D, Trisciuzzi D, Mansouri K, Mangiatordi GF, Nicolotti O. 2019. Prediction of acute oral systemic toxicity using a multifingerprint similarity approach. Toxicol Sci 167(2):484-495. https://doi.org/10.1093/toxsci/kfy255.

Bell SM, Chang X, Wambaugh JF, Allen DG, Bartels M, Brouwer KLR, Casey WM, Choksi N, Ferguson SS, Fraczkiewicz G, Jarabek AM, Ke A, Lumen A, Lynn SG, Paini A, Price PS, Ring C, Simon TW, Sipes N, Sprankle CS, Strickland J, Troutman J, Wetmore BA, Kleinstreuer NC. 2018. In vitro to in vivo extrapolation for high throughput prioritization and decision making. Toxicol In Vitro 47:213-227. https://doi.org/10.1016/j.tiv.2017.11.016.

Bernasconi C, Pelkonen O, Andersson TB, Strickland J, Wilk-Zasadna I, Asturiol D, Cole T, Liska R, Worth A, Müller-Vieira U, Richert L, Chesne C, Coecke S. 2019. Validation of in vitro methods for human cytochrome P450 enzyme induction: Outcome of a multi-laboratory study. Toxicol In Vitro 60:212-228. https://doi.org/10.1016/j.tiv.2019.05.019.

Borrel A, Kleinstreuer NC, Fourches D. 2018. Exploring drug space with ChemMaps.com. Bioinformatics 34(21):3773-3775. https://doi.org/10.1093/bioinformatics/bty412.

Browne P, Kleinstreuer NC, Ceger P, Deisenroth C, Baker N, Markey K, Thomas RS, Judson RJ, Casey W. 2018. Development of a curated Hershberger database. Reprod Toxicol 81:259-271. https://doi.org/10.1016/j.reprotox.2018.08.016.

Burgdorf T, Peirsma AH, Landsiedel R, Clewell R, Kleinstreuer N, Oelgeschlager M, Desprez B, Kienhuis A, Bos P, de Vries R, de Wit L, Seidle T, Scheel J, Schonfelder G, van Benthem J, Vinggard AM, Eskes C, Ezendam J. 2019. Workshop on the validation and regulatory acceptance of innovative 3R approaches in regulatory toxicology - evolution versus revolution. Toxicol In Vitro 59:1-11. https://doi.org/10.1016/j.tiv.2019.03.039.

Casati S, Aschberger K, Barroso J, Casey W, Delgado I, Kim TS, Kleinstreuer N, Kojima H, Lee JK, Lowit A, Park HK, Regimbald-Krnel MJ, Strickland J, Whelan M, Yang Y, Zuang V. 2018. Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods. Arch Toxicol 92:611-617. https://doi.org/10.1007/s00204-017-2097-4.

Casey WM, Chang X, Allen DG, Ceger P, Choksi NY, Hsieh J-H, Wetmore BA, Ferguson SS, DeVito MJ, Sprankle CS, Kleinstreuer NC. 2018. Evaluation and optimization of pharmacokinetic models for in vitro to in vivo extrapolation of estrogenic activity for environmental chemicals. Environ Health Perspect 126(9):97001. https://doi.org/10.1289/EHP1655.

Casey W, Lowit A. 2019. USA: ICCVAM and NICEATM. In: Balls M, Combes R, Worth A. 2019. The History of Alternative Test Methods in Toxicology. London: Academic Press. https://doi.org/10.1016/B978-0-12-813697-3.00015-9.

Chesnut M, Yamada T, Adams T, Knight D, Kleinstreuer N, Kass G, Luechtefeld T, Hartung T. 2018. Regulatory acceptance of read-across. ALTEX 35(3):413-419. https://doi.org/10.14573/altex.1805081.

Choksi NY, Truax J, Layton A, Matheson J, Mattie D, Varney T, Tao J, Yozzo K, McDougal AJ, Merrill J, Lowther D, Barroso J, Linke B, Casey W, Allen D. 2019. United States regulatory requirements for skin and eye irritation testing. Cutan Ocular Toxicol 38(2):141-155. PMID 30418044. https://doi.org/10.1080/15569527.2018.1540494.

Clippinger AJ, Allen D, Behrsing H,  BéruBé KA, Bolger MB, Casey W, DeLorme M, Gaça M, Gehen SC, Glover K, Hayden P, Hinderliter P, Hotchkiss JA, Iskandar A, Keyser B, Luettich K, Ma-Hock L, Maione AG, Makena P, Melbourne J, Milchak L, Ng SP, Paini A, Page K, Patlewicz G, Prieto P, Raabe H, Reinke EN, Roper C, Rose J, Sharma M, Spoo W, Thorne PS, Wilson DM, Jarabek AM. 2018. Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity. Toxicol In Vitro 52:131-145. https://doi.org/10.1016/j.tiv.2018.06.009Honorable Mention winner, Best Paper of 2018, Society of Toxicology Biological Modeling Specialty Section.

Clippinger AJ, Allen D, Jarabek AM, Corvaro M, Gaça M, Gehen S, Hotchkiss JA, Patlewicz G, Melbourne J, Hinderliter P, Yoon M, Huh D, Lowit A, Buckley B, Bartels M, BéruBé K, Wilson DM, Indans I, Vinken M. 2018. Alternative approaches for acute inhalation toxicity testing to address global regulatory and non-regulatory data requirements: An international workshop report. Toxicol In Vitro 48:53-70. https://doi.org/10.1016/j.tiv.2017.12.011.

Corton JC, Kleinstreuer NC, Judson RS. 2019. Identification of potential endocrine disrupting chemicals using gene expression biomarkers. Toxicol Appl Pharmacol 380:114683. https://doi.org/10.1016/j.taap.2019.114683.

Daniel AB, Strickland J, Allen D, Casati S, Zuang V, Barroso J, Whelan M, Regimbald-Krnel MJ, Kojima H, Nishikawa A, Park HK, Lee JK, Kim TS, Delgado I, Rios L, Yang Y, Wang G, Kleinstreuer N. 2018. International regulatory requirements for skin sensitization testing. Regul Toxicol Pharmacol 95:52-65. https://doi.org/10.1016/j.yrtph.2018.03.003.

Fujita M, Yamamoto Y, Watanabe S, Sugawara T, Wakabayashi K, Tahara Y, Horie N, Fujimoto K, Kusakari K, Kurokawa Y, Kawakami T, Kojima K, Sozu T, Nakayama T, Kusao T, Richmond J, Kleinstreuer N, Kim B-H, Kojima H, Kasahara T, Ono T. 2019. The within- and between-laboratory reproducibility and predictive capacity of the in chemico amino acid derivative reactivity assay: Results of validation study implemented in four participating laboratories. J Appl Toxicol 39(11)1492-1505. https://doi.org/10.1002/jat.3834.

Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM. 2019. Chronic inflammation in the etiology of disease across the life span. Nat Med 25(12):1822-1832. https://doi.org/10.1038/s41591-019-0675-0.

Gadaleta D, Vukovic K, Toma C, Lavado GJ, Karmaus AL, Mansouri K, Kleinstreuer NC, Benfenati E, Roncaglioni A. 2019. SAR and QSAR modeling of a large collection of LD50 rat acute oral toxicity data. J Cheminfor 11, 58. https://doi.org/10.1186/s13321-019-0383-2.

Haggard D, Karmaus AL, Martin MT, Judson RS, Setzer RW, Paul-Friedman K. 2018. High-throughput H295R steroidogenesis assay: utility as an alternative and a statistical approach to characterize effects on steroidogenesis. Toxicol Sci 162(2): 509-534. https://doi.org/10.1093/toxsci/kfx274.

Hamm JT, Ceger P, Allen D, Stout M, Maull EA, Baker G, Zmaroski A, Padilla S, Perkins E, Planchart A, Stedman D, Tal T, Tanguay RL, Volz DC, Wilbanks MS, Walker NJ. 2019. Characterizing sources of variability in zebrafish embryo screening protocols. ALTEX 36(1):103-120. https://doi.org/10.14573/altex.1804162.

Huang R, Xia M, Sakamuru S, Zhao J, Lynch C, Zhao T, Zhu H, Austin CA, Simeonov A. 2018. Expanding biological space coverage enhances the prediction of drug adverse effects in human using in vitro activity profiles. Sci Rep 8, 3783. https://doi.org/10.1038/s41598-018-22046-w.

Harrill J, Shah I, Setzer RW, Haggard D, Auerbach S, Judson R, Thomas RS. 2019. Considerations for strategic use of high-throughput transcriptomics chemical screening data in regulatory decisions. Curr Opin Toxicol 15:64-75. https://doi.org/10.1016/j.cotox.2019.05.004.

Hoffman S, Kleinstreuer NC, Alepee N, Allen D, Api AM, Ashikaga T, Clouet E, Cluzel M, Desprez B, Gellatly N, Goebel C, Kern PS, Klaric M, Kuhnl J, Lalko JF, Martinozzi-Teisslier S, Mewes K, Miyazawa M, Parakhia R, van Vliet E, Zang Q, Petersohn D. 2018. Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database. Crit Rev Toxicol 48(5):344-358. https://doi.org/10.1080/10408444.2018.1429385.

Huang R, Grishagin I, Wang Y, Zhao T, Greene J, Obenauer JC, Ngan D, Nguyen DT, Guha R, Jadhav A, Southall N, Simeonov A, Austin CP. 2019. The NCATS Bioplanet – an integrated platform for exploring the universe of cellular signaling pathways for toxicology, systems biology, and chemical genomics. Front Pharmacol. DOI: https://doi.org/10.3389/fphar.2019.00445.

Judson RS, Paul Friedman K, Houck K, Mansouri K, Browne P, Kleinstreuer NC. 2018. New approach methods for testing chemicals for endocrine disruption potential. Curr Opin Toxicol 9:40-47. https://doi.org/10.1016/j.cotox.2018.10.002.

Judson RS, Thomas RS, Baker N, Simha A, Howey XM, Marable C, Kleinstruer NC, Houck KA. 2018. Workflow for defining reference chemicals for assessing performance of in vitro assays. ALTEX 36(2):261-276. >https://doi.org/10.14573/altex.1809281.

Kleinstreuer NC, Browne P, Chang X, Judson R, Casey W, Ceger P, Deisenroth C, Baker N, Markey K, Thomas RS. 2018. Evaluation of androgen assay results using a curated Hershberger database. Reprod Toxicol 81:272-280. https://doi.org/10.1016/j.reprotox.2018.08.017.

Kleinstreuer NC, Hoffman S, Alepee N, Allen D, Ashikaga T, Casey W, Clouet E, Cluzel M, Desprez B, Gellatly N, Gobel C, Kern PS, Klaric M, Kuhnl J, Martinozzi-Teisslier S, Mewes K, Miyazawa M, Strickland J, van Vliet E, Zang Q, Petersohn D. 2018. Non-animal methods to predict skin sensitization (II): an assessment of defined approaches. Crit Rev Toxicol 48(5);359-374. https://doi.org/10.1080/10408444.2018.1429386Winner, Best Paper of 2018, Society of Toxicology Risk Assessment Specialty Section.

Kleinstreuer NC, Karmaus A, Mansouri K, Allen DG, Fitzpatrick JM, Patlewicz G. 2018. Predictive models for acute oral systemic toxicity: a workshop to bridge the gap from research to regulation. Computational Toxicol 8:21-24. https://doi.org/10.1016/j.comtox.2018.08.002.

Kojima H, Yamaguchi H, Sozu T, Kleinstreuer N, Chae-Hyung L, Chen W, Watanabe M, Fukuda T, Yamashita K, Takezawa K. 2019. Multi-laboratory validation study of the Vitrigel-Eye Irritancy Test Method as an alternative to in vivo eye irritation testing. Altern Lab Anim 47(3-4):140-157. https://doi.org/10.1177/0261192919886665.

Kolanjiyil AV, Kleinstreuer C, Kleinstreuer NC, Pham W, Sadikot RT. 2019. Mice-to-men comparison of inhaled drug-aerosol deposition and clearance. Respir Physiol and Neurobiol 260:82-94. https://doi.org/10.1016/j.resp.2018.11.003.

Kornberg TG, Stueckle TA, Coyle J, Derk R, Demokritou P, Rojanasakul Y, Rojanasakul LW. 2019. Iron oxide nanoparticle-induced neoplastic-like cell transformation in vitro is reduced with a protective amorphous silica coating. Chem Res Toxicol 32(12):2382-2397. https://doi.org/10.1021/acs.chemrestox.9b00118.

Li S, Zhao J, Huang R, Santillo MF, Xia M. 2019. Use of high-throughput enzyme-based assay with xenobiotic metabolic capability to evaluate the inhibition of acetylcholinesterase activity by organophosphorus pesticides. Toxicol In Vitro 56:93-100. https://doi.org/10.1016/j.tiv.2019.01.002.

Linakis MW, Sayre RR, Pearce RG, Sfier MA, Sipes NS, Pangburn HA, Gearhart JM, Wambaugh JF. 2020. Development and evaluation of a high throughput inhalation model for organic chemicals [in press]. J Exposure Science Environ Epidemiology. https://doi.org/10.1038/s41370-020-0238-y.

Mahony C, Currie R, Daston G, Kleinstreuer N, van de Water B. 2018. Highlight report: 'Big data in the 3Rs: outlook and recommendations', a roundtable summary. Arch Toxicol 92:1015-1020. https://doi.org/10.1007/s00204-017-2145-0.

Manganelli S, Roncaglioni A, Mansouri K, Judson RS, Benfenati E, Manganaro A, Ruiz P. 2019. Development, validation and integration of in silico models to identify androgen active chemicals. Chemosphere 220:204-215. https://doi.org/10.1016/j.chemosphere.2018.12.131.

Mansouri K, Cariello NF, Korotcov A, Tkachenko V, Grulke CM, Sprankle CS, Allen D, Casey WM, Kleinstreuer NC, Williams AJ. 2019. Open-source QSAR models for pKa prediction using multiple machine learning approaches. J Cheminfor 11:60. https://doi.org/10.1186/s13321-019-0384-1.

Mansouri K, Grulke CM, Judson RS, Williams AJ. 2018. OPERA models for predicting physicochemical properties and environmental fate endpoints. J Cheminform 10(1):10. https://doi.org/10.1186/s13321-018-0263-1.

Marshall LJ, Austin CP, Casey W, Fitzpatrick SC, Willett C. 2018. Recommendations toward a human pathway-based approach to disease research. Drug Discov Today 23(11):1824-1832. https://doi.org/10.1016/j.drudis.2018.05.038.

Myatt GJ, Ahlberg E, Akahori Y, Allen D, Amberg A, Anger LT, Aptula A, Auerbach S, Beilke L, Bellion P, Benigni R, Bercu J, Booth ED, Bower D, Brigo A, Burden N, Cammerer Z, Cronin MTD, Cross KP, Custer L, Dettwiler M, Dobo K, Ford KA, Fortin MC, Gad-McDonald SE, Gellatly N, Gervais V, Glover KP, Glowienke S, Van Gompel J, Gutsell S, Hardy B, Harvey JS, Hillegass J, Honma M, Hsieh J-H, Hsu C-W, Hughes K, Johnson C, Jolly R, Jones D, Kemper R, Kenyon MO, Kim MT, Kruhlak NL, Kulkami SA, Kummerer K, Leavitt P, Majer B, Masten S, Miller S, Moser J, Mumtaz M, Muster W, Neilson L, Oprea TI, Patlewicz G, Paulino A, Lo Piparo E, Powley M, Quigley DP, Reddy MV, Richarz A-N, Ruiz P, Schilter B, Serafimova R, Simpson W, Stavitskaya L, Stidl R, Suarez-Rodriguez D, Szabo DT, Teasdale A, Trejo-Martin A, Valentin J-P, Vuorinen A, Wall BA, Watts P, White AT, Wichard J, Witt KL, Woolley A, Woolley D, Zwickl C, Hasselgren C. 2018. In silico toxicology protocols. Regul Toxicol Pharmacol 96:1-17. https://doi.org/10.1016/j.yrtph.2018.04.014.

Patlewicz G, Lizarraga L, Rua D, Allen DG, Daniel A, Fitzpatrick SC, Garcia-Reyero N, Gordon J, Hakkinen P, Howard AS, Karmaus A, Matheson J, Mumtaz M, Richarz AN, Ruiz P, Scarano L, Yamada T, Kleinstreuer N. 2019. Exploring current read-across applications and needs among selected U.S. federal agencies. Regul Toxicol Pharmacol 106:197-209. https://doi.org/10.1016/j.yrtph.2019.05.011.

Poston R, Hill R, Allen C, Casey W, Gatewood D, Levis R, Mallet L, Smith D, Srivinas G, Stirling C, Allen D. 2019. Achieving scientific and regulatory success in implementing non-animal approaches to human and veterinary rabies vaccine testing: A NICEATM and IABS workshop report. Biologicals 60:8-14. https://doi.org/10.1016/j.biologicals.2019.06.005.

Prior H, Casey W, Kimber I, Whelan M, Sewell F. 2019. Reflections on the progress towards non-animal methods for acute toxicity testing of chemicals. Regul Toxicol Pharmacol 102:30-33. https://doi.org/10.1016/j.yrtph.2018.12.008.

Ramaiahgari SC, Auerbach SS, Saddler TO, Rice JR, Dunlap PE, Sipes NS, DeVito MJ, Shah RR, Bushel PR, Merrick BA, Paules RS, Ferguson SS. 2019. The power of resolution: contextualized understanding of biological responses to liver injury chemicals using high-throughput transcriptomics and benchmark concentration modeling. Toxicol Sci 169(2):553-566. https://doi.org/10.1093/toxsci/kfz065.

Rooney JP, Chorley B, Kleinstreuer N, Corton JC. 2018. Identification of androgen receptor modulators in a prostate cancer cell line microarray compendium. Toxicol Sci 166(1):146-162. https://doi.org/10.1093/toxsci/kfy187.

Russo DP, Strickland J, Karmaus AL, Wang W, Shende S, Hartung T, Aleksunes LM, Zhu H. 2019. Nonanimal models for acute toxicity evaluations: applying data-driven profiling and read-across. Environ Health Perspect 127(4):47001. https://doi.org/10.1289/EHP3614.

Saili KS, Franzosa JA, Baker NC, Ellis-Hutchings RG, Settivari RS, Carney EW, Spencer R, Zurlinden TJ, Kleinstreuer NC, Li S, Xia M, Knudsen TB. 2019. Systems modeling of developmental vascular toxicology. Curr Opin Toxicol 15:55-63. https://doi.org/10.1016/j.cotox.2019.04.004.

Smirnova L, Kleinstreuer N, Corvi R, Levchenko A, Fitzpatrick SC, Hartung T. 2018. 3S - Systematic, systemic, and systems biology and toxicology. ALTEX 35(2):139-162. https://doi.org/10.14573/altex.1804051.

Solecki R, Rauch M, Gall A, Buschmann J, Kellner R, Kucheryavenko O, Schmitt A, Delrue N, Li W, Hu J, Fujiwara M, Kuwagata M, Mantovani A, Makris SL, Paumgartten F, Schonfelder G, Schneider S, Vogl S, Kleinstreuer N, Schneider M, Schulze F, Fritsche E, Clark R, K Shiota, Chahoud. 2019. Update of the DevTox data database for harmonized risk assessment and alternative methodologies in developmental toxicology: Report of the 9th Berlin Workshop on Developmental Toxicity. Reprod Toxicol 89:124-129. https://doi.org/10.1016/j.reprotox.2019.07.003.

Strickland J, Clippinger AJ, Brown J, Allen D, Jacobs A, Matheson J, Lowit A, Reinke EN, Johnson MS, Quinn MJ. 2018. Status of acute toxicity testing requirements and data uses by U.S. regulatory agencies. Reg Toxicol Pharmacol 94:183-196. https://doi.org/10.1016/j.yrtph.2018.01.022.

Strickland J, Daniel AB, Allen D, Aguila C, Ahir S, Bancos S, Craig E, Germolec D, Ghosh C, Hudson NL, Jacobs A, Lehmann DM, Matheson J, Reinke EN, Sadrieh N, Vukmanovic S, Kleinstreuer N. 2019. Skin sensitization testing needs and data uses by U.S. regulatory and research agencies. Arch Toxicol 92(2):273-291. https://doi.org/10.1007/s00204-018-2341-6.

Strickland J, Paris MW, Allen D, Casey W. 2019. Approaches to reducing animal use for acute toxicity testing: retrospective analyses of pesticide data. In: Kojima H, Seidle T, Spielmann H. (eds), Alternatives to Animal Testing. Springer, Singapore. https://doi.org/10.1007/978-981-13-2447-5.

Thomas RS, Paules RS, Simeonov A, Fitzpatrick SC, Crofton KM, Casey WM, Mendrick DL. 2018. The US federal Tox21 program: a strategic and operational plan for continued leadership. ALTEX 35(2):163-168. https://doi.org/10.14573/altex.1803011.

Wei Z, Sakamuru S, Zhang L, Zhao J, Huang R, Kleinstreuer NC, Chen Y, Shu Y, Knudsen TB, Xia M. 2019. Identification and profiling of environmental chemicals that inhibit the TGFβ/SMAD signaling pathway. Chem Res Toxicol 32(12):2433-2444. https://doi.org/10.1021/acs.chemrestox.9b00228.