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Research Articles

New approach methodologies (NAM) to characterize neurotoxic chemicals for use in risk assessment: case study of four neurotoxic pesticides

Pages 1226-1260 | Received 08 May 2023, Accepted 25 Aug 2023, Published online: 25 Sep 2023

References

  • Abedini J, Cook B, Bell SM, Chang X, Choksi N, Daniel AB, Hines D, Karmaus AL, Mansouri K, McAfee E, et al. 2021. Application of new approach methodologies: ICE tools to support chemical evaluations. Comput Toxicol. 20:100184. doi: 10.1016/j.comtox.2021.100184.
  • Amweg EL, Weston DP, Ureda NM. 2005. Use and toxicity of pyrethroid pesticides in the Central Valley, California, USA. Environ Toxicol Chem. 24(4):966–972. ndoi: 10.1897/04-146r1.1.
  • Anand SS, Bruckner JV, Haines WT, Muralidhara S, Fisher JW, Padilla S. 2006. Characterization of deltamethrin metabolism by rat plasma and liver microsomes. Toxicol Appl Pharmacol. 212(2):156–166. doi: 10.1016/j.taap.2005.07.021.
  • ATSDR. 2000. Toxicological Profile for Endosulfan. Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch.
  • Atterberry TT, Burnett WT, Chambers JE. 1997. Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism. Toxicol Appl Pharmacol. 147(2):411–418. doi: 10.1006/taap.1997.8303.
  • Baumann J, Gassmann K, Masjosthusmann S, DeBoer D, Bendt F, Giersiefer S, Fritsche E. 2016. Comparative human and rat neurospheres reveal species differences in chemical effects on neurodevelopmental key events. Arch Toxicol. 90(6):1415–1427. doi: 10.1007/s00204-015-1568-8.
  • Baumann N, Pham-Dinh D. 2001. Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev. 81(2):871–927. doi: 10.1152/physrev.2001.81.2.871.
  • Behl M, Ryan K, Hsieh J-H, Parham F, Shapiro AJ, Collins BJ, Sipes NS, Birnbaum LS, Bucher JR, Foster PMD, et al. 2019. Screening for developmental neurotoxicity at the national toxicology program: the future is here. Toxicol Sci. 167(1):6–14. doi: 10.1093/toxsci/kfy278.
  • Bell SM, Abedini J, Ceger P, Chang X, Cook B, Karmaus AL, Lea I, Mansouri K, Phillips J, McAfee E, et al. 2020. An integrated chemical environment with tools for chemical safety testing. Toxicol In Vitro. 67:104916. doi: 10.1016/j.tiv.2020.104916.
  • Bell SM, Chang X, Wambaugh JF, Allen DG, Bartels M, Brouwer KLR, Casey WM, Choksi N, Ferguson SS, Fraczkiewicz G, et al. 2018. In vitro to in vivo extrapolation for high throughput prioritization and decision making. Toxicol In Vitro. 47:213–227. doi: 10.1016/j.tiv.2017.11.016.
  • Betancourt AM, Burgess SC, Carr RL. 2006. Effect of developmental exposure to chlorpyrifos on the expression of neurotrophin growth factors and cell-specific markers in neonatal rat brain. Toxicol Sci. 92(2):500–506. doi: 10.1093/toxsci/kfl004.
  • Bouchard MF, Bellinger DC, Wright RO, Weisskopf MG. 2010. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics. 125(6):e1270–7. doi: 10.1542/peds.2009-3058.
  • Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr DB, et al. 2011. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect. 119(8):1189–1195. doi: 10.1289/ehp.1003185.
  • Breen M, Ring CL, Kreutz A, Goldsmith M-R, Wambaugh JF. 2021. High-throughput PBTK models for in vitro to in vivo extrapolation. Expert Opin Drug Metab Toxicol. 17(8):903–921. doi: 10.1080/17425255.2021.1935867.
  • Cao Z, Shafer TJ, Murray TF. 2011. Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons. J Pharmacol Exp Ther. 336(1):197–205. doi: 10.1124/jpet.110.171850.
  • Carstens KE, Carpenter AF, Martin MM, Harrill JA, Shafer TJ, Paul-Friedman K. 2022. Integrating data from in vitro new approach methodologies for developmental neurotoxicity. Toxicol Sci. 187(1):62–79. doi: 10.1093/toxsci/kfac018.
  • Casey KA. 2005. Chlorpyrifos in Human Breast Milk? [Doctoral dissertation]. Knoxville (TN/USA): University of Tennessee. http://trace.tennessee.edu/utk_graddiss/672/.
  • Casida JE, Quistad GB. 2004. Organophosphate toxicology: safety aspects of nonacetylcholinesterase secondary targets. Chem Res Toxicol. 17(8):983–998. doi: 10.1021/tx0499259.
  • Casida JE. 2017. Organophosphorus xenobiotic toxicology. Annu Rev Pharmacol Toxicol. 57(1):309–327. doi: 10.1146/annurev-pharmtox-010716-104926.
  • CDPR. 2008. Endosulfan risk characterization document. Medical Toxicology and Worker Health and Safety Branches Department Of Pesticide Regulation California Environmental Protection Agency. https://wwwcdprcagov/docs/whs/active_ingredient/indexhtm.
  • CDPR. 2008. Endosulfan risk characterization document. Sacramento (CA/USA): Medical Toxicology and Worker Health and Safety Branches Department Of Pesticide Regulation California Environmental Protection Agency. https://www.cdpr.ca.gov/docs/whs/active_ingredient/index.htm.
  • CDPR. 2018. Evaluation of chlorpyrifos as a toxic air contaminant: addendum to the risk characterization of spray drift, dietary, and aggregate exposures to residential bystanders human. Sacramento (CA/USA): Human Health Assessment Branch, Department of Pesticide Regulation, California Environmental Protection Agency. http://www.cdpr.ca.gov/docs/whs/active_ingredient/chlorpyrifos.htm.
  • CFR. 2022. Cyfluthrin and the isomer beta-cyfluthrin; tolerances for residues. Code of Federal Regulations Title 40, Chapter 1, Subchapter E. Part 180, Subpart C. 180:436.
  • Chang X, Palmer JA, Lumen A, Lee UJ, Ceger P, Mansouri K, Sprankle CS, Donley E, Bell S, Knudsen TB, et al. 2022. Quantitative in vitro to in vivo extrapolation for developmental toxicity potency of valproic acid analogues. Birth Defects Res. 114(16):1037–1055. doi: 10.1002/bdr2.2019.
  • Chang X, Tan YM, Allen DG, Bell S, Brown PC, Browning L, Ceger P, Gearhart JM, Hakkinen PJ, Kabadi SV, et al. 2022. IVIVE: facilitating the use of in vitro toxicity data in risk assessment and decision making. Toxics. 10(5):232. doi: 10.3390/toxics10050232.
  • Cole LM, Casida JE. 1986. Polychlorocycloalkane insecticide-induced convulsions in mice in relation to disruption of the GABA-regulated chloride ionophore. Life Sci. 39(20):1855–1862. doi: 10.1016/0024-3205(86)90295-x.
  • Crofton KM, Reiter LW. 1988. The effects of type I and II pyrethroids on motor activity and the acoustic startle response in the rat. Fundam Appl Toxicol. 10(4):624–634. doi: 10.1016/0272-0590(88)90189-3.
  • Deepika D, Kumar S, Bravo N, Esplugas R, Capodiferro M, Sharma RP, Schuhmacher M, Grimalt JO, Blanco J, Kumar V. 2022. Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB). Neurotoxicology. 93:152–162. doi: 10.1016/j.neuro.2022.09.010.
  • Dourson ML, Felter SP, Robinson DT. 1996. Evolution of science-based uncertainty factors in noncancer risk assessment. Regul Toxicol Pharmacol. 24(2 Pt 1):108–120. doi: 10.1006/rtph.1996.0116.
  • Duffus JH, Nordberg M, Templeton DM. 2007. Glossary of terms used in toxicology, 2nd edition (IUPAC Recommendations 2007). Pure and Applied Chemistry. 79(7):1153–1344. doi: 10.1351/pac200779071153.
  • Eaton DL, Daroff RB, Autrup H, Bridges J, Buffler P, Costa LG, Coyle J, McKhann G, Mobley WC, Nadel L, et al. 2008. Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment. Crit Rev Toxicol. 38 Suppl 2(sup2):1–125. doi: 10.1080/10408440802272158.
  • El-Masri H, Kleinstreuer N, Hines RN, Adams L, Tal T, Isaacs K, Wetmore BA, Tan YM. 2016. Integration of life-stage physiologically based pharmacokinetic models with adverse outcome pathways and environmental exposure models to screen for environmental hazards. Toxicol Sci. 152(1):230–243. doi: 10.1093/toxsci/kfw082.
  • EPA. 2010. Endosulfan phase-out. https://archive.epa.gov/pesticides/reregistration/web/html/endosulfan-agreement.html#agreement.
  • Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, Furlong CE, Holland NT. 2004. Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environ Health Perspect. 112(10):1116–1124. doi: 10.1289/ehp.6789.
  • Eskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, Morga N, Jewell NP. 2007. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ Health Perspect. 115(5):792–798. doi: 10.1289/ehp.9828.
  • Ferreira LK, Busatto GF. 2013. Resting-state functional connectivity in normal brain aging. Neurosci Biobehav Rev. 37(3):384–400. doi: 10.1016/j.neubiorev.2013.01.017.
  • Ffrench-Constant RH, Anthony N, Aronstein K, Rocheleau T, Stilwell G. 2000. Cyclodiene insecticide resistance: from molecular to population genetics. Annu Rev Entomol. 45(1):449–466. doi: 10.1146/annurev.ento.45.1.449.
  • Filer DL, Kothiya P, Setzer RW, Judson R, Martin MT. 2017. Tcpl: the ToxCast pipeline for high-throughput screening data. Bioinformatics. 33(4):618–620. doi: 10.1093/bioinformatics/btw680.
  • Filer DL. 2019. The new ToxCast analysis; [accessed 2023 Feb 10]. https://www.epa.gov/sites/default/files/2015-01/documents/the_new_toxcast_analysis_v2.pdf.
  • Frank CL, Brown JP, Wallace KB, Wambaugh JF, Shah I, Shafer TJ. 2018. Defining toxicological tipping points in neuronal network development. Toxicol Appl Pharmacol. 354:81–93. doi: 10.1016/j.taap.2018.01.017.
  • Gant DB, Eldefrawi ME, Eldefrawi AT. 1987. Cyclodiene insecticides inhibit GABAA receptor-regulated chloride transport. Toxicol Appl Pharmacol. 88(3):313–321. doi: 10.1016/0041-008x(87)90206-7.
  • Garcia SJ, Seidler FJ, Slotkin TA. 2005. Developmental neurotoxicity of chlorpyrifos: targeting glial cells. Environ Toxicol Pharmacol. 19(3):455–461. doi: 10.1016/j.etap.2004.12.007.
  • Goh JO. 2011. Functional dedifferentiation and altered connectivity in older adults: neural accounts of cognitive aging. Aging Dis. 2(1):30–48.
  • Guo L, Gu C, Huang T, Gao H, Zhao Y, Mao X, Ma J. 2022. Signatures of Indian Endosulfan usage in China’s environment. Chemosphere. 306:135644. doi: 10.1016/j.chemosphere.2022.135644.
  • Harada H, Tamaoka A, Ishii K, Shoji S, Kametaka S, Kametani F, Saito Y, Murayama S. 2006. Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer’s disease brains. Neurosci Res. 54(1):24–29. doi: 10.1016/j.neures.2005.10.001.
  • Harrill JA, Everett LJ, Haggard DE, Sheffield T, Bundy JL, Willis CM, Thomas RS, Shah I, Judson RS. 2021. High-throughput transcriptomics platform for screening environmental chemicals. Toxicol Sci. 181(1):68–89. doi: 10.1093/toxsci/kfab009.
  • Harrill JA, Freudenrich T, Wallace KB, Ball K, Shafer TJ, Mundy WR. 2018. Testing for developmental neurotoxicity using a battery of in vitro assays for key cellular events in neurodevelopment. Toxicol Appl Pharmacol. 354:24–39. doi: 10.1016/j.taap.2018.04.001.
  • Hines DE, Bell S, Chang X, Mansouri K, Allen D, Kleinstreuer N. 2022. Application of an accessible interface for pharmacokinetic modeling and in vitro to in vivo extrapolation. Front Pharmacol. 13:864742. doi: 10.3389/fphar.2022.864742.
  • ICE. 2023. ICE IVIVE Tool. National Toxicology Program, US Department of Health and Human Services, National Institute of Environmental Health Sciences, Bethesda (MD), version 4; [accessed 2023 Apr 30). https://icentpniehsnihgov/.
  • Jacob TC, Moss SJ, Jurd R. 2008. GABAA receptor trafficking and its role in the dynamic modulation of neuronal inhibition. Nat Rev Neurosci. 9(5):331–343. doi: 10.1038/nrn2370.
  • James A, Emmanuel D. 2021. An overview of endosulfan and the aftermath of its biohazardous administration in Southern India. Eur J Mol Clin Med. 8:212–218.
  • Jia Z, Misra HP. 2007. Developmental exposure to pesticides zineb and/or endosulfan renders the nigrostriatal dopamine system more susceptible to these environmental chemicals later in life. Neurotoxicology. 28(4):727–735. doi: 10.1016/j.neuro.2007.04.003.
  • Judson R, Filer D, Brown J, Zurlinden T, Kothiya P, Setzer WR, Martin MT, Paul-Friedman K. 2022. ToxCast data analysis pipeline package 'tcpl’. US EPA publication version 210; [accessed 2022 Dec 2]. https://githubcom/USEPA/CompTox-ToxCast-tcpl.
  • Judson R, Houck K, Martin M, Knudsen T, Thomas RS, Sipes N, Shah I, Wambaugh J, Crofton K. 2014. In vitro and modelling approaches to risk assessment from the US environmental protection agency ToxCast programme. Basic Clin Pharmacol Toxicol. 115(1):69–76. doi: 10.1111/bcpt.12239.
  • Judson R, Houck K, Martin M, Richard AM, Knudsen TB, Shah I, Little S, Wambaugh J, Woodrow Setzer R, Kothiya P, et al. 2016. Editor’s highlight: analysis of the effects of cell stress and cytotoxicity on in vitro assay activity across a diverse chemical and assay space. Toxicol Sci. 152(2):323–339. doi: 10.1093/toxsci/kfw092.
  • Judson R, Houck K, Paul-Friedman K, Brown JP, Browne P, Johnston PA, Close D, Kamel M, Kleinstreuer N. 2020. Selecting a minimal set of androgen receptor assays for screening chemicals. Regul Toxicol Pharmacol. 117:104764. doi: 10.1016/j.yrtph.2020.104764.
  • Judson R, Kavlock RJ, Setzer RW, Hubal EAC, Martin MT, Knudsen TB, Houck KA, Thomas RS, Wetmore BA, Dix DJ. 2011. Estimating toxicity-related biological pathway altering doses for high-throughput chemical risk assessment. Chem Res Toxicol. 24(4):451–462. doi: 10.1021/tx100428e.
  • Kleinstreuer NC, Ceger P, Watt ED, Martin M, Houck K, Browne P, Thomas RS, Casey WM, Dix DJ, Allen D, et al. 2017. Development and validation of a computational model for androgen receptor activity. Chem Res Toxicol. 30(4):946–964.,. doi: 10.1021/acs.chemrestox.6b00347.
  • Knudsen T, Fitzpatrick SC, Abrew K, Birnbaum L, Chappelle A, Daston G, Dolinoy D, Elder A, Euling S, Faustman E, et al. 2021. FutureTox IV workshop summary: predictive toxicology for healthy children. Toxicol Sci. 180(2):198–211. doi: 10.1093/toxsci/kfab013.
  • Knudsen TB, Spielmann M, Megason SG, Faustman EM. 2021. Single‐cell profiling for advancing birth defects research and prevention. Birth Defects Res. 113(7):546–559. doi: 10.1002/bdr2.1870.
  • Kosnik MB, Strickland JD, Marvel SW, Wallis DJ, Wallace KB, Richard AM, Reif DM, Shafer TJ. 2020. Concentration–response evaluation of ToxCast compounds for multivariate activity patterns of neural network function. Arch Toxicol. 94(2):469–484. doi: 10.1007/s00204-019-02636-x.
  • Kwok ESC. 2021. Toxicological priority index framework for prioritizing pesticide products into human exposure and health risk assessments. Hum Ecol Risk Asses. 27(8):2080–2103. doi: 10.1080/10807039.2021.1951156.
  • Lakshmanan PS, Eeckhaut T, Van Huylenbroeck J, Van Bockstaele E. 2013. Micronucleation by mitosis inhibitors in developing microspores of Spathiphyllum wallisii Regel. Plant Cell Rep. 32(3):369–377. doi: 10.1007/s00299-012-1370-5.
  • Lovasi GS, Quinn JW, Rauh VA, Perera FP, Andrews HF, Garfinkel R, Hoepner L, Whyatt R, Rundle A. 2011. Chlorpyrifos exposure and urban residential environment characteristics as determinants of early childhood neurodevelopment. Am J Public Health. 101(1):63–70. doi: 10.2105/AJPH.2009.168419.
  • Lowe ER, Poet TS, Rick DL, Marty MS, Mattsson JL, Timchalk C, Bartels MJ. 2009. The effect of plasma lipids on the pharmacokinetics of chlorpyrifos and the impact on interpretation of blood biomonitoring data. Toxicol Sci. 108(2):258–272. doi: 10.1093/toxsci/kfp034.
  • MacKenzie KM, Felton SM, Dickie SM, et al. 1981. Teratology study with FMC 5462 in rabbits. Raltech Study No 80070 MRID504800201. Issue submitted to U.S. Environmental Protection Agency.
  • Mallick P, Moreau M, Song G, Efremenko AY, Pendse SN, Creek MR, Osimitz TG, Hines RN, Hinderliter P, Clewell HJ, et al. 2020. Development and application of a life-stage physiologically based pharmacokinetic (PBPK) model to the assessment of internal dose of pyrethroids in humans. Toxicol Sci. 173(1):86–99. doi: 10.1093/toxsci/kfz211.
  • Marty MS, Andrus AK, Bell MP, Passage JK, Perala AW, Brzak KA, Bartels MJ, Beck MJ, Juberg DR. 2012. Cholinesterase inhibition and toxicokinetics in immature and adult rats after acute or repeated exposures to chlorpyrifos or chlorpyrifos-oxon. Regul Toxicol Pharmacol. 63(2):209–224. doi: 10.1016/j.yrtph.2012.03.015.
  • Marty MS, Andrus AK. 2010. Comparison of cholinesterase (ChE) inhibition in young adult and pre-weanling CD rats after acute and repeated chlorpyrifos or chlorpyrifos-oxon exposures toxicology & environmental research and consulting. Midland, MI: The Dow Chemical Company.
  • Menezes RG, Qadir TF, Moin A, Fatima H, Hussain SA, Madadin M, Pasha SB, Al Rubaish FA, Senthilkumaran S. 2017. Endosulfan poisoning: an overview. J Forensic Leg Med. 51:27–33. doi: 10.1016/j.jflm.2017.07.008.
  • Najjar A, Punt A, Wambaugh J, Paini A, Ellison CA, Fragki S, Bianchi E, Zhang F, Westerhout J, Mueller D, et al. 2022. Towards best use and regulatory acceptance of generic physiologically based kinetic (PBK) models for in vitro-to-in vivo extrapolation (IVIVE) in chemical risk assessment. Arch Toxicol. 96(12):3407–3419. doi: 10.1007/s00204-022-03356-5.
  • Ozoe Y, Matsumura F. 1986. Structural requirements for bridged bicyclic compounds acting on picrotoxinin receptor. J Agric Food Chem. 34(1):126–134. doi: 10.1021/jf00067a035.
  • Patlewicz G, Shah I. 2023. Towards systematic read-across using Generalised Read-Across (GenRA). Comput Toxicol. 25:1–15. doi: 10.1016/j.comtox.2022.100258.
  • Paul Friedman K, Gagne M, Loo LH, Karamertzanis P, Netzeva T, Sobanski T, Franzosa JA, Richard AM, Lougee RR, Gissi A, et al. 2020. Utility of in vitro bioactivity as a lower bound estimate of in vivo adverse effect levels and in risk-based prioritization. Toxicol Sci. 173(1):202–225. doi: 10.1093/toxsci/kfz201.
  • Paul Friedman K. 2018. ToxCast pipeline, example, and building additional context for use. file:///C:/Users/Owner/Downloads/SETAC_HT_ToxCast_CEETOX_Uncertainty_Apr18.pdf.
  • Paul-Friedman K, Watt ED, Hornung MW, Hedge JM, Judson RS, Crofton KM, Houck KA, Simmons SO. 2016. Tiered high-throughput screening approach to identify thyroperoxidase inhibitors within the ToxCast phase I and II chemical libraries. Toxicol Sci. 151(1):160–180. doi: 10.1093/toxsci/kfw034.
  • Pearce RG, Setzer RW, Strope CL, Sipes NS, Wambaugh JF. 2017. httk: r Package for High-Throughput Toxicokinetics. J Stat Softw. 79(4):1–26. doi: 10.18637/jss.v079.i04.
  • Pham LL, Watford SM, Pradeep P, Martin MT, Thomas RS, Judson RS, Setzer RW, Paul-Friedman K. 2020. Variability in in vivo studies: defining the upper limit of performance for predictions of systemic effect levels. Comput Toxicol. 15:1–100126. doi: 10.1016/j.comtox.2020.100126.
  • Pradeep P, Paul Friedman K, Judson R. 2020. Structure-based QSAR models to predict repeat dose toxicity points of departure. Comput Toxicol. 16:100139. doi: 10.1016/j.comtox.2020.100139.
  • Prior H, Casey WM, 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. doi: 10.1016/j.yrtph.2018.12.008.
  • Punt A, Firman J, Boobis AR, Cronin M, Gosling JP, Wilks MF, Hepburn PA, Thiel A, Fussell KC. 2020. Potential of ToxCast data in the safety assessment of food chemicals. Toxicol Sci. 174(2):326–340. doi: 10.1093/toxsci/kfaa008.
  • Qiao D, Seidler FJ, Padilla S, Slotkin TA. 2002. Developmental neurotoxicity of chlorpyrifos: what is the vulnerable period? Environ Health Perspect. 110(11):1097–1103. doi: 10.1289/ehp.021101097.
  • Rauch SA, Braun JM, Barr DB, Calafat AM, Khoury J, Montesano AM, Yolton K, Lanphear BP. 2012. Associations of prenatal exposure to organophosphate pesticide metabolites with gestational age and birth weight. Environ Health Perspect. 120(7):1055–1060. doi: 10.1289/ehp.1104615.
  • Rauh V, Arunajadai S, Horton M, Perera F, Hoepner L, Barr DB, Whyatt R. 2011. Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect. 119(8):1196–1201. doi: 10.1289/ehp.1003160.
  • Rauh V, Garfinkel R, Perera FP, Andrews HF, Hoepner L, Barr DB, Whitehead R, Tang D, Whyatt RW. 2006. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics. 118(6):e1845-59–e1859. doi: 10.1542/peds.2006-0338.
  • Rauh V, Perera FP, Horton MK, Whyatt RM, Bansal R, Hao X, Liu J, Barr DB, Slotkin TA, Peterson BS. 2012. Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci U S A. 109(20):7871–7876. doi: 10.1073/pnas.1203396109.
  • Rauh V. 2008. Discussion of analyses of prenatal chlorpyrifos exposure and neurodevelopmental outco. New York: Columbia Center for Children’s Environmental Health, Mailman School of Public Health, Columbia University. http://www.epa.gov/scipoly/sap/meetings/2008/september/rauh.pdf.
  • Rauh VA, Garcia WE, Whyatt R, Horton MK, Barr DB, Louis ED. 2015. Prenatal exposure to the organophosphate pesticide chlorpyrifos and childhood tremor. Neurotoxicology. 51:80–86. doi: 10.1016/j.neuro.2015.09.004.
  • Richard AM, Huang R, Waidyanatha S, Shinn P, Collins BJ, Thillainadarajah I, Grulke CM, Williams AJ, Lougee RR, Judson RS, et al. 2021. The Tox21 10K compound library: collaborative chemistry advancing toxicology. Chem Res Toxicol. 34(2):189–216. doi: 10.1021/acs.chemrestox.0c00264.
  • Rodríguez JL, Ares I, Castellano V, Martínez M, Martínez-Larrañaga MR, Anadón A, Martínez MA. 2016. Effects of exposure to pyrethroid cyfluthrin on serotonin and dopamine levels in brain regions of male rats. Environ Res. 146:388–394. doi: 10.1016/j.envres.2016.01.023.
  • Saavedra L, Wallace KB, Freudenrich TF, Mall M, Mundy WR, Davila J, Shafer TJ, Wernig M, Haag D. 2021. Comparison of acute effects of neurotoxic compounds on network activity in human and rodent neural cultures. Toxicol Sci. 180(2):295–312. doi: 10.1093/toxsci/kfab008.
  • Saiyed H, Dewan A, Bhatnagar V, Shenoy U, Shenoy R, Rajmohan H, Patel K, Kashyap R, Kulkarni P, Rajan B, et al. 2003. Effect of endosulfan on male reproductive development. Environ Health Perspect. 111(16):1958–1962. doi: 10.1289/ehp.6271.
  • Scremin OU, Chialvo DR, Lavarello S, Berra HH, Lucero MA. 2011. The environmental pollutant endosulfan disrupts cerebral cortical function at low doses. Neurotoxicology. 32(1):31–37. doi: 10.1016/j.neuro.2010.12.001.
  • Seth PK, Saidi NF, Agrawal AK, Anand M. 1986. Neurotoxicity of endosulfan in young and adult rats. Neurotoxicology. 7:623–635.
  • Shafer TJ, Brown JP, Lynch B, Davila-Montero S, Wallace KB, Paul-Friedman K. 2019. Evaluation of chemical effects on network formation in cortical neurons grown on microelectrode arrays. Toxicol Sci. 169(2):436–455. doi: 10.1093/toxsci/kfz052.
  • Shelton JF, Geraghty EM, Tancredi DJ, Delwiche L, Schmidt RJ, Ritz B, Hansen RL, Hertz-Picciotto I. 2014. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect. 122(10):1103–1109. doi: 10.1289/ehp.1307044.
  • Silva MH, Beauvais SL. 2010a. Human health risk assessment of endosulfan. Toxicol Haz Identif Regul Toxicol Pharmacol. 56:4–17. doi: 10.1016/j.yrtph.2009.08.013.
  • Silva MH, Beauvais SL. 2010b. Human health risk assessment of endosulfan. I: toxicology and hazard identification. Regulatory Toxicology and Regul Toxicol Pharmacol. 56(1):4–17. doi: 10.1016/j.yrtph.2009.08.013.
  • Silva MH, Gammon D. 2009. An assessment of the developmental, reproductive, and neurotoxicity of endosulfan. Birth Defects Res B Dev Reprod Toxicol. 86(1):1–28. doi: 10.1002/bdrb.20183.
  • Silva MH. 2020. Effects of low-dose chlorpyrifos on neurobehavior and potential mechanisms: a review of studies in rodents, zebrafish, and Caenorhabditis elegans. Birth Defects Res. 112(6):445–479. doi: 10.1002/bdr2.1661.
  • Sipes NS, Martin MT, Kothiya P, Reif DM, Judson R, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB. 2013. Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 26(6):878–895. doi: 10.1021/tx400021f.
  • Sipes NS, Wambaugh JF, Pearce RG, Auerbach SS, Wetmore BA, Hsieh J-H, Shapiro AJ, Svoboda D, DeVito MJ, Ferguson SS. 2017. An intuitive approach for predicting potential human health risk with the Tox21 10k library. Environ Sci Technol. 51(18):10786–10796. doi: 10.1021/acs.est.7b00650.
  • Slotkin TA, Seidler FJ. 2007. Comparative developmental neurotoxicity of organophosphates in vivo: transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems. Brain Res Bull. 72(4-6):232–274. doi: 10.1016/j.brainresbull.2007.01.005.
  • Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, Sargent D, Stevens JT, Weiner ML. 2002. Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment. Toxicology. 171(1):3–59. doi: 10.1016/s0300-483x(01)00569-8.
  • Soderlund DM. 2012. Pyrethroid actions on sodium channels: isoform and species specificity, vol. 1099. Washington (DC): Parameters for Pesticide QSAR and PBPK/PD Models for Human Risk Assessment; p. 217–28.
  • Song G, Moreau M, Efremenko A, Lake BG, Wu H, Bruckner JV, White CA, Osimitz TG, Creek MR, Hinderliter PM, et al. 2019. Evaluation of age-related pyrethroid pharmacokinetic differences in rats: physiologically-based pharmacokinetic model development using in vitro data and in vitro to in vivo extrapolation. Toxicol Sci. 169(2):365–379. doi: 10.1093/toxsci/kfz042.
  • Sutherland TD, Home I, Weir KM, Russell RJ, Oakeshott JG. 2004. Toxicity and residues of endosulfan isomers, Springer New York (NY. Rev Environ Contam Toxicol. 183:99–113. doi: 10.1007/978-1-4419-9100-3_4.
  • Tan YM, Liao KH, Clewell HJ. III. 2007. Reverse dosimetry: Interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic modeling. J Expo Sci Environ Epidemiol. 17(7):591–603. doi: 10.1038/sj.jes.7500540.
  • Testai E, Buratti FM, Di Consiglio E. 2010. Chapter 70: chlorpyrifos. Hayes. In Handbook of pesticide toxicology Elsevier Inc. 3rd ed. USA and UK: Elsevier Inc.
  • Thomas RS, Bahadori T, Buckley TJ, Cowden J, Deisenroth C, Dionisio KL, Frithsen JB, Grulke CM, Gwinn MR, Harrill JA, et al. 2019. The next generation blueprint of computational toxicology at the US Environmental Protection Agency. Toxicol Sci. 169(2):317–332. doi: 10.1093/toxsci/kfz058.
  • Thomason ME, Grove LE, Lozon TA, Vila AM, Ye Y, Nye MJ, Manning JH, Pappas A, Hernandez-Andrade E, Yeo L, et al. 2015. Age-related increases in long-range connectivity in fetal functional neural connectivity networks in utero. Dev Cogn Neurosci. 11:96–104. doi: 10.1016/j.dcn.2014.09.001.
  • US EPA. 1998. Health effect test guidelines (OPPS 870). Prevention, pesticides and toxic substances (7101). Washington (DC): United States Environmental Protection Agency. [accessed 2023 March 15]. https://wwwepagov/test-guidelines-pesticides-and-toxic-substances/series-870-health-effects-test-guidelines.
  • US EPA. 2002. A review of the reference dose and reference concentration processes. Washington (DC/USA): United States Environmental Protection Agency. [accessed 2022 Apr 12]. https://www.epa.gov/sites/production/files/2014-12/documents/rfd-final.pdf.
  • US EPA. 2011. Chlorpyrifos: preliminary human health risk assessment for registration review. Office of chemical safety and pollution prevention. Washington (DC): United States Environmental Protection Agency. [accessed 2023 Apr 25]. https://www.regulations.gov/document?D=EPA-HQ-OPP-2008-0850-0025.
  • US EPA. 2011. Chlorpyrifos: revised Acute (Probabilistic) and chronic dietary exposure and risk assessments for food only (with and without food handling use included) and for water only for the registration review action - typical use rates/water included. June 30, 2011. PC Code: 059101. DP Barcode: 388166.
  • US EPA. 2014. Chlorpyrifos: revised human health risk assessment for registration review. Washington (DC/USA): Office of Chemical Safety and Pollution Prevention, United States Environmental Protection Agency. [accessed 2022 Feb 12]. https://oehhacagov/media/downloads/crnr/usepachlorpyrifoshhriskassessment2014_0pdf.
  • US EPA. 2016. Chlorpyrifos: revised Human Health Risk Assessment for Registration Review. Washington (DC/USA): Memorandum: Office of Chemical Safety and Pollution Prevention, United States Environmental Protection Agency. [accessed 2022 Mar 15]. https://wwwregulationsgov/document?D=EPA-HQ-OPP-2015-0653-0459.
  • US EPA. 2017. Cyfluthrin and Beta-Cyfluthrin. Draft human health risk assessment for registration review office of chemical safety and pollution prevention. Washington (DC): United States Environmental Protection Agency. [accessed 2023 April 28]. https://wwwregulationsgov/docket/EPA-HQ-OPP-2010-0684/document.
  • US EPA. 2018. Atrazine. Draft human health risk assessment for registration review. Fed Reg. 83:35472–35473.
  • US EPA. 2020. Chlorpyrifos: third revised human health risk assessment for registration review. Washington (DC/USA): Office of Chemical Safety and Pollution Prevention, United States Environmental Protection Agency. [accessed 2023 Mar 28]. https://betaregulationsgov/document/EPA-HQ-OPP-2008-0850-0944.
  • US EPA. 2023. CompTox chemicals dashboard: search 1,200,059 chemicals. Ver 2.2. United States Environmental Protection Agency. [accessed 2023 Apr 30]. https://comptoxepagov/dashboard/.
  • Wang YJ, Chan MH, Chen L, Wu SN, Chen HH. 2016. Resveratrol attenuates cortical neuron activity: roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels. J Biomed Sci. 23(1):47. doi: 10.1186/s12929-016-0259-y.
  • Watt ED, Judson R. 2018. Uncertainty quantification in ToxCast high throughput screening. PLoS One. 13(7):e0196963. doi: 10.1371/journal.pone.0196963.
  • Webster F, Gagné M, Patlewicz G, Pradeep P, Trefiak N, Judson RS, Barton-Maclaren TS. 2019. Predicting estrogen receptor activation by a group of substituted phenols: an integrated approach to testing and assessment case study. Regul Toxicol Pharmacol. 106:278–291. doi: 10.1016/j.yrtph.2019.05.017.
  • Weldon RH, Barr DB, Trujillo C, Bradman A, Holland N, Eskenazi B. 2011. A pilot study of pesticides and PCBs in the breast milk of women residing in urban and agricultural communities of California. J Environ Monit. 13(11):3136–3144. doi: 10.1039/c1em10469a.
  • Wetmore BA, Wambaugh JF, Ferguson SS, Sochaski MA, Rotroff DM, Freeman K, Clewell HJ, Dix DJ, Andersen ME, Houck KA, et al. 2012. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol Sci. 125(1):157–174. doi: 10.1093/toxsci/kfr254.
  • WHO. 2017. Guidance document on evaluating and expressing uncertainty in hazard characterization. Geneva: World Health Organization. https://apps.who.int/iris/bitstream/handle/10665/259858/9789241513548-eng.pdf;sequence=1#:∼:text=GUIDANCE%20DOCUMENT%20ON%20EVALUATING%20AND%20EXPRESSING%20UNCERTAINTY%20IN,sponsorship%20of%20the%20World%20Health%20Organization%2C%20the%20International.
  • Williams AJ, Grulke CM, Edwards J, McEachran AD, Mansouri K, Baker NC, Patlewicz G, Shah I, Wambaugh JF, Judson R, et al. 2017. The CompTox chemistry dashboard: a community data resource for environmental chemistry. J Cheminform. 9(1):61. doi: 10.1186/s13321-017-0247-6.
  • Wilson WW, Shapiro LP, Bradner JM, Caudle WM. 2014. Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring. Neurotoxicology. 44:279–287. doi: 10.1016/j.neuro.2014.07.008.
  • Wolansky MJ, Gennings C, Crofton KM. 2006. Relative potencies for acute effects of pyrethroids on motor function in rats. Toxicol Sci. 89(1):271–277. doi: 10.1093/toxsci/kfj020.
  • Wolansky MJ, Harrill JA. 2008. Neurobehavioral toxicology of pyrethroid insecticides in adult animals: a critical review. Neurotoxicol Teratol. 30(2):55–78. doi: 10.1016/j.ntt.2007.10.005.

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