Superfund Research Program

Airborne PCBs and their Metabolites: Risk Factors for Adverse Neurodevelopmental Outcomes in Adolescence

Project Leader: Hans-Joachim Lehmler
Co-Investigators: Jonathan A. Doorn, Hanna E. Stevens
Grant Number: P42ES013661
Funding Period: 2020-2025

Project-Specific Links

Publications

2024

• Duffel MW, Lehmler H. 2024. Complex roles for sulfation in the toxicities of polychlorinated biphenyls. Crit Rev Toxicol doi:10.1080/10408444.2024.2311270 PMID:38363552
• Griffin J, Li X, Lehmler H, Holland EB. 2024. Predicted versus observed activity of PCB mixtures toward the ryanodine receptor. Neurotoxicology 100:25-34. doi:10.1016/j.neuro.2023.12.003 PMID:38065417 PMCID:10842331

2023

• Behan-Bush RM, Liszewski JN, Schrodt MV, Vats B, Li X, Lehmler H, Klingelhutz AJ, Ankrum J. 2023. Toxicity impacts on human adipose mesenchymal stem/stronal cells acutely exposed to aroclor and non-aroclor mixtures of polychorinated biphenyl. Environ Sci Technol 57(4):1731-1742. doi:10.1021/acs.est.2c07281 PMID:36651682 PMCID:PMC9893815
• Bullert AJ, Li X, Chunyun Z, Lee K, Pulliam CF, Cagle B, Doorn JA, Klingelhutz AJ, Robertson LW, Lehmler H. 2023. Disposition and metabolomic effects of 2,2',5,5'-tetrachlorobiphenyl in female rats following intraperitoneal exposure. Environ Toxicol Pharmacol 102:104245. doi:10.1016/j.etap.2023.104245 PMID:37572994
• Gourronc FA, Chimenti MS, Lehmler H, Ankrum J, Klingelhutz AJ. 2023. Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes. Toxicol Vitro 89:105568. doi:10.1016/j.tiv.2023.105568 PMID:36804509 PMCID:PMC10081964
• Li X, Bullert AJ, Han W, Yang W, Zhang Q, Ding X, Lehmler H. 2023. Enantiomeric fractions reveal differences in the atroposelective disposition of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) in wildtype, cyp2abfgs-null, and CYP2A6-humanized mice. Chem Res Toxicol doi:10.1021/acs.chemrestox.3c00128 PMID:37467352
• Mouat JS, Li X, Neier K, Zhu Y, Mordaunt CE, La Merrill MA, Lehmler H, Jones MP, Lein PJ, Schmidt RJ, LaSalle J. 2023. Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment. Environ Res 220:115227. doi:10.1016/j.envres.2023.115227 PMID:36608759
• Paranjape N, Dean LE, Martinez A, Tjalkens RB, Lehmler H, Doorn JA. 2023. Structure-activity relationship of lower chlorinated biphenyls and their human-relevant metabolites for astrocyte toxicity. Chem Res Toxicol 36(6):971-981. doi:10.1021/acs.chemrestox.3c00095 PMID:37279407 PMCID:PMC10283044
• Wang H, Bullert AJ, Li X, Stevens HE, Klingelhutz AJ, Ankrum J, Adamcakova-Dodd A, Thorne PS, Lehmler H. 2023. Use of a polymeric implant system to assess the neurotoxicity of subacute exposure to 2,2',5,5'-tetrachlorobiphenyl-4-ol, a human metabolite of PCB 52, in male adolescent rats. Toxicology 500:153677. doi:10.1016/j.tox.2023.153677 PMID:37995827 PMCID:PMC10757425
• Zhang C, Li X, Stietz KP, Sethi S, Yang W, Marek RF, Ding X, Lein PJ, Hornbuckle KC, Lehmler H. 2023. Rebuttal to correspondence on "machine learning-assisted identification and quantification of hydroxylated metabolites of polychlorinated biphenyls in animal samples". Environ Sci Technol 57(15):6251-6252. doi:10.1021/acs.est.3c01659 PMID:37017328

2022

• Gourronc FA, Helm BK, Robertson LW, Chimenti MS, Joachim-Lehmler H, Ankrum J, Klingelhutz AJ. 2022. Transcriptome sequencing of 3,3',4,4',5-Pentachlorobiphenyl (PCB126)-treated human preadipocytes demonstrates progressive changes in pathways associated with inflammation and diabetes. Toxicol Vitro 83:105396. doi:10.1016/j.tiv.2022.105396 PMID:35618242 PMCID:PMC9423686
• Gourronc FA, Helm BK, Robertson LW, Chimenti MS, Lehmler H, Ankrum J, Klingelhutz AJ. 2022. Dataset of transcriptomic changes that occur in human preadipocytes over a 3-day course of exposure to 3,3',4,4',5-Pentachlorobiphenyl (PCB126). Data Brief 45:108571. doi:10.1016/j.dib.2022.108571 PMID:36131953 PMCID:PMC9483567
• Lehmler H, Uwimana E, Dean LE, Kovalchuk N, Zhang Q, Ding X. 2022. Probing the role of CYP2 enzymes in the atroposelective metabolism of polychlorinated biphenyls using liver microsomes from transgenic mouse models. Chem Res Toxicol 35(12):2310-2323. doi:10.1021/acs.chemrestox.2c00276 PMID:36473170
• Li X, Hefti MM, Marek RF, Hornbuckle KC, Wang K, Lehmler H. 2022. Assessment of polychlorinated biphenyls and their hydroxylated metabolites in postmortem human brain samples: Age and brain region differences. Environ Sci Technol 56(13):9515-9526. doi:10.1021/acs.est.2c00581 PMID:35658127 PMCID:PMC9260965
• Li X, Lim JJ, Wang K, Prasad B, Bhatt D, Cui JY, Lehmler H. 2022. The disposition of polychlorinated biphenyls (PCBs) differs between germ-free and conventional mice. Environ Toxicol Pharmacol 92:103854. doi:10.1016/j.etap.2022.103854 PMID:35331926 PMCID:PMC9090986
• Saktrakulkla P, Li X, Martinez A, Lehmler H, Hornbuckle KC. 2022. Hydroxylated polychlorinated biphenyls are emerging legacy pollutants in contaminated sediments. Environ Sci Technol 56:2269-2278. doi:10.1021/acs.est.1c04780 PMID:35107261 PMCID:PMC8851693
• Wang H, Adamcakova-Dodd A, Lehmler H, Hornbuckle KC, Thorne PS. 2022. Toxicity assessment of 91-day repeated inhalation exposure to an indoor school air mixture of PCBs. Environ Sci Technol doi:10.1021/acs.est.1c05084 PMID:34994547
• Yaghoobi B, Miller GW, Holland EB, Li X, Harvey D, Li S, Lehmler H, Pessah IN, Lein PJ. 2022. Ryanodine receptor-active non-dioxin-like polychlorinated biphenyls cause neurobehavioral deficits in larval zebrafish. Front Toxicol 4:947795. doi:10.3389/ftox.2022.947795 PMID:36278027 PMCID:PMC9582434
• Zhang C, Li X, Flor S, Ruiz P, Kruve A, Ludewig G, Lehmler H. 2022. Metabolism of 3-chlorobiphenyl (PCB 2) in a human-relevant cell line: evidence of dechlorinated metabolites. Environ Sci Technol 56(17):12460-12472. doi:10.1021/acs.est.2c03687 PMID:35994059 PMCID:PMC9573771
• Zhang C, Li X, Stietz KP, Sethi S, Yang W, Marek RF, Ding X, Lein PJ, Hornbuckle KC, Joachim-Lehmler H. 2022. Machine learning-assisted identification and quantification of hydroxylated metabolites of polychlorinated biphenyls in animal samples. Environ Sci Technol 56(18):13169-13178. doi:10.1021/acs.est.2c02027 PMID:36047920
• Zhang D, Saktrakulkla P, Marek RF, Lehmler H, Wang K, Thorne PS, Hornbuckle KC, Duffel MW. 2022. PCB sulfates in serum from mothers and children in urban and rural US communities. Environ Sci Technol doi:10.1021/acs.est.2c00223 PMID:35500099 PMCID:PMC9118556

2021

• Bullert AJ, Doorn JA, Stevens HE, Lehmler H. 2021. The effects of polychlorinated biphenyl exposure during adolescence on the nervous system: A comprehensive review. Chem Res Toxicol 34(9):doi:10.1021/acs.chemrestox.1c00226 PMID:34491731 PMCID:PMC8456429
• Duffel MW, Tuttle K, Lehmler H, Robertson LW. 2021. Human hepatic microsomal sulfatase catalyzes the hydrolysis of polychlorinated biphenyl sulfates: A potential mechanism for retention of hydroxylated PCBs. Environ Toxicol Pharmacol 88(6):103757. doi:10.1016/j.etap.2021.103757 PMID:34688910 PMCID:PMC8595862
• Zhang C, Flor S, Ruiz P, Ludewig G, Lehmler H. 2021. Characterization of the metabolic pathways of 4-chlorobiphenyl (PCB3) in HepG2 cells using the metabolite profiles of its hydroxylated metabolites. Environ Sci Technol 55:9052-9062. doi:10.1021/acs.est.1c01076 PMID:34125531 PMCID:PMC8264946
• Zhang D, Saktrakulkla P, Tuttle K, Marek RF, Lehmler H, Wang K, Hornbuckle KC, Duffel MW. 2021. Detection and quantification of polychlorinated biphenyl sulfates in human serum. Environ Sci Technol 55:2473-2481. doi:10.1021/acs.est.0c06983 PMID:33502843 PMCID:PMC7924310

2020

• Egusquiza RJ, Ambrosio ME, Wang SG, Kay KM, Zhang C, Lehmler H, Blumberg B. 2020. Evaluating the role of the steroid and xenobiotic receptor (SXR/PXR) in PCB-153 metabolism and protection against associated adverse effects during perinatal and chronic exposure in mice. Environ Health Perspect 128:16. doi:10.1289/EHP6262 PMID:32352317 PMCID:PMC7228131
• Grimm FA, Klaren WD, Li X, Lehmler H, Karmakar M, Robertson LW, Chiu WA, Rusyn I. 2020. Cardiovascular effects of polychlorinated biphenyls and their major metabolites. Environ Health Perspect 128:77008. doi:10.1289/EHP7030 PMID:32701041 PMCID:PMC7377239
• Li X, Zhang C, Wang K, Lehmler H. 2020. Fatty liver and impaired hepatic metabolism alter the congener-specific distribution of polychlorinated biphenyls (PCBs) in mice with a liver-specific deletion of cytochrome P450 reductase. Environ Pollut 266:115233. doi:10.1016/j.envpol.2020.115233 PMID:32712482 PMCID:PMC7492420
• Wang H, Adamcakova-Dodd A, Flor S, Gosse L, Klenov V, Stolwijk J, Lehmler H, Hornbuckle KC, Ludewig G, Thorne PS. 2020. Comprehensive subchronic inhalation toxicity assessment of an indoor school air mixture of PCBs. Environ Sci Technol 54:15976-15985. doi:10.1021/acs.est.0c04470 PMID:33256405 PMCID:PMC7879961
• Zhang C, Flor S, Ruiz P, Dhakal RC, Hu X, Teesch LM, Ludewig G, Lehmler H. 2020. 3,3'-dichlorobiphenyl is metabolized to a complex mixture of oxidative metabolites, including novel methoxylated metabolites, by HepG2 cells. Environ Sci Technol 54:12345-12357. doi:10.1021/acs.est.0c03476 PMID:32910851 PMCID:PMC7544623