PMID- 37995827 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240323 IS - 1879-3185 (Electronic) IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 500 DP - 2023 Dec TI - 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. PG - 153677 LID - S0300-483X(23)00264-0 [pii] LID - 10.1016/j.tox.2023.153677 [doi] AB - Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that ubiquitously exist in the environment. PCB exposure has been linked to cancer and multi-system toxicity, including endocrine disruption, immune inhibition, and reproductive and neurotoxicity. 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) is one of the most frequently detected congeners in the environment and human blood. The hydroxylated metabolites of PCB 52 may also be neurotoxic, especially for children whose brains are still developing. However, it is challenging to discern the contribution of these metabolites to PCB neurotoxicity because the metabolism of PCB is species-dependent. In this study, we evaluated the subacute neurotoxicity of a human-relevant metabolite, 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-52), on male adolescent Sprague Dawley rats, via a novel polymeric implant drug delivery system grafted subcutaneously, at total loading concentrations ranging from 0%, 1%, 5%, and 10% of the implant (w/w) for 28 days. Y-maze, hole board test, open field test, and elevated plus maze were performed on exposure days 24-28 to assess their locomotor activity, and exploratory and anxiety-like behavior. 4-52 and other possible hydroxylated metabolites in serum and vital tissues were quantified using gas chromatography with tandem mass spectrometry (GC-MS/MS). Our results demonstrate the sustained release of 4-52 from the polymeric implants into the systemic circulation in serum and tissues. Dihydroxylated and dechlorinated metabolites were detected in serum and tissues, depending on the dose and tissue type. No statistically significant changes were observed in the neurobehavioral tasks across all exposure groups. The results demonstrate that subcutaneous polymeric implants provide a straightforward method to expose rats to phenolic PCB metabolites to study neurotoxic outcomes, e.g., in memory, anxiety, and exploratory behaviors. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Wang, Hui AU - Wang H AD - Department of Occupational and Environmental Health, the University of Iowa, Iowa City, IA, USA. FAU - Bullert, Amanda J AU - Bullert AJ AD - Department of Occupational and Environmental Health, the University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Neuroscience, the University of Iowa, Iowa City, IA, USA. FAU - Li, Xueshu AU - Li X AD - Department of Occupational and Environmental Health, the University of Iowa, Iowa City, IA, USA. FAU - Stevens, Hanna AU - Stevens H AD - Interdisciplinary Graduate Program in Neuroscience, the University of Iowa, Iowa City, IA, USA; Department of Psychiatry, the University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Human Toxicology, the University of Iowa, Iowa City, IA, USA. FAU - Klingelhutz, Aloysius J AU - Klingelhutz AJ AD - Department of Microbiology & Immunology, the University of Iowa, Iowa City, IA, USA. FAU - Ankrum, James A AU - Ankrum JA AD - Roy J. Carver Department of Biomedical Engineering, the University of Iowa, Iowa City, IA, USA. FAU - Adamcakova-Dodd, Andrea AU - Adamcakova-Dodd A AD - Department of Occupational and Environmental Health, the University of Iowa, Iowa City, IA, USA. FAU - Thorne, Peter S AU - Thorne PS AD - Department of Occupational and Environmental Health, the University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Neuroscience, the University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Human Toxicology, the University of Iowa, Iowa City, IA, USA. FAU - Lehmler, Hans-Joachim AU - Lehmler HJ AD - Department of Occupational and Environmental Health, the University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Neuroscience, the University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Human Toxicology, the University of Iowa, Iowa City, IA, USA. Electronic address: hans-joachim-lehmler@uiowa.edu. LA - eng GR - P30 ES005605/ES/NIEHS NIH HHS/United States GR - P42 ES013661/ES/NIEHS NIH HHS/United States GR - P50 HD103556/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20231122 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 1EH557950R (2,5,2',5'-tetrachlorobiphenyl) RN - DFC2HB4I0K (Polychlorinated Biphenyls) SB - IM MH - Child MH - Rats MH - Humans MH - Male MH - Adolescent MH - Animals MH - *Polychlorinated Biphenyls/chemistry MH - Rats, Sprague-Dawley MH - Tandem Mass Spectrometry MH - *Neoplasms MH - *Neurotoxicity Syndromes/etiology PMC - PMC10757425 MID - NIHMS1951577 OTO - NOTNLM OT - 2,2',5,5'-tetrachlorobiphenyl-4-ol OT - Adolescent rats OT - Neurotoxicity OT - Polymeric implant OT - Subacute exposure COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/11/24 00:42 MHDA- 2023/12/17 09:44 PMCR- 2024/12/01 CRDT- 2023/11/23 19:27 PHST- 2023/09/05 00:00 [received] PHST- 2023/11/06 00:00 [revised] PHST- 2023/11/18 00:00 [accepted] PHST- 2024/12/01 00:00 [pmc-release] PHST- 2023/12/17 09:44 [medline] PHST- 2023/11/24 00:42 [pubmed] PHST- 2023/11/23 19:27 [entrez] AID - S0300-483X(23)00264-0 [pii] AID - 10.1016/j.tox.2023.153677 [doi] PST - ppublish SO - Toxicology. 2023 Dec;500:153677. doi: 10.1016/j.tox.2023.153677. Epub 2023 Nov 22.