A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment DOI Creative Commons
Lucia Vergauwen, Lola Bajard, Sabrina Tait

et al.

Open Research Europe, Journal Year: 2024, Volume and Issue: 4, P. 242 - 242

Published: Nov. 6, 2024

Thyroid hormone system disruption (THSD) is a growing concern in chemical hazard assessment due to its impact on human and environmental health the scarce methods available for assessing THSD potential of chemicals. In particular, general lack validated silico vitro THS activity high concern. This manuscript provides an inventory test relevant THSD. Building Organisation Economic Co-operation Development (OECD) Guidance Document 150 recent international developments, we highlight progress methods, as well vivo assays. The provided categorizes according levels OECD Conceptual Framework, with validation status each method. At Level 1, 12 models that have been statistically are directly related identified. 2, 67 listed including those assessed key initiatives such European Union Network Laboratories Validation Alternative Methods (EU-NETVAL) study identify thyroid disruptors. Levels 3-5, THSD-sensitive endpoints being included existing fish-based Test Guidelines complement amphibian total, counts 108 entries comprising established (e.g., Guidelines) citable under further development some cases ready or initial stages validation. work aims support ongoing strategies regulatory assessment, integrated approaches testing (IATAs), endocrine disruptors, addressing critical gaps current landscape both contexts.

Language: Английский

Aged Biodegradable Nanoplastics Enhance Body Accumulation Associated with Worse Neuronal Damage in Caenorhabditis elegans DOI
Tianshu Wu, Jing He,

Zongjian Ye

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The environmental and health challenges posed by petroleum-based biodegradable plastics, such as polybutylene succinate (PBS) polybutyleneadipate-co-terephthalate (PBAT), are a significant concern because they increasingly present in the environment contribute substantial proportion of microplastics (MPs) or nanoplastics (NPs). In this study, ultraviolet (UV)-aged PBS-NPs PBAT-NPs found to have higher propensity accumulate within body Caenorhabditis elegans (C. elegans) prolonging defecation interval, which could induce severe neuronal damage compared pristine NPs. increased accumulation (BNPs) subsequent impairments neurobehavior highly attributed their reduced particle size altered surface properties, including changed chemical bonds functional groups after photoaging. Aged BNPs also cause more GABAergic neurons neurotransmitter receptors, resulting disrupted homeostasis behaviors. Overall, both PBS PBAT components show no differences biological mechanisms neural damage, highlighting commonalities characteristics adverse effects on nervous system. Our study opens up exploration impacts photoaging degradation state that environment.

Language: Английский

Citations

1
Assessment of developmental neurotoxicity of pharmaceuticals using zebrafish behavior DOI
Yuhei Nishimura

Folia Pharmacologica Japonica, Journal Year: 2025, Volume and Issue: 160(2), P. 115 - 119

Published: Feb. 28, 2025

妊娠期・周産期における医薬品の利用は,児へ影響することなく,母体の健康状態を改善することが求められる.この安全性を担保するためには,医薬品の発達神経毒性も加味して評価する必要がある.経済協力開発機構(OECD)は医薬品を含む様々な化学物質の発達神経毒性評価のテストガイドライン(TG426)を制定している.TG426では,妊娠および授乳期の動物(主にラット)に化学物質を投与し,脳重量や神経病理学的検査と,自発運動量や感覚機能,学習・記憶などの行動評価を用いて,離乳前から離乳後の育成期間の児の影響を評価する.TG426は多大な費用・時間・労力を要することもあり,これまでにTG426を用いて発達神経毒性が評価された化学物質は200程度にとどまっている.より多くの化学物質の発達神経毒性評価の実現に向け,OECDは幹細胞やオルガノイドなどのin vitro試験を組み合わせた発達神経毒性評価の新たな指針(No. 377)を制定するとともに,ゼブラフィッシュを用いた行動解析の利用について検討を進めている.本稿では,ヒトにおける発達神経毒性が疫学的に実証されており,OECDが定めた発達神経毒性陽性化合物でもあるバルプロ酸に焦点を絞り,ゼブラフィッシュ仔魚と成魚の行動解析を用いた医薬品の発達神経毒性評価の有用性・妥当性について考察する.

Language: Английский

Citations

0
Enantiospecific Positive Allosteric Modulation of α4β2 Nicotinic Receptor Subtypes DOI

Josue Gaona,

Pradip K. Gadekar,

Khaldoun S. Abdelwahed

et al.

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Nicotinic acetylcholine receptors (nAChRs) are integral to brain function, playing critical roles in cognition and reward pathways. Among these, α4β2 nAChRs key targets for developing therapeutics address nicotine addiction cognitive disorders. Here, we report the synthesis, stereochemical resolution, pharmacological evaluation of GAT2800, a racemic compound identified as positive allosteric modulator (PAM) nAChRs. Enantiomeric resolution yielded inactive S-enantiomer (GAT2801) pharmacologically active R-enantiomer (GAT2802), with their configurations confirmed via X-ray crystallography. Two-electrode voltage-clamp recordings from Xenopus oocytes expressing revealed that GAT2802, but not GAT2801, significantly potentiates current responses both high-sensitivity (HS) (α4)2(β2)3 low-sensitivity (LS) (α4)3(β2)2 isoforms, EC50 values ∼1 ∼0.8 μM, respectively. Notably, GAT2802 enhanced ACh efficacy more profoundly HS nAChR while showing minimal activity at α3-containing Computational docking analyses provided insight into potential binding sites subunit interfaces within transmembrane domain. Mutational α4Cys233 located first helix projecting β2:α4 interface, molecular determinant selectivity α4- over Safety demonstrated negligible cellular toxicity HEK cells no significant developmental effects zebrafish larvae concentrations up 100 μM. These findings establish promising lead development selective PAMs, therapeutic

Language: Английский

Citations

0
Exploring the Mechanisms of Neurotoxic effects from Combined Exposure to Polystyrene and Microcystin-LR in Caenorhabditis elegans DOI

Luyu Pei,

Lina Sheng, Yongli Ye

et al.

Aquatic Toxicology, Journal Year: 2025, Volume and Issue: 284, P. 107403 - 107403

Published: May 7, 2025

Language: Английский

Citations

0
An Overview of Current New Approach Methodologies for Developmental Toxicity and the Current Research Gaps DOI
Elizabeth M. Martin,

J Vidal

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment DOI Creative Commons
Lucia Vergauwen, Lola Bajard, Sabrina Tait

et al.

Open Research Europe, Journal Year: 2024, Volume and Issue: 4, P. 242 - 242

Published: Nov. 6, 2024

Thyroid hormone system disruption (THSD) is a growing concern in chemical hazard assessment due to its impact on human and environmental health the scarce methods available for assessing THSD potential of chemicals. In particular, general lack validated silico vitro THS activity high concern. This manuscript provides an inventory test relevant THSD. Building Organisation Economic Co-operation Development (OECD) Guidance Document 150 recent international developments, we highlight progress methods, as well vivo assays. The provided categorizes according levels OECD Conceptual Framework, with validation status each method. At Level 1, 12 models that have been statistically are directly related identified. 2, 67 listed including those assessed key initiatives such European Union Network Laboratories Validation Alternative Methods (EU-NETVAL) study identify thyroid disruptors. Levels 3-5, THSD-sensitive endpoints being included existing fish-based Test Guidelines complement amphibian total, counts 108 entries comprising established (e.g., Guidelines) citable under further development some cases ready or initial stages validation. work aims support ongoing strategies regulatory assessment, integrated approaches testing (IATAs), endocrine disruptors, addressing critical gaps current landscape both contexts.

Language: Английский

Citations

1