Toxnet: A computerized collection of toxicological and environmental health information

Fonger, George Charles; Stroup, Dorothy; Thomas, Phillip L.; Wexler, Philip

doi:10.1177/074823370001600101

Cited by 36 publications

(20 citation statements)

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“…The most common, acute exposures to TMT appear to be occupational during plastic manufacture or other industrial processes that require heating of plastic. Ingestion of organotin polluted food or water in areas heavily affected by plastics manufacturing is also likely to be of increasing concern (Fonger et al, 2000; Tang et al, 2010). Intoxication with TMT leads to profound behavioral and cognitive deficits in both humans (Fortemps et al, 1978) and experimental animals (Fonger et al, 2000; Hlinak et al, 2008; Ishida et al, 1997; Kim et al, 2009; Niittykoski et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Ingestion of organotin polluted food or water in areas heavily affected by plastics manufacturing is also likely to be of increasing concern (Fonger et al, 2000; Tang et al, 2010). Intoxication with TMT leads to profound behavioral and cognitive deficits in both humans (Fortemps et al, 1978) and experimental animals (Fonger et al, 2000; Hlinak et al, 2008; Ishida et al, 1997; Kim et al, 2009; Niittykoski et al, 1998). The neurotoxic presentation most frequently reported in human cases is a limbic-cerebellar syndrome, the manifestations of which include memory defects, confusion, seizures, tinnitus, insomnia, and depression (Saary and House, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Trimethyltin chloride (TMT) neurobehavioral toxicity in embryonic zebrafish

Chen

Huang

Zheng

et al. 2011

Neurotoxicology and Teratology

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Trimethyltin chloride (TMT) is a neurotoxicant that is widely present in the aquatic environment, primarily from the manufacture of PVC plastic, but few studies have evaluated aquatic neurotoxicity. We have examined TMT dose-dependent malformation and neurobehavioral toxicity in the embryonic zebrafish model. Exposure of embryos to TMT (0–10 μM) from 48–72 hours post fertilization (hpf) elicited a concentration-related increase (0–100%) in malformation incidence with an EC25 of 5.55 μM. TMT also significantly modulated the frequency of tail flexion, the earliest motor behavior observed in developing zebrafish, and the ability to respond to a mechanical tail touch. Exposure to 5 μM TMT from 48–72 hpf modulated the photomotor response at 4 and 5 days post fertilization and significantly promoted apoptosis in the tail. Our study demonstrates the morphological and behavioral sensitivity of the developing zebrafish to TMT and establishes a platform for future identification of the affected pathways and chemical modulators of TMT toxicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trimethyltin chloride (TMT) neurobehavioral toxicity in embryonic zebrafish

Chen

Huang

Zheng

et al. 2011

Neurotoxicology and Teratology

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“…Surviving hits were docked into the binding pocket of MGL using LibDock docking engine (Diller & Merz, ; Rao et al., ). Successful agrochemicals were prioritized for in vitro and in vivo testing based on their oral LD 50 values (for rats) as reported in TOXNET (Fonger, Stroup, Thomas, & Wexler, ). LD 50 refers to the amount of ingested substance that kills 50 percent of tested animals.…”

Section: Resultsmentioning

confidence: 99%

The herbicide quinclorac as potent lipase inhibitor: Discovery via virtual screening and in vitro/in vivo validation

2019

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Lipolysis is primarily controlled by the stepwise action of hormone‐sensitive lipase (HSL) and monoglyceride lipase (MGL) to release free fatty acids and glycerol. A high level of circulating free fatty acids is well‐known to mediate insulin resistance. Thus, the need to discover lipase inhibitors against both enzyme systems remains urgent. Agrochemicals are tightly regulated chemicals and therefore are potential source of new medicinal agents. Accordingly, we implemented a computational workflow to search for new lipase inhibitory leads by virtually screening commercial agrochemicals against HSL and MGL employing binding pharmacophores and docking experiments. Ten agrochemicals were identified as potential lipase inhibitors, out of which quinclorac, a safe herbicide, achieved high‐ranking score. Subsequent in vitro evaluation against rat epididymal lipase activity showed quinclorac to exhibit nanomolar anti‐lipase IC50. Subsequent in vivo testing showed quinclorac to significantly decrease blood glycerol levels after acute exposure (150 mg/kg) and multiple dosing (50 or 25 mg/kg) (p < 0.05).

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“…Data contained in these databases are generally curated as far as possible, which make them suitable to build a dataset for predictive modeling. The “Supplier” group contained a majority of databases that are supported by governmental agencies, such as PubChem, ChEMBL, DSSTox, TOXNET, ToxCast, Open TG‐GATEs, DTP, or even DrugMatrix . Most of them contains in vitro and/or in vivo assays, as well as information about experimental protocols, which is important to create homogeneous datasets .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Network Map of ADME‐Tox Databases

Canault

Bourg

Vayer

et al. 2017

Molecular Informatics

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In the last decade, many statistical-based approaches have been developed to improve poor pharmacokinetics (PK) and to reduce toxicity of lead compounds, which are one of the main causes of high failure rate in drug development. Predictive QSAR models are not always very efficient due to the low number of available biological data and the differences in the experimental protocols. Fortunately, the number of available databases continues to grow every year. However, it remains a challenge to determine the source and the quality of the original data. The main goal is to identify the relevant databases required to generate the most robust predictive models. In this study, an interactive network of databases was proposed to easily find online data sources related to ADME-Tox parameters data. In this map, relevant information regarding scope of application, data availability and data redundancy can be obtained for each data source. To illustrate the usage of data mining from the network, a dataset on plasma protein binding is selected based on various sources such as DrugBank, PubChem and ChEMBL databases. A total of 2,606 unique molecules with experimental values of PPB were extracted and can constitute a consistent dataset for QSAR modeling.

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Toxnet: A computerized collection of toxicological and environmental health information

Cited by 36 publications

References 0 publications

Trimethyltin chloride (TMT) neurobehavioral toxicity in embryonic zebrafish

Trimethyltin chloride (TMT) neurobehavioral toxicity in embryonic zebrafish

The herbicide quinclorac as potent lipase inhibitor: Discovery via virtual screening and in vitro/in vivo validation

Comprehensive Network Map of ADME‐Tox Databases

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