Chemicals In Man Research Articles

Multi-library synchronization for suspect screening using LC-HRMS: The importance of InChIkeys

To generate two major LC-HRMS semi-targeted screening libraries in addition to the in-house targeted library: (1) an extended general toxicology library by synchronizing an in-house targeted library with compounds found in Baselt's 12th Edition of Disposition of Toxic Drugs and Chemicals in Man, and (2) the extended general toxicology library synchronized with HighResNPS, a comprehensive database of NPS. Firstly, InChiKeys for the compounds ( n = 1765) in the Waters Forensic Toxicology Screening Library (i.e. the targeted Library) were extracted in addition to the observed retention times and product ions. Secondly, compounds listed in Baselt ( n = 2057) were extracted from the contents and then converted to simplified molecular-input line-entry system (SMILES) strings and InChIKeys using Python's cheminformatics package, rdkit. Compounds which were not suited for LC-ESI-MS analysis, such as volatiles and elements, and compounds with masses either less than 50 Da or greater than 1,000 Da were removed. The precursor ion masses of the remaining compounds were calculated from the SMILES string. Lastly, the January 2022 library was downloaded from HighResNPS ( n = 2166), which contained InChIKeys and, both observed ( n = 351) and predicted ( n = 1815) retention times. Using the connectivity layer of the InChIKey, i.e. the first 14 characters, the target library and the Baselt library were combined so that only the unique compounds from each library were included to create the Baselt semi-target library. Similarly, the Baselt semi-target library was then combined with the HighResNPS library to create the HighResNPS semi-target library. These libraries were then converted to a Waters Corporation UNIFI library format (.ulc) and applied to special cases submitted in 2021–2022. The Baselt semi-target library consisted of 2690 compounds of which 925 were unique to the Baselt library while the HighResNPS semi-targeted library consisted of 4242 compounds of which, 1552 were unique to the HighResNPS library. The application of the Baselt semi-target library to selected special cases resulted in the detection of compounds like vortioxetine, darunavir, abacavir, zonisamide, drotaverine and brexpiprazole were detected in blood. Similarly, 3-Me-PCPy and 5F-3,5-AB-PFUPPYCA were detected in seized material using the HighResNPS semi-target library. The use of only the in-house targeted libraries would have missed these relevant compounds in both forensic toxicology and forensic chemistry contexts. The use of InChIKeys rather than compound names or other standard identifiers made it easy to identify the unique compounds in each of the selected libraries with little effort and thus increased the scope by 52% and 140% relative to the target library. Inclusion of InChIKeys in target libraries offers the possibility for laboratories to synchronize their libraries with libraries from other laboratories to broaden their screening capacity.

Disposition of Toxic Drugs and Chemicals in Man, 12th Edition

Disposition of Toxic Drugs and Chemicals in Man, 12th Edition

Extrapolation of in vitro structural alerts for mutagenicity to the in vivo endpoint.

As part of the hazard and risk assessment of chemicals in man, it is important to assess the ability of a chemical to induce mutations in vivo. Because of the commonalities in the molecular initiating event, mutagenicity in vitro can correlate well to the in vivo endpoint for certain compound classes; however, the difficulty lies in identifying when this correlation holds true. In silico alerts for in vitro mutagenicity may therefore be used as the basis for alerts for mutagenicity in vivo where an expert assessment is carried out to establish the relevance of the correlation. Taking this into account, a data set of publicly available transgenic rodent gene mutation assay data, provided by the National Institute of Health Sciences of Japan, was processed in the expert system Derek Nexus against the in vitro mutagenicity endpoint. The resulting predictivity was expertly reviewed to assess the validity of the observed correlations in activity and mechanism of action between the two endpoints to identify suitable in vitro alerts for extension to the in vivo endpoint. In total, 20 alerts were extended to predict in vivo mutagenicity, which has significantly improved the coverage of this endpoint in Derek Nexus against the data set provided. Updating the Derek Nexus knowledge base in this way led to an increase in sensitivity for this data set against this endpoint from 9% to 66% while maintaining a good specificity of 89%.

Disposition of Toxic Drugs and Chemicals in Man—11th Edition

Disposition of Toxic Drugs and Chemicals in Man—11th Edition

Disposition of Toxic Drugs and Chemicals in Man

Disposition of Toxic Drugs and Chemicals in Man

R. C. Baselt (ed.): Disposition of toxic drugs and chemicals in man, 10th edition

R. C. Baselt (ed.): Disposition of toxic drugs and chemicals in man, 10th edition

Case reports in forensic toxicology

Case reports in forensic toxicology

Book Review: Disposition of Toxic Drugs and Chemicals in Man (9th ed)

Book Review: Disposition of Toxic Drugs and Chemicals in Man (9th ed)

Review of Disposition of Toxic Drugs and Chemicals in Man, Ninth Edition

Review of Disposition of Toxic Drugs and Chemicals in Man, Ninth Edition

Book Review: Disposition of Toxic Drugs and Chemicals in Man, Ninth Edition

Book Review: Disposition of Toxic Drugs and Chemicals in Man, Ninth Edition

Disposition of Toxic Drugs and Chemicals in Man, 8th ed

American Journal of Therapeutics: March 2009 - Volume 16 - Issue 2 - p 199 doi: 10.1097/MJT.0b013e31818de2e2

Review of: Disposition of Toxic Drugs and Chemicals in Man, 8th ed.

Review of: <i>Disposition of Toxic Drugs and Chemicals in Man, 8th ed.</i>

Review of: Disposition of Toxic Drugs and Chemicals in Man, 7th Edition

Review of: Disposition of Toxic Drugs and Chemicals in Man, 7th Edition

Disposition of toxic drugs and chemicals in man, 7th edn

Disposition of toxic drugs and chemicals in man, 7th edn

Review of: Experimental and Clinical Neurotoxicology

Abstract For practicing postmortem forensic toxicologists there are a small number of undisputed first line texts, such as Baselt's Disposition of Toxic Drugs and Chemicals in Man, relied on daily for interpretive assistance. There are then the second line texts such as Ellenhorn and Barceleoux, and Goodman and Gilman, relied on for more specific pharmacological information, and clinical presentation, and in cases where there is no prior published data to assist in interpretation. Spencer and Schaumburg's text would fit well on the shelf beside these other volumes, as a resource for some of the specific neurotoxicological mechanisms that can be invoked to rationalize or explain the evident consequences of overdose with therapeutic or abuse drugs, or exposure to environmental, bacterial, animal, and fungal toxins.

Review of: Drug Effects on Psychomotor Performance

Abstract The first book reached for by most forensic toxicologists practicing in the postmortem drug testing arena is Baselt's Disposition of Toxic Drugs and Chemicals in Man, currently in its fourth edition. Baselt has, with this new volume, provided those toxicologists practicing in the impaired driving arena with a similarly valuable resource. Covering most of the commonly prescribed, centrally acting drugs, and a wide range of illicit drugs, the book contains 140 monographs. The format will be familiar to users of Baselt's original work. Each section succinctly reviews the pharmacology of each drug, considering publications of clinical trial data, recommended doses and associated plasma concentrations of both the parent and metabolites, when they are known, the drug's metabolism, and the warnings contained in the Physicians Desk Reference for the drug with respect to its potential effects on driving, or psychomotor skills. This is followed by a review of laboratory studies, which have included assessment of psychomotor effects from the use of the drug. Review of these studies is made more intelligible by the inclusion of a glossary of technical terms. Further sections are included on driving studies (where they exist) and epidemiology. Finally, Baselt summarizes all the material in terms of whether, and in what circumstances, there is evidence of psychomotor impairment. He is careful, however, to stress when these conclusions are based on specific driving studies and when they are inferred from more primary effects.

Disposition of Toxic Drugs and Chemicals in Man, 5th ed. R.C. Baselt. Foster City, CA: Chemical Toxicology Institute, 1999, 900 pp., $119.00. ISBN 0-9626523-3-4.

As budgets tighten, many laboratories and clinical laboratory scientists opt not to buy each new edition of the volumes that line our bookcases. Baselt’s Disposition of Toxic Drugs and Chemicals in Man is one for which I make an exception. Now in its 5th edition, this book continues to be a quick and easy reference for those calls on Friday afternoon or …

Scope and Limitation of Some Approaches to Predicting Contact Hypersensitivity

Allergic contact dermatitis (ACD) is the endpoint of a complex sequence of events. Construction of a predictive computational assay requires a combination of statistical analyses, semi-empirical modelling, chemical acumen and a good understanding of prohapten activation. Main events on the path to the altered self are chemical and microbial conversion on and in the stratum corneum (SC), epidermal penetration, non-specific binding, and finally hapten–protein conjugation. This report reviews the principal approaches currently taken in the prediction of ACD, using computer-based SAR, QSAR and expert systems, and also includes the BIOSAR models, which combine statistical analysis with chemical knowledge. Specifically designed to predict the ACD potential of chemicals in man, the BIOSAR approach of two-value regression analysis achieved a success rate of 88% when trained on a set of 72 compounds of wide diversity, with a sensitivity of 83% and specificity of 100%.

Percutaneous Absorption of Salicylic Acid, Theophylline, 2,4-Dimethylamine, Diethyl Hexyl Phthalic Acid, andp-Aminobenzoic Acid in the Isolated Perfused Porcine Skin Flap Compared to Manin Vivo

Human risk assessment for topical exposure requires percutaneous absorption data to link environmental contamination to potential systemic dose. Human absorption data are not readily available, so absorption models are used.In vitrodiffusion systems are easy to use but have proved to be somewhat unreliable and are not validated to man. This study compares percutaneous absorption in the isolated perfused porcine skin flap (IPPSF) system with that in manin vivo.The study design utilized the same compounds and the same dose concentration and vehicle in both systems. Methodology for each system was that which is routinely used ineach system. The skin surface was not protected during the absorption dosing period. Percutaneous absorption values were, for man and the IPPSF system, respectively: salicylic acid (6.5 ± 5.0%; 7.5 ± 2.6%), theophylline (16.9 ± 11.3%; 11.8 ± 3.8%), 2,4-dimethylamine (1.1 ± 0.3%; 3.8 ± 0.6%), diethyl hexyl phthalic acid (1.8 ± 0.5%; 3.9 ± 2.4%), andp-aminobenzoic acid (11.5 ± 6.3%; 5.9 ± 3.7%) (correlation coefficient was 0.78;p< 0.04).The skin surface wash recovery postapplication was similar for salicylic acid in man (53.4 ± 6.3%) and the IPPSF system (48.2 ± 4.9%). With the other compounds the majority of surface chemical was recovered in the surface wash and skin tape strip in the IPPSF system. With man, other than salicylic acid, only a few percent applied dose was recovered with surface washing and tape stripping. Since the wash procedure was effective with pig skin, we can assume that these chemicals in man were lost to adsorption to any clothing or bedding with the volunteers. The absorption in man was not less than that in the IPPSF. Assuming the dose was lost in man, it seems plausible that whatever compound was to penetrate human skin in solvent vehicle did so in the period of time before the chemical was removed.The IPPSF system appears to be a good model for predicting percutaneous absorption relative to man. This study design should be used to validate other systems to humansin vivo.

Review of Disposition of Toxic Drugs and Chemicals in Man (Fourth Edition)

Abstract It has been over 15 years since the first edition of Baselt's “Disposition of Toxic Drugs and Chemicals in Man” was published and it is hard to imagine the practice of forensic toxicology without this valuable resource. Over the years, from the first edition to the current fourth edition, several changes have occurred. The organization of the book has changed, from a two volume set divided into centrally acting drugs and peripherally acting/other toxicants to its current alphabetical listing of toxicants. Beginning with the third edition and continuing with this edition, Robert Cravey has joined Dr. Baselt as a co-editor. Most dramatically, the number of toxic substances has more than doubled, from less than 200 in the first edition to over 400 in the fourth edition.