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Overview of Forensic Toxicology, Yesterday, Today and in the Future

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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 22818

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Special Issue Editors

Dr. Antonina Argo

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Guest Editor

Pro.Mi.Se. Department, University of Palermo, 90133 Palermo, Italy
Interests: legal medicine, forensic toxicology; DFSA, forensic pathology; victims of sexual abuse and violent crime; diagnostic and medico legal assessment; ethics in research
Special Issues, Collections and Topics in MDPI journals

Dr. Marija Caplinskiene

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Guest Editor

State Forensic Medicine Service, Mykolas Romeris University, Vilnius, Lithuania
Interests: forensic medicine; forensic toxicology; forensic genetics; forensic pathology; legal medicine

Special Issue Information

Dear Colleagues,

Forensic toxicology is currently facing the challenges of great analytical complexity and of increasingly sophisticated interpretative models of laboratory parameters. These developments imply a continued improvement in the investigative methodologies useful for the evaluation of xenobiotics both in living and in post-mortem samples. This Special Issue of Toxics aims to explore all areas of scientific research concerning traditional and emerging substances of abuse, inviting elaborations of their forensic and clinical implications; discussions of analytical approaches to different samples of the human body; the impact of drugs on human health and behavior, with a focus on vulnerable populations such as child exposed to drugs of abuse; adverse drug events in inmates; guidelines on medical approaches to maintenance and tolerance treatment, drug misuse and related death. Interdisciplinary and integrated forensic toxicology studies that meet these requirements are welcomed by this Special Issue.

Case studies concerning intoxication from substance abuse and overdoses of psychotropic drugs are welcomed. Other topics of interest include translational, pharmacogenetic and pharmacogenomic research, relating to substances of abuse and psychotropic drugs, in living people and post-mortem forensic casuistry; driving under the influence of alcohol and other substances of abuse; drug-facilitated sexual assault; emerging studies of postmortem biochemistry; in-depth examinations of death from intentional poisoning; suicidal and homicidal deaths induced by drugs and substances of abuse; and child accidental intoxication.

We look forward to receiving your contributions.

Dr. Antonina Argo
Dr. Marija Caplinskiene
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

forensic toxicology
analytical data
abuse
psychotropic drugs
pharmacogenetic
pharmacogenomic
poisoning
vulnerable population

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Published Papers (9 papers)

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Research

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13 pages, 616 KiB

Open AccessArticle

Effect of CYP2D6, 2C19, and 3A4 Phenoconversion in Drug-Related Deaths

by Sanaa M. Aly, Benjamin Hennart, Jean-Michel Gaulier and Delphine Allorge

Toxics 2024, 12(4), 260; https://doi.org/10.3390/toxics12040260 - 30 Mar 2024

Cited by 1 | Viewed by 1777

Abstract

Molecular autopsy is a very important tool in forensic toxicology. However, many determinants, such as co-medication and physiological parameters, should be considered for optimal results. These determinants could cause phenoconversion (PC), a discrepancy between the real metabolic profile after phenoconversion and the phenotype determined by the genotype. This study’s objective was to assess the PC of drug-metabolizing enzymes, namely CYP2D6, 2C19, and 3A4, in 45 post-mortem cases where medications that are substrates, inducers, or inhibitors of these enzymes were detected. It also intended to evaluate how PC affected the drug’s metabolic ratio (MR) in four cases. Blood samples from 45 cases of drug-related deaths were analyzed to detect and determine drug and metabolite concentrations. Moreover, all the samples underwent genotyping utilizing the HaloPlex Target Enrichment System for CYP2D6, 2C19, and 3A4. The results of the present study revealed a statistically significant rate of PC for the three investigated enzymes, with a higher frequency of poor metabolizers after PC. A compatibility was seen between the results of the genomic evaluation after PC and the observed MRs of venlafaxine, citalopram, and fentanyl. This leads us to focus on the determinants causing PC that may be mainly induced by drug interactions. This complex phenomenon can have a significant impact on the analysis, interpretation of genotypes, and accurate conclusions in forensic toxicology. Nevertheless, more research with more cases in the future is needed to confirm these results. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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11 pages, 1567 KiB

Open AccessArticle

Carbohydrate-Deficient Transferrin (CDT) as a Biomarker of Alcohol Abuse: A Retrospective Study of the Italian Drinking Trend among Drivers from 2016 to 2022

by Denise Fiorelli, Leonardo Romani, Michele Treglia, Margherita Pallocci, Pierluigi Passalacqua, Luca Coppeta, Luigi Tonino Marsella and Roberta Tittarelli

Toxics 2023, 11(11), 914; https://doi.org/10.3390/toxics11110914 - 7 Nov 2023

Cited by 1 | Viewed by 2425

Abstract

Alcohol abuse is still one of the leading causes of death worldwide. Early diagnosis of alcohol abuse enables preventive intervention on the effects and risks associated with its consumption. Carbohydrate-deficient transferrin (CDT) is one of the most reliable biomarkers of chronic alcohol misuse. We retrospectively studied a population of 12,624 subjects who had their driving license suspended for driving under the influence of alcohol or drugs from 2016 to 2022. The analytical determination of CDT was performed following a certified high-performance liquid chromatography (HPLC) method. Data were split by year, age and gender. The majority of subjects with positive %CDT were male, although the trend of positivity was similar between males and females. A steady increase in both the number of tests performed and the number of positives was observed over the years. Patients aged 41–50 years had the highest prevalence, followed by 51–60, 31–40 and 18–30 years. CDT continues to be a steady marker for diagnosis of alcohol abuse in the majority of cases. Data emerging from our study are in line with the increasing national trends on traffic accidents, injuries and deaths related to alcohol and drug DUI (driving under the influence), requiring the implementation of preventive measures to limit this ever-growing phenomenon. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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10 pages, 304 KiB

Open AccessFeature PaperArticle

Lead, Mercury, and Cadmium Concentrations in Blood Products Transfused to Neonates: Elimination Not Just Mitigation

by Sanaa M. Aly, Samar Elfiky, Yasmine G. Mohamed, Radwa A. M. Soliman, Nancy Shalaby, Nicolas Beauval, Jean-Michel Gaulier, Delphine Allorge and Ahmed Omran

Toxics 2023, 11(8), 712; https://doi.org/10.3390/toxics11080712 - 18 Aug 2023

Cited by 2 | Viewed by 1930

Abstract

Lead (Pb), mercury (Hg), and cadmium (Cd) are identified as potent developmental neurotoxicants. Neonates are the main group receiving multiple blood transfusions. The exposure of neonates to these heavy metals (HMs) can occur through blood transfusions. This study aimed to determine the concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in various blood products (plasma, platelets, packed red blood cells (pRBCs), and whole blood (WB)) to explore the probability of concurrent exposure of these HMs and to identify the metal load per transfusion with risk assessment. Residual bloods from blood bank bags were collected after neonatal transfusion. Pb, Hg, and Cd concentrations were determined in 120 samples of blood products by inductively coupled plasma mass spectrometry (ICP-MS). Pb and Cd levels were over the normal levels in 19.2 and 5.9% of all blood units, respectively. In 35 and 0.8% of blood units, the Pb and Cd concentrations, respectively, were higher than that recommended for transfusions in premature neonates. The anticipated safe value was surpassed by 2.5% for Cd of all transfusions, primarily because of WB. However, Hg was detected only in 5.8% of all samples and their concentrations were within the normal range. The concurrent neonatal exposure to Pb, Hg, and Cd was statistically significant. Hazard quotients of Hg and Cr were >1 and Pb cancer risk was 2.41 × 10⁻⁴. To the best of our knowledge, this study is the first report examining Pb, Hg, and Cd in blood products other than WB and pRBCs using ICP-MS. This study demonstrated the exposure of neonates to Pb, Hg, and Cd during transfusion with a considerable amount of Pb. It confirms the significant concurrent exposure to the three HMs, which maximize their potential developmental neurotoxicity with a high probability of developing non-carcinogenic and carcinogenic health effects. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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14 pages, 4067 KiB

Open AccessArticle

Trends in Illicit Cannabis Potency based on the Analysis of Law Enforcement Seizures in the Southern Area of Rome

by Francesca Vernich, Lucrezia Stefani, Denise Fiorelli, Federico Mineo, Margherita Pallocci, Michele Treglia, Luigi Tonino Marsella and Roberta Tittarelli

Toxics 2023, 11(8), 648; https://doi.org/10.3390/toxics11080648 - 26 Jul 2023

Cited by 4 | Viewed by 1623

Abstract

Cannabis remains the most illicitly produced and consumed substance worldwide, and the average trans-Δ9-tetrahydrocannabinol (THC) content in cannabis products (marijuana, hashish) has increased over time. This paper presents data about THC concentration in cannabis resin samples seized by law enforcement from 2015 to 2022 in the southern area of Rome (Italy). From 2015 to 2022, more than 1000 hashish samples were analyzed; the average THC content was 18.0% and dramatically increased from 13.7% (2015) to 27.1% (2022). The potency of THC in some samples characterized by unusual shape and color was higher than 24% and, in a few cases, higher than 40%. The age group most involved in seizures of cannabis resin concerned males aged between 15 and 36 years old. The spread of this phenomenon increases the risk of adverse health outcomes. Many observational studies compare the increased cannabis potency with the onset of psychosis, depression, anxiety and cannabis use disorders (CUDs), mainly in young adults. THC-potency monitoring provides data that can be helpful to create a network of communication and interaction between universities, and legislative and public health institutions to support education, awareness and surveillance related to cannabis abuse. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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Review

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25 pages, 962 KiB

Open AccessReview

Volumetric Absorptive Microsampling in Toxicology

by Bruno Pires, Gonçalo Catarro, Sofia Soares, Joana Gonçalves, Tiago Rosado, Mário Barroso, André R. T. S. Araujo and Eugenia Gallardo

Toxics 2025, 13(1), 25; https://doi.org/10.3390/toxics13010025 - 30 Dec 2024

Viewed by 697

Abstract

Volumetric absorptive microsampling (VAMS) is an emerging technique in clinical and forensic toxicology. It is recognized as a promising alternative to traditional sampling methods, offering an accurate and minimally invasive means of collecting small volumes of biological samples, such as blood, urine, and saliva. Unlike conventional methods, VAMS provides advantages in terms of sample stability, storage, and transportation, as it enables samples to be collected outside laboratory environments without requiring refrigeration. This review explores several VAMS methodologies, with a particular focus on its application for the quantification of drugs and other substances in clinical and forensic toxicology. It compares VAMS to other microsampling techniques, such as dried blood spots (DBSs), highlighting VAMS’s superiority in addressing issues related to sample volume consistency and environmental impact. Despite its advantages, VAMS also presents certain limitations, including higher costs and difficulties in detecting underfilled samples. Overall, VAMS stands out as a microsampling technique with the potential to enhance patient compliance and operational efficiency, positioning itself as a viable tool for toxicological analysis in both clinical and forensic contexts. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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Other

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1 pages, 152 KiB

Open AccessRetraction

RETRACTED: Albano et al. Systematic Review of Fatal Sodium Nitrite Ingestion Cases: Toxicological and Forensic Implications. Toxics 2024, 12, 124

by Giuseppe Davide Albano, Corinne La Spina, Roberto Buscemi, Mattia Palmeri, Giuliana Malandrino, Fausto Licciardello, Mauro Midiri, Antonina Argo and Stefania Zerbo

Toxics 2024, 12(11), 819; https://doi.org/10.3390/toxics12110819 - 15 Nov 2024

Viewed by 631

Abstract

The journal retracts the article titled “Systematic Review of Fatal Sodium Nitrite Ingestion Cases: Toxicological and Forensic Implications” [...] Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

16 pages, 1128 KiB

Open AccessEditor’s ChoiceSystematic Review

RETRACTED: Systematic Review of Fatal Sodium Nitrite Ingestion Cases: Toxicological and Forensic Implications

Toxics 2024, 12(2), 124; https://doi.org/10.3390/toxics12020124 - 1 Feb 2024

Cited by 4 | Viewed by 4610 | Retraction

Abstract

Documented cases of sodium nitrite toxicity are almost exclusively caused by accidental ingestion; however, self-poisoning with sodium nitrite represents an increasing trend in nitrate-related deaths. This systematic review summarizes the most crucial evidence regarding the fatal toxicity of sodium nitrite. It identifies gaps and differences in the diagnostic forensic approaches and the detection methods of sodium nitrite intoxication. A total of eleven research articles were selected for qualitative and quantitative data. Most of the studies (6/11) were case reports. Fifty-three cases of fatal intoxication with sodium nitrite were chosen for the review. More research is required to develop cost-effective techniques and uniform cutoffs for blood nitrite and nitrate levels in the event of deadly sodium nitrite poisoning. There is still a lack of critical information on other matrices and the impact of time since death on toxicological results in such situations. The available evidence provides useful recommendations for forensic pathologists and health practitioners engaged in instances of sodium nitrite poisoning or death. The data should also set off alarm bells in the public health system, in prosecutor’s offices, and for policymakers so that they may undertake preventative measures to stop and restrict the unregulated market for these substances. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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10 pages, 1840 KiB

Open AccessCase Report

Severe and Fatal Fentanyl Poisonings from Transdermal Systems after On-Skin and Ingestion Application

by Karina Sommerfeld-Klatta, Wiktoria Jiers, Magdalena Łukasik-Głębocka, Artur Tezyk, Klaudia Dolińska-Kaczmarek, Kamil Walter, Paweł Świderski, Szymon Rzepczyk, Barbara Zielińska-Psuja and Czesław Żaba

Toxics 2023, 11(10), 872; https://doi.org/10.3390/toxics11100872 - 20 Oct 2023

Cited by 3 | Viewed by 2605

Abstract

In recent years, the administration of fentanyl (FNTL) implicitly in transdermal drug delivery systems (TDDS) has vastly increased in chronic pain treatment. Non-medical and uncontrolled use of FNTL in TFDS (transdermal fentanyl delivery systems) may reveal toxic effects by the route of exposure, dermal or alternative, by ingestion of patches, and drug release in the stomach. The purpose of this study was to present three different cases of FNTL poisonings, two of which resulted in death due to TFDS abuse. The first case is a 66-year-old woman treated for accidental FTNL poisoning resulting in acute respiratory distress syndrome. Two remaining cases are a 31-year-old woman and a 25-year-old man who died as a result of FNTL overdose after on-skin and ingestion application of the drug patches. During the hospitalization of the 66-year-old patient, in blood samples, FNTL was confirmed at a concentration of 10.0 ng/mL. Tests run on blood taken from the corpses of 25- and 31-year-old patients exhibited FNTL presence in concentrations of 29.1 ng/mL and 38.7 ng/mL, respectively. The various routes of administration and ultimately toxic effects are important to present because, in TDDS, fentanyl can be a reason for severe to fatal poisoning, as shown by the three cases above. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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8 pages, 257 KiB

Open AccessCase Report

Causes of Death during the Intravenous Infusion of Dimethylsulphoxide and Hydrogen Peroxide in the Course of Alternative Medicine Therapy

by Szymon Rzepczyk, Paweł Świderski, Karina Sommerfeld-Klatta, Artur Tezyk, Magdalena Łukasik-Głębocka, Barbara Zielińska-Psuja, Zbigniew Żaba and Czesław Żaba

Toxics 2023, 11(8), 652; https://doi.org/10.3390/toxics11080652 - 28 Jul 2023

Cited by 2 | Viewed by 4896

Abstract

Unconventional (alternative, natural) medicine in Poland and worldwide includes hundreds of non-scientifically verified “treatment” modalities. Among the most popular are biological therapies using chemical or natural compounds administered with injection or drip infusion. The latter has found the most excellent use in treating rheumatological and dermatological diseases and certain types of cancer. Vitamin infusions, curcumin, glutathione, perhydrol and dimethylsulphoxide (DMSO) have gained popularity among clients of natural medicine clinics. The present study aims to analyse the case of a 37-year-old woman who was administered infusions containing perhydrol and DMSO (0.5 mL 0.04% hydrogen peroxide/0.5 mL p.d.a DMSO in saline) due to a MTHFR A1298C mutation. After having the next infusion, the woman complained of nausea and then became unconscious. Subsequently, she suffered respiratory and cardiac arrest. Adequate resuscitation was undertaken. After being taken to the hospital, the patient was in critical condition and died due to increasing multiple-organ failure. Initially, there was suspected DMSO poisoning as it was the only compound to have been administered as an intravenous infusion. However, it was not until the analysis of the secured evidence that it became clear that the patient had also been given an intravenous solution of hydrogen peroxide, H₂O₂, and that there had been a mistake in preparing the intravenous perhydrol solution. The autopsy concluded that the immediate cause of death was an acute cardiopulmonary failure due to the toxic effects of intravenously administered hydrogen peroxide. This conclusion was established after the toxicological testing of the evidence and biological material secured during the patient’s treatment and autopsy. Products containing DMSO and perhydrol are not included in the lists of medicinal/therapeutical forms and preparations and thus are not authorised for marketing in Poland. In the case of perhydrol, apart from the topical use of diluted preparations for washing and cleansing wounds, no data on therapeutic use exist in the available scientific literature. Furthermore, “DMSO and perhydrol therapy” cannot even be considered a placebo effect, as both are toxic compounds which could, at most, cause poisoning symptoms rather than improve health. Full article

(This article belongs to the Special Issue Overview of Forensic Toxicology, Yesterday, Today and in the Future)

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