Clinical and Post-Mortem Toxicology

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

Deadline for manuscript submissions: closed (20 November 2023) | Viewed by 21034

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Special Issue Editor


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Guest Editor
Department of Clinical Pharmacy, OLVG Hospital, Amsterdam, The Netherlands
Interests: clinical toxicology; post-mortem toxicology; clinical pharmacology; radiopharmacology

Special Issue Information

Dear Colleagues,

It is my pleasure to invite you to submit papers in the field of clinical, post-mortem, and forensic toxicology. Papers (also review papers) addressing the methodology of comprehensive toxicology screening (e.g., LC-MS libraries), as well as the presentation of clinical cases and case series, are welcome. Further, we will welcome papers dealing with post-mortem and forensic toxicology.

This Special Issue will address the challenges in detecting exposure and intoxications of various (recreative) drugs and novel active psychoactive drugs that are widely available on the internet. How do we detect these agents and their metabolites in body fluids? What are the potentials and limitations of comprehensive and targeted toxicology screening in both clinical and forensic settings? What are the options and challenges for drugs testing at the point of care and crime? This Special Issue also addresses novel options for the clinical management of intoxicated patients, including the prevention of (re)absorption, and the extracorporally enhanced elimination of drugs and specific antidotes. In cases of post-mortem toxicology, how do we interpret drug levels in blood and how do we deal with post-mortem redistribution and degradation?

Dr. Eric J. F. Franssen
Guest Editor

Manuscript Submission Information

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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

  • clinical toxicology
  • comprehensive toxicology screening
  • post-mortem toxicology
  • forensic toxicology
  • drugs testing and analysis
  • point-of-care drug testing
  • LC-MS toxicology screening

Published Papers (11 papers)

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Editorial

Jump to: Research, Review, Other

6 pages, 188 KiB  
Editorial
Editorial “Special Issue Clinical and Post Mortem Toxicology”
by Eric J. F. Franssen
Toxics 2024, 12(3), 205; https://doi.org/10.3390/toxics12030205 - 08 Mar 2024
Viewed by 885
Abstract
This Special Issue addresses the challenges faced in detecting the exposure and intoxications of various (recreative) drugs and novel active psychoactive drugs [...] Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)

Research

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15 pages, 901 KiB  
Article
11-Nor-9-Carboxy Tetrahydrocannabinol Distribution in Fluid from the Chest Cavity in Cannabis-Related Post-Mortem Cases
by Torki A. Zughaibi, Hassan Alharbi, Adel Al-Saadi, Abdulnasser E. Alzahrani and Ahmed I. Al-Asmari
Toxics 2023, 11(9), 740; https://doi.org/10.3390/toxics11090740 - 29 Aug 2023
Cited by 1 | Viewed by 1252
Abstract
In this study, the presence of 11-nor-Δ9-carboxy tetrahydrocannabinol (THC-COOH) in postmortem fluid obtained from the chest cavity (FCC) of postmortem cases collected from drug-related fatalities or criminal-related deaths in Jeddah, Saudi Arabia, was investigated to evaluate its suitability for use as [...] Read more.
In this study, the presence of 11-nor-Δ9-carboxy tetrahydrocannabinol (THC-COOH) in postmortem fluid obtained from the chest cavity (FCC) of postmortem cases collected from drug-related fatalities or criminal-related deaths in Jeddah, Saudi Arabia, was investigated to evaluate its suitability for use as a complementary specimen to blood and biological specimens in cases where no bodily fluids are available or suitable for analysis. The relationships between THC-COOH concentrations in the FCC samples and age, body mass index (BMI), polydrug intoxication, manner, and cause of death were investigated. Methods: Fifteen postmortem cases of FCC were analyzed using fully validated liquid chromatography-positive-electrospray ionization tandem mass spectrometry (LC-MS/MS). Results: FCC samples were collected from 15 postmortem cases; only THC-COOH tested positive, with a median concentration of 480 ng/mL (range = 80–3010 ng/mL). THC-COOH in FCC were higher than THC-COOH in all tested specimens with exception to bile, the median ratio FCC/blood with sodium fluoride, FCC/urine, FCC/gastric content, FCC/bile, FCC/liver, FCC/kidney, FCC/brain, FCC/stomach wall, FCC/lung, and FCC/intestine tissue were 48, 2, 0.2, 6, 4, 6, 102, 11, 5 and 10-fold, respectively. Conclusion: This is the first postmortem report of THC-COOH in the FCC using cannabinoid-related analysis. The FCC samples were liquid, easy to manipulate, and extracted using the same procedure as the blood samples. The source of THC-COOH detected in FCC could be derived from the surrounding organs due to postmortem redistribution or contamination due to postmortem changes after death. THC-COOH, which is stored in adipose tissues, could be a major source of THC-COOH found in the FCC. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
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13 pages, 1450 KiB  
Article
Fatalities Involving Khat in Jazan, Saudi Arabia, 2018 to 2021
by Ghassan Shaikhain, Mohammed Gaballah, Ahmad Alhazmi, Ibrahim Khardali, Ahmad Hakami, Magbool Oraiby, Sultan Alharbi, Mohammad Tobaigi, Mohammed Ghalibi, Mohsen Fageeh, Mohammed Albeishy and Ibraheem Attafi
Toxics 2023, 11(6), 506; https://doi.org/10.3390/toxics11060506 - 04 Jun 2023
Cited by 1 | Viewed by 1472
Abstract
Interpreting fatalities involving khat is challenging due to a lack of data on cathinone and cathine reference concentrations in postmortem tissues. This study investigated the autopsy findings and toxicological results of fatalities involving khat in Saudi Arabia’s Jazan region from 1 January 2018 [...] Read more.
Interpreting fatalities involving khat is challenging due to a lack of data on cathinone and cathine reference concentrations in postmortem tissues. This study investigated the autopsy findings and toxicological results of fatalities involving khat in Saudi Arabia’s Jazan region from 1 January 2018 to 31 December 2021. All confirmed cathine and cathinone results in postmortem blood, urine, brain, liver, kidney, and stomach samples were recorded and analyzed. Autopsy findings and the manner and cause of death of the deceased were assessed. Saudi Arabia’s Forensic Medicine Center investigated 651 fatality cases over four years. Thirty postmortem samples were positive for khat’s active constituents, cathinone and cathine. The percentage of fatalities involving khat was 3% in 2018 and 2019 and increased from 4% in 2020 to 9% in 2021, when compared with all fatal cases. They were all males ranging in age from 23 to 45. Firearm injuries (10 cases), hanging (7 cases), road traffic accident (2 cases), head injury (2 cases), stab wounds (2 cases), poisoning (2 cases), unknown (2 cases), ischemic heart disease (1 case), brain tumor (1 case), and choking (1 case) were responsible for the deaths. In total, 57% of the postmortem samples tested positive for khat only, while 43% tested positive for khat with other drugs. Amphetamine is the drug most frequently involved. The average cathinone and cathine concentrations were 85 and 486 ng/mL in the blood, 69 and 682 ng/mL in the brain, 64 and 635 ng/mL in the liver, and 43 and 758 ng/mL in the kidneys, respectively. The 10th–90th percentiles of blood concentrations of cathinone and cathine were 18–218 ng/mL and 222–843 ng/mL, respectively. These findings show that 90% of fatalities involving khat had cathinone concentrations greater than 18 ng/mL and cathine concentrations greater than 222 ng/mL. According to the cause of death, homicide was the most common fatality involving khat alone (77%). More research is required, especially toxicological and autopsy findings, to determine the involvement of khat in crimes and fatalities. This study may help forensic scientists and toxicologists investigate fatalities involving khat. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
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33 pages, 1695 KiB  
Article
Heroin-Related Fatalities in Jeddah, Saudi Arabia, between 2008 and 2018
by Ahmed I. Al-Asmari, Hassan Alharbi, Abdulnasser E. Al-Zahrani and Torki A. Zughaibi
Toxics 2023, 11(3), 248; https://doi.org/10.3390/toxics11030248 - 06 Mar 2023
Cited by 2 | Viewed by 2131
Abstract
To date, epidemiological studies have not evaluated heroin-related deaths in the Middle East and North African regions, especially Saudi Arabia. All heroin-related postmortem cases reported at the Jeddah Poison Control Center (JPCC) over a 10-year period (21 January 2008 to 31 July 2018) [...] Read more.
To date, epidemiological studies have not evaluated heroin-related deaths in the Middle East and North African regions, especially Saudi Arabia. All heroin-related postmortem cases reported at the Jeddah Poison Control Center (JPCC) over a 10-year period (21 January 2008 to 31 July 2018) were reviewed. In addition, liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was utilized to determine the 6-monoacetylmorphine (6-MAM), 6-acetylcodeine (6-AC), morphine (MOR), and codeine contents in unhydrolyzed postmortem specimens. Ninety-seven heroin-related deaths were assessed in this study, and they represented 2% of the total postmortem cases at the JPCC (median age, 38; 98% male). In the blood, urine, vitreous humor, and bile samples, the median morphine concentrations were 280 ng/mL, 1400 ng/mL, 90 ng/mL, and 2200 ng/mL, respectively; 6-MAM was detected in 60%, 100%, 99%, and 59% of the samples, respectively; and 6-AC was detected in 24%, 68%, 50%, and 30% of the samples, respectively. The highest number of deaths (33% of total cases) was observed in the 21–30 age group. In addition, 61% of cases were classified as “rapid deaths,” while 24% were classified as “delayed deaths.” The majority (76%) of deaths were accidental; 7% were from suicide; 5% were from homicide; and 11% were undetermined. This is the first epidemiological study to investigate heroin-related fatalities in Saudi Arabia and the Middle East and North African region. The rate of heroin-related deaths in Jeddah remained stable but increased slightly at the end of the study period. Most patients were heroin-dependent abusers and from the middle-aged group. The availability of urine, vitreous humor, and bile specimens provided valuable information regarding the opioids that were administered and the survival time following heroin injection. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
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Review

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15 pages, 2967 KiB  
Review
Quetiapine-Related Deaths: In Search of a Surrogate Endpoint
by Ivan Šoša
Toxics 2024, 12(1), 37; https://doi.org/10.3390/toxics12010037 - 03 Jan 2024
Viewed by 2206
Abstract
Quetiapine is a second-generation antipsychotic drug available for two and half decades. Due to increased misuse, prescription outside the approved indications, and availability on the black market, it is being encountered in medicolegal autopsies more frequently. For instance, it has been linked to [...] Read more.
Quetiapine is a second-generation antipsychotic drug available for two and half decades. Due to increased misuse, prescription outside the approved indications, and availability on the black market, it is being encountered in medicolegal autopsies more frequently. For instance, it has been linked to increased mortality rates, most likely due to its adverse effects on the cardiovascular system. Its pharmacokinetic features and significant postmortem redistribution challenge traditional sampling in forensic toxicology. Therefore, a systematic literature review was performed, inclusive of PubMed, the Web of Science—core collection, and the Scopus databases; articles were screened for the terms “quetiapine”, “death”, and “autopsy” to reevaluate each matrix used as a surrogate endpoint in the forensic toxicology of quetiapine-related deaths. Ultimately, this review considers the results of five studies that were well presented (more than two matrices, data available for all analyses, for instance). The highest quetiapine concentrations were usually measured in the liver tissue. As interpreted by their authors, the results of the considered studies showed a strong correlation between some matrices, but, unfortunately, the studies presented models with poor goodness of fit. The distribution of quetiapine in distinct body compartments/tissues showed no statistically significant relationship with the length of the postmortem interval. Furthermore, this study did not confirm the anecdotal correlation of peripheral blood concentrations with skeletal muscle concentrations. Otherwise, there was no consistency regarding selecting an endpoint for analysis. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
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Other

9 pages, 262 KiB  
Case Report
Biodetoxification Using Intravenous Lipid Emulsion, a Rescue Therapy in Life-Threatening Quetiapine and Venlafaxine Poisoning: A Case Report
by Cristian Cobilinschi, Liliana Mirea, Cosmin-Andrei Andrei, Raluca Ungureanu, Ana-Maria Cotae, Oana Avram, Sebastian Isac, Ioana Marina Grințescu and Radu Țincu
Toxics 2023, 11(11), 917; https://doi.org/10.3390/toxics11110917 - 09 Nov 2023
Cited by 2 | Viewed by 1305
Abstract
The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an [...] Read more.
The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an antidote for other lipophilic drugs is still under debate. Venlafaxine (an antidepressant acting as a serotonin–norepinephrine reuptake inhibitor (SNRI)) and quetiapine (a second-generation atypical antipsychotic) are widely used in the treatment of psychotic disorders. Both are lipophilic drugs known to induce cardiotoxicity and central nervous depression. We report the case of a 33-year-old man with a medical history of schizoaffective disorder who was admitted to the emergency department (ED) after having been found unconscious due to a voluntary ingestion of 12 g of quetiapine and 4.5 g of venlafaxine. Initial assessment revealed a cardiorespiratory stable patient but unresponsive with a GCS of 4 (M2 E1 V1). In the ED, he was intubated, and gastric lavage was performed. Immediately after the admission to the intensive care unit (ICU), his condition quickly deteriorated, developing cardiovascular collapse refractory to crystalloids and vasopressor infusion. Junctional bradycardia occurred, followed by spontaneous conversion to sinus rhythm. Subsequently, frequent ventricular extrasystoles, as well as patterns of bigeminy, trigeminy, and even episodes of non-sustained ventricular tachycardia, occurred. Additionally, generalized tonic–clonic seizures were observed. Alongside supportive therapy, antiarrhythmic and anticonvulsant therapy, intravenous lipid emulsion bolus, and continuous infusion were administered. His condition progressively improved over the following hours, and 24 h later, he was tapered off the vasopressor. On day 2, the patient repeated the cardiovascular collapse and a second dose of ILE was administered. Over the next few days, the patient’s clinical condition improved, and he was successfully weaned off ventilator and vasopressor support. ILE has the potential to become a form of rescue therapy in cases of severe lipophilic drug poisoning and should be considered a viable treatment for severe cardiovascular instability that is refractory to supportive therapy. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
10 pages, 1092 KiB  
Case Report
Fatal Overdose with the Cannabinoid Receptor Agonists MDMB-4en-PINACA and 4F-ABUTINACA: A Case Report and Review of the Literature
by Gábor Simon, Mónika Kuzma, Mátyás Mayer, Karola Petrus and Dénes Tóth
Toxics 2023, 11(8), 673; https://doi.org/10.3390/toxics11080673 - 05 Aug 2023
Cited by 1 | Viewed by 1738
Abstract
A case of a 26-year-old male who died from consuming synthetic cannabinoid receptor agonists MDMB-4en-PINACA and 4F-ABUTINACA is reported. MDMB-4en-PINACA and 4F-ABUTINACA are potent synthetic cannabinoid receptor agonists (SCRAs). This is the first detailed reporting of MDMB-4-en-PINACA and 4F-ABUTINACA associated fatality, which can [...] Read more.
A case of a 26-year-old male who died from consuming synthetic cannabinoid receptor agonists MDMB-4en-PINACA and 4F-ABUTINACA is reported. MDMB-4en-PINACA and 4F-ABUTINACA are potent synthetic cannabinoid receptor agonists (SCRAs). This is the first detailed reporting of MDMB-4-en-PINACA and 4F-ABUTINACA associated fatality, which can help the routine forensic work. The scientific literature on the symptoms associated with these substances are evaluated, along with the pharmacological properties and possible mechanism of death. A forensic autopsy was performed according to Recommendation No. R (99)3 of the Council of Europe on medico-legal autopsies. Histological samples were stained with hematoxylin and eosin (HE). Complement component C9 immunohistochemistry was applied to all heart samples. Toxicological analyses were carried out by supercritical fluid chromatography coupled with tandem mass spectrometry (SFC-MS/MS) and headspace gas chromatography with a flame ionization detector (HS-GC-FID). The literature was reviewed to identify reported cases of MDMB-4en-PINACA and 4F-ABUTINACA use. Autopsy findings included brain edema, internal congestion, petechial bleeding, pleural ecchymoses, and blood fluidity. Toxicological analyses determined 7.2 ng/mL of MDMB-4en-PINACA and 9.1 ng/mL of 4F-ABUTINACA in the peripheral blood. MDMB-4en-PINACA and 4F-ABUTINACA are strong, potentially lethal SCRA, and their exact effects and outcome are unpredictable. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
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5 pages, 241 KiB  
Case Report
Internet-Purchased Sodium Azide Used in a Fatal Suicide Attempt: A Case Report and Review of the Literature
by Lisa T. van der Heijden, Karen E. van den Hondel, Erik J. H. Olyslager, Lutea A. A. de Jong, Udo J. L. Reijnders and Eric J. F. Franssen
Toxics 2023, 11(7), 608; https://doi.org/10.3390/toxics11070608 - 13 Jul 2023
Viewed by 2251
Abstract
There has been a significant increase in sodium azide intoxications since the 1980s. Intoxications caused by sodium azide are becoming increasingly prevalent in the Netherlands as a result of its promotion for the purpose of self-euthanasia. The mechanism of toxicity is not completely [...] Read more.
There has been a significant increase in sodium azide intoxications since the 1980s. Intoxications caused by sodium azide are becoming increasingly prevalent in the Netherlands as a result of its promotion for the purpose of self-euthanasia. The mechanism of toxicity is not completely understood but is dose-dependent. The presented case describes a suicide by sodium azide of a young woman (26 years old) with a history of depression and suicide attempts. The decedent was found in the presence of prescription medicine, including temazepam, domperidone in combination with omeprazole, and the chemical preservative sodium azide. Quantitative toxicology screening of whole blood revealed the presence of 70 µg/L temazepam (toxic range > 1000 µg/L) and 28 mg/L sodium azide (fatal range: 2.6–262 mg/L). Whole blood qualitative analysis revealed the presence of temazepam, temazepam-glucuronide, olanzapine, n-desmethylolanzapine, and acetaminophen. In circles promoting sodium azide, it is recommended to use sodium azide in combination with medications targeting sodium azide’s negative effects, such as analgesics, antiemetics, and anti-anxiety drugs. The medicines recovered at the body’s location, as well as the results of the toxicology screens, were consistent with the recommendations of self-euthanasia using sodium azide. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
7 pages, 242 KiB  
Case Report
Toxicological Analysis in Tissues Following Exhumation More Than Two Years after Death (948 Days): A Forensic Perspective in a Fatal Case
by Giuseppe Davide Albano, Stefania Zerbo, Corinne La Spina, Mauro Midiri, Daniela Guadagnino, Tommaso D’Anna, Roberto Buscemi and Antonina Argo
Toxics 2023, 11(6), 485; https://doi.org/10.3390/toxics11060485 - 26 May 2023
Viewed by 1737
Abstract
Exhumations are performed in accordance with a court order and are crucial instruments in the investigation of death allegations. When a death is thought to be the result of drug misuse, pharmaceutical overdose, or pesticide poisoning, this process may be used on human [...] Read more.
Exhumations are performed in accordance with a court order and are crucial instruments in the investigation of death allegations. When a death is thought to be the result of drug misuse, pharmaceutical overdose, or pesticide poisoning, this process may be used on human remains. However, after a protracted postmortem interval (PMI), it might be difficult to detect the cause of death by looking at an exhumed corpse. The following case report reveals problems associated with postmortem drug concentration changes following exhumation more than two years after death. A 31-year-old man was found dead in a prison cell. Onan inspection of the place, two blister packs, one with a tablet and the other empty, were taken and kept by the police officers. The evening before, the deceased would have taken cetirizine and food supplements consisting of carnitine–creatine tablets. No relevant autopsy findings have been observed. The toxicological analysis was performed by gas chromatography coupled to mass spectrometry and was negative for substances of abuse. Proteomic analysis was positive for creatine detection and negative for other drugs (clarithromycin, fenofibrate, and cetirizine). The presented case shows the methods, the findings, and the limitations of toxicological analysis in an exhumation case with a long postmortem interval (PMI). Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
6 pages, 544 KiB  
Case Report
Successful Use of Continuous Veno-Venous Haemodialysis in a Case of Potential Lethal Caffeine Intoxication
by Elles J. Reimerink, Daan W. Huntjens, Lindsey G. Pelkmans, Jan-Willem H. J. Geerts and Eric J. F. Franssen
Toxics 2023, 11(2), 196; https://doi.org/10.3390/toxics11020196 - 20 Feb 2023
Viewed by 2574
Abstract
Here we describe the case of a potentially lethal caffeine intoxication after the reported ingestion of 10 g of caffeine. Due to hemodynamic instability with tachycardia and hypertension with an insufficient effect of continuous labetalol infusion, the patient was started on continuous veno-venous [...] Read more.
Here we describe the case of a potentially lethal caffeine intoxication after the reported ingestion of 10 g of caffeine. Due to hemodynamic instability with tachycardia and hypertension with an insufficient effect of continuous labetalol infusion, the patient was started on continuous veno-venous haemodialysis (CVVHD). After successful treatment for 15 h, CVVHD could be discontinued, and the patient was discharged home the next day. This case report is the first to report the use of CVVHD as a haemodialysis modality in the case of caffeine intoxication and illustrate the effect on caffeine clearance. We stress the importance of an early recognition of caffeine intoxication, so that haemodialysis can be considered in the case of a potentially lethal intoxication. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
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4 pages, 477 KiB  
Case Report
Rat Bait, Not Healthy Rice!
by Kuan-I Lee, Jing-Hua Lin, Yen-Jung Chu, Jou-Fang Deng, Wei-Lan Chu and Dong-Zong Hung
Toxics 2023, 11(1), 60; https://doi.org/10.3390/toxics11010060 - 08 Jan 2023
Viewed by 2163
Abstract
Bromadiolone, a potent, long-acting anticoagulant rodenticide is frequently tinted to a red or pink color and mixed with cereals as rat bait. Six peoples working in a small factory suffered from a severe bleeding tendency several weeks after consuming a rice meal that [...] Read more.
Bromadiolone, a potent, long-acting anticoagulant rodenticide is frequently tinted to a red or pink color and mixed with cereals as rat bait. Six peoples working in a small factory suffered from a severe bleeding tendency several weeks after consuming a rice meal that was tainted with bromadiolone mistaken to be healthy food. High serum levels of bromadiolone and excessive bleeding were found in these individuals, and they needed vitamin K1 therapy for weeks. These cases indicated that long-acting anticoagulant rodenticide might induce cumulative toxicity in repeated, low-dose exposure, and the blood levels of bromadiolone might be an indicator for antidote therapy if available. Full article
(This article belongs to the Special Issue Clinical and Post-Mortem Toxicology)
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