Toxicology News Update – Weekly Summary

Every week, we provide a brief overview of the major toxicology research, poisoning reports, and new areas related to drug and chemical safety. This report summarizes key research findings and how they relate to clinical practice, research, and public health professionals.

Individual Variability in Behavioral Responses to Xylazine and Opioid–Xylazine Combinations in Male Rat

The purpose of this research was to study the effects of xylazine alone and in conjunction with opioids on behaviour and physiology in male rats. Movement, body temperature, subjective drug effects, and respiratory profiles were evaluated. The results showed that xylazine decreased movement and lowered body temperature, but the amount of each of these effects varied between individual rats. Some of the rats experienced drug-like effects of xylazine that are similar to that of fentanyl and made the effects of fentanyl last longer.

Additionally, the study found that combining xylazine and opioids resulted in a greater degree of respiratory depression from opioids; this finding is critical to understanding overdose potential. Atipamezole is an antagonist that reverses the excess respiratory suppression from the combination of xylazine and morphine. In conclusion, the data suggest that there is considerable individual variability in the behavioural effects of xylazine and xylazine-opioid combined, which may partially account for the variability in experiences of people who use both products.

https://pubmed.ncbi.nlm.nih.gov/41372547/

Fatality Rate of CO Poisoning in North Korean Hospitals

This meta-analysis studies the mortality among those treated in hospital settings due to unintentional carbon monoxide (CO) poisoning within the Democratic People's Republic of Korea (North Korea). As the use of low quality fuels to heat homes has become very common within the DPRK, the study aggregated available data to provide a more accurate estimate of deaths among those admitted to hospitals for this condition.

According to PubMed, the estimated hospital fatality rate associated with CO poisoning in North Korea is 6.49%, approximately 2.5 times greater than South Korean patients using hyperbaric oxygen treatment- (i.e., 2.62%). The data showed that non-hyperbaric South Korean patients died at nearly the same rate as North Korean hospital death rates (i.e., ~6.26%). suggesting that differences in treatment access may influence outcomes. Ultimately, the high level of morbidity and mortality which results from CO poisoning in North Korea, has demonstrated the utility of identifying evidence-based intervention strategies and improving indoor heating processes to lower rates of preventable morbidity and mortality.

https://pubmed.ncbi.nlm.nih.gov/41365552/

Fe₃O₄@MOF Nanozyme for Chlorpyrifos Detection and Bioaccumulation in Rice

This research presents a novel Fe₃O₄@metal-organic framework (MOF) core-shell nanozyme that can detect and track the pesticide chlorpyrifos in rice. This core-shell nanozyme features high adsorption, magnetic separation properties, and improved oxidase-like activityUsing chlorpyrifos’ effect on acetylcholinesterase, the system produced a measurable response, with a detection limit of 0.35 ng/mL The sensor is selective, exhibits resistance to interference from other chemicals, and will allow for longitudinal tracking of chlorpyrifos levels in a sample.

added part (not from the article): Chlorpyrifos, a member of the organophosphorus pesticide family, inhibits the action of acetylcholinesterase in humans. Acetylcholinesterase plays a vital role in the propagation of nerve impulses that permit muscle movement. If acetylcholinesterase is inhibited by chlorpyrifos, people may exhibit many of the same symptoms as they would experience if they were exposed to high levels of chlorpyrifos.

https://pubmed.ncbi.nlm.nih.gov/41371014/

Acute Respiratory Failure from Gelsemium elegans Poisoning: Case Report

A case report detailing a 64 years old male with significant Gelsemium poisoning after consuming approximately 40 ml of Gelsemium herbal tea is presented. After presenting with blurred vision the patient developed sudden cardiac arrest due to respiratory failure during gastric lavage. The emergency department was involved in the intubation and mechanical ventilation of the patient. After performing a hemoperfusion procedure and providing supportive medical care in an ICU setting, he regained spontaneous respiration, could be weaned from the ventilator, and had an uneventful recovery without residual side effects.

Gelsemium elegans poisoning has rapid and potentially life-threatening effects on respiratory functions and requires rapid resuscitation efforts and advanced supportive care. This report highlights the need for both prompt initiation of respiratory support and hemoperfusion as effective interventions against Gelsemium poisonings.

https://pubmed.ncbi.nlm.nih.gov/41371305/

Opioid Overdose Mortality in the U.S. (1999–2024)

This study examined mortality due to opioid overdose in the United States using data from the CDC WONDER Multiple Cause‑of‑Death database for the years 1999 to 2024.

Opioid overdose death data were determined through the use of ICD-10 codes; data calculated to determine by way of a Mortality Rate (by Year/Sex/Age/Race or Ethnicity/Region). There were a total of 806,765 (806) deaths due to an opioid overdose during this time frame, with an Age-Adjusted Mortality Rate (AAMR) increasing from 4.41 per 100,000 people in 1999 to 22.84 per 100,000 in the year 2024.

The data clearly indicates that throughout this time frame, Men have consistently had higher mortality rates than Women; there were also very noticeable differences in mortality rates by Race and Region. The groups that exhibited the highest rates of opioid overdose deaths were Non-Hispanic American Indian or Alaska Native; Non-Hispanic White; and Non-Hispanic Black. The group that exhibited the highest Crude Mortality Rate was Adults aged 35-44 years; the region where opioid overdose deaths were the most prevalent during this time frame was Northeast. The discrepancies illustrated here demonstrate that opioid overdose remains a serious public health problem in the United States, with continuing disparities among Demographic groups and Regions.

https://pubmed.ncbi.nlm.nih.gov/41371771/

Tirzepatide Overdose Causing Severe Effects and ICU Admission

This case study details a patient with an overdose of tirzepatide (Tz), whose overdose resulted in serious side effects. As a result, the patient was admitted to the Intensive Care Unit (ICU) due to complications resulting from the overdose. The patient needed multiple forms of support as well as extensive rehabilitation to recover from the severe consequences of the overdose. This report also emphasizes the potential dangers associated with overdoses of tirzepatide and the importance of careful monitoring in instances where there is unintentional or intentional overdosing.

https://pubmed.ncbi.nlm.nih.gov/41368024/

Colistin Effects on Lettuce Growth and Antioxidant System

By developing a rapid and efficient green alternative for the determination of the antibiotic colistin in lettuce via LC-MS/MS, this study also examined the effects of colistin through exposure on the growth of lettuce as well as the oxidative stress and the metabolism of lettuce. Colistin demonstrated a good linear relationship across all spiked levels with a high recovery for the colistin detected in the lettuce samples.

Overall, the results from this study indicate that when exposed to colistin, lettuce will experience an inhibitory effect on the growth of lettuce in a dose-dependent way. In addition, colistin interrupts the normal function of both the mitochondria and the chloroplasts associated with photosynthesis and the energy metabolism process and induces oxidative stress by altering the concentration of antioxidant enzymes and metabolite profiles in the tissues of the lettuce. Additionally, the testing of supermarket lettuce samples from the study indicated that the level of colistin consumed through the diet will have a minimal health risk for those local residents who consume it. However, the need for further investigation into the potential combined toxicities of colistin with other contaminants and the potential for the development of antibiotic-resistant bacteria has been identified.

https://pubmed.ncbi.nlm.nih.gov/41372773/

Venetoclax Toxicity-Efficacy Balance in Real-World AML Patients

In this study, we examined the pharmacokinetics and Exposure-Response relationship of Venotloclax (VEN) in 48 adults diagnosed with Acute Myeloid Leukemia (AML) who did not qualify for Standard-of-Care chemotherapy treatments. The patients were treated with VEN plus Azacitidine. The results showed significant variability both between and within individuals for plasma VEN concentration. Additionally, higher concentrations of VEN were associated with improved response rates to treatment (i.e., higher hematological response rates). Overall survival for the cohort was 17.8 months, and the 1-and 2-year Survival Rates were 51% and 36.4%, respectively. When comparing two VEN treatment protocols (14-Day regimen & 28-Day regimen), the 14-Day Regimen allowed for multiple treatments without an increased risk of toxicity. The researchers suggest that Therapeutic Drug Monitoring (TDM) may be an effective strategy for improving both the efficacy and safety of treatment.

https://pubmed.ncbi.nlm.nih.gov/41372707/

Final thoughts

The results of the highlights for this week serve as a reminder that it is still critical to monitor and understand the toxic effects of drugs, pesticides and all forms of naturally occurring toxins. The findings of preclinical research, real-world patient data, food safety and environmental exposures all support the need for a high level of therapeutic monitoring, implementing harm reduction strategies and conducting additional research to decrease risk and enhance health results.