Poisonings due to storage in a secondary container reported to the National Poison Data System, 2007-2017.

BACKGROUND: Transfer of xenobiotics from their original container to an unlabeled or secondary container is a well-identified risk factor for poisoning. Nonetheless, recent large-scale data on the practice are unavailable. The objective of this study is to describe the incidence and features of poisonings in the United States due to xenobiotics stored in a secondary container. METHODS: This was a retrospective review of the National Poison Data System (NPDS) from 2007 to 2017. Non-suicidal exposures associated with the scenario "container transfer involved (product transferred from original container to unlabeled container, incorrectly labeled container, or food container for use or storage and patient accessed product from second container)" were included. RESULTS: Forty-five thousand five hundred and twelve cases were included. The median age of subjects was 30 years (interquartile range: 6-53); 52% were female. Cleaning products (38.2%), disinfectants (17.3%), and hydrocarbons (5.0%) were the most common xenobiotics reported. The annual incidence of cases increased over the study period. There were 9369 (20.6%) ED visits and 1856 (4.1%) hospital admissions. Most cases (72%) were deemed nontoxic or resulted in no effects; 4.4% resulted in serious outcomes (moderate effects, major effects, or death), including 23 deaths. Morbidity was highest for pesticides, prescription medications, and herbicides, with 10.3%, 9.8%, and 7.6% of cases resulting in serious outcomes, respectively. Hydrofluoric acid and herbicides were associated with the most deaths (13/23 [57%]). CONCLUSIONS: Transfer of xenobiotics to a secondary container is a scenario increasingly reported to U.S. poison centers. Although most exposures do not result in significant toxicity, ED visits are common and substantial morbidity can occur. This represents an opportunity for public health intervention to curb the practice.

Diagnostic Challenges and Guidelines Pertaining to Suspected Ruminant Intoxications.

This article addresses diagnostic challenges involving toxicology cases that are multifactorial in nature, often involving sublethal exposures to multiple toxicants and/or other etiologies that are not toxic. Gold standard diagnostic approaches were developed under the assumption that cases were undoubtedly intoxications, and they still are applicable to those cases. A more integrated diagnostic approach, focusing on the initial problem list, is consistent with how veterinarians diagnose most cases. Livestock ownership attitudes continue to evolve. Ongoing threats to the financial well-being of animal agriculture ultimately will have an impact on the ability of producers to maintain health and performance of livestock.

A retrospective observational study on patients intoxicated by drugs and other xenobiotics.

OBJECTIVES: Many research studies conducted in various toxicology centers point to drugs as the most common cause of intoxication. Long-term observations make it possible to clarify the nature of these poisonings. The aim of this study was to examine the trends and reasons of intoxication in patients hospitalized over a 10-year observation period (2005-2015), as well as to compare the number of patients poisoned with nonsteroidal anti-inflammatory drugs (NSAIDs), mainly over-the-counter (OTC) drugs. MATERIAL AND METHODS: A retrospective observational study examined the medical documentation of patients hospitalized in the Department of Toxicology and Internal Diseases of the T. Marciniak Lower Silesian Specialist Hospital in Wroclaw in 2005-2015, including the analysis of the causes of intoxication as well as total poisoning-related death statistics. Quarterly and annual analyses of the numerical data, and comparisons of the frequency of poisonings were included. The patient population from the area of Lower Silesia, Poland, was examined. RESULTS: The number of hospitalized patients has increased, with attempted suicide being the leading cause of death. Male intoxication and mortality have been found to predominate. Drugs are the most common cause of poisoning, and among these the most common are sedatives and psychotropic drugs. Intoxication due to NSAIDs, especially OTC drugs, increased significantly in the observation period. In 2005 no fatal cases were reported as a result of NSAID intoxication, while in 2015 mortality significantly increased to 43%. CONCLUSIONS: The lack of a common trend in poisonings is observed but the number of hospitalized patients has increased, especially among young people, which is consistent with global trends. Drugs are the most common cause of mortality, and a significant increase in NSAID (mainly OTC) poisonings in particular indicates the growing prevalence of an uncontrolled use of these drugs. Int J Occup Med Environ Health. 2019;32(4):489-501.

Usefulness of Transthoracic Echocardiography Parameters and Brain Natriuretic Peptide as Mortality Predictors in Hospitalized Acutely Poisoned Patients: A Prospective Observational Study.

Acute poisonings represent a common cause of morbidity and mortality worldwide. The prognostic utility of the transthoracic echocardiography (TTE) parameters combined with brain natriuretic peptide (BNP) in acute poisoning with different xenobiotics, upon admission in the hospital, was not evaluated. This prospective observational cohort study included 229 acutely poisoned non-diabetic adults, with a median age of 44 years (range 18-90 years), 50.7% women, with an in-hospital mortality rate of 8.7%. Univariate logistic regression analysis showed that age, the left ventricle kinetic abnormalities, the E-wave deceleration time (EDT) and BNP correlated significantly with mortality in acutely poisoned patients. Multivariate logistic regression showed that only EDT [odds ratio (OR) 3.44, 95% confidence interval (CI) 1.54-7.69, p 0.003], BNP (OR 1.61, 95% CI: 1.02-2.55, p 0.04) and age (OR 2.66, 95% CI: 1.23-5.76, p 0.013) are predictive for mortality. The receiver-operating characteristic (ROC) analysis proved EDT [area under the ROC curve (AUC), 0.85; CI: 0.76-0.94; p 0.001], BNP (AUC, 0.83; CI: 0.75-0.91; p 0.001) and age (AUC, 0.82; CI: 0.74-0.90; p 0.001) as indicators for fatalities. In hospitalized patients acutely intoxicated with undifferentiated poisons, EDT as a parameter of left ventricle diastolic function and BNP are useful to early predict mortality.

Untargeted screening of unknown xenobiotics and potential toxins in plasma of poisoned patients using high-resolution mass spectrometry: Generation of xenobiotic fingerprint using background subtraction.

A novel analytical workflow was developed and applied for the detection and identification of unknown xenobiotics in biological samples. High-resolution mass spectrometry (HRMS)-based data-independent MSE acquisition was employed to record full scan MS and fragment spectral datasets of test and control samples. Then, an untargeted data-mining technique, background subtraction, was utilized to find xenobiotics present only in test samples. Structural elucidation of the detected xenobiotics was accomplished by database search, spectral interpretation, and/or comparison with reference standards. Application of the workflow to analysis of unknown xenobiotics in plasma samples collected from four poisoned patients led to generation of xenobiotic profiles, which were regarded as xenobiotic fingerprints of the individual samples. Among 19 xenobiotics detected, 11 xenobiotics existed in a majority of the patients' plasma samples, thus were considered as potential toxins. The follow-up database search led to the tentative identification of azithromycin (X5), α-chaconine (X9) and penfluridol (X12). The identity of X12 was further confirmed with its reference standard. In addition, one xenobiotic component (Y5) was tentatively identified as a penfluridol metabolite. The remaining unidentified xenobiotics listed in the xenobiotic fingerprints can be further characterized or identified in retrospective analyses after their spectral data and/or reference compounds are available. This HRMS-based workflow may have broad applications in the detection and identification of unknown xenobiotics in individual biological samples, such as forensic and toxicological analysis and sport enhancement drug screening.

SERUM ANTIOXIDANT PARAMETERS IN PATIENTS POISONED BY DIFFERENT XENOBIOTICS.

There is a great diversity of the acute drugs overdose cases in clinical toxicology. Clinical situation is complicated by the coexistence of factors predisposing to the development of adverse drug reactions (chronic use of drugs, polypharmacy, alcohol or drugs dependence, nutritional disorders) and by the presence of chronic organ damage, especially the liver and the kidney. The aim of this study was to evaluate whether there are sensitive plasma markers belonging to the antioxidant system in patients exposed to various xenobiotics. We measured the activity of antioxidant parameters: catalase (CAT), glutathione peroxidase (GPX3), glutathione (GSH), sulfhydryl groups (-SH), carbonyl groups (=CO) and free radicals (2,2-diphenyl-1-picrylhydrazyl, DPPH, assay) in serum of 49 patients with acute intoxication caused by carbamazepine (CBZ, n = 9), mixed drug intoxication (MDI) (n = 9), alcohol withdrawal syndrome (AWS, n = 9), acetaminophen (APAP, n = 7), tricyclic antidepressants (TCAs) (n = 5), valproic acids (VA, n = 4), narcotics (N, n = 3), and three others (benzodiazepines, BZD, n = 2; barbiturates, n = 1). The results were compared with the parameters of not intoxicated patients (n = 39). All patients had lower catalase activity in comparison to the control group (41.9 ± 16.5 vs. 196.0 ± 82.2 U/mg protein, p = 0.000), while the increase of GSH level was particularly apparent only in patients with AWS (391.3 ± 257.9 µmol/mg protein) compared to the control group (171.4 ± 88.4 µmol/mg protein, p = 0.034) and to patients intoxicated with carbamazepine (152.8 ± 102.5 µmol/mg protein, p = 0.027). Some differences, but without statistical significance, were also observed in GPX3 activity between different groups of poisoned patients.

Data-Driven Method to Estimate Nonlinear Chemical Equivalence.

There is great need to express the impacts of chemicals found in the environment in terms of effects from alternative chemicals of interest. Methods currently employed in fields such as life-cycle assessment, risk assessment, mixtures toxicology, and pharmacology rely mostly on heuristic arguments to justify the use of linear relationships in the construction of "equivalency factors," which aim to model these concentration-concentration correlations. However, the use of linear models, even at low concentrations, oversimplifies the nonlinear nature of the concentration-response curve, therefore introducing error into calculations involving these factors. We address this problem by reporting a method to determine a concentration-concentration relationship between two chemicals based on the full extent of experimentally derived concentration-response curves. Although this method can be easily generalized, we develop and illustrate it from the perspective of toxicology, in which we provide equations relating the sigmoid and non-monotone, or "biphasic," responses typical of the field. The resulting concentration-concentration relationships are manifestly nonlinear for nearly any chemical level, even at the very low concentrations common to environmental measurements. We demonstrate the method using real-world examples of toxicological data which may exhibit sigmoid and biphasic mortality curves. Finally, we use our models to calculate equivalency factors, and show that traditional results are recovered only when the concentration-response curves are "parallel," which has been noted before, but we make formal here by providing mathematical conditions on the validity of this approach.

Effects of caste on the expression of genes associated with septic injury and xenobiotic exposure in the Formosan subterranean termite.

As social insects, termites live in densely populated colonies with specialized castes under conditions conducive to microbial growth and transmission. Furthermore, termites are exposed to xenobiotics in soil and their lignocellulose diet. Therefore, termites are valuable models for studying gene expression involved in response to septic injury, immunity and detoxification in relation to caste membership. In this study, workers and soldiers of the Formosan subterranean termite, Coptotermes formosanus, were challenged by bacterial injection or by no-choice feeding with a sublethal concentration (0.5%) of phenobarbital. Constitutive and induced expression of six putative immune response genes (two encoding for lectin-like proteins, one for a ficolin-precursor, one for the Down syndrome cell adhesion molecule, one for a chitin binding protein, and one for the gram-negative binding protein 2) and four putative detoxification genes (two encoding for cytochrome P450s, one for glutathione S-transferase, and one for the multi antimicrobial extrusion protein), were measured via quantitative real time polymerase chain reaction and compared within and among 1) colonies, 2) treatment types and 3) castes via ANOVA. Eight genes were inducible by septic injury, feeding with phenobarbital or both. Colony origin had no effect on inducibility or differential gene expression. However, treatment type showed significant effects on the expression of the eight inducible genes. Caste effects on expression levels were significant in five of the eight inducible genes with constitutive and induced expression of most target genes being higher in workers than in soldiers.

Lipid rescue 911: Are poison centers recommending intravenous fat emulsion therapy for severe poisoning?

Intravenous fat emulsion (IFE) therapy is a novel treatment that has been used to reverse the acute toxicity of some xenobiotics with varied success. We sought to determine how US Poison Control Centers (PCCs) have incorporated IFE as a treatment strategy for poisoning. A closed-format multiple-choice survey instrument was developed, piloted, revised, and then sent electronically to every medical director of an accredited US PCC in March 2011. Addresses were obtained from the American Association of Poison Control Centers listserv, and participation was voluntary and remained anonymous. Data were analyzed using descriptive statistics. The majority of PCC medical directors completed the survey (45 out of 57; 79 %). Of the 45 respondents, all felt that IFE therapy played a role in the acute overdose setting. Most PCCs (30 out of 45; 67 %) have a protocol for IFE therapy. In a scenario with "cardiac arrest" due to a single xenobiotic, directors stated that their center would "always" or "often" recommend IFE after overdose of bupivacaine (43 out of 45; 96 %), verapamil (36 out of 45; 80 %), amitriptyline (31 out of 45; 69 %), or an unknown xenobiotic (12 out of 45; 27 %). In a scenario with "shock" due to a single xenobiotic, directors stated that their PCC would "always" or "often" recommend IFE after overdose of bupivacaine (40 out of 45; 89 %), verapamil (28 out of 45; 62 %), amitriptyline (25 out of 45; 56 %), or an unknown xenobiotic (8 out of 45; 18 %). IFE therapy is being recommended by US PCCs; protocols and dosing regimens are nearly uniform. Most directors feel that IFE is safe but are more likely to recommend IFE in patients with cardiac arrest than in patients with severe hemodynamic compromise.

Comparison of comet assay parameters for estimation of genotoxicity by sum of ranking differences.

The genotoxic potential of waters in six rivers and reservoirs from Serbia was monitored in different tissues of chub (Squalius cephalus L. 1758) with the alkaline comet assay. The comet assay, or single-cell gel electrophoresis, has a wide application as a simple and sensitive method for evaluating DNA damage in fish exposed to various xenobiotics in the aquatic environment. Three types of cells, erythrocytes, gill cells, and liver cells, were used for assessing DNA damage. Images of randomly selected cells were analyzed with a Leica fluorescence microscope and image analysis by software (Comet Assay IV Image analysis system, PI, UK). Three parameters (tail length-l, tail intensity-i, and Olive tail moment-m) were analyzed on 1,700 nuclei per cell type. The procedure for sum of ranking differences (SRD) was implemented to compare different types of cells and different parameters for estimation of DNA damage. Regarding our nine different estimations of genotoxicity: tail length, intensity, and moment in erythrocytes (rel, rei, rem), liver cells (rll, rli, rlm), and gill cells (rgl, rgi, rgm), the SRD procedure has shown that the Olive tail moment and tail intensity are (almost) equally good parameters; the SRD value was lower for the tail moment and tail intensity than for tail length in the case of all types of cells. The least reliable parameter was rel; close to the borderline case were rei, rll, and rgl (~5 % probability of random ranking).

[Brain death and transplantological issues in patients deceased due to poisonings]. / Smierc mózgowa oraz aspekty transplantologiczne u chorych zmarlych w wyniku zatruc.

The classical definition of human death, based on the statement of the definitive cessation of blood circulation, is still in use except the cases, where the death took the brain, but the blood circulation remained active for some time. In these cases, a "new definition of death" based on the statement of brain death, should be used. The diagnosis of brain death is made by performing of clinical tests and ancillary investigations in order to confirm patient's irreversible coma, lack of brainstem reflexes, lack of motor activity and apnea. Brain death results from the massive damage of brain tissue caused by various pathological processes including the direct and indirect effects of xenobiotics poisoning. Patients who deceased due to poisoning can be donors of tissues and organs for transplantation.

[Consciousness disturbances during poisonings: pathophysiology, clinical picture, and basic principles of diagnosis and management]. / Zaburzenia swiadomosci w przebiegu zatruc: podstawy patofizjologiczne, obraz kliniczny oraz zarys postepowania diagnostycznego i terapeutycznego.

Consciousness is the physiological state of the central nervous system, during which an individual maintain arousal (level of consciousness, vigilance) and realize the internal thoughts as well as the external stimuli (awareness, consciousness content). The toxicity of multiple xenobiotics may lead to impairment of both consciousness categories, presenting clinically as consciousness disturbances, quantitative and qualitative, respectively. Based on the behavioral criteria, different consciousness disorders are diagnosed, among others: brain death, coma, vegetative state, minimally conscious state, akinetic mutism. In the present paper, pathophysiology, clinical picture, as well as basic diagnostic and therapeutic principles of conscious disturbances are described, especially in poisoned patients.

[Xenobiotic-induced seizures and epileptic states as a cause of consciousness disturbances]. / Napady i stany padaczkowe indukowane ksenobiotykami jako przyczyna zaburzen swiadomosci.

Poisoning with many xenobiotics may result in seizures, which are usually generalized. Seizures leading to unexplained disturbances of consciousness are usually generalized tonic-clonic, absence seizures and complex partial seizures Prolonged seizures without recovery of consciousness during interictal period are called status epilepticus. This paper presents the etiology, patomechanism, clinical characteristics, as well as diagnostic and therapeutic principles of toxic seizures. Additionally, the clinical description of nonepileptic psychogenic seizures is given, which often need to be differentiated with true seizures.

[Rare consciousness disturbances in toxicological practice: akinetic mutism, somnambulism, locked-in syndrome, and psychogenic coma]. / Rzadkie zaburzenia swiadomosci w praktyce toksykologicznej: mutyzm akinetyczny, somnambulizm, zespól zamkniecia i spiaczka psychogenna.

The toxicity of xenobiotics can result inrare disorders of consciousness, such as akinetic mutism and somnambulism as well as syndromes mimicking consciousness disturbances, such as locked-in syndrome and psychogenic coma. Akinetic mutism is a condition characterized by a lack of spontaneous movements and little or no vocalization. Somnambulism include performing of complex motor activity in an automatic manner during deep sleep, without any awareness of its execution. The locked-in syndrome is a state with quadriplegia coexisting with cranial nerves palsies and mutism, but with fully preserved consciousness. Psychogenic coma is a condition in which the patient has preserved level of consciousness and awareness, but does not communicate with theenvironment and does not exhibit the external manifestations of consciousness. This paper presents the etiology, clinical characteristics, as well as diagnostic and therapeutic issues for the above syndromes.

[Selected sociological aspects in patients intentionally intoxicated with xenobiotics]. / Wybrane aspekty socjologiczne u pacjentów po zamierzonym zatruciu ksenobiotykami.

UNLABELLED: A lot of data in medical literature shows significant influence of social factors on the incidence of suicide attempts. The aim of this study was to evaluate the significance of several sociological aspects in cases of patients after deliberate self poisoning with xenobiotics, who in the 2002-2005 period were treated in our Department. We analysed all self-poisoning cases of hospitalized patients. The study group consisted of 1416 patients: 836 (59.1%) female and 580 (40.9%) male. The average age of the subjects was 35.4 +/- 15.5 years. The sociological aspects included in the analysis were as follows: marital status, dwelling situation, financial situation and employment status or current level of education (in cases of patients still attending school). Among 1416 hospitalized subjects, 38.6% were married or cohabited; 35.7% described themselves as single and 12.2% were divorced or separated. Patients who in the moment of a suicide attempt were living with their families or friends represented the largest proportion of subjects (87.2%). Nearly a half of the patients (47.8%) stated that the financial means at their disposal hardly covered their most basic existential needs while more than 41% described their financial situation in the moment of a suicide attempt as poor. The largest group of the subjects consisted of professionally active people (27%), the second largest (25.6%) - of the unemployed. Almost 20% of patients willing to commit suicide were drawing a state pension due to their partial or complete incapacity to work. Just under 6% of patients in question were retired. The proportion of the unemployed or pensioners in the population aged 15-64 (n=1339) was as large as 47.9%. The dominant group in the population of patients still in their school years consisted of students of post-secondary schools. CONCLUSIONS: More than a half of the patients treated due to a suicide poisoning attempt claimed to live a single life, without a long-lasting relationship. The percentage of the divorced or the separated in the analysed popu- lation was high. In the group of the deliberately self-poisoned patients in their productive age (15-64 years), the proportion of the unemployed or pensioners reached almost 48%. Over 90% of the subjects after a suicidal episode described their financial situation as bad or unsatisfying.

[Seasonality in acute intoxication with xenobiotics]. / Sezonowosc w ostrych zatruciach ksenobiotykami.

UNLABELLED: There is a lot of data in medical literature which point at the phenomenon of seasonality of suicide attempts through self-intoxication. The aim of this study was to evaluate the seasonality of acute, suicide poisonings in 2002-2005 period. We analysed all self-poisoning cases hospitalized in 2002-2005 period in our Department. The study group consisted of 1416 patients including 836 female (59.1%) and 580 (40.9%) male. The average age was 35.4 +/- 15.5 years. The evaluation of suicide attempts' seasonality was made on two levels, i.e. days of the week and months of the year. This means we analysed the number of admissions to the Clinic due to deliberate self-poisoning in each month of the year and each day of the week. Based on the analysis of the number of cases admitted to the Department due to suicide poisoning it was established that there was a phenomenon of seasonality on both levels (days of the week and months of the year). The number of intoxication-related admissions proved to be significantly higher on Monday whereas significantly lower on Saturday. As far as the yearly seasonality is concerned the number of admissions to the Clinic was significantly below the average in February and in the period from August to October while it was significantly above the average in January and March. In respect to gender however we examined no statistically significant differences in the prevalence of intoxication in each day of the week or each month of the year. CONCLUSIONS: 1. The seasonality of suicide attempts was detected on both day of the week and month of the year levels. 2. No significant differences in the prevalence of intoxication were established in respect to gender on either day of the week or month of the year levels.

Variation in xenobiotic transport and metabolism genes, household chemical exposures, and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk. METHODS: We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures. RESULTS: We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively. CONCLUSIONS: Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants.

Poison prevention: engineering in primary prevention.

OBJECTIVES: Over the past 50 years we have seen improvements in outcomes of poisonings in the United States. I intend to discuss the approaches to prevention. METHODS: I review various primary, secondary, and tertiary prevention strategies in relationship to poison prevention. CONCLUSIONS: We have made strong efforts in some ways, but our efforts in primary prevention have often been less than maximal. We propose requiring lockable medicine cabinets and lockable storage cabinets for dangerous substances.

Molecular mechanisms underlying chemical liver injury.

The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals.