Fatal metaldehyde poisoning in a dog confirmed by gas chromatography.

BACKGROUND: Metaldehyde is a toxic pesticide used mainly as a molluscicide, responsible for intoxication and deaths in both humans and animals. Accidental exposure to metaldehyde in dogs is considered rare, but severe. Data concerning clinical and veterinary forensic toxicology are largely incomplete, especially regarding case reports in dogs. The present work reports a complete and detailed description of a case from the history, clinical evolution, pathological exams and toxicological diagnosis in an accidental case of metaldehyde poisoning in dog. CASE PRESENTATION: An eleven-month-old, 3.0 kg, male German Spitz was presented for emergency care with acute vomiting and seizures 3 hours after suspected accidental ingestion of commercial molluscicide containing 3% metaldehyde (Lesmax®). The animal was in lateral recumbency and showed stuporous mentation, salivation, tonic-clonic status epilepticus, systemic tremors, bilateral miosis, absent palpebral, corneal, oculovestibular and gag reflexes, severely depressed spinal reflexes, dyspnea and tachycardia. Despite treatment, the patient progressed to comatose mentation and died. Necropsy examination revealed discrete lesions in the liver and central nervous system, while stomach examination revealed content of feed, activated charcoal and blue-green granules, compatible to the commercial formula of metaldehyde. Histology examination revealed extensive hemorrhage and severe centrolobular necrosis of the liver and tumefaction of Kupfer cells. Brain samples showed discrete hemorrhage and hyperemia. In order to confirm the diagnosis, samples from feces, stomach content, spleen, liver, heart, kidneys and brain were submitted gas chromatography analysis. Results confirmed the presence of metaldehyde in all samples. We describe clinicopathological abnormalities of a fatal case of metaldehyde poisoning in a dog, as well as postmortem diagnosis using gas chromatography. CONCLUSION: Metaldehyde poisoning is rarely reported, since the diagnosis is often difficult and the notifications scarce. To our knowledge, this is the first report describing clinical signs, pathological findings and chromatographic diagnosis. This report aims to contribute to the understanding of the pathogenesis of metaldehyde intoxication, to further explore veterinary forensic toxicology diagnosis.

Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1).

BACKGROUND: Co-exposure to cigarette smoke and alcohol leads to the generation of high concentrations of acetaldehyde and malondialdehyde in the lung. These aldehydes being highly electrophilic in nature react with biologically relevant proteins such as surfactant protein D (SPD) through a Schiff base reaction to generate SPD adducted malondialdehyde-acetaldehyde adduct (SPD-MAA) in mouse lung. SPD-MAA results in an increase in lung pro-inflammatory chemokine, keratinocyte chemoattractant (KC), and the recruitment of lung lavage neutrophils. Previous in vitro studies in bronchial epithelial cells and macrophages show that scavenger receptor A (SR-A1/CD204) is a major receptor for SPD-MAA. No studies have yet examined the in vivo role of SR-A1 in MAA-mediated lung inflammation. Therefore, we hypothesize that in the absence of SR-A1, MAA-induced inflammation in the lung is reduced or diminished. METHODS: To test this hypothesis, C57BL/6 WT and SR-A1 KO mice were nasally instilled with 50 µg/mL of SPD-MAA for 3 weeks (wks). After 3 weeks, bronchoalveolar lavage (BAL) fluid was collected and assayed for a total cell count, a differential cell count and CXCL1 (KC) chemokine. Lung tissue sections were stained with hematoxylin and eosin (H&E) and antibodies to MAA adduct. RESULTS: Results showed that BAL cellularity and influx of neutrophils were decreased in SR-A1 KO mice as compared to WT following repetitive SPD-MAA exposure. MAA adduct staining in the lung epithelium was decreased in SR-A1 KO mice. In comparison to WT, no increase in CXCL1 was observed in BAL fluid from SR-A1 KO mice over time. CONCLUSIONS: Overall, the data demonstrate that SR-A1/CD204 plays an important role in SPD-MAA induced inflammation in lung.

Alcohol consumption and risk of gastric cancer: a cohort study of men in Kaunas, Lithuania, with up to 30 years follow-up.

BACKGROUND: Gastric cancer is the second most common cause of death from cancer in the world. Epidemiological findings on alcohol use in relation to gastric cancer remain controversial. The aim of this study was to examine the effect of alcohol consumption on the risk of gastric cancer. METHODS: The association between alcohol intake and the risk of gastric cancer was examined in a population-based cohort of 7,150 men in Kaunas, Lithuania, who were enrolled during 1972-1974 or 1976-1980. After up to 30 years of follow-up, 185 gastric cancer cases were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). The attained age was used as a time-scale. RESULTS: After adjustment for smoking, education level and body mass index, the HR of gastric cancer was 2.00 (95% CI: 1.04-3.82) for the highest alcohol consumption frequency (2-7 times per week) compared with occasional drinking (a few times per year) and 1.90 (95% CI: 1.13-3.18) for ≥ 100.0 g ethanol/week versus 0.1-9.9 g ethanol/week. A stronger effect of alcohol consumption on gastric cancer risk was observed during the second half of the study (1993-2008). In the analysis of gastric cancer risk by alcoholic beverage type, all beverages were included simultaneously in the model. The multivariate HR for men who consumed ≥ 0.5 litre of wine per occasion (compared with those who consumed <0.5 litre) was 2.95 (95% CI: 1.30-6.68). Higher consumption of beer or vodka was not statistically significantly associated with gastric cancer risk. After adjustment for smoking, education level, body mass index and ethanol, we found no excess risk of gastric cancer in association with total acetaldehyde intake. CONCLUSIONS: This study supports a link between alcohol consumption (primarily from ethanol) and the development of gastric cancer in the Lithuanian population. Although an association with heavy wine consumption was observed, the effect of exposure to acetaldehyde on the development of gastric cancer in this cohort was not confirmed. Further research is needed to provide a more detailed evaluation of alcohol drinking and gastric cancer risk.

Retrospective evaluation of the use of hemodialysis in dogs with suspected metaldehyde poisoning (2012-2017): 11 cases.

OBJECTIVE: To evaluate dogs treated with hemodialysis for severe metaldehyde intoxication and to compare them with conventionally-managed patients. DESIGN: Retrospective study (2012-2017). SETTING: University teaching hospital. ANIMALS: Data from 18 dogs with severe metaldehyde intoxication were analyzed. Eleven dogs were treated with intermittent hemodialysis and 7 managed conventionally. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Metaldehyde poisoning was diagnosed based on clinical signs and toxicological analysis or presence of turquoise material in the gastrointestinal content. Clinical signs, additional treatments, dialysis prescription, duration of anesthesia and hospitalization, complications, and outcome were documented. Results were analyzed by t-test, Mann-Whitney U-test, and Chi-square test. P < 0.05 was considered significant. Dialysis was performed for median (range) 180 min (150-420 min) with median of 2.28 L/kg (1.66-4.48 L/kg) blood volume processed. In the hemodialysis group, anesthesia was discontinued at a median of 3.0 hours (1.5-6.7 h) after starting dialysis. The conventional-group received general anesthesia for a median of 17.5 hours (7.0-30.5 h). No further anticonvulsive treatment was necessary for the hemodialysis group. Time to hospital discharge was shorter in dialyzed dogs (median 18 h; 15-41 h) compared to conventionally treated dogs (median 89 h; 61-168 h; P = 0.0014). Aspiration pneumonia was reported in 5 conventionally treated dogs and none of the dialyzed dogs (P = 0.001). Five dialyzed dogs developed hematoma at the dialysis catheter site. One dog in each group was euthanized. CONCLUSION: Hemodialysis significantly decreases the requirement for anesthesia and length of hospitalization in dogs with metaldehyde intoxication. Aspiration pneumonia occurred less often in dialyzed patients. Prospective studies are warranted to confirm the clinical utility of hemodialysis in dogs with metaldehyde poisoning.

Alcohol oxidation in rate inhibited by pyrazole, oximes, and amides.

Pyrazole, previously reported to inhibit ethanol oxidation in the rat, also effectively blocks the in vivo metabolism of methanol, propanol, isopropanol, n-butanol, and isobutanol. A variety of oximes and amides are also effective inhibitors of ethanol metabolism. These various inhibitors may prove important in the elucidation of several facets of alcohol metabolism and also may have application in the treatment of methanol poisoning and in the reduction of the sequelae of the disulfiram-ethanol reaction syndrome in man.

Determination of metaldehyde in human serum by headspace solid-phase microextraction and gas chromatography-mass spectrometry.

A rapid headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method has been developed for the determination of metaldehyde in human serum samples. Metaldehyde is extensively used as a molluscicide for the control of slugs and snails, and cases of metaldehyde poisoning have been reported. Metaldehyde was headspace-extracted on a polydimethylsiloxane (PDMS) fiber at 70 degrees C for 25 min, desorbed, and analyzed rapidly by GC-MS. The method was validated for limit of detection (LOD), linearity, precision, and recovery. Although the recovery of the sample was very low, the method itself was rapid with a low detection limit of 0.25 microg/ml, R.S.D. value 12.6%, and linearity range 0.5-25.0 microg/ml (r(2)=0.999). The results demonstrated that the SPME-GC-MS method for the analysis of metaldehyde is simple, rapid, solvent-free, and does not require any pre-analysis conversions.

Self-poisoning with metaldehyde.

Metaldehyde poisoning is rare. This case report details the largest toxic dose of self-poisoning with metaldehyde ever recorded in the literature to the authors' knowledge, the aim being to emphasise the features of metaldehyde toxicity and the potential for good clinical outcome. The patient was admitted unconscious with features consistent with poisoning. Appropriate critical care was instituted early with correction of his acid-base disorder, ventilatory support, correction of haemodynamic instability, anticonvulsant therapy and early admission to the critical care unit. An almost complete recovery was seen over the following weeks, the only lasting deficit being to short-term memory, a finding common to other reported incidents of metaldehyde toxicity. This case is notable in that the patient took more than one and a half times what is considered to be a lethal dose of metaldehyde (the largest reported), but has had a remarkably good clinical outcome that is proposed to be due to methodical and timely interventions delivered according to basic principles irrespective of the absence of the early identification of the poison. The case demonstrates several of the key features of metaldehyde toxicity and the emergency management of such a situation. The published literature pertaining to metaldehyde overdose is reviewed.

Geographical characteristics influencing the risk of poisoning in pet dogs: Results of a large population-based epidemiological study in Italy.

Pets can act as sentinels for human health and thus surveillance of pet dogs has the potential to improve awareness of emerging risks for animal and public health. The aim of this study was to investigate factors associated with the risk of canine poisoning. In a large population-based epidemiological investigation in Italy performed from January 2015 to January 2016 and April 2016 to April 2017, descriptive statistics were acquired and analysed to determine variables associated with poisoning events in pet dogs. Results were validated in a test population and forecast analysis of risk was performed. The cumulative incidence of poisoning events was low (10.2/1000 dogs/year). Anticoagulant rodenticides, organophosphate pesticides, metaldehyde and strychnine were the most frequent causes of intoxications. Territory characteristics significantly modulated both the frequency and the nature of the involved substances. The seashore area was associated with poisoning by rodenticides (odds ratio, OR, 1.81, 95% confidence interval, CI, 1.54-2.13) and metaldehyde (OR 1.61, 95% CI 1.16-2.28). The hill country area was associated with poisoning by organophosphate pesticides (OR 1.73, 95% CI 1.38-2.15), metaldehyde (OR 2.26, 95% CI 1.53-3.25) and strychnine (OR 1.86, 95% CI, 1.34-2.57). The mountain area was associated with strychnine poisoning (OR 3.79, 95% CI 2.84-5.06). The prospective cumulative incidence of poisoning over 10 years was 9.74% (95% CI 9.57-9.91). These results may be useful for predicting the risk of poisoning and for estimating the risk index related to specific toxic compounds in specific territories. This study suggests that poisoning events in dogs may represent a problem of public health with the potential to affect wildlife and human beings.

Super-refractory nonconvulsive status epilepticus due to self-poisoning with metaldehyde.

INTRODUCTION: Metaldehyde self-poisoning in adults is uncommon and, to the best of our knowledge, an episode of super-refractory nonconvulsive status epilepticus (sr-NCSE) following an suicide attempt has not been previously demonstrated. CASE REPORT: A 68-year-old woman was admitted to our Intensive Care Unit (ICU) in coma. On neurologic examination, the pupils were reactive, brainstem reflexes were present and plantar responses were flexor bilaterally. Routine laboratory tests were unremarkable. Arterial blood gas analysis revealed a mixed acidosis. A computed tomography (CT) scan of the brain and angio-CT were normal. The family confirmed that the patient had had suicidal ideation, and they had discovered a bag of slug killer (metaldehyde 5%) in her room. Two hours after the admission at the ICU, her neurological state remained unchanged. Sedation with intravenous propofol and antiepileptic therapy with levetiracetam (1000 mg/24 h) were started. The next day, propofol infusion was stopped but the level of consciousness of the patient did not improve. A video-electroencephalograhy (v-EEG) showed continuous generalized paroxysms of spike-wave and sharp-slow wave complexes compatible with the diagnosis of generalized NCSE. On day 3, the episode of NCSE was controlled. Finally, 15 days after ICU admission she was discharged with a normal neurological examination. CONCLUSION: This clinical case highlights that in comatose patients as consequence of metaldehyde poisoning, a v-EEG evaluation should be perform in order to rule out the existence of NCSE.

Clinical, neurological and clinicopathological signs, treatment and outcome of metaldehyde intoxication in 18 dogs.

OBJECTIVES: To describe the clinical signs, clinicopathological abnormalities and outcome of metaldehyde intoxication in dogs. METHODS: Medical records of dogs presenting between 1989 and 2005 with a diagnosis of metaldehyde toxicity were reviewed retrospectively. Data obtained from the medical record included signalment, history, clinical signs, laboratory tests results, hospitalisation period length, treatments and outcome. RESULTS: Eighteen dogs fulfilled the inclusion criteria. The most prevalent clinical signs were seizures, hyperthermia, tachycardia and muscle tremors. Serum biochemistry abnormalities included increased serum muscle enzymes activities, acidaemia (six dogs) and decreased blood bicarbonate (eight dogs). Treatment was symptomatic and supportive. Hyperbilirubinaemia was observed in two dogs. Diazepam was the most commonly used anticonvulsant followed by phenobarbitone and pentobarbital. General inhalant anaesthesia was required in nine of 18 dogs with seizures unresponsive to anticonvulsants. The survival was 83 per cent (15 of 18 dogs). CLINICAL SIGNIFICANCE: This clinical study recorded, for the first time in the veterinary literature, several clinicopathological abnormalities from severely intoxicated dogs. Metabolic acidosis was common, while acute or delayed hepatotoxicity was an uncommon complication.

Evaluation of the in vitro efficacy of hemodialysis, hemoperfusion, and the combined approach on the removal of metaldehyde from canine plasma.

OBJECTIVE: To evaluate the effect of hemodialysis, hemoperfusion, and a combined approach on the removal of metaldehyde from canine plasma. DESIGN: In vitro study. SETTING: University veterinary teaching hospital laboratory. ANIMALS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Metaldehyde-fortified canine plasma was prepared. Hemodialysis (HD), charcoal hemoperfusion (HP), and in-series hemodialysis and charcoal hemoperfusion (HD/HP) were applied in triplicate to eliminate metaldehyde from plasma. Plasma samples were obtained before starting the procedure and subsequently after every processed total plasma volume until plasma had been processed 10 times. Plasma metaldehyde concentration was quantitatively assayed by gas chromatography-mass spectrometry. Statistical analysis was performed using one-way ANOVA, repeated measures ANOVA, and Bonferroni post hoc test, and by calculating the coefficient of variation from duplicate measurements, binomial distribution, and by Bland-Altman analysis. Statistically significant reduction in metaldehyde concentration was reached by all 3 techniques. Reduction of metaldehyde concentration of more than 95% was achieved after processing the plasma volume 4 times applying HD, 8 times applying HP, and 2 times applying HD/HP. Efficacy in reduction of metaldehyde concentration differed significantly between the 3 procedures (P < 0.001). In-series hemodialysis and charcoal hemoperfusion was more effective in metaldehyde removal than HD (P = 0.003) and HP (P < 0.001), and HD was more effective than HP (P = 0.002). CONCLUSIONS: Metaldehyde was effectively removed by all applied extracorporeal blood purification techniques in vitro. However, the combination of both techniques was more effective than HD or HP alone. Further clinical studies are warranted to confirm therapeutic benefits in patients.

Fatal acute alcohol intoxication in an ALDH2 heterozygote: a case report.

On an evening in November, a 25-year-old man was found dead in his bedroom. There were many empty snap-out sheets for flunitrazepam tablets in the trash at his bedside. He had been beaten by a gang of young people earlier in the morning of the same day. At the medico-legal autopsy, although there were many bruises and/or abrasions on the whole body, only slight subdural hemorrhage was observed, and none of them was thought to be the cause of death. Flunitrazepam and its metabolites were not detected in his body fluid by gas chromatography-mass spectrometry (GC-MS). Marked lung edema and a severe congestion of organs were observed. His blood alcohol concentration from the femoral vein was 2.00 mg/ml. Fatal cases of acute alcohol intoxication usually have shown higher alcohol concentration (2.25-6.23 mg/ml). Although the genotype of aldehyde dehydrogenase 2 (ALDH2) has not previously been mentioned as a contributing factor in determining the cause of death, in this case the genotype of ALDH2 was ALDH2*1/2 and thus is important. Those who possess the ALDH2*2 gene show high concentrations of acetaldehyde (AcH) at even comparatively lower alcohol levels. Consequently, the cause of death was considered to be acute alcohol intoxication including AcH poisoning.

Persistence of metaldehyde during acute molluscicide poisoning.

A case is presented in which a 37-year-old man took an overdose of Slugit, liquid containing metaldehyde. Significant concentrations were found in his serum and urine for several days afterwards. Acetaldehyde and ethanol were not detected. The significance of these findings is discussed.

Pesticide poisoning of livestock: a review of cases investigated.

The cases of suspected poisoning of livestock by a range of organic chemicals, mainly pesticides, investigated at the Central Veterinary Laboratory during the period 1977 to 1980 are reviewed. The incidences of poisoning by various types of compound and the species most at risk are discussed. Organophosphorus pesticides and rodenticides were the commonest causes of poisoning. Pesticides accounted for one in 25 of all fatal poisonings listed by the veterinary investigation diagnosis analysis (VIDA) of the Ministry of Agriculture, Fisheries and Food.

Three cases of metaldehyde poisoning in cattle.

Poisoning of dairy cows and of calves by metaldehyde is reported. The clinical signs, post mortem and toxicological findings are described. Confirmations of the diagnoses was obtained by biochemical estimations. It would appear that a dose as low as 0.2 g/kg in adult cattle, and even less in calves, can be lethal.

Measurements of carbonyls in a 13-story building.

BACKGROUND, AIM AND SCOPE: Formaldehyde and acetaldehyde are emitted by many mobile and stationary sources and secondary aldehydes are intermediates in the photo-oxidation of organic compounds in the atmosphere. These aldehydes are emitted indoors by many materials such as furniture, carpets, heating and cooling systems, an by smoking. Carbonyls, mainly formaldehyde and acetaldehyde, have been studied because of their adverse health effects. In addition, formaldehyde is a suspected carcinogen. Therefore, the concentrations of formaldehyde and acetaldehyde were determined to assess the inhalation exposure doses to carbonyls for people who work in a 13-story building and in order to evaluate the cancer hazard. METHODS: Carbonyl compounds in indoor and outdoor air were measured at a 13-story building located in Mexico City. The mezzanine, fifth and tenth floors, and the third level-parking garage were selected for sampling. Samples were collected in two sampling periods, the first from April 20 to 29, 1998 and the second from December 1 to 20, 1998. Carbonyls were sampled by means of DNHP-coated cartridges at a flow rate of 1 l min(-1) from 9:00 to 19:00 hours, during 2-hour time intervals and analyzed by HPLC with hours, during 2-hour time intervals and analyzed by HPLC with UV/VIS detection. RESULTS: Mean carbonyl concentrations were highest in the 3rd level-parking garage, with the formaldehyde concentration being the highest ranging from 108 to 418 microg m(-3). In working areas, the highest carbonyl arithmetic mean concentrations (AM) were observed on the 5th floor. Acetone and formaldehyde concentrations were highest in April ranging from 161 to 348 microg m(-3) (AM = 226) and from 157 to 270 microg m(-3) (AM = 221), respectively. Propionaldehyde and butyraldehyde were present in smaller concentrations ranging from 2 to 25 and 1 to 28 microg m(-3), respectively, considering all the samples. Mean indoor/outdoor ratios of carbonyls ranged from 1.8 to 9.6. A reduction of inhalation exposure doses of 41% and 45% was observed in the fifth floor air after the air conditioning systems had been repaired. Formaldehyde and acetaldehyde concentrations were higher in smoking environments. CONCLUSION: Indoor carbonyl concentrations were significantly greater than outdoor concentrations. Tobacco smoke seems to be the main indoor source of formaldehyde. After the air conditioning system was maintained and repaired (as was recommended), an important reduction in the emission of formaldehyde and acetaldehyde was achieved on all floors, except for the 3rd level parking garage, thereby reducing the inhalation exposure doses. RECOMMENDATION: The results obtained in this research demonstrated that maintenance of air conditioning systems must be carried out regularly in order to avoid possible adverse effects on health. Additionally, it is mandatory that isolated smoking areas, with air extraction systems, be installed in every public building.

Epidemiological features of snail and slug bait poisoning in dogs and cats.

Snail and slug baits were the most common cause of poisoning in dogs and cats in a survey of 34 veterinary practices. During a 7-month period, 280 dogs and 12 cats were poisoned by metaldehyde (57%) or methiocarb (43%) containing baits with case fatality rates of 8.1% and 9.1% in dogs and 16.7% and 50% in cats, respectively. The ages of poisoned dogs ranged from 2 months to 17 years and cats from 3 months to 5 years. There was no decrease in frequency of poisoning or case fatality rate demonstrated with increasing body size in dogs. Poisoning was most frequent in the month of October. Baits were eaten off the ground or obtained from storage areas, often despite a variety of preventive measures. It is suggested that these products should be reformulated to make them less attractive to domestic pets.

The diminution of liver glutathione content and changes in activities of antioxidant enzymes in long-term acetaldehyde poisoning.

The effect of acetaldehyde administration for 4 weeks on antioxidant protection systems was investigated in liver of rats. Liver SOD activity was decreased from control value 542.4 U/g of tissue to 411.2 U/g of tissue in experimental group (24% decrease). GSH-Px activity was practically unchanged and liver CAT activity was significantly decreased (35%). Sulfhydryl compounds in liver non-proteins following ACH treatment were decreased from 4.22 mumol/g of tissue in control group to 2.86 mumol/g of tissue (23%). Furthermore acetaldehyde treatment caused significant increase in MDA level in liver (78% increase).

The liver: a pharmacologic perspective.

One of the may vital functions of the liver is the biodegradation of foreign substances. The enzyme systems responsible for this liver function are frequently the site of drug interactions, both therapeutic and detrimental. Various substances can alter these enzymes by inducing, inhibiting, or competing with them, thus affecting drug response. In most instances, the liver detoxifies and deactivates chemicals, protecting the body from their harmful effects. In some biotransformation processes, however, toxic metabolites are produced that may be injurious to liver tissue as well as other body organs and systems. The effect of alcohol on the liver is a prime example. Although significant strides have been made in recent years, much is yet to be learned concerning the effect of the liver on drugs, the effect of drugs on the liver, and the pharmacologic management of various liver diseases.