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Background: There are no reliable studies in Poland evaluating the scale of acute intoxications with different types of xenobiotics., Objective: The aim of the study was to evaluate selected problems referring to the patients intoxicated with glycol and methanol, who were given the medical treatment in all Toxicological (TUs) and Intensive Care Units (ICUs), having contract with Polish National Fund of Health, in the year 2009., Methods: All cases of acute intoxications treated in Polish hospitals in 2009 and reported to the Polish National Fund of Health were included to the analysis. To further analysis were chosen only those patients, whose main diagnosis or comorbidities were coded as T51.1 or T52.3 according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision and, according to the state of health, patients were treated in TUs and ICUs. All the cases, in which intoxication was not the main health problem were excluded., Results: There were 85 398 acute intoxications in Poland in 2009, 470 of them referred to glycol and methanol poisonings. 192 patients were treated in TUs and ICUs. The most common methods of therapy in those units were extracorporeal toxin removal (60.2% in TUs and 62.5% in ICUs) and conservative treatment (39.8% in TUs and 37.5% in ICUs). The mortality rate in glycol and methanol poisonings in TUs and ICUs were 24.2%, and 56.3% respectively. In the conservatively treated group the mortality rates in TUs and ICUs were 23.5%, and 66.7% respectively, while in extracorporeal toxin removal group the mortality rates in TUs and ICUs were 24.7%, and 50% respectively. The authors also observed two regions (Maków Mazowiecki and Słubice), in which the amount of glycol and methanol intoxications was much higher than in the rest part of the country., Conclusions: 1. All the cases of acute intoxications of glycol and methanol should be consulted with Polish Poison Control Centers. 2. It is necessary to establish diagnostic and treatment protocols for intoxicated patients in Poland. 3. There is a strong need for popularization of the modern methods of glycol and methanol poisonings therapy and increasing the availability of modern antidotes. 4. It is necessary to monitor diagnostics, treatment and mortality rate of glycol and methanol intoxicated patients in all types of hospital units in Poland. 5. There is a need of further toxicological education of medical students and doctors as well. 6. The cases of abnormally high rate of glycol and methanol intoxications in some hospitals should be investigated.

Introduction: The use and clinical efficacy of the alcohol dehydrogenase inhibitor fomepizole is well established for the treatment of ethylene glycol and methanol poisonings in adults., Methods: A computerized search of the U.S. National Academy of medicine and EMBase databases was undertaken to identify published cases of patients treated with fomepizole. This search strategy identified 14 published cases related to the topic of this review: 10 due to ethylene glycol poisoning, 1 due to diethylene glycol poisoning, 1 due to butoxyethanol ingestion, and 2 due to methanol poisoning. The median age of these cases was 5.5 years old. FOMEPIZOLE IN GLYCOL AND GLYCOL ETHER POISONING: For the 10 ethylene glycol poisoned patients, the median recorded values of their arterial pH was 7.27 (range 7.03-7.38), serum bicarbonate concentration was 13 mEq/L (range 2-25), and ethylene glycol concentration was 2,140 mg/L (range 130-3,840). Eight of these patients were not hemodialyzed. The eight patients who were not hemodialyzed had ethylene glycol concentrations as high as 3,500 mg/L and serum bicarbonate concentrations as low as 4 mEq/L. All 10 patients had resolution of their metabolic acidosis and recovered without sequelae. The half-times of ethylene glycol elimination ranged from 9 to 15 h during fomepizole therapy, which is faster than the 19.7 h reported in adults. The two patients who ingested diethylene glycol or butoxyethanol all recovered without sequelae. The patient who ingested the butoxyethanol had a serum bicarbonate concentration of 13 mEq/L and was not hemodialyzed. FOMEPIZOLE IN METHANOL POISONING: One of the two children who ingested methanol was hemodialyzed. Both cases had a similar degree of severity. DOES FOMEPIZOLE OBVIATE THE NEED FOR HEMODIALYSIS?: Based on the experience reviewed herein it appears that, as in adults, hemodialysis may not be necessary in most cases of pediatric ethylene glycol poisoning if treated with fomepizole. FOMEPIZOLE PHARMACOKINETICS: Plasma fomepizole concentrations were measured in three cases and were found to be therapeutic with apparent Michaelis-Menton kinetics, having a zero-order elimination rate of 0.6-1 mg/L/h at higher concentrations and a first-order elimination with an apparent elimination half-time of 3.9 h at lower concentrations. FOMEPIZOLE REGIMEN: Most cases used the current U.S.-approved regimen. ADVERSE EFFECTS OF FOMEPIZOLE: The one adverse effect reported during fomepizole therapy was transient nystagmus in a 6-year-old with a serum ethylene glycol concentration of 130 mg/L and a serum bicarbonate concentration of 2 mEq/L; it is likely that ethylene glycol itself was the cause. COMPARISON OF FOMEPIZOLE WITH ETHANOL THERAPY: Two cases were originally treated with ethanol but switched to fomepizole because of adverse effects. In both cases, the adverse reactions to ethanol resolved once fomepizole treatment was initiated., Conclusions: The limited data available suggest that fomepizole, using the same dosage regimen as that used for adults, is efficacious and well tolerated in pediatric patients. In many cases of pediatric ethylene glycol poisoning treated with fomepizole, hemodialysis may not be necessary despite high concentrations and the presence of metabolic acidosis.

Background: The Poisons Information Centre receives many inquiries about acute exposures to chemical products. Our aim was to characterise the frequency and severity of such exposures and to raise awareness of chemicals that rarely cause poisoning, but may lead to serious systemic toxicity even in small amounts., Material and Methods: Data were collected from inquiries to the Poisons Information Centre in the period 2004-2006 and from the Product Register on the use of selected chemicals., Results: In 2004-2006, the Poisons Information Centre received 35,802 inquiries regarding acute exposures to chemicals or chemical products. Most of the exposures (72%) were assessed as non-toxic or involving risk of minor poisoning, while only 7.8% were assessed as involving risk of severe poisoning. The substances most frequently involved were cleaning agents, cosmetics/personal care products and hydrocarbon fuels, whereas risk of severe poisoning is related to alkali and hydrocarbon exposures. Poisonings with hydrofluoric acid and glycols/glycol ethers are rare, but the outcome is often severe. As many as 84% of the hydrofluoric acid exposures and 36% of the ingestions of ethylene glycol by children were assessed as involving risk of moderate or severe poisoning., Interpretation: Exposure to chemicals or chemical products is frequent, but rarely leads to severe poisonings. Data from inquiries to the Poisons Information Centre are representative of the chemical exposure conditions. It is important to have detailed product information readily available to assure correct treatment after exposure incidents.

Alcohol-related intoxications, including methanol, ethylene glycol, diethylene glycol, and propylene glycol, and alcoholic ketoacidosis can present with a high anion gap metabolic acidosis and increased serum osmolal gap, whereas isopropanol intoxication presents with hyperosmolality alone. The effects of these substances, except for isopropanol and possibly alcoholic ketoacidosis, are due to their metabolites, which can cause metabolic acidosis and cellular dysfunction. Accumulation of the alcohols in the blood can cause an increment in the osmolality, and accumulation of their metabolites can cause an increase in the anion gap and a decrease in serum bicarbonate concentration. The presence of both laboratory abnormalities concurrently is an important diagnostic clue, although either can be absent, depending on the time after exposure when blood is sampled. In addition to metabolic acidosis, acute renal failure and neurologic disease can occur in some of the intoxications. Dialysis to remove the unmetabolized alcohol and possibly the organic acid anion can be helpful in treatment of several of the alcohol-related intoxications. Administration of fomepizole or ethanol to inhibit alcohol dehydrogenase, a critical enzyme in metabolism of the alcohols, is beneficial in treatment of ethylene glycol and methanol intoxication and possibly diethylene glycol and propylene glycol intoxication. Given the potentially high morbidity and mortality of these intoxications, it is important for the clinician to have a high degree of suspicion for these disorders in cases of high anion gap metabolic acidosis, acute renal failure, or unexplained neurologic disease so that treatment can be initiated early.

A simple extraction and derivatization procedure for the analysis of eight glycols (ethylene glycol, EG; diethylene glycol, DEG; triethylene glycol, TEG; 1,2-propanediol, 1,2-PD; 1,3-propanediol, 1,3-PD; 1,2-butanediol, 1,2-BD; 2,3-butanediol, 2,3-BD; and hexylene glycol, HXG) using a 2-microL serum or blood sample is described. Following deproteinisation with acetonitrile, derivatization to its mono or di TMS derivative, glycols were detected using gas chromatography-electron impact mass spectrometry equipped with a split-spitless inlet and a DB-5MS column in the scan mode from 40 to 500 amu. Gamma-hydroxybutyrate-d6 (GHB-d6) was used as the internal standard. The limits of detection and quantitation in 2 pL of serum ranged, respectively, from 0.7 mg/L for EG to 8.5 mg/L for TEG and from 1.3 mg/L for EG to 18.2 mg/L for 1,2-PD. A linear response was observed over the concentration range from 1 to 800 mg/L for EG and 18 from 800 for TEG and 1,2-PD for serum and blood. Coefficients of variation for both intra-assay precision and interassay reproductibility ranged respectively between 1.9% for TEG to 4.9% for 1,2-PD (11.8% for HXG) and 3.5% for DEG to 9% for 2,3-BD (20.4 for HXG) at the 400 mg/L serum level. The method was applied to plasma and whole blood.

The toxicologic pathology of petroleum and oilfield-related chemicals is reviewed, and a field guide for toxicopathologic evaluation of cattle is given. Cattle will voluntarily ingest petroleum and chemicals used in the exploration, production and transportation of crude petroleum. Variability in chemical composition of petroleum from different fields will alter the type and severity of lesions observed. When airborne pollutants are present, cattle are continually exposed and make excellent sentinel animals. The lung, kidney, liver, gastrointestinal tract, heart and brain are target organs for petroleum hydrocarbons. Exposure to elemental sulfur can produce pulmonary pathology. Sulfur-containing gases are irritating to the mucosa of the eye and respiratory tract. Arsenic and lead cause lesions in the gastrointestinal tract, brain, liver and kidney. Glycols are hepato-, nephro- and neurotoxic, and oral exposure to diethylene glycol produces corneal lesions. Invert drilling fluids are fetotoxic. Nonpesticide organophosphate esters target the peripheral and central nervous systems. Toxicopathy is a strategic tool in the diagnosis of intoxications occurring in cattle after exposure to oilfield chemicals. Cattle are sensitive to oilfield pollutants and are a useful biomonitoring species.

Changes in the distribution of stainable gap substance and subaxolemmal density at peripheral nodes of Ranvier in hexacarbon-intoxicated rats have been studied by light and electron microscopy. Cupric ion binding to the nodal gap substance was seen in normal nodes as a discrete annulus by the formation with ferrocyanide of Hatchett's Brown reaction product. Staining of osmicated fibres with ferrocyanide ions alone gave a deposit of black reaction product at the subaxolemmal region at nodes of Ranvier. Paranodal distension by neurofilamentous masses and separation of the terminal myelin loops in the early phase of paranodal dilatation produced no change in the distribution of the two kinds of stainable material. Paranodal myelin retraction with increases both in nodal gap width and nodal axon diameter resulted in displacement and attenuation of both stained regions. Axonal protrusion at the nodal region tended only to displace the stained gap substance, but sometimes it resulted in its attenuation. Occasionally loss of subaxolemmal staining was found. The possible functional relevance of these abnormal findings is discussed in relation to changes in conduction in affected nerves.

A study has been made of the structural changes of nodal and paranodal regions of the nodes of Ranvier of peripheral nerves of rats in which marked accumulations of neurofilaments have occurred within axons under the influence of 2,5-hexanediol over 10 weeks. The neurofilamentous masses caused distension of the axon at two points of apparent weakness as they attempted to slide through the axonal constriction at the nodes. Principally, a spiral axonal protrusion pushed into the zone of unattached myelin loops in the proximal paranodal spinous bracelet of Nageotte. This led to a conical widening of the paranodal constriction and considerable attenuation of the overlying myelin. No degeneration of the myelin occurred however. Alternatively, or additionally, a protrusion occurred of the axon at the nodal region which increased the nodal gap width and occasionally compressed and displaced the adjacent distal paranodal constriction which could have led to some obstruction of axoplasmic flow. Swelling of distal paranodal regions occurred later and was usually associated with proximal swelling. It was also accompanied by evidence suggesting transnodal passage of filamentous material. Sometimes, however, striking nodal constriction occurred in association with symmetrical paranodal swelling. These observations suggest that the spiral glial-axonal relationships at nodes of Ranvier are capable of marked deformation that might allow the intra-axonal neurofilamentous masses to move distally. These findings are discussed in relation to the structural features of the paranodal constrictions.

Rats were given 2,5-hexanediol in their water for more than 5 weeks. The changes in the optic pathways were studied both qualitatively and quantitatively. Increase in 10-nm filaments within axons was noticeable from 10 days onwards in the superior colliculus and in the brachium of the superior colliculus. From then onwards there was a steady increase in the number of affected axons, and their gross enlargement occurred. The proportion of affected fibres in the brachia was in fact few, but all fibres were of retinotectal origin. Less than half of those in the superior colliculus that were swollen were of retinal origin. Measurement of axon diameter versus myelin sheath thickness showed gross relative thinning of the latter. Axon degeneration did not occur but there was increasing ultrastructural evidence of impairment of transport of organelles both centrifugally and centripetally as the filamentous masses accumulated.

Experimental investigations were undertaken to establish the acute and subacute inhalatory, oral and dermal toxicity of glycolmonophosphate. Modern toxicologic, biochemical and pathomorphologic methods were used. It was found that glucomonoacetate has a mild acute and subacute inhalatory, oral and dermal toxicity. The changes in some enzyme activities (GOT, GPT, AP, HE) and the parenchymatous dystrophy of the liver are considered transient and of functional nature. The toxic effect of glucomonoacetate is studied for the first time. Its use in the production of cigarette filters has a definite economical effect.

Rats have been dosed with 2,5-hexanediol for 48 days and then allowed to recover. The changes in the accumulations of neurofilamentous masses in various pathways in CNS and PNS have been followed by light microscopy over the subsequent 9 weeks. It was found that many CNS pathways allow the argyrophilic masses to pass to their terminals from whence they subsequently disappear, usually over 5-6 weeks. Little or no axonal degeneration is seen where this happens. The same occurs in many peripheral nerves, particularly cranial nerves. However, in many tracts in the spinal cord and in many axons in the longer peripheral nerves, filamentous masses remain and becomes associated with axon degeneration, and, in tracts, gliosis. The importance of paranodal constrictions at nodes of Ranvier which tend to be greater in larger diameter axons is emphasized as a likely mechanism for the axon degeneration which largely took place during the recovery period.