Cases Of Human Poisoning Research Articles

Gas chromatography of simple phenols in biological fluids

Acid hydrolysis of phenol conjugates in urine by concentrated H 3PO 4 followed by extraction of phenols with n-hexane and their acetylation before gas chromatography on columns packed with OV-1 or OV-17 is described. The sensitivity of the method is sufficient to monitor normal levels of phenol and p-cresol or phenol and o-cresol after exposure to benzene or toluene vapours. The detection limit is 1 mg/l. The method can also be used to diagnose acute oral intoxication by phenol or cresols and to estimate its significance in clinical or forensic toxicology. Normal urine levels of phenols and those in different cases of human intoxication are evaluated.

Rapid determination of ethylene glycol at toxic levels in serum and urine

The rapid gas chromatographic detection and determination of ethylene glycol in biological fluids is described. Phenylboronic acid in acetone was used for the esterification of glycol. The phenylboronates of ethylene glycol and 1,2-propylene glycol are not separated on a packed column of medium polarity (OV-17), but they can be separated on a non-polar column (OV-101). In both instances, 1,3-propylene glycol can be used as an internal standard. The method requires only 100 microliters of serum or urine and is suitable for trace analysis in an emergency toxicological laboratory. The utility of the method is demonstrated on two cases of human intoxication with ethylene glycol.

Bistramide A, a new toxin from the urochordata Lissoclinum bistratum Sluiter: Isolation and preliminary characterization

D. Gouiffes, M. Juge, N. Grimaud, L. Welin, M. P. Sauviat, Y. Barbin, D. Laurent, C. Roussakis, J. P. Henichart and J. F. Verbist. Bistramide A, a new toxin from the urochordata Lissoclinum bistratum Sluiter: isolation and preliminary characterization. Toxicon 26, 1129–1136, 1988.—Two cases of human intoxication caused by the lyophilized powder of Lissoclinum bistratum Sluiter, a New Caledonian ascidian, are reported. The symptoms observed were caused by a substance designated bistramide A (C 40H 68N 2O 8) of hitherto unknown chemical structure. Preliminary toxicological investigations indicate that bistramide A may effect the central nervous system, leading to paresthesia and loss of muscle tone. A progressive decrease in cardiac rhythm was also observed in animals. Bistramide A (1.4 × 10 −6 M) did not alter the resting potential of frog heart and skeletal muscle but reduced the amplitude and duration of cardiac action potential and prolonged the interval between action potentials. Bistramide A also has a marked cytotoxic effect on cancer cells KB ( ic 50 = 4.5 × 10 −8 M ) and P 388 ( ic 50 = 2.0 × 10 −8 M ) and on normal endothelial cells ( ic 50 = 2.2 × 10 −8 M ). However, it has not been possible to relate the cytotoxic property to the symptoms of intoxication. Bistramide A may originate from the urochordate itself or from symbiotic algae.

Prostaglandin E2: A candidate for causative agent of "ogonori" poisoning.

Two cases of human intoxication resulting from consumption of red marine algae Gracilaria verrucosa (Japanes name, ogonori) and G. chorda (tsurushiramo) have recently occurred in Japan. Large amounts of inorganic salts present in these seaweeds has been suggested to be responsible for the poisoning. We however found that the extracts prepared from these algae which had been steeped in freshwater evoked severe diarrhea in mice; the main symptom of human victims. Two active principles have been isolated pure from G. verrucosa that was soaked in distilled water for20h. The principal compound was identified to be prostaglandin E2 by spectral data, chemical transformation and direct comparison with authentic specimens, while the less active substance to be prostaglandin A2. Responsibility of the prostaglandins, particularly PGE2, for the “ ogonori ” poisoning has been suggested. It was also proposed that an inhibitor of prostaglandin synthesis is present in the algae of the genus Gracilaria.

The use of acute toxicity data in poison information centres.

Abstract Of the various animal test data the poison information centres consider the eye and skin irritation tests to be useful and the findings transferreble to man for evaluation of acute exposure risks.The LD50 and LC50 data are considered of doubtful value and even to involve some risks. Presented as uncommented figures, especially if placed alongside physical data on a chemical substance, they are given a nimbus of exactness that they are not entitled to because of the known reasons of species differences etc. LD50‐s are mortality data but what the poison information centres need are morbidity data. Doses lower than LD50 are as TD‐s therefore more of interest, provided they are given with a detailed description of the developing intoxication symptoms, preferrably also with information on the steepness of the dose‐symptoms curve. The facilities today to prevent death due to acute poisonings place the residual symptoms at survival more in the centre of interest and responsibility. Careful postmortems of the test animals are therefore also needed. Although examinations may have been performed on the animals killed by the LD50 dose they might have died too early for a late organ damage to appear (e.g. in paraquat poisoning the animal may die in kidney insufficiency which comes earlier than the obliteration of the bronchioli respiratorii) or the killing factor may be another than the one involved in the residual symptoms (e.g. CO‐poisoning, where COHb is the life‐limiting factor in gross exposure but does not seem to be related to the severe late CNS symptoms).When rating the toxicity of closely related but different compounds LD50 has some value.Suggestions: Symptoms developing at different TD‐s should be presented. Organs should be examined macro‐ and microscopically (had this been done the vacuoles in the CNS might have been seen early in the animal testing of hexachlorophene and human poisonings thereby prevented). The human poisoning cases — now not used to the extent they could be for drawing information regarding the poisoning — should be studied much more in detail and the information from different countries pooled. Poison information centres could act as a network.LDlow and TDlow in man would then be better and earlier known. The clinicians should, however, then be given better facilities of collaboration with toxicological laboratories, to make it possible to widen the scope of investigations, which now often must be limited to the need of the individual case. Starting from clinical findings animal tests — as is already the practice — should be done to deepen the understanding of mechanisms. Cultures of surviving cells could in some situations add important information and will probably be increasingly used.

Naturally occurring toxicants in foods and their significance in the human diet.

Among the many biologically active and potentially toxic factors known to be present in plant foodstuffs normally consumed by man, those that are present in legumes have received the most attention. Two categories of legume toxins will be considered - those whose effects have been extensively studied in experimental animals but whose significance in man must remain open to conjecture, and those which are known to produce toxic effects in man but whose identity remains uncertain because similar effects are not readily reproduced in animal models. The protease inhibitors have, over the years, been the object of much study in experimental animals where they have been observed to have an adverse effect on growth and to cause pancreatic enlargement. The relevance of these observations to human nutrition remains obscure, however, because of our lack of knowledge concerning the effect of soybean trypsin inhibitors on the human pancreas. Lectins from certain legumes such as the common bean (Phaseolus vulgaris) have been shown to be toxic to animals upon oral ingestion presumably because of the damage which they inflict upon binding to the cells lining the intestinal mucosa. Lectins may therefore be responsible for reported cases of human intoxication associated with the consumption of inadequately cooked beans. Lathyrism and favism are diseases in man which are associated with the consumption of Lathyrus sativus and Vicia faba respectively. Evidence leading to the probable identification of the causative factors of these diseases and the steps necessary for their elimination will be discussed.

Review of the toxicity of hexachlorophene.

Hexachlorophene has been used extensively as an antibacterial agent for the past 20 years. A review of the literature revealed several cases of human poisoning. A single dose of 250 mg/kg of hexachlorophene administered orally seems to be fatal in children, and daily doses of 20 mg/kg taken for three days cause toxic symptoms. Hexachlorophene is also absorbed by the intact and denuded skin. Central nervous system symptoms developed in a normal infant who was treated with a 3% hexachlorophene solution as a lotion after bath for four days. Work in our laboratory and reports in the literature indicate that rats and pigs develop paralysis when they are exposed to high doses, but the effect on the central nervous system is reversible when exposure to hexachlorophene is discontinued.

Alkylmercury Contamination of Foods

No cases of human poisoning by alkylmercury compounds in intended foodstuffs have been reported in North America to date. 1 However, its symptoms are well known, from accidental poisonings and the tragic episodes at Minamata and Niigata, Japan. The chief culprit has been methylmercury. Summarized, these symptoms include, more or less in order of ascending severity, ( a ) excessive weakness, fatigue, apathy, lack of interest; ( b ) paresthesias of perioral area and extremities; ( c ) tunnel vision, hearing difficulties, fits of rage, depression; ( d ) dysarthria, dysdiadochokinesia, ataxia, alexia, agraphia, clumsiness in handling familiar objects, intention tremor; ( e ) gross motor incoordination, spasticity, paralysis, coma, death. Minamata disease, first reported in Japan in 1953, affected 121 persons, causing 46 deaths. Its origin was methylmercury chloride, discharged into the Minamata Bay and River by a plastics plant; fish containing 20

Methyl chloride intoxication; report of two cases; one complicating pregnancy.

EARLY in the development of electric refrigeration methyl chloride was a commonly used refrigerant. However, the toxic properties of this gas brought about the development and present use of nontoxic agents to replace it.1 In 1947 Smith and Von Oettingen2 reviewed the clinical literature dealing with methyl chloride poisoning. As of that date over 200 cases of human poisoning had been reported, including 15 deaths. This type of intoxication was most commonly seen in refrigeration workmen who were exposed to the gas at work or in persons who were victims of leaky refrigeration systems in their households.Despite the known . . .

Acute poisoning with sodium fluoroacetate (compound 1080).

Since the report of Kalmbach1on the rodenticide activity of fluoroacetate (compound 1080) this compound has been extensively used by government agencies, the armed forces, and privately employed exterminators. In spite of its high toxicity to all species, relatively few cases of human poisonings have been reported so far, none of which have ended fatally.2All of the victims took small, but unidentified, quantities of fluoroacetate. The toxic dose for human beings has not been established, but on the basis of animal studies it has been theorized as being approximately 5 mg. per kilogram of body weight. The case reported here ended fatally, pathological examination was performed, and the quantities of fluoroacetate in the organs were determined. For the experimental literature on fluoroacetate we may refer the reader to the recent reviews by Chenoweth3and by us.4 REPORT OF CASE A white man, about 40 years

THE PHARMACOLOGY OF THE LOCAL ANESTHETICS

Acute intoxication in man from the use of the local anesthetics is far more common than is indicated by the number of recorded cases. We undertook to investigate the causes of such intoxication, and sought to find means of avoiding it, or combating it when it arises. This investigation has included a study of the literature of the more important cases of human intoxication, and the performance of over 300 experiments on cats. The details of this work are published elsewhere, 1 the present communication being limited to a short discussion of the more important facts brought to light, especially with reference to their bearing on the clinical problem. Nine of the local anesthetics were studied, and the maximum toxicity of each was determined by rapid intravenous injection into cats. The drugs used, the fatal dose of each, the concentrations of the solutions employed, and the relative toxicities of the