Toxicological reviews最新文献

{"title":"Human parathion poisoning. A toxicokinetic analysis.","authors":"Florian Eyer,&nbsp;Veronika Meischner,&nbsp;Daniela Kiderlen,&nbsp;Horst Thiermann,&nbsp;Franz Worek,&nbsp;Michael Haberkorn,&nbsp;Norbert Felgenhauer,&nbsp;Thomas Zilker,&nbsp;Peter Eyer","doi":"10.2165/00139709-200322030-00003","DOIUrl":"https://doi.org/10.2165/00139709-200322030-00003","url":null,"abstract":"<p><p>The mortality rate of suicidal parathion poisoning is particularly high, the onset of fulminant cholinergic signs, and the patients frequently present to the emergency physician with life-threatening symptoms. Despite this uniformity, subsequent clinical course differs significantly among patients, mostly not as a result of different delays in treatment or insufficiency of primary care. Probably, the differences depend on the amount of poison absorbed and/or the disposition of the active poison, paraoxon. We followed the toxicokinetics of parathion and tried to quantify the actual poison load. To this end, we monitored parathion-intoxicated patients (patients requiring artificial ventilation) for plasma levels of parathion and paraoxon along with the activity of erythrocyte acetylcholinesterase and its reactivatability. Plasma obidoxime concentrations were followed as well as the cumulative urinary para-nitrophenol conjugate excretion as a measure of total poison load. All patients received a standard obidoxime scheme of a 250 mg bolus dose intravenously, followed by continuous infusion with 750 mg per 24 hours as long as reactivation could be expected (usually 1 week). All other treatment was instituted as judged by the physician. It was recommended to use atropine at low doses to achieve dry mucous membranes, no bronchoconstriction and no bradycardia. Usually 1-2 mg/h were sufficient. Seven selected cases are presented exemplifying toxicokinetic peculiarities. All patients were severely intoxicated, while the amount of parathion absorbed varied widely (between 0.12 and 4.4 g; lethal dose 0.02-0.1 g) and was generally much lower than anticipated from the reports of relatives. It remains open whether the discrepancies between reports and findings were due to exaggeration or to effective decontamination (including spontaneous vomiting, gastric lavage and activated charcoal). Absorption of parathion from the gastrointestinal tract was sometimes retarded, up to 5 days, resulting in fluctuating plasma profiles. The volume of distribution at steady-state (Vdss) of parathion was around 20 L/kg. Post-mortem analysis in one patient revealed a 66-fold higher parathion concentration in fat tissue compared with plasma, 16 days after ingestion. Biotransformation of parathion varied widely and was severely retarded in one patient receiving fluconazole during worsening of renal function, while phenobarbital (phenobarbitone) sedation (two cases) had apparently no effect. The proportion of plasma parathion to paraoxon varied from 0.3-30, pointing also to varying paraoxon elimination, as illustrated by one case with particularly low paraoxonase-1 activity. Obidoxime was effective at paraoxon concentrations below 0.5 microM, provided aging was not too advanced. This concentration correlated poorly with the paration concentration or the poison load. The data are discussed in light of the pertinent literature.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 3","pages":"143-63"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322030-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health implications of exposure to environmental nitrogenous compounds.","authors":"Tjeert T Mensinga,&nbsp;Gerrit J Speijers,&nbsp;Jan Meulenbelt","doi":"10.2165/00139709-200322010-00005","DOIUrl":"https://doi.org/10.2165/00139709-200322010-00005","url":null,"abstract":"<p><p>All living systems need nitrogen for the production of complex organic molecules, such as proteins, nucleic acids, vitamins, hormones and enzymes. Due to the intense use of synthetic nitrogen fertilisers and livestock manure in modern day agriculture, food (particularly vegetables) and drinking water may contain higher concentrations of nitrate than in the past. The mean intake of nitrate per person in Europe is about 50-140 mg/day and in the US about 40-100 mg/day. In the proximal small intestine, nitrate is rapidly and almost completely absorbed (bioavailability at least 92%). In humans, approximately, 25% of the nitrate ingested is secreted in saliva, where some 20% (about 5-8% of the nitrate intake) is converted to nitrite by commensal bacteria. The nitrite so formed is then absorbed primarily in the small intestine. Nitrate may also be synthesised endogenously from nitric oxide (especially in case of inflammation), which reacts to form nitrite. Normal healthy adults excrete in the urine approximately 62 mg nitrate ion/day from endogenous synthesis. Thus, when nitrate intake is low and there are no additional exogenous sources (e.g. gastrointestinal infections), the endogenous production of nitrate is more important than exogenous sources. Nitrate itself is generally regarded nontoxic. Toxicity is usually the result of the conversion of nitrate into the more toxic nitrite. There are two major toxicological concerns regarding nitrite. First, nitrite may induce methaemoglobinaemia, which can result in tissue hypoxia, and possibly death. Secondly, nitrite may interact with secondary or N-alkyl-amides to form N-nitroso carcinogens. However, epidemiological investigations and human toxicological studies have not shown an unequivocal relationship between nitrate intake and the risk of cancer. The Joint Expert Committee of the Food and Agriculture Organization of the United Nations/World Health Organization (JECFA) and the European Commission's Scientific Committee on Food have set an acceptable daily intake (ADI) for nitrate of 0-3.7 mg nitrate ion/kg bodyweight; this appears to be safe for healthy neonates, children and adults. The same is also true of the US Environmental Protection Agency (EPA) Reference Dose (RfD) for nitrate of 1.6 mg nitrate nitrogen/kg bodyweight per day (equivalent to about 7.0 mg nitrate ion/kg bodyweight per day). This opinion is supported by a recent human volunteer study in which a single dose of nitrite, equivalent to 15-20 times the ADI for nitrate, led to only mild methaemoglobinaemia (up to 12.2%), without other serious adverse effects. The JECFA has proposed an ADI for nitrite of 0-0.07 mg nitrite ion/kg bodyweight and the EPA has set an RfD of 0.1 mg nitrite nitrogen/kg bodyweight per day (equivalent to 0.33 mg nitrite ion/kg bodyweight per day). These values are again supported by human volunteer studies.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 1","pages":"41-51"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322010-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diazepam in the treatment of organophosphorus ester pesticide poisoning.","authors":"Timothy C Marrs","doi":"10.2165/00139709-200322020-00002","DOIUrl":"https://doi.org/10.2165/00139709-200322020-00002","url":null,"abstract":"<p><p>Although the main site of action of diazepam, as with other benzodiazepines, is at the gamma-aminobutyric acid A (GABAA) receptor, the degree to which the beneficial actions of diazepam in organophosphorus (OP) ester pesticide poisoning are mediated through the GABAA receptor has been a matter of controversy. Although in most series of OP intoxications, convulsions have been relatively uncommon, it is probable that convulsions produce long-term sequelae in the central nervous system by causing structural damage. Animal studies have demonstrated that diazepam prevents and treats convulsions produced by OPs and may prevent the late effects caused by damage to the central nervous system induced by such convulsions. Consequently, the use of diazepam is an important part of the treatment regimen of severe OP poisoning as it prevents, or at least reduces the duration of, convulsions. In addition, case reports suggest that diazepam will also ameliorate muscle fasciculation, a subjectively unpleasant feature of OP pesticide poisoning. There are no data, either experimental or clinical, demonstrating any clear effect of diazepam alone on lethality in OP poisoning. In fact, in one study of large animals, diazepam, given alone, increased lethality. In animals experimentally poisoned with OPs, combined treatment with atropine and diazepam significantly lowered lethality compared with atropine treatment alone, indicating a clear beneficial effect. There are numerous case reports of the use of diazepam, generally as an adjunct to other more specific OP antidotes such as atropine and/or pyridinium oximes. Based on this evidence and pharmacodynamic studies in experimental animals, diazepam should be given to patients poisoned with OPs whenever convulsions or pronounced muscle fasciculation are present. In severe poisoning, diazepam administration should be considered even before these complications develop. Although diazepam has a large therapeutic index, there appears to be no place for its routine use in OP poisoning. Diazepam should be given intravenously to patients treated in hospital for OP poisoning, although the intramuscular route is used to administer diazepam outside hospital, such as on the battlefield, when an auto-injector is employed. It should be recognised, however, that absorption by the intramuscular route is poor.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 2","pages":"75-81"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322020-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24459001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical drug overdose case reports. From the world literature.","authors":"","doi":"10.2165/00139709-200322020-00007","DOIUrl":"https://doi.org/10.2165/00139709-200322020-00007","url":null,"abstract":"<p><p>All pharmaceutical drugs have the potential to be misused or wrongly administered, which can result in toxic amounts of drug being ingested. To help you keep up-to-date with the latest data on outcomes and management of overdoses, both accidental and intentional, we have selected the following case reports recently published in the world's medical literature and summarised in Reactions Weekly. Any claim of first report has been verified by a search of the Adisbase (a proprietary database of Adis International) and Medline. In addition, the World Health Organization (WHO) Adverse Drug Reaction database is also searched. This database, maintained by the Uppsala Monitoring Centre in Sweden, is the largest and most comprehensive adverse drug reaction source in the world, with information obtained from the National Centres of over 70 affiliate countries. Each case report is assessed for seriousness using the FDA MedWatch definition for a serious event.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 2","pages":"119-28"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322020-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24459006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and blood levels of polychlorinated biphenyls.","authors":"Marcello Lotti","doi":"10.2165/00139709-200322040-00003","DOIUrl":"https://doi.org/10.2165/00139709-200322040-00003","url":null,"abstract":"<p><p>Despite the enormous number of reports on polychlorinated biphenyl (PCB) toxicology, both the causal interpretation of epidemiological studies and the risk assessment of human exposures have been hampered by the lack of information on the pharmacokinetics of various PCB isomers and congeners. Thus, the assessment of exposure by means of measuring either total PCBs or individual congeners in the blood has so far been unsatisfactory. For example, the concentration and the pattern of congeners in the blood did not correlate with that at site(s) of action. In fact, the same levels of blood PCBs correlated with either toxic effects or no effects (both in clinical and epidemiological studies). In addition, when toxicity caused by PCBs was observed, the severity of the signs did not correlate with blood levels. Reasons for such a qualified failure are manifold and include different ways of reporting blood measurements, the different toxicological characteristics of each PCB, and different timing of sampling the blood, etc. Therefore, only limited conclusions can be drawn concerning what blood PCB measurements mean.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 4","pages":"203-15"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322040-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24559053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abrin poisoning.","authors":"Kirsten J Dickers,&nbsp;Sally M Bradberry,&nbsp;Paul Rice,&nbsp;Gareth D Griffiths,&nbsp;J Allister Vale","doi":"10.2165/00139709-200322030-00002","DOIUrl":"https://doi.org/10.2165/00139709-200322030-00002","url":null,"abstract":"<p><p>Abrin is a toxic protein obtained from the seeds of Abrus precatorius (jequirity bean), which is similar in structure and properties to ricin. Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 microgram/kg, and has caused death after accidental and intentional poisoning. Abrin can be extracted from jequirity beans using a relatively simple and cheap procedure. This satisfies one criterion of a potential chemical warfare agent, although the lack of large scale production of jequirity seeds means that quantity is unavailable for ready mass production of abrin for weapons. This contrasts with the huge cultivation of Ricinus seeds for castor oil production. At the cellular level, abrin inhibits protein synthesis, thereby causing cell death. Many of the features observed in abrin poisoning can be explained by abrin-induced endothelial cell damage, which causes an increase in capillary permeability with consequent fluid and protein leakage and tissue oedema (the so-called vascular leak syndrome). Most reported cases of human poisoning involve the ingestion of jequirity beans, which predominantly cause gastrointestinal toxicity. Management is symptomatic and supportive. Experimental studies have shown that vaccination with abrin toxoid may offer some protection against a subsequent abrin challenge, although such an approach is unlikely to be of benefit in a civilian population that in all probability would be unprotected.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 3","pages":"137-42"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322030-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human exposure to polychlorinated biphenyls and health effects: a critical synopsis.","authors":"Renate D Kimbrough,&nbsp;Constantine A Krouskas","doi":"10.2165/00139709-200322040-00004","DOIUrl":"https://doi.org/10.2165/00139709-200322040-00004","url":null,"abstract":"<p><p>Polychlorinated biphenyls (PCBs) are a mixture of chemicals. Some congeners of the mixture are highly persistent both in the environment and in humans. Although PCBs have not been used commercially since about 1977 in the US, they can still be detected in human blood and tissues in this country. PCB levels are declining and are often no longer detectable in younger people. A cursory review of recent animal studies is provided. Studies to determine whether PCBs cause cancer in humans, neurobehavioural effects, abnormal thyroid and immune function in children and low birth weight are discussed in more detail. These studies are inconclusive and do not provide clinical evidence that PCBs at levels encountered with human exposure produce adverse health effects. The differences in PCB blood or tissue concentrations between controls and cases, or between the upper and lower end of various environmentally exposed groups of children or adults, are small. Although some effects are statistically significantly different, they do not appear to be biologically significant. Many studies on the effects of PCBs are difficult to interpret because the range of normal values for clinical and neurobehavioural tests are not provided or appropriately considered, there was no, or inadequate, control for potential confounders. In occupational mortality studies, exposures were much higher. In some studies, various specific cancers were elevated. However, these appear to be chance observations resulting from multiple comparisons since the increase of specific cancers was not consistent between studies and was no longer present in some cohorts when studies were repeated at a later date with longer follow-up. Overall, the data fail to demonstrate conclusive adverse health effects of PCBs at concentrations encountered with human exposures.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 4","pages":"217-33"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322040-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24558401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperbaric Oxygen for Carbon Monoxide Poisoning","authors":"N. Buckley, G. Isbister, D. Juurlink","doi":"10.2165/00139709-200524030-00007","DOIUrl":"https://doi.org/10.2165/00139709-200524030-00007","url":null,"abstract":"","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"24 1","pages":"159-160"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200524030-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68154977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}