Toxicological reviews最新文献

{"title":"Pharmaceutical drug overdose case reports. From the World Literature.","authors":"","doi":"10.2165/00139709-200322030-00005","DOIUrl":"https://doi.org/10.2165/00139709-200322030-00005","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 international 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.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 3","pages":"191-7"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322030-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552486","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":"Poisoning with amitraz.","authors":"Alex T Proudfoot","doi":"10.2165/00139709-200322020-00001","DOIUrl":"https://doi.org/10.2165/00139709-200322020-00001","url":null,"abstract":"<p><p>Amitraz, an insecticide and veterinary medicine, has been available in many countries since 1974 but reports of poisoning with it have only become prominent in the last 7 years. The vast majority of cases have occurred in Turkey and have involved children. The data available, both human and animal, do not allow clear separation of the features of toxicity of amitraz from those of the hydrocarbon solvents in which it is commonly dissolved. Amitraz stimulates alpha 2-adrenoceptors resulting in impairment of consciousness, respiratory depression, convulsions, bradycardia, hypotension, hypothermia and hypoglycaemia. Even the most severely poisoned patients recover with nothing more than intensive care; only one possible death has been documented. Animal studies indicate that the alpha 2-adrenoceptor antagonists, yohimbine and atipamezole, can reverse amitraz-induced toxicity but they have not been assessed in poisoned humans.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 2","pages":"71-4"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322020-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24459104","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":"Idiopathic environmental intolerance: Part 1: A causation analysis applying Bradford Hill's criteria to the toxicogenic theory.","authors":"Herman Staudenmayer,&nbsp;Karen E Binkley,&nbsp;Arthur Leznoff,&nbsp;Scott Phillips","doi":"10.2165/00139709-200322040-00005","DOIUrl":"https://doi.org/10.2165/00139709-200322040-00005","url":null,"abstract":"<p><p>Idiopathic environmental intolerance (IEI) is a descriptor for a phenomenon that has many names including environmental illness, multiple chemical sensitivity and chemical intolerance. Toxicogenic and psychogenic theories have been proposed to explain IEI. This paper presents a causality analysis of the toxicogenic theory using Bradford Hill's nine criteria (strength, consistency, specificity, temporality, biological gradient, biological plausibility, coherence, experimental intervention and analogy) and an additional criteria (reversibility) and reviews critically the scientific literature on the topic. The results of this analysis indicate that the toxicogenic theory fails all of these criteria. There is no convincing evidence to support the fundamental postulate that IEI has a toxic aetiology; the hypothesised biological processes and mechanisms are implausible.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 4","pages":"235-46"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322040-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24558402","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":"Is there a causal relationship between exposure to diesel exhaust and multiple myeloma?","authors":"Otto Wong","doi":"10.2165/00139709-200322020-00004","DOIUrl":"https://doi.org/10.2165/00139709-200322020-00004","url":null,"abstract":"<p><p>This article presents a comprehensive critical review of the epidemiology of multiple myeloma in relation to occupational diesel exhaust exposure. The review includes cohort and proportional mortality studies of workers exposed to diesel exhaust, and population-based case-control studies of multiple myeloma. None of the cohort or proportional mortality studies reported a significant increase of multiple myeloma in relation to diesel exhaust, with the exception of a study of Danish truck drivers. Several limitations in this Danish study (such as inadequate cohort identification, small number of multiple myeloma deaths and inappropriate analytical method) made the result unreliable. Furthermore, the data in this study of Danish truck drivers were part of and, hence, superseded by a large study in Denmark, which did not find any increased risk of multiple myeloma. Similarly, none of the case-control studies reported a significant increase of multiple myeloma in relation to diesel exhaust, with the exception of the smallest case-control study based on multiple myeloma patients in central and southeast Sweden. The result of this small Swedish study was not reliable because of incomplete case ascertainment, inappropriate controls and confounding. Furthermore, the data in this small Swedish study were part of and, hence, superseded by a large national study of workers exposed to diesel exhaust in Sweden, which did not find any increased risk of multiple myeloma. Other than the study of Danish truck drivers and the small case-control study of multiple myeloma patients in central and southeast Sweden, all other epidemiological investigations consistently reported no increase of multiple myeloma in relation to occupational diesel exhaust exposure. Furthermore, none of the studies reported a positive exposure-response relationship between diesel exhaust and multiple myeloma. Several studies that analysed data by jobs or occupations according to level of exposure and by duration of exposure did not find any upward trend. In addition to the review, a formal causation analysis based on an application of the Hill criteria confirms that there is no causal relationship between diesel exhaust and multiple myeloma.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 2","pages":"91-102"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322020-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24459003","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":"The role of oximes in the management of organophosphorus pesticide poisoning.","authors":"Peter Eyer","doi":"10.2165/00139709-200322030-00004","DOIUrl":"https://doi.org/10.2165/00139709-200322030-00004","url":null,"abstract":"<p><p>The number of intoxications with organophosphorus pesticides (OPs) is estimated at some 3,000,000 per year, and the number of deaths and casualties some 300,000 per year. OPs act primarily by inhibiting acetylcholinesterase (AChE), thereby allowing acetylcholine to accumulate at cholinergic synapses, disturbing transmission at parasympathetic nerve endings, sympathetic ganglia, neuromuscular endplates and certain CNS regions. Atropine is the mainstay of treatment of effects mediated by muscarine sensitive receptors; however, atropine is ineffective at the nicotine sensitive synapses. At both receptor types, reactivation of inhibited AChE may improve the clinical picture. The value of oximes, however, is still a matter of controversy. Enthusiastic reports of outstanding antidotal effectiveness, substantiated by laboratory findings of reactivated AChE and improved neuromuscular transmission, contrast with many reports of disappointing results. In vitro studies with human erythrocyte AChE, which is derived from the same single gene as synaptic AChE, revealed marked differences in the potency and efficacy of pralidoxime, obidoxime, HI 6 and HLö 7, the latter two oximes being considered particularly effective in nerve agent poisoning. Moreover, remarkable species differences in the susceptibility to oximes were revealed, requiring caution when animal data are extrapolated to humans. These studies impressively demonstrated that any generalisation regarding an effective oxime concentration is inappropriate. Hence, the 4 mg/L concept should be dismissed. To antagonise the toxic effects of the most frequently used OPs, pralidoxime plasma concentrations of around 80 mumol/L (13.8 mg/L pralidoxime chloride) should be attained while obidoxime plasma concentrations of 10 mumol/L (3.6 mg/L obidoxime chloride) may be sufficient. These concentrations should be maintained as long as circulating poison is expected to be present, which may require oxime therapy for up to 10 days. Various dosage regimens exist to reach this goal. The most appropriate consists of a bolus short infusion followed by a maintenance dosage. For pralidoxime chloride, a 1 g bolus over 30 minutes followed by an infusion of 0.5 g/h appears appropriate to maintain the target concentrtion of about 13 mg/L (70 kg person). For obidoxime chloride, the appropriate dosage is a 0.25 g bolus followed by an infusion of 0.75 g/24 h. These concentrations are well tolerated and keep a good portion of AChE in the active state, thereby retarding the AChE aging rate. AChE aging is particularly rapid with dimethyl phosphoryl compounds and may thwart the effective reactivation by oximes, particularly in suicidal poisoning with excessive doses. In contrast, patients with diethyl OP poisoning may particularly benefit from oxime therapy, even if no improvement is seen during the first days when the poison load is high. The low propensity to aging with diethyl OP poisoning may allow reactivation after severa","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 3","pages":"165-90"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322030-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552484","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":"Ricin poisoning.","authors":"Sally M Bradberry,&nbsp;Kirsten J Dickers,&nbsp;Paul Rice,&nbsp;Gareth D Griffiths,&nbsp;J Allister Vale","doi":"10.2165/00139709-200322010-00007","DOIUrl":"https://doi.org/10.2165/00139709-200322010-00007","url":null,"abstract":"<p><p>Ricin is a naturally occurring toxin derived from the beans of the castor oil plant Ricinus communis. It is considered a potential chemical weapon. Ricin binds to cell surface carbohydrates, is internalised then causes cell death by inhibiting protein synthesis. Oral absorption is poor and absorption through intact skin most unlikely; the most hazardous routes of exposure being inhalation and injection. Features of toxicity mainly reflect damage to cells of the reticuloendothelial system, with fluid and protein loss, bleeding, oedema and impaired cellular defence against endogenous toxins. It has been estimated that in man, the lethal dose by inhalation (breathing in solid or liquid particles) and injection (into muscle or vein) is approximately 5-10 micrograms/kg, that is 350-700 micrograms for a 70 kg adult. Death has ensued within hours of deliberate subcutaneous injection. Management is supportive. Prophylactic immunisation against ricin toxicity is a developing research initiative, although presently not a realistic option in a civilian context.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 1","pages":"65-70"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322010-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045351","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":"Biopesticides.","authors":"Daniel L Sudakin","doi":"10.2165/00139709-200322020-00003","DOIUrl":"https://doi.org/10.2165/00139709-200322020-00003","url":null,"abstract":"<p><p>The term 'biopesticide' encompasses a broad array of microbial pesticides, biochemicals derived from micro-organisms and other natural sources, and processes involving the genetic incorporation of DNA into agricultural commodities that confer protection against pest damage (plant-incorporated protectants). Some microbial pesticides, such as Bacillus thuringiensis, have a long history of safe and effective use as a biological insecticide. More recent developments in microbial pest control include the utilisation of other bacterial and fungal species that may competitively inhibit the growth of pathogenic and toxigenic micro-organisms on important agricultural commodities. The use of microbes and their gene products introduces additional considerations to the toxicological dose-response relationship, including a need to determine the plausibility of infectious and immunological effects in association with human exposure to these biopesticides in food or the environment. Studies of substantial equivalence suggest that foods currently derived from plant-incorporated protectants are not likely to differ from conventional foods. However, there is general consensus that the scientific methods to assess risks from genetically modified foods and micro-organisms will continue to evolve in the future.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 2","pages":"83-90"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322020-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24459002","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":"Tear gases and irritant incapacitants. 1-chloroacetophenone, 2-chlorobenzylidene malononitrile and dibenz[b,f]-1,4-oxazepine.","authors":"Peter G Blain","doi":"10.2165/00139709-200322020-00005","DOIUrl":"https://doi.org/10.2165/00139709-200322020-00005","url":null,"abstract":"<p><p>Irritant incapacitants, also called riot control agents, lacrimators and tear gases, are aerosol-dispersed chemicals that produce eye, nose, mouth, skin and respiratory tract irritation. Tear gas is the common name for substances that, in low concentrations, cause pain in the eyes, flow of tears and difficulty in keeping the eyes open. Only three agents are likely to be deployed: (i) 1-chloroacetophenone (CN); (ii) 2-chlorobenzylidene malononitrile (CS); or (iii) dibenz[b,f]-1,4-oxazepine (CR). CN is the most toxic lacrimator and at high concentrations has caused corneal epithelial damage and chemosis. It has accounted for at least five deaths, which have resulted from pulmonary injury and/or asphyxia. CS is a 10-times more potent lacrimator than CN but is less systemically toxic. CR is the most potent lacrimator with the least systemic toxicity and is highly stable. CN, CS and CR cause almost instant pain in the eyes, excessive flow of tears and closure of the eyelids, and incapacitation of exposed individuals. Apart from the effects on the eyes, these agents also cause irritation in the nose and mouth, throat and airways and sometimes to the skin, particularly in moist and warm areas. In situations of massive exposure, tear gas, which is swallowed, may cause vomiting. Serious systemic toxicity is rare and occurs most frequently with CN; it is most likely to occur when these agents are used in very high concentrations within confined non-ventilated spaces. Based on the available toxicological and medical evidence, CS and CR have a large safety margin for life-threatening or irreversible toxic effects. There is no evidence that a healthy individual will experience long-term health effects from open-air exposures to CS or CR, although contamination with CR is less easy to remove.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 2","pages":"103-10"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322020-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24459004","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":"Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue.","authors":"Sally M Bradberry","doi":"10.2165/00139709-200322010-00003","DOIUrl":"https://doi.org/10.2165/00139709-200322010-00003","url":null,"abstract":"<p><p>Methaemoglobin is formed by oxidation of ferrous (FeII) haem to the ferric (FeIII) state and the mechanisms by which this occurs are complex. Most cases are due to one of three processes. Firstly, direct oxidation of ferrohaemoglobin, which involves the transfer of electrons from ferrous haem to the oxidising compound. This mechanism proceeds most readily in the absence of oxygen. Secondly, indirect oxidation, a process of co-oxidation which requires haemoglobin-bound oxygen and is involved, for example, in nitrite-induced methaemoglobinaemia. Thirdly, biotransformation of a chemical to an active intermediate that initiates methaemoglobin formation by a variety of mechanisms. This is the means by which most aromatic compounds, such as amino- and nitro-derivatives of benzene, produce methaemoglobin. Methaemoglobinaemia is an uncommon occupational occurrence. Aromatic compounds are responsible for most cases, their lipophilic nature and volatility facilitating absorption during dermal and inhalational exposure, the principal routes implicated in the workplace. Methaemoglobinaemia presents clinically with symptoms and signs of tissue hypoxia. Concentrations around 80% are life-threatening. Features of toxicity may develop over hours or even days when exposure, whether by inhalation or repeated skin contact, is to relatively low concentrations of inducing chemical(s). Not all features observed in patients with methaemoglobinaemia are due to methaemoglobin formation. For example, the intravascular haemolysis caused by oxidising chemicals such as chlorates poses more risk to life than the methaemoglobinaemia that such chemicals induce. If an occupational history is taken, the diagnosis of methaemoglobinaemia should be relatively straightforward. In addition, two clinical observations may help: firstly, the victim is often less unwell than one would expect from the severity of 'cyanosis' and, secondly, the 'cyanosis' is unresponsive to oxygen therapy. Pulse oximetry is unreliable in the presence of methaemoglobinaemia. Arterial blood gas analysis is mandatory in severe poisoning and reveals normal partial pressures of oxygen (pO2) and carbon dioxide (pCO2,), a normal 'calculated' haemoglobin oxygen saturation, an increased methaemoglobin concentration and possibly a metabolic acidosis. Following decontamination, high-flow oxygen should be given to maximise oxygen carriage by remaining ferrous haem. No controlled trial of the efficacy of methylene blue has been performed but clinical experience suggests that methylene blue can increase the rate of methaemoglobin conversion to haemoglobin some 6-fold. Patients with features and/or methaemoglobin concentrations of 30-50%, should be administered methylene blue 1-2 mg/kg/bodyweight intravenously (the dose depending on the severity of the features), whereas those with methaemoglobin concentrations exceeding 50% should be given methylene blue 2 mg/kg intravenously. Symptomatic improvement usually occurs ","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 1","pages":"13-27"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322010-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045501","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":"Pentachlorophenol poisoning.","authors":"Alex T Proudfoot","doi":"10.2165/00139709-200322010-00002","DOIUrl":"https://doi.org/10.2165/00139709-200322010-00002","url":null,"abstract":"<p><p>Despite being banned in many countries and having its use severely restricted in others, pentachlorophenol (PCP) remains an important pesticide from a toxicological perspective. It is a stable and persistent compound. In humans it is readily absorbed by ingestion and inhalation but is less well absorbed dermally. Its distribution is limited, its metabolism extensive and it is eliminated only slowly. Assessment of the toxicity of PCP is confounded by the presence of contaminants known to cause effects identical to those attributed to PCP. However, severe exposure by any route may result in an acute and occasionally fatal illness that bears all the hallmarks of being mediated by uncoupling of oxidative phosphorylation. Tachycardia, tachypnoea, sweating, altered consciousness, hyperthermia, convulsions and early onset of marked rigor (if death occurs) are the most notable features. Pulmonary oedema, intravascular haemolysis, pancreatitis, jaundice and acute renal failure have been reported. There is no antidote and no adequate data to support the use of repeat-dose oral cholestyramine, forced diuresis or urine alkalinisation as effective methods of enhancing PCP elimination in poisoned humans. Supportive care and vigorous management of hyperthermia should produce a satisfactory outcome. Chronic occupational exposure to PCP may produce a syndrome similar to acute systemic poisoning, together with conjunctivitis and irritation of the upper respiratory and oral mucosae. Long-term exposure has also been reported to result in chronic fatigue or neuropsychiatric features in combination with skin infections (including chloracne), chronic respiratory symptoms, neuralgic pains in the legs, and impaired fertility and hypothyroidism secondary to endocrine disruption. PCP is a weak mutagen but the available data for humans are insufficient to classify it more strongly than as a probable carcinogen.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 1","pages":"3-11"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322010-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045500","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}