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Assumptions about the equal reliability of competing accounts of risk deserve to be examined empirically while the scope for interpretative flexibility when addressing risk issues is clearly extensive. Indicates that the U.K. evaluation was not only less precautionary than its U.S. equivalent but was also less well-constructed and therefore less reliable. (Contains 64 references.) (Author/YDS)

Background and aims: Xylazine is a non‐opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. Methods: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co‐detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug‐testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug‐testing postal service with the date, location, purchase intent and co‐detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. Results: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug‐testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. Conclusions: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies. [ABSTRACT FROM AUTHOR]

The further optimization of consumer safety through risk assessment of chemicals present in food will require adaptability and flexibility to utilize the accelerating developments in safety science and technology. New Approach Methodologies (NAMs) are gaining traction as a systematic approach to support informed decision making in chemical risk assessment. The vision is to be able to predict risk more accurately, rapidly and efficiently. The opportunity exists now to use these approaches which requires a strategy to translate the science into future regulatory implementation. Here we discuss new insights obtained from three recent workshops on how to translate the science into future regulatory implementation. To assist the UK in this endeavor, the Food Standards Agency (FSA) and the scientific advisory committee on chemical toxicity (COT) have been developing a roadmap. In addition, we discuss how these new insights fit into the bigger picture of the new chemical landscape for better consumer safety and the importance of international harmonization. [ABSTRACT FROM AUTHOR]

Background Low-level exposure to carbon monoxide (CO) is a significant health concern but is difficult to diagnose. This main study aim was to establish the prevalence of low-level CO poisoning in Emergency Department (ED) patients. Methods A prospective cross-sectional study of patients with symptoms of CO exposure was conducted in four UK EDs between December 2018 and March 2020. Data on symptoms, a CO screening tool and carboxyhaemoglobin were collected. An investigation of participants' homes was undertaken to identify sources of CO exposure. Results Based on an ED assessment of 4175 participants, the prevalence of suspected CO exposure was 0.62% (95% CI; 0.41–0.91%). CO testing in homes confirmed 1 case of CO presence and 21 probable cases. Normal levels of carboxyhaemoglobin were found in 19 cases of probable exposure and in the confirmed case. Conclusion This study provides evidence that ED patients with symptoms suggestive of CO poisoning but no history of CO exposure are at risk from CO poisoning. The findings suggest components of the CO screening tool may be an indicator of CO exposure over and above elevated COHb. Clinicians should have a high index of suspicion for CO exposure so that this important diagnosis is not missed. [ABSTRACT FROM AUTHOR]

Background We investigated whether military personnel involved in chemical warfare agent research at Porton Down had increased rates of mortality or cancer incidence. Methods This was a historical cohort study comprising male UK veterans who participated in the 'Service Volunteer Programme', 1941–89, identified from Porton Down experiment books, and a comparison group of similar 'non-Porton Down' veterans identified from military personnel files. Of 19 233 records retrieved for each group, 18 133 (94%) Porton Down and 17 591 (92%) non-Porton Down were included in our analytical sample. Mortality and cancer incidence data were obtained from national registries up to December 2019. Results Over a median follow-up of 48.1 years, 10 935 Porton Down veterans (60.3%) and 10 658 non-Porton Down veterans (60.6%) had died. After adjustment for age, year of birth and military service characteristics, overall, Porton Down veterans had a 6% higher rate of all-cause mortality compared with non-Porton Down veterans [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 1.03–1.09]. For cause-specific mortality, Porton Down veterans had higher rates of death from genitourinary diseases (HR = 1.34, 95% CI 1.05–1.70) and deaths attributable to alcohol (HR = 1.44, 95% CI 1.07–1.94), with weaker associations observed for deaths from infectious and parasitic diseases (HR = 1.32, 95% CI 0.99–1.78), lung cancer (HR = 1.10, 95% CI 1.01–1.20) and external causes (HR = 1.15, 95% CI 1.00–1.32). Associations with all-cause mortality were stronger for veterans who attended Porton Down between 1960 and 1964 (HR = 1.34, 95% CI 1.19–1.50); likelihood-ratio test, P  = 0.006. There was no association between attendance at Porton Down and overall cancer incidence (HR = 1.00, 95% CI 0.95–1.03). Conclusions Overall, mortality rates were slightly higher in Porton Down veterans, but there was no difference in cancer incidence. Associations for mortality were stronger in Porton Down veterans who attended in the early 1960s. [ABSTRACT FROM AUTHOR]

Few methods are available for transparently combining different evidence streams for chemical risk assessment to reach an integrated conclusion on the probability of causation. Hence, the UK Committees on Toxicity (COT) and on Carcinogenicity (COC) have reviewed current practice and developed guidance on how to achieve this in a transparent manner, using graphical visualisation. All lines of evidence, including toxicological, epidemiological, new approach methodologies, and mode of action should be considered, taking account of their strengths/weaknesses in their relative weighting towards a conclusion on the probability of causation. A qualitative estimate of the probability of causation is plotted for each line of evidence and a combined estimate provided. Guidance is provided on integration of multiple lines of evidence for causation, based on current best practice. Qualitative estimates of probability for each line of evidence are plotted graphically. This ensures a deliberative, consensus conclusion on likelihood of causation is reached. It also ensures clear communication of the influence of the different lines of evidence on the overall conclusion on causality. Issues on which advice from the respective Committees is sought varies considerably, hence the guidance is designed to be sufficiently flexible to meet this need. [Display omitted] • Approach to improve the consistency, transparency and communication of current practice of scientific advisory committees. • Emphasis is on weight of evidence and integration of different evidence streams, where all evidence is considered. • Visualisation tool is proposed, to help communicate the overall conclusion and contribution of different lines of evidence. • The conclusion on causality and its graphical representation is qualitative, and based on expert judgement. • Collaboration and ongoing dialogue between the different disciplines in risk assessment are strongly advised. [ABSTRACT FROM AUTHOR]

It has been suggested that knowledge domains which emerge within regulatory science represent a compromise between technical knowledge and policy priorities. This article investigates the claim through consideration of the emergence of animal tests to evaluate chemical safety in the UK between 1945 and 1960. During this period there was a proliferation of new chemical-based innovations in consumer products. The situation gave rise to concerns about the potential impact on public health. Solutions required development of a knowledge domain that would fulfil policy requirements, outside the remit of academic science. Lack of consensus in the scientific field gave rise to debate over the best means to collect accurate data. This resulted in emergence of the new specialty of safety testing, in response to political and industrial needs. The socio-political context of this case illustrates the impact that organisational setting can have on shaping knowledge claims. • Toxicology emerged as a regulatory science. • Debates between biological scientists influenced biochemical testing regimes for policy. • Non-academic sciences have distinct knowledge characteristics. [ABSTRACT FROM AUTHOR]

Background and Aims: Between March 2019 and February 2020 there was an outbreak of acute lung injury associated with vaping tetrahydrocannabinol (THC), contaminated with vitamin E acetate, in the United States. To date, there has been no comprehensive study of drug‐related deaths associated with vaping products in the United Kingdom. We aimed to identify any trends in drug‐related deaths associated with vaping product use in the United Kingdom. Methods: We retrospectively identified any deaths associated with the use of vaping products reported to the UK National Programme on Substance Abuse Deaths (NPSAD). This contains voluntarily reported information from UK Coroners on more than 42 000 deaths related to psychoactive drugs, other than nicotine or caffeine, which occurred between 1997 and 2020. Results: Two drug‐related deaths were reported which were associated with vaping products, one person having died in 2017 and one in 2018. Both decedents were men currently serving prison sentences in England and were aged 26 and 42 years at the time of death. Both deaths were associated with recent use of Synthetic Cannabinoid Receptor Agonists (SCRAs), with no other substances found to be implicated in death. No details regarding the type of vaping products were available. Conclusions: In a UK sample (1997 to 2020) of 42 000 deaths related to psychoactive drugs other than nicotine or caffeine, only two deaths were associated with vaping products, and those involved use of synthetic cannabinoid receptor agonists. [ABSTRACT FROM AUTHOR]

The Royal College of Emergency Medicine Toxicology Special Interest Group in collaboration with the UK National Poisons Information Service and the Clinical Toxicology Department at Guy's and St Thomas' NHS Foundation Trust has produced guidance to support clinicians working in the ED with the assessment and management of adults with acute opioid toxicity.Considerations regarding identification of acute opioid toxicity are discussed and recommendations regarding treatment options and secondary prevention are made. There is a focus on making recommendations on the best available evidence., Competing Interests: Competing interests: MB—unpaid member of RCEM Toxicology Advisory Group. RG has no declarations of interest. DMW is a member of the UK Advisory Council on the Misuse of Drugs and an expert advisor to the European Monitoring Centre for Drugs and Drug Addiction and the United Nations Office on Drugs and Crime. He is also a clinical coordinator at the UK National Confidential Enquiry into Patient Outcomes and Death (NCEPOD), and on the editorial board of the Journal of Medical Toxicology. His work on these guidelines was independent of his roles with these organisations. RT—his work on these guidelines was in his role as director of NPIS (Newcastle). CH is an editor for the Emergency Medicine Journal, has received payments from Elsevier for educational articles, has been reimbursed for travel expenses by RCEM and is a recipient of grants from the Centre for Precision Cell Therapy for the Liver. His work on these guidelines was in his role as a member of the RCEM Toxicology Special Interest Group. PID is an adviser to the UK Advisory Council on the Misuse of Drugs, the European Monitoring Centre for Drugs and Drug Addiction the United Nations Office on Drugs and Crime, and the WHO. He is also a commissioner to the UK Commission Human Medicines, on the senior editorial board of Clinical Toxicology, and is the president elect of the European Association of Poisons Control Centres and Clinical Toxicologists. His work on these guidelines was independent of his roles with these organisations., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Children are at higher risk of medication errors due to the complexity of drug prescribing and administration in this patient group. Intravenous (IV) paracetamol overdose differs from overdose by ingestion as there is no enteral absorptive buffering. We provide the first national UK data focusing on paediatric IV paracetamol poisoning., Methods: All telephone enquiries to the National Poisons Information Service between 2008 and 2021 regarding children less than 18 years old in the UK concerning IV paracetamol overdose were extracted from the UK Poisons Information Database (UKPID). Data were analysed using descriptive statistics., Results: Enquiries were made concerning 266 children, mostly involving children under the age of 1 year (n=145; 54.5%). Acute and staggered overdoses were the most frequent types of exposure. Common error themes included 10-fold overdose in 45 cases (16.9%) and inadvertent concomitant oral and IV dosing in 64 cases (24.1%). A high proportion of cases were asymptomatic (87.1%), with many calls regarding overdoses below the treatable dose of 60 mg/kg (41.4%). Treatment with the antidote acetylcysteine was advised in 113 cases (42.5%)., Conclusions: Inadvertent IV paracetamol overdose appears to occur more frequently in young children. A significant proportion were calculation errors which were often 10-fold errors. While these errors have the potential for causing serious harm, thankfully most cases were asymptomatic. Errors with IV paracetamol might be reduced by electronic prescribing support systems, better communication regarding administration and consideration of whether other routes are more appropriate., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Lead exposure from discharged lead dust is a recognised risk at firing ranges. We report a lead poisoning outbreak among staff and their close contacts at a UK civilian indoor 24 m firing range., Methods: A retrospective review was undertaken of data collected on all patients at risk of lead poisoning identified either by direct referral to the Clinical Toxicology clinicians at the West Midlands Poisons Unit, or via the Trace Elements Supra-Regional Assay Service Laboratory at Sandwell hospital., Results: Eighty-seven patients were identified as having possible lead exposure, either at the firing range or via close contacts. Of these, 63 patients aged between 6 months and 78 years attended for blood lead concentration (BLC) testing. The highest BLC at presentation was 11.7 µmol/L (242 µg/dL). Only nine patients reported any symptoms at presentation. Fifteen patients received lead chelation therapy with oral dimercaptosuccinic acid (or succimer) 30 mg/kg/day or intravenous sodium calcium edetate (EDTA) 75 mg/kg/day, dependent on stock availability., Discussion: This report highlights the need for vigilance of lead poisoning as an occupational hazard in the UK, including at recreational facilities such as indoor firing ranges. It emphasises the importance of regulation of lead exposure in the workplace, particularly given the vague symptoms of lead poisoning, and proposes re-appraisal of UK legislation. This report also highlights potential issues surrounding stock availability of rarely used antidotes for uncommon presentations in the event of an outbreak of poisoning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Specific Escherichia coli isolates lysogenised with prophages that express Shiga toxin (Stx) can be a threat to human health, with cattle being an important natural reservoir. In many countries the most severe pathology is associated with enterohaemorrhagic E. coli (EHEC) serogroups that express Stx subtype 2a. In the United Kingdom, phage type (PT) 21/28 O157 strains have emerged as the predominant cause of life-threatening EHEC infections and this phage type commonly encodes both Stx2a and Stx2c toxin types. PT21/28 is also epidemiologically linked to super-shedding (>103 cfu/g of faeces) which is significant for inter-animal transmission and human infection as demonstrated using modelling studies. We demonstrate that Stx2a is the main toxin produced by stx2a+/stx2c+ PT21/28 strains induced with mitomycin C and this is associated with more rapid induction of gene expression from the Stx2a-encoding prophage compared to that from the Stx2c-encoding prophage. Bacterial supernatants containing either Stx2a and/or Stx2c were demonstrated to restrict growth of bovine gastrointestinal organoids with no restriction when toxin production was not induced or prevented by mutation. Isogenic strains that differed in their capacity to produce Stx2a were selected for experimental oral colonisation of calves to assess the significance of Stx2a for both super-shedding and transmission between animals. Restoration of Stx2a expression in a PT21/28 background significantly increased animal-to-animal transmission and the number of sentinel animals that became super-shedders. We propose that while both Stx2a and Stx2c can restrict regeneration of the epithelium, it is the relatively rapid and higher levels of Stx2a induction, compared to Stx2c, that have contributed to the successful emergence of Stx2a+ E. coli isolates in cattle in the last 40 years. We propose a model in which Stx2a enhances E. coli O157 colonisation of in-contact animals by restricting regeneration and turnover of the colonised gastrointestinal epithelium. [ABSTRACT FROM AUTHOR]

Background: Acute behavioural disturbance (ABD) is a term used in law enforcement and healthcare, but there is a lack of clarity regarding its meaning. Common language should be used across staff groups to support the identification, prioritisation and delivery of care to this group of patients. The terminology currently used is inconsistent and confusing. This study aimed to reach a consensus on the criteria for identification and management of ABD, and to agree when other care pathways or guidelines might be more appropriately used., Methods: A modified Delphi study with participation from stakeholder organisation representatives was conducted in January-April 2023 online. In round 1, statements were generated by participants in response to broad questions. Participants then rated their level of agreement with statements in subsequent rounds, with statements achieving a consensus removed for inclusion in the final derived consensus statement. Non-consensus statement responses were assessed for stability., Results: Of 430 unique statements presented for rating, 266 achieved a consensus among 30 participants representing eight stakeholder organisations. A derived consensus statement was generated from these statements. The median group response to statements which failed to achieve a consensus was reliable (Krippendorff's alpha=0·67)., Conclusions: There is a consensus across stakeholder organisations that ABD is not a separate entity to agitation, and guidance should instead be altered to address the full range of presentations of agitation. While the features of concern in this severely agitated group of patients can be described, the advice for recognition may vary depending on staff group. Criteria for recognition are provided and potential new terminology is described., Competing Interests: Competing interests: CH—access to University of Edinburgh Read & Publish agreement, reimbursed for travel expenses to speak at conferences for Royal College of Emergency Medicine (RCEM), unpaid member of RCEM Toxicology advisory group, lead author of RCEM guidelines on ABD, cannabinoid hyperemesis syndrome and nitrous oxide toxicity. AW—acted as expert witness in one coroner’s inquest related to ABD in 2021, chair of UK EMS Clinical Practice Guidelines Committee, lead of committee for UK ABD guidelines for paramedic practice, chair of RCEM ABD guidelines committee, reimbursed for travel expenses to speak at 2023 RCEM conference. AK, AS and JS—none., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Kratom (Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events.Aims: This study details the characteristics of such fatalities and provides a 'state-of-the-art' review.Methods: UK cases were identified from mortality registers by searching with the terms 'kratom', 'mitragynine', etc. Databases and online media were searched using these terms and 'death', 'fatal*', 'overdose', 'poisoning', etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis.Results: Typical case characteristics (n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues.Conclusions: These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom's safety profile remains only partially understood; toxic and fatal levels require quantification. [ABSTRACT FROM AUTHOR]

As part of the safety assessment of new drugs, the use of two species (a rodent and a nonrodent) for regulatory toxicology studies is the typical approach taken for small molecules. For biologics, species selection is dictated by pharmacological relevance, and single species toxicology packages (typically using the nonhuman primate) are common. The UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research and the Association of the British Pharmaceutical Industry are collaborating on a project to review the utility of two species in regulatory toxicology studies, with the aim to explore whether there are wider circumstances when data from a single species could be sufficient to enable safe progression in humans. An international working group consisting of 37 representatives from pharmaceutical and biotechnology companies, contract research organizations, academia, and regulatory bodies is coordinating a large-scale data sharing exercise to examine the potential for changes in current practice to reduce the number of species used for nonclinical safety testing at different stages of development. The challenge will be to determine whether two species toxicology adds significant value or whether in some instances data from a single species are sufficient (across a broader range of molecules than is currently the case) without compromising human safety. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: CH is an emergency medicine representative on the Department of Health and Social Care Drug Harms Assessment and Response Team and a member of the RCEM Toxicology Special Interest Group. Both roles are unpaid, and neither group had a role in the authoring of this article.

The article reports on the findings of the investigation conducted by the Royal College of Physicians on the role of e-cigarettes in tobacco harm reduction. Topics discussed include e-cigarettes' provision of a viable alternative to tobacco smoking and recognition for the hazards posed by the electronic device. The close monitoring of the patterns of use and health impacts of electronic and tobacco cigarettes and the communication of both the risks and benefits of usage are mentioned.

Four commercial rapid screening methods for Diarrhetic Shellfish Poisoning were applied to the analysis of naturally contaminated shellfish samples from GB. The performance of each kit was assessed through comparison with the reference LC-MS/MS method on a range of both positive and negative bivalve mollusc samples. A quantitative PP2A protein phosphatase assay was the only assay to show the complete absence of false negative results. It showed a fair correlation with LC-MS/MS but with an overall overestimation of sample toxicity together with some indications of interference from sample matrix, most notably within oyster species. A quantitative competitive ELISA also gave a fair correlation with LC-MS/MS, with no evidence of toxicity overestimation and with a good response to samples containing little or no DST's, although one false negative was recorded. The two qualitative lateral flow assays both provided a high percentage agreement with the LC-MS/MS results and there were no indications of false positive results, although both kits also returned one false negative result. The false negative results returned by the three assays were all associated with samples containing high proportions of DTX2, a toxin which occurs commonly in UK shellfish. The scanners provided with both lateral flow assays were easy to use and the provision of numerical results enables a semi-quantitative assessment of toxicities which would significantly benefit the end user. Whilst key differences exist between the proposed assays they are all rapid, do not require expensive equipment and the work here has provided some evidence for suitability for indicative testing for some species of bivalve shellfish from GB. Further work is required however using a larger number of test kit batches on a greater number of samples, particularly for those containing high proportions of DTX2. [ABSTRACT FROM AUTHOR]

Background: European Union law prohibits companies from marketing drugs off-label. In the United Kingdom--as in some other European countries, but unlike the United States--industry self-regulatory bodies are tasked with supervising compliance with marketing rules. The objectives of this study were to (1) characterize off-label promotion rulings in the UK compared to the whistleblower-initiated cases in the US and (2) shed light on the UK self-regulatory mechanism for detecting, deterring, and sanctioning off-label promotion.Methods and Findings: We conducted structured reviews of rulings by the UK self-regulatory authority, the Prescription Medicines Code of Practice Authority (PMCPA), between 2003 and 2012. There were 74 off-label promotion rulings involving 43 companies and 65 drugs. Nineteen companies were ruled in breach more than once, and ten companies were ruled in breach three or more times over the 10-y period. Drawing on a typology previously developed to analyse US whistleblower complaints, we coded and analysed the apparent strategic goals of each off-label marketing scheme and the practices consistent with those alleged goals. 50% of rulings cited efforts to expand drug use to unapproved indications, and 39% and 38% cited efforts to expand beyond approved disease entities and dosing strategies, respectively. The most frequently described promotional tactic was attempts to influence prescribers (n = 72, 97%), using print material (70/72, 97%), for example, advertisements (21/70, 30%). Although rulings cited prescribers as the prime target of off-label promotion, competing companies lodged the majority of complaints (prescriber: n = 16, 22%, versus companies: n = 42, 57%). Unlike US whistleblower complaints, few UK rulings described practices targeting consumers (n = 3, 4%), payers (n = 2, 3%), or company staff (n = 2, 3%). Eight UK rulings (11%) pertaining to six drugs described promotion of the same drug for the same off-label use as was alleged by whistleblowers in the US. However, while the UK cases typically related to only one or a few claims made in printed material, several complaints in the US alleged multifaceted and covert marketing activities. Because this study is limited to PMCPA rulings and whistleblower-initiated federal cases, it may offer a partial view of exposed off-label marketing.Conclusion: The UK self-regulatory system for exposing marketing violations relies largely on complaints from company outsiders, which may explain why most off-label promotion rulings relate to plainly visible promotional activities such as advertising. This contrasts with the US, where Department of Justice investigations and whistleblower testimony have alleged complex off-label marketing campaigns that remain concealed to company outsiders. UK authorities should consider introducing increased incentives and protections for whistleblowers combined with US-style governmental investigations and meaningful sanctions. UK prescribers should be attentive to, and increasingly report, off-label promotion. [ABSTRACT FROM AUTHOR]

The article discusses the surveillance report of the Animal and Plant Health Agency (APHA) on various diseases in Great Britain. These include the toxicity of Vitamin D in sows, Campylobacter infection in a lamb and Salmonella Dublin spinal osteomyelitis in calves. It also notes the case of Klebsiella pneumoniae septicaemia among weaned pigs.

Aim: To provide an up-to-date assessment of the demographics, patient characteristics and substances involved in deliberate self-poisoning (DSP) presentations to a UK emergency department (ED). Method: A retrospective observational study was undertaken at Ealing Hospital ED between 1st August 2011 and 31st July 2012. Scanned ED records were reviewed to collect data from potential DSP presentations. Results: 368 DSP presentations were identified, accounting for 0.9% of total ED attendances. The mean age was 34.2 years and the female : male ratio 1.85 : 1. All 12 patients under 16 years were female. 561 substances were used in total. Paracetamol was the most frequently used substance, taken by 150 (40.8%) patients (with the addition of compound analgesics). The next most frequent substances were NSAIDs (16.8% of patients), hypnotics and anxiolytics (15.2%), SSRIs (13.9%), compound analgesics (8.7%) and atypical antipsychotics (8.4%). 533 (95.0%) of the substances were medications listed in the BNF. Household cleaning products were the most common of five other groups. Specific treatments were administered to 77 (20.9%) patients. 122 (33.2%) patients required specialty admission. Conclusion: DSP remains a common ED presentation and presents the challenge of managing both medical complications and psychiatric risks. Observational studies on DSP are an important source of information on trends in demographics and substances; this can inform future prevention strategies. A detailed assessment of DSP presentations is provided in this study. A national surveillance system or study is recommended to improve knowledge and a consensus on classification of substances would aid comparisons between studies. [ABSTRACT FROM AUTHOR]

In accordance with Article 6 of Regulation (EC) No 396/2005, the United Kingdom (hereafter - evaluating Member State UK (EMS UK)), received an application from the company BASF to modify the existing MRLs for chlormequat in cereals and several commodities of animal origin. The EMS UK proposed to raise MRLs in rye and oat grain and several animal commodities to accommodate the NEU use of chlormequat on cereals. The Netherlands (EMS NL) received an application from Nederlandse Fruittelers Organisatie to maintain the temporary MRL of 0.1 mg/kg for chlormequat in pears until 31 July 2017, in order to accommodate for carry-over of chlormequat residues due to formerly authorized uses on pear trees. The targeted monitoring data provide evidence that, in general, chlormequat residues in pears produced in the Netherlands and Belgium are declining. In 2013 and onwards, 95 % of the samples of pears produced in the Netherlands and Belgium in areas where chlormequat was used in pear orchards before 2003 will contain residues at or below the level of 0.1 mg/kg. The submitted residue trials on cereals indicate that a higher MRL is required for oat and rye grain to support the intended NEU use. The new use on cereals results in a need to raise the existing MRLs for chlormequat in ruminant muscle, liver, kidney, swine kidney and milk. Based on the risk assessment results, EFSA concludes that the temporary MRL for pears and the intended use of chlormequat on rye and oats and the subsequent residues in animal commodities will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a public health concern. [ABSTRACT FROM AUTHOR]

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. [ABSTRACT FROM AUTHOR]

Abstract: There has been a significant increase during the last decade in the UK of the incidence of the Lyme disease. It is transmitted through tick bites, and can have serious health consequences if not treated early. This study examined how the responsibility for managing and communicating the health risks from Lyme disease to forest workers and recreational visitors was constructed and acted upon by 21 interviewees in key managerial positions within one of the largest UK forestry organisations. The in-depth, semi-structured interviews were analysed using discourse analysis within a Foucauldian framework. The results demonstrated that the construction of responsibility towards the workforce and visitors was embedded into broader representations of the forest as a working, recreational and natural environment, as well as into the binary conceptualisation of forest hazards as natural and human-made. These constructions prescribed respective subject positions which differentially informed assumptions of responsibility, and consequent actions, towards the workforce and the public. [Copyright &y& Elsevier]

Objective Phenazepam (fenazepam; 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2 H-1,4-benzodiazepin-2-one; PNZ, 'Bonsai') is a benzodiazepine developed in the former Soviet Union during the 1970s to treat neurological disorders, epilepsy, and alcohol withdrawal syndrome. Its recreational use appears to have increased over recent years. Because of the lack of accessible data on this substance, it is important that information is made available to health professionals. Methods A literature search was conducted in relevant databases (Medline, Toxbase, PsychInfo, etc.), grey literature (using Google Scholar) and Internet sites to identify key data on phenazepam, including epidemiology such as availability, price, supply sources, confiscations, and health-related problems. Results Information from these sources indicates the potential for serious adverse health consequences for this drug when taken recreationally and that its use is spreading in the USA and Europe. Although first use was reported in the UK in October 2009, major concerns in the UK arose in summer 2010 when individuals across Britain were admitted to hospital following overdose. Nine UK fatalities were reported in which phenazepam was detected in post mortem toxicology but not implicated in death. The first UK death directly involving phenazepam was notified in July and the second in November 2011. Conclusions This paper summarises the key information about phenazepam abuse and health problems of which health professionals, especially those in Emergency Departments, should be aware and presents new information in respect of fatalities caused by the drug. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A thorough analysis of a case that involves a medication that may have caused or contributed to an adverse outcome, or a comparison of two compounds in a patent dispute, requires consideration of many processes that affect the clinical effects of a medication. These include its chemical structure, its pharmacological actions (pharmacodynamics), the pharmaceutical formulation, and its absorption, distribution, metabolism, and excretion (pharmacokinetics). They also include analysis of clinical details, including the diagnosis, the quality of the prescribing decisions, the accuracy of the prescription, dispensing, and administration of medications, and how appropriately the case was managed, including monitoring. A causality assessment should be attempted for both the general case and the particular case. Knowledge of the systems that describe a medication's mechanisms of action (EIDOS) and the dose-relationships and time-courses of adverse outcomes and individual susceptibilities to them (DoTS) can inform several aspects of the analysis. Reports should be written in clear English and should not contain statements that rely on expertise that the expert does not possess. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims To assess the patterns of use, subjective effect profile and dependence liability of mephedrone, supported by corroborative urine toxicology. Design Cross-sectional structured telephone interview. Setting UK-based drug users associated with the dance music scene. Participants A total of 100 mephedrone users, recruited through their involvement with the dance music scene. Measurements Assessment of pattern of use, acute and after effects, DSM dependence criteria and gas chromatography-mass spectrometry urinalysis. Findings Mephedrone consumption results in typical stimulant-related subjective effects: euphoria, increased concentration, talkativeness, urge to move, empathy, jaw clenching, reduced appetite and insomnia. Thirty per cent of the sample potentially met criteria for DSM-IV dependence and there was evidence of a strong compulsion to use the drug (47% had used the drug for 2 or more consecutive days). Self-reported recent consumption of mephedrone was confirmed by toxicological analysis in all of the 14 participants who submitted a urine sample. Conclusion Mephedrone has a high abuse and health risk liability, with increased tolerance, impaired control and a compulsion to use, the predominant reported dependence symptoms. [ABSTRACT FROM AUTHOR]

BACKGROUND: The global public health community has closely monitored the unfolding of the 2009 H1N1 influenza pandemic to best mitigate its impact on society. However, little attention has been given to the impact of this response on the environment. Antivirals and antibiotics prescribed to treat influenza are excreted into wastewater in a biologically active form, which presents a new and potentially significant ecotoxicologic challenge to microorganisms responsible for wastewater nutrient removal in wastewater treatment plants (WWTPs) and receiving rivers. OBJECTIVES: We assessed the ecotoxicologic risks of a pandemic influenza medical response. METHODS: To evaluate this risk, we coupled a global spatially structured epidemic model that simulates the quantities of antivirals and antibiotics used during an influenza pandemic of varying severity and a water quality model applied to the Thames catchment to determine predicted environmental concentrations. An additional model was then used to assess the effects of antibiotics on microorganisms in WWTPs and rivers. RESULTS: Consistent with expectations, our model projected a mild pandemic to exhibit a negligible ecotoxicologic hazard. In a moderate and severe pandemic, we projected WWTP toxicity to vary between 0-14% and 5-32% potentially affected fraction (PAF), respectively, and river toxicity to vary between 0-14% and 0-30% PAF, respectively, where PAF is the fraction of microbial species predicted to be growth inhibited (lower and upper 95% reference range). CONCLUSIONS: The current medical response to pandemic influenza might result in the discharge of insufficiently treated wastewater into receiving rivers, thereby increasing the risk of eutrophication and contamination of drinking water abstraction points. Widespread drugs in the environment could hasten the generation of drug resistance. Our results highlight the need for empirical data on the effects of antibiotics and antiviral medications on WWTPs and freshwater ecotoxicity. [ABSTRACT FROM AUTHOR]

The article offers information on the theory and practice of the traditional Chinese herbal (CHM) medicine. It explores the history of CHM, the five flavors and four energies of Chinese herbs, and the classic or modern herbal formula. It elaborates the different ways of decoction for the CHM formula, the levels of herb toxicity, and the practice of CHM in Great Britain.

There are substantial differences between the information required in a diagnostic histopathology report and an experimental pathology report. A diagnostic report rests on the authority of the person issuing it, so there is less emphasis on the data and analysis on which the diagnosis is based being in the report. By contrast, an experimental report gains its authority from the integrity of the data and the objective analysis of that data. It is recommended that the current diagnostic reporting of the histopathology component of toxicological studies be changed to a more experimental report approach. [ABSTRACT FROM PUBLISHER]

Fatalities in infants resulting from methadone toxicity are rare within the United Kingdom. We report two cases of fatality attributed to methadone toxicity in infants aged 3½ and 15 months of age, respectively. One of the two cases was also associated with diazepam ingestion. We discuss the difficulties with the interpretation of paediatric forensic toxicology and review the current literature related to methadone and diazepam toxicity in infants and older children. [ABSTRACT FROM AUTHOR]

Background. The National Poisons Information Service and the Association of Clinical Biochemists in the United Kingdom published guidelines on laboratory analyses for poisoned patients in 2002. In 2003, U.S. guidelines were prepared by an expert panel of analytical toxicologists and emergency department (ED) physicians. Some professional associations in different countries quote these guidelines but there are no data to support adherence to these recommendations in the medical literature. Objective. To analyze the availability of 15 quantitative laboratory analyses, specifically relating to the management of the poisoned patient, in Ireland. Methods. A questionnaire relating to the provision of toxicological analyses was compiled and distributed to 39 acute care hospital laboratories in Ireland. The availability of 15 quantitative analyses (carbamazepine, carboxyhemoglobin, digoxin, ethanol, ethylene glycol, iron, lithium, methemoglobin, methanol, paracetamol, paraquat, phenobarbital, salicylate, theophylline, and valproic acid), specifically relating to the management of the poisoned patient, was analyzed. The reporting units for these analyses were also collected. The acute care hospitals were sorted into groups according to their number of ED attendances: A) <20,000, B) 20,000–30,000, C) 30,000–40,000, D) 40,000–50,000, and E) >50,000 based on ED activity data for 2008. The median number of assays provided by each hospital group was calculated. Results. The response rate was 100%, allowing complete national data to be ascertained. Hospital laboratories provided a more comprehensive testing service when ED attendances exceeded 30,000 per annum. Sixteen hospital laboratories (41.0%) performed at least 10 of the 15 toxicological investigations. The most widely available assay was paracetamol (74.4%, n = 29) and the least widely available assays were methanol, ethylene glycol, and paraquat (2.6%, n = 1). Only one hospital laboratory provided all 15 analyses. Hospital laboratories in groups A and B carried out a median number of 3/15 assays (range 0–8) and 4/15 assays (range 0–10), respectively. Hospital laboratories where ED attendances exceeded 30,000 per annum carried out a median number of 11/15 toxicological assays (range 1–15). There was a lack of consistency in the reporting units with both molar and mass units used. Conclusion. There is wide availability of toxicological analyses among hospital laboratories in Ireland. Most analyses were provided with 24-h availability. Hospitals with ED attendances in excess of 30,000 provided a more comprehensive laboratory service with respect to the number of analyses performed. The lack of consistency with units used by Irish hospital laboratories could present challenges with the reporting and interpretation of quantitative results. This study could be carried out in other countries to establish what analyses are available for the treatment of poisoned patients. [ABSTRACT FROM AUTHOR]

Abstract: Toxicological assessment of pharmaceutical and non-pharmaceutical chemicals is a regulatory requirement to ensure all compounds likely to be exposed to humans or the environment are safe. These studies rely on the use of large numbers of animals and involve a number of assumptions and extrapolations that remain controversial in assuring consumer safety. The UK''s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has taken a collaborative approach to identify opportunities for implementation of the 3Rs principles (Replacement, Reduction and Refinement) to drive innovation and support animal welfare in toxicity testing. This review highlights the mechanisms by which the NC3Rs is working with the pharmaceutical and chemical industries and regulatory authorities to achieve these goals. [Copyright &y& Elsevier]

The article discusses subspecialisation in emergency medicine (EM), Topics discussed include EM in the Great Britain represented by the Royal College of Emergency Medicine (RCEM) authorises training programmes for EM trainees and awards the certificate of completion of training (CCT), paediatric EM in the country and emergency medicine subspecialisation in the U.S, along with lessons that can be leaned by Australia.

Simple Summary: Before any new medicine can be administered to humans, or new chemical marketed, some tests using animals such as fish, mice, rats, rabbits, dogs, or monkeys are performed in order to satisfy the legal requirements of international regulatory and government agencies. These assess the potential for harmful side effects in humans or species found in the environment and to explore how the compound is processed within the body. The housing conditions and procedures performed (such as dosing of compounds and removal of small blood samples) are designed to minimize any pain, suffering, distress, or lasting harm that may be experienced by the animals. These refinements improve animal welfare but can also improve the data quality. Examples of new processes, technologies, or equipment that have been introduced within some UK facilities are shared in this article and provide opportunities to benefit many more animals undergoing testing across the world in the future. During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction with metabolism and toxicity studies using animals. The required studies are outlined within international regulatory guidelines which acknowledge and support the application of the 3Rs to reduce the number of animals used or to refine the procedures performed when these studies are deemed to be necessary. The continued development of new technologies and adoption of best-practice approaches to laboratory animal housing and study procedures has generated a series of refinements that can be incorporated into animal studies throughout the package. These refinements benefit the welfare of fish, mice, rats, rabbits, dogs, minipigs, and non-human primates (NHPs) whilst maintaining or improving data quality within general toxicology, metabolism, and other studies and can also bring efficiencies to processes that benefit study costs and timings. Examples are shared which cover the following topics: social housing of dogs and NHPs, surgical refinements in the rat bile duct cannulation model for collection of data for metabolism studies, whether fasting is really required prior to clinical pathology sampling, and the use of microsampling for toxicokinetics. [ABSTRACT FROM AUTHOR]

Because many occupational epidemiologic studies use exposure surrogates rather than quantitative exposure metrics, the UMass Lowell and Yale study of autobody shop workers provided an opportunity to evaluate the relative utility of surrogates and quantitative exposure metrics in an exposure response analysis of cross-week change in respiratory function. A task-based exposure assessment was used to develop several metrics of inhalation exposure to isocyanates. The metrics included the surrogates, job title, counts of spray painting events during the day, counts of spray and bystander exposure events, and a quantitative exposure metric that incorporated exposure determinant models based on task sampling and a personal workplace protection factor for respirator use, combined with a daily task checklist. The result of the quantitative exposure algorithm was an estimate of the daily time-weighted average respirator-corrected total NCO exposure (μ g/m3). In general, these four metrics were found to be variable in agreement using measures such as weighted kappa and Spearman correlation. A logistic model for 10% drop in FEV1 from Monday morning to Thursday morning was used to evaluate the utility of each exposure metric. The quantitative exposure metric was the most favorable, producing the best model fit, as well as the greatest strength and magnitude of association. This finding supports the reports of others that reducing exposure misclassification can improve risk estimates that otherwise would be biased toward the null. Although detailed and quantitative exposure assessment can be more time consuming and costly, it can improve exposure-disease evaluations and is more useful for risk assessment purposes. The task-based exposure modeling method successfully produced estimates of daily time-weighted average exposures in the complex and changing autobody shop work environment. The ambient TWA exposures of all of the office workers and technicians and 57% of the painters were found to be below the current U.K. Health and Safety Executive occupational exposure limit (OEL) for total NCO of 20 μ g/m3. When respirator use was incorporated, all personal daily exposures were below the U.K. OEL. [ABSTRACT FROM AUTHOR]

Abstract: While there are a few national schemes for accreditation/certification of toxicologic pathologists (e.g. in Japan and UK), a global recognition system for bench toxicologic pathologists is missing, as are universal standards defining their core competencies. This paper summarizes the basic means, how proficiency in toxicologic pathology is acquired, provides an overview over examinations of interest to toxicologic pathologists and emphasizes the value of practical experience in the field. The paper then discusses basic approaches to evaluate the proficiency of toxicologic pathologists and examines potential means to recognize qualified toxicologic pathologists. With progressive globalization it is important that the toxicologic pathology community intensifies the discussion regarding a global recognition of their discipline and seeks to agree on the way forward. [Copyright &y& Elsevier]

The development of reference materials for toxicology and metrology is a critical component in establishing testing strategies and methods for human health hazard assessment of nanoparticles. A UK-based project (REFNANO) employed a workshop-based process to identify a priority list of candidate reference materials to support the measurement, toxicology and risk assessment of engineered nanoparticles. Consensus was reached amongst leading UK experts in toxicology, metrology and risk assessment from academia, government and industry on: (i) A rationale for the selection and development of priority reference/test materials; (ii) a priority listing of reference/test materials; (iii) the quantities of materials needed and the matrix in which they are present; and (iv) a recommended set of characteristics to be determined for the reference/test materials. The project also identified a series of actions for the development and promulgation of reference materials for nanoparticles for further consideration, both nationally and internationally. [ABSTRACT FROM AUTHOR]

Abstract: Veterinary medicines are used widely in the United Kingdom (UK) to protect animal health, prevent economic loss, and to help ensure a safe food supply. Veterinary medicine active ingredients (AIs) have been detected in various environmental media, including surface and groundwater, suggesting the potential for indirect human exposure from such residues. To fully assess the potential level of such exposures and the resultant potential risks to humans from all veterinary medicine AIs would be resource intensive. This paper proposes a method for prioritising veterinary medicine AIs according to estimates of their potential for indirect human exposure via the environment and their toxicity profile, and demonstrates its feasibility using an initial set of 83 veterinary medicine AIs approved for use in the UK. Overall, 13 AIs were classified as ‘High’ priority for detailed risk assessment, 19 as ‘Medium’ priority, 5 as ‘Low’ priority, and 46 as ‘Very low’ priority. The veterinary medicine AIs classified as ‘High’ or ‘Medium’ priority for detailed risk assessment included 15 different chemical groups and 10 different therapeutic indications. Overall, the proposed prioritisation scheme was demonstrated to provide a scientifically robust and pragmatic means of assessing the relative priority of veterinary medicine AIs for further detailed risk assessment regarding human exposure. However, there remain a number of data gaps that, if filled, would improve the accuracy of the resultant prioritisation. [Copyright &y& Elsevier]

The article presents information on occupational exposure, compensation, and epidemiology. Occupational exposures in Great Britain from 1998-2003 have been reviewed by the Health Protection Agency. The first epidemiological evidence that radiation increases the risk of cancer was provided by occupational exposure to ionizing radiation. In Great Britain, a compensation scheme for cancers caused by radiation was introduced by British Nuclear Fuels plc in 1982. A government-sponsored compensation scheme in the U.S. for radiation workers is also noted.

The tolerable upper intake level (UL) for vitamin D is 50 mcg/d (2000 iu/d) in North America and in Europe. In the United Kingdom a guidance level exists for vitamin D, 25 mcg/d (1000 iu/d), defined as the dose "of vitamins and minerals that potentially susceptible individuals could take daily on a life-long basis, without medical supervision in reasonable safety." Exposure of skin to sunshine can safely provide an adult with vitamin D in an amount equivalent to an oral dose of 250 mcg/d. The incremental consumption of 1 mcg/d of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D ] by approximately 1 nmol/L (0.4 microg/L). Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L (200 microg/L). Older adults are advised to maintain serum 25(OH)D concentrations >75 nmol/L. The preceding numbers indicate that vitamin D3 intake at the UL raises 25(OH)D by approximately 50 nmol/L and that this may be more desirable than harmful. The past decade has produced separate North American, European, and U.K. reports that address UL or guidance-level values for vitamin D. Despite similar well-defined models for risk assessment, each report has failed to adapt its message to new evidence of no adverse effects at higher doses. Inappropriately low UL values, or guidance values, for vitamin D have hindered objective clinical research on vitamin D nutrition, they have hindered our understanding of its role in disease prevention, and restricted the amount of vitamin D in multivitamins and foods to doses too low to benefit public health. [ABSTRACT FROM AUTHOR]

Woodward, K. N. Veterinary pharmacovigilance. Part 2. Veterinary pharmacovigilance in practice– the operation of a spontaneous reporting scheme in a European Union country– the UK, and schemes in other countries.J. vet. Pharmacol. Therap.28, 149–170.Veterinary pharmacovigilance, as it operates in the European Union (EU), covers a very broad remit, including adverse effects in treated animals, exposed humans and the environment, and in addition, it extends to cover the violation of maximum residue limits. The mainstay of veterinary pharmacovigilance is the spontaneous reporting scheme working along side other systems such as those reporting on residues surveillance. One of the most well established schemes in the EU is that operating in the UK and this paper examines the evolution of that scheme and some of its findings, data from other countries, and information available from the literature. It also tentatively examines the ways that pharmacovigilance can be used for regulatory purposes, and the contribution from pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

An educational pilot project on the bio-monitoring of air quality was carried out in the Umbria Region of Central Italy. It involved about 1000 young students (ages 4 to 16) from 42 schools of 16 municipalities in active biomonitoring of tropospheric ozone with bio-indicator sensitive tobacco seedlings. Some 6500 raw biological readings were used and these were reinforced by data captured with two photometric analysers. Under guidance from teachers, the students had several opportunities to practise basic and applied study techniques; and they were introduced to the scientific method in a simple and absorbing manner. Though primarily an educational exercise, the survey had a research element and the picture of air pollution that emerged has increased the knowledge of the air quality situation in the region. Biological monitoring of air quality is a powerful tool to improve awareness and involvement in key topics of environmental education. In addition, it promotes the active participation of citizens in the assessment of the state of the environment. [ABSTRACT FROM AUTHOR]

Pre-clinical toxicology studies in rodents and Phase I clinical trial data are summarised for 14 novel anticancer therapies. With only one exception, an antifolate antimetabolite, rodent toxicology predicted a safe Phase I trial starting dose and the majority of the dose limiting toxicities, in particular haematological toxicity. For targeted agents with well-defined pharmacodynamic markers, illustrated in the current study by 3 anti-endocrine drugs and one resistance modifier, the definition of a maximum tolerated dose can be avoided. Together with earlier data, the current study confirms that pre-clinical toxicology studies in a non-rodent species are not routinely needed for the safe conduct of early clinical trials with new cancer chemotherapies. [Copyright &y& Elsevier]

This paper looks at toxicology digital sources produced and available in the United Kingdom (UK). It includes products aggregating a number of sources, which may include information from other countries, and for the convenience of the reader and information seeker these have also been described. [Copyright &y& Elsevier]

Pesticides are an important hazard in agriculture. In developed countries their use is strictly regulated. Risk assessment for new pesticides includes comparison of the potential exposures of spray operators and other farm workers with a reference value. Usually, this is derived from toxicological studies in animals with allowance for the uncertainties in extrapolating between and within species. Older pesticides undergo periodic reviews, for which epidemiological data may also be available. Unintentional fatal poisoning by pesticides is extremely rare in Britain. Documented reports of non‐fatal acute poisoning are also uncommon, but there may be substantial under‐ascertainment of minor incidents. Pesticides have been linked with various chronic diseases, but few associations have been clearly established. A particular concern recently in Britain has been the possibility that organophosphate insecticides can cause chronic neuropsychiatric illness. [ABSTRACT FROM PUBLISHER]

Aims To examine the use and uptake of TOXBASE, an Internet database for point of care provision of poisons information in the United Kingdom during its first calendar year of web-based access. Methods Interrogation of the database software to examine: use by different types of user and geographical origin; profile of ingredient and product access; time of access to the system; profile of access to other parts of the database. Results Registered users of the system increased in the first full year of operation (1224 new users) and usage of the system increased to 111 410 sessions with 190 223 product monograph accesses in 2000. Major users were hospitals, in particular accident and emergency departments. NHS Direct, a public access information service staffed by nurses, also made increasing use of the system. Usage per head of population was highest in Northern Ireland and Scotland, and least in southern England. Ingredients accessed most frequently were similar in all four countries of the UK. Times of use of the system reflect clinical activity, with hospitals making many accesses during night-time hours. The most popular parts of the database other than poisons information were those dealing with childhood poisoning, information on decontamination procedures, teratology information and slang terms for drugs of abuse. Conclusions This Internet system has been widely used in its first full year of operation. The provision of clinically relevant, up to date, information at the point of delivery of patient care is now possible using this approach. It has wide implications for the provision of other types of therapeutic information in clinical areas. Web-based technology represents an opportunity for clinical pharmacologists to provide therapeutic information for clinical colleagues at the bedside. [ABSTRACT FROM AUTHOR]

Prior to controlled clinical trials in human volunteers or patients it is required that novel pharmaceuticals are evaluated for pre-clinical safety in a rodent and a non-rodent ('second') species. In most cases the rodent species used has been the rat and the second species has been the dog or macaque (usually cynomolgus or rhesus) monkey. However, there is an increasing trend within the United Kingdom (UK) pharmaceutical industry to use the common marmoset (Callithrix jacchus) for pre-clinical toxicology programmes. This paper examines the practicality of using the common marmoset (henceforth referred to as 'the marmoset') in toxicological testing and reviews metabolic and pharmacodynamic similarities between this species and humans. It then discusses some of the advantages and disadvantages of the use of this species when compared with two other alternatives to the dog and macaque, namely the ferret and minipig. In particular, the marmoset has clear advantages over the macaque in terms of animal welfare and practicality. There is regulatory acceptance of this species for Investigational New Drug (IND), Clinical Trial Exemption (CTX), New Drug Application (NDA) and Marketing Authorization Application (MAA) registrations. Whilst the dog is likely to be maintained as the primary non-rodent species in toxicology, the marmoset has been, and will likely continue to be, adopted as an additional non-rodent species in pre-clinical toxicology programmes where appropriate. [ABSTRACT FROM AUTHOR]