Gillian Cooper

Methoxetamine toxicity reported to the National Poisons Information Service: clinical characteristics and patterns of enquiries (including the period of the introduction of the UK's first Temporary Class Drug Order)

Objective To report the demographic and clinical characteristics of cases of methoxetamine toxicity reported to The National Poisons Information Service (NPIS) by healthcare professionals. To assess the pattern of enquiries from health professionals to the UK NPIS related to methoxetamine, including the period of the making of the UK first Temporary Class Drug Order (TCDO). Methods All telephone enquiries to and user sessions for TOXBASE, the NPIS on-line information resource, related to methoxetamine (and synonyms ‘MXE’, ‘mket’ and ‘2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone’) were reviewed from 1 April 2010 to 1 August 2012. Data were compared for the 3 months before and after the TCDO. Results There were 47 telephone enquiries and 298 TOXBASE sessions regarding methoxetamine during the period of study. Comparing the 3 months before and after the TCDO, TOXBASE sessions for methoxetamine fell by 79% (from 151 to 32) and telephone enquiries by 80% (from 15 to 3). Clinical features reported by enquirers were consistent with case reports of analytically confirmed methoxetamine toxicity and typical toxidromes were of stimulant (36%), reduced consciousness (17%), dissociative (11%) and cerebellar (6.4%) types, but also particularly featured acute disturbances in mental heath (43%). Conclusions Structured NPIS data may reveal trends in drugs of abuse use and toxicity when interpreted within their limitations. Since April 2012, there have been fewer enquiries to NPIS from clinicians, indicating reduced presentations with suspected methoxetamine toxicity to healthcare services. It is unclear if this is related to the TCDO made on 5 April 2012.

Flumazenil use in benzodiazepine overdose in the UK: a retrospective survey of NPIS data.

Objective Benzodiazepine (BZD) overdose (OD) continues to cause significant morbidity and mortality in the UK. Flumazenil is an effective antidote but there is a risk of seizures, particularly in those who have co-ingested tricyclic antidepressants. A study was undertaken to examine the frequency of use, safety and efficacy of flumazenil in the management of BZD OD in the UK. Methods A 2-year retrospective cohort study was performed of all enquiries to the UK National Poisons Information Service involving BZD OD. Results Flumazenil was administered to 80 patients in 4504 BZD-related enquiries, 68 of whom did not have ventilatory failure or had recognised contraindications to flumazenil. Factors associated with flumazenil use were increased age, severe poisoning and ventilatory failure. Co-ingestion of tricyclic antidepressants and chronic obstructive pulmonary disease did not influence flumazenil administration. Seizure frequency in patients not treated with flumazenil was 0.3%. The frequency of prior seizure in flumazenil-treated patients was 30 times higher (8.8%). Seven patients who had seizures prior to flumazenil therapy had no recurrence of their seizures. Ventilation or consciousness improved in 70% of flumazenil-treated patients. Flumazenil administration was followed by one instance each of agitation and brief seizure. Conclusions Flumazenil is used infrequently in the management of BZD OD in the UK. It was effective and associated with a low incidence of seizure. These results compare favourably with the results of published randomised controlled trials and cohort studies, although previous studies have not reported the use of flumazenil in such a high-risk population. This study should inform the continuing review of national guidance on flumazenil therapy.

Increasing frequency of severe clinical toxicity after use of 2,4-dinitrophenol in the UK: a report from the National Poisons Information Service

Objective 2,4-Dinitrophenol (DNP) increases energy consumption by uncoupling oxidative phosphorylation. Although not licensed as a medicine, it is sometimes used by ‘body sculptors’ and for weight loss as a ‘fat burning’ agent. This research was performed to characterise patterns of presentation, clinical features and outcomes of patients reported to the National Poisons Information Service (NPIS) in the UK after exposure to DNP. Methods NPIS telephone enquiry records and user sessions for TOXBASE, the NPIS online information database, related to DNP, were reviewed from 1 January 2007 to 31 December 2013. Results Of the 30 separate systemic exposures to DNP reported by telephone to NPIS during the study period (27 males, 3 females, with a median age of 23.5 years), there were 3 during 2007–2011 (inclusive), 5 during 2012 and 22 during 2013. TOXBASE user sessions also increased sharply from 6 in 2011 to 35 in 2012 and 331 in 2013. The modes of exposure reported in telephone enquiries were chronic (n=2), acute (n=12) and subacute (n=16). Commonly reported clinical features were fever (47%), tachycardia (43%), sweating (37%), nausea or vomiting (27%), skin discolouration or rash (23%), breathing difficulties (23%), abdominal pain (23%), agitation (13%) and headache (13%). There were five (17%, 95% CI 6.9% to 34%) fatalities, four involving acute overdose. Conclusions The study indicates a substantial recent increase in clinical presentations with toxicity caused by exposure to DNP in the UK with an associated high mortality. Further steps are needed to warn potential users of the severe and sometimes fatal toxicity that may occur after exposure to this compound.

Patterns of presentation and clinical toxicity after reported use of alpha methyltryptamine in the United Kingdom. A report from the UK National Poisons Information Service

Abstract Objective. To characterise the patterns of presentation, clinical effects and possible harms of acute toxicity following recreational use of alpha methyltryptamine (AMT) in the United Kingdom, as reported by health professionals to the National Poisons Information Service (NPIS) and to compare clinical effects with those reported after mephedrone use. Methods. NPIS telephone enquiries and TOXBASE® user sessions, the NPIS online information database, related to AMT were reviewed from March 2009 to September 2013. Telephone enquiry data were compared with those for mephedrone, the recreational substance most frequently reported to the NPIS, collected over the same period. Results. There were 63 telephone enquiries regarding AMT during the period of study, with no telephone enquiries in 2009 or 2010, 19 in 2011, 35 in 2012 and 9 in 2013 (up to September). Most patients were male (68%) with a median age of 20 years. The route of exposure was ingestion in 55, insufflation in 4 and unknown in 4 cases. Excluding those reporting co-exposures, clinical effects recorded more frequently in AMT (n = 55) compared with those of mephedrone (n = 488) users including acute mental health disturbances (66% vs. 32%; Odds Ratio [OR], 4.00; 95% Confidence Intervals [CI], 2.22–7.19), stimulant effects (66% vs. 40%; OR, 2.82; 95% CI 1.57–5.06) and seizures (14% vs. 2%; OR, 9.35; 95% CI 3.26–24.18). Conclusions. Although still infrequent, toxicity following reported exposure to AMT has been encountered in the United Kingdom since January 2011. Stimulant features, acute mental health disturbances and seizures are more frequently reported than in those presenting following reported use of mephedrone.

Patterns of presentation and clinical features of toxicity after reported use of ([2-aminopropyl]-2,3-dihydrobenzofurans), the 'benzofuran' compounds. A report from the United Kingdom National Poisons Information Service.

Abstract Objective. To characterise the patterns of presentation and clinical features of toxicity following reported recreational use of benzofuran compounds ((2-aminopropyl)-2,3-dihydrobenzofurans) in the UK, as reported to the National Poisons Information Service (NPIS), and to compare clinical features of toxicity with those after reported mephedrone use. Methods. NPIS patient-specific telephone enquiries and user sessions for TOXBASE®, the NPIS online information database, related to (2-aminopropyl)-2,3-dihydrobenzofurans and associated synonyms were reviewed from March 2009 to August 2013. These data were compared with those of mephedrone, the recreational substance most frequently reported to NPIS, collected over the same period. Results. There were 63 telephone enquiries concerning 66 patients and 806 TOXBASE® user sessions regarding benzofuran compounds during the period of study. The first telephone enquiry was made in July 2010 and the highest numbers of enquiries were received in August 2010 (33 calls, 112 TOXBASE® sessions). Patients were predominantly male (82%) with a median age of 29 years; 9 reported co-ingestion of other substances. Comparing the 57 patients who reported ingesting benzofuran compounds alone with 315 patients ingesting mephedrone alone, benzofurans were more often associated with stimulant features, including tachycardia, hypertension, mydriasis, palpitation, fever, increased sweating, and tremor, (72% vs. 38%, odds ratio [OR] 4.2, 95% confidence interval [CI] 2.27–7.85, P < 0.0001) and mental health disturbances (58% vs. 38%, OR 2.3, 95% CI 1.29–4.07, P = 0.006). Other features reported after benzofuran compound ingestion included gastrointestinal symptoms (16%), reduced level of consciousness (9%), chest pain (7%), and creatinine kinase elevation (5%). Conclusions. Reported ingestion of benzofuran compounds is associated with similar toxic effects to those of amphetamines and cathinones. Mental health disturbances and stimulant features were reported more frequently following reported ingestion of benzofuran compounds than after ingestion of mephedrone.

Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service.

AIMS Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti‐inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). METHODS NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. RESULTS Of 22 937 patient‐specific telephone enquiries, 10 398 did not involve co‐ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. CONCLUSIONS Mefenamic acid overdose is associated with a much larger and dose‐related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit–risk profile of mefenamic acid should now be re‐evaluated in light of effective and less toxic alternatives.

Overdose in young children treated with anti-reflux medications: Poisons enquiry evidence of excess 10-fold dosing errors with ranitidine:

Background: Accidental drug overdose is a common problem in young children. We examined the influence of formulation and dose in enquiries for different gastro-oesophageal reflux disease treatments in children under 5 years to the UK’s National Poisons Information Service. Methods: Overdose characteristics with ranitidine, omeprazole or domperidone were compared with those of metoclopramide and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June 2015. Results: There were a total of 1092 ranitidine, 618 domperidone and 1193 omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole cases occurred in children <5 years. In comparison, 17% (34/424) of metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517) of ranitidine overdose enquiries in children <5 years were under 6 months of age, higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%), chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine. Conclusions: Tenfold overdoses in children (<5 years) were a feature of ranitidine enquiries, likely due to the high concentration of the syrup. This has relevance to other liquid formulations used for non-licenced indications in young children. Such therapeutic errors cause significant carer anxiety and healthcare utilization. Assistance is needed from manufacturers and legislators in modifying formulation so that drugs can be safely used in young children. Education of prescribers and carers is also needed to reduce the incidence of such errors that cause significant carer anxiety and healthcare utilization.

Iron overdose epidemiology, clinical features and iron concentration-effect relationships: the UK experience 2008–2017

Abstract Background: Iron poisoning is potentially serious, but mortality has fallen worldwide since implementation of pack size and packaging restrictions, and changes in iron use during pregnancy. The management of individual cases of overdose remains problematic due to uncertainty about indications for antidote. We examine the epidemiology of iron overdose in hospital cases referred to the UK National Poisons Information Service (NPIS) and evaluate the toxicokinetics of iron in patients ingesting only iron preparations. Methods: Anonymized hospital referral patient data from the NPIS database were collated for the period 1 January 2008 to 31 July 2017. Information was extracted, where recorded, on type of ingestion [iron alone (single), or combined with other agents (mixed)], reported dose, iron salt, timed iron concentrations and symptoms. In single-agent ingestions, the relationships between reported elemental iron dose, early concentrations (4–6 h), and symptoms were evaluated in teenagers and adults (≥13 years) and children (≤12 years) using standard statistical techniques (correlation and unpaired nonparametric comparisons). In those patients with sufficient sample points (three or more), a simple kinetic analysis was conducted. Results: Of 2708 patients with iron overdoses referred by UK hospitals for advice during the 9.7 years study period, 1839 were single-agent ingestions. There were two peaks in age incidence in single-agent exposures; 539/1839 (28.4%) were <6 years (54.1% males) while 675/1839 (36.7%) were between 13 and 20 years (91% females), the latter a substantial excess over the proportion in the totality of hospital referrals to the NPIS in the same period (13–20 years: 23,776/144,268 16.5%; 67.5% female) (p < .0001 overall and for female %). In 475 teenagers and adults and 86 children, with at least one-timed iron concentration available, there was no correlation between stated dose and iron concentration measured 4–6 h post-ingestion. Observed peak iron concentrations were not related to reported symptoms in adults. Initial iron concentrations were significantly higher in 30 patients (25 adults, 5 children) who received desferrioxamine (DFO) compared to those that did not [no DFO: mean 63.8 μmol/L (95% CI 62.1–65.6), median 64; DFO: mean 78.5 μmol/L (95% CI 69.2–87.7), median 78.1; Mann–Whitney p < .0018). No significant differences in symptoms were observed pre-treatment between DFO-treated and untreated groups. No patients died in this cohort. Conclusion: Single-agent iron exposures reported from UK hospitals were most common in children <5 years and young people aged 13–20 years. Poisoning with organ failure was not identified and there were no fatalities. No correlations were observed between reported iron doses and early concentrations, or between iron concentrations and symptoms in this cohort of mild-to-moderate poisoning.

Examining methotrexate exposures reported to the UK National Poisons Information Service 2004-2015: highlighting adverse reactions and avoidable therapeutic errors

36th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 24–27 May, 2016, Madrid, Spain 1. Intramuscular and intravenous e-liquid injection: a new phenomenon? Eleri Thomas, J. Allister Vale, Michael Eddleston, Simon HL Thomas and John P Thompson NPIS Cardiff, University Hospital Llandough, Cardiff, UK; NPIS Birmingham, City Hospital, Birmingham, UK; NPIS Edinburgh, Scottish Poisons Information Bureau, Edinburgh, UK; NPIS Newcastle, Regional Drug and Therapeutics Centre, Newcastle upon Tyne, UK Objective: Electronic cigarette design and shape have altered noticeably since their introduction to the UK market. Current e-cigarettes exist as disposable and re-chargeable devices. Cartridges of liquid nicotine solution can be placed inside these devices, or alternatively, a nicotine containing solution (known as e-liquid) can be used to replenish e-cigarette reservoirs. The solution typically contains nicotine, propylene glycol or vegetable glycerine, flavouring and water.[1] Solutions may also contain unspecified ingredients such as methyl salicylate (oil of wintergreen) [2] and nitrosamine.[1] Previous National Poisons Information Service (NPIS) data suggest that these highly concentrated, toxic liquids can be misused by means of ingestion. Recently, the NPIS has received enquiries concerning the parenteral administration of e-cigarette refill liquid. We sought to determine if the pattern of enquiries made to the UK NPIS concerning exposure to e-liquids containing nicotine is changing. Methods: Telephone enquiries to the NPIS between 1 April 2014 and 31 October 2015 relating to exposures concerning injections of liquid nicotine solution were examined to determine incidence and clinical features. Results: Of 379 enquiries identified relating to e-cigarettes and e-cigarette refill liquid, five were in relation to liquid nicotine solution administrated by injection. Cases involved individuals aged 39 to 59 years. All exposures were acute. Four patients were male, 2 patients injected e-liquid intramuscularly, 1 intravenously and 2 subcutaneously. E-liquid was injected both intentionally (n1⁄4 2) and as a result of recreational abuse (n1⁄4 2). One patient, who was accidentally exposed to the solution, remained asymptomatic. Three patients developed mild features including a localised skin reaction, somnolence, fever and palpitations. This corresponded to a maximum poisons severity score (PSS) [3] of one. Chest pain and QT prolongation occurred in one case resulting in a maximum PSS score of two. Conclusion: Parenteral use of e-liquid, including recreational use, is occasionally encountered. Although local problems such as extravasation injury, skin necrosis and compartment syndrome may be expected after injection of this agent, as nicotine is extremely irritating to tissues, serious outcomes were not encountered in this small case series. References [1] Wollscheid KA, Kremzner ME. Electronic cigarettes: safety concerns and regulatory issues. Am J Health Syst Pharm.36th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 24-27 May, 2016, Madrid, Spain36th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 24–27 May, 2016, Madrid, Spain 1. Intramuscular and intravenous e-liquid injection: a new phenomenon? Eleri Thomas, J. Allister Vale, Michael Eddleston, Simon HL Thomas and John P Thompson NPIS Cardiff, University Hospital Llandough, Cardiff, UK; NPIS Birmingham, City Hospital, Birmingham, UK; NPIS Edinburgh, Scottish Poisons Information Bureau, Edinburgh, UK; NPIS Newcastle, Regional Drug and Therapeutics Centre, Newcastle upon Tyne, UK Objective: Electronic cigarette design and shape have altered noticeably since their introduction to the UK market. Current e-cigarettes exist as disposable and re-chargeable devices. Cartridges of liquid nicotine solution can be placed inside these devices, or alternatively, a nicotine containing solution (known as e-liquid) can be used to replenish e-cigarette reservoirs. The solution typically contains nicotine, propylene glycol or vegetable glycerine, flavouring and water.[1] Solutions may also contain unspecified ingredients such as methyl salicylate (oil of wintergreen) [2] and nitrosamine.[1] Previous National Poisons Information Service (NPIS) data suggest that these highly concentrated, toxic liquids can be misused by means of ingestion. Recently, the NPIS has received enquiries concerning the parenteral administration of e-cigarette refill liquid. We sought to determine if the pattern of enquiries made to the UK NPIS concerning exposure to e-liquids containing nicotine is changing. Methods: Telephone enquiries to the NPIS between 1 April 2014 and 31 October 2015 relating to exposures concerning injections of liquid nicotine solution were examined to determine incidence and clinical features. Results: Of 379 enquiries identified relating to e-cigarettes and e-cigarette refill liquid, five were in relation to liquid nicotine solution administrated by injection. Cases involved individuals aged 39 to 59 years. All exposures were acute. Four patients were male, 2 patients injected e-liquid intramuscularly, 1 intravenously and 2 subcutaneously. E-liquid was injected both intentionally (n1⁄4 2) and as a result of recreational abuse (n1⁄4 2). One patient, who was accidentally exposed to the solution, remained asymptomatic. Three patients developed mild features including a localised skin reaction, somnolence, fever and palpitations. This corresponded to a maximum poisons severity score (PSS) [3] of one. Chest pain and QT prolongation occurred in one case resulting in a maximum PSS score of two. Conclusion: Parenteral use of e-liquid, including recreational use, is occasionally encountered. Although local problems such as extravasation injury, skin necrosis and compartment syndrome may be expected after injection of this agent, as nicotine is extremely irritating to tissues, serious outcomes were not encountered in this small case series. References [1] Wollscheid KA, Kremzner ME. Electronic cigarettes: safety concerns and regulatory issues. Am J Health Syst Pharm.36th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 24-27 May, 2016, Madrid, Spain

Methoxetamine toxicity reported to the National Poisons Information Service: Clinical characteristics and the effect of the UK's first Temporary Class Drug Order

Objective: On-site drug tests (ODTs) are frequently used in hospitals to screen the urine of patients admitted for suspected poisoning. The purpose of this study is to evaluate the accuracy of such ...1. Methanol outbreak in the Czech Republic in 2012: Epidemiology and clinical features Daniela Pelclova1, Sergej Zakharov1, Tomas Navratil1 Knut Erik Hovda2 1Toxicological Information Centre, 1st Medical Faculty, Charles University in Prague, Czech Republic; 2The Norwegian Center for NBC Medicine, Department of Acute Medicine, Oslo University Hospital, Norway Objective: Mass methanol poisonings are a challenge for treating physicians due to the unpredictable onset and scenario, diagnostic difficulties, severe toxicity, expensive treatment, high mortality and frequently serious sequelae.1–4 We report the features of a large methanol outbreak that started in the Czech republic in September 2012 due to the illegal production and sale of adulterated spirits. Methods: Discharge reports and questionnaires of hospitalized patients with confirmed methanol poisoning, received by the Toxicological Information Centre were analyzed. Statistical evaluation used: normality of distribution, arithmetic mean, standard deviation, skew, median, mode, Student’s t-test, F-test, confidence intervals, correlation coefficient, and Chi-Square-test. Results: A total of 73 discharge reports were analyzed. A further 20 patients died at home or before hospital and 5 reports of recently deceased subjects could not yet be analyzed. Among the 73 hospitalized patients, 56 (77%) were males, mean age 51 (range 25–79) years, and 17 (23%) females, mean age 54 (range 23–69) years. Only 9 patients (12%) were admitted within 12 hours of ingestion, 50% after 12–48 hours, and 38% later. All patients who died were admitted 12 or more hours after ingestion. The methanol content of the beverage drunk (25–50%) was known in 42/73 patients (58%), 18/73 (25%) subjects drank other alcoholic beverages (wine, beer, whisky, home-made spirits) in addition. There were 32/73 (44%) daily alcohol users. Admission data: Median serum methanol was 0.939 g/L (range 0–7.307), i.e. 29.4 mmol/L (range 0–229); median ethanol level 0.437 g/L, (range 0–4.460), i.e. 9.6 mmol/L (range 0–98). Median pH was 7.17 (6.57–7.46; N 7.37–7.43), median pCO2 4.07 kPa (0.97-14.9 kPa; N 4.3-6.0), median HCO3  8.8 mmol/L (2–25.5; N 21.8-27.6), median base deficit 17.2 mmol/L (range 0.1–38.1; N 3–3), median lactic acid 3 mmol/L (0–19.4; N 0.6–2.1), median anion gap 28.8 mmol/L (range 11.1–54.8; N 16–20), median osmolality 348 mmol/kg (283–529, N 275–295), and osmolal gap 45.8 mmol/kg (2.4–235, N 10–25). Clinical symptoms: Only 12/73 patients (26%) were asymptomatic on admission, 7 appeared inebriated; at least 3 of them without measurable ethanol in blood. Among the 61 symptomatic patients, the most frequent symptoms were gastrointestinal (63%), visual disturbances (59%), dyspnoea (46%), coma (29%) and chest pain (17%). Other symptoms included fatigue, headache, dizziness, hangover, somnolence, anxiety, tremor, seizures, alcoholic delirium, respiratory and cardiac arrest. Treatment included alkalinization in 64%, ethanol in 79%, fomepizole in 5%, or a combination of antidotes in 12% patients. because there was limited availability of fomepizole, it was only recommended for the most severely poisoned subjects with methanol level above 0.500 g/L (15.65 mmol/L) or formic acid above 0.400 g/L (8.7 mmol/L) or pH lower than 7.0. Folates were administered in 72% of subjects (folic acid in 33 patients, folinic acid in 20 patients); whereas haemodialysis was performed in 58/73 (79.5%) subjects and started on average 4 hours after admission to the hospital (range 0.5–44). Continuous veno-venous haemodialysis (CVVHD) was performed in 50% of subjects; lasting a median of 36 hours (range 3.5–95). Conventional intermittent haemodialysis (IHD) was performed for a median duration of 8 hours (range 4–18.5). Outcomes: There were 13/73 (18%) fatalities, 44/73 (60%) survivors without sequelae, and 16/73 (22%) survivors with sequelae: visual impairment alone in 7/73 (10%), central nervous system (CNS) impairment in 5/73 (6.5%) and both visual and CNS damage in 4/73 (5.5%). The mortality was 75% among the patients admitted with respiratory arrest and 52% among those comatose on admission. The patients who died were more (p  0.05) acidotic (median pH 6.75, median base deficit 30 mmol/L) than the survivors with sequelae (median pH 7.02, median base deficit 19 mmol/L) and than those without (median pH 7.26, median base deficit 8 mmol/L), (p  0.05). No significant differences were found between the 3 groups regarding serum methanol, osmolal gap, and HCO3 . The groups differed only in pCO2, pH and base deficit (all p  0.05). Among the patients who recovered without sequelae, there was a trend towards lower pCO2 when pH was decreasing, whilst the trend was the opposite amongst the victims (pH decreased and pCO2 increased). The difference between these groups was highly significant (p  0.001). Lactic acid was significantly higher in victims than survivors (p  0.01). Among the 58 patients treated with ethanol, 9 (16%) died, 9 (16%) survived with sequelae, and 40 (68%) recovered fully. Among the 13 patients treated with fomepizole or the combination of antidotes, 3 (23%) died, 6 (46%) survived with sequelae, and 4 (31%) recovered, i.e. the outcome was worse in the second group (p  0.023). There was no difference in survival between the patients treated with continuous veno-venous haemodialysis (CVVHD) and IHD (p  0.17).Background: Of the 90,000 exposures involving children younger than 6 years of age reported to German poison centers (PCs) every year a !fth are caused by plants. A list of especially poisonous plants, which should not be planted in children’s playgrounds, was published in the “Bundesanzeiger” (Federal Gazette) in 2000. The BfR-Committee “Assessment of Intoxications” founded a work- ing group to re-assess the toxicity of plants to protect especially children from severe plant poisoning. Methods: The members of the working group de!ned criteria for risk assessment of plants in the close proximity of children’s playgrounds. Human exposure data, provided by the German PCs in Berlin, Freiburg and Erfurt and by the Swiss PC Zurich were reviewed as well as scienti!c publications about human exposures and about toxicity of ingredients of plants. Following the assess- ment of the toxicity of chemicals in analogy to the German Regula- tions on Dangerous Substances, poisonous plants were re-classifed into three categories, namely plants which could lead to minor poisoning, moderate poisoning and severe or deadly poisoning. Results: Out of 43,000 con!rmed accidental plant exposures from PCs in Freiburg and Berlin moderate or severe poisoning was expe- rienced in 1.3% restricted to 39 plants. Altogether, 280 plants were re-evaluated. Risk assessment changed for some of the especially poisonous plants of the 2000 list. For example the formerly moder- ate poisonous plants Lantana camara, Ilex spec., and Euonymus spec. were re-assessed as minor poisonous, and the formerly minor toxic Chelidonium majus was re-assessed as moderately toxic for the eyes. Conclusion: Human data about the risk of health damage after accidental ingestion of small amounts or by accidental dermal or ocular contact are mainly restricted to published case reports. The toxicity of ingredients and of preparations of plants for medical or psychoactive purposes may be completely different. The exposure data of PCs are very useful for risk assessment of plants present in the close proximity of children’s playgrounds, kindergartens, etc. The re-assessment and the !nal table of especially poisonous plants will be published again in the “Bundesanzeiger”.Background On the 21st June 2010, the management advice on TOXBASE® (the UK poisons database) for toothpaste ingestion changed, from advising medical assessment in patients developing anything other than minor gastrointestinal symptoms to advising observations in patients ingesting over 5 mg/kg fluoride, and further management in those ingesting over 10 mg/kg fluoride. We investigated the amounts ingested, features present, and advice given in cases of acute toothpaste ingestion reported to the NPIS three years before, and two years after, this change.Background: In 2009, in a joint cooperation, the Federal Institute for Risk Assessment (BfR) carried out an investigation concerning the poisoning situation of children, but with indifferent results for the poisoning risks in migrants. Between 2010 and 2011 some scientific assumptions were published in Germany that migrants could carry a higher risk of childhood poisoning. A feasibility study in Berlin, however, evaluated the options for achieving access to families with a migrant background in order to develop a framework for further, enlarged and systematically established scientific studies. Method: Existing data on migration background were evaluated regarding risks of chemical consumer products being responsible for childhood household poisoning accidents. The main instrument was a semi-standardised questionnaire for parents. Subject matter was focused on poisoning accidents which had occurred; knowledge about chemical products; attitudes towards the use of those products, their household storage and safety aspects and an important item “looking through the keyhole”. This means that if respondents agreed an expert would make a home-visit to evaluate real household product knowledge together with poisoning risks for children. Results: Regarding the cases of childhood poisoning accidents, the study did not support the assumption of a higher rate of relevant accidents in families with a migrant background - on the contrary, accidents occurred mainly in families with minor chemical use. There was no obvious correlation between age of the parents, family status, job, dwelling, knowledge about the products or their possible risks and causes of poisonings. In three-quarters of the cases, the affected children were the eldest. Possible impacts to be evaluated are e.g. the knowledge which might well have its origin in a specific cultural setting - about handling and risks of chemical products and the level of knowledge of the German language. Furthermore, more than half of the respondents agreed to an expert’s visit to their home. Conclusion: In order to develop adequate means of prevention in childhood poisoning, the focus has to be taken to special target groups and the evaluation of specific instruction materials. It is of nationwide importance to get personal access to the migrants. A combination of legal and educationally oriented measures seems promising.Objective: Since 20 January 2009, the EU-CLP Regulation (EC) No. 1272/2008 (Classification, labelling and packaging of substances and mixtures) has been in effect. Article 45 stipulates compulsory reporting of formulations of mixtures by industry for emergency health services. For adaptation of the CLP Regulation on a national level, the German government implemented Art. 45 CLP-Regulation into the § 16e (Chemicals Law - Chemikaliengesetz). For a transition period (9th November 2011 limited to the 1st July 2014) German industry can already start to use “Art. 45-Electronic Product Notification” via an adapted BfR-Electronic Product Notification Portal. Methods: Since 2007, notification of formulations of detergents and cleaning agents has been performed by file transfer in XML-format. This procedure was developed by the BfR and had been well adopted by industry. This format was refined by the BfR to ensure that data on all notifiable products and data reported on a voluntary basis can be transmitted in XML-format. This prototype and the procedures have been practice-tested in cooperation with a major enterprise (Henkel, Dusseldorf). After final testing the BfR-database has been adapted to the new requirements of the CLP-Regulation on e.g. labelling and all important data, including clear identifiers (e.g. product identification element) which can be exchanged in the new format. Results: The § 16e (new) has been successfully adapted to the CLP Regulation (EC) No. 1272/2008: 1) governed by public law with a transition period in awaiting the EU-harmonisation dataset for product notifications and 2) technical in having an adapted BfR-XML Electronic Notification Portal which carries all the requirements for the rapid adaptation to the future EU standard data set. With the new § 16e the notification of dangerous mixtures is considerably extended. Products with all hazard identifiers – commercial/non-commercial – have to be notified. The increase is already visible in 2012. From January to October 38,735 dangerous mixtures (excluding biocides) had been notified. This represents a 25-fold increase compared to 2011. Conclusion: A universal electronic notification procedure for industry will enable BfR to considerably increase the number of product notifications received, processed and communicated to German PCCs.Background A survey of all European Poisons Centres (PCs) was carried out in 2012 by the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) in order to identify staffing, organisation, In 2012 all centres required information staff to have at least a university degree, with the exception of one that employed nongraduate nurses (96.9% compared with 81.7% requiring a university degree in 2000). services provided, research and training. The objective was to describe the working of the centres and perhaps to provide help where needed in the future.