Current Awareness in Clinical Toxicology Editors: Damian Ballam MSc and Allister Vale MD

January 2016

CONTENTS General Toxicology 8 Metals 38 Management 20 Pesticides 40 Drugs 22 Chemical Warfare 42 Chemical Incidents & 33 Plants 43 Pollution Chemicals 34 Animals 44

CURRENT AWARENESS PAPERS OF THE MONTH

Sea-dumped chemical weapons: environmental risk, occupational hazard Greenberg MI, Sexton KJ, Vearrier D. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1121272: Introduction Chemical weapons dumped into the ocean for disposal in the twentieth century pose a continuing environmental and human health risk. Objective In this review we discuss locations, quantity, and types of sea-dumped chemical weapons, related environmental concerns, and human encounters with sea-dumped chemical weapons. Methods We utilized the Ovid (http://ovidsp.tx.ovid.com) and PubMed (http://www.pubmed.org) search engines to perform MEDLINE searches for the terms 'sea-dumped chemical weapons', 'chemical warfare agents', and 'chemical munitions'. The searches returned 5863 articles. Irrelevant and non-English articles were excluded. A review of the references for these articles yielded additional relevant sources, with a total of 64 peer-reviewed articles cited in this paper. History and geography of chemical weapons dumping at sea Hundreds of thousands of tons of chemical munitions were disposed off at sea following

Current Awareness in Clinical Toxicology is produced monthly for the American Academy of Clinical Toxicology by the Birmingham Unit of the UK National Poisons Information Service, with contributions from the Cardiff, Edinburgh, and Newcastle

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World War II. European, Russian, Japanese, and United States coasts are the areas most affected worldwide. Several areas in the Baltic and North Seas suffered concentrated large levels of dumping, and these appear to be the world's most studied chemical warfare agent marine dumping areas. Chemical warfare agents Sulfur mustard, Lewisite, and the nerve agents appear to be the chemical warfare agents most frequently disposed off at sea. Multiple other type of agents including organoarsenicals, blood agents, choking agents, and lacrimators were dumped at sea, although in lesser volumes. Environmental concerns Numerous geohydrologic variables contribute to the rate of release of chemical agents from their original casings, leading to difficult and inexact modeling of risk of release into seawater. Sulfur mustard and the organoarsenicals are the most environmentally persistent dumped chemical agents. Sulfur mustard in particular has a propensity to form a solid or semi-solid lump with a polymer coating of breakdown products, and can persist in this state on the ocean floor for decades. Rates of solubility and hydrolysis and levels of innate toxicity of a chemical agent are used to predict the risk to the marine environments. The organoarsenicals eventually breakdown into arsenic, and thus present an indefinite timeline for contamination. Generally, studies assaying sediment and water levels of parent chemical agents and breakdown products at dumpsites have found minimal amounts of relevant chemicals, although arsenic levels are typically higher in dumpsites than reference areas. Studies of marine organisms have not shown concerning amounts of chemical agents or breakdown products in tissue, but have shown evidence of chronic toxicity. There is believed to be minimal risk posed by seafood consumption. Microbiota assays of dumpsites are significantly altered in species composition compared to reference sites, which may imply unseen but significant changes to ecosystems of dumpsites. Human health concerns The major human health risk at this time appears to arise from acute exposure to an agent by either accidental recovery of a chemical weapon on a fishing vessel, or by munitions washed ashore onto beaches. Conclusions Improving technology continues to make the deep sea more accessible, thus increasing the risk of disturbing munitions lying on or buried in the seabed. Pipe laying, cable burying, drilling, scuba diving, trawling, and undersea scientific research are the activities posing the most risk. The long-term threat to the benthic habitat via increased arsenic concentrations, shifts in microbiota speciation, and chronic toxicity to vertebrates and invertebrates is not currently understood. The risk to the environment of massive release via disturbance remains a distinct possibility. Terrorist recovery and re-weaponization of chemical agents is a remote possibility. Full text available from: http://dx.doi.org/10.3109/15563650.2015.1115056

New regimens for intravenous acetylcysteine, where are we now? Bateman DN, Dear JW, Thomas SHL. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1121545: Acetylcysteine has been used as a treatment for paracetamol overdose as a 20.25- or 21-h infusion for nearly 40 years. These regimens give 50% of the dose in the first 15 min or 1 h, and are associated with high rates of adverse reactions. A randomised controlled trial has demonstrated that a shorter (12 h) and simpler (two infusions) acetylcysteine regimen using

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a slower initial infusion rate produces lower rates of adverse events than the original 20.25- h regimen. However, this study was not sufficiently large to show therapeutic equivalence as a hepatoprotective therapy in paracetamol overdose. Two further studies are now reported, which also suggest lower rates of adverse reactions with lower initial rates of acetylcysteine administration. These modified regimens can now be accepted as better tolerated, but it is unlikely that a randomised study of sufficient size to demonstrate non-inferiority of any novel regimen would ever be funded. Against this background we suggest what can be done to establish the efficacy of these less toxic and potentially shorter alternative acetylcysteine regimens and to establish them into routine clinical use. Full text available from: http://dx.doi.org/10.3109/15563650.2015.1121545

A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning Isbister GK, Downes MA, Mcnamara K, Berling I, Whyte IM, Page CB. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1115057: Context The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15-60 min and frequently results in adverse reactions. Objective We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. Materials and methods A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4–9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. Results 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15–98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31–39%): 173 (26.5%; 95% CI: 23–30%) only gastrointestinal, 50 (8%; 95% CI: 6–10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1–1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13–28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. Conclusion A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations. Full text available from: http://dx.doi.org/10.3109/15563650.2015.1115057

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Plasma neutrophil gelatinase-associated lipocalin as a predictive biomarker for the detection of acute kidney injury in adult poisoning Ahn JY, Lee MJ, Seo JS, Choi D, Park JB. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1118487: Context Acute kidney injury (AKI) is a serious complication in intoxicated patients. Recently, a new biomarker - neutrophil gelatinase-associated lipocalin (NGAL) - was used to predict AKI in patients who were critically ill or had sepsis. Objective To evaluate the utility of plasma NGAL as an early predictor of AKI in adults with acute poisoning. Materials and methods This retrospective, observational, cohort study was conducted between December 2013 and November 2014. A total of 157 consecutive adult patients who presented to the emergency department (Level 1 regional center) of Kyungpook National University Hospital, a tertiary teaching hospital in Daegu, Korea, within 24 h of poisoning were included. Initial plasma NGAL levels and laboratory parameters were concurrently measured upon hospital arrival. AKI was defined according to Acute Kidney Injury Network criteria. Development of AKI was predicted using plasma NGAL levels and by analyzing the area under the receiver operating characteristic curve (AUC). Results The overall rate of AKI was 14.6% (n = 23). Plasma NGAL levels in the AKI group were higher than those in the non-AKI group (median, 310 vs. 86 ng/mL; p <0.001). Additionally, baseline NGAL levels allowed for better prediction of AKI than initial creatinine levels. The AUC of plasma NGAL was 0.895 (95% confidence interval [CI]: 0.832-0.941), with a cut-off value of 227 ng/mL (sensitivity, 76.2%; specificity, 95.8%). Plasma NGAL had a higher predictive capacity for AKI than serum creatinine (AUC 0.741, 95% CI: 0.662–0.810), base deficit (AUC 0.795, 95% CI: 0.701–0.870), lactate (AUC 0.781, 95% CI: 0.690–0.856), and anion gap (AUC 0.636, 95% CI: 0.535–0.730). Conclusion Plasma NGAL may serve as a good predictor of AKI in cases of adult poisoning. Full text available from: http://dx.doi.org/10.3109/15563650.2015.1118487

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic drugs Chase PB, Hawkins J, Mosier J, Jimenez E, Boesen K, Logan BK, Walter FG. Clin Toxicol 2016; 54: 14-9. Context Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic or marijuana, as well as to clinical toxicologists who care for patients with complications from and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and

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behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. Methods Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9- (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. Results 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19–23 years). Median age for the marijuana group (n = 25, 21 males) was 20 years (IQR 19–24 years) (p = 0.46). In the synthetic cannabinoid group, 94% (15/16) admitted to using synthetic cannabinoids. In the marijuana group, 96% (24/25) admitted to using marijuana. Blood was available for testing in 96% (24/25) of the marijuana group; 21 of these 24 had quantitative levels of THC (mean + SD = 10.7 + 5 ng/mL) and THC-COOH (mean + SD = 57.8 + 3 ng/mL). Blood was available for testing in 63% (10/16) of the synthetic cannabinoid group, with 80% (8/10) of these positive for synthetic cannabinoids. Those in the synthetic cannabinoid group were more frequently confused (7/16 [44%] vs. 0/25 [0%], p 0.003) and disoriented (5/16 [31%] vs. 0/25 [0%], p 0.003), and more frequently had incoherent, slurred speech (10/16 [63%] vs. 3/25 [12%], p = 0.0014) and horizontal gaze nystagmus (8/16 [50%] vs. 3/25 [12%], p = 0.01) than those in the marijuana group. Conclusion Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs. Full text available from: http://dx.doi.org/10.3109/15563650.2015.1101769

Agricultural pesticide exposure and chronic kidney disease: new findings and more questions Calvert GM. Occup Environ Med 2016; 73: 1-2. Abstract and full text available from: http://dx.doi.org/10.1136/oemed-2015-103132

Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study Lebov JF, Engel LS, Richardson D, Hogan SL, Hoppin JA, Sandler DP. Occup Environ Med 2016; 73: 3-12. Abstract and full text available from: http://dx.doi.org/10.1136/oemed-2014-102615

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A multicenter retrospective survey of poisoning after ingestion of herbicides containing glyphosate potassium salt or other glyphosate salts in Japan Kamijo Y, Takai M, Sakamoto T. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1121271: Introduction A multicenter retrospective survey of patients poisoned by herbicides containing glyphosate salts in Japan was conducted to identify differences in symptoms and outcome of poisoning. Methods Participants were patients who were transported to emergency facilities between October 2006 and March 2014 after consuming herbicides containing glyphosate potassium salt (GlyK+) (the K-group) or other glyphosate salts (the O-group). Questionnaires were mailed to 38 emergency facilities that agreed to participate in the study. Results Serum potassium levels upon arrival were significantly higher (p < 0.01), and abnormal electrocardiogram findings were significantly more common (p < 0.01) in the K-group (n = 55) than in the O-group (n = 62). Conversely, acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) (p = 0.05) and liver injury (LI) (p < 0.01) were significantly more common during hospitalization in the O-group, although no significant differences in the duration of hospital stay (p = 0.92) or outcomes (p = 0.95) were observed between the two groups. Discussion and conclusion The ingestion of products containing glyphosate isopropylamine or ammonium salts, and polyoxyethyleneamine (POEA) as a surfactant, can cause severe organ injury. Physicians should note that the ingestion of products containing glyphosate potassium salt and surfactants other than POEA can cause hyperkalemia, potentially leading to fatal arrhythmias or cardiac arrest. Full text available from: http://dx.doi.org/10.3109/15563650.2015.1121271

Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring Gallegos CE, Bartos M, Bras C, Gumilar F, Antonelli MC, Minetti A. Neurotoxicology 2016; 53: 20-8. Abstract and full text available from: http://dx.doi.org/10.1016/j.neuro.2015.11.015

The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis Bérard A, Iessa N, Chaabane S, Muanda FT, Boukhris T, Zhao J-P. Br J Clin Pharmacol 2015; online early: doi: 10.1111/bcp.12849: Abstract and full text available from: http://dx.doi.org/10.1111/bcp.12849

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Effect of systematic follow-up by general practitioners after deliberate self-poisoning: a randomised controlled trial Grimholt TK, Jacobsen D, Haavet OR, Sandvik L, Jorgensen T, Norheim AB, Ekeberg O. PLoS ONE 2015; 10: e0143934. Abstract and full text available from: http://dx.doi.org/10.1371/journal.pone.0143934

Focused use of drug screening in overdose patients increases impact on management Erdmann A, Werner D, Hugli O, Yersin B. Swiss Med Wkly 2015; 145: w14242. Abstract and full text available from: http://www.smw.ch/content/smw-2015-14242/

A new kid on the block: outcomes with Kcentra 1 year after approval Berndtson AE, Huang W-T, Box K, Kobayashi L, Godat LN, Smith AM, Weingarten D, Coimbra R. J Trauma Acute Care Surg 2015; 79: 1004-8. Abstract and full text available from: http://dx.doi.org/10.1097/TA.0000000000000868

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B Garcia J, Costa VM, Carvalho ATP, Silvestre R, Duarte JA, Dourado DFAR, Arbo MD, Baltazar T, Dinis-Oliveira RJ, Baptista P, de Lourdes Bastos M, Carvalho F. Arch Toxicol 2015; 89: 2305-23. Abstract and full text available from: http://dx.doi.org/10.1007/s00204-015-1582-x

Clinicopathological effects of pepper (oleoresin capsicum) spray Yeung MF, Tang WYM. Hong Kong Med J 2015; 21: 542-52. Abstract and full text available from: http://dx.doi.org/10.12809/hkmj154691

Prospective assessment of the false positive rate of the Australian Snake Venom Detection Kit in healthy human samples Nimorakiotakis V, Winkel KD. Toxicon 2015; online early: doi: 10.1016/j.toxicon.2015.12.002: Abstract and full text available from: http://dx.doi.org/10.1016/j.toxicon.2015.12.002

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de Oliveira MH, Ferreira PCL, Carlos G, Salazar FR, Bergold TOXICOLOGY AM, Pechansky F, Limberger RP, Fröehlich PE. General Validation and application of a liquid chromatography- Asadi R, Afshari R, Dadpour B. electrospray ionization mass spectrometric method for The measurement of disability weights for 18 prevalent determination of mazindol in human plasma and urine. acute poisoning conditions. J Pharmacol Toxicol Methods 2015; 79: 1-6. Hum Exp Toxicol 2015; online early: doi: 10.1177/0960327115617229: Frison G, Zamengo L, Zancanaro F, Tisato F, Traldi P. Characterization of the deschloroketamine (2- Beauchamp GA. methylamino-2-phenylcyclohexanone) by gas chromatog- The toxicologist's role in community outreach: engaging raphy/ mass spectrometry, liquid chromatography/ high- fellows in education and advocacy efforts. resolution mass spectrometry, multistage mass spec- J Med Toxicol 2015; online early: doi: 10.1007/s13181- trometry, and nuclear magnetic resonance. 015-0530-8: Rapid Commun Mass Spectrom 2016; 30: 151-60.

Langley G, Austin CP, Balapure AK, Birnbaum LS, Bucher Garg U, Zhang YV. JR, Fentem J, Fitzpatrick SC, Fowle JR, III, Kavlock RJ, Mass spectrometry in clinical laboratory: applications in Kitano H, Lidbury BA, Muotri AR, Peng S-Q, Sakharov D, therapeutic drug monitoring and toxicology. Seidle T, Trez T, Tonevitsky A, van de Stolpe A, Whelan Methods Mol Biol 2016; 1383: 1-10. M, Willett C. Lessons from toxicology: developing a 21st-century George R, Lobb M, Haywood A, Khan S, Hardy J, Good P, paradigm for medical research. Hennig S, Norris R. Environ Health Perspect 2015; 123: A268-A272. Quantitative determination of the enantiomers of in human plasma and saliva by chiral column Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. chromatography coupled with mass spectrometric 2014 Annual report of the American Association of Poison detection. Control Centers' National Poison Data System (NPDS): Talanta 2016; 149: 142-8. 32nd annual report. Clin Toxicol 2015; 53: 962-1147. Grapp M, Sauer C, Vidal C, Müller D. GC-MS analysis of the designer drug -pyrrolidino- Rhyee SH, Farrugia L, Campleman SL, Wax PM, Brent J, valerophenone and its metabolites in urine and blood in an On behalf of the Toxicology Investigators Consortium. acute poisoning case. The Toxicology Investigators Consortium Case Registry– Forensic Sci Int 2015; online early: The 2014 experience. doi: 10.1016/j.forsciint.2015.12.020: J Med Toxicol 2015; 11: 388-409. Grobério TS, Zacca JJ, Botelho ÉD, Talhavini M, Braga JWB. Discrimination and quantification of and adulterants Analytical toxicology in seized drug samples by infrared spectroscopy and PLSR. Al-Hroub H, Alkhawaja B, Alkhawaja E, Arafat T. Forensic Sci Int 2015; 257: 297-306. Sensitive and rapid HPLC-UV method with back-extraction step for the determination of sildenafil in human plasma. Haage P, Kronstrand R, Carlsson B, Kugelberg FC, J Chromatogr B Biomed Sci Appl 2016; 1009-1010: 1-6. Josefsson M. Quantitation of the enantiomers of and its three Blakey K, Boyd S, Atkinson S, Wolf J, Slottje PM, main metabolites in human whole blood using LC-MS/MS. Goodchild K, McGowan J. J Pharm Biomed Anal 2016; 119: 1-9. Identification of the novel synthetic cannabimimetic 8- quinolinyl 4-methyl-3-(1-piperidinylsulfonyl)benzoate (QMPSB) Hartung B, Schwender H, Pawlik E, Ritz-Timme S, and other designer drugs in herbal incense. Mindiashvili N, Daldrup T. Forensic Sci Int 2015; online early: Comparison of venous blood alcohol concentrations and doi: 10.1016/j.forsciint.2015.12.001: breath alcohol concentrations measured with Draeger Alcotest 9510 DE Evidential. Broséus J, Gentile N, Bonadio Pont F, Garcia Gongora JM, Forensic Sci Int 2016; 258: 64-7. Gasté L, Esseiva P. Qualitative, quantitative and temporal study of cutting Jing S-J, Li Q-L, Jiang Y. agents for cocaine and over 9 years. A new simultaneous derivatization and microextration Forensic Sci Int 2015; 257: 307-13. method for the determination of hydrochloride in human plasma. Choe S, Lee J, Choi H, Park Y, Lee H, Jo J, Park Y, Kim E, J Chromatogr B Biomed Sci Appl 2016; 1008: 26-31. Pyo J, Lee HJ, Kim S. Estimation of the synthetic routes of seized meth- Johnson-Davis KL, Sadler AJ, Genzen JR. using GC-MS and multivariate analysis. A retrospective analysis of urine drugs of abuse Forensic Sci Int 2015; online early: immunoassay true positive rates at a national reference doi: 10.1016/j.forsciint.2015.12.018: laboratory. J Anal Toxicol 2015; online early: doi: 10.1093/jat/bkv133: Choi H, Kim S, Ahn S, Chang H, Lee S, Lee Y. Development of an analytical method for simultaneous Kim K-Y, Cho S-H, Song Y-H, Nam M-S, Kim C-W. detection of psychotropic phenylalkylamines in hair by LC- Direct injection LCMS/MS method for the determination MS/MS with a multi-mode reversed-phase column using of teicoplanin in human plasma. pH gradient elution. J Chromatogr B Biomed Sci Appl 2016; 1008: 125-31. Forensic Sci Int 2015; online early: doi: 10.1016/j.forsciint.2015.12.016: Lan X, Mingdao L, Huilin G, Wei G, Lvjiang H, Yan Z, Gang L.

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Simultaneous determination of 2',3'-dideoxyinosine and the Slawson MH, Johnson-Davis KL. active metabolite, 2',3'-dideoxyadenosine-5'-triphosphate in Quantitation of , fluphenazine, perphenazine, and human peripheral-blood mononuclear cell by HPLC-MS/MS thiothixene in serum or plasma using liquid chromatography- and the application to cell pharmacokinetics. tandem mass spectrometry (LC-MS/MS). J Chromatogr B Biomed Sci Appl 2015; 1002: 337-42. Methods Mol Biol 2016; 1383: 49-57.

Leung KW, Wong ZCF, Ho JYM, Yip AWS, Ng JSC, Ip SPH, Stone J. Ng WYY, Ho KKL, Duan R, Zhu KY, Tsim KWK. Broad-spectrum drug screening using liquid chromatography- Determination of hair cut-off value from Hong hybrid triple-quadrupole linear ion trap mass spectrometry. Kong ketamine users by LC-MS/MS analysis. Methods Mol Biol 2016; 1383: 133-51. Forensic Sci Int 2016; 259: 53-8. Vikingsson S, Strömqvist M, Svedberg A, Hansson J, Li Y, Li Y, Liang N, Yang F, Kuang Z. Höiom V, Gréen H. A reversed-phase high performance liquid chromatography Novel rapid liquid chromatography tandem masspectrometry method for quantification of methotrexate in cancer method for vemurafenib and metabolites in human plasma, patients serum. including metabolite concentrations at steady-state. J Chromatogr B Biomed Sci Appl 2015; 1002: 107-12. Biomed Chromatogr 2015; online early: doi: 10.1002/bmc.3672: Lin A, Su X, She D, Qiu K, He Q, Liu Y.

LCMS/MS determination and comparative pharmaco- Wang J-W, Chiang M-H, Lu C-M, Tsai T-H. kinetics of strychnine, brucine and their metabolites in rat Determination the active compounds of herbal preparation plasma after intragastric administration of each monomer by UHPLC-MS/MS and its application on the preclinical and the total alkaloids from Semen Strychni. pharmacokinetics of pure ephedrine, single herbal extract J Chromatogr B Biomed Sci Appl 2016; 1008: 65-73. of Ephedra, and a multiple herbal preparation in rats.

J Chromatogr B Biomed Sci Appl 2015; online early: doi: Marin SJ, McMillin GA. 10.1016/j.jchromb.2015.12.027: Quantitation of buprenorphine, norbuprenorphine, bu- prenorphine glucuronide, norbuprenorphine glucuronide, and naloxone in urine by LC-MS/MS. Wu AH, Colby J. Methods Mol Biol 2016; 1383: 69-78. High-resolution mass spectrometry for untargeted drug screening. Meng M, Smith B, Johnston B, Carter S, Brisson J, Roth SE. Methods Mol Biol 2016; 1383: 153-66. Simultaneous quantitation of delamanid (OPC-67683) and its eight metabolites in human plasma using UHPLCMS/MS. Yang X, Poddar I, Hernandez CM, Terry AV, Jr., Bartlett MG. J Chromatogr B Biomed Sci Appl 2015; 1002: 78-91. Simultaneous quantitation of quetiapine and its active metabolite norquetiapine in rat plasma and brain tissue by Niec D, Kunicki PK. high performance liquid chromatography/electrospray Validation of an assay for quantification of free ionization tandem mass spectrometry (LC-MS/MS). normetanephrine, metanephrine and methoxytyramine in J Chromatogr B Biomed Sci Appl 2015; 1002: 71-7. plasma by high performance liquid chromatography with coulometric detection: comparison of peak-area vs. peak- Youn S-C, Chen L-Y, Chiou R-J, Lai T-J, Liao W-C, Mai F-D, height measurements. Chang H-M. J Chromatogr B Biomed Sci Appl 2015; 1002: 63-70. Comprehensive application of time-of-flight secondary ion mass spectrometry (TOF-SIMS) for ionic imaging and bio- Poklis JL, Wolf CE, Nanco CR, Poklis A. energetic analysis of club drug-induced cognitive deficiency. Recommendations for specimen collection for NBOMe Sci Rep 2015; 5: 18420. analysis in clinical toxicology. Clin Toxicol 2015; online early: Zhang X, Hou H, Chen H, Liu Y, Wang A, Hu Q. doi: 10.3109/15563650.2015.1118489: A column-switching LCMS/MS method for simultaneous quantification of biomarkers for 1,3-butadiene exposure Ramoo B, Funke M, Frazee C, Garg U. and oxidative damage in human urine. Comprehensive urine drug screen by gas chromatography/ J Chromatogr B Biomed Sci Appl 2015; 1002: 123-9. mass spectrometry (GC/MS). Methods Mol Biol 2016; 1383: 125-31. Biomarkers

Scanlon KA, Stoppacher R, Blum LM, Starkey SJ. Ahn JY, Lee MJ, Seo JS, Choi D, Park JB. Comprehensive duloxetine analysis in a fatal overdose. Plasma neutrophil gelatinase-associated lipocalin as a J Anal Toxicol 2015; online early: predictive biomarker for the detection of acute kidney doi: 10.1093/jat/bkv134: injury in adult poisoning. Clin Toxicol 2015; online early: Schofield RC, Ramanathan LV, Murata K, Fleisher M, doi: 10.3109/15563650.2015.1118487: Pessin MS, Carlow DC. Development of an assay for methotrexate and its Borghini A, Gianicolo EA, Andreassi MG. metabolites 7-hydroxy methotrexate and DAMPA in serum Usefulness of biomarkers as intermediate endpoints in by LC-MS/MS. health risks posed by occupational lead exposure. Methods Mol Biol 2016; 1383: 213-22. Int J Occup Med Environ Health 2016; 29: 167-78.

Slawson MH, Johnson-Davis KL. Brown K, Phillips M, Grulke C, Yoon M, Young B, Quantitation of flecainide, mexiletine, propafenone, and McDougall R, Leonard J, Lu J, Lefew W, Tan Y-M. amiodarone in serum or plasma using liquid chromatography- Reconstructing exposures from biomarkers using exposure- tandem mass spectrometry (LC-MS/MS). pharmacokinetic modeling  A case study with carbaryl. Methods Mol Biol 2016; 1383: 11-9. Regul Toxicol Pharmacol 2015; 73: 689-98.

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Dabass A, Talbott EO, Venkat A, Rager J, Marsh GM, Di Paolo M, Aimo A, Barison A, Aquaro GD, Roas L, Emdin M. Sharma RK, Holguin F. The heart after idarubicin overdose. Cardiac death in a

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Senthilkumaran S, Ananth C, Menezes RG, Suicide Thirumalaikolundusubramanian P. Dura H, Morar S, Cipaian CR. Aluminium phosphide poisoning: need for revised Chemical suicide by inhalation of hydrogen sulfide in Sibiu treatment guidelines. County, Romania. Case report and literature review. Indian J Anaesth 2015; 59: 831-2. Rom J Legal Med 2015; 23: 289-92. Venkatesh C, Srinivasan S. Elling R, Spehl MS, Wohlfarth A, Auwaerter V, Hermanns- Snake bite: emulating the Indian model might help save Clausen M. thousands of lives. Prolonged hypoglycemia after a suicidal ingestion of Br Med J 2015; 351: h6276. repaglinide with unexpected slow plasma elimination. Clin Toxicol 2015; online early: Webb TE, Marshall DC. doi: 10.3109/15563650.2015.1122793: Immobilised UGT1A9 may be used to treat paracetamol overdose. Gerace E, Salomone A, Di Corcia D, Mazzucco P, Vincenti M. Med Hypotheses 2015; 85: 1040. Postmortem redistribution of triazolam, alprazolam, delorazepam (chlordesmethyldiazepam) and zolpidem in a Yaraghi A, Mood NE, Dolatabadi LK. suicide case. Comparison of capillary and venous blood glucose levels Toxicol Anal Clin 2015; 27: 233-8. using glucometer and laboratory blood glucose level in poisoned patients being in coma. Kim J, Kim M, Kim Y-R, Choi KH, Lee K-U. Adv Biomed Res 2015; 4: 247. High prevalence of psychotropics overdose among suicide attempters in Korea. Zazzeron L, Liu C, Franco W, Nakagawa A, Farinelli WA, Clin Psychopharmacol Neurosci 2015; 13: 302-7. Bloch DB, Anderson RR, Zapol WM. Pulmonary phototherapy for treating carbon monoxide Skopp G, Gutmann I, Schwarz C-S, Schmitt G. poisoning. An unnatural death by propan-1-ol and propan-2-ol. Am J Respir Crit Care Med 2015; 192: 1191-9. Int J Legal Med 2015; online early: doi: 10.1007/s00414- 015-1302-3: Antidotes Connors JM. MANAGEMENT Antidote for factor Xa anticoagulants. N Engl J Med 2015; 373: 2471-2. General D'sa SR, Peter JV, Chacko B, Pichamuthu K, Sathyendra S. Yip SW, Chan YC. Intra-aortic balloon pump (IABP) rescue therapy for Antidotes for patients taking novel oral anti-coagulants. refractory cardiogenic shock due to scorpion sting World J Emerg Med 2015; 6: 311-2. envenomation. Clin Toxicol 2015; online early: Acetylcysteine doi: 10.3109/15563650.2015.1116043: Bateman DN, Dear JW, Thomas SHL. New regimens for intravenous acetylcysteine, where are Erdmann A, Werner D, Hugli O, Yersin B. we now? Focused use of drug screening in overdose patients Clin Toxicol 2015; online early: increases impact on management. doi: 10.3109/15563650.2015.1121545: Swiss Med Wkly 2015; 145: w14242. Isbister GK, Downes MA, McNamara K, Berling I, Whyte Kim H-C, Jang T-W, Chae H-J, Choi W-J, Ha M-N, Ye B-J, IM, Page CB. Kim B-G, Jeon M-J, Kim S-Y, Hong Y-S. A prospective observational study of a novel 2-phase Evaluation and management of lead exposure. infusion protocol for the administration of acetylcysteine in Ann Occup Environ Med 2015; 27: 30. paracetamol poisoning. Clin Toxicol 2015; online early: Leão SC, de Araújo JF, Silveira AR, Queiroz AAF, Souto doi: 10.3109/15563650.2015.1115057: MJS, Almeida RO, Maciel DC, de Andrade Rodrigues TM. Management of exogenous intoxication by carbamates Khayyat A, Tobwala S, Hart M, Ercal N. and organophosphates at an emergency unit. N-acetylcysteine amide, a promising antidote for ac- AMB Rev Assoc Med Bras 2015; 61: 440-5. etaminophen toxicity.

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Toxicol Lett 2016; 241: 133-42. Silibinin Lacombe G, St-Onge M. Activated charcoal BET 1: Silibinin in suspected amatoxin-containing mushroom Ponampalam R. poisoning. Effectiveness of multiple-dose activated charcoal in Emerg Med J 2016; 33: 76-7. digoxin overdose: a case report. Toxicol Lett 2015; 238: S141. Alpha-2 agonists Leong C, Rachwalski E, Lizza B, Cooper C. Antivenom Retrospective comparison of -2 agonists for alcohol Miller M, O'Leary MA, Isbister GK. withdrawal in the MICU. Towards rationalisation of antivenom use in funnel-web Crit Care Med 2015; 43: 138. spider envenoming: enzyme immunoassays for venom concentrations. Extracorporeal treatments Clin Toxicol 2015; online early: Haemofiltration doi: 10.3109/15563650.2015.1122794: Suarez-de-la-Rica A, Hernández-Gancedo C, López-Tofiño

A, Maseda E, Gilsanz F. Severe cefepime-induced status epilepticus treated with Barbier L, Canini F, Giroud C, Beaup C, Foquin A, Maury R, haemofiltration. Denis J, Peinnequin A, Dorandeu F. Rev Esp Anestesiol Reanim 2015; online early: doi: Beneficial effects of a ketamine/atropine combination in 10.1016/j.redar.2015.08.005: soman-poisoned rats under a neutral thermal environment. Neurotoxicology 2015; 50: 10-9. Herbal medicines

Ferraz MC, de Oliveira JL, de Oliveira Junior JR, Cogo JC, Fomepizole Dos Santos MG, Franco LM, Puebla P, Ferraz HO, Ferraz Maskell KF, Beckett S, Cumpston KL. HG, da Rocha MM, Hyslop S, San FA, Oshima-Franco Y. Methanol kinetics in chronic kidney disease after The triterpenoid betulin protects against the neuromuscular fomepizole: a case report. effects of Bothrops jararacussu snake venom in vivo. Am J Ther 2015; online early: Evid Based Complement Altern Med 2015; 2015: 939523. doi: 10.1097/MJT.0000000000000394: Wang L, Pan S. Hyperbaric oxygen therapy Adjuvant treatment with crude rhubarb for patients with acute organophosphorus pesticide poisoning: a meta- Akcilar R, Akcilar A, Simsek H, Koçak FE, Koçak C, Yümün analysis of randomized controlled trials. G, Bayat Z. Complement Ther Med 2015; 23: 794-801. Hyperbaric oxygen treatment ameliorates lung injury in paraquat intoxicated rats. Int J Clin Exp Pathol 2015; 8: 13034-42. Ketamine Barbier L, Canini F, Giroud C, Beaup C, Foquin A, Maury R, Idarucizumab Denis J, Peinnequin A, Dorandeu F. Beneficial effects of a ketamine/atropine combination in Eikelboom JW, Quinlan DJ, Van Ryn J, Weitz JI. soman-poisoned rats under a neutral thermal environment. Idarucizumab: the antidote for reversal of dabigatran. Neurotoxicology 2015; 50: 10-9. Circulation 2015; 132: 2412-22.

Opioid maintenance therapy Lipid emulsion therapy Procopio G, Gupta A, Hernandez M, Charles P, Patel R. Methadone Lipid emulsion for inadvertent intrathecal administration of Cousins G, Boland F, Courtney B, Barry J, Lyons S, Fahey T. local anesthetics in the ED. Risk of mortality on and off methadone substitution Crit Care Med 2015; 43: 309. treatment in primary care: a national cohort study. Addiction 2016; 111: 73-82. Tse J, Ferguson K, Whitlow KS, Erickson K. The use of intravenous lipid emulsion therapy in acute Buprenorphine methamphetamine toxicity. Berger E. Am J Emerg Med 2015; online early: National institutes of health study shows benefit of doi: 10.1016/j.ajem.2015.12.055: emergency department use of buprenorphine in opiate withdrawal. Oximes Ann Emerg Med 2015; 66: A20-A22. Antonijevic E, Musilek K, Kuca K, Djukic-Cosic D, Curcic M, Brkic D, Antonijevic B. Naloxone Ability of oxime K027 to reactivate brain AChE in rats Anon. acutely poisoned by a direct acetylcholinesterase inhibitor. Naloxone (Narcan) nasal spray for opioid overdose. Toxicol Lett 2015; 238: S339-S340. Med Lett Drugs Ther 2016; 58: 1-2.

Chambers JE, Meek EC, Bennett JP, Bennett WS, Beheshti A, Lucas L, Dunz T, Haydash M, Chiodi H, Chambers HW, Leach CA, Pringle RB, Wills RW. Edmiston B, Ford C, Bohn N, Stein JH, Berrett A, Sobota B, Novel substituted phenoxyalkyl pyridinium oximes Horzempa J. enhance survival and attenuate seizure-like behavior of An evaluation of naloxone use for opioid overdoses in rats receiving lethal levels of nerve agent surrogates. West Virginia: a literature review. Toxicology 2016; 339: 51-7. Am Med J 2015; 6: 9-13.

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Bird SM, McAuley A, Perry S, Hunter C. Focused use of drug screening in overdose patients Effectiveness of Scotland's national naloxone programme increases impact on management. for reducing opioid-related deaths: a before (2006-10) Swiss Med Wkly 2015; 145: w14242. versus after (2011-13) comparison. Addiction 2015; online early: doi: 10.1111/add.13265: Gómez-Lechón MJ, Tolosa L, Donato MT. Metabolic activation and drug-induced liver injury: in vitro Frank JW, Levy C, Calcaterra SL, Hoppe JA, Binswanger IA. approaches for the safety risk assessment of new drugs. Naloxone administration in US emergency departments, J Appl Toxicol 2015; online early: doi: 10.1002/jat.3277: 20002011. J Med Toxicol 2015; online early: doi: 10.1007/s13181- Kristoffersen L, Strand DH, Liane VH, Vindenes V, Tvete 015-0525-5: IF, Aldrin M. Determination of safety margins for whole blood Pamidronate concentrations of alcohol and nineteen drugs in driving under the influence cases. Kara C, Çetinkaya S, Gündüz S, Can Yilmaz G, Aycan Z, Ayd NM. Forensic Sci Int 2015; online early: Efficacy and safety of pamidronate in children with vitamin doi: 10.1016/j.forsciint.2015.12.009: D intoxication. Pediatr Int 2015; online early: doi: 10.1111/ped.12875: Lee HJ, Shin JH, Lee SJ, Shin S. Clinical characteristics of drug intoxicated patients who present to emergency department with acute altered Polymyxin B mental status. Garcia J, Costa VM, Carvalho ATP, Silvestre R, Duarte JA, Toxicol Lett 2015; 238: S154-S155. Dourado DFAR, Arbo MD, Baltazar T, Dinis-Oliveira RJ, Baptista P, de Lourdes Bastos M, Carvalho F. Lev R, Petro S, Lucas J, Stuck A, Vilke GM, Castillo EM. A breakthrough on Amanita phalloides poisoning: an A description of medical examiner prescription related effective antidotal effect by polymyxin B. deaths and prescription drug monitoring program data. Arch Toxicol 2015; 89: 2305-23. Am J Emerg Med 2015; online early: doi: 10.1016/j.ajem.2015.12.023: Myhrer T, Mariussen E, Enger S, Aas P. Loke YK. Supralethal poisoning by any of the classical nerve agents The thorough QT study - Do we need more of the same? is effectively counteracted by procyclidine regimens in Br J Clin Pharmacol 2015; online early: rats. doi: 10.1111/bcp.12871: Neurotoxicology 2015; 50: 142-8. Phillips EJ. Prothrombin complex concentrates Classifying ADRs – Does dose matter? Berndtson AE, Huang W-T, Box K, Kobayashi L, Godat LN, Br J Clin Pharmacol 2016; 81: 10-2. Smith AM, Weingarten D, Coimbra R. A new kid on the block: outcomes with Kcentra 1 year Roberts R, Callander R, Duffy P, Jacobsen M, Knight R, after approval. Boobis A. J Trauma Acute Care Surg 2015; 79: 1004-8. Target organ profiles in toxicity studies supporting human dosing: does severity progress with longer duration of Wang Y, Kotik V, Fahim G, Alagusundaramoorthy S, exposure? Eltawansy SA, Mathis S, Saleh J. Regul Toxicol Pharmacol 2015; 73: 737-46. Treatment of brodifacoum overdose with prothrombin complex concentrate. Salcido DD, Torres C, Koller AC, Orkin AM, Schmicker RH, Am J Health Syst Pharm 2016; 73: e14-e17. Morrison LJ, Nichol G, Stephens S, Menegazzi JJ. Regional incidence and outcome of out-of-hospital cardiac arrest associated with overdose. DRUGS Resuscitation 2015; online early: General doi: 10.1016/j.resuscitation.2015.11.010: Barratt MJ, Ezard N. Drug checking interventions can track the nature and size Slawson MH, Johnson-Davis KL. of the discrepancy between self-report and actual drugs Quantitation of haloperidol, fluphenazine, perphenazine, consumed. and thiothixene in serum or plasma using liquid chro- Addiction 2015; online early: doi: 10.1111/add.13194: matography-tandem mass spectrometry (LC-MS/MS). Methods Mol Biol 2016; 1383: 49-57. Basaran AA. Reported target organ toxicity of doping substances: Slawson MH, Johnson-Davis KL. animal studies and human case reports. Quantitation of flecainide, mexiletine, propafenone, and Toxicol Lett 2015; 238: S43. amiodarone in serum or plasma using liquid chro- matography-tandem mass spectrometry (LC-MS/MS). Carasco CF, Fletcher P, Maconochie I. Methods Mol Biol 2016; 1383: 11-9. Review of commonly used age based weight estimates for paediatric drug dosing in relation to the pharmacokinetic Wang X, Drummer OH. properties of resuscitation drugs. Review: Interpretation of drug presence in the hair of Br J Clin Pharmacol 2015; online early: children. doi: 10.1111/bcp.12876: Forensic Sci Int 2015; 257: 458-72.

Erdmann A, Werner D, Hugli O, Yersin B. Acetaminophen (see paracetamol)

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Aconitine The use of intravenous lipid emulsion therapy in acute Chen X, Wu R, Jin H, Gao R, Yang B, Wang Q. methamphetamine toxicity. Successful rescue of a patient with acute aconitine Am J Emerg Med 2015; online early: poisoning complicated by polycystic renal hemorrhage. doi: 10.1016/j.ajem.2015.12.055:

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TT, Nguyen TNN, de Wit J. Adrenaline -type stimulant use among men who have Niec D, Kunicki PK. sex with men (MSM) in Vietnam: results from a socio- Validation of an assay for quantification of free ecological, community-based study. normetanephrine, metanephrine and methoxytyramine in Drug Alcohol Depend 2015; online early: plasma by high performance liquid chromatography with doi: 10.1016/j.drugalcdep.2015.11.016: coulometric detection: comparison of peak-area vs. peak- height measurements. Wang L, Qu G, Dong X, Huang K, Kumar M, Ji L, Wang Y, J Chromatogr B Biomed Sci Appl 2015; 1002: 63-70. Yao J, Yang S, Wu R, Zhang H. Long-term effects of methamphetamine exposure in Alkyl nitrites (Poppers) adolescent mice on the future ovarian reserve in adulthood. Zhang H, Teng T, Lu H, Zhao Y, Liu H, Yin L, Sun Z, He X, Toxicol Lett 2016; 242: 1-8. Qian H-Z, Ruan Y, Shao Y, Vermund SH. Poppers use and risky sexual behaviors among men who Anaesthetics have sex with men in Beijing, China. Liu SS, Ortolan S, Sandoval MV, Curren J, Fields KG, Drug Alcohol Depend 2015; online early: Memtsoudis SG, YaDeau JT. doi: 10.1016/j.drugalcdep.2015.11.037: Cardiac arrest and seizures caused by local anesthetic systemic toxicity after peripheral nerve blocks: should we Amfetamines and MDMA (ecstasy) still fear the reaper? Choe S, Lee J, Choi H, Park Y, Lee H, Jo J, Park Y, Kim E, Reg Anesth Pain Med 2015; online early: Pyo J, Lee HJ, Kim S. doi: 10.1097/AAP.0000000000000329: Estimation of the synthetic routes of seized metham- phetamines using GC-MS and multivariate analysis. Molina Aragonés JM, Ayora Ayora A, Ribalta AB, Gascó Aparici Forensic Sci Int 2015; online early: A, Medina Lavela JA, Sol Vidiella J, Herreros López M. doi: 10.1016/j.forsciint.2015.12.018: Occupational exposure to volatile anaesthetics: a systematic review. Occup Med (Oxf) 2015; online early: Fujikawa DG, Pais ES, Aviles Jr ER, Hsieh K-C, Bashir MT. doi: 10.1093/occmed/kqv193: Methamphetamine-induced neuronal necrosis: the role of electrographic seizure discharges. Procopio G, Gupta A, Hernandez M, Charles P, Patel R. Neurotoxicology 2016; 52: 84-8. Lipid emulsion for inadvertent intrathecal administration of

local anesthetics in the ED. Hill V, Stowe N, Schaffer M. Crit Care Med 2015; 43: 309. Comments on 'Ethnic hair care products may increase false positives in hair drug testing' by Kidwell et al. Forensic Sci Int 2015; online early: Antiandrogens doi: 10.1016/j.forsciint.2015.11.008: Abiraterone Moore DC, Moore A. Kidwell DA, Smith FP, Shepherd AR. Abiraterone-induced rhabdomyolysis: a case report. Ethnic hair care products may increase false positives in J Oncol Pharm Pract 2015; online early: hair drug testing. doi: 10.1177/1078155215620921: Forensic Sci Int 2015; 257: 160-4. Antibiotics Nielsen KL, Telving R, Andreasen MF, Hasselstrøm JB, Ferrer P, Amelio J, Ballarín E, Sabaté M, Vidal X, Johannsen M. Rottenkolber M, Schmiedl S, Laporte J-R, Ibáñez L, The A metabolomics study of retrospective forensic data from PROTECT Work Package. whole blood samples of humans exposed to 3,4-methylene- Systematic review and meta-analysis: macrolides and dioxymethamphetamine (MDMA) – A new approach for amoxicillin/clavulanate-induced acute liver injury. identifying drug metabolites and changes in metabolism Basic Clin Pharmacol Toxicol 2015; online early: doi: related to drug consumption. 10.1111/bcpt.12550: J Proteome Res 2015; online early: doi: 10.1021/acs.jproteome.5b01023: Cefepime Paratz ED, Cunningham NJ, MacIsaac AI. Suarez-de-la-Rica A, Hernández-Gancedo C, López-Tofiño The cardiac complications of methamphetamines. A, Maseda E, Gilsanz F. Heart Lung Circ 2015; online early: Severe cefepime-induced status epilepticus treated with doi: 10.1016/j.hlc.2015.10.019: haemofiltration. Rev Esp Anestesiol Reanim 2015; online early: doi: Sliman S, Waalen J, Shaw D. 10.1016/j.redar.2015.08.005: Methamphetamine-associated congestive heart failure: increasing prevalence and relationship of clinical outcomes Ciprofloxacin to continued use or abstinence. Oldenkamp R, Huijbregts MAJ, Ragas AMJ. Cardiovasc Toxicol 2015; online early: Uncertainty and variability in human exposure limits  A doi: 10.1007/s12012-015-9350-y: chemical-specific approach for ciprofloxacin and metho- trexate. Tse J, Ferguson K, Whitlow KS, Erickson K. Crit Rev Toxicol 2015; online early:

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doi: 10.3109/10408444.2015.1112768: Prothrombin complex concentrate vs. freshfrozen plasma in warfarin-associated ICH. Metronidazole Crit Care Med 2015; 43: 122. Haridas A, Trivedi TH, Moulick ND, Joshi AR. Metronidazole-induced encephalopathy in chronic diarrhoea. Romley JA, Gong C, Jena AB, Goldman DP, Williams B, J Assoc Physicians India 2015; 63: 77-9. Peters A. Association between use of warfarin with common Teicoplanin sulfonylureas and serious hypoglycemic events: retrospective Kim K-Y, Cho S-H, Song Y-H, Nam M-S, Kim C-W. cohort analysis. Direct injection LCMS/MS method for the determination Br Med J 2015; 351: h6223. of teicoplanin in human plasma. J Chromatogr B Biomed Sci Appl 2016; 1008: 125-31. Anticonvulsants

Lamotrigine Anticoagulants Gastrup S, Stage TB, Fruekilde PBN, Damkier P. Cohen D. Paracetamol decreases steady-state exposure to lamotrigine Data on trial of anticoagulant is to be reanalyzed after by induction of glucuronidation in healthy subjects. discovery that investigators used faulty device. Br J Clin Pharmacol 2015; online early: Br Med J 2015; 351: h6431. doi: 10.1111/bcp.12840:

Connors JM. Antidote for factor Xa anticoagulants. Hajiali F, Nassiri-Asl M. N Engl J Med 2015; 373: 2471-2. Report of severe menorrhagia following the maximum amount of lamotrigine overdose. Sholzberg M, Pavenski K, Shehata N, Cserti-Gazdewich C, Iran J Pharm Res 2015; 14: 1289-93. Lin Y. Bleeding complications from the direct oral anticoagulants. Pregabalin BMC Hematology 2015; 15: 18. Puolakka T, Vuorialho M, Väänänen P, Honkaniemi J.

Cervical myelopathy associated with deep neck muscle Yip SW, Chan YC. rhabdomyolysis after buprenorphine and pregabaline Antidotes for patients taking novel oral anti-coagulants. abuse. World J Emerg Med 2015; 6: 311-2. J Neurol Sci 2015; 357: e41.

Dabigatran Eikelboom JW, Quinlan DJ, Van Ryn J, Weitz JI. Valproate Idarucizumab: the antidote for reversal of dabigatran. Juliandi B, Tanemura K, Igarashi K, Tominaga T, Circulation 2015; 132: 2412-22. Furukawa Y, Otsuka M, Moriyama N, Ikegami D, Abematsu M, Sanosaka T, Tsujimura K, Narita M, Kanno J, Vlad I, Armstrong J, Ridgley J, Pascu O. Nakashima K. Dabigatran deliberate overdose: two cases and suggestions Reduced adult hippocampal neurogenesis and cognitive for laboratory monitoring. impairments following prenatal treatment of the antiepileptic Clin Toxicol 2016; online early: drug valproic acid. doi: 10.3109/15563650.2015.1126287: Stem Cell Reports 2015; 5: 996-1009.

Rivaroxaban Antidepressants Vernon HM, O'Bryan EC, Nielsen AK. Armitage MC, Woolfield KI, Page CB. Hypersensitivity reaction after administration of rivaroxaban Serotonin toxicity caused by the interaction of fentanyl (Xarelto). and serotonergic medications. Am J Emerg Med 2015; online early: Emerg Med Australas 2015; online early: doi: 10.1016/j.ajem.2015.12.021: doi: 10.1111/1742-6723.12521:

Warfarin Borg L, Julkunen A, Madsen KR, Strøm T, Toft P. Al-Majzoub O, Rybak E, Reardon DP, Krause P, Connors JM. Antidepressant or antipsychotic overdose in the intensive Evaluation of warfarin reversal with 4-factor prothrombin care unit – Identification of patients at risk. complex concentrate compared to 3-factor prothrombin Basic Clin Pharmacol Toxicol 2015; online early: complex concentrate at a tertiary academic medical center. doi: 10.1111/bcpt.12541: J Emerg Med 2016; 50: 7-13.

Berndtson AE, Huang W-T, Box K, Kobayashi L, Godat LN, Tianeptine Smith AM, Weingarten D, Coimbra R. Bence C, Bonord A, Rebillard C, Vaast P, Alexandre C, A new kid on the block: outcomes with Kcentra 1 year Jardri R, Rolland B. after approval. Neonatal abstinence syndrome following tianeptine J Trauma Acute Care Surg 2015; 79: 1004-8. dependence during pregnancy. Pediatrics 2015; online early: doi: 10.1542/peds.2015-1414: Heffler E, Campisi R, Ferri S, Crimi N. A bloody mess: an unusual case of diffuse alveolar hemorrhage because of warfarin overdose. Antifungal drugs Am J Ther 2015; online early: Jadeja D, Jaiswal CS, Panchasra A, Tripathi CB. doi: 10.1097/MJT.0000000000000397: Griseofulvin and/or terbinafine induced toxic epidermal necrolysis in an adult female patient – A case report. Hite M, Silinskie K. Curr Drug Saf 2015; online early: PMID:26695069:

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Antineoplastic drugs Olanzapine Capecitabine Johnson JT, Everly AG, Kpakima FEF, Detke HC. Postmortem redistribution of olanzapine following Anon. intramuscular administration of olanzapine pamoate in dogs. Capecitabine: toxic encephalopathy. Forensic Sci Int 2015; 257: 353-8. Prescrire Int 2015; 24: 269.

Epirubicin Quetiapine Yang X, Poddar I, Hernandez CM, Terry AV, Jr., Bartlett MG. Framarino-Dei-Malatesta M, Perrone G, Giancotti A, Simultaneous quantitation of quetiapine and its active Ventriglia F, Derme M, Iannini I, Tibaldi V, Galoppi P, metabolite norquetiapine in rat plasma and brain tissue by Sammartino P, Cascialli G, Brunelli R. high performance liquid chromatography/electrospray Epirubicin: a new entry in the list of fetal cardiotoxic drugs? ionization tandem mass spectrometry (LC-MS/MS). Intrauterine death of one fetus in a twin pregnancy. Case J Chromatogr B Biomed Sci Appl 2015; 1002: 71-7. report and review of literature.

BMC Cancer 2015; 15: 951. Antituberculous drugs Fluorouracil Delamanid Thomas SA, Tomeh N, Theard S. Meng M, Smith B, Johnston B, Carter S, Brisson J, Roth SE. Fluorouracil-induced hyperammonemia in a patient with Simultaneous quantitation of delamanid (OPC-67683) and colorectal cancer. its eight metabolites in human plasma using UHPLCMS/MS. Anticancer Res 2015; 35: 6761-3. J Chromatogr B Biomed Sci Appl 2015; 1002: 78-91.

Idarubicin Antiviral drugs Di Paolo M, Aimo A, Barison A, Aquaro GD, Roas L, Emdin M. Didanosine The heart after idarubicin overdose. Cardiac death in a Lan X, Mingdao L, Huilin G, Wei G, Lvjiang H, Yan Z, Gang L. patient with acute promyelocitic leukaemia. Simultaneous determination of 2',3'-dideoxyinosine and the Int J Cardiol 2016; 203: 997-9. active metabolite, 2',3'-dideoxyadenosine-5'-triphosphate in human peripheral-blood mononuclear cell by HPLC-MS/MS Methotrexate and the application to cell pharmacokinetics. Li Y, Li Y, Liang N, Yang F, Kuang Z. J Chromatogr B Biomed Sci Appl 2015; 1002: 337-42. A reversed-phase high performance liquid chromatography method for quantification of methotrexate in cancer Baclofen patients serum. Charifou Y, Martinet O, Jabot J, Gauzere BA, Allyn J, J Chromatogr B Biomed Sci Appl 2015; 1002: 107-12. Vandroux D. Baclofen intoxication cases in an intensive care unit. Oldenkamp R, Huijbregts MAJ, Ragas AMJ. Anaesth Crit Care Pain Med 2015; online early: doi: Uncertainty and variability in human exposure limits  A 10.1016/j.accpm.2015.10.003: chemical-specific approach for ciprofloxacin and metho- trexate. Benzodiazepines Crit Rev Toxicol 2015; online early: Gerace E, Salomone A, Di Corcia D, Mazzucco P, Vincenti M. doi: 10.3109/10408444.2015.1112768: Postmortem redistribution of triazolam, alprazolam,

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Sauvaigo S, Sarrazy F, Batal M, Caillat S, Pitiot B, Mouret Colchicum autumnale (Autumn crocus) S, Cléry-Barraud C, Boudry I, Douki T. Kyan R, Uemura S, Tanno K, Sawamoto K, Harada K, Impact of topical application of sulfur mustard on mice Sakawaki E, Fujita Y, Endo S, Narimatsu E. skin and distant organs DNA repair enzyme signature. Severe accidental colchicine poisoning by the autumn Toxicol Lett 2016; 241: 71-81. crocus: a case of successful treatment. J Acute Med 2015; 5: 103-6. Shoeibi N, Balali-Mood M, Abrishami M. Sulfur mustard exposure and non-ischemic central retinal vein occlusion. Lagenaria siceraria (Bottle gourd) Iran J Med Sci 2016; 41: 59-63. Verma A, Jaiswal S. Bottle gourd (Lagenaria siceraria) juice poisoning. Riot control agents World J Emerg Med 2015; 6: 308-9.

Yeung MF, Tang WYM. Clinicopathological effects of pepper (oleoresin capsicum) Mitragyna speciosa (Kratom) spray. Cinosi E, Martinotti G, Simonato P, Singh D, Demetrovics Hong Kong Med J 2015; 21: 542-52. Z, Roman-Urrestarazu A, Bersani FS, Vicknasingam B, Piazzon G, Li J-H, Yu W-J, Kapitány-Fövény M, Farkas J, di Nerve agents Giannantonio M, Corazza O. Following "the roots" of Kratom (Mitragyna speciosa): the Chambers JE, Meek EC, Bennett JP, Bennett WS, evolution of an enhancer from a traditional use to increase Chambers HW, Leach CA, Pringle RB, Wills RW. work and productivity in Southeast Asia to a recreational Novel substituted phenoxyalkyl pyridinium oximes psychoactive drug in western countries. enhance survival and attenuate seizure-like behavior of BioMed Res Int 2015; 2015: 968786. rats receiving lethal levels of nerve agent surrogates.

Toxicology 2016; 339: 51-7. Mushrooms Myhrer T, Mariussen E, Enger S, Aas P. Seki T. Supralethal poisoning by any of the classical nerve agents is Tincu RC, Macovei RA, Ghiorghiu Z, Cobilinschi C. effectively counteracted by procyclidine regimens in rats. Stevens-Johnson-TEN overlap syndrome induced by Neurotoxicology 2015; 50: 142-8. mushroom poisoning. Toxicol Lett 2015; 238: S144. Wright LK, Lee RB, Vincelli NM, Whalley CE, Lumley LA. Comparison of the lethal effects of chemical warfare nerve Amanita mushrooms agents across multiple ages. Garcia J, Costa VM, Carvalho ATP, Silvestre R, Duarte JA, Toxicol Lett 2016; 241: 167-74. Dourado DFAR, Arbo MD, Baltazar T, Dinis-Oliveira RJ, Baptista P, de Lourdes Bastos M, Carvalho F. Soman A breakthrough on Amanita phalloides poisoning: an Barbier L, Canini F, Giroud C, Beaup C, Foquin A, Maury R, effective antidotal effect by polymyxin B. Denis J, Peinnequin A, Dorandeu F. Arch Toxicol 2015; 89: 2305-23. Beneficial effects of a ketamine/atropine combination in soman-poisoned rats under a neutral thermal environment. Lacombe G, St-Onge M. Neurotoxicology 2015; 50: 10-9. BET 1: Silibinin in suspected amatoxin-containing mushroom poisoning. Perkins MW, Wong B, Rodriguez A, Devorak JL, Dao TT, Emerg Med J 2016; 33: 76-7. Leuschner JA, Kan RK, Sciuto AM. Vapor inhalation exposure to soman in conscious Pimpinella anisum (Aniseed) untreated rats: preliminary assessment of neurotoxicity. Inhal Toxicol 2015; online early: Samojlik I, Petkovic S, Stilinovic N, Vukmirovic S, Mijatovic V, Božin B. doi: 10.3109/08958378.2015.1125973: Pharmacokinetic herb-drug interaction between essential oil

of aniseed (Pimpinella Anisum L., Apiaceae) and ac- PLANTS etaminophen and caffeine: a potential risk for clinical Averrhoa carambola (Star fruit) practice. Phytother Res 2015; online early: doi: 10.1002/ptr.5523: Abeysekera RA, Wijetunge S, Nanayakkara N, Wazil AWM,

Ratnatunga NVI, Jayalath T, Medagama A. Star fruit toxicity: a cause of both acute kidney injury and Piper methysticum (Kava) chronic kidney disease: a report of two cases. Kuchta K, Schmidt M, Nahrstedt A. BMC Res Notes 2015; 8: 796. German kava ban lifted by court: the alleged hepatotoxicity of kava (Piper methysticum ) as a case of Barretti P. ill-defined herbal drug identity, lacking quality control, and Star fruit intoxication in chronic kidney disease patients: misguided regulatory politics. from the first clinical description to caramboxin. Planta Med 2015; 81: 1647-53. J Bras Nefrol 2015; 37: 429-30. Rhododendron spp. Camellia sinensis (Tea) Yaylaci S, Ayyildiz O, Aydin E, Osken A, Karahalil F, Varim C, Rivera H, Varon J. Demir MV, Genç AB, Sahinkus S, Can Y, Kocayigit I, Bilir C. Green tea and cardiac arrest: just in case! Is there a difference in mad honey poisoning between Am J Emerg Med 2015; online early: geriatric and non-geriatric patient groups? doi: 10.1016/j.ajem.2015.12.056: Eur Rev Med Pharmacol Sci 2015; 19: 4647-53.

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Salvia divinorum (Diviner's sage) Rägo L, Marroquin AMP, Nübling CM, Sawyer JC. Mahendran R, Lim HA, Tan JY, Chua SM, Winslow M. Treating snake bites–A call for partnership. Salvia divinorum: an overview of the usage, misuse, and Lancet 2015; 386: 2252. addiction processes. Asia Pac Psychiatry 2015; online early: Sahan M, Duru M, Çaliskan K, Karakus A, Özcan O, doi: 10.1111/appy.12225: Kahraman A, Kuvandik G. Snake envenomation to the face of a child - Rare case. Prague Med Rep 2015; 116: 314-20. ANIMALS Arthropods Simões de Oliveira PR, Neto A, González A, Arcia IR. Haddad Junior V, Amorim PC, Haddad Junior WT, Cardoso JL. Poisonous serpentes of Angola. Venomous and poisonous arthropods: identification, Toxicol Lett 2015; 238: S143. clinical manifestations of envenomation, and treatments used in human injuries. Simões de Oliveira PR. Rev Soc Bras Med Trop 2015; 48: 650-7. Epidemiology of snakebites in Angola. Toxicol Lett 2015; 238: S143.

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Snake bites Spiders Gutiérrez JM. Miller M, O'Leary MA, Isbister GK. Understanding and confronting snakebite envenoming: the Towards rationalisation of antivenom use in funnel-web harvest of cooperation. spider envenoming: enzyme immunoassays for venom Toxicon 2016; 109: 51-62. concentrations. Clin Toxicol 2015; online early: Nimorakiotakis V, Winkel KD. doi: 10.3109/15563650.2015.1122794: Prospective assessment of the false positive rate of the Australian Snake Venom Detection Kit in healthy human Yan S, Wang X. samples. Recent advances in research on widow spider venoms and Toxicon 2015; online early: toxins. doi: 10.1016/j.toxicon.2015.12.002: Toxins (Basel) 2015; 7: 5055-67.

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INDEX

1,3-butadiene ...... 34 Chlorpyrifos ...... 42 2,4-D ...... 41 Chromium ...... 39 4-methylanisole ...... 34 Ciprofloxacin ...... 23 Abiraterone ...... 23 Cocaine...... 26 Acetaminophen ...... 30 Codeine ...... 30 Acetylcysteine ...... 20 Colchicum autumnale...... 43 Aconitine ...... 23 Copper ...... 39 Acrolein ...... 34 Cosmetics ...... 35 Activated charcoal ...... 21 Cow dung powder ...... 35 Adrenaline ...... 23 Crotalinae ...... 44 Air pollution ...... 33 Cyadox ...... 26 Alcohol ...... 34 Dabigatran ...... 24 Algae ...... 44 Dasotraline...... 26 Alkyl nitrites ...... 23 Delamanid ...... 25 Alpha-2 agonists ...... 21 Dermal toxicity ...... 11 Aluminium ...... 39 Designer drugs ...... 26 Aluminium phosphide ...... 41 Desomorphine ...... 27 Amanita mushrooms ...... 43 Developmental toxicology ...... 11 Amfetamines ...... 23 Dexmedetomidine...... 32 Anaesthetics ...... 23 DFP ...... 42 Analytical toxicology ...... 8 Diacetylmorphine...... 28 Animals, general ...... 44 Diaveridine ...... 27 Aniseed ...... 43 Diazinon ...... 42 Anthrax ...... 42 Didanosine ...... 25 Antiandrogens ...... 23 Dietary supplements ...... 28 Antibiotics ...... 23 Diethylamine ...... 35 Anticoagulants ...... 24 Digoxin ...... 28 Anticonvulsants ...... 24 Dimethyl fumarate ...... 28 Antidepressants ...... 24 Diquat ...... 42 Antidotes ...... 20 Disinfectants ...... 35 Antifungal drugs ...... 24 Disinfection byproducts ...... 35 Antineoplastic drugs ...... 25 Diviner's sage ...... 44 Antipsychotics ...... 25 Driving under the influence ...... 11 Antiseptics ...... 34 Drugs, general ...... 22 Antituberculous drugs ...... 25 Duloxetine ...... 32 Antivenom ...... 21 Dusts ...... 35 Antiviral drugs ...... 25 E-cigarettes ...... 36 Aristolochic acid ...... 34 Ecstasy ...... 23 Arsenic ...... 39 Epidemiology...... 12 Arthropods ...... 44 Epirubicin ...... 25 Asbestos...... 34 Essential oils ...... 36 Atropine ...... 21 Ethanol ...... 34 Autumn crocus ...... 43 Ethnic remedies ...... 28 Averrhoa carambola ...... 43 Ethylene glycol ...... 36 Baclofen ...... 25 Ethylene glycol methyl ether ...... 36 Benzodiazepines ...... 25 Exhaust fumes ...... 33 Biological warfare...... 42 Extracorporeal treatments ...... 21 Biomarkers ...... 9 Fentanyl...... 30 Bisphenol A ...... 34 Fish/marine poisoning ...... 44 Bottle gourd ...... 43 Flame retardants ...... 36 Brodifacoum ...... 42 Fluorouracil ...... 25 Bromodichloromethane ...... 35 Fomepizole...... 21 Buprenorphine ...... 21, 30 Food colourants ...... 36 Caffeine...... 25 Forensic toxicology ...... 13 Calciferol ...... 33 Formaldehyde ...... 36 Camellia sinensis ...... 43 Gamma hydroxybutyrate ...... 28 Cannabis ...... 26 Gasoline ...... 37 Capecitabine ...... 25 Genotoxicity ...... 14 Carbamate insecticides ...... 41 Glufosinate ...... 41 Carbaryl ...... 41 Glyphosate ...... 41 Carbon monoxide ...... 35 Haemofiltration ...... 21 Carcinogenicity ...... 10 Hazardous waste ...... 33 Cardiotoxicity ...... 10 Hepatotoxicity ...... 14 Cefepime ...... 23 Herbal medicines ...... 21, 28 Ceramide 3 ...... 35 Herbicides ...... 41 Chemical warfare, general ...... 42 Heroin ...... 28 Chemicals, general ...... 34 Hexachloronaphthalene ...... 36 Chlorhexidine ...... 35 Honey ...... 36

46

Hydrazine ...... 36 Paratoluenediamine ...... 37 Hydrogen peroxide ...... 36 Paroxetine...... 32 Hydrogen sulphide ...... 36 Permethrin ...... 42 Hyperbaric oxygen therapy ...... 21 Pesticides and cancer...... 40 Hypnotics ...... 28 Pesticides, general ...... 40 Hypoglycaemics ...... 29 Petrol...... 37 Idarubicin ...... 25 Petroleum coke ...... 37 Idarucizumab ...... 21 Phenethylamines ...... 27 Inhalation toxicity ...... 15 Phenylalkylamines ...... 27 Iron ...... 39 Phthalate esters ...... 37 Isocyanates ...... 36 Pimpinella anisum ...... 43 Kava ...... 28, 43 Piper methysticum ...... 43 Ketamine ...... 21, 29 Piperazines...... 31 Kinetics ...... 15 Pit vipers ...... 44 Kratom ...... 29, 43 Plants, general ...... 43 Krokodil ...... 27 Pollution ...... 33 Lagenaria siceraria ...... 43 Polybrominated diphenyl ethers ...... 37 Lamotrigine ...... 24 Polychlorinated biphenyls ...... 37 Lead...... 39 Polymorphisms ...... 19 Linezolid ...... 29 Polymyxin B ...... 22 Lipid emulsion therapy ...... 21 Poppers ...... 23 Lithium ...... 29, 40 Pregabalin ...... 24 Malathion ...... 42 Procyclidine ...... 22 Management, general ...... 20 Propofol ...... 28 Marijuana ...... 26 Prothrombin complex concentrates ...... 22 Mazindol ...... 29 Psychiatric aspects ...... 19 MDMA ...... 23 Psychotropic drugs ...... 31 Mechanisms ...... 15 Pyrethroid insecticides, general ...... 42 Medication errors ...... 15 Quetiapine ...... 25 Memantine hydrochloride ...... 29 Radiation ...... 37 Mercury ...... 40 Radon ...... 38 Metabolism ...... 15 Ranolazine ...... 31 Metals, general ...... 38 Repaglinide ...... 29 Metformin ...... 29 Reprotoxicity ...... 19 Methadone ...... 21, 30 Rhododendron spp...... 43 Methanol ...... 36 Riot control agents ...... 43 Methotrexate ...... 25 Risk assessment ...... 19 Methyl bromide ...... 36 Rivaroxaban ...... 24 Methyl tertiary butyl ether ...... 37 Rodenticides ...... 42 Methylphenidate ...... 29 Salicylate ...... 31 Metronidazole ...... 24 Salvia divinorum ...... 31, 44 Miglyol 812 ...... 37 Scopolamine ...... 31 Mitragyna speciosa...... 43 Scorpions ...... 44 Monoamine oxidase inhibitors ...... 29 Sedatives ...... 32 Monoclonal antibodies ...... 29 Selenium ...... 40 Mushrooms ...... 43 Sildenafil ...... 32 Mustard gas ...... 42 Silibinin ...... 21 Naloxone ...... 21 Silica gel ...... 38 Nanoparticles ...... 37 Snake bites ...... 44 Nephrotoxicity ...... 15 Sodium lauryl sulfate ...... 38 Nerve agents ...... 43 Solvents ...... 38 Neurotoxicity ...... 16 Soman ...... 43 N-hexane ...... 37 Spiders ...... 44 Nicotine ...... 29 SSRIs and SNRIs ...... 32 Nitrogen mustard ...... 37 Star fruit ...... 43 Nitrous oxide ...... 29, 37 Steroids ...... 32 Occupational toxicology ...... 16 Strychnine ...... 42 Olanzapine ...... 25 Styrene ...... 38 Opioid maintenance therapy ...... 21 Substance abuse ...... 32 Opioids ...... 29 Suicide ...... 20 Opium ...... 30 Sulfonylureas ...... 33 Organochlorine pesticides, general ...... 41 Synthetic cannabinoids ...... 27 Organophosphorus insecticides, general ...... 41 Synthetic cathinones ...... 27 Oxalic acid ...... 37 Tea ...... 43 Oximes ...... 21 Teicoplanin ...... 24 Ozone ...... 37 Tetrabromobisphenol A ...... 38 Paediatric toxicology ...... 18 Tianeptine ...... 24 Pamidronate ...... 22 Tobacco ...... 38 Parabens ...... 37 Toluene ...... 38 Paracetamol ...... 30 Toxicology, general ...... 8 Paraphenylenediamine ...... 37 Tramadol ...... 30 Paraquat ...... 42 Transfluthrin ...... 42

47

Trastuzumab ...... 29 Vitamins...... 33 True vipers ...... 44 Warfarin ...... 24 Turpentine ...... 38 Water ...... 38 Uranium ...... 40 Water pollution ...... 33 Valproate ...... 24 Zinc phosphide ...... 42 Vemurafenib ...... 25 Zolpidem ...... 28 Viperinae ...... 44 Zopiclone ...... 29 Vitamin E ...... 33

Current Awareness in Clinical Toxicology is produced monthly for the American Academy of Clinical Toxicology by the Birmingham Unit of the UK National Poisons Information Service, with contributions from the Cardiff, Edinburgh, and Newcastle Units.

The NPIS is commissioned by Public Health England