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

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

September 2015

CONTENTS

General Toxicology 7 Metals 35 Management 17 Pesticides 37 Drugs 20 Chemical Warfare 39 Chemical Incidents & 30 Plants 40 Pollution Chemicals 31 Animals 40

CURRENT AWARENESS PAPERS OF THE MONTH A descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose Curtis RM, Sivilotti MLA. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1077968: Context Risk prediction following acetaminophen (paracetamol, APAP) overdose is based on serum APAP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. One recently proposed risk stratification tool, the APAPxAT multiplication product, uses either AST or ALT, whichever is higher, yet their interrelation is not well known following APAP- induced hepatic injury. Objective To describe the kinetics of AST and ALT release into and disappearance from the circulation following APAP overdose. Materials and Methods An observational case series of adult patients with peak AST or ALT > 100 IU/L attributable

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

to APAP toxicity. Cases were identified by electronic search of hospital laboratory database and by discharge diagnosis corroborated by structured explicit medical record review. Results Of 68 cases identified (mean age (SD): 39 (18) years, 63% female, and 21% ethanol co- ingested), 28 (41%) developed hepatotoxicity (peak AST or ALT > 1000 IU/L), 28 (41%) coagulopathy (international normalized ratio or INR > 2), and 21 (31%) both. Three patients (4%) were transferred for liver transplantation and ultimately six (8.8%) died. Serum AST and ALT activity rose in a closely aligned 1:1 AST:ALT ratio, but fell at distinctly different rates: AST activity fell with a half-life (interquartile range [IQR]) of 15.1 (12.2, 19.4) hours, and ALT 39.6 (32.9, 47.6) hours. Using an aminotransferase falling to below 50% of peak as the basis for discontinuing acetylcysteine would have resulted in antidotal treatment being stopped 24 (IQR: 9.6, 40) hours earlier (and in no cases later) using AST rather than ALT. Only six patients had an AST:ALT ratio greater than 2:1 at the time of acetylcysteine administration; of these six, four died and one survivor developed coagulopathy. Discussion AST and ALT release into the circulation appears tightly linked and numerically similar, except in the sickest patients. Once the aminotransferases peak, AST returns to baseline more quickly. Conclusion Either AST or ALT can be used for early risk stratification tools when only one is known. Any criterion for N-AC discontinuation should be based on the decline of AST rather than ALT, with a potential benefit measured in days. Full text available from: http://www.tandfonline.com/doi/abs/10.3109/15563650.2015.1077968

Phencyclidine analog use in Sweden–intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project Bäckberg M, Beck O, Helander A. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1079325: Background 3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP ("Angel dust"), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. Study design Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. Patients and methods. Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic–tandem mass spectrometric (LC–MS/MS) and LC–high-resolution MS (LC–HRMS) methods. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records.

Results The Poisons Information Centre registered its first call related to methoxylated PCP analogs in July 2013, while analytically confirmed cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO-PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The 59 patients were aged 14–55 (median: 26) years and 51 (86%) were men. Co-exposure to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%) indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical signs seen in the latter cases were hypertension (systolic blood pressure = 140 mmHg; 7 cases), tachycardia (= 100/min; 5 cases), and altered mental status (4 cases) including confusion, disorientation, dissociation, and/or hallucinations. Mixed-drug users displayed not only the same clinical features, but also more sympathomimetic effects including agitation (38%) and dilated pupils (33%). Patients testing positive for 3-/4-MeO-PCP were typically under medical care for 1–2 days (85%), and 37% of all cases were graded as severe intoxications (Poisoning Severity Score 3). Besides standard supportive therapy, 49% of the patients were treated with benzodiazepines and/or propofol. Conclusion Laboratory analysis constitutes an important basis for the assessment of NPS hazard and availability. The adverse effects noted in cases of acute intoxications involving 3- and/or 4- MeO-PCP resembled those of other dissociatives such as PCP, ketamine, and methoxetamine. However, similar to intoxications involving other NPS, poly-substance use was found to be common. Full text available from: http://www.tandfonline.com/doi/abs/10.3109/15563650.2015.1079325

Disproportionate effect on child admissions of the change in MHRA guidance for management of paracetamol poisoning: an analysis of hospital admissions for paracetamol overdose in England and Scotland Narayan H, Thomas SH, Eddleston M, Dear JW, Sandilands E, Bateman DN. Br J Clin Pharmacol 2015; online early: doi: 10.1111/bcp.12779: Abstract and full text available from: http://dx.doi.org/10.1111/bcp.12779

Paracetamol overdose in Hong Kong: is the 150-treatment line good enough to cover patients with paracetamol-induced liver injury? Chan STB, Chan CK, Tse ML. Hong Kong Med J 2015; online early: doi: 10.12809/hkmj144481: Abstract and full text available from: http://dx.doi.org/10.12809/hkmj144481 Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new Eddleston M, Chowdhury FR. Br J Clin Pharmacol 2015; online early: doi: 10.1111/bcp.12784: Abstract and full text available from: http://dx.doi.org/10.1111/bcp.12784

Long-acting anticoagulant rodenticide (superwarfarin) poisoning: a review of its historical development, epidemiology, and clinical management King N, Tran M-H. Transfus Med Rev 2015; online early: doi: 10.1016/j.tmrv.2015.06.002: Abstract and full text available from: http://dx.doi.org/10.1016/j.tmrv.2015.06.002 Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double- blind phase 1 trial Glund S, Stangier J, Schmohl M, Gansser D, Norris S, Van Ryn J, Lang B, Ramael S, Moschetti V, Gruenenfelder F, Reilly P, Kreuzer J. Lancet 2015; 386: 15-21. Abstract and full text available from: http://dx.doi.org/10.1016/S0140-6736(15)60732-2 Aminocaproic acid and tranexamic acid fail to reverse dabigatran-induced coagulopathy Levine M, Huang M, Henderson SO, Carmelli G, Thomas SH. Am J Ther 2015; online early: doi: 10.1097/MJT.0000000000000216: Abstract and full text available from: http://dx.doi.org/10.1097/MJT.0000000000000216 Calcium channel and beta-blocker antagonist antidotes and adjunct therapies Graudins A, Lee HM, Druda D. Br J Clin Pharmacol 2015; online early: doi: 10.1111/bcp.12763: Abstract and full text available from: http://dx.doi.org/10.1111/bcp.12763 Buprenorphine infrequently found in fatal overdose in New York City Paone D, Tuazon E, Stajic M, Sampson B, Allen B, Mantha S, Kunins H. Drug Alcohol Depend 2015; online early: doi: 10.1016/j.drugalcdep.2015.08.007: Abstract and full text available from: http://dx.doi.org/10.1016/j.drugalcdep.2015.08.007 Role of extracorporeal membrane oxygenation in aluminum phosphide poisoning-induced reversible myocardial dysfunction: a novel therapeutic modality Mohan B, Gupta V, Ralhan S, Gupta D, Puri S, Wander GS, Singh B. J Emerg Med 2015; online early: doi: 10.1016/j.jemermed.2015.06.071: Abstract and full text available from: http://dx.doi.org/10.1016/j.jemermed.2015.06.071

Acute toluene intoxication-clinical presentation, management and prognosis: a prospective observational study Camara-Lemarroy CR, Rodríguez-Gutiérrez R, Monreal-Robles R, González-González JG. BMC Emerg Med 2015; 15: 19. Abstract and full text available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539858/ Reversible oligohydramnios in the second trimester of pregnancy in two patients with long-term diclofenac exposure Scherneck S, Schöpa FL, Entezami M, Kayser A, Weber-Schoendorfer C, Schaefer C. Reprod Toxicol 2015; 58: 61-4. Abstract and full text available from: http://dx.doi.org/10.1016/j.reprotox.2015.08.002 Epidemiology of ciguatera in Florida Radke EG, Reich A, Morris JG, Jr. Am J Trop Med Hyg 2015; 93: 425-32. Abstract and full text available from: http://dx.doi.org/10.4269/ajtmh.14-0400 Injuries from methamphetamine-related chemical incidents – Five states, 2001-2012 Melnikova N, Orr MF, Wu J, Christensen B. Morbidity and Mortality Weekly Report (MMWR) 2015; 64: 909-12. Abstract and full text available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6433a4.htm Novel psychoactive substances or 'legal highs' Bonnici KS, Dargan PI, Wood DM. Br J Hosp Med (Lond ) 2015; 76: C130- C134. Abstract and full text available from: http://dx.doi.org/10.12968/hmed.2015.76.9.C130 Manganese-induced Parkinsonism is not idiopathic Parkinson's disease: environmental and genetic evidence Guilarte TR, Gonzales KK. Toxicol Sci 2015; 146: 204-12. Abstract and full text available from: http://dx.doi.org/10.1093/toxsci/kfv099 T1 relaxation rate (R1) indicates nonlinear Mn accumulation in brain tissue of welders with low-level exposure Lee E-Y, Flynn MR, Du G, Lewis MM, Fry R, Herring AH, Van Buren E, Van Buren S, Smeester L, Kong L, Yang Q, Mailman RB, Huang X. Toxicol Sci 2015; 146: 281-9. Abstract and full text available from: http://dx.doi.org/10.1093/toxsci/kfv088 Manganese homeostasis in the nervous system Chen P, Chakraborty S, Mukhopadhyay S, Lee E, Paoliello MMB, Bowman AB, Aschner M. J Neurochem 2015; 134: 601-10. Abstract and full text available from: http://dx.doi.org/10.1111/jnc.13170

Medical documentation, bioanalytical evidence of an accidental human exposure to sulfur mustard and general therapy recommendations Steinritz D, Striepling E, Klaus-Dieter R, Schröder-Kraft C, Püschel K, Hullard- Pulstinger A, Koller M, Thiermann H, Gandor F, Gawlik M, Haralda J. Toxicol Lett 2015; online early: doi: 10.1016/j.toxlet.2015.08.1105: Abstract and full text available from: http://dx.doi.org/10.1016/j.toxlet.2015.08.1105 Reassessment of MTBE cancer potency considering modes of action for MTBE and its metabolites Bogen KT, Heilman JM. Crit Rev Toxicol 2015; online early: doi: 10.3109/10408444.2015.1052367: Abstract and full text available from: http://dx.doi.org/10.3109/10408444.2015.1052367 A critical review finds styrene lacks direct endocrine disruptor activity Gelbke H-P, Banton M, Leibold E, Pemberton M, Samson SL. Crit Rev Toxicol 2015; online early: doi: 10.3109/10408444.2015.1064091: Abstract and full text available from: http://dx.doi.org/10.3109/10408444.2015.1064091

Burch PT, Lambert LM, Sherwin CMT, Reilly CA, Spigarelli MG. TOXICOLOGY Quantitative assay validation for oxandrolone in human General plasma using LC–MS-MS. Behal N, Wong A, Mantara R, Cantrell FL. J Anal Toxicol 2015; 39: 526-31. Human poisoning through atypical routes of exposure. J Community Health 2015; online early: Liu Y, Liu D, Liu H, Song H, Song L, Yao X, Wu F, Shu C, doi: 10.1007/s10900-015-0074-5: Ma X, Zhou H, Jiang J, Hu P. Simultaneous determination of imigliptin and its three Faria MA. metabolites in human plasma and urine by liquid The death of Stalin – was it a natural death or poisoning? chromatography coupled to tandem mass spectrometry. Surg Neurol Int 2015; 6: 128. J Chromatogr B Biomed Sci Appl 2015; 1002: 300-312

Gundert-Remy U, Barth H, Bürkle A, Degen GH, Landsiedel R. Marino MA, Voyer B, Cody RB, Dane AJ, Veltri M, Huang L. Toxicology: a discipline in need of academic anchoring-the Rapid identification of synthetic cannabinoids in herbal point of view of the German Society of Toxicology. incenses with DART-MS and NMR. Arch Toxicol 2015; online early: J Forensic Sci 2015; online early: doi: 10.1007/s00204-015-1577-7: doi: 10.1111/1556-4029.12932:

Rovida C, Asakura S, Daneshian M, Hofman-Huether H, McIntyre IM, Trochta A, Gary RD, Storey A, Corneal J, Leist M, Meunier L, Reif D, Rossi A, Schmutz M, Valentin J-P, Schaber B. Zurlo J, Hartung T. A fatality related to two novel hallucinogenic compounds: Food for Thought...: Toxicity testing in the 21st century 4-methoxyphencyclidine and 4-hydroxy-N-methyl-N- beyond environmental chemicals. ethyltryptamine. ALTEX 2015; 32: 171-81. J Anal Toxicol 2015; online early: doi: 10.1093/jat/bkv089: Thümmler S. Carbamazepine overdosage despite low residual plasma Rhee J, Cho B, Lee J, Moon S, Yum H. concentration? Liquid chromatography with tandem mass spectrometry Eur J Paediatr Neurol 2015; 19 Supplement 1: S98. for the determination of flufenoxuron in blood using automatic solid phase extraction and its application to a fatal case of flufenoxuron poisoning. Analytical toxicology Forensic Sci Int 2015; 257: 49-53. Bertol E, Vaiano F, Di Milia MG, Mari F. In vivo detection of the new psychoactive substance AM- Saito T, Umebachi R, Namera A, Oikawa H, Miyazaki S, 694 and its metabolites. Fujita Y, Inokuchi S. Forensic Sci Int 2015; 256: 21-7. Identification and quantification of aconitines and

colchicine in serum, urine, and plants using MonoSpin C18 Chericoni S, Stefanelli F, Da Valle Y, Giusiani M. and LC-MSMS. A direct aqueous derivatization GSMS method for Chromatographia 2015; 78: 1041-8. determining benzoylecgonine concentrations in human urine. Yan H, Zhuo X, Shen B, Xiang P, Shen M. J Forensic Sci 2015; 60: 1355-1359. Determination of nitrite in whole blood by high- performance liquid chromatography with electrochemical Christodoulides N, De La Garza R, II, Simmons GW, detection and a case of nitrite poisoning. McRae MP, Wong J, Newton TF, Smith R, Mahoney JJ, III, J Forensic Sci 2015; online early: Hohenstein J, Gomez S, Floriano PN, Talavera H, Sloan DJ, doi: 10.1111/1556-4029.12918: Moody DE, Andrenyak DM, Kosten TR, Haque A, McDevitt JT. Application of programmable bio-nano-chip system for the quantitative detection of drugs of abuse in oral fluids. Biomarkers Drug Alcohol Depend 2015; 153: 306-13. Andreoli R, Spatari G, Pigini D, Poli D, Banda I, Goldoni M, Riccelli MG, Petyx M, Protano C, Vitali M, Barbaro M, Mutti A. Cone EJ, DePriest AZ, Heltsley R, Black DL, Mitchell JM, Urinary biomarkers of exposure and of oxidative damage LoDico C, Flegel R. in children exposed to low airborne concentrations of Prescription opioids. IV: disposition of hydrocodone in oral benzene. fluid and blood following single-dose administration. Environ Res 2015; 142: 264-72. J Anal Toxicol 2015; 39: 510-8. Azab M, Khabour OF, Alzoubi KH, Mahmoud SAH, Jeong Y-D, Kim MK, Suh SI, In MK, Kim JY, Paeng K-J. Anabtawi M, Quttina M. Rapid determination of benzodiazepines, zolpidem and Assessment of genotoxicity of waterpipe smoking using 8- their metabolites in urine using direct injection liquid OHdG biomarker. chromatography-tandem mass spectrometry. Genet Mol Res 2015; 14: 9555-61. Forensic Sci Int 2015; 257: 84-92. Bellei E, Monari E, Bergamini S, Cuoghi A, Tomasi A, Liang H, Kuang S, Guo L, Yu T, Rao Y. Guerzoni S, Ciccarese M, Pini LA. Assessment of the role played by n-propanol found in Validation of potential candidate biomarkers of drug- postmortem blood in the discrimination between induced nephrotoxicity and allodynia in medication- antemortem consumption and postmortem formation of overuse headache. ethanol using rats. J Headache Pain 2015; 16: 77. J Forensic Sci 2015; online early: doi: 10.1111/1556-4029.12921: Carcinogenicity Allen EM, Alexander BH, MacLehose RF, Nelson HH, Ryan AD, Linakis MW, Stockmann C, Campbell SC, Williams RV, Ramachandran G, Mandel JH.

Occupational exposures and lung cancer risk among Abboud ME, Frasure SE. Minnesota taconite mining workers. Bradycardia caused by intravenous nicardipine in an Occup Environ Med 2015; 72: 633-9. elderly patient with acute ischemic infarct. Am J Emerg Med 2015; online early: Amerio A, Gálvez JF, Odone A, Dalley SA, Ghaemi SN. doi: 10.1016/j.ajem.2015.08.030: Carcinogenicity of psychotropic drugs: a systematic review of US Food and Drug Administration-required preclinical in Evans B, Cox A, Nicol E, Mead MP, Behr E. vivo studies. Drug-associated arrhythmia in the military patient. Aust N Z J Psychiatry 2015; 49: 686-96. J R Army Med Corps 2015; online early: doi: 10.1136/jramc-2015-000492: Bailey LA, Nascarella MA, Kerper LE, Rhomberg LR. Hypothesis-based weight-of-evidence evaluation and risk Johannesen L, Vicente J, Mason JW, Erato C, Sanabria C, assessment for naphthalene carcinogenesis. Waite-Labott K, Hong M, Lin J, Guo P, Mutlib A, Wang J, Crit Rev Toxicol 2015; online early: Crumb WJ, Blinova K, Chan D, Stohlman J, Florian J, doi: 10.3109/10408444.2015.1061477: Ugander M, Stockbridge N, Strauss DG. Late sodium current block for drug-induced long QT Bogen KT, Heilman JM. syndrome: results from a prospective clinical trial. Reassessment of MTBE cancer potency considering modes Clin Pharmacol Ther 2015; online early: of action for MTBE and its metabolites. doi: 10.1002/cpt.205: Crit Rev Toxicol 2015; online early: doi: 10.3109/10408444.2015.1052367: Lippi G, Cervellin G, Sanchis-Gomar F. Energy drinks and myocardial ischemia: a review of case Hrudey SE, Backer LC, Humpage AR, Krasner SW, reports. Michaud DS, Moore LE, Singer PC, Stanford BD. Cardiovasc Toxicol 2015; online early: Evaluating evidence for association of human bladder doi: 10.1007/s12012-015-9339-6: cancer with drinking-water chlorination disinfection byproducts. Long VP, III, Carnes CA. J Toxicol Environ Health B Crit Rev 2015; online early: Treating cocaine cardiotoxicity: does receptor subtype doi: 10.1080/10937404.2015.1067661: matter? Trends Cardiovasc Med 2015; 25: 527-8. Marinaccio A, Binazzi A, Bonafede M, Corfiati M, Di Marzio D, Scarselli A, Verardo M, Mirabelli D, Gennaro V, Mensi C, Menke NB, Walsh SJ, King AM. Schallemberg G, Merler E, Negro C, Romanelli A, Chellini E, Cardiotoxicodynamics: toxicity of cardiovascular xenobiotics. Silvestri S, Cocchioni M, Stracci F, Ascoli V, Trafficante L, Emerg Med Clin North Am 2015; 33: 563-95. Angelillo I, Musti M, Cavone D, Cauzillo G, Tallarigo F, Tumino R, Melis M, ReNaM Working Group. Mohan B, Gupta V, Ralhan S, Gupta D, Puri S, Wander GS, Malignant mesothelioma due to non-occupational asbestos Singh B. exposure from the Italian national surveillance system Role of extracorporeal membrane oxygenation in (ReNaM): epidemiology and public health issues. aluminum phosphide poisoning-induced reversible Occup Environ Med 2015; 72: 648-55. myocardial dysfunction: a novel therapeutic modality. J Emerg Med 2015; online early: Morfeld P, Spallek M. doi: 10.1016/j.jemermed.2015.06.071: Diesel engine exhaust and lung cancer risks - Evaluation of the meta-analysis by Vermeulen et al. 2014. Nishikawa T, Miyahara E, Kurauchi K, Watanabe E, Ikawa K, J Occup Med Toxicol 2015; 10: 31. Asaba K, Tanabe T, Okamoto Y, Kawano Y. Mechanisms of fatal cardiotoxicity following high-dose Ohgami N, Yamanoshita O, Thang ND, Yajima I, Nakano C, cyclophosphamide therapy and a method for its Wenting W, Ohnuma S, Kato M. prevention. Carcinogenic risk of chromium, copper and arsenic in CCA- PLoS ONE 2015; 10: e0131394. treated wood. Environ Pollut 2015; 206: 456-60. Regina A, Su M, Shroff H, Cragun J. Prolonged QT risk assessment in antipsychotic overdose Pannu TS, Sukhmani, Gill KS. using the QT nomogram. Uranium-toxicity and uranium-induced osteosarcoma using Ann Emerg Med 2015; 66: 215-6. a new regimen and surgery : a first-time experience. J Clin Diagn Res 2015; 9: RD01-RD03. Salvo F, Pariente A, Shakir S, Robinson P, Arnaud M, Thomas SHL, Raschi E, Fourrier-Réglat A, Moore N, Swiatkowska B, Szubert Z, Sobala W, Sturkenboom M, Hazell L, on behalf of Investigators of the Szeszenia-Dabrowska N. ARITMO consortium. Predictors of lung cancer among former asbestos-exposed Sudden cardiac and sudden unexpected death related to workers. antipsychotics: a meta-analysis of observational studies. Clin Pharmacol Ther 2015; online early: Lung Cancer 2015; 89: 243-8. doi: 10.1002/cpt.250:

Cardiotoxicity Sethi R. Aasa KL, Maciver RD, Ramchandani S, Adams MA, Cardiac dysfunction subsequent to exposre to ozone; an Ozolinš TRS. air pollutant. In utero exposure to a cardiac teratogen causes reversible Cardiology (Switzerland) 2015; 131 Supplement 2: 337. deficits in postnatal cardiovascular function, but altered adaptation to the burden of pregnancy. Srinivasan G, Wyawahare M, Mathen PG, Subrahmanyam DK. Toxicol Sci 2015; online early: Life-threatening bradyarrhythmia with oral phenytoin doi: 10.1093/toxsci/kfv169: overdose.

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Sci Total Environ 2015; 537: 197-202. Organochlorine pesticides General Terekhov S, Smirnov I, Bobik T, Shamborant O, Zenkova M, Byrne S, Miller P, Waghiyi V, Buck CL, von Hippel FA, Chernolovskaya E, Gladkikh D, Murashev A, Dyachenko I, Carpenter DO. Palikov V, Palikova Y, Knorre V, Belogurov A, Jr., Persistent organochlorine pesticide exposure related to a Ponomarenko N, Blackburn GM, Masson P, Gabibov A. formerly used defense site on St. Lawrence Island, Alaska: A novel expression cassette delivers efficient production of data from sentinel fish and human sera. exclusively tetrameric human butyrylcholinesterase with J Toxicol Environ Health A 2015; 78: 976-92. improved pharmacokinetics for protection against organophosphate poisoning. Mustafa M, Garg N, Banerjee BD, Sharma T, Tyagi V, Dar SA, Biochimie 2015; 118: 51-59. Guleria K, Ahmad RS, Vaid N, Tripathi AK. Inflammatory-mediated pathway in association with Yesilbas O, Kihtir HS, Altiti M, Petmezci MT, Balkaya S, organochlorine pesticides levels in the etiology of Duramaz BB, Ersoy M, Sevketoglu E. idiopathic preterm birth. Acute severe organophosphate poisoning in a child who was Reprod Toxicol 2015; 57: 111-20. successfully treated with therapeutic plasma exchange, high-volume hemodiafiltration, and lipid infusion. Sharma A, Sharma P, Sharma P, Joshi SC. J Clin Apheresis 2015; online early: A review on organochlorine pesticides and reproductive doi: 10.1002/jca.21417: toxicity in males. Int J Pharm Sci Res 2015; 6: 3123-38. Phorate

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Caenorhabditis elegans as an alternative in vivo model to Zinc phosphide determine oral uptake, nanotoxicity, and efficacy of Saraf V, Pande S, Gopalakrishnan U, Balakrishnan D, melatonin-loaded lipid-core nanocapsules on paraquat Menon RN, Sudheer OV, Dhar P, Sudhindran S. damage. Acute liver failure due to zinc phosphide containing Int J Nanomedicine 2015; 10: 5093-106. rodenticide poisoning: clinical features and prognostic indicators of need for liver transplantation. Gales L, Amorim R, Afonso CMM, Carvalho F, Indian J Gastroenterol 2015; online early: Dinis-Oliveira RJ. doi: 10.1007/s12664-015-0583-2: Decreasing the toxicity of paraquat through the complexation with sodium salicylate: stoichiometric analysis. CHEMICAL WARFARE, Toxicology 2015; 336: 96-8. BIOLOGICAL WARFARE AND

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INDEX

2,4-dinitrophenol ...... 38 Carcinogenicity ...... 7 Acetaminophen ...... 27 Cardiotoxicity ...... 8 Acetylcysteine ...... 18 Chelating agents ...... 18 Acne drugs ...... 20 Chemical incidents ...... 30 Aconitine ...... 21 Chemical incidents and pollution ...... 30 Adrenaline ...... 21 Chemicals, general ...... 31 Agent Orange ...... 39 Chlormequat ...... 37 Air pollution ...... 30 Chlorpyrifos ...... 38 Alcohol ...... 31 Chromium ...... 36 Alpha lipoic acid ...... 23 Ciguatera ...... 40 Aluminium phosphide ...... 37 Clozapine ...... 23, 25 Amfetamines ...... 21 Cobra ...... 40 Amiodarone ...... 21 Cocaine...... 25 Amlodipine ...... 24 Colchicine ...... 25 Anabolic steroids ...... 21 Colchicum autumnale (Autumn crocus) ...... 40 Anaesthetics ...... 21 Contrast media ...... 32 Analytical toxicology ...... 7 Copper ...... 36 Animals, general ...... 40 Cosmetics ...... 32 Anthrax ...... 39 Coumarins ...... 21 Antiarrhythmic drugs ...... 21 Cyanide ...... 32 Antibiotics ...... 21 Cyclophosphamide ...... 23 Anticoagulants ...... 21 Cyclosporine...... 25 Anticonvulsants ...... 22 Dabigatran ...... 21 Antidepressants ...... 22 DDT ...... 38 Antidotes ...... 18 Deltamethrin ...... 39 Antiemetics ...... 22 Dermal toxicity ...... 9 Antihistamines ...... 23 Designer drugs ...... 28 Antineoplastic drugs ...... 23 Developmental toxicology ...... 9 Antioxidants...... 23 Dextromethorphan ...... 23 Antipsychotics ...... 23 Diacetylmorphine...... 26 Antituberculous drugs ...... 23 Diclofenac ...... 27 Antitussives ...... 23 Dietary supplements ...... 26 Antivenom ...... 18 Digoxin ...... 25 Antiviral drugs ...... 23 Diisocyanates ...... 33 Apricots ...... 40 Diquat ...... 38 Arsenic ...... 35 Disnfection byproducts...... 33 Asbestos...... 31 Domperidone ...... 25 Azacitidine ...... 23 Doxorubicin ...... 23 Baclofen ...... 23 Driving under the influence ...... 10 Barbiturates ...... 24 Drug abuse ...... 29 Batteries ...... 32 Drugs, general ...... 20 Benzene ...... 32 E-cigarettes ...... 33 Benzodiazepines ...... 24 Ecstasy ...... 21 Benzoylecgonine ...... 24 Epidemiology...... 10 Beryllium ...... 35 Ethanol ...... 31 Beta-blockers ...... 24 Ethnic remedies ...... 26 Biofuels ...... 32 Ethylene glycol ...... 33 Biological warfare...... 39 Ethylphenidate ...... 29 Biomarkers ...... 7 Exhaust fumes ...... 30 Bioscavengers ...... 19 Extracorporeal membrane oxygenation ...... 19 Bisphenol A ...... 32 Extracorporeal treatments ...... 19 Blighia sapida (Ackee fruit) ...... 40 Fish/marine poisoning ...... 40 Buprenorphine ...... 19, 24 Flufenoxuron ...... 38 Butalbital ...... 24 Flumazenil ...... 18 Butane ...... 32 Fluoride ...... 33 Cadmium ...... 36 Forensic toxicology ...... 11 Calcium channel blockers...... 24 Formaldehyde ...... 33 Cannabis ...... 24 Gamma hydroxybutyrate ...... 25 Carbamazepine ...... 22 Genotoxicity ...... 11 Carbon monoxide ...... 32 Glycine ...... 25

Glyphosate ...... 38 Oleic acid ...... 34 Haemodialysis ...... 19 Opioid maintenance therapy ...... 19 Haemoperfusion...... 19 Opioids ...... 27 Hazardous waste ...... 30 Opium ...... 27 Heavy metals ...... 36 Organochlorine pesticides, general ...... 38 Hepatotoxicity ...... 11 Organophosphorus insecticides, general ...... 38 Herbal medicines ...... 26 Orlistat ...... 27 Herbicides ...... 38 Oxandrolone ...... 21 Heroin ...... 26 Oxcarbazepine ...... 22 Hexachlorobenzene ...... 33 Ozone ...... 34 Histamine ...... 26 Paediatric toxicology ...... 14 Hydrochlorothiazide ...... 26 Paracetamol ...... 27 Hydrocodone ...... 27 Paraquat ...... 38 Hydrofluoric acid ...... 33 Perfluorinated compounds ...... 34 Hydroxyzine ...... 23 Permethrin ...... 39 Hypoglycaemic drugs ...... 26 Perphenazine ...... 23 Idarucizumab ...... 19 Pesticides, general ...... 37 Imigliptin ...... 26 Phenazepam ...... 24 Immunosuppressants ...... 26 Phencyclidine ...... 28 Indoxacarb ...... 38 Phenprocoumon ...... 39 Inhalation toxicity ...... 12 Phenytoin...... 22 Isoniazid...... 23 Phorate ...... 38 Kinetics ...... 12 Phthalate esters ...... 34 Lead...... 36 Pioglitazone ...... 28 Lefetamine ...... 27 Plants, general ...... 40 Lenalidomide ...... 26 Plasticisers ...... 34 Levamisole ...... 26 Poison information centres ...... 16 Lidocaine ...... 21 Poisons information ...... 16 Limestone dust ...... 33 Pollution ...... 30 Lipid emulsion therapy ...... 19 Polycyclic aromatic hydrocarbons ...... 34 Lithium ...... 26, 36 Polymorphisms ...... 16 Management, general ...... 17 Potassium permanganate ...... 34 Manganese ...... 36 Propyphenazone ...... 28 Marijuana ...... 24 Psychiatric aspects ...... 16 Maripiprazole ...... 23 Psychotropic drugs ...... 28 MDMA ...... 21 Pyrethroid insecticides, general ...... 39 Mercury ...... 26, 37 Reprotoxicity ...... 16 Metals, general ...... 35 Rhinella schneideri (Rococo toad) ...... 40 Metformin ...... 26 Risk assessment ...... 17 Methadone ...... 19, 26 Ritonavir ...... 23 Methanol ...... 33 Rivaroxaban ...... 22 Methotrexate ...... 26 Rodenticides ...... 39 Methyl ethyl ketone peroxide ...... 33 Sertraline ...... 28 Methyl iodide ...... 38 Silica ...... 34 Methyl tertiary butyl ether ...... 33 Smoke ...... 34 Methylisothiazolinone ...... 33 Snake bites ...... 40 Methylisothiazolinones ...... 34 Spiders ...... 41 Methylthioninium chloride (methylene blue) ...... 19 SSRIs...... 28 Metoclopramide ...... 22 Styrene ...... 35 Metronidazole ...... 21 Substance abuse ...... 28 Mineral fibres ...... 34 Suicide ...... 17 Mirtazepine ...... 22 Sulfoxide ...... 29, 35 Monoclonal antibodies ...... 19 Synthetic cannabinoids ...... 29 Montelukast ...... 26 Telmisartan ...... 29 Moxonidine ...... 27 Tenofovir/emtricitabine ...... 23 Mushrooms ...... 40 Thyroxine...... 29 Mustard gas ...... 39 Timolol ...... 24 Naloxone ...... 19, 27 Tobacco ...... 35 Naphthalene ...... 34 Toluene ...... 35 Nephrotoxicity ...... 12 Topical retinoids ...... 29 Nerve agents ...... 39 Toxicology, general ...... 7 Neurotoxicity ...... 12 Tramadol ...... 27, 29 Nicardipine ...... 24 Triptans ...... 29 Nicotine ...... 34 Tryptamines ...... 29 Nilotinib ...... 23 Turtles ...... 40 Nitrite ...... 34 Uranium ...... 37 Nitrobenzene ...... 34 Valproate ...... 29 NSAIDs ...... 27 Vancomycin ...... 21 Nutmeg ...... 40 Varenicline ...... 30 Occupational toxicology ...... 13 Vigabatrin ...... 22 Ocular toxicity ...... 14 Vinyl chloride ...... 35 Olanzapine ...... 23 Vipers ...... 40

VR ...... 39 Wood smoke ...... 35 Warfarin ...... 22 Zinc phosphide ...... 39 Welding fumes ...... 35 Zolpidem ...... 30

The NPIS is commissioned by Public Health England