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

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

August 2017

CONTENTS General Toxicology 8 Metals 27 Management 14 Pesticides 27 Drugs 16 Chemical Warfare 28 Chemical Incidents & 24 Plants 28 Pollution Chemicals 24 Animals 29

CURRENT AWARENESS PAPERS OF THE MONTH

Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment Richards JR, Lapoint JM, Burillo-Putze G. Clin Toxicol 2017; online early: doi: 10.1080/15563650.2017.1349910: Introduction Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. Objectives In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated.

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

Methods An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1 Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits a novel type of desensitization analgesia. Transient receptor potential vanilloid 1 receptors also respond to noxious stimuli, such as heat (>43 °C), acids (pH <6), pain, change in osmolarity, and endovanilloids. The action of topical capsaicin may mimic the effect of heat-activation of transient receptor potential vanilloid 1.Endocannabinoid system and transient receptor potential vanilloid 1: Cannabinoid hyperemesis syndrome may result from a derangement in the endocannabinoid system secondary to chronic exogenous stimulation. The relief of cannabinoid hyperemesis syndrome symptoms from heat and use of transient receptor potential vanilloid 1 agonists suggests a complex interrelation between the endocannabinoid system and transient receptor potential vanilloid 1. Temperature regulation Hot water hydrotherapy is a mainstay of self-treatment for cannabinoid hyperemesis syndrome patients. This may be explained by heat-induced transient receptor potential vanilloid 1 activation. "Sensocrine" antiemetic effects Transient receptor potential vanilloid 1 activation by heat or capsaicin results in modulation of tachykinins, somatostatin, pituitary adenylate-cyclase activating polypeptide, and calcitonin gene-related peptide as well as histaminergic, cholinergic, and serotonergic transmission. These downstream effects represent further possible explanations for transient receptor potential vanilloid 1-associated antiemesis. Conclusions These complex interactions between the endocannabinoid systems and transient receptor potential vanilloid 1, in the setting of cannabinoid receptor desensitization, may yield important clues into the pathophysiology and treatment of cannabinoid hyperemesis syndrome. This knowledge can provide clinicians caring for these patients with additional treatment options that may reduce length of stay, avoid unnecessary imaging and laboratory testing, and decrease the use of potentially harmful medications such as opioids. Full text available from: http://dx.doi.org/10.1080/15563650.2017.1349910

Evaluation of toxicity after acute accidental methotrexate ingestions in children under 6 years old: a 16-year multi-center review Hays H, Beuhler MC, Spiller HA, Weber J, Mowry JB, Ryan ML, Spiller NE, Webb A. Clin Toxicol 2017; online early: doi: 10.1080/ 15563650.2017.1349319: Context There is little data on the frequency of adverse events following acute methotrexate ingestions in pediatric patients. Likewise, recommendations for observation length, site and management strategies in this population are not well established. Therefore, most recommendations are modeled after management of chronic overdose in patients with underlying medical conditions. Objective The primary objective of this study is to determine the frequency of acute toxicity after acute methotrexate accidental unsupervised ingestions in patients less than six years. In addition, we describe the frequency of late toxicity and characterize the management site and approaches. Materials and Methods This is a retrospective cohort study of pediatric accidental unsupervised methotrexate ingestions reported to six poison centers in the United States over a 16 year period. Demographic information, exposure details, signs, symptoms, treatments, length and location of observation and outcomes were collected. Results 103 patients met inclusion criteria. Methotrexate dose was reported in 86 patients (84%) and ranged from 1.3 mg–75 mg. The majority of cases (97%) ingested a dose ≤20 mg. The significant majority of cases experienced no clinical effects (99 of 103 cases; 96%). Three children experienced minor outcome (3%). There were no patients with a major outcome or death. Conclusions The incidence of toxicity from pediatric single, acute ingestions of methotrexate is rare and when it occurs is generally limited to no or only minimally concerning effects. Because concentrations from single ingestions were consistent with low subtoxic exposures, we believe that home monitoring without hospital referral and without methotrexate specific therapy is reasonable in those with acute ingestions up to 20 mg. Full text available from: http://dx.doi.org/10.1080/15563650.2017.1349319

Evaluation of dose and outcomes for pediatric vilazodone ingestions Gaw CE, Spiller HA, Russell JL, Chounthirath T, Smith GA. Clin Toxicol 2017; online early: doi: 10.1080/15563650.2017.1347263: Background Selective serotonin reuptake inhibitor (SSRI) exposures among children younger than 6 years of age are generally well tolerated. Vilazodone is an SSRI with partial agonism at the

5-HT1A receptor with demonstrated clinical efficacy for depression whose off-label usage is likely to increase. Recent evidence suggests that unintentional ingestion of vilazodone in children under 6 years old is associated with more severe clinical effects than other SSRIs. We chose to evaluate dose and outcomes for pediatric vilazodone ingestions.

Methods A retrospective analysis of single-substance exposures associated with vilazodone among children younger than 6 years of age from 2011 through 2016 was conducted using data from the National Poison Data System. Results During 2011–2016, 753 vilazodone ingestions among children <6 years old were reported to US poison control centers. A near majority (49.0%, n = 369) experienced one or more clinical effects. The dose ingested was reported for 596 children (79%). The median dose associated with major effects was 50.0mg (Mean: 106.0) compared with 40.0mg (Mean 81.1) for moderate effects. Half (50.0%) of children with a major effect and 54.0% with a moderate effect ingested ≤40 mg of vilazodone. As the dose of vilazodone ingested increased, the proportions of exposures admitted to a healthcare facility (HCF) (p < .001) and with serious outcomes (p < .001) both increased. Children ≤2 years had higher proportions of HCF admission (33.8% vs 23.1%) and serious outcomes (27.0% vs 17.7%) than children 3–5 years of age. Clinical effects, such as coma, seizures, ataxia, and hallucinations/delusions, were observed among children ingesting doses of vilazodone as low as 10 mg. Conclusions Exposure to vilazodone poses a unique and potentially serious threat to children <6 years of age. Children in this age group who are exposed to vilazodone should be evaluated promptly in a clinical setting. Off-label use of vilazodone in children under 6 years should be discouraged until further research is conducted regarding its safety in this population. Full text available from: http://dx.doi.org/10.1080/15563650.2017.1347263

Safety and effectiveness of physostigmine: a 10-year retrospective review Arens AM, Shah K, Al-Abri S, Olson KR, Kearney T. Clin Toxicol 2017; online early: doi: 10.1080/15563650.2017.1342828: Background Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed. Objectives To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium. Methods A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI's), and p values. Results Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non- diphenhydramine antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n = 3) had 100% response to physostigmine, whereas anticholinergic plants (n = 46/67; 68.7%, OR: 0.70; CI: 0.36–1.35), diphenhydramine (n = 43/56; 64.2%, OR: 1.30; CI: 0.63–2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30–7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with

physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED). Discussion Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6 h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED. Conclusions In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2 mg. Full text available from: http://dx.doi.org/10.1080/15563650.2017.1342828

Persistence of mercury-induced motor and sensory neurotoxicity: systematic review of workers previously exposed to mercury vapor Fields CA, Borak J, Louis ED. Crit Rev Toxicol 2017; online early: doi: 10.1080/10408444.2017.1342599: Abstract and full text available from: http://dx.doi.org/10.1080/10408444.2017.1342599

Causes of death in patients with Itai-itai disease suffering from severe chronic cadmium poisoning: a nested case–control analysis of a follow-up study in Japan Nishijo M, Nakagawa H, Suwazono Y, Nogawa K, Kido T. BMJ Open 2017; 7: e015694. Abstract and full text available from: http://dx.doi.org/10.1136/bmjopen-2016-015694

The socio-economic burden of snakebite in Sri Lanka Kasturiratne A, Pathmeswaran A, Wickremasinghe AR, Jayamanne SF, Dawson A, Isbister GK, de Silva HJ, Lalloo DG. PLoS Negl Trop Dis 2017; 11: e0005647. Abstract and full text available from: http://dx.doi.org/10.1371/journal.pntd.0005647

Endosulfan poisoning: an overview Menezes RG, Qadir TF, Moin A, Fatima H, Hussain SA, Madadin M, Pasha SB, Al Rubaish FA, Senthilkumaran S. J Forensic Leg Med 2017; 51: 27-33. Abstract and full text available from: http://dx.doi.org/10.1016/j.jflm.2017.07.008

Patterns of acute poisoning with pesticides in the paediatric age group Dayasiri KC, Jayamanne SF, Jayasinghe CY. Int J Emerg Med 2017; 10: 22. Abstract and full text available from: http://dx.doi.org/10.1186/s12245-017-0148-5

Intermittent versus continuous renal replacement therapy in acute methanol poisoning: comparison of clinical effectiveness in mass poisoning outbreaks Zakharov S, Rulisek J, Nurieva O, Kotikova K, Navratil T, Komarc M, Pelclova D, Hovda KE. Ann Intensive Care 2017; 7: 77. Abstract and full text available from: http://dx.doi.org/10.1186/s13613-017-0300-7

Simplifying the hemodialysis prescription in patients with ethylene glycol poisoning Roberts DM, Lea-Henry TN. Kidney Int 2017; 92: 291-3. Abstract and full text available from: http://dx.doi.org/10.1016/j.kint.2017.03.051

Approaches to prevent bleeding associated with anticoagulants: current status and recent developments Kalathottukaren MT, Haynes CA, Kizhakkedathu JN. Drug Deliv Transl Res 2017; online early: doi: 10.1007/s13346-017-0413-4: Abstract and full text available from: http://dx.doi.org/10.1007/s13346-017-0413-4

Incomplete dabigatran reversal with idarucizumab Steele AP, Lee JA, Dager WE. Clin Toxicol 2017; online early: doi: 10.1080/15563650.2017.1349911: Context With increasing use of direct oral anticoagulants (DOACs), urgent reversal of these agents becomes a growing concern. Idarucizumab is a humanized monoclonal antibody fragment that specifically binds to dabigatran with higher affinity than thrombin, rapidly neutralizing its anticoagulant effect without increased risk of thrombosis. Case details We describe two cases in which the recommended dose of idarucizumab was unsuccessful in completely reversing the anticoagulant effects of dabigatran. Both of these patients were noted to have supratherapeutic international normalized ratios (INRs) and high dabigatran concentrations. In the first case, an 86-year-old male underwent an emergent procedure and experienced excessive hemorrhaging refractory to blood product repletion, idarucizumab, and factor eight inhibitor bypass activity (FEIBA). In the second case, a 62- year-old female in shock was found to have elevated dabigatran concentrations despite two doses of idarucizumab, continuous renal replacement therapy (CRRT), blood product repletion, and FEIBA. Both patients ultimately expired from their coagulopathies.

Discussion These cases illustrate the potential for incomplete reversal of dabigatran with the recommended 5 g of idarucizumab and emphasize the importance of early detection of dabigatran toxicity. While direct dabigatran serum concentrations are not readily available, the INR may be a useful surrogate marker for supratherapeutic dabigatran concentrations. Full text available from: http://dx.doi.org/10.1080/15563650.2017.1349911

First reported case of hemopericardium related to dabigatran use reversed by new antidote idarucizumab Song S, Cook J, Goulbourne C, Meade M, Salciccioli L, Lazar J. Case Rep Cardiol 2017; 2017: 6458636. Abstract and full text available from: http://dx.doi.org/10.1155/2017/6458636

Grafinger KE, Hdener M, König S, Weinmann W. TOXICOLOGY Study of the in vitro and in vivo metabolism of the General tryptamine 5-MeO-MiPT using human liver microsomes Anon. and real case samples. Toxicological terms - use and misuse - Part one. Drug Test Anal 2017; online early: doi: 10.1002/dta.2245: J Biochem Mol Toxicol 2017; 31: e21961. Liu X, Ma T, Li L-L, Qu B, Liu Z. Hartung T. Predictive values of urine paraquat concentration, dose of Thresholds of toxicological concern – Setting a threshold poison, arterial blood lactate and APACHE II score in the for testing below which there is little concern. prognosis of patients with acute paraquat poisoning. ALTEX 2017; 34: 331-51. Exp Ther Med 2017; 14: 79-86.

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Api AM, Belsito D, Botelho D, Browne D, Bruze M, Burton GA, Bui TT, Xu F, Van den Eede N, Cousins AP, Covaci A, Jr., Buschmann J, Dagli ML, Date M, Dekant W, Deodhar C, Cousins IT. Fryer AD, Joshi K, La Cava S, Lapczynski A, Liebler DC, Probing the relationship between external and internal O'Brien D, Parakhia R, Patel A, Penning TM, Ritacco G, human exposure of organophosphate flame retardants Romine J, Salvito D, Schultz TW, Sipes IG, Thakkar Y, Tokura using pharmacokinetic modelling. Y, Tsang S, Wahler J. Environ Pollut 2017; 230: 550-60. RIFM fragrance ingredient safety assessment, 4- carvomenthenol, CAS registry number 562-74-3. Yadav IC, Devi NL, Zhong G, Li J, Zhang G, Covaci A. Food Chem Toxicol 2017; online early: Occurrence and fate of organophosphate ester flame doi: 10.1016/j.fct.2017.07.040: retardants and plasticizers in indoor air and dust of Nepal: implication for human exposure. Api AM, Belsito D, Botelho D, Browne D, Bruze M, Burton GA, Environ Pollut 2017; 229: 668-78. Jr., Buschmann J, Calow P, Dagli ML, Date M, Dekant W, Deodhar C, Fryer AD, Joshi K, La Cava S, Lapczynski A, Fluoroacetamide Liebler DC, O'Brien D, Parakhia R, Patel A, Penning TM, Wen W, Gao H, Kang N, Lu A, Qian C, Zhao Y. Ritacco G, Romine J, Salvito D, Schultz TW, Sipes IG, Thakkar Treatment of severe fluoroacetamide poisoning in patient Y, Tsang S, Wahler J. with combined multiple organ dysfunction syndrome by RIFM fragrance ingredient safety assessment, p- evidence-based integrated Chinese and Western medicines: methoxybenzonitrile, CAS Registry Number 874-90-8. a case report. Food Chem Toxicol 2017; online early: Medicine (Baltimore) 2017; 96: e7256. doi: 10.1016/j.fct.2017.07.004:

Api AM, Belsito D, Botelho D, Browne D, Bruze M, Burton GA, Plasticizers Jr., Buschmann J, Dagli ML, Date M, Dekant W, Deodhar C, Yadav IC, Devi NL, Zhong G, Li J, Zhang G, Covaci A. Fryer AD, Joshi K, La Cava S, Lapczynski A, Liebler DC, Occurrence and fate of organophosphate ester flame O'Brien D, Parakhia R, Patel A, Penning TM, Ritacco G, retardants and plasticizers in indoor air and dust of Nepal: Romine J, Salvito D, Schultz TW, Sipes IG, Thakkar Y, Tokura implication for human exposure. Y, Tsang S, Wahler J. Environ Pollut 2017; 229: 668-78. RIFM fragrance ingredient safety assessment, 2,2,4- trimethyl-4-phenyl-butane-nitrile CAS registry number 75490-39-0. Polybrominated diphenyl ethers Food Chem Toxicol 2017; online early: Khalil A, Parker M, Brown SE, Cevik SE, Guo LW, Jensen J, doi: 10.1016/j.fct.2017.07.037: Olmsted A, Portman D, Wu H, Suvorov A. Perinatal exposure to 2,2',4'4'- tetrabromodiphenyl ether Api AM, Belsito D, Botelho D, Browne D, Bruze M, Burton GA, induces testicular toxicity in adult rats. Jr., Buschmann J, Dagli ML, Date M, Dekant W, Deodhar C, Toxicology 2017; 389: 21-30. Fryer AD, Joshi K, La Cava S, Lapczynski A, Liebler DC, O'Brien D, Parakhia R, Patel A, Penning TM, Ritacco G, Polycyclic aromatic hydrocarbons Romine J, Salvito D, Schultz TW, Sipes IG, Thakkar Y, Tokura Loh A, Yim UH, Ha SY, An JG, Kim M. Y, Tsang S, Wahler J. Contamination and human health risk assessment of RIFM fragrance ingredient safety assessment, citronellyl polycyclic aromatic hydrocarbons (PAHs) in oysters after nitrile, CAS registry number 51566-62-2. the Wu Yi San Oil Spill in Korea. Food Chem Toxicol 2017; online early: Arch Environ Contam Toxicol 2017; 73: 103-17. doi: 10.1016/j.fct.2017.07.043: Pyrrolizidine alkaloids Pinkas A, Goncalves CL, Aschner M. Habs M, Binder K, Krauss S, Muller K, Ernst B, Valentini L, Neurotoxicity of fragrance compounds: a review. Koller M. Environ Res 2017; 158: 342-9. A balanced risk-benefit analysis to determine human risks

associated with pyrrolizidine alkaloids (PA)–The case of Melamine tea and herbal infusions. Chang H, Wu G, Yue Z, Ma J, Qin Z. Nutrients 2017; 9: 717. Melamine poisoning pediatric urolithiasis treatment in Gansu, China 5-yr follow-up analysis. Radiation Urology 2017; online early: Harrison JD, Smith T, Fell T, Smith J, Ham G, Haylock R, doi: 10.1016/j.urology.2017.06.043: Hodgson A, Etherington G. Collateral contamination concomitant to the polonium-210 Methanol poisoning of Mr Alexander Litvinenko. Peterová K, Brožová H, Klempír J, Lišková I, Bezdícek O, J Radiol Prot 2017; online early: doi: 10.1088/1361- Ridzon P, Vanecková M, Zakharov S, Pelclov D, Miovsky M, 6498/aa80f5: Ružicka E. Gait and balance impairment after acute methanol poisoning. Smoke Basic Clin Pharmacol Toxicol 2017; online early: Budani MC, Tiboni GM. doi: 10.1111/bcpt.12853: Ovotoxicity of cigarette smoke: a systematic review of the literature. Zakharov S, Rulisek J, Nurieva O, Kotikova K, Navratil T, Reprod Toxicol 2017; online early: Komarc M, Pelclova D, Hovda KE. doi: 10.1016/j.reprotox.2017.06.184: Intermittent versus continuous renal replacement therapy in acute methanol poisoning: comparison of clinical effectiveness in mass poisoning outbreaks. Sodium Ann Intensive Care 2017; 7: 77. Lee M, Jr., Lee JY. Iatrogenic salt overdosage in 2 children. Am J Health Syst Pharm 2017; 74: 1127-8. Nanoparticles Smolkova B, Dusinska M, Gabelova A. Mohammadi Kojidi H, Rahbar Taramsari M, Badsar A, Nanomedicine and epigenome. Possible health risks. Attarchi M. Food Chem Toxicol 2017; online early: Suicide by fire extinguisher powder ingestion: a case doi: 10.1016/j.fct.2017.07.020: report. Acta Med Iran 2017; 55: 348-51. Ozone Koman PD, Mancuso P. Sweeteners Ozone exposure, cardiopulmonary health, and obesity: a Carocho M, Morales P, Ferreira ICFR. substantive review. Sweeteners as food additives in the XXI century: a review Chem Res Toxicol 2017; 30: 1384-95. of what is known, and what is to come. Food Chem Toxicol 2017; 107: 302-17. Perfluorinated compounds Méndez-Martínez S, Calvo P, Rodriguez-Marco NA, Faus F, Tobacco Abecia E, Pablo L. Budani MC, Tiboni GM. Blindness related to presumed retinal toxicity after using Ovotoxicity of cigarette smoke: a systematic review of the perfluorocarbon liquid during vitreiretinal surgery. literature. Retina 2017; online early: Reprod Toxicol 2017; online early: doi: 10.1097/IAE.0000000000001783: doi: 10.1016/j.reprotox.2017.06.184:

Kassem NOF, Kassem NO, Liles S, Jackson SR, Chatfield Did the Romans die of antimony poisoning? the case of a DA, Jacob P, III, Benowitz NL, Hovell MF. Pompeii water pipe (79 CE). Urinary NNAL in hookah smokers and non-smokers after Toxicol Lett 2017; online early: attending a hookah social event in a hookah lounge or a doi: 10.1016/j.toxlet.2017.07.876: private home. Regul Toxicol Pharmacol 2017; 89: 74-82. Barium Zhang N, Liu Z, Tian X, Chen M, Deng Y, Guo Y, Li N, Yu P, Lee PN, Fry JS, Hamling JS. Yang J, Zhu J. Investigation into the risk of ultra-low tar cigarettes and Barium exposure increases the risk of congenital heart lung cancer. defects occurrence in offspring. Regul Toxicol Pharmacol 2017; 89: 112-7. Clin Toxicol 2017; online early: doi: 10.1080/15563650.2017.1343479: Mohammadi S, Domeno C, Nerin I, Aznar M, Samper P, Khayatian G, Nerin C. Toxic compounds from tobacco in placenta samples analyzed Cadmium by UPLC-QTOF-MS. Isermann J, Prager H-M, Ebbinghaus R, Janasik B, Wasowicz W, Dufaux B, Meyer H-F, Widera A, Selinski S, J Pharm Biomed Anal 2017; 145: 331-8. Hengstler JG, Golka K.

Urinary cadmium levels in active and retired coal miners. van Osch FHM, Pauwels CGGM, Jochems SHJ, Fayokun R, J Toxicol Environ Health A 2017; online early: doi: James ND, Wallace DMA, Cheng K, Bryan RT, van Schooten 10.1080/10937404.2017.1304710: FJ, Zeegers MP.

Tar, nicotine and carbon monoxide yield of UK cigarettes and the risk of non-muscle-invasive and muscle-invasive Nishijo M, Nakagawa H, Suwazono Y, Nogawa K, Kido T. bladder cancer. Causes of death in patients with Itai-itai disease suffering Eur J Cancer Prev 2017; online early: from severe chronic cadmium poisoning: a nested case- control analysis of a follow-up study in Japan. doi: 10.1097/CEJ.0000000000000404: BMJ Open 2017; 7: e015694.

Triclosan Lead Goodman M, Naiman DQ, LaKind JS. Monebenimp F, Kuepouo G, Chelo D, Anatole PC, Kany Systematic review of the literature on triclosan and health Bissek A-CZK, Gottesfeld P. outcomes in humans. Blood lead levels among children in Yaoundé Cameroon. Crit Rev Toxicol 2017; online early: Front Public Health 2017; 5: 163. doi: 10.1080/10408444.2017.1350138:

Sadler M, Bell S. METALS Ayurvedic plumbism. General Intern Med J 2017; 47: 823-5.

Saghazadeh A, Rezaei N. Systematic review and meta-analysis links autism and Mercury toxic metals and highlights the impact of country Carter M, Abdi A, Naz F, Thabet F, Vyas A. development status: Higher blood and erythrocyte levels A mercury toxicity case complicated by hyponatremia and for mercury and lead, and higher hair antimony, cadmium, abnormal endocrinological test results. lead, and mercury. Pediatrics 2017; 140: e20161402. Prog Neuropsychopharmacol Biol Psychiatry 2017; 79, Part B: 340-68. Fields CA, Borak J, Louis ED. Persistence of mercury-induced motor and sensory Shim YK, Lewin MD, Ruiz P, Eichner JE, Mumtaz MM. neurotoxicity: systematic review of workers previously Prevalence and associated demographic characteristics of exposed to mercury vapor. exposure to multiple metals and their species in human Crit Rev Toxicol 2017; online early: populations: the United States NHANES, 2007–2012. doi: 10.1080/10408444.2017.1342599: J Toxicol Environ Health A 2017; online early: doi: 10.1080/15287394.2017.1330581: Fields CA, Borak J, Louis ED. Mercury-induced motor and sensory neurotoxicity: systematic Skroder H, Kippler M, Nermell B, Tofail F, Levi M, Rahman review of workers currently exposed to mercury vapor. SM, Raqib R, Vahter M. Crit Rev Toxicol 2017; online early: Major limitations in using element concentrations in hair doi: 10.1080/10408444.2017.1342598: as biomarkers of exposure to toxic and essential trace elements in children. Polonium Environ Health Perspect 2017; 125: 067021. Harrison JD, Smith T, Fell T, Smith J, Ham G, Haylock R, Hodgson A, Etherington G. Zeng X, Xu X, Boezen HM, Vonk JM, Wu W, Huo X. Collateral contamination concomitant to the polonium-210 Decreased lung function with mediation of blood poisoning of Mr Alexander Litvinenko. parameters linked to e-waste lead and cadmium exposure in J Radiol Prot 2017; online early: doi: 10.1088/1361- preschool children. 6498/aa80f5: Environ Pollut 2017; 230: 838-48.

Antimony PESTICIDES Charlier P, Bou Abdallah F, Bruneau R, Jacqueline S, General Augias A, Bianucci R, Perciaccante A, Lippi D, Appenzeller Corvaro M, Gehen S, Andrews K, Chatfield R, Macleod F, O, Rasmussen KL. Mehta J.

A retrospective analysis of in vivo eye irritation, skin Organophosphorus insecticides irritation and skin sensitisation studies with agrochemical formulations: setting the scene for development of General alternative strategies. Kobayashi S, Okubo R, Ugawa Y. Regul Toxicol Pharmacol 2017; 89: 131-47. Delayed polyneuropathy induced by organophosphate poisoning. Dayasiri KC, Jayamanne SF, Jayasinghe CY. Intern Med 2017; 56: 1903-5. Patterns of acute poisoning with pesticides in the paediatric age group. Monocrotophos Int J Emerg Med 2017; 10: 22. Turkdogan KA, Duman A, Avcil M, Akoz A, Canakci SE, Kantekin B. Gyenwali D, Vaidya A, Tiwari S, Khatiwada P, Lamsal DR, Treatment methods following suicidal self-administration Giri S. of IV organophosphate: what can additional lipid admin- Pesticide poisoning in Chitwan, Nepal: a descriptive epi- istration change? demiological study. Am J Emerg Med 2017; online early: BMC Public Health 2017; 17: 619. doi: 10.1016/j.ajem.2017.06.058:

Aluminium phosphide Paraoxon Asghari MH, Moloudizargari M, Abdollahi M. Pavlikova R, Misik J, Cabal J, Marek J, Kuca K. In response to the comments on our recently published In vitro skin decontamination of paraoxon - wet type paper entitled "on the mechanisms of melatonin in cleansing effect of selected detergents. protection of aluminum phosphide cardiotoxicity". Cutan Ocul Toxicol 2017; online early: Arch Toxicol 2017; online early: doi: 10.1007/s00204- doi: 10.1080/15569527.2017.1354216: 017-2029-3: Terbufos Shetab-Boushehri SV. Liang Y, Tong F, Zhang L, Li W, Huang W, Zhou Y. Comment on Asghari et al. 2017: On the mechanisms of Fatal poisoning by terbufos following occupational melatonin in protection of aluminum phosphide cardio- exposure. toxicity. Arch Toxicol [Epub ahead of print]. doi:10.1007/ Clin Toxicol 2017; online early: s00204-017-1998-6. doi: 10.1080/15563650.2017.1340647: Arch Toxicol 2017; online early: doi: 10.1007/s00204-017-2028-4: Pyrethroid insecticides Amitraz General Marettova E, Maretta M, Legáth J. Shashidhara S, Mundkur SC, Hebbar SA, Kumar A, Effect of pyrethroids on female genital system. Review. Sambasivan V. Anim Reprod Sci 2017; online early: Amitraz: a perpetual silent menace among children in doi: 10.1016/j.anireprosci.2017.07.007: developing countries–A case report.

Pediatr Emerg Care 2017; online early: doi: 10.1097/PEC.0000000000001247: CHEMICAL WARFARE, BIOLOGICAL WARFARE AND Bipyridyl herbicides Liu X, Ma T, Li L-L, Qu B, Liu Z. RIOT CONTROL AGENTS Predictive values of urine paraquat concentration, dose of Chemical warfare poison, arterial blood lactate and APACHE II score in the prognosis of patients with acute paraquat poisoning. General Exp Ther Med 2017; 14: 79-86. Althoff MA, Bertsch A, Metzulat M, Klapötke TM, Karaghiosoff KL.

Application of headspace and direct immersion solid-phase Monte AA, Sun H, Rapp-Olsson AMM, Mohamed F, microextraction in the analysis of organothiophosphates Gawarammana I, Buckley NA, Evans CM, Yang IV, Schwartz related to the Chemical Weapons Convention from water DA. and complex matrices. The plasma concentration of MUC5B is associated with Talanta 2017; 174: 295-300. clinical outcomes in paraquat poisoned patients.

Am J Respir Crit Care Med 2017; online early: doi: 10.1164/rccm.201705-0866LE: Nitrogen mustard Das LM, Binko AM, Traylor ZP, Duesler L, Lu KQ. Wang Y, Chen Y, Mao L, Zhao G, Hong G, Li M, Wu B, Defining the timing of 25(OH)D rescue following nitrogen Chen X, Tan M, Wang N, Lu Z. mustard exposure. Effects of hemoperfusion and continuous renal replacement Cutan Ocul Toxicol 2017; online early: therapy on patient survival following paraquat poisoning. doi: 10.1080/15569527.2017.1355315: PLoS ONE 2017; 12: e0181207. PLANTS Organochlorine pesticides Abrus precatorius (Jequirity) Endosulfan Huang J, Zhang W, Li X, Feng S, Ye G, Wei H, Gong X. Menezes RG, Qadir TF, Moin A, Fatima H, Hussain SA, Acute abrin poisoning treated with continuous renal Madadin M, Pasha SB, Al Rubaish FA, Senthilkumaran S. replacement therapy and hemoperfusion successfully: a Endosulfan poisoning: an overview. case report. J Forensic Leg Med 2017; 51: 27-33. Medicine (Baltimore) 2017; 96: e7423.

O'Connor AD, Padilla-Jones A, Ruha A-M. Cerbera manghas (Sea mango) Severe bark scorpion envenomation in adults. Mu H-W, Chen C-H, Yang K-W, Hung D-Z. Clin Toxicol 2017; online early: Cerbera manghas poisoning survived by using extra- doi: 10.1080/15563650.2017.1353095: corporeal life support. Clin Toxicol 2017; online early: Silva BAJD, Fé NF, Gomes AADS, Souza ADS, Sachett JAG, doi: 10.1080/15563650.2017.1343478: Fan HW, Melo GC, Monteiro WM. Implication of Tityus apiacas (Lourenco, 2002) in scorpion envenomations in the Southern Amazon border, Brazil. Mitragyna speciosa (Kratom) Rev Soc Bras Med Trop 2017; 50: 427-30. Cumpston KL, Carter M, Wills BK. Clinical outcomes after Kratom exposures: a poison center case series. Snake bites Am J Emerg Med 2017; online early: Kasturiratne A, Pathmeswaran A, Wickremasinghe AR, doi: 10.1016/j.ajem.2017.07.051: Jayamanne SF, Dawson A, Isbister GK, de Silva HJ, Lalloo DG. The socio-economic burden of snakebite in Sri Lanka. Mushrooms PLoS Negl Trop Dis 2017; 11: e0005647. Nomura C, Masayama A, Yamaguchi M, Sakuma D, Kajimura K. Spyres MB, Ruha A-M, Kleinschmidt K, Vohra R, Smith E, PCR-based method for the detection of toxic mushrooms Padilla-Jones A. causing food-poisoning incidents. Epidemiology and clinical outcomes of snakebite in the Shokuhin Eiseigaku Zasshi 2017; 58: 132-42. elderly: a ToxIC database study. Clin Toxicol 2017; online early: Voelker R. doi: 10.1080/15563650.2017.1342829: Toxic mushrooms in California. JAMA 2017; 318: 117. Crotalinae (Pit vipers) Namal Rathnayaka RMMK, Ranathunga PEAN, Kularatne SAM. ANIMALS Epidemiology and clinical features of Green pit viper Fish/marine poisoning (Trimeresurus trigonocephalus) envenoming in Sri Lanka. Toxicon 2017; 137: 99-105. Jellyfish Bouyer-Monot D, Pelczar S, Ferracci S, Boucaud-Maitre D. Retrospective study of jellyfish envenomation in Elapidae emergency wards in Guadeloupe between 2010 and 2016: Mao Y-C, Liu P-Y, Chiang L-C, Liao S-C, Su H-Y, Hsieh S-Y, when to diagnose Irukandji syndrome? Yang C-C. Toxicon 2017; 137: 73-7. Bungarus multicinctus multicinctus snakebite in Taiwan. Am J Trop Med Hyg 2017; 96: 1497-504. Suzuki S, Miyata Y, Jinno M, Kishino Y, Homma T, Ota S, Tanaka A, Yokoe T, Ohnishi T, Sagara H, Kurata N, Viperinae (True vipers) Shimakura K, Kurose K. Tirosh-Levy S, Solomovich R, Comte J, Sutton GA, An adult case of anaphylaxis caused by allergy to jellyfish. Steinman A. Arerugi 2017; 66: 804-8. Daboia (Vipera) palaestinae envenomation in horses: clinical and hematological signs, risk factors for mortality Insects and construction of a novel severity scoring system. Toxicon 2017; 137: 58-64. Chomchai S, Chomchai C.

Histamine poisoning from insect consumption: an outbreak investigation from Thailand. Spiders Clin Toxicol 2017; online early: Hu Y, Xu Y. doi: 10.1080/15563650.2017.1349320: The optical imaging of Tarantula hair corneal injury: one case report and review of the literature. Scorpions Photodiagnosis Photodyn Ther 2017; online early: doi: 10.1016/j.pdpdt.2017.07.005: Amr ZS, Al Zou'bi R, Abdo N, Bani Hani R.

Scorpion stings in Jordan: an update.

Wilderness Environ Med 2017; online early: doi: 10.1016/j.wem.2017.05.003:

INDEX

Abrus precatorius ...... 28 Amitraz ...... 28 Acetaminophen ...... 22 Amitriptyline ...... 23 Acetylcysteine ...... 14 Amlodipine ...... 19 Adrenaline ...... 17 Amphoteric solutions ...... 15 Alcohol ...... 24 Anaesthetics...... 17 Allopurinol ...... 15 Analytical toxicology ...... 8 Alpha-2 agonists ...... 17 Animals, general ...... 29 Aluminium phosphide ...... 28 Antiarrhythmic drugs ...... 17 Amfetamines ...... 17 Antibiotics ...... 17 Amiodarone ...... 17 Anticoagulants...... 17

Anticonvulsants ...... 17 Fluorouracil ...... 18 Antidotes ...... 14 Forensic toxicology ...... 10 Antimalarial drugs ...... 18 Fragrance chemicals ...... 25 Antimony ...... 27 Gabapentin ...... 17 Antineoplastic drugs ...... 18 Haemodialysis ...... 15 Antipsychotics ...... 18 Haemoperfusion ...... 15 Antiviral drugs ...... 18 Haloperidol ...... 18 Aripiprazole ...... 18 Hazardous waste ...... 24 Asenapine ...... 18 Hepatotoxicity ...... 11 Atipamezole ...... 14 Herbal medicines ...... 19 Auriculatone ...... 15 Heroin ...... 19 Baclofen ...... 18 Hyperbaric oxygen therapy ...... 14 Barium ...... 27 Ibogaine ...... 22 Benzalkonium chloride ...... 24 Ibuprofen ...... 22 Benzodiazepines ...... 18 Idarucizumab ...... 14 Beta-blockers ...... 19 Immunosuppressants ...... 20 Biofuels ...... 24 Inhalation toxicity ...... 11 Biological warfare...... 28 Insects...... 29 Biomarkers ...... 8 Insulin ...... 20 Bipyridyl herbicides ...... 28 Jellyfish...... 29 Bisphenol A ...... 24 Jequirity ...... 28 Bisphosphonates ...... 19 Kinetics ...... 12 Body packers ...... 9 Kratom ...... 20, 29 Butane ...... 24 Lead ...... 27 Cadmium ...... 27 Levetiracetam ...... 16, 20 Caffeine...... 19 Lipid emulsion therapy ...... 14 Calcium channel blockers...... 19 Management, general ...... 14 Cannabis ...... 19 Marijuana ...... 19 Capecitabine ...... 18 MDMA ...... 17 Capsaicin ...... 15 Mechanisms ...... 12 Carbamazepine ...... 17 Medication errors ...... 12 Carbon monoxide ...... 24 Melamine ...... 26 Carcinogenicity ...... 9 Melatonin ...... 16 Cardiotoxicity ...... 9 Mephedrone ...... 20 Cerbera manghas ...... 29 Mercury ...... 27 Chemical incidents ...... 24 Metabolism ...... 12 Chemical warfare, general ...... 28 Metals, general ...... 27 Chemicals, general ...... 24 Methanol...... 26 Chloroquine ...... 18 Methotrexate ...... 18 Clozapine...... 18 Methylthioninium chloride ...... 20 Cocaine ...... 19 Metoprolol ...... 19 Corrosives ...... 25 Mitragyna speciosa ...... 29 Crotalinae ...... 29 Monocrotophos...... 28 Dabigatran ...... 17 Mushrooms ...... 29 Darunavir ...... 18 Naloxone ...... 15 Dermal toxicity...... 9 Nanomedicines ...... 20 Designer benzodiazepines...... 21 Nanoparticles ...... 26 Desomorphine ...... 19 Nephrotoxicity ...... 12 Developmental toxicology ...... 9 Neurotoxicity ...... 12 Diacetylmorphine ...... 19 Nicotine ...... 20 Dietary supplements ...... 19 Nitrogen mustard ...... 20, 28 Diltiazem ...... 19 Novel psychoactive substances ...... 20 Donepezil ...... 19 NSAIDs ...... 22 Driving under the influence ...... 9 Occupational toxicology ...... 12 Drugs, general ...... 16 Ocular toxicity ...... 12 Dust ...... 25 Opioids ...... 22 E-cigarettes and e-liquids ...... 25 Organochlorine pesticides, general ...... 28 Ecstasy ...... 17 Organophosphorus insecticides, general ...... 28 Elapidae ...... 29 Oxycodone ...... 22 Endosulfan ...... 28 Ozone ...... 26 Enoxaparin ...... 17 Paediatric toxicology ...... 13 Epidemiology ...... 10 Paracetamol ...... 22 Ethanol...... 24 Paraoxon ...... 28 Ethnic remedies ...... 19 Perfluorinated compounds ...... 26 Ethylene glycol ...... 25 Pesticides, general ...... 27 Extracorporeal treatments ...... 15 Phenethylamines ...... 21 Fentanyl ...... 22 Physostigmine ...... 15 Fish/marine poisoning ...... 29 Pit vipers ...... 29 Flame retardants ...... 25 Plants, general ...... 28 Flucloxacillin ...... 17 Plasticizers ...... 26 Flumazenil ...... 14 Pollution ...... 24 Fluoroacetamide ...... 25 Polonium...... 27

Polybrominated diphenyl ethers ...... 26 Substance abuse ...... 23 Polycyclic aromatic hydrocarbons ...... 26 Suicide ...... 14 Propafenone ...... 17 Sweeteners ...... 26 Propranolol ...... 19 Synthetic cannabinoids ...... 21 Psychotropic drugs ...... 23 Synthetic cathinones ...... 21 Pyrethroid insecticides, general ...... 28 Synthetic opioids ...... 21 Pyrrolizidine alkaloids ...... 26 Tacrolimus ...... 20 Quinidine ...... 17 Tapentadol ...... 22 Radiation ...... 26 Terbufos ...... 28 Reprotoxicity ...... 14 Tobacco ...... 26 Risk assessment...... 14 Toxicology, general ...... 8 Salicylates ...... 23 Tranylcypromine ...... 23 Scorpions ...... 29 Triclosan ...... 27 Sea mango ...... 29 Tricyclic antidepressants ...... 23 Sedatives...... 23 True vipers...... 29 Sertraline...... 23 Valproate ...... 18 Smoke ...... 26 Verapamil ...... 19 Snake bites ...... 29 Veterinary products ...... 23 Sodium ...... 26 Vilazodone ...... 23 Spiders ...... 29 Viperinae ...... 29 SSRIs ...... 23 Zoledronic acid ...... 19

The NPIS is commissioned by Public Health England