Letter to the Editor
Pancreatic damage induced by chlorothalonil acute intentional intoxication
Lesión pancreática inducida por intoxicación aguda intencional por clorotanolil
Irene Romera-Sáncheza, Rosa María Alcaraz-Peñarrochaa,b, Juan Carlos Ruiz-Rodrígueza,b,
Corresponding author
a Intensive Care Department, Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
b Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
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Lesion of the main pancreatic duct (grade IV) next to a zone of glandular necrosis. Significant amount of free intra-abdominal fluid with thickening and enhancement of peritoneal leaves suggestive of chemical peritonitis.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Chlorothalonil is a benzonitrile halogenated fungicide considered the third most widely utilized pesticide in the United States in 1997. Years later it was banned in several countries due to high fish and amphibian toxicity and potential carcinogenic effect on mammals. Toxicity is mainly based on its irritating nature and there is no available treatment or antidot.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report a case of an 18-year-old Pakistani woman, with no relevant medical history, that deliberately ingested approximately 100<span class="elsevierStyleHsp" style=""></span>mL of an industrial pesticide. Within a few minutes she became nauseous and vomited. She was transferred to the emergency room (ER) of our hospital where vomits, epigastric pain and decreased level of consciousness until Glasgow Coma Scale of 10/15 points (oral: 2; verbal: 2; motor: 6) were observed. The pesticide was identified as chlorothalonil, that the family kept at home for domestic use. During her stay in the ER, the patient presented deviation of the gaze to the left and tonic movements of the four extremities. An urgent cranial CT was normal and the EEG ruled out any critical activity. The patient was intubated and mechanical ventilation initiated, as well as treatment with activated carbon. Then she was admitted in the Intensive Care Unit. Progressively during the first days of admission, the hepatic profile was altered with an increase in serum amylase up to 516<span class="elsevierStyleHsp" style=""></span>IU/L, aspartate transaminase 428<span class="elsevierStyleHsp" style=""></span>IU/L, alanine aminotransferase 426<span class="elsevierStyleHsp" style=""></span>IU/L, alkaline phosphatase 911<span class="elsevierStyleHsp" style=""></span>IU/L and gamma-glutamyl transferase of 3274<span class="elsevierStyleHsp" style=""></span>IU/L. Abdominal CT showed a grade IV pancreatic laceration and pancreatic necrosis with extensive chemical peritonitis (<a class="elsevierStyleCrossRef" href="#fig0005">Image 1</a>). Nothing by mouth and parenteral nutrition were started. Fourteen days later a new abdominal CT showed stability of the hypodense lesion in the pancreatic neck and progressive decrease in intra-abdominal fluid. During her ICU admission she also presented encephalopathy, myopathy and rhabdomyolysis, requiring percutaneous tracheostomy. After twenty-nine days of ICU stay patient was transferred to the hospitalization ward and was discharged from the hospital 10 days later.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Chlorothalonil is an organic compound classified as a benzonitrile halogenated fungicide and specifically as a poly-chlorinated aromatic (2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> It has a wide spectrum of activity against diseases of vegetables, ornamentals plants, orchards and lawns. It was introduced in 1965 by Diamond Shamrock Corp. and was first registered in 1966 within the United States as an agricultural fungicide. In 1997, it was recognized as the third most widely utilized fungicide in the United States.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Later, in 2019, it was banned in the European Union after a review that classified this compound as highly toxic for fish and amphibians, as well as for its potential damage to cellular DNA.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The mechanism of action is based on blocking the glycolytic and respiratory enzymatic pathways of fungal cells, blocking spore germination and the inactivation of fungal glutathione. The known adverse effects are mainly based on its irritating nature. According to the US Environmental Protection Agency it is an important eye irritant with category I toxicity. In inhalation cases it is considered moderately toxic (category II) and non-toxic (category IV) in cases of ingestion or skin contact. However, acute exposure to very high doses in mammals has been associated with ataxia, hyperactivity, epistaxis, vaginal bleeding, dermatitis, vomiting, and even death.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> There is no available treatment or antidote. Furthermore, it is suspected to be a human carcinogen (Group B2) and kidney and gastric tumors have been described in animals with chronic exposure to a diet contaminated with chlorothalonil.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In this particular case, we hypothesize that chlorothalonil may act as an endocrine disruptor. It has been associated with dysfunction of pancreatic beta and Langerhans cells on previous studies in mice<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3,4</span></a> and a case of diabetic ketoacidosis and insulin resistance after occupational subacute human exposure to chlorothalonil has been reported.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> The mechanism of the pancreatic affectation is not clear, but it seems to be reversible. In our patient, the pancreatic lesion evolved satisfactorily with stability of the hypodensity at the pancreas without further intervention.</p><p id="par0030" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first report of acute human intentional intoxication by a chloronitrile fungicide (PubMed research, period 1970–2020, chlorothalonil AND poisoning, chlorobenzenes AND poisoning). We believe that there is an association between the toxic and the pancreatic damage but, due to the infrequency of the intoxication, it is difficult to prove.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Consent for publication</span><p id="par0035" class="elsevierStylePara elsevierViewall">All authors consent for publication of this study.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">Not applicable.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Consent for publication" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Image 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 545 "Ancho" => 1300 "Tamanyo" => 98295 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Abdominal CT sections at the level of the pancreas (day +7) showing a wedge lesion in the pancreatic neck/body, corresponding to a laceration with probable complete section of the parenchyma (red arrow). Lesion of the main pancreatic duct (grade IV) next to a zone of glandular necrosis. Significant amount of free intra-abdominal fluid with thickening and enhancement of peritoneal leaves suggestive of chemical peritonitis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Environmental fate and toxicology of chlorothalonil" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.R. Van Scoy" 1 => "R.S. 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