Caracterización de las consultas realizadas a un Centro de Información Toxicológica por productos de aseo y productos cosméticos en niños / Characterization of the phone-calls made to a poison center related to household and cosmetics products exposition in pediatrics

INTRODUCCIÓN: Los productos de aseo y cosméticos son necesarios en el diario vivir y ampliamente utilizados por la población. Sin embargo, su uso puede no estar exento de riesgos, especialmente cuando no se utilizan o almacenan según lo recomendado. Es importante caracterizar las exposiciones, ya que eso es útil para implementar estrategias para reducir la morbilidad, mortalidad y costos asociados, especialmente en la población infantil. OBJETIVO: Caracterizar los reportes asociados a exposiciones a productos de aseo y productos cosméticos en pacientes menores de 12 años reportados al Centro de Información Toxicológica de la Universidad Católica de Chile (CITUC). PACIENTES Y MÉTODO: Estudio descriptivo transversal de llamados telefónicos reportados a CITUC durante el año 2016. Se analizaron las variables: edad, sexo, agente, interlocutor, localización del interlocutor e inciden te, circunstancia de exposición, vía(s) de exposición, sintomatología, y severidad, mediante fichas de registro manual y desde el software de registro electrónico denominado "INTOX Data Manage ment System" de la OMS. RESULTADOS: Cumplieron criterios de inclusión 3.415 casos. Los menores de 5 años representaron el 91% de las exposiciones y el 58,5% correspondió al sexo masculino. Un 99,4% correspondió a exposiciones accidentales y el 98,6% ocurrieron en el hogar. El 68,3% no presentó síntomas, tras la exposición. Las llamadas fueron realizadas por familiares (57%) y personal de salud (42%). Los 4 agentes con mayor incidencia fueron cloro doméstico (27,6%), limpiadores y lustres de pisos (13,1%), lavalozas (7,9%) y perfumes/colonias (5,8%). La principal vía de exposición fue digestiva (89,4%). CONCLUSIONES: Los productos de aseo y cosméticos son causas comunes de exposiciones especialmente en menores de 5 años. Si bien son productos de baja mortalidad y morbilidad, es importante educar a la población para prevenir posibles intoxicaciones en la población infantil.

INTRODUCTION: Household cleaning products and cosmetics are necessary for daily life and widely used by the population. However, their use may not be risk-free, especially when they are not used or stored as recommended. It is important to characterize exposures, as this is useful for developing stra tegies to reduce morbidity, mortality, and health costs associated, especially in the child population. OBJECTIVE: To describe reports associated with household cleaning products and cosmetics exposure in patients under the age of 12, reported to the Poison Information Center of the Catholic University of Chile (CITUC). PATIENTS AND METHOD: Descriptive cross-sectional study of phone calls to CITUC during 2016. The analyzed variables were age, sex, product, caller, caller and incident location, ex posure circumstances, exposure route(s), symptoms, and severity from manual records and from the WHO's electronic record software 'INTOX Data Management System'. RESULTS: 3,415 cases met the inclusion criteria. Children under the age of five represented 91% of the exposures, and 58.5% were male. 99.4% were accidental exposures, and 98.6% occurred at home. Family members (57%) and health personnel (42%) made the calls. 68.3% of the patients had no symptoms after exposure. The four products with the highest incidence were household bleach (27.6%), floor cleaners and polishers (13.1%), dish soap (7.9%), and perfume/cologne (5.8%). The main exposure route was by ingestion (89.4%). CONCLUSIONS: Household cleaning products and cosmetics are common causes of exposures especially in children under the age of five. Although these products have a low morbidity and mortality rate, it is important to educate the population to prevent possible poisonings in the child population.

Aplicação da análise multivariada para o mapeamento dos casos de intoxicações agudas atendidos no Centro de Controle de Intoxicações da cidade de São Paulo / Application of multivariate analysis for the mapping of acute intoxication cases attended in Poison Control Center of the São Paulo city

A Toxicologia tem desempenhado um importante papel na identificação de efeitos nocivos à população, gerando subsídios para a tomada de decisões na prática clínica, auxiliando desta forma no bom prognóstico de pacientes intoxicados. De acordo com a Pan American Health Organization, o sucesso em qualquer intervenção em saúde somente pode ser obtido com a criação e manutenção de um banco de dados confiável, que seja capaz de predizer as diversas particularidades das intoxicações, como a população-alvo e suas suscetibilidades. Assim, recomenda-se que médicos, especialistas, legisladores e administradores em saúde adotem em sua rotina uma coleta de dados sistêmica e integrada para o mapeamento e caracterização das intoxicações. Neste cenário, técnicas de análises multivariadas poderiam ser empregadas para evidenciar possíveis intercorrelações; entretanto, seu uso ainda não é comum na toxicologia clínica. Neste trabalho foram identificados e quantificados agentes exógenos em amostras biológicas (sangue e urina) provenientes do Centro de Controle de Intoxicações da cidade de São Paulo, correlacionando os dados obtidos dessas análises com o perfil clínico e prognóstico dos pacientes. Fármacos benzodiazepínicos, antidepressivos, anticonvulsivantes, paracetamol, drogas de abuso e praguicidas foram selecionados de acordo com a incidência reportada por esse centro no período de 2013 a 2014. Do total de amostras analisadas (n = 320), 192 foram positivas para alguma substância, sendo 101 positivas para etanol e 131 positivas para as demais substâncias. Os dados obtidos foram submetidos à análise de correspondência múltipla e análise hierárquica de cluster. A partir da análise multivariada foi possível agrupar os indivíduos em 3 clusters, o que correspondeu a 66,5% do total de informações. No primeiro eixo houve a separação dos pacientes do gênero feminino, que se intoxicaram ou foram expostos a medicamentos e drogas de abuso, por tentativa de suicídio, dos pacientes do gênero masculino, de idade entre 30 a 39 anos, que se intoxicaram com drogas de abuso. No segundo eixo fatorial foram agrupados os pacientes que se intoxicaram com etanol isoladamente, juntamente com pacientes que se intoxicaram com diazepam. Este trabalho contribuiu para o mapeamento dos casos de intoxicação atendidos pelo CCI-SP e foi um estudo inicial para a criação de um banco de dados que poderá ser alimentado constantemente e assim, oferecer ao sistema de toxicovigilância uma base para políticas educativas

Toxicology has played an important role in the identification of harmful effects to the population, generating subsidies for decision making in clinical practice, helping in this way the good prognosis of acutely intoxicated patients. According to the Pan American Health Organization, success in any health intervention can only be achieved by creating and maintaining a reliable database that is capable of predicting the various characteristics of intoxications, such as the target population and their susceptibilities. Thus, it is recommended that doctors, specialists, legislators and health administrators adopt in their routine a systemic and integrated data collection for the mapping and characterization of intoxications. In this scenario, multivariate analysis techniques could be used to evidence possible intercorrelations; however, its use is not yet common in clinical toxicology. In this work, were identified and quantified exogenous agents in biological samples (blood and urine) from the Poison Control Center São Paulo city, correlating the data obtained from these analyzes with the clinical and prognostic profile of the patients. Benzodiazepines, antidepressants, anticonvulsants, acetaminophen, drugs of abuse and pesticides were selected according to the incidence reported by this center in the period from 2013 to 2014. Of the total number of samples analyzed (n = 320), 192 samples have shown to be positive for some of the analytes, from these 100 were positive for ethanol and 131 positive for other substances. The data were submitted to multiple correspondence analysis and hierarchical cluster analysis. From the multivariate analysis it was possible to group the individuals into 3 clusters, which corresponded to 66.5% of the total information. In the first axis, the patients were separated from the female gender, who were intoxicated or were exposed to drugs and suicide attempt of the male patients, aged between 30 and 39 years, who became intoxicated with drugs of abuse. In the second factorial axis were grouped the patients who were intoxicated with ethanol, together with patients who became intoxicated with diazepam. This work contributed to the mapping of intoxication cases attended by the CCI-SP and was a initial study for the creation of a database that could be fed constantly and thus provide the toxicovigilance system with a basis for educational policies

Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta).

Background & objectives: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 μg)] and combination rabies vaccine [CRV (100 μg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. Methods: As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. Results: In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28th day. Interpretation & conclusions: The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.

Toxicología clínica comunitaria / Community Clinical Toxicology

En algunos países de América Latina las intoxicaciones agudas se manejan de manera profesional por médicos especialistas en la mate-ria. Algo similar ocurre con las intoxicaciones crónicas de origen laboral en el sector formal. No obstante, una realidad diferente ocurre en cuanto a la evaluación de las intoxicaciones crónicas de origen ambiental, dado que éstas por su naturaleza, son más difíciles de diagnosticar. Para el tratamiento de las intoxicaciones agudas se han organizado Centros de Información y Atención Toxicológica, pero para las intoxicaciones crónicas ambientales no se ha generado organismos semejantes. Por consiguiente, en este trabajo sugerimos un modelo de atención de la intoxicaciones crónicas a través de grupos multidisciplinarios bajo el esquema de una nueva disciplina: la Toxicología Clínica Comunitaria, cuyo objetivo sería la atención simultánea de las intoxicaciones agudas que generalmente se atienden en un ámbito hospitalario y de las intoxicaciones ambientales que por lo normal se presentan a nivel comunitario. El objetivo final es aprovechar la experiencia que existe en la Región en cuanto a Toxicología Clínica para organizar el trabajo comunitario.

In some Latin American countries acute intoxication is professionally managed by specialized physicians qualified in the area. Something similar occurs with work-related chronic intoxication in the formal sector. However, a different reality prevails for the assessment of chronic intoxication of environmental origin, since it is by definition more difficult to diagnose. For treatment of acute intoxication, Toxicological Information and Care Centers have been set up, though similar bodies have not been created for chronic environmental intoxication. Therefore, in this study a model of chronic intoxication care is proposed, using multidisciplinary teams adopting a new approach, namely Community Clinical Toxicology, the goal of which would be the simultaneous care of acute intoxication which is generally treated in hospital, and environmental intoxication that is normal dealt with at community level. The ultimate goal is to take advantage of the expertise that exists in the Region in terms of Clinical Toxicology to organize community work.

Estudo de toxicologia clínica de um fitoterápico contendo Passiflora incarnata L., Crataegus oxyacantha L., Salix alba L. em voluntários saudáveis / Clinical toxicology study of an herbal medicine with Passiflora incarnata L., Crataegus oxyacantha L., Salix alba L. in healthy volunteers

O Pasalix® é um produto fitoterápico contendo uma associação de três plantas medicinais: Passiflora incarnata, Salix alba e Crataegus oxyacantha. Sua principal indicação é para o tratamento da ansiedade e insônia. O objetivo desse estudo foi avaliar a toxicologia clínica dessa formulação em voluntários saudáveis. Para isso realizou-se um ensaio clínico não aleatório, aberto, com 24 voluntários sadios do sexo masculino, que receberam ambulatorialmente dois (2) comprimidos revestidos do fitoterápico duas vezes ao dia, durante 28 dias ininterruptos. Os voluntários foram incluídos no estudo somente quando considerados saudáveis após avaliação clínica, exame físico e exames laboratoriais que antecederam o estudo. A avaliação laboratorial incluiu análise hematológica, bioquímica e sorológica. A avaliação clínica e laboratorial foi repetida após a 1ª, 2ª, 3ª e 4ª semanas de tratamento e 7 dias após a última administração. O Pasalix® foi bem tolerado pelos 24 voluntários não apresentando eventos adversos graves. Os exames clínicos, eletrocardiográficos e laboratoriais efetuados antes, durante e após o ensaio não evidenciaram sinais de toxicidade nos diversos órgãos e sistemas avaliados, confirmando a segurança da preparação para utilização em ensaios de eficácia terapêutica.

Pasalix® is an herbal medicine containing a combination of three medicinal plants: Passiflora incarnata, Salix alba and Crataegus oxyacantha. Its main indication is to treat anxiety and insomnia. The purpose of this study was to evaluate the clinical toxicology of that formulation in healthy volunteers. For this, a non-randomized open clinical trial was conducted with 24 healthy male volunteers, who received two (2) coated tablets of the herbal medicine twice a day for 28 uninterrupted days. The volunteers were included in the study only when considered healthy after clinical assessment, physical examination and laboratory tests which preceded the study. The laboratory tests included: hematological, biochemical and serological analysis. The clinical and laboratory evaluation was repeated after the 1st, 2nd, 3rd and 4th weeks of the treatment and 7 days after the last administration. Pasalix® was well tolerated by the 24 volunteers, and it has showed no serious adverse events. The clinical, laboratory, and electrocardiographic data assessed before, during and after the test showed no signals of toxicity in various organs and systems evaluated, confirming the safety of the preparation for use in trials of therapeutic efficacy.

Verificação da ocorrência de óbitos com carbamatos no Distrito Federal entre os anos 2000 e 2004 por análise de laudos necroscópicos / A survey of occurrence of deaths caused by carbamates in the Federal District of Brazil between the years 2000 and 2004 through the analysis of autopsy reports

Introdução: O presente estudo teve como objetivo quantificar, junto ao Instituto de Medicina Legal do Distrito Federal, o número de óbitos após intoxicação por inseticidas carbamatos, no Distrito Federal, entre os anos 2000 e 2004. Método: Por meio de levantamento nas fichas de análise de laudos necroscópicos investigou-se os dados de intoxicação humana por carbamatos e, posteriormente à necropsia, a identificação do agente tóxico. Resultados: Foram selecionados 72 casos com suspeita de intoxicação por carbamatos, dos quais 13,9% (10) foram confirmados. Desses, emnove casos (90%) o agente foi identificado como “chumbinho”, constatado pela presença do ingrediente ativo aldicarb e, em apenas um caso (10%), houve a identificação do ingrediente ativo carbofurano. Conclusão: Observou-se que, embora o quantitativo de óbitos tenha sido aparentemente pequeno, houve um aumento considerável no último ano da pesquisa, reforçando assim a necessidade de maior controle na comercialização de agrotóxicos e particularmente daqueles considerados ilegais e vendidos clandestinamente, como é o caso do “chumbinho”.

Introduction: The objective of this paper is to present a survey of deaths due to intoxication with carbamate insecticides in the Federal District of Brazil, between the years 2000 and 2004, recorded by the Institute of Forensic Medicine of the Federal District. Method: Through the analysis of necroscopic reports, we investigated data concerning human intoxication by carbamates and, through necropsy, we sought to identify the nature of the toxic agent. Results: 72 cases of suspicion of intoxication by carbamates were selected. Only 13,9% (10) were confirmed and 85,1% (62) non-confirmed. In nine cases (90%) the agent was identified as “chumbinho”, verified through the detection of the active ingredient aldicarb, and only one (10%) was identified as the active ingredient carbofuran. Conclusion: We observed that although the number of deaths has been relatively small, there was a significative increase in the last year of the research, which supports the need for major control action in the trade of pesticides and mainly of those illegal and secretly sold, as it is the case of “chumbinho.”