Moderate Toxicity of Potential Boron-containing Therapeutic, Dipotassium-trioxohydroxytetrafl uorotriborate - K2 (B3 O3 F4 OH) in Rats and Mice

Abstract Biological activity of boron-containing compounds (BCCs) has been well-known. Growing interest and numerous applications for BCCs have been reported. Boron and boron-containing acids show low acute toxicity in mammals but data on halogenated boroxine (HB) - dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH) acute toxicity have not been reported before. This compound, characterized as a potential therapeutic for skin changes, exhibits no observable genotoxicity in doses lower that 0.1 mg/ml in vitro and 55 mg/kg in vivo. It has also been confirmed as an antitumour agent both in vitro and in vivo as well as an inhibitor of enzymes involved in antioxidant mechanisms. The aim of this study was to assess the acute toxicity of HB and to determine the maximum tolerated dose as well as a dose free of any signs of toxicity in different test organisms. Acute toxicity of HB was tested in Sprague-Dawley and Wistar rats and BALB/c mice after single parenteral application of different doses. We determined doses free of any sign of toxicity and LD50 after single dose administration. LD50 of HB ranges from 63 to 75 mg/kg in different test models, meaning that HB shows moderate toxicity

Anti-inflammatory effects and acute oral toxicity of Copaifera spp. essential oil-loaded nanoemulsion / Efectos antiinflamatorios y toxicidad oral aguda de nanoemulsión cargada de aceite esencial de Copaifera spp

Copaifera spp. essential oil (EOC) was extracted by hydrodistillation of Copaifera oleoresin (COR). The EOC was characterized by GC/MS and a novel EOC-loaded nanoemulsion was developed to enhance the EOC solubility and to evaluate its utility as antinflammatory. EOC contain 14 volatile compounds (including ß-caryophyllene: 51.52%) having a required HLB of 11. The Surfactant: EOC: Water ratio of 13:15:75 (%, w:w:w) produced the optimal formulation (particle size: 94.47 nm). The EOC-loaded nanoemulsion presented a pseudoplastic/thixotropic behavior with excellent shelf stability for 6 months. The anti-inflammatory effect of the nanoemulsion was more potent than that of the EOC, and statistically equal to diclofenac (50 mg/kg). The EOC-loaded nanoemulsion showed no oral acute toxicity (in mice) at 2000 mg/kg; hence, it is considered a nontoxic product. The development of the EOC-loaded nanoemulsion added value to both the COR and the EOC by providinga suitable formulation that could be used as an anti-inflammatory product.

El aceite esencial (EOC) fue extraído por hidrodestilación de oleoresina de Copaifera spp. El EOC fue caracterizado químicamente por GC/MS. Se formuló una nanoemulsión con EOC para mejorar la solubilidad del EOC y evaluar su utilidad como antiinflamatorio. El EOC contiene 14 compuestos volátiles (incluido el ß-cariofileno: 51,52%) con un HLB requerido de 11. La relación Tensioactivo: EOC: Agua de 13:15:75 (%, p:p:p) produjo la formulación óptima (tamaño de partícula: 94,47 nm).. La nanoemulsión cargada con EOC presentó un comportamiento pseudoplástico/tixotrópico con una excelente estabilidad en almacenamiento durante 6 meses. El efecto antiinflamatorio de la nanoemulsión fue más potente que el del EOC y estadísticamente igual al diclofenaco (50 mg/kg). La nanoemulsión cargada con COE no mostró toxicidad aguda oral (en ratones) a 2000 mg/kg; por lo tanto, se considera un producto no tóxico. El desarrollo de la nanoemulsión cargada con EOC agregó valor tanto al COR como al EOC al proporcionar una formulación adecuada que podría usarse como un producto antiinflamatorio.

Toxicity evaluation of water extract of tissue-cultured Taraxacum formosanum by acute, subacute administration, and Ames test

BACKGROUND: Taraxacum species (commonly known as dandelion) used as herbal medicine have been reported to exhibit an antiproliferative effect on hepatoma cells and antitumor activity in non-small-cell lung cancer cells. Although several investigations have demonstrated the safety of Taraxacum officinale, the safety of tissue-cultured plants of T. formosanum has not been assessed so far. Therefore, the present study examines the safety of the water extract of the entire plant of tissue cultured T. formosanum based on acute and subacute toxicity tests in rats, as well as the Ames tests. RESULTS: No death or toxicity symptoms were observed in the acute and subacute tests. The results of the acute test revealed that the LD50 (50% of lethal dose) value of the T. formosanum water extract for rats exceeded 5 g/kg bw. No abnormal changes in the body weight, weekly food consumption, organ weight, or hematological, biochemical, and morphological parameters were observed in the subacute toxicity test. Thus, the no observed adverse effect level (NOAEL) of T. formosanum water extract was estimated to be higher than 2.0 g/kg. Finally, the results of the Ames test revealed that T. formosanum water extract was not genotoxic at any tested concentration to any of five Salmonella strains. CONCLUSIONS: The water extract of tissue-cultured T. formosanum was non-toxic to rats in acute and subacute tests and exhibited no genotoxicity to five Salmonella strains.

Fatores Preditores de Complicações após Radioterapia Conformacional 3D em Pacientes com Adenocarcinoma de Próstata / Predictors of Complications following 3D Conformational Radiotherapy in Patients with Prostate Adenocarcinoma / Factores Predictores de Complicaciones después de la Radioterapia Conformacional 3D en Pacientes con Adenocarcinoma de Próstata

Introdução: O câncer de próstata é considerado a neoplasia maligna mais comum que acomete homens em todas as Regiões do país, à exceção do câncer de pele não melanoma. Se diagnosticado e tratado precocemente, o câncer de próstata tem alta taxa de cura; contudo, terapêuticas como a radioterapia podem gerar complicações agudas que podem impactar as atividades cotidianas. Apesar das complicações no pós-tratamento, a radioterapia tem sido um método bastante praticado e que apresenta resultados positivos, ocasionando melhoria da sobrevida livre de doença. Objetivo: Avaliar os principais fatores preditores de complicações agudas que acometem pacientes em tratamento radioterápico para câncer de próstata. Método: Para identificação de fatores preditores de complicações agudas pós-radioterapia, avaliaram-se, consecutiva e prospectivamente, 208 pacientes diagnosticados com adenocarcinoma de próstata tratados com radioterapia conformacional 3D em um centro referência vinculado ao SUS entre os anos 2016 e 2017. Realizou-se ainda avaliação retrospectiva de prontuários para coleta de dados adicionais. A análise estatística foi realizada por meio dos testes qui-quadrado, exato de Fisher, Anova e regressão logística ordinal. Resultados: Após análise da amostra, evidenciou-se que, entre as complicações agudas, as de maior incidência foram radiodermite, cistite e enterite/retite, de forma que tais complicações tiveram como fatores associados volume irradiado, tratamento prévio e sintomas prévios ao tratamento. Conclusão: O estudo sugere que, apesar da existência de complicações ao final do tratamento, a grande maioria é de baixa complexidade e que pacientes submetidos a procedimentos cirúrgicos prévios podem evoluir com presença de complicações mais graves.

Introduction: Prostate cancer is considered the most common malignancy that affects men in all regions of the country, except for non-melanoma skin cancer. If diagnosed and treated early, prostate cancer has a high cure rate; however, therapies such as radiotherapy can generate acute complications that can impact daily activities. Despite post-treatment complications, radiotherapy has been a widely practiced method and has shown positive results, leading to improved disease-free survival. Objective: To evaluate the main predictive factors for acute complications that affect patients undergoing radiotherapy for prostate cancer. Method: To identify predictive factors for acute post-radiotherapy complications, 208 patients diagnosed with prostate adenocarcinoma treated with 3D conformational radiotherapy were consecutively and prospectively evaluated at a referral center linked to SUS between the years 2016 and 2017. It was carried out retrospective evaluation of medical records to collect additional data. Statistical analysis was performed using the chi-square test, Fisher's exact, Anova and ordinal logistic regression. Results: After analyzing the sample, it was evidenced that among the acute complications, those with the highest incidence were radiodermatitis, cystitis, enteritis/rectitis, so that these complications had associated predictive factors as irradiated volume, previous treatment and symptoms. Conclusion: The study suggests that despite the existence of complications at the end of the treatment, the vast majority are of low complexity and that the patients submitted to previous surgical procedures can evolve with the presence of more severe complications.

Introducción: El cáncer de próstata se considera la neoplasia maligna más común que afecta a los hombres en todas las regiones del país, con la excepción del cáncer de piel no melanoma. Si se diagnostica y trata temprano, el cáncer de próstata tiene una alta tasa de curación; sin embargo, las terapias como la radioterapia pueden generar complicaciones agudas que pueden afectar las actividades diarias. A pesar de las complicaciones posteriores al tratamiento, la radioterapia ha sido un método ampliamente practicado y ha mostrado resultados positivos, lo que lleva a una mejor supervivencia libre de enfermedad. Objetivo: Evaluar los principales predictores de complicaciones agudas que afectan a los pacientes sometidos a radioterapia para el cáncer de próstata. Método: Para identificar los factores predictivos de complicaciones agudas posteriores a la radioterapia, 208 pacientes diagnosticados con adenocarcinoma de próstata tratados con radioterapia conformacional 3D fueron evaluados consecutiva y prospectivamente en un centro de referencia vinculado al SUS entre los años 2016 y 2017. Se realizó evaluación retrospectiva de registros médicos para recopilar datos adicionales. El análisis estadístico se realizó utilizando la prueba de chi-cuadrado, exacta de Fisher, de Anova y la regresión logística ordinal. Resultados: Después de analizar la muestra, se evidenció que, entre las complicaciones agudas, las de mayor incidencia fueron radiodermatitis, cistitis, enteritis/retitis y síntomas obstructivos, por lo que estas complicaciones tenían factores predictivos asociados, como el volumen irradiado, el tratamiento previo y los síntomas. Conclusión: El estudio sugiere que a pesar de la existencia de complicaciones al final del tratamiento, la gran mayoría son de baja complejidad. Como factores predictivos encontrados, se puede mencionar el volumen irradiado, la existencia de tratamiento previo y los síntomas en la consulta inicial.

Verification on the Developmental Toxicity of Short-term Exposure to Phenol in Rats / 生物医学与环境科学（英文）

Objective@#To verify the health advisory for short-term exposure to phenol.@*Methods@#The method of this validation experiment was the same as the US Environmental Protection Agency (EPA) methodology for toxicology experiments used to determine phenol drinking water equivalent level (DWEL). Pregnant female Sprague-Dawley rats were administered phenol in distilled water by gavage at daily doses of 15, 30, 60, 120, and 240 mg/kg body weight (b.w.) from implantation (the 6th day post-mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). The following information was recorded: general behavior; body weight; number of corpus luteum, live birth, fetus, stillbirth, and implantation; fetal gender; body weight; body length; tail length; and abnormalities and pathomorphological changes in the dams.@*Results@#In the 60 mg/kg b.w. dose group, the mortality of pregnant rats increased with increasing doses, suggesting maternal toxicity. Fetal and placental weights decreased as phenol dose increased from 30 mg/kg b.w., and were significantly different compared those in the vehicle control group, which suggested developmental toxicity in the fetuses. However, the phenol-exposed groups showed no significant change in other parameters compared with the vehicle control group ( > 0.05).@*Conclusion@#Despite using the same method as the US EPA, a different NOEAL of 15 mg/(kg·d) was obtained in this study.

Preclinical studies of hydroalcoholic extract of Calea uniflora Less / Estudios preclínicos de extracto hidroalcohólico de Calea uniflora Less

Calea uniflora Less known popularly as Arnica in Brazil, is a native plant from Brazil, popular used by coastal populations from south of Santa Catarina. The purpose of this study was to verify the safety profile in of hydroalcoholic extract of C. uniflora in florescences.The hydroalcoholic extract of C. uniflora in florescences was evaluated for its acute and sub-acute toxicity. Acute topical toxicity was performed using the methodology of guideline 402 from OECD. Acute oral toxicity was performed using the methodology of guideline 423 from OECD and sub-acute toxicity was performed using the methodology adapted of guideline 407 from OECD. The single dose for oral or topical administration of C. uniflora showed DL50> 5000 mg/kg b.w. The sub-acute treatment induced animal death in groups, which was administered extract in the doses 100, 250, 500 and 1000 mg/kg. The main signs of toxicity observed were respiratory difficulty, increase in lung weigh, lung damage and muscular relation. The topical or oral administration of C. uniflora extract in short period did not caused toxicological effects in animals, however, when administered for a longer period and in concentrations of 250, 500 and 1000 mg/kg (oral.) caused lung damage and even the death of the animal.

Calea uniflora Less conocida popularmente como Arnica en Brasil, es una planta nativa de Brasil, popularmente utilizada por poblaciones costeras del sur de Santa Catarina. El objetivo de este estudio fue verificar el perfil de seguridad del extracto hidroalcoólico de inflorescencias de C. uniflora. El extracto hidroalcoólico de inflorescencias de C. uniflora fue evaluado en cuanto a su toxicidad aguda y subaguda. La toxicidad tópica aguda se realizó utilizando la metodología de la directriz 402 de la OECD. La toxicidad oral aguda fue realizada usando la metodología de la directriz 423 de la OECD y la toxicidad subaguda fue realizada usando la metodología adaptada de la directriz 407 de la OECD. La dosis única para administración oral o tópica de C. uniflora mostro DL50> 5000 mg/kg. El tratamiento subagudo indujo la muerte de animales en grupos a los que se administró extracto en las dosis de 100, 250, 500 y 1000 mg/kg. Los principales signos de toxicidad observados fueron dificultad respiratoria, aumento del peso del pulmón, daño pulmonar y relación muscular. La administración tópica oral del extracto de C. uniflora a corto plazo no causó efectos toxicológicos en los animales, mientras que, cuando se administró por un período mayor y en las concentraciones de 250, 500 y 1000 mg/kg (oral) causaron danos en los pulmones y hasta la muerte del animal.

Comparative study with dry crude extracts of Ananas comosus L. Merril using LC50 and erythrocyte osmotic fragility as toxicity parameters / Estudio comparativo con extractos crudos secos de Ananas comosus L. Merril utilizando CL50 y fragilidad osmótica eritrocitaria como parámetros de toxicidad

Ananas comosus, conocido popularmente como piña, tiene una anatomía de planta bien definida y numerosos fitoquí­micos farmacológicamente activos. Algunos de éstos son responsables del potencial antimicrobiano de la especie, que ha sido ampliamente estudiado dada la resistencia bacteriana a los antibióticos actualmente utilizados. Teniendo esto en cuenta, se define que la característica principal de un medicamento es la ausencia de efectos tóxicos, por lo tanto, es necesario buscar datos sobre la toxicidad de A. comosus, colaborando para su posible uso como fármaco. Comparando extractos hidroalcohólicos de las hojas de la corona, cáscara y pulpa de la infrutescencia, fue posible determinar que los tres extractos probados no son tóxicos, siendo el de menor toxicidad para Artemia salina Leach (extracto de hojas con CL50 igual a 994 μg/mL) y a sangre de cordero (extracto de pulpa con porcentaje de hemólisis igual a 0,83%). Los estudios sobre principios y metodologías similares a los utilizados aquí han encontrado resultados comparables que indican la baja toxicidad de la planta. Estos resultados aportan a las investigaciónes que promueven el uso de la piña como agente fitoterapéutico y reafirman su presencia en el Sistema Único de Salud de Brasil.

Ananas comosus, popularly known as pineapple, has well defined plant anatomy and numerous pharmacologically active phytochemicals. Some of these are responsible for the species antimicrobial potential, which has been widely studied given the bac­terial resistance to the currently used antibiotics. Considering this, it is defined that the main characteristic of a drug is the absence of toxic effects, thus, there is a need to seek data regarding the toxicity of A. comosus, collaborating for its possible use as a drug. Comparing hydroalcoholic extracts from the crown leaves, skin and pulp of the infructescence, it was possible to determine that the three tested extracts are non-toxic, being the one with the lowest toxicity to Artemia salina Leach (leaves extract with LC50 equal to 994 μg/mL) and to lamb's blood (pulp extract with percentage of haemolysis equal to 0.83%). Studies concerning principles and methodologies similar to those used here have found comparable results stating the low toxicity of the plant. These results contribute to the research that promotes the use of pineapple as a phytotherapeutic agent and reaffirms its presence in the Brazilian Unified Health System.

Acute Toxicity Study of Intravenous Administration of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) in Sprague Dawley Rats

@#Introduction: Thymoquinone (TQ), a bioactive compound from Nigella sativa is known for its various medicinal properties. Due to the low solubility of TQ, nanostructured lipid carrier (NLC) has been used as a delivery system to improve its efficacy. Nevertheless, the effect of TQ-NLC when administered intravenously is unclear. This study investigated the acute toxicity profile of intravenous administration of TQ-NLC in an in vivo model. Methods: Twelve female Sprague dawley rats were assigned randomly into two groups (n=6); a control and a treatment group that received normal saline and 25 mg/kg TQ-NLC, respectively, via intravenous injection. The rats were observed for 14 days for any alterations to their usual physical conditions such as behaviour and mortality, body weight, food intake, organ-to-body weight ratio, and haematological, biochemical and histopathological profile. Results: There were no significant changes (p>0.05) in the body weight, food intake, organ-to-body weight ratio, and haematological, biochemical and histopathological profile between TQ-NLC treatment and the control group. However, inflammation was observed at the site of injection on the rat’s tail. Conclusion: Intravenous administration of TQ-NLC (25 mg/kg) did not exert acute toxic effect in female Sprague dawley rats. The data can be used as a basis to further develop TQNLC as a potential therapeutic drug.

Evaluation of Acute Toxicity Induced by Supercritical Carbon Dioxide Extract of Canarium odontophyllum (CO) Miq. Pulp Oil in SPF Sprague Dawley Rats

@#Introduction: Different solvents extraction was used to extract the good fatty acid composition of Dabai fruits. Nevertheless, solvents extraction may exhibit harmful effects. The present study was aimed to evaluate the safety of using supercritical carbon dioxide extraction (SCO2) of dabai pulp oil by acute toxicity study in Specific Pathogen Free (SPF) Sprague-Dawley (SD) rats. Methods: The CO pulp oil extract was prepared by SCO2 extraction of the freezedried pulp and was administered orally to SPF SD rats (consisted of 5 rats/sex/group) at upper limit dose 5000 mg/kg body weight (BW) for 14 days. The study includes the control and treatment groups, each consisting of 5 male and female rats. The rats were fed and allowed to drink sterilized water ad libitum. Fatty acid composition (FAC) of the extract was determined using GC-FID. Electrolytes and biochemical parameters in blood, as well as relative organs weight were measured. Results: The extract at a single dose of 5000 mg/kg did not cause any acute toxicity effects or mortality to the treatment of rats during observation periods in 14 days. FAC of the SCO2 extracted oil exhibited high content of palmitic and linoleic acids. The relative organs weights (ROW) and histopathology of rats were within normal range. Conclusion: Thus, the LD50 was estimated to be more than 5000 mg/kg of CO pulp oil extract and can be considered for further investigation for its therapeutic efficacy in a larger animal model

Acute toxicity mechanism of Panax notoginseng saponins in larvae zebrafish based on metabonomics / 中国中药杂志

Based on metabolomics,the metabolites of larvae zebrafish with overdose of Panax notoginseng saponins( PNS) were compared with those in normal group of larvae zebrafish to investigate the possible toxicity mechanism of overdose PNS in larvae zebrafish. An experimental animal model of long-term toxicity induced by PNS overdose was established by administering 1-6 dpf at low,medium and high doses of PNS,respectively. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry( UPLC-Q-TOF-MS) technique was combined with principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA) to screen and identify biomarkers associated with toxicity,and then the MetaboAnalyst database was used to analyze metabolism-related pathways. The results showed that the metabolites of each group could be distinguished distinctly,and they deviated more from the normal group in a time and dose dependent manner. Twenty-nine potential biomarkers related to toxicity( VIP>1,P<0. 05) were identified preliminarily,mainly involving six metabolic pathways. From the metabonomics point of view,the toxicity mechanism of overdose PNS may be related to the disorders of lipid metabolism,amino acid metabolism and energy metabolism.

Evaluación toxicológica y de metales (Cu, Pb, Ni, Zn y Cd) en el sedimento del reservorio Paiva Castro en Mairiporã-SP, Brasil / Toxicological and metal evaluation (Cu, Pb, Ni, Zn and Cd) in the sediment of Paiva Castro reservoir, in Mairiporã-SP, Brasil

El hombre ha cambiado el ambiente para sostener la demanda global de recursos naturales como el agua. La gestión de los cuerpos hídricos tiene que ser constante, con el propósito preventivo y correctivo, dependiendo del estado de antropización de cada sistema. El objetivo de este artículo fue analizar la toxicidad del sedimento y los metales Mn, Zn, Pb, Ni, Cd y Cu, en el reservorio Paiva Castro, que abastece la Region Metropolitana de São Paulo. Se realizaron 2 muestreos (Mayo 2011, estación seca y Enero de 2012, estación húmeda) y se analizaron 5 puntos próximos a la captación de agua por la Companhia de Saneamento Básico do Estado de São Paulo. Se realizaron ensayos de toxicidad aguda y crónica en sedimento, a través de ensayos biológicos con el cladócero Daphnia similis y el insecto Chironomus xanthus. El tratamiento de datos se realizó con el test de Fisher (mortalidad). El nivel de asociación entre las variables en sedimento y en los test ecotoxicológicos fueron evaluados por test no-paramétricos, a través del coeficiente de correlación de Spearman's. Los resultados del presente trabajo señalaron bajas concentracones de metales en el sedimento del área de estudio y ausencia de toxicidad en los organismos ensayados. Se puede concluir que área estudiada del reservorio Paiva Castro se encuentra poco impactada por los metales, sin efectos directos sobre la calidad de vida los organismos bentónicos: D. similis y C. xanthus.

Man had changed the natural environment in an attempt trying to supply the global demand for resources. The management of the hydric bodies has to be constant, with preventive and corrective purpose, depending on the eutrophization state of each one. The objective of this article was to analyze the sediment toxicity and the metals Mn, Zn, Pb, Ni, Cd and Cu, in the Paiva Castro reservoir, that supply the Metropolitan Region of São Paulo. It was made 2 collections (May 2011, dry season and January 2012, wet season). It was analyzed 5 points next to the water captation station by the Companhia de Saneamento Básico do Estado de São Paulo. The sediment was analyzed as for acute and chronic toxicity through bioassays with the cladocerans Daphnia similis and the insect Chironomus xanthus. Data treatment was done with Fisher Exact Test (mortality). The association level between the variables in sediment and ecotoxicological tests was available in non-parametric tests, through the Spearman's correlation coefficient. Oriented on the results presented in this work, pointing low concentrations of heavy metals in the sediments presented in the collect local, and the absence of toxicity, we can say that at this reservoir, at least in the collect area, it's low impacted, not implicating in direct interferences in the quality of life of benthonic organisms.

Toxicidad a dosis repetidas (28 días) por vía oral del agua termomineral de San Antonio de Putina, Puno / Repeated dose 28-day oral toxicity study of hot springs water from San Antonio de Putina, Puno

Objetivo. Determinar la toxicidad a dosis repetidas durante 28 días, de la ingestión por vía oral del agua termal de San Antonio de Putina-SAP-(Puno), en un modelo murino. Materiales y métodos. Diseño experimental, se utilizaron diez ratas de experimentación de cepa Holtzman, los que fueron divididos en dos grupos de cinco cada uno: un grupo de estudio, al que se le administró en forma repetida, agua termal traída de SAP, en una dosis de 1000 mg/kg en un volumen de 2 mL/100g, y un grupo control con agua potable esterilizada en el mismo volumen. Se realizaron observaciones clínicas diarias, determinación semanal del peso corporal, y después de 28 días se procedió con el estudio histopatológico de órganos (corazón, riñón, hígado y pulmón) y la determinación de parámetros hematológicos y bioquímicos; previo sacrificio de los animales de experimentación. Resultados. No se produjeron muertes (DL50> 1000 mg/kg) ni alteraciones permanentes de signos clínicos. Se observó aumento de peso, sin diferencias estadísticas entre los grupos. Los resultados hematológicos y bioquímicos reflejaron ligeras variaciones no significativas entre grupos, pero dentro del rango de la normalidad. No se observaron alteraciones histopatológicas. Conclusiones. No se encontraron signos de toxicidad aguda ante la administración de agua termomineral de San Antonio de Putina (Puno) en dosis repetidas por un periodo de 28 días.

Objective. To determine 28-day oral acute toxicity at repeated doses of hot springs water from San Antonio de Putina ­SAP- (Puno) in rats. Materials and methods. Experimental design, ten Holtzman rats were used, which were divided into two groups of five each: a study group that was exposed to repeated administration of SAP hot spring water in a dose of 1000 mg / kg in a volume of 2 mL/100g; and a control group, which sterilized water was given in the same volume. Daily clinical observations were made, weekly determination of body weight; and after 28 days; previous sacrifice of animals, the histopathological study of organs (heart, kidney, liver and lung) and determination of hematological and biochemical parameters were made. Results. No deaths (LD50> 1000 mg/kg) or permanent alterations of clinical signs were observed. Weight gain without statistical differences between the groups was observed. The hematological and biochemical results showed slight nonsignificant variations between groups, but in normality levels. No histopathological alterations were observed. Conclusions. No signs of acute toxicity were found after 28-days repeated administration of hot spring water from San Antonio de Putina (Puno).

Investigation of Filamentous Fungi Producing Safe, Functional Water-Soluble Pigments

The production of water-soluble pigments by fungal strains indigenous to South Korea was investigated to find those that are highly productive in submerged culture. Among 113 candidates, 34 strains that colored the inoculated potato dextrose agar medium were selected. They were cultured in potato dextrose broth and extracted with ethanol. The productivity, functionality (radical-scavenging activities), and color information (CIELAB values) of the pigment extracts were measured. Five species produced intense yellowish pigments, and two produced intense reddish pigments that ranked the highest in terms of absorbance units produced per day. The pigment extracts of Penicillium miczynskii, Sanghuangporus baumii, Trichoderma sp. 1, and Trichoderma afroharzianum exhibited high radical-scavenging activity. However, the S. baumii extract showed moderate toxicity in the acute toxicity test, which limits the industrial application of this pigment. In conclusion, P. miczynskii KUC1721, Trichoderma sp. 1 KUC1716, and T. afroharzianum KUC21213 were the best fungal candidates to be industrial producers of safe, functional water-soluble pigments.

Acute toxicity study of a polysaccharide based hydrogel from linseed for potential use in drug delivery system

ABSTRACT Linseed hydrogel (LSH) was evaluated by acute toxicity for its potential application in oral drug delivery design. White albino mice and rabbits were divided in four groups (I-IV) and different doses of LSH (1, 2 and 5 g/kg body weight) were given except to the control group (I) that was left untreated. Rabbits were monitored for eye irritation, acute dermal toxicity and primary dermal irritation, whereas, body weight, food and water consumption, hematology and clinical biochemistry, gross necropsy and histopathology of vital organs were scrutinized in mice. LSH was considered safe after eye irritation test as no adverse signs or symptoms were seen in the eye. In dermal toxicity and irritation study, skin of treated rabbits was found normal in color without any edema or erythema. After oral administration, there was no sign of any abnormalities in treated group animals (II-IV). The hematology and clinical biochemistry of treated group animals was comparable with the control group. Histopathology of vital organs has not shown any lesion or abnormalities. In the light of these outcomes, it can be concluded that LSH is not a hazardous biomaterial and could be incorporated as an excipient in oral and dermal preparations.

Appraisal of acute oral toxicity of glucuronoxylan hydrogel from Mimosa pudica seeds

Glucuronoxylan hydrogel (GXH) isolated from M. pudica seeds was assessed for acute toxicology in albino mice that were alienated into four groups. Three groups, i.e., II, III and IV received GXH at a dose of 1, 2 and 5 g/kg, respectively while group I was retained untreated and provided routine diet. After administering GXH, mice were examined for vomiting, diarrhea, allergy and tremors for 8 h. All animals were carefully observed for food and water consumption at 1, 2, 3, 7 and 14 day after administering GXH. At the end of studies, blood samples were drawn for investigation of hematological and biochemical parameters. All animals were sacrificed, relative body weight of vital organs was calculated and their histopathology was studied. It was concluded that there was insignificant difference in body weight, behavioral pattern, food and water intake among treated and control groups. Haematology and biochemistry of blood samples from all groups were found analogous. Histopathological evaluation of vital body organs exhibited no lesions in all groups. Ocular, cardiac and dermal safety of GXH was also established on albino rabbits.

Evaluation of acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. in Wistar rats / 中西医结合学报

<p><b>OBJECTIVE</b>This study investigated the acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. (AEVM) in rats for evaluating its safety profile.</p><p><b>METHODS</b>AEVM for the acute (2000 and 5000 mg/kg) and subacute (200, 400 and 600 mg/kg) toxicity studies was administered orally to rats according the guidelines 425 and 407 of Organization for Economic Cooperation and Development, respectively. Food and water intake as well as body and organ weight of animals were recorded. Signs of toxicity were assessed, and hematological, biochemical and histopathological analyses were performed.</p><p><b>RESULTS</b>In the acute toxicity study, a single dose of the aqueous extract at 2000 or 5000 mg/kg caused no mortality in the animals, suggesting that the median lethal dose is greater than 5000 mg/kg. In the subacute toxicity study, administration of the extract for 28 d, at all doses, caused no significant changes in the body weights or organ weights of rats in the treated groups when compared with the control group. In addition, hematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological sections of the heart, liver and kidney from test animals showed no signs of degeneration.</p><p><b>CONCLUSION</b>These results showed that AEVM at dosage levels up to 600 mg/kg is nontoxic and could also offer protection on some body tissues. AEVM could, therefore, be considered safe.</p>

Ecotoxicidad de nanopartículas metálicas y superparamagnéticas de óxido de hierro en dos especies / Ecotoxicity of metalic and superparamagnetics iron oxide nanoparticles in two species

Introducción: la nanotecnología y el empleo de materiales a nano escala son un área relativamente nueva de la ciencia y la tecnología con un gran crecimiento en el mercado global. Muchos de los productos no cuentan con estudios que garanticen su uso seguro, tanto para el hombre como para los ecosistemas. Los estudios ecotoxicológicos permiten evaluar los efectos de un determinado xenobiótico sobre especies representativas de los diferentes compartimentos ambientales. Objetivo: evaluar los efectos tóxicos de nanopartículas de Ag, Au, Ag/Ag y superparamagnéticas de óxido de hierro, en dos especies bioindicadoras de los ecosistemas terrestre y acuático. Métodos: como parte de los estudios de seguridad se realizaron ensayos de toxicidad aguda por contacto en lombriz de tierra de la especie Eisenia andrei, con una duración de 96 horas y estudios en anfibios de la especie Osteopillus septentrionales en diferentes etapas del desarrollo (embrionario y larval). Se evaluó la ocurrencia de mortalidad y de efectos tóxicos, en el caso del ensayo en lombriz de tierra; se determinó además la viabilidad celular. Resultados: los efectos tóxicos más significativos en el caso de la lombriz de tierra fueron, la ocurrencia de alteraciones fisiológicas y conductuales al ser expuesta a NPs de Ag de 3 nm y superparamagnéticas de óxido de hierro, estas últimas provocaron citotoxicidad a la concentración 1,38 mg/mL. En el caso de los anfibios se evidenció toxicidad en NPs de Ag 3 nm y superparamagnéticas de óxido de hierro. Conclusiones: todas las nanopartículas mostraron efectos tóxicos en las especies bioindicadoras evaluadas(AU)

Introduction: Nanotechnology and the use of nanoscale materials are a relatively new area of science and technology with big growth in the global market. Many of these products don't have studies that guarantee their safe use, both for man and for ecosystems. Ecotoxicological studies allow the evaluation of the effects of a particular xenobiotic on representative species of the different environmental compartments. Objective: To evaluate the toxic effects of nanoparticles of Ag, Au, Ag / Ag and super paramagnetic iron oxide in two bioindicators of terrestrial and aquatic ecosystems. Methods: Acute contact toxicity tests were carried out on ground worm of the Eisenia andrei species, with a duration of 96 hours and studies on amphibians of the species Osteopillus septentrionales at different stages of development (embryonic and larval). The occurrence of mortality and toxic effects was evaluated in the case of earthworm test; cell viability was also determined. Results: The most significant toxic effects in the case of earthworms were the occurrence of physiological and behavioral alterations when exposed to 3 nm Ag of superparamagnetic iron oxide nanoparticles, where the latter caused cytotoxicity at concentration of 1.38 mg / mL. In the case of amphibians, toxicity was evidenced in Ag 3 nm nanoparticles and superparamagnetic iron oxide. Conclusions: All nanoparticles showed toxic effects in the evaluated bioindicator species(AU)

Synthesis, acute toxicity, analgesic activity and cytotoxicity of Some bisthiourea derivatives

Bisthiourea derivatives were synthesized by the reaction of benzoylisothiocyanate and diamines to give 1,2-Bis [N'-benzoylthioureidobenzene [1], l,3-di[benzoylthioureido] benzene [2] and l,4-di [benzoylthioureido] benzene [3] in acetone. Acute toxicity study revealed that LD[50] of compound [1] and [3] is 120 mg/kg body weight. Visceral pain induced by injecting i.p acetic acid in mice were strongly inhibited by all the compounds. 94.65, 95.25 and 85.54% analgesic activity were observed in compounds [1], [2] and [3] at 15 mg/kg and [2] and [3] shows 97.63 and 96.42% at 30 mg/kg body weight respectively while [1] gives 100% analgesic activity. 100% cytotoxicity was observed in compounds [2] and [3] and 96% in compound [1] at 750 ppm. The results suggest that these compounds may have potential values for treatment of cancer and painful disorders

Synthesis, characterization and antinociceptive activities of Novel 2-[2,4-dichlorophenyl]-4H-chromen-4-one

A novel flavone derivative has been synthesized in good yield from ketone and aldehyde. The structure has been established by different spectroscopic techniques like H NMR, C NMR, IR and elemental analysis. The compound was then screened for its acute toxicity and antinociceptive activity studies on animal model. The novel compound was safe upto a maximum dose of 500mg/kg body weight oral dose in mice and showed 65.92 and 82.18% pheriperal analgesic activity at 15 and 30mg/kg body weight doses. Central antinociceptive activity of the compound was 53.13 and 64.44% at 15 and 30mg/kg body weight respectively

Acute oral toxicity from a fraction rich in phenolic compounds from the leaf extract of Swietenia macrophylla king in a murine model / Determinación de la toxicidad aguda oral de una fracción rica en compuestos fenólicos del extracto de hojas Swietenia macrophylla king en un modelo murino

Background: The mahogany tree (Swietenia macrophylla King) is widely used in traditional medicine, especially its seeds, which are used in Malaysia, Indonesia and some countries of South America. Recently an active fraction of the leaf ethanolic extract (labelled "Sm13-16,23"), showed promising results against some toxins of South American pit vipers. Objectives: In this study the aim was to evaluate the acute oral toxicity of fraction Sm13-16,23 from the leaf ethanolic extract, using Swiss Webster mice. Methods: Fraction Sm13-16,23 was administered orally in a single dose to 2000 mg/kg and 300 mg/kg, clinical follow-up for 14 days was performed and then euthanasia, necropsy and histopathology of organs were performed. Results: Overall, there were not deaths recorded during the study period. Further not signs of toxicity in doses of 300mg/kg were observed, but at doses of 2000 mg/kg, histopathological lesions in the liver, as karyomegaly and binucleation were observed. Conclusions: Fraction Sm13-16, 23 does not produce toxicity lesion at doses of 300mg/kg, indicating that the acute oral toxicity risk is low.

Antecedentes: El árbol de la caoba (Swietenia macrophylla King) es utilizado ampliamente en la medicina tradicional, especialmente sus semillas, que son usadas en Malasia, Indonesia y algunos países de Suramérica. Recientemente una fracción activa del extracto etanólico de las hojas (llamada "Sm13-16,23"), demostró resultados promisorios frente algunas toxinas de las víboras suramericanas. Objetivos: En este estudio se evaluó la toxicidad aguda oral de la fracción Sm13-16,23 del extracto etanólico de las hojas de S. macrophylla utilizando ratones Swiss Webster. Métodos: La fracción Sm13-16,23 se administró vía oral como dosis única a 2000 mg/kg y 300 mg/kg, se realizó seguimiento clínico de los animales durante 14 días y finalmente se les aplicó la eutanasia. Se practicó la necropsia de cada animal y se tomaron algunos órganos para su evaluación histopatológica. Resultados: No se registraron muertes durante el tiempo de estudio, ni se evidenciaron signos de toxicidad a dosis de 300mg/kg, sin embargo, a la dosis de 2000 mg/kg, se encontraron lesiones histopatológicas en el hígado; como cariomegalia y binucleación de los hepatocitos. Conclusión: La fracción Sm13-16,23 no produjo lesiones de toxicidad a dosis de 300mg/ kg, lo que indicia que el riesgo de toxicidad aguda oral es bajo.