Intoxicación cronica por metales tóxicos en supervivientes de artefactos explosivos improvisados con fragmentos incorporados y su potencial neoplásico. Revisión sistemática exploratoria / Chronic heavy metal intoxication in survivors of improvised explosive devices with embedded fragments and its neoplastic potential. Exploratory systematic review

Resumen Introducción: Los artefactos explosivos improvisados son armas no convencionales que pueden provocar múltiples lesiones y dejar esquirlas a modo de cuerpos extraños que pueden contener metales tóxicos, con potencial afectación a la salud de las víctimas según reportes datados desde 1977, los cuales mencionan alta mortalidad por cáncer y otros síntomas compatibles con toxicidad crónica Objetivo: Describir los resultados de investigación que informen sobre la toxicidad crónica producida por metales en personas víctimas de artefactos explosivos improvisados con esquirlas internalizadas, y sus posibles relaciones con cáncer. Metodología: Revisión sistemática exploratoria de literatura publicada y gris que se realizó entre los meses de marzo a mayo de 2021 en diferentes repositorios de tesis y bases de datos (Scielo, Pubmed, Academic Search Complete, JSTOR, Biblioteca Virtual en Salud, Freepdf, Google Académico, Open Grey); sin límite temporal o geográfico. Se incluyeron artículos originales de revistas indexadas o informes finales no publicados, correspondientes a investigaciones científicas con texto completo, en inglés, español y portugués. Resultados: De 56 documentos evaluados, solamente tres cumplieron criterios de inclusión. Todos estaban escritos en idioma inglés. Solo un estudio iraquí abordó población civil y los otros trabajos aludían a veteranos norteamericanos. Los niveles elevados de metales tóxicos, asociados con alteraciones tisulares circunscritas, fueron hallazgos recurrentes. No hubo reportes de patologías instauradas o manejos clínicos. Conclusión: Fue escasa la evidencia científica recabada; sin embargo, sí se han reportado cambios tisulares circundantes a esas esquirlas. Se considera necesario realizar más estudios relacionados con el tema, incluyendo seguimientos a largo plazo de las afectaciones tisulares detectadas.

Abstract Introduction: Improvised explosive devices are unconventionalweapons that can cause multiple injuries and splinters internalized containing heavy metals, potentially affecting the victim's health, according to reports dating from 1977, which mention high mortality from cancer and other symptoms suggestive of chronic metal toxicity. Objective: To describe the research results that report on the chronic toxicity produced by heavy metals in people who are victims of improvised explosive devices with internalized splinters, and its possible links with cancer. Methodology: Systematic exploratory review of published and grey literature which was carried out between march and may of 2021, in thesis repositories and different databases (Scielo, Pubmed, Academic Search Complete, JSTOR, Biblioteca Virtual en Salud, Freepdf, Google Académico, Open Grey); without time or geographical limit. Original articles from indexed scientific research journals or unpublished final reports were included, corresponding to scientific research with full text, in english, spanish and portuguese. Results: 56 documents were evaluated, three were selected fulfilling the inclusion criteria. They were all written in the english language. Only one Iraqi study addressed the civilian population and the other studies referred to North American veterans. Elevated heavy metal levels, associated with circumscribed tissue abnormalities, were recurrent findings. There were no reports of established pathologies or clinical management. Conclusion: The scientific evidence was scarce; as well as its relationship with established cancer, however, tissue changing surrounding these splinters have been reported. It is considered necessary to carry out more studies related to the subject, including long-term follow-up of detected tissue damage.

Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action

BACKGROUND@#The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats.@*METHODS@#Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined.@*RESULTS@#Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis.@*CONCLUSION@#These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.

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.

Assessment of the single and mixture ecotoxicity of pharmaceuticals of environmental concern using aquatic test organisms / Avaliação da ecotoxicidade individual e das misturas de fármacos de preocupação ambiental usando organismos-teste aquáticos

Pharmaceuticals are contaminants of emerging concern which have been a target of increasing attention by the scientific community. Pharmaceuticals presenting high consumption, incomplete metabolism and incomplete removal at wastewater treatment plants have been frequently detected in aquatic ecosystems worldwide. This is the case of the pharmaceuticals metformin (MET), bisoprolol (BIS), sotalol (SOT) and ranitidine (RAN). However, ecotoxicity data for these contaminants are scarce, especially regarding behavior effects and chronic toxicity. In addition, the knowledge regarding the joint toxicity of these pharmaceuticals on non-target organisms is still incipient, which makes their environment risk assessment uncertain. This study aimed to fill these knowledge gaps for these four pharmaceuticals, by carrying out toxicity tests using five test organisms from three trophic levels. Different endpoints were assessed in tests with Raphidocelis subcapitata (algae), Lemna minor (macrophyte), Daphnia similis (crustacean), Hydra attenuate (cnidarian) and Danio rerio (fish). The binary and quaternary mixture acute toxicity for these pharmaceuticals were assessed on D. similis and D. rerio embryo tests, respectively. This study also aimed to evaluate the predictive accuracy of the Concentration addition (CA) and the Independent action (IA) classic models. In addition, the nature of the possible toxicological interactions between the pharmaceuticals in binary mixtures were also evaluated, using the Combination Index-isobologram (CI) method. The modelling of the concentration-response curves and the associated statistical analyses were performed using the automated spreadsheet ToxCalcMix v.1.0 and the software OriginPro 2015. The software CompuSyn was used for performing the mixture analyses with the CI method. The experimental planning of the binary mixture tests was performed using the fractioned factorial design, in order to cover several possible ratio and level-dependent effects with a reduced number of test organisms. The results obtained in this study are shown in four articles. In article 1, we provided a critical review and discussed the misunderstandings, deficiencies and data gaps on the ecotoxicity data of pharmaceuticals and personal care products mixtures published in the literature. In the following articles, the results obtained from the single and mixture toxicity tests performed in this study were presented and discussed. The pharmaceuticals MET (article 2) and BIS (article 3) were classified as hazardous to the aquatic environment, in the acute toxicity category. However, an ecological risk is not expected for the pelagic freshwater species exposed to these two pharmaceuticals, based on the chronic data obtained. The results obtained from the mixture toxicity tests (article 4) showed that most of the observed toxicity effects from the binary mixtures were in the zone between the predicted effects by the CA and IA models. The CI model showed to be an useful tool to describe the possible toxicological interactions occurring between the pharmaceuticals in joint action. Even statistically significant non-effect concentrations of the pharmaceuticals added up to induce significant adverse effects in mixtures (something from nothing). It was concluded that ecological risk assessment based on single toxic effects can underestimate the real impact of environmental contaminants on aquatic ecosystems

A contaminação ambiental por fármacos tem sido alvo de crescente preocupação pela comunidade científica. Fármacos de elevado consumo, incompleto metabolismo e remoção incompleta em estações de tratamento de esgoto, como é o caso da metformina (MET), bisoprolol (BIS), sotalol (SOT) e ranitidina (RAN), têm sido frequentemente detectados em matrizes aquáticas do mundo todo. Apesar disso, dados ecotoxicológicos consistentes para esses contaminantes são escassos, principalmente com relação a efeitos comportamentais e oriundos de estudos crônicos. Além disso, o entendimento dos efeitos de suas ações combinadas em organismos não-alvo é ainda incipiente, o que gera incertezas na avaliação dos seus riscos ambientais. Esta pesquisa teve por objetivo preencher essas lacunas de conhecimentos para esses quatro fármacos, por meio da realização de testes com cinco diferentes organismos-teste de três diferentes níveis tróficos. Foram analisados diferentes parâmetros avaliativos em testes com os organismos aquáticos Raphidocelis subcapitata (alga), Lemna minor (macrófita), Daphnia similis (crustáceo), Hydra attenuata (cnidário) e Danio rerio (peixe). As toxicidades agudas das misturas binárias e quaternárias desses quatro fármacos também foram avaliadas em testes com D. similis e embriões de D. rerio, respectivamente. Este trabalho também teve por objetivo avaliar a acurácia preditiva dos modelos de adição de concentração (CA) e ação independente (IA) e analisar a natureza das possíveis interações toxicológicas entre os fármacos, em misturas binárias, usando o modelo do Índice de Combinação (CI). A modelagem das relações concentração-resposta e as análises estatísticas associadas foram realizadas empregando-se a planilha automatizada ToxCalcMix versão 1.0 e o software OriginPro 2015. O software CompuSyn foi utilizado para as análises envolvendo o CI. O planejamento experimental dos testes de misturas binárias foi realizado por meio do design fatorial fracionado, a fim de cobrir diversas possíveis interações em várias proporções e níveis de efeitos, com a redução do número de organismos-teste. Os resultados desta pesquisa estão apresentados em quatro artigos. No artigo 1, realizou-se uma revisão crítica com relação às lacunas de conhecimentos e deficiências identificadas a partir da análise da literatura sobre a ecotoxicologia de misturas de fármacos e de produtos de higiene pessoal. Nos artigos seguintes, foram apresentados e discutidos os resultados oriundos dos testes com os quatro fármacos avaliados neste estudo. Os fármacos MET (artigo 2) e BIS (artigo 3) foram classificados como perigosos para o ambiente aquático, na categoria de toxicidade aguda. Contudo, um risco ecológico não é esperado para as espécies pelágicas de água doce expostas a esses dois fármacos, com base nos dados de toxicidade crônica obtidos. Os resultados dos testes de misturas (artigo 4) permitiram concluir que a maior parte dos efeitos observados das misturas binárias estiveram na zona entre os efeitos preditos pelos modelos clássicos de CA e IA. O modelo do CI mostrou-se uma ferramenta útil para descrever a natureza das possíveis interações toxicológicas que ocorrem entre os fármacos em ações combinadas. Mesmo concentrações de nenhum efeito estatisticamente significativo dos fármacos causaram efeitos adversos significativos quando em misturas (something from nothing). Concluiu-se que avaliações de risco ecológicas baseadas em efeitos tóxicos individuais de contaminantes ambientais podem subestimar o real impacto desses compostos em ecossistemas aquáticos

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.

Chronic effects of nitrogenous compounds on survival and growth of juvenile pink shrimp / Efeito crônico de compostos nitrogenados sobre a sobrevivência e crescimento de juvenis de camarão rosa

Abstract In response to growing worldwide market demand, intensive shrimp farming, based on high feed, has developed over the past decade. The nitrogenous compounds mainly generated by animal excretion can cause deterioration of water quality and produce chronic or even acute toxicity to aquatic animals. As prevention, theoretical safety levels have been estimated from acute toxicity tests and they are traditionally used to prevent toxic effects on biota. However, are those concentrations of nitrogenous compounds really safe to Farfantepenaeus paulensis? The current study aimed to investigate the lethal and sublethal effects of ammonia, nitrite and nitrate to juvenile F. paulensis based on safety levels. Each experiment was performed independently in 100 L tanks for 30 days. The survival rates and wet weight of all shrimps were recorded every 10 days. The concentrations tested for ammonia, nitrite and nitrate were respectively: treatment "T1/4", a quarter of the safety level (0.91 mg/L TA-N, 2.55 mg/L NO2--N and 80.7 mg/L NO3--N); treatment "TSL", the safety level (3.65 mg/L TA-N, 10.2 mg/L NO2--N and 323 mg/L NO3--N); and treatment "T2X", twice the safety level (7.30 mg/L TA-N, 20.4 mg/L NO2--N and 646 mg/L NO3--N). For F. paulensis cultivation, the real safety level for nitrite was estimated to be 2.55 mg/L NO2--N. For ammonia and nitrate, the recommended concentrations were <0.91 mg/L TA-N corresponding to 0.045 mg/L NH3-N and <80.7 mg/L NO3--N, respectively.

Resumo Em resposta à crescente demanda do mercado mundial, a carcinicultura intensiva tem se desenvolvido ao longo da última década. Os compostos nitrogenados gerados principalmente pela excreção dos animais podem causar a deterioração da qualidade da água e produzir toxicidade crônica ou mesmo aguda para os animais cultivados. Como prevenção, os níveis de segurança teóricos são estimados a partir de testes de toxicidade aguda e são tradicionalmente usados para evitar efeitos tóxicos sobre a biota. No entanto, as estimativas das concentrações dos compostos nitrogenados são realmente seguras para Farfantepenaeus paulensis? O presente estudo teve como objetivo investigar os efeitos letais e subletais da amônia, nitrito e nitrato em juvenis de camarão marinho F. paulensis com base em níveis de segurança. Cada experimento foi realizado de forma independente em tanques com capacidade de 100 L durante 30 dias. As taxas de sobrevivência e peso úmido de todos os camarões foram registrados a cada 10 dias. As concentrações testadas para amônia, nitrito e nitrato foram respectivamente: "T1/4", um quarto do nível de segurança (0,91 mg/L N-AT, 2,55 mg/L de N-NO2- e 80,7 mg/L N-NO3-); "TSL", nível de segurança (3,65 mg/L N-AT, 10,2 mg/L de N-NO2- e 323 mg/L N-NO3-); e "T2X", duas vezes o nível de segurança (7,30 mg/L N-AT, 20,4 mg/L de N-NO2- e 646 mg/L de N-NO3-). Para a criação de F. paulensis, o nível de segurança real para nitrito foi estimado em 2,55 mg/L N-NO2-. Para amônia e nitrato, concentrações recomendadas foram: <0,91 mg/L N-AT correspondente a 0,045 mg/L N-NH3 e <80,7 mg/L N-NO3-, respectivamente.

Efecto de la administración crónica del látex liofilizado de Croton lechleri Muell. Arg. "sangre de drago" en Rattus norvegicus var. Albinus / Effect of chronic administration of latex lyophilised Croton lechleri Muell. Arg. "sangre de drago" in Rattus norvegicus var. Albinus

Objetivo: Determinar si la administración crónica (90 días) del látex liofilizado de Croton lechleri Muell. Arg. "Sangre de drago" modifica los parámetros hematológicos y bioquimicos en Rattus norvegicus var albinus. Materiales y métodos: Se utilizó ratas con un peso corporal (p.c.) entre 150 g a 170 g, distribuidos en Grupo A (control) y Grupos B y C (experimentales), de 20 especímenes cada uno (10 hembras y 10 machos) a las que se administró por vía oral NaCl 0.9% y una dosis diaria de 100 y 200 mg de látex liofilizado/Kg p.c. respectivamente, durante 90 días. Se tomaron muestras de sangre cada 15 días para determinar parámetros hematológicos (hematocrito, linfocitos, leucocitos y segmentados) y bioquímicos (glucosa, urea, creatinina, colesterol total y perfil hepático). Resultados: Todos los valores se encontraron dentro del rango normal. Se encontraron diferencias significativas al comparar los grupos de estudio en los resultados de glucosa (Control vs Grupo I: p<0.001 y Grupo II: p=0.003) y creatinina (Grupo II vs Grupo I: p=0.008 y control: p<0.001). Los valores de bilirrubina total y proteínas totales variaron significativamente durante el tiempo de estudio (p=0.001 y p<0.001, respectivamente). El resto de parámetros no presentaron variaciones significativas por grupos (p>0.05). Conclusión: El látex liofilizado de Croton lechleri Muell. Arg. no generó toxicidad en los parámetros hematológicos y bioquímicos estudiados en Rattus norvegicus var Albinus.

Acute and sub-chronic toxicity of tetrandrine in intravenously exposed female BALB/c mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine (TET) in female BALB/c mice.</p><p><b>METHODS</b>The median lethal dose (LD) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET (30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period.</p><p><b>RESULT</b>LDwas found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically signifificant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET (P >0.05). In the sub-acute toxicity study, no signifificant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group (P >0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions.</p><p><b>CONCLUSIONS</b>The overall fifindings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.</p>

Toxic effects of atrazine on reproductive system of male rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study was designed to evaluate the toxic effects of Atrazine (ATZ) on the reproductive system of male rats.</p><p><b>METHODS</b>Male Sprague-Dawley rats were exposed to ATZ by gavage at dosages of 0, 38.5, 77, and 154 mg/kg bw/day for 30 d. The toxic effects of ATZ to rats were assessed through histopathologcal observation, spermatozoa quality evaluation, testicular marker enzyme indicators, antioxidant capacity and reproductive hormone levels.</p><p><b>RESULTS</b>Significant adverse effects on reproductive system were observed in rats exposed to ATZ at different dosages compared with 0 mg/kg group, including an irregular and disordered arrangement of the seminiferous epithelium in 154 mg/kg group; a decreased spermatozoa number and an increased spermatozoa abnormality rate in 77 and 154 mg/kg groups; decreased levels of acid phosphatase (ACP), alkaline phosphatase (AKP), lactic dehydrogenase (LDH), and succinate dehydrogenase (SDH) with the increasing of ATZ concentration; a decreased level of total antioxidant capacity (TAC) in a dose-dependent manner, and a decreased reduced glutathione (GSH) level and an increased malondialdehyde (MDA) content in 154 mg/kg group; and decreased serum levels of testosterone (T) and inhibin-B (INH-B) and an increased serum level of follicle stimulating hormone (FSH) in 77 and 154 mg/kg groups, and an increased serum level of luteinizing hormone (LH) in 154 mg/kg group.</p><p><b>CONCLUSION</b>These results suggested that relatively high doses of ATZ could exert reproductive toxicity of male rats.</p>

Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>Thirty-two male SD rats were randomly and equally divided into 4 groups: control group and high-, middle-, and low-dose exposure groups. The rats in high-, middle-, and low-dose exposure groups were fed with the feed mixed with AlCl(3) (120.0, 12.0, and 1.2 mg/kg, respectively), while the rats in control group were fed conventionally. After 6 months of feeding, brain aluminum levels were determined by inductively coupled plasma mass spectrometry; Morris water maze was employed to test the learning and memory abilities; the expression and content of BDNF in brain tissue were measured by Western blot and enzyme-linked immuno sorbent assay (ELISA).</p><p><b>RESULTS</b>The high- and middle-dose exposure groups had significantly higher brain aluminum levels than the control group (P<0.05). The Morris water maze test showed that the high- and middle-dose exposure groups had significantly prolonged escape latency (P<0.05), significantly prolonged time taken to first reach the target quadrant (P<0.01), and significantly decreased number of platform crossings and time spent in the target quadrant (P<0.05), as compared with the control group. The Western blot and ELISA showed that the expression and content of BDNF in brain tissue decreased as the dose of AlCl(3) increased, and they were significantly lower in the high- and middle-dose exposure groups than in the control group (P<0.05).</p><p><b>CONCLUSION</b>Chronic aluminum exposure (12.0 and 120.0 mg/kg) can lead to cognitive dysfunction in rats, and the decreased expression of BDNF may be one of the mechanisms of learning and memory deficits induced by aluminum.</p>

Toxicidad en peces de herbicidas formulados con glifosato / Toxicity in fishes of herbicides formulated with glyphosate

En nuestro país existe una gran extensión de hectáreas cultivadas con soja transgénica, la misma ha sido modificada genéticamente para soportar la acción de un herbicida denominado glifosato. Debido a la gran cantidad de formulaciones comerciales que incluyen glifosato es de importancia analizar el impacto ambiental producido por éstas. La evaluacion de la toxicidad aguda de dos herbicidas comerciales formulados con glifosato y de una solución del mismo; frente a peces de la especie Poecilia reticulata "lebistes" acusa que una de las soluciones produce mortalidad del 100 % de los especimenes a 100 μl/l (equivalente a 48 mg/l de principio activo); la otra a 50 μl/l (equivalente a 24 mg/l de principio activo) y la solución formulada con glifosato puro no produce mortalidad aún a concentraciones de 400 mg/l. Utilizando dosis sub letales en función de los datos obtenidos en el ensayo de toxicidad aguda se determinó que a largo plazo especimenes de Cyprinus carpio haematopterus "carpa koi", manifestaron severas alteraciones hematológicas principalmente frente a una de las formulaciones evaluadas.

Nowadays, transgenic soya, modified in order to withstand the impact of the herbicide glyphosate, in one of the main crops grown in Argentina. Due to the large number of commercial formulations that include this drug, is important to analyze both, the acute and chronic environmental impact that they cause. Here the acute toxicity of two commercial herbicides glyphosatebased toward the fish Poecilia reticulate "guppy" was evaluated and compared with pure glyphosate solutions. Interestingly, while commercial herbicides formulations induce a 100% of mortality at concentration ranged between 50 and 100 μl/l, the pure glyphosathe does not present mortality even at doses higher than 400 mg/l. When some long term effects toward Cyprinus carpio haematopterus "koi" were determined by using the sub-lethal doses already calculated it was demonstrated that one of the commercial herbicides induces severe haematological alterations.

Injuria pulmonar aguda en la intoxicación por ácido acetilsalicílico: Caso clínico y revisión bibliográfica / Acute lung injury due to acetylsalicylic acid poisoning: Case report and review

La intoxicación por salicilatos frecuentemente no es tenida en cuenta como causa de edema pulmonar no cardiogénico y de alteración del sensorio en pacientes adultos. Se describe el caso de una mujer de 52 años de edad, la cual presentó dos episodios de edema pulmonar no cardiogénico habiendo requerido para su manejo, asistencia ventilatoria mecánica. La presentación clínica de la intoxicación fue reconocida al ingreso al servicio de urgencias y llevó al diagnóstico correcto. Se le realizó hemodiálisis y alcalinización urinaria llevando a una rápida resolución del edema pulmonar. Varios aspectos de la presentación clínica sugirieron que la paciente tenía una intoxicación crónica, una condición que a menudo no es diagnosticada oportunamente, lo que contribuye al aumento de la morbi-mortalidad en estos pacientes. Frente a un caso de edema pulmonar agudo no cardiogénico debe considerarse la posibilidad de intoxicación con salicilatos, porque la institución rápida de una terapia apropiada, incluyendo la hemodiálisis, una vez establecido el diagnóstico, es un factor determinante de los resultados en esta grave intoxicación.

Salicylate intoxication is frequently overlooked as a cause of noncardiogenic pulmonary edema and altered mental status in adult patients. We described the case of a 52 years-old woman who presented two episodes of recurrent non-cardiogenic pulmonary edema requiring intubation. On admission, recognition of the clinical syndrome in the emergency department led to the correct diagnosis of salicylate intoxication. The patient was successfully treated with hemodialysis and urinary alkalinization, leading to rapid resolution of pulmonary edema and extubation. Several aspects of the clinical presentation suggest that the patient suffered from chronic salicylism, a condition often misdiagnosed or diagnosed late in the course of disease, contributing to substantial morbidity and mortality in these patients. This poisoning should be considered in the differential diagnosis of acute pulmonary edema not cardiogenic and altered sensorium because rapid institution of appropriate therapy, including hemodialysis, once the diagnosis is established is an important determinant of outcome in this serious disorder.

Chronic exposure to trace chromium induces oxidative stress in mouse liver cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effects of chronic exposure to trace chromium (VI) as a result of metal-on-metal hip arthroplasty on oxidative stress in mouse liver cells.</p><p><b>METHODS</b>Eighty NIH mice were randomly divided into 4 groups and subject to intraperitoneal injection of CrO(3) at the dose of 0, 5, 10 or 20 mg/kg every other day for 16 weeks. Five mice from each group were selected every 4 weeks for determining the content of chromium (VI) in the whole blood and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR) activity, and glutamate cysteine ligase (GCL) expression in the liver cells. The ultrastructural changes of the liver cells were also observed using transmission electron microscopy.</p><p><b>RESULTS</b>Exposure to 5 and 10 mg/kg CrO(3) caused significantly increased blood chromium concentration and ROS level, which reached the peak level at 8 weeks and became stabilized, whereas at the dose of 20 mg/kg, CrO(3) exposure resulted in progressive, time-dependent increase of blood chromium concentration and ROS level. MDA showed no significant changes in the 4 groups. With the prolongation of the exposure time, GSH content and GR activity were decreased in these groups. In 5 and 10 mg/kg CrO(3) groups, GCL expression increased at each time point of measurement, but in 20 mg/kg group, GCL expression decreased gradually with a prolonged exposure. Transmission electron microscopy revealed apoptotic changes of the liver cells in 20 mg/kg group.</p><p><b>CONCLUSION</b>The slow accumulation of trace chromium (VI) after metal-on-metal hip arthroplasty may cause oxidative stress and changes in the oxidative stress system in the liver cells.</p>

Toxicity study of realgar / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic.</p><p><b>METHOD</b>Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement, and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of realgar and no-observed adverse effect level (NOAEL) was evaluated.</p><p><b>RESULT</b>With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic < or = 1.7 mg x g(-1)) for an adult of the body weight about 60 kg could be 10-160 mg depending on the variation of the treatment duration.</p><p><b>CONCLUSION</b>Long term use of realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.</p>

Toxicidade aguda e crônica do extrato de NIM (Azadirachta indica) para Ceriodaphnia dubia / Acute and chronic toxicity of the extract of Nee (Azadirachta indica) to Ceriodaphnia dubia

A preocupação com as questões ambientais tem levado ao crescimento de pesquisas relacionadas aos compostos com potencial no controle de pragas na agricultura, direcionando alternativas que minimizem os impactos ao ambiente. Nesse sentido acredita-se que a utilização de produtos proveniente de plantas possa representar opção eficaz para o controle de pragas com menor risco ambiental.Objetivou-se com este trabalho avaliar a toxicidade aguda e crônica de uma formulação comercial de nim para Ceriodaphnia dubia. A CE50 (48h) determinada foi de 0,032 mL·L-1, e os valores de CENO, CEO e VC foram respectivamente em mL·L-1:0,004; 0,008 e 0,006. Os testes de toxicidade mostraram efeitos do produto tanto na mobilidade como na reprodução de C. dubia.

Chronic toxicity bioassay with populations of the crustacean Artemia salina exposed to the organophosphate diazinon

A chronic toxicity bioassay was conducted with the microcrustacean Artemia salina as the testing organism for the toxic organophosphate diazinon in order to determine if the species is an appropriate indicator of pollution in aquatic environments. Tests of animal exposure to different concentrations of the toxicant were performed for 24, 48 and 72 hours after larvae hatching. Registered mortality data was used to obtain the lethal dose 50 (LD50) of the organophosphate for each exposure time, considering the immobilization of A. salina larvae as the mortality parameter. The lethal concentration (LD50) in the same exposure times was calculated by evaluating morphological changes on the three initial stages of larval development. Both doses were determined by using probit statistical analysis. Results indicate greater dose-response exactitude after 24 hours of exposure to the toxicant. High sensitivity of the organism to the toxicant was determined, thus indicating that A. salina is an appropriate ecotoxicological bioindicator of aquatic environments polluted with pesticides, with the special consideration that this species is a natural resident of saline water bodies, and thus could be used to control pollution in these environments as a result of the unrestrained usage of such toxic substances.

Expression and significance of Clara cell secretory protein in injury lungs of Kunming mice after n-hexane long-term inhalation / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the expression of Clara cell secretory protein(CCSP) in the Kunming mouse model of n-hexane long-term inhalation, and to discuss the functions of Clara cell in injury lung induced by n-hexane.</p><p><b>METHODS</b>24 healthy mice were randomly divided into 4 groups: one control group and three n-hexane groups (4 w, 8 w and 12 w), 6 each group. Primary concentration of n-hexane was 17.6 g/m3, 8 hours per day, 6 d per week. After inhalation, n-hexane concentration of blood from celiac artery was detected. The lungs were embedded with paraffin and HE staining in the routine. The ratio of Clara cells with CCSP reaction in bronchiole and the number of macrophage cells with lysozyme reaction were determined by immuno-histochemistry.</p><p><b>RESULTS</b>In the poisoning groups, the average n-hexane concentration of blood was significantly higher than that of the control group (P < 0.01). There were apparent pathologic damages in lungs of the poisoning mice. In poisoning 4 w, 8 w and 12 w groups, the ratio of Clara cells was significantly decreased [(73.33 +/- 4.21)%, (60.98 +/- 4.94)%, (34.04 +/- 2.33)% in terminal bronchiole, and (75.44 +/- 7.91)%, (58.54 +/- 4.86)%, (33.35 +/- 2.67)% in respiratory bronchiole] as compared with the control mice [(80.26 +/- 6.43)% and (81.74 +/- 7.75)%, P < 0.05 or P < 0.01], meanwhile the numbers of macrophage cells were gradually increased [(21.39 +/- 7.41), (28.54 +/- 10.73), (48.97 +/- 19.55) per microscopic field at 200x] in poisoning mice than those in control mice [(7.84 +/- 3.12) per microscopic field at 200x, P < 0.05 or P < 0.01].</p><p><b>CONCLUSION</b>In injury lungs after n-hexane inhalation, Clara cells are the target cells of n-hexane toxicity effect. Clara cells play an extensive protective role in lung inflammation.</p>

Subchronic toxicity studies of the ethanolic root extract of croton zambesicus

Subchronic toxicity study of the crude root extract of Croton zambesicus [27-81mg/kg], which is used traditionally as malarial remedy, was carried out in rodents to evaluate the safety profile. Effect of the extract on body weights, haematological indices as well as liver and kidney functions and histology of various organs were investigated. Subchronic treatment of rats for 21 days caused comparable increase in body weights of rats in extract treated and control groups. The extract caused a dose-dependent increases in RBC, PCV, Hb, WBC, bleeding time and clotting time. The increases were only significant [P<0.05] at the highest dose of the extract [81mg/kg] for RBC and WBC when compared to control. There was no significant [P>0.05] differences in the means of other haematological parameters in the extract treated groups compared to control. The extract caused significant [P<0.05-0.01] increases in the level of serum total protein, ALT, ALP, total bilirubin and total cholesterol. The was no significant [P>0.05] changes in the levels of albumin and AST. The extract did not produce any significant [P>0.05] changes in the mean concentrations of urea, creatinine, Na+, K+, and Cl- ions of rats in the extract treated groups compared to that of control. Histopathologic analysis of the vital organs revealed no significant lesions in the brain, liver, kidney, heart, spleen, ovary, and testis. The results suggest the extract to be safe when taken orally though with an insignificant effect on the liver

Biomarcadores histológicos: toxicidade crônica pelo Roundup em piauçu (Leporinus macrocephalus) / Histological biomarkers: chronic toxicity for roundup in piauçu (Leporinus macrocephalus)

Avaliou-se o uso de brânquias, fígado e rins como biomarcadores histológicos em ensaio de toxicidade crônica com o herbicida Roundup® em piauçu (Leporinus. macrocephalus). Para tanto, os animais foram expostos a 1,58mg/L, dose equivalente a 1/10 da CL50 para a espécie por 14 e 28 dias, sendo utilizados cinco animais por tratamento correspondentes aos dias 0, 14 e 28. Hemorragia e necrose hepática e congestão renal foram as alterações que apresentaram diferenças entre os animais expostos e os não expostos. Dentre os órgãos usados como biomarcadores histopatológicos, o fígado foi o que apresentou os melhores resultados, seguido pelo rim.

The use of gills, liver, and kidneys as histological biomarkers was evaluated in a chronic toxicity analysis with herbicide Roundup® in piauçu (Leporinus macrocephalus). The animals were exposed to 1/10 of LC50 (1.58mg/L), during a period of 14 and 28 days. Five animals were used for treatment (days 0, 14, and 28). Hepatic hemorrhage and necrosis and renal congestion were the alterations that presented differences between exposed and non-exposed animals. Among the organs used as histological biomarkers, the liver presented the best results, followed by the kidneys.

Chronic toxicity of 97% isopropyl thioxanthone in rat by oral administration for 2 years / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the oral chronic toxicity of 97% isopropyl thioxanthone (97% ITX) in rats, determine the no-observed adverse effect levels (NOAEL).</p><p><b>METHODS</b>Four groups of rats were fed with foodstuff containing 97% ITX in the dosage of 1000.0, 250.0, 62.5 mg/kg respectively for 2 years. The general behavior, body weight, food availability ect. were observed during the experiment. At the end of the experiment, blood and urine samples were collected for routine and biochemical assays. The internal organs were taken for calculating their organ coefficients and histopathological examinations.</p><p><b>RESULTS</b>During the experimental period, no obvious abnormality were found in the experimental animals. The body weight and the total food availability rate in the high dosage group of male were lower than that of control (P < 0.05). Hematology examination showed that the quantity of Hb and RBC in high dosage groups of both the male and female and Hb in the male middle group were all lower than the control group (P < 0.01 or P < 0.05). Analysis of correlation indicated that r = -0.433, P < 0.01 in male, r = -0.337, P < 0.01 in female of Hb; r = -0.266, P < 0.05 in male, r = -0.317, P < 0.01 in female of RBC. There were obviously negative correlation. Serum biochemistry examination showed the concentration of CHO in the high and middle dosage treated rats of male and female were higher than that of the control (P < 0.01 or P < 0.05). Analysis of correlation indicated that r = 0.497, P < 0.01 in male, r = 0.417, P < 0.01 in female. No abnormality were found in urine examination. The organ weight and organ coefficient such as liver, were higher than control group (P < 0.01). The result of histopathological examinations displayed that the renal tubule Cast and the tubulointerstitial nephritis in the treated groups were higher than that of control group (P < 0.01).</p><p><b>CONCLUSION</b>97% ITX could obviously interfere with the animals' physical condition, and reduce the number of RBC and the concentration of Hb in the blood, interact metabolism of lipoid and induce the concentration of CHO in the serum. The livers of the treated rats are compensatory enlarged. And kidneys of the poisoning animals are damaged. The 2 years oral NOAEL of 97% ITX in rats are more than 4.63 mg/kg for female rats, and larger than 4.06 mg/kg for male rats.</p>