Retrospective mining of toxicology data to discover multispecies and chemical class effects: Anemia as a case study.

Predictive toxicity models rely on large amounts of accurate in vivo data. Here, we analyze the quality of in vivo data from the U.S. EPA Toxicity Reference Database (ToxRefDB), using chemical-induced anemia as an example. Considerations include variation in experimental conditions, changes in terminology over time, distinguishing negative from missing results, observer and diagnostic bias, and data transcription errors. Within ToxRefDB, we use hematological data on 658 chemicals tested in one or more of 1738 studies (subchronic rat or chronic rat, mouse, or dog). Anemia was reported most frequently in the rat subchronic studies, followed by chronic studies in dog, rat, and then mouse. Concordance between studies for a positive finding of anemia (same chemical, different laboratories) ranged from 90% (rat subchronic predicting rat chronic) to 40% (mouse chronic predicting rat chronic). Concordance increased with manual curation by 20% on average. We identified 49 chemicals that showed an anemia phenotype in at least two species. These included 14 aniline moiety-containing compounds that were further analyzed for their potential to be metabolically transformed into substituted anilines, which are known anemia-causing chemicals. This analysis should help inform future use of in vivo databases for model development.

Evaluación de la seguridad de una arcilla modificada y su extracto de migración en bazo de ratas Wistar expuestas de forma subcrónica / Influence of a subchronical exposure to a modified clay and its migration extract in the spleen of Wistar rats

Las ventajas tecnológicas de la incorporación de arcillas modificadas en polímeros para el envasado de alimentos son bien conocidas, pero aún quedan muchas incertidumbres sobre la seguridad de estos materiales. El Instituto Tecnológico del Embalaje, Transporte y Logística ha desarrollado una arcilla, Clay1, modificando una montmorillonita con una sal de amonio cuaternario. Esta organoarcilla, incorporada al polímero (ácido poliláctico), da lugar a un material nanocompuesto, reforzándose así el material de partida. El principal objetivo de este estudio es evaluar la actividad de biomarcadores de estrés oxidativo en bazo de ratas expuestas durante 90 días a Clay1 (40 mg/kg/día) y al extracto de migración obtenido a partir del material nanocompuesto resultante. Los parámetros evaluados fueron la peroxidación lipídica y las actividades enzimáticas superóxido dismutasa y catalasa. Además, se realizó un análisis del contenido en bazo de los metales más característicos que componen la organoarcilla (Al, Ca, Fe, Mg, Si) para comprobar su posible acumulación. En dicho estudio se trabajó con tres grupos de ratas Wistar (n=10): control (comida estándar + agua como bebida), Clay1 (comida estándar mezclada con 40mg/kg/día de arcilla + agua) y extracto de Clay1 (comida estándar + extracto como bebida). Tras el tiempo de exposición los animales se sacrificaron y se extrajo el bazo. De forma general, no se observaron diferencias significativas en ninguno de los parámetros evaluados con respecto al grupo control, por lo que Clay1 muestra un buen perfil toxicológico respecto a los biomarcadores ensayados con vistas a su uso en la industria alimentaria (AU)

The technological advantages of the incorporation of modified clays into polymers for food packaging are well known. However, there are still many uncertainties about the safety of these materials. The Technological Institute of Packaging, Transport and Logistic has developed Clay1, a modified clay with a quaternary ammonium salt. This organoclay is incorporated into the polymer (polylactic acid), giving a nanocomposite material and reinforcing the bulk material. The aim of this study is to evaluate the activity of several oxidative stress biomarkers in the spleen of rats exposed for 90 days to Clay1 (40 mg/kg/day) and its migration extract obtained from the resultant nanocomposite material. The parameters evaluated were lipid peroxidation and superoxide dismutase and catalase activities. Moreover, the characteristic metallic components of the organoclay (Al, Ca, Fe, Mg, Si) were also analyzed to test the possible accumulation. In this study, three groups of Wistar rats (n=10) were used: control (standard food + water), Clay1 (food with Clay1+water) and Clay1 extract (standard food+ Clay1 extract as water). After the exposure the spleen was removed. In general, no significant differences were observed in any of the parameters evaluated compared to the control group, therefore Clay1 showed a good toxicologic profile regarding the biomarkers assayed for its use in the food industry (AU)

Effects of subchronic exposure to simazine on zebrafish (Danio rerio).

OBJECTIVES: Simazine is a triazine herbicide which has been used for a long period in agriculture and in the aquatic environment for control of weeds and algae. The aim of this study was to investigate the effects of subchronic exposure to simazine on growth and the development of histopathological changes in selected organs (gills, kidney, liver) in Danio rerio. METHODS: Juvenile growth tests were performed on D. rerio according to the OECD method No. 215. Fish at the age of 20 days were exposed to the environmental simazine concentration commonly detected in Czech rivers (0.06 µg.L-1) and a range of sublethal concentrations of simazine (0.6, 6.0 and 60.0 µg.L-1) for 28 days. RESULTS: There were no significant differences (p<0.05) between the specific growth rates (r) of the test groups and those of both control groups. Histopathological examination revealed pathological changes in fish exposed to a simazine concentration of 60.0 µg.L-1. The values of NOEC and LOEC of simazine were 6.0 µg.L-1 and 60.0 µg.L-1. CONCLUSIONS: The environmental concentration of simazine in Czech rivers did not have any effects on the growth and development of histopathological changes in D. rerio.