Individual and joint effects of glyphosate and cypermethrin formulations on two human cell lines.

The final effect of pesticides and their mixtures on living organisms is determined by the particular toxicodynamics of the system. Oxidative stress is one of the most studied molecular mechanisms of toxicity due to increasing evidence supporting its association with the toxic effects of different agrochemicals. In the present study we evaluated the presence of redox balance alterations in the cell lines HEp-2 and A549 exposed to formulations of glyphosate (March®) and cypermethrin (Superfina®) used separately or in combination (in a proportion equivalent to that used in soybean fields). We determined the activity of catalase, superoxide dismutase, glutathione S-transferase, intracellular GSH content, content of oxidized proteins (as measure of damage) and intracellular ROS content in both cell lines at two different mixture concentrations. Additionally, we evaluated the presence of statistical interaction to determine if the effect of the mixture on the parameters evaluated was additive, synergistic, or antagonistic. For this purpose, we used the Combination Subthresholding, Cooperative Effect and Statistical Linear Interaction approaches. We found that the interaction between pesticides depended on their concentration and the cellular models studied.

Glyphosate commercial formulation causes cytotoxicity, oxidative effects, and apoptosis on human cells: differences with its active ingredient.

In the present study, the effects on oxidative balance and cellular end points of glyphosate, aminomethylphosphonic acid (AMPA), and a glyphosate formulation (G formulation) were examined in HepG2 cell line, at dilution levels far below agricultural recommendations. Our results show that G formulation had toxic effects while no effects were found with acid glyphosate and AMPA treatments. Glyphosate formulation exposure produced an increase in reactive oxygen species, nitrotyrosine formation, superoxide dismutase activity, and glutathione (GSH) levels, while no effects were observed for catalase and GSH-S-transferase activities. Also, G formulation triggered caspase 3/7 activation and hence induced apoptosis pathway in this cell line. Aminomethylphosphonic acid exposure produced an increase in GSH levels while no differences were observed in other antioxidant parameters. No effects were observed when the cells were exposed to acid glyphosate. These results confirm that G formulations have adjuvants working together with the active ingredient and causing toxic effects that are not seen with acid glyphosate.

Influence of the spray adjuvant on the toxicity effects of a glyphosate formulation.

In the present study, the influence of the spray adjuvant on the toxicity effects of a glyphosate formulation was examined in HEp-2 cell line. We determined the median lethal concentration (LC50) of Atanor® (glyphosate formulation), Impacto® (spray adjuvant) and the mixture of both agrochemicals. We also compared the toxicities of the pesticides individually and in mixture and we analyzed the effects on oxidative balance from each treatment. Our results showed that all the agrochemicals assayed induce dose and time-dependent cytotoxicity and that the toxicity of Impacto® with Atanor® (mixture) was additive on HEp-2 cell line. All the agrochemicals assayed produced an increase in catalase activity and glutathione levels, while no effects were observed for superoxide dismutase and glutathione-S-transferase activities. We found an important increase in ROS production in cells treated with Atanor® and mixture. Besides, all the agrochemicals used triggered caspase 3/7 activation and hence induced apoptosis pathway in this cell line. In conclusion, our results demonstrated that the addition of adjuvant to glyphosate formulation increase the toxicity of the mixture in cell culture. Furthermore, cell culture exposed to agrochemical mixture showed an increased ROS production and antioxidant defenses.

Dietary copper effects in the estuarine crab, Neohelice (Chasmagnathus) granulata, maintained at two different salinities.

We analyzed the dietary copper effects in the estuarine crab Neohelice (Chasmagnathus) granulata and its interaction with water salinity. Crabs were maintained at 2 per thousand and 30 per thousand salinity for 5 weeks and they were fed with commercial food supplemented with the green alga Scenedesmus vacuolatus previously exposed to copper. No mortalities were observed, but crabs maintained at 2 per thousand salinity accumulated on average 40% more copper compared to animals maintained at 30 per thousand salinity. At 2 per thousand salinity, superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels were increased at the first and second weeks, respectively, while lipid peroxidation and protein oxidation were evident after 4 weeks of copper exposure. At 30 per thousand salinity, all measured variables increased progressively but were significantly higher only at the end of the assay (5th week), except for protein oxidation that remained unchanged throughout the experiment. The hepatosomatic index (HSI) was significantly decreased in response to copper exposure, but only in crabs acclimated to 2 per thousand. These findings have suggested that dietary copper exposure induces greater metal accumulation and larger oxidative stress responses in crabs maintained at 2 per thousand salinity.

Genotoxicidad de mezclas de pesticidas: ¿algo más que la suma de las partes? / Pesticide mixtures genotoxicity: More than the sum of its parts?

Un factor decisivo de la Revolución Verde ha sido el desarrollo y aplicación de plaguicidas para combatir una gran variedad de organismos considerados perjudiciales por el hombre, que afectan la productividad de los cultivos de interés agronómico. Sin embargo, el incremento sostenido del uso de pesticidas trajo aparejado un aumento de la presencia de los mismos en el ambiente, llegando a afectar a los ecosistemas y a la salud humana. La exposición de las poblaciones a plaguicidas, se da en forma de mezclas complejas, tanto por la aplicación de distintos plaguicidas en simultáneo como por la presencia de aditivos en las formulaciones comerciales. Teniendo en cuenta la producción científica relacionada en los últimos años, el objetivo de este trabajo fue evaluar los avances sobre la genotoxicidad de pesticidas y sus mezclas, en concentraciones similares a las encontradas en el ambiente. Además, dada la complejidad de los estudios de monitoreo y la imposibilidad de establecer correlaciones directas, se propone reconocer la utilidad de los ensayos de corto plazo en niveles de evaluación de menor complejidad como una aproximación al contexto real.

A crucial factor of the Green Revolution has been the development and application of pesticides to prevent the potential harm of a variety of organisms that affect crop yields of agronomic interest. However, the sustained increase in the use of these compounds resulted in an enhancement of their presence in the environment, affecting ecosystems and human health. Populations are exposed to complex pesticide mixtures because they are usually combined and commercial formulations content several additives. Considering the scientifc output on the subject in recent years, the aim of this work is to evaluate advancement on the genotoxicity of pesticides and their mixtures at similar concentrations to those found in the environment. Moreover, given the complexity of monitoring studies and the lack of certainty to establish direct correlations, it is proposed to recognize the applicability of short-term tests of minor complexity as an approximation to the real context.