Perinatal exposure to parasiticide ivermectin: Long-term effects on reproductive parameters of adult male rats

Ivermectin is one of the most widely used antiparasitic drugs globally. The aim of this study was to evaluate the chronic effects of perinatal exposure to ivermectin on male reproductive parameters in rats. Pregnant rats were treated daily by oral gavage with 0.4 or 1.6 mg kg -1 of ivermectin or vehicle, from gestational day 6 until post-natal day 10. In the adulthood stage, there were significant reductions in the relative testicular weight of rats exposed to the low dose and in relative prostate weight of male rats exposed to the high dose of ivermectin. Furthermore, the animals exposed to the low dose also presented an increased seminal vesicle weight compared to controls. However, neither of the ivermectin doses interfered in daily sperm production, sperm number in testis, or sexual behavior of exposed males. In conclusion, perinatal exposure to ivermectin neither altered the male reproductive system development markedly, nor produced any adverse effects on the parameters evaluated. © 2011 Taylor & Francis.

Effects of insecticides used in corn on immature stages of trichogramma atopovirilia (hymenoptera: trichogrammatidae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of atrazine and picloram on grass carp: acute toxicity and histological assessment

The aim of this study was to evaluate the acute toxicity of atrazine and picloram separately to grass carp (Ctenopharyngodon idella). Firstly, fingerlings were exposed to nominal concentrations of these herbicides to determine the lethal concentration (LC50) (96 h). After this, the animals were treated with sub-acute concentrations of the herbicides to measure the effects on gill histology. The LC50 (96 h) of the atrazine and picloram were, respectively, 37mg L-1 and 4.4 mgL(-1). Four types of alterations were found in gills exposed to atrazine, which were epithelial lifting, partial cell proliferation, lamellar fusion, and aneurysm. Nominal concentrations of picloram caused epithelial lifting, partial cell proliferation, and lamellar fusion.

Zebrafish (Danio rerio) neuromast: promising biological endpoint linking developmental and toxicological studies

Aquatic toxicology is facing the challenge to assess the impact of complex mixtures of compounds on diverse biological endpoints. So far, ecotoxicology focuses mainly on apical endpoints such as growth, lethality and reproduction, but does not consider sublethal toxic effects that may indirectly cause ecological effects. One such sublethal effect is toxicant-induced impairment of neurosensory functions which will affect important behavioural traits of exposed organisms. Here, we critically review the mechanosensory lateral line (LL) system of zebrafish as a model to screen for chemical effects on neurosensory function of fish in particular and vertebrates in general. The LL system consists of so-called neuromasts, composed of centrally located sensory hair cells, and surrounding supporting cells. The function of neuromasts is the detection of water movements that is essential for the fish's ability to detect prey, to escape predator, to socially interact or to show rheotactic behaviour. Recent advances in the study of these organs provided researchers with a broad area of molecular tools for easy and rapid detection of neuromasts dysfunction and/or disturbed development. Further, genes involved in neuromasts differentiation have been identified using auditory/mechanosensory mutants and morphants. A number of environmental toxicants including metals and pharmaceuticals have been shown to affect neuromasts development and/or function. The use of the LL organ for toxicological studies offers the advantage to integrate the available profound knowledge on developmental biology of the neuromasts with the study of chemical toxicity. This combination may provide a powerful tool in environmental risk assessment.

A comparative study of different in vitro lung cell culture systems to assess the most beneficial tool for screening the potential adverse effects of carbon nanotubes

To determine the potential inhalatory risk posed by carbon nanotubes (CNTs), a tier-based approach beginning with an in vitro assessment must be adopted. The purpose of this study therefore was to compare 4 commonly used in vitro systems of the human lung (human blood monocyte-derived macrophages [MDM] and monocyte-derived dendritic cells [MDDC], 16HBE14o- epithelial cells, and a sophisticated triple cell co-culture model [TCC-C]) via assessment of the biological impact of different CNTs (single-walled CNTs [SWCNTs] and multiwalled CNTs [MWCNTs]) over 24h. No significant cytotoxicity was observed with any of the cell types tested, although a significant (p < .05), dose-dependent increase in tumor necrosis factor (TNF)-α following SWCNT and MWCNT exposure at concentrations up to 0.02mg/ml to MDM, MDDC, and the TCC-C was found. The concentration of TNF-α released by the MDM and MDDC was significantly higher (p < .05) than the TCC-C. Significant increases (p < .05) in interleukin (IL)-8 were also found for both 16HBE14o- epithelial cells and the TCC-C after SWCNTs and MWCNTs exposure up to 0.02mg/ml. The TCC-C, however, elicited a significantly (p < .05) higher IL-8 release than the epithelial cells. The oxidative potential of both SWCNTs and MWCNTs (0.005-0.02mg/ml) measured by reduced glutathione (GSH) content showed a significant difference (p < .05) between each monoculture and the TCC-C. It was concluded that because only the co-culture system could assess each endpoint adequately, that, in comparison with monoculture systems, multicellular systems that take into consideration important cell type-to-cell type interactions could be used as predictive in vitro screening tools for determining the potential deleterious effects associated with CNTs.

Food colours:a study of the effects of regulation

In the 1960s the benefits of government regulation of technology were believed to outweigh any costs. But recent studies have claimed that regulation has negative effects on innovation, health and consumer choice. This case study on food colours examines such claims. EFFECTS ON HEALTH were measured by allocating a hazard rating to each colour. The negative list of 1925 removed three harmful colours which were rapidly replaced, so the benefits were short-lived. Had a proposed ban been adopted in the 1860s it would have prevented many years exposure to hazardous mineral colours. The positive list of 1957 reduced the proportion of harmful coal tar dyes from 54% of the total to 20%. Regulations brought a greater reduction in hazard levels than voluntary trade action. Delays in the introduction of a positive list created a significant hazard burden. EFFECTS ON INNOVATION were assessed from patents and discovery dates. Until the 1950s food colours were adopted from textile colours. The major period of innovation for coal tar colours was between 1856 and 1910, finishing well before regulations were made in 1957, so regulations cannot be blamed for the decline. Regulations appear to have spurred the development of at least one new coal tar dye, and many new plant colours, creating a new sector of the dye industry. EFFECTS ON CONSUMER CHOICE were assessed by case studies. Coloured milk, for example, was banned despite its popularity. Regulations have restricted choice, but have removed from the market foods that were nutritionally impoverished and poor value for money. Compositional regulations provided health protection because they reduced total exposure to colours from certain staple foods. Restricting colours to a smaller range of foods would be an effective way of coping with problems of quality and imperfect toxicological knowledge today.

The effects of the fungicides fenhexamid and myclobutanil on SH-SY5Y and U-251 MG human cell lines

Mixtures of pesticides in foodstuffs and the environment are ubiquitous in the developed world and although agents are usually exhaustively tested individually, the toxicological implications of pesticide mixtures are underreported. In this study, the effects of two fungicides, fenhexamid and myclobutanil were investigated individually and in combination on two human cell lines, SH-SY5Y neuronal cells and U-251 MG glial cells. After 48. h of incubation with increasing concentrations of pesticides ranging from 1 to 1000. μM, gene expression profiles were studied in addition to toxicity end points, including cell viability, mitochondrial depolarisation as well as cellular glutathione maintenance. There were no significant differences between the susceptibility of the two cell lines in terms of cell viability assessment or mitochondrial membrane potential, when agents were administered either individually or in combination. By contrast, in the presence of the fungicides, the SH-SY5Y cells showed significantly greater susceptibility to oxidative stress in terms of total thiol depletion in comparison with the astrocytic cells. Treatment with the two pesticides led to significant changes in the cell lines' expression of several genes which regulate cell cycle control and growth (RB1, TIMP1) as well as responses to DNA attrition (ATM and CDA25A) and control of apoptosis (FAS). There was no evidence in this study that the combination of fenhexamid and myclobutanil was significantly more toxic than individual exposure, although gene expression changes suggested there may be differences in the sub-lethal response of both cell lines to both individual and combined exposure.

Comprehensive forensic toxicological analysis of designer drugs

New designer drugs are constantly emerging onto the illicit drug market and it is often difficult to validate and maintaincomprehensive analytical methods for accurate detection of these compounds. Generally, toxicology laboratories utilize a screening method, such as immunoassay, for the presumptive identification of drugs of abuse. When a positive result occurs, confirmatory methods, such as gas chromatography (GC) or liquid chromatography (LC) coupled with mass spectrometry (MS), are required for more sensitive and specific analyses. In recent years, the need to study the activities of these compounds in screening assays as well as to develop confirmatory techniques to detect them in biological specimens has been recognized. Severe intoxications and fatalities have been encountered with emerging designer drugs, presenting analytical challenges for detection and identification of such novel compounds. The first major task of this research was to evaluate the performance of commercially available immunoassays to determine if designer drugs were cross-reactive. The second major task was to develop and validate a confirmatory method, using LC-MS, to identify and quantify these designer drugs in biological specimens.^ Cross-reactivity towards the cathinone derivatives was found to be minimal. Several other phenethylamines demonstrated cross-reactivity at low concentrations, but results were consistent with those published by the assay manufacturer or as reported in the literature. Current immunoassay-based screening methods may not be ideal for presumptively identifying most designer drugs, including the "bath salts." For this reason, an LC-MS based confirmatory method was developed for 32 compounds, including eight cathinone derivatives, with limits of quantification in the range of 1-10 ng/mL. The method was fully validated for selectivity, matrix effects, stability, recovery, precision, and accuracy. In order to compare the screening and confirmatory techniques, several human specimens were analyzed to demonstrate the importance of using a specific analytical method, such as LC-MS, to detect designer drugs in serum as immunoassays lack cross-reactivity with the novel compounds. Overall, minimal cross-reactivity was observed, highlighting the conclusion that these presumptive screens cannot detect many of the designer drugs and that a confirmatory technique, such as the LC-MS, is required for the comprehensive forensic toxicological analysis of designer drugs.^

The Repellent DEET Potentiates Carbamate Effects via Insect Muscarinic Receptor Interactions: An Alternative Strategy to Control Insect Vector-Borne Diseases.

International audience

Mineral and organic pollution in river Sabor (Northeastern Portugal): ecotoxicological effects on freshwater fauna

Aquatic ecosystems are final collectors of all kinds of pollution as an outcome of anthropogenic inputs, such us untreated industrial and municipal sewage and agricultural pollutants. There are several aquatic ecosystems that are threatened by mineral and organic pollution. In Northeastern Portugal, near Bragança, different watercourses are suffering negative impacts of human activities. It has been developed several studies in the monitoring of environmental impacts in these river basins, namely in Rio Fervença, affected by organic pollution, and in Portelo stream, affected, since 2009, by the collapse and continuous input of mining deposits. In this sense, the present study aimed to continue the monitoring study of ecological status of freshwater ecosystems of Northeastern Portugal, namely the following objectives: a) mineral pollution effects of mining deposits sudden incorporated into Portelo stream; b) organic pollution due to domestic and industrial inputs in River Fervença. Also, since fish are useful experimental models to evaluate toxicological mechanisms of contaminants, c) acute toxicity tests with Cu were conducted in laboratory conditions. During 2015/2016, it was made abiotic and biotic characterization of 16 sampling sites distributed by both Portelo and Fervença rivers, tributaries of main River Sabor (Douro Basin). Several physicochemical parameters were determined and Riparian Quality (QBR Index) and Channel Quality (GQC) Indexes were determined for habitat evaluation. Fish and invertebrate communities were sampled, according to protocols of Water Framework Directive (WFD). Several metrics were determined, with particular emphasis on the Biotic Index IBMWP and the Northern Portuguese Invertebrate Index (IPtIN). Acute toxicity tests were conducted with an Iberian fish species, common barbel (Luciobarbus bocagei) and some plasmatic electrolytes levels were evaluated, to assess their contribution to mitigate osmoregulatory adverse effects of Cu. Also, same electrolytes were measured after changing to clean water, in attempt to assess fish capacity to reverse this situation. Results obtained for both rivers showed a significant level of disturbance that affected decisively water, habitat and biological quality of aquatic ecosystems. Mineral and Organic Pollution in River Sabor (NE Portugal): Ecotoxicological Effects on Freshwater Fauna Due to this change of environmental conditions in Portelo stream (extreme pH values, high conductivity and presence of heavy metals), several biological metrics (e.g. taxonomic richness, abundance, diversity, evenness) confirmed, comparatively with reference sites, a substantial decrease on ecological integrity status. The same pattern was found for Fervença River; however other water parameters, namely the content of most limiting nutrients (e.g. N and P) seemed to have more influence in the composition and structure of macroinvertebrate and fish communities. In fact, despite the operation of the Sewage Treatment Plant of Bragança, Fervença River presented significant levels of disturbance that affected decisively the quality and ecological integrity of the aquatic ecosystem. The synergic effect of domestic and industrial pollution, intensive agriculture, regulation and degradation of aquatic and riparian habitats contributed to the decrease of ecological condition, namely in the downstream zones (after Bragança). The results for acute toxicity, showed that fish can change Na+ and K+ levels face to Cu exposition and, depending of Cu concentration tested, can also return to normal levels, providing some insights to that are believed to occurred in fish population, near the Portelo mines. The low ecological integrity status detected in the lotic ecosystems in NE Portugal as a result of mineral and organic pollution deserves the development of several measures for rehabilitation and improving of water quality. On the other hand, environmental education actions are needed to contribute to improvement of ecological integrity of the river and its conservation.

Toxicological impact of JWH-018 and its phase I metabolite N-(3-hydroxypentyl) on human cell lines

"The emergence and abuse of synthetic cannabinoids has been increasing as an alternative to cannabis, mainly among youth. As their appearance on the drug market has been recent, the pharmacological and toxicological profiles of these psychoactive substances are poorly understood. Current studies suggest that they have stronger effects compared to their natural alternatives and their metabolites retain affinity towards CB1 receptors in CNS. Since studies on its toxicological properties are scarce, the effects of the drug in human derived cell lines were investigated. The present study was designed to explore the toxicological impact of parent drug versus phase I metabolites of synthetic cannabinoids on human cells with and without CB1 receptor. The human cell line of neuroblastoma SH-SY5Y and human kidney cell line HEK-293T were exposed to JWH-018 and to its N-(3-hydroxypentyl) metabolite. Cell toxicity was evaluated using the MTT and LDH assay. Additionally, a dual staining methodology with fluorescent Annexin V-FITC and propidium iodide was performed to address the question of whether JWH-018 N-(3-hydroxypentyl) metabolite is inducing cell death through apoptosis or necrosis, in HEK293T and SH-SY5Y cell lines. The obtained results show that JWH-018 does not cause a statistically significant decrease in cell viability, in contrast to its N-(3-hydroxypentyl) metabolite, which at ≥25μM causes a significant decrease in cell viability. Both cell lines are affected by JWH-018 metabolite. Our results point to higher toxicity of JWH-018 metabolite when compared to its parent drug, suggesting a non-CB1 receptor mediated toxicological mechanism. Comparing the results from Annexin V/PI with MTT and LDH assays of SH-SY5Y and HEK293T in the presence of the synthetic cannabinoid metabolite, emerges the picture that cellular viability decreases and associated death is occurring through necrosis."