A fundamental goal of toxicology is to determine safe levels of exposure to potentially poisonous substances for humans and the environment. Traditionally, safe levels have been estimated in laboratory toxicity bioassays by calculating the non-observable effect level (NOEL) of a chemical to a variety of organisms which are representative of certain taxa, i.e. mammals, birds, fish, crustaceans, algae, etc. There are, however, fundamental problems with the validity of this approach, both conceptual and statistical in nature, as indicated by Landis and Chapman and other authors. Thus, the outdated NOEL concept is being replaced by the no-effect concentration (NEC) level, which assumes that toxic chemicals do not have any effect on a population of organisms at very low concentrations.

The mode of action of insecticides is responsible for their higher or lower toxicity to non-target organisms. However, the large variations in susceptibility among different animal taxa indicate that certain biochemical traits particular to a group of organisms are responsible for a specific level of sensitivity. A review of toxicity data to non-target organisms is presented here. Aquatic arthropods are most susceptible to all types of insecticides because they share many physiological features with the target insects. Other aquatic organisms, such as fish and amphibians, are very sensitive to broad-spectrum neurotoxic and respiratory inhibitor insecticides, but not so much to selective insecticides such as IGRs and stomach poisons. Terrestrial vertebrates are also sensitive to most neuro-toxicants and respiratory inhibitors, with the exception of those insecticides derived from natural toxins produced by plants or fungi (e.g. pyrethroids, neonicotinoids, avermectins, spinosad), which appear to have little or no toxicity in birds and mammals.

An ideal model organism should generally have three essential characteristics: successful sexual crosses should be easy to perform; a fully sequenced genome should be available; and it should be easy to induce reliable and reproducible DNA mutations. The nematode Caenorhabditis elegans (C. elegans), introduced to the broad scientific community by Brenner in 1974, fulfills each of these three essential guidelines. Although initially used extensively by the developmental biology community, its recent adoption by the biomedical and environmental toxicology scientists has strengthened experimental design power in these fields. Relative to traditional model organisms, e.g. rat, mouse, dog (mammals) and Arabidopsis (plants), the invertebrate species C. elegans has begun to be recognized as invaluable. For example, it requires a relatively small budget project compared to other possible organisms, is quite small and transparent, has a short lifespan and has relatively simple anatomy and physiology.

Background: We have previously shown that Diethyldithiophosphate (DEDTP), a metabolite of Organophosphorous (OP) compounds biotransformation with longer half life than its parental compound, can modulate T CD4 lymphocyte functions. To explore if DEDTP can also alter T CD8 homeostasis and proliferation we evaluated cellular viability and proliferation by propidium iodide (PI) incorporation and carboxyfluorescein succinimidyl ester (CFSE) assay by flow cytometry, respectively, in peripheral blood mononuclear cells (PBMCs) and T CD8 cells from healthy male donors.
Results: In vitro exposure to 1-50 μM DEDTP decreased T CD4 vs. T CD8 proportion on resting T CD3 lymphocytes. DEDTP decreased T CD8 viability in a dose-dependent manner after 24 h without affecting the rest of T CD3 lymphocytes. DEDTP also decreases CFSE dilution in T CD8 cells stimulated with anti-CD3/CD28 by arresting cells at the first round of division (M1). Decrease in cell proliferation was not only due to cellular arrest, but also to a consequence of cell death. Although cell death and cell cycle arrest were observed in the majority of the T CD8 cells, some particular T CD8 subset clones presented a high proliferative rate in the presence of DEDTP.
Conclusion: DEDTP showed higher toxicity and cytostaticity in T CD8 cells than in T CD4 lymphocytes. This is relevant in exposed individuals as their ability to deal with viral infections and cancer cells could be limited by exposure to OP pesticides.

The recent development of high spatial resolution analytical methods for inorganic element imaging enables the sensitive determination of inorganic and organometallic-based pesticides, at the cellular and subcellular levels. Some organic agrochemicals can also be investigated providing they contain one or more hetero-element, such as the halogens fluorine or bromine. Several micro-chemical imaging methods are currently available and will be reviewed in this article: Electron Microscopy combined to Energy Dispersive X-ray Spectrometry (EM-EDS), PIXE (Particle Induced X-ray Emission), SXRF (Synchrotron Radiation X-ray Fluorescence) combined to micro-XAS (X-ray Absorption Spectroscopy), and Secondary Ion Mass Spectrometry (SIMS). Although these methods offer a high potential in the understanding of the cellular mechanisms of pesticides toxicity, they have not been much used yet in this domain of investigation. The aim of this article is to make known these imaging methods to the scientific community interested in the toxicology of pesticides. Some examples of applications taken from our own investigations, and from other researchers, will be presented to illustrate the kind of information can be gathered from these methods. In particular, the subcellular distribution of Maneb in neuronal cells will be discussed, as well as the subcellular chemical speciation of arsenic in human ovarian cells.

The publication of a study in 2010 showing that a glyphosate herbicide formulation and glyphosate alone caused malformations in the embryos of Xenopus laevis and chickens caused a scientific and political controversy. Debate centred on the effects of the production and consumption of genetically modified Roundup® Ready® soy, which is engineered to tolerate applications of glyphosate herbicide. This study, along with others indicating teratogenic and reproductive effects from glyphosate herbicide exposure, was rebutted by the German Federal Office for Consumer Protection and Food Safety, BVL, as well as in industry-sponsored papers. These rebuttals relied partly on unpublished industry-sponsored studies commissioned for regulatory purposes, which, it was claimed, showed that glyphosate is not teratogenic or a reproductive toxin. However, examination of the German authorities’ draft assessment report (DAR) on the industry studies, which underlies glyphosate’s EU authorisation, revealed further evidence of glyphosate’s teratogenicity. Nevertheless, the German and EU authorities minimized these findings in their assessment and set a potentially unsafe acceptable daily intake (ADI) level for glyphosate. This paper reviews the evidence on the teratogenicity and reproductive toxicity of glyphosate herbicides and concludes that a new and transparent risk assessment needs to be conducted by scientists who are independent of industry and of the regulatory bodies that were involved in the existing authorisation of glyphosate.

The purpose of the current study was to investigate the immunological impacts of chronic imidacloprid insecticide toxicity in broiler chickens and the protective effects of vitamin E and selenium. Broiler chicks (n=90) aged day old were randomly segregated into three groups of 30 chicks each and were kept in separate pens. Newcastle disease (ND) vaccine was given on day 7 and 28 of age. On day 8, chicks in group I were administered 5 mg/kg bw (1/20 LD50) imidacloprid orally. Chicks in group II were given imidacloprid 5 mg/kg bw orally plus a mixture of vitamin E and selenium ≅ 200 mg/kg diet, while group III was given distilled water (DW) orally and served as a control. The treatments were given daily based on weekly body weight till day 45. Antibody titration, serum total immunoglobulins, circulating immune complexes, cell-mediated immunity and histopathology of bursa of Fabricius and spleen were examined. Imidacloprid produced significant decline in the titer of antibodies against ND vaccine, total immunoglobulins and circulating immune complexes in imidacloprid treated group on day 45 as compared to control group. There were no significant changes in the skin thickness between treated chickens and chickens of control group. Histopathology of the bursa of Fabricius revealed edema, lymphocytic depletion in the medulla and cortex and mild interfollicular fibrosis in imidacloprid treated group. The spleen showed mild haemorrhages and lymphocytic depletion. Supplementation of vitamin E and selenium resulted in marked improvements in humoral immunity and pathology of lymphoid organs. It is concluded that imidacloprid insecticide has immunological deleterious effects in chickens targeting the humoral immune responses and vitamin E and selenium supplementation decreased the ill effects of imidacloprid.