The Greening of Pesticide–Environment Interactions: Some Personal Observations

Background: Pesticide–environment interactions are bidirectional. The environment alters pesticides by metabolism and photodegradation, and pesticides in turn change the environment through nontarget or secondary effects

Environ Res

Epidemiologic studies suggest that occupational exposure to pesticides might increase Parkinson disease risk. Some pesticides, such as the organophosphorus insecticide chlorpyrifos, appear to increase the expression of \uce\ub1-synuclein, a protein critically involved in Parkinson disease. Therefore, we assessed total blood cell \uce\ub1-synuclein in 90 specimens from 63 agricultural pesticide handlers, mainly Hispanic men from central Washington State, who participated in the state's cholinesterase monitoring program in 2007-2010. Additionally, in age-adjusted linear regression models for repeated measures, we assessed whether \uce\ub1-synuclein levels were associated with butyrylcholinesterase-chlorpyrifos adducts or cholinesterase inhibition measured in peripheral blood, or with self-reported pesticide exposure or paraoxonase (PON1) genotype. There was no evidence by any of those indicators that exposure to chlorpyrifos was associated with greater blood \uce\ub1-synuclein. We observed somewhat greater \uce\ub1-synuclein with the PON1-108T (lower paraoxonase enzyme) allele, and with \ue2\u2030\ua5 10 h of exposure to cholinesterase inhibiting insecticides in the preceding 30 days, but neither of these associations followed a clear dose-response pattern. These results suggest that selected genetic and environmental factors may affect \uce\ub1-synuclein blood levels. However, longitudinal studies with larger numbers of pesticide handlers will be required to confirm and elucidate the possible associations observed in this exploratory cross-sectional study.ES016873/ES/NIEHS NIH HHS/United StatesES019277/ES/NIEHS NIH HHS/United StatesP30 ES007033/ES/NIEHS NIH HHS/United StatesP30ES007033/ES/NIEHS NIH HHS/United StatesP42 ES004696/ES/NIEHS NIH HHS/United StatesR01 ES016873/ES/NIEHS NIH HHS/United StatesR01 ES019277/ES/NIEHS NIH HHS/United StatesT32 ES015459/ES/NIEHS NIH HHS/United StatesU01 NS082137/NS/NINDS NIH HHS/United StatesU01NS082137/NS/NINDS NIH HHS/United StatesU54 HD083091/HD/NICHD NIH HHS/United StatesU54 OH007544/OH/NIOSH CDC HHS/United StatesU54OH007544/OH/NIOSH CDC HHS/United States2016-01-01T00:00:00Z25460623PMC454829

The Pragmatic Strategy to Detect Endocrine-Disrupting Activity of Xenobiotics in Food

Endocrine-disrupting activity induced by xenobiotics might pose a possible health threat. Facing so many chemicals, there is an issue on how we detect them precisely and effectively. The whole embryo culture (WEC) test, an ex vivo exposure lasting 48 hours with rat embryos of 10.5 days old, is used to detect prenatal developmental toxicity. We extended the WEC function to detect the endocrine-disrupting activity induced by environmental chemicals. Results showed that in the development of rat embryo, basically 17ß-estradiol, triiodothyronine, triadimefon, penconazole, and propiconazole exhibited no significant effect on yolk sac circulatory system, allantois, flexion, heart caudal neural tube, hindbrain, midbrain, forebrain, otic system, optic system, olfactory system, maxillary process, forelimb, hind limb, yolk sac diameter, crown-rump length, head length, and developmental score. In the immunohistochemistry, the positive control of 17ß-estradiol showed positive effect for its receptor expressions. These three triazoles induced expressions of ERα and ERß in WEC. This result basically meets the mode of action that triazoles were designed to disrupt the synthesis of steroid hormone. Here we gave a strategy to detect possible endocrine-disrupting activity induced by xenobiotics in food. This strategy is quick to initiate the whole rat embryo culture with 10.5 days to detect the hormone receptors such as androgen, estrogen, thyroid, aromatase activity and its related receptors

THE ROLE OF CAR AND PXR IN TOXICANT SENSITIVITY

The Constitutive Androstane Receptor (CAR) and the Pregnane X Receptor (PXR) are nuclear receptors of significant importance in the regulation of enzymes that metabolize, detoxify and eliminate compounds from the body. In this study we assessed the protective role of CAR and PXR in the basal and inducible regulation of Cytrochrome P450s (CYPs), and the potential of CAR and PXR to help protect individuals from the organophosphate, parathion and the plasticizer, nonylphenol, putatively due to improved metabolism and elimination. Knockout models of these receptors were used to model susceptible populations such as children that are known to have lower CAR and PXR expression during the first six months of age. A humanized model was used to extrapolate findings to human populations. Overall, the data suggests that individuals with low CAR or PXR (newborn children), or low CAR/PXR activation (elderly) may be more susceptible to xenobiotic toxicity putatively because of the lower expression of CAR and PXR resulting in a lower expression of CYPs which leads to the inability to metabolize, detoxify and eliminate toxic compounds

Štetno djelovanje organofosfornih pesticida na jetra: kratki pregled četrdesetogodišnjeg istraživanja

Organophosphorus pesticides (OPs) are widely used volatile pesticides that have harmful effects on the liver in acute and chronic exposures. This review article summarises and discusses a wide collection of studies published over the last 40 years reporting on the effects of OPs on the liver, in an attempt to propose general mechanisms of OP hepatotoxicity and possible treatment. Several key biological processes have been reported as involved in OP-induced hepatotoxicity such as disturbances in the antioxidant defence system, oxidative stress, apoptosis, and mitochondrial and microsomal metabolism. Most studies show that antioxidants can attenuate oxidative stress and the consequent changes in liver function. However, few studies have examined the relationship between OP structures and the severity and mechanism of their action. We hope that future in vitro, in vivo, and clinical trials will answer the remaining questions about the mechanisms of OP hepatotoxicity and its management.Organofosforni pesticidi (OP) imaju veoma široku primjenu, ali i štetno djeluju na jetru pri akutnoj i kroničnoj izloženosti. Ovaj članak daje pregled 40 godina istraživanja djelovanja OP-ova na jetru s namjerom da predloži neke zajedničke mehanizme njihova toksičnog djelovanja na jetru i liječenje. U istraživanjima se izdvaja nekoliko ključnih bioloških procesa koji sudjeluju u hepatotoksičnosti OP-ova, poput narušavanja antioksidacijskoga obrambenog sustava, oksidacijskoga stresa, apoptoze te mitohondrijskoga i mikrosomalnoga metabolizma. Rezultati većine istraživanja potvrdili su da antioksidansi uspješno ublažavaju posljedice oksidacijskoga stresa u jetri. Međutim, gotovo da i nije istražena povezanost između strukture OP-ova i njihove štetnosti odnosno mehanizama djelovanja. Nadamo se da će buduća in vitro i in vivo istraživanja te klinička ispitivanja odgovoriti na preostala pitanja vezana uz mehanizme hepatotoksičnoga djelovanja OP-ova i njegova uspješnoga liječenja

Chromatophores as cell-based biosensors for the detection of chemically and biologically toxic substances

Cell-based biosensors are function-based detectors that use the physiological response of a living cell to sense biologically stimulating agents. This emerging technology extends the application of current detection methods by reporting on the toxicity of a sample and the potential to cause disease. Previously, Betta splendens erythrophores have been described as a method to detect toxic agents such as pesticides, chemicals, purified bacterial toxins and food-associated bacteria. The first objective of this study was to examine the B. splendens erythrophore response to Gram-negative food-associated bacteria by investigating the response to Salmonella typhimurium. Erythrophores aggregated in the presence of S. typhimurium in a growth-phase-dependent manner and this response was distinct from the media control. Additionally, it was found that erythrophore aggregation was dependent on the bacterial cell and erythrophores were not responsive to secreted bacterial products found in the culture supernatant. Transposon mutagenesis of S. typhimurium ATCC 700720 resulted in an interruption of the promoter region of operon prgHIJK. This insertion inactivated the expression of the SPI-1 T3SS structural proteins. The mutation resulted in a delayed erythrophore aggregation, implying that the SPI-1 T3SS is an important component contributing to erythrophore aggregation. The second objective of this study was to characterize the Oncorhynchus tshawytscha melanophore in terms of its responsiveness to aggregative and dispersive controls. It was hypothesized that the pigment response was biologically conserved between O. tshawytscha melanophores and B. splendens erythrophores. The data presented support this hypothesis and highlight potential applications. Melanophores aggregated in response to mercuric chloride and sodium arsenite but dispersed in the presence of ammonia. Additionally, melanophores aggregated in response to salmonid bacterial pathogens Aeromonas salmonicida, Yersinia ruckeri and Flavobacterium psychrophilum. Melanophores were capable of differentiating between healthy and diseased fish tissues. These results warrant a continued investigation into the full potential of the O. tshawytscha melanophore system. In conclusion, this study investigated two cell-based biosensor models; B. splendens erythrophores and O. tshawytscha melanophores. The data presented suggests that these models can be applied for the detection of foodborne bacterial pathogens and for the detection of chemical and bacterial contaminants pertinent to the aquaculture industry

Developmental neurotoxicity testing of chemical mixtures in zebrafish embryos

Developmental neurotoxicity (DNT) is an understudied problem. Every day, people are exposed to complex mixtures of several chemical substances via food intake, inhalation and dermal contact. Nevertheless, risk assessment is performed on single compounds only under the assumption that the individual exposure levels (below no observed adverse effect levels, NOAELs) are predictive of the mixture effect. In the EuroMix project, a method has been developed to evaluate the effects of mixtures of substances, even at or below NOAELs. This method follows the strategy proposed by the European Food Safety Authority (EFSA), and further implements the Adverse Outcome Pathway (AOP) concept as a basis. Currently, assessment of the DNT potential of compounds is performed in costly and time-consuming in vivo rodent studies involving a large number of animals studied over more than one generation. Therefore, from a 3Rs (Replacement, Reduction, Refinement) perspective an alternative approach is needed. The zebrafish (Danio rerio) embryo (ZFE) provides an interesting and potentially useful model to study DNT as neurodevelopment occurs fast with a large resemblance to the higher vertebrate including the human system. Also, from a legal perspective, experimental work with zebrafish embryos within 120 hours post-fertilization, is not considered an animal experiment. Combined with the ease of culture and the high reproduction rate this renders the ZFE a suitable model for high throughput DNT testing in vitro. One of the suitable readouts for DNT testing is neurobehavior since it provides integrated information on the functionality/status of the full nervous system of the embryo. Within 120 hpf the embryo develops from a fertilized egg to a fully functional embryo responsive to environmental stimuli such as light and sound (vibration). The present Ph.D. study investigated the potential human health risk caused by the simultaneous exposure of chemical substances and the need to include the mixtures in the risk assessment. To obtain a real-life picture ofenvironmental pollution by chemical mixtures, an UHPLC-MS/MS-MRM method was developed and validated for screeining pesticide residues on raw and processed tomatoes. Then, the attention was focused on the potential use of the zebrafish model for assessing the chemical mixtures effects in DNT. Recognised that pharmaceuticals display a well-known MOA and are known to cause DNT, their use as model compounds instead of pesticides was preferred. Therefore, the combined effect of three psychoactive pharmaceuticals of concern, Carbamazepine (CBZ), Fluoxetine (FLX), Venlafaxine (VNX) and their main metabolites, Carbamazepine 10,11 -epoxide (CBZ 10,11E), Norfluoxetine (norFLX), and Desvenlafaxine (desVNX), was studied using the zebrafish embryos as a study model. At first, single-compound concentration-effect relationships were assessed as input for dose-response modelling following the benchmark approach leading to a classification of compounds based on potency. Subsequently, a binary mixture was composed based on the relative potency of the individual compounds and tested for their effect on neurological development. To support the assessment of developmental neurotoxicity, the gene expression of three specific DNT markers was investigated

Pesticides in the Modern World

The introduction of the synthetic organochlorine, organophosphate, carbamate and pyrethroid pesticides by 1950's marked the beginning of the modern pesticides era and a new stage in the agriculture development. Evolved from the chemicals designed originally as warfare agents, the synthetic pesticides demonstrated a high effectiveness in preventing, destroying or controlling any pest. Therefore, their application in the agriculture practices made it possible enhancing crops and livestock's yields and obtaining higher-quality products, to satisfy the food demand of the continuously rising world's population. Nevertheless, the increase of the pesticide use estimated to 2.5 million tons annually worldwide since 1950., created a number of public and environment concerns. This book, organized in two sections, addresses the various aspects of the pesticides exposure and the related health effects. It offers a large amount of practical information to the professionals interested in pesticides issues