Diazinon Exposure Research Articles

Actinomycetota, a central constituent microbe during long-term exposure to diazinon, an organophosphorus insecticide

Microbial biodegradation is a primary pesticide remediation pathway. Despite diazinon is one of the most frequently used organophosphate insecticides worldwide, its effect on soil microbial community remains obscure. We hypothesize that diazinon exposure reshapes microbial community, among them increased microbes may play a crucial role in diazinon degradation. To investigate this, we collected soil from an organic farming environment, introduced diazinon, cultivated it in a greenhouse, and then assessed its effects on soil microbiomes at three distinct time points: 20, 40, and 270 days after treatment (DAT). Results from HPLC showed that the level of diazinon was gradually degraded by 98.8% at 270 DAT when compared with day zero, whereas 16S rRNA gene analysis exhibited a significant reduction in the bacterial diversity, especially at the early two time points, indicating that diazinon may exert selection pressure to the bacteria community. Here, the relative abundance of phylum Actinomycetota increased at 20 and 40 DATs. In addition, the bacterial functional gene profile employing PICRUSt2 prediction also revealed that diazinon exposure induced the genomic function related to xenobiotics biodegradation and metabolism in soil, such as CYB5B, hpaC, acrR, and ppkA. To validate if bacterial function is caused by increased relative abundance in diazinon enriched soil, further bacteria isolation resulted in obtaining 25 diazinon degradation strains out of 103 isolates. Notably, more than 70% (18 out of 25) isolates are identified as phylum Actinomycetota, which empirically confirms and correlates microbiome and PICRUSt2 results. In conclusion, this study provides comprehensive information from microbiome analysis to obtaining several bacteria isolates responsible for diazinon degradation, revealing that the phylum Actinomycetota is as a key taxon that facilitates microbial biodegradation in diazinon spoiled soil. This finding may assist in developing a strategy for microbial detoxification of diazinon, such as using an Actinomycetota rich synthetic community (SynCom).

Persistent diazinon induced neurotoxicity: The effect on inhibitory avoidance memory performance, amyloid precursor proteins, and TNF-α levels in the prefrontal cortex of rats.

Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex. Rats were divided into 4 groups and recived 2mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels. Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant. Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.

Protective effects of HSP Inducer on diazinon-exposed stellate sturgeon (Acipenser stellatus) fry: Insights on HSP70 gene expression, immune response, and enzyme indices.

Aquatic environments face frequent exposure to organophosphate pesticides, such as diazinon, which are frequently utilized in agriculture. The goal of this study was to evaluate the effects of diazinon exposure on fish and to investigate the potential of the HSP inducer (HSPi) in developing a defense mechanism. To achieve this, several factors were analyzed, including the HSP70 gene expression, levels of immunity markers (lysozyme, IgM, and C3), antioxidant status, and the activity of acetylcholine esterase (AChE). Stellate sturgeon (Acipenser stellatus) fry, was exposed to diazinon (25, 50, and 75% of 96h-LC50) for 6 days after pre-treatment with an HSP inducer (HSPi), TEX-OE® (a prickly pear cactus extract), for 4 hours. Two HSPi concentrations, 100 and 200 mg.L-1, were used. Pre-treatment with HSPi significantly enhanced HSP70 gene expression in the gill and liver, as well as immune markers in the blood of Acipenser stellatus. Diazinon-treated groups exhibited higher antioxidant activities of SOD, CAT, and T-AOC. Increased activity also observed in control fish pre-treated with HSPi. However, stellate sturgeon receiving both diazinon and HSPi+diazinon experienced a significant decrease in AChE activity in comparison with control group. Cortisol levels were elevated in the fish that were subjected to diazinon. Those subjected to diazinon after receiving HSPi showed a significant decrease in cortisol levels. In conclusion, the study suggests that HSPi-mediated HSP70 induction may have a protective effect. The presence of an HSP inducer offers a potential strategy to mitigate the consequences of diazinon exposure in stellate sturgeon.

Evaluating Silymarin Extract as a Potent Antioxidant Supplement in Diazinon-Exposed Rainbow Trout: Oxidative Stress and Biochemical Parameter Analysis.

This study aimed to investigate the effects of diazinon on fish, focusing on hepatotoxic biomarkers and the potential protective effects of silymarin supplementation. One hundred eighty rainbow trout were randomly assigned to four groups: control, diazinon exposed (0.1 mg L-1), silymarin supplemented (400 mg kg-1), and diazinon + silymarin. Blood samples and liver tissue were collected after 7, 14, and 21 days of exposure to analyze biochemical parameters and oxidative biomarkers. Diazinon exposure in fish resulted in liver damage, as indicated by increased antioxidant enzyme activities in the hepatocytes. Silymarin showed the potential to mitigate this damage by reducing oxidative stress and restoring enzyme activities. Nevertheless, diazinon increased creatine phosphokinase activity, which may not be normalized by silymarin. Exposure to diazinon increased glucose, triglyceride, and cholesterol levels, whereas total protein, albumin, and globulin levels were significantly decreased in fish. However, silymarin controlled and maintained these levels within the normal range. Diazinon increased creatinine, urea, uric acid, and ammonia contents. Silymarin could regulate creatinine, urea, and uric acid levels while having limited effectiveness on ammonia excretion. Furthermore, diazinon increased malondialdehyde in hepatocytes, whereas administration of silymarin could restore normal malondialdehyde levels. Overall, silymarin showed potential as a therapeutic treatment for mitigating oxidative damage induced by diazinon in fish, but its effectiveness on creatine phosphokinase, glutathione reductase, and ammonia may be limited.

The protective effect of vitamin C on growth, digestive enzymes, immune response, and gill histology in Caspian roach (Rutilus rutilus caspicus) under diazinon stress

In recent years, the increase in the use of agricultural pesticides has endangered the production of marine creatures. However, exposing farmed creatures to water contaminated with pesticides is one of the current challenges. This study aims to investigate the defensive impact of diets containing varying amounts of vitamin C on the growth, digestive enzyme activity, immune response, and resistance of Caspian roach (Rutilus rutilus caspicus) exposed to diazinon. Fish (average weight: 1.12 ± 0.17 g) were fed diets containing 0 (control; C0), 500 (C1), 1000 (C2), and 1500 (C3) mg/kg of vitamin C for 56 days. Then they were exposed to diazinon stress for 14 days (0.32 mg/liter). The highest final weight and lowest feed conversion ratio were obtained in fish fed a diet containing vitamin C. The highest protease activity and lowest amounts of lipase and amylase were observed in the C3 group. At the end of the feeding period, lysozyme activity, total immunoglobulin amount, and complement (ACH50) in the C3 treatment were significantly higher than in the control treatment. After the stress period, lysozyme and complement activity were higher in all groups fed vitamin C supplements than in the control treatment. The highest levels of stress indicators (cortisol and alkaline phosphatase) were detected in the control group before and after stress. Based on the preparation of gill tissue sections, most lesions included edema, hyperplasia, adhesion of secondary lamellae, and necrosis of gill-covering cells. Overall, the results indicate that adding vitamin C to the diet can be used as a sustainable bioremediation tactic and reduce the adverse effects of diazinon exposure in Caspian roach.

Effects of Diazinon Exposure on Urinary Shedding of Leptospira interrogans Serogroup Hebdomadis in Mice.

Wild rodents are natural hosts of Leptospira spp. and are exposed to various pesticides, some of which are immunotoxic. Rodent urine is an important source of infection for humans and other animals. We evaluated the effects of pesticide exposure on Leptospira growth in mice. Diazinon, at doses of 0.2, 1, and 5 mg/kg/day, was orally administered continuously to mice infected with Leptospira interrogans serogroup Hebdomadis for 32 days. The numbers of L. interrogans in urine and kidney tissues were significantly lower in mice exposed to 5 mg/kg/day diazinon than in unexposed mice (p < 0.05). The urinary concentration of 2-isopropyl-6-methyl-4-pyrimidinol, the metabolite of diazinon, was comparable with the concentration at which viability of L. interrogans was decreased in in vitro assay, suggesting that it had toxic effects on L. interrogans in the proximal renal tubules. Diazinon exposure reinforced Leptospira-induced expression of inflammatory cytokine genes in kidney tissues, and an enhanced immune system might suppress Leptospira growth. These results suggest that diazinon exposure may not increase the risk of Leptospira transmission to humans through mice. This novel study evaluated the relationship between pesticide exposure and Leptospira infection in mice, and the results could be useful for risk assessment of leptospirosis.

Coenzyme Q10 treatment and diazinon exposure in parental male rats: effects of the exposure on their neonatal brains.

Prenatal acute and chronic exposure to organophosphorus pesticides may evoke physical and behavioral impairments in offspring development. However, the mechanism of antioxidant consumption repair to cure these impairments remains unclear. This study aimed to investigate the protective effects of COQ10 against DZN toxicity by measuring Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, the expression of MH2A, DNMT1, H2AZ, and HDAC3, and the histopathology in the brain of neonatal Wistar albino rats whose male parents were exposed to DZN and COQ10. The results showed that COQ10 could significantly decrease MDA level, histopathological alteration, and expression of DNMT1 and HDAC3 in the neonatal brain (P<0.05). Also, an increase in SOD activity and expression of MH2A and H2AZ were observed in the neonatal brain of this group (P<0.05). These investigations suggest that COQ10 can reduce the effects of DZN on neuronal oxidative stress and its damage to the neonatal brain.

Integrated multi-biomarker responses in Mozambique tilapia, Oreochromis mossambicus under acute and chronic Diazinon® exposures

ABSTRACT The pesticide ecosystem impacts are very diverse, and depending on their persistence could exert their intrinsic toxicity within an acute to a chronic timeframe. This study examined the toxic effects of Diazinon on haematological and biochemical endpoints in Oreochromis mossambicus after chronic exposure. After a prior range fining test, fishes were exposed to predetermined diazinon concentrations (T1-0.906 mg/L) and (T2-1.812 mg/L) and sampled after 28 days for toxicity endpoints. In Diazinon-exposed fish, haemoglobin content, Total Red Blood Cells, Total White Blood Cells, and MCH levels were substantially lower (p < 0.05) than in the control fish group. The total blood glucose concentrations in treated fish were substantially greater (p < 0.05) than in the control group, whereas serum protein concentrations were significantly lower (p < 0.05). Observation for most biomarkers revealed patterns of decreasing values with increasing toxicant concentration and exposure duration. The integrated indices (IBR and BRI) indexes were used to provide visual and understandable depictions of toxicity effects and emphasised the relativity of biomarkers in terms of sensitivity and magnitude or severity of responses under graded toxicant exposures. In acute and chronic diazinon exposure circumstances, the analysed metrics show significant impairment to Oreochromis mossambicus.

Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin.

Diazinon (DZN) is an insecticide extensively used to control pests in crops and animals. However, its indicriminated use may lead to liver damage in animals and humans. This study aimed to evaluate the toxicity of DZN (25-150µM) on human hepatoblastoma (HepG2) cells after 24 and 48h of exposure and the role of its biotransformation on the toxicological potential. We also tested the protective effect of tetrahydrocurcumin (THC), an antioxidant agent, in the DZN-induced citotoxicity. DZN caused cytotoxicity in the HepG2 cells, inhibiting cell proliferation and reducing cell viability in a dose- and time-dependent manner. The pre-incubation of HepG2 cells with chemical inducers of cytochrome P450 monooxygenase 3-methylcholanthrene and phenobarbital resulted in a further decrease of cell viability associated with DZN exposure. In addition, the metabolite diazoxon was more toxic than DZN. Our results also revealed that THC alleviated DZN-induced cytotoxicity and reactive oxygen and nitrogen species (RONS) generation in HepG2 cells. In conclusion, our data provide novel insights into the involvement of biotransformation in the mechanisms of DZN-induced cytotoxicity and suggest that amelioration of RONS accumulation might be involved in the protective effect of THC on DZN-induced liver injury.

Epigallocatechin gallate improves meiosis maturation against Diazinon exposure in porcine oocytes

Diazinon (DZN) is a refractory organophosphorus pesticide (OP) in the surrounding environment due to its overuse in agriculture. The antioxidant activity of Epigallocatechin gallate (EGCG) from green tea is at least 100 times greater than that of vitamin C. This study aimed to study the effects of DZN on the meiotic maturation of porcine oocytes, as well as the protective roles of EGCG. Firstly, the effects of DZN and EGCG on meiotic nuclear maturation of porcine oocytes were detected, and then embryonic development was investigated by chemical parthenogenetic activation. Next, the spindle assembly, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), DNA damage, and finally the early apoptosis of oocytes were examined by immunofluorescence staining. The results revealed that DZN exposure significantly reduced the quality of porcine oocytes, such as failure of nuclear and cytoplasmic maturation, evidenced by abnormal spindle assembly, disordered chromosome alignment, low MMP, observably increased ROS, severe DNA damage, and early apoptosis. Appropriate EGCG could significantly reduce all these defects caused by DZN. In conclusion, EGCG can help prevent the harm that DZN exposure can do. These findings offer convincing support for enhancing the oocyte quality from EGCG through daily ordinary beverages.

Melatonin improves meiosis maturation against diazinon exposure in mouse oocytes

AimsOrganophosphorus pesticide diazinon (DZN) has adverse effects on animals and humans by direct contact or the spread of food chain. The antioxidant melatonin has protective effects on female reproduction. This study aimed to explore the effects of DZN on meiosis maturation in mouse cumulus oocyte complexes (COCs) and the effects of melatonin. Main methodsDifferent concentrations of DZN and melatonin were added during the in vitro maturation of COCs. Then we detected the extrusion rate of the first polar body, the number of sperms binding to oocyte, mitochondrial membrane potential, reactive oxygen species (ROS), early apoptosis. Subsequently, the expression of Juno, CX37, CX43 and ERK1/2 were detected by immunofluorescence staining and Western blotting. Key findingsDZN exposure results in the failure of nuclear and cytoplasmic maturation of oocyte meiosis. Destruction of repositioning and function of mitochondria increases the levels of ROS and early apoptosis. The DZN-exposed oocytes express less Juno resulting to bind less sperms than normal. The loss of gap junctions and failure to activate ERK1/2 also contribute to the failure of cytoplasmic maturation. All these ultimately lead to the poor oocyte quality and low fertility. Appropriate melatonin can effectively restore all these defects. SignificanceUnder DZN exposure, melatonin can significantly improve the quality of oocytes, and melatonin promotes oocyte maturation by protecting gap junction and restoring ERK1/2 pathway, which is a new breakthrough for improving female fertility.

Persistent neurobehavioral and neurochemical anomalies in middle-aged rats after maternal diazinon exposure

Diazinon is an organophosphate pesticide that has a history of wide use. Developmental exposures to organophosphates lead to neurobehavioral changes that emerge early in life and can persist into adulthood. However, preclinical studies have generally evaluated changes through young adulthood, whereas the persistence or progression of deficits into middle age remain poorly understood. The current study evaluated the effects of maternal diazinon exposure on behavior and neurochemistry in middle age, at 1 year postpartum, comparing the results to our previous studies of outcomes at adolescence and in young adulthood (4 months of age) (Hawkey 2020). Female rats received 0, 0.5 or 1.0 mg/kg/day of diazinon via osmotic minipump throughout gestation and into the postpartum period. The offspring were tested on a battery of locomotor, affective, and cognitive tests at young adulthood and during middle age. Some of the neurobehavioral consequences of developmental DZN seen during adolescence and young adulthood faded with continued aging, whereas other neurobehavioral effects emerged with aging. At middle age, the rats showed few locomotor effects, in contrast to the locomotor hyperactivity that had been observed in adolescence. Notably, though, DZN exposure during development impaired reference memory performance in middle-aged males, an effect that had not been seen in the younger animals. Likewise, middle-aged females exposed to DZN showed deficient attentional accuracy, an effect not seen in young adults. Across adulthood, the continued potential for behavioral defects was associated with altered dopaminergic function, characterized by enhanced dopamine utilization that was regionally-selective (striatum but not frontal/parietal cortex). This study shows that the neurobehavioral impairments from maternal low dose exposure to diazinon not only persist, but may continue to evolve as animals enter middle age.

Effects of short-term sub-lethal diazinon® exposure on behavioural patterns and respiratory function in Clarias batrachus: inferences for adaptive capacity in the wild

ABSTRACT The potentials for neurotoxicity and respiratory distress under 96 h acute diazinon exposures was examined using behavioural indices and opercular movement respectively in walking catfish, Clarias batrachus. Diazinon exposure concentrations were correlated with toxicological (lethal and sublethal) endpoints. The LC50 values and 95% confidence limits at 24, 48, 72 and 96 h, were 21.85 (19.09- 28.199 mg/L), 19.081 (17.15-21.65 mg/L), 16.07 (14.49- 17.86 mg/L) and 12.85 (10.92-14.39 mg/L) respectively. Concentration-dependent mortality and altered behavioural responses including uncoordinated swim movements, excessive mucus secretion, imbalanced and erratic swimming patterns and brief inactivity prior to mortality was observed. The altered behavioural patterns reflecting neurotoxicity, and increased opercular movement indicating respiratory distress in the catfish increased proportionally with elevated levels diazinon and exposure time. The inactive and almost non-motile state prior to death indicates paralysis and muscle seizure typical in the late stages of cholinergic toxicity. The severity of behavioural and respiratory effects on adult C. batrachus, a hardy species, portends catastrophic consequences for less hardy and more susceptible aquatic taxa like fish in the field, including considerable loss of adaptive ability.

Melatonin Improves Meiosis Maturation Against Diazinon Exposure in Mouse Oocytes

Melatonin Improves Meiosis Maturation Against Diazinon Exposure in Mouse Oocytes

Resveratrol: a panacea compound for diazinon-induced renal toxicity

Diazinon (DZN) is an organophosphate insecticide that has been globally used in agriculture and domestic areas for several years, leading to a variety of negative effects in different targets of humans. This study focused on evaluating the kidney protective role of resveratrol (Res) against sub-chronic DZN exposure by estimating oxidative, anti-oxidative, inflammatory, and apoptotic markers, along with renal function indexes. Overall, 30 Wistar rats were randomly divided into five groups. Groups 1 (control group), 2, 3, 4, and 5 received corn oil, DZN (70 mg/kg), DZN (70 mg/kg) plus Res 5 mg/kg, DZN (70 mg/kg) plus Res 10 mg/kg, and DZN (70 mg/kg) plus Res 20 mg/kg orally, respectively. DZN increased the serum and kidney level of malondialdehyde, total oxidant status, tumor necrosis factor-α (TNF-α), and the expression ratio of Fox-1 and Bax-2. On the other hand, DZN decreased the serum and kidney level of of Total Antioxidant Capacity (TAC), Superoxide dismutase (SOD), Catalase activities (CAT), and the expression ratio of Forkhead box protein O1 (Foxo1); sirtuin 1(Sirt-1);. Based on the results, blood urea nitrogen (BUN) and creatinine (Cr) as the kidney function index were notably changed in all groups. Res treatment inversed DZN-induced kidney toxicity, Finally, Res improved DZN-induced kidney histopathological changes. Overall, these results first demonstrated that Res has protective effects on renal toxicities induced by DZN.

Chronic Effects of Diazinon® Exposures Using Integrated Biomarker Responses in Freshwater Walking Catfish, Clarias batrachus

Diazinon exposures have been linked to the onset of toxic pathways and adverse outcomes in aquatic species, but the ecological implications on model species are not widely emphasized. The objective of this study was to determine how the organophosphate pesticide diazinon affected hematological (hemoglobin, total red blood count, total white blood count, and mean corpuscular hemoglobin), growth (condition factor, hepatosomatic index, specific growth rate), biochemical (total serum glucose, total serum protein), and endocrine (growth hormone, tri-iodothyronine, and thyroxine) parameters in Clarias batrachus after chronic exposure. Diazinon was administered at predefined exposure doses (0.64 and 1.28 mg/L) and monitored at 15, 30, and 45 days into the investigation. Observation for most biomarkers revealed patterns of decreasing values with increasing toxicant concentration and exposure duration. Correlation analysis highlighted a significant inverse relationship between variables (mean corpuscular hemoglobin, condition factor, specific growth rate, tri-iodothyronine, thyroxine, and total serum protein) and elevated chronic diazinon exposure concentrations. The integrated indices (IBR and BRI) indexes were used to provide visual and understandable depictions of toxicity effects and emphasized the relativity of biomarkers in terms of sensitivity and magnitude or severity of responses under graded toxicant exposures. The significant damage reflected by evaluated parameters in diazinon exposure groups compared to control portends risks to the health of local fish populations, including Clarias batrachus in aquatic systems adjacent to agrarian landscapes.

Combined Exposure to Diazinon and Nicotine Exerts a Synergistic Adverse Effect In Vitro and Disrupts Brain Development and Behaviors In Vivo.

A real-life environment during pregnancy involves multiple and simultaneous exposures to toxic chemicals. Perinatal exposures to toxic chemicals have been reported to exert an inhibitory effect on mouse neural development and behaviors. However, the effect of combined exposures of organophosphate and nicotine has not been previously reported. In this study, we investigated whether a combined exposure of diazinon and nicotine can have a synergistic effect. The effects of the combined chemical exposure on cell viability and neuronal differentiation were examined using mouse Sox1-GFP cells. Additionally, mice were maternally administered 0.18 mg/kg diazinon, a no adverse effect level (NOAEL) dose, combined with 0.4, 1, and 2 mg/kg nicotine. Mice offspring underwent behavior tests to assess locomotor, depressive, cognitive, and social behaviors. Morphological change in the brain was investigated with immunolocalization. We revealed that the combined exposure to diazinon and nicotine can have a synergistic adverse effect in vitro. In addition, the chemical-treated mouse offspring showed abnormalities in motor learning, compulsive-like behaviors, spatial learning, and social interaction patterns. Moreover, 0.18 mg/kg diazinon and 2 mg/kg nicotine co-exposure resulted in an increase in tyrosine hydroxylase (TH)-positive dopaminergic neurons. Thus, the findings suggest that perinatal co-exposure to nicotine and diazinon can result in abnormal neurodevelopment and behavior, even at low-level administration.

Effects of diazinon on olfactory epithelium and genes related to olfactory signal transduction in Caspian roach, Rutilus caspicus

Olfaction in fishes is biologically-essential chemoreceptors. It provokes important behaviors for the survival of fish such as feeding, reproduction, avoiding predator and intraspecific communication. Pesticides can affect the olfactory epithelium and genes related to olfactory transduction and impair olfactory function. The present study aims to determine how toxicity of diazinon impacts olfaction of Caspian roach, Rutilus caspicus in histological and gene levels. We exposed fish (0.7 ± 0.05 g in weight) to 0, 1, 2 and 3 mg L-1 diazinon (60 fish in each 3- replicate 60-L glass tank) for 7 days in freshwater. Diazinon concentrations were chosen based on reports on its concentration in surface waters. Mortality rate, histological events of olfactory epithelium, and genes expression at the 7th day after diazinon exposure included a significant decrease in the number of olfactory receptor cells (ORCs), while increased goblet cells (GCs). In addition, G­protein αi (Gpαi) was significantly upregulated, whereas calmodulin-dependent kinase II α (CaMKIIα) was significantly downregulated after 7 days as compared to the control group. These results indicate that diazinon can impair olfactory function through effect on the olfactory epithelium and olfactory signal transduction pathways in the Caspian roach fingerlings.

Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon

The present study predicts in vivo human and rat red blood cell (RBC) acetylcholinesterase (AChE) inhibition upon diazinon (DZN) exposure using physiological based kinetic (PBK) modelling-facilitated reverse dosimetry. Due to the fact that both DZN and its oxon metabolite diazoxon (DZO) can inhibit AChE, a toxic equivalency factor (TEF) was included in the PBK model to combine the effect of DZN and DZO when predicting in vivo AChE inhibition. The PBK models were defined based on kinetic constants derived from in vitro incubations with liver fractions or plasma of rat and human, and were used to translate in vitro concentration–response curves for AChE inhibition obtained in the current study to predicted in vivo dose–response curves. The predicted dose–response curves for rat matched available in vivo data on AChE inhibition, and the benchmark dose lower confidence limits for 10% inhibition (BMDL10 values) were in line with the reported BMDL10 values. Humans were predicted to be 6-fold more sensitive than rats in terms of AChE inhibition, mainly because of inter-species differences in toxicokinetics. It is concluded that the TEF-coded DZN PBK model combined with quantitative in vitro to in vivo extrapolation (QIVIVE) provides an adequate approach to predict RBC AChE inhibition upon acute oral DZN exposure, and can provide an alternative testing strategy for derivation of a point of departure (POD) in risk assessment.

Effects of maternal diazinon exposure on frontal cerebral cortical development in mouse embryo

Background Diazinon including organophosphate (OP) that is widely used in agriculture and animal husbandry industry and the risk of human infection with the toxin and their toxicity. Methods Pregnant balb/c mice (30–35 g) were randomly divided into five groups of five: the control group (no intervention), two sham groups (emulsifier 0.52, and 5.2 liters/volume). From the seventh to the eighteenth day of pregnancy, two experimental groups received diazinon inhaled 1.3 (EXP1) and 13 liters/volume (EXP2) for 40 min every other day, respectively. On the 18th day of pregnancy, the animals were killed and their embryos were removed to appraisal the growth of fetus and development of the frontal cortex. A computer-assisted morphometric quantitative images analysis were performed on the frontal cerebral cortex (FCC) including cortical plate (CP), intermediate zone (IZ) and matrix (proliferative) zone (MZ) of the mouse embryos. Findings The average of crown-rump length and weight of the embryos in the experimental groups were increased without any significant difference. The mean fetal FCC thickness in the EXP2 group was significantly reduced compared to the control group, CP thickness was remarkably increased in fetuses exposed to diazinon. Comparing the mean thickness of MZ and IZ in EXP groups with the sham and control groups indicated a significant decrease. The positive K-67 cells in the FCC of the EXP2 group were significantly reduced. Discussion Exposing diazinon during pregnancy can reduce brain development and would be neurotoxic to the developing brain and can lead to behavioral changes in the offspring.