Gestational and perinatal exposure to diazinon causes long-lasting neurobehavioral consequences in the rat.

Diazinon is a widely-used organophosphate pesticide. Pulsatile exposure to diazinon during neonatal development has previously been shown cause long-term neurobehavioral impairments in rats. However, the effects of chronic low concentration exposures during perinatal development remain unclear. This experiment evaluated such effects in Sprague-Dawley rats by implanting osmotic pumps in breeder females prior to conception (N = 13-15 litters per condition) which then delivered chronic, zero order kinetic low-level infusions of 0, 114 or 228 ug/day of diazinon throughout pregnancy. One male and one female from each litter was assessed with a battery of behavioral tests that continued from four weeks of age into adulthood. Litter was used as the unit of variance for the analysis of variance test of significance, with sex as a within litter factor. Diazinon treatment condition was the between subjects factor and time or sessions were repeated measures. Chronic diazinon exposure from pre-mating until the neonatal period caused a significant (p < 0.05) increase in percent of time spent on the open arms of the elevated plus maze, an index of risk-taking behavior. Gestational and lactational diazinon exposure also caused a significant (p < 0.05) degree of hyperactivity in the Figure-8 apparatus during adolescence, specifically affecting the early part of the hour-long test session. This effect had dissipated by the time the rats reached adulthood. Diazinon exposure also caused a significant impairment in novel object recognition, a test of cognitive function. Offspring exposed to 228 ug/day diazinon (p < 0.05) showed significantly less preference for the novel vs. familiar object than controls during the first five minutes of the novel object recognition test.

Influence of selective treatment of bulls on the infestation of Haematobia irritans on untreated cows.

The distribution of Hematobia irritans is not homogeneous in cattle populations. Generally, between 15% and 30% of bovines carry more than 50% of the flies, and higher infestations occur in bulls. In this study, the effect of treating the bulls with ear tags containing 40% diazinon on the infestation of flies on the herd during the breeding season was evaluated. Four groups of cattle were made, each containing one bull and 35 Braford cows. Groups 1 and 2 were on pastures in highlands. Groups 3 and 4 were on pastures in lowlands. At the beginning of the trial, each bull from Groups 1 and 3 was treated with an ear tag. Bulls from Groups 2 and 4 remained untreated. Weekly, for 10 weeks, horn flies were counted from each bull and 15 cows from each group. A repeated measures linear mixed model was used with cows as random effects. The number of horn flies in the treated groups was lower than that in the untreated group, suggesting that selective treatment of bulls could be an effective strategy to control horn flies on the herd. The number of flies was higher in the lowland than that in the highland groups, suggesting an effect of the environment on horn fly infestations. In addition, we estimated the cow level predictions from the model to estimate the cow effect on fly counts, and we compared those values with the observed weekly quartiles for each group. Fly-susceptible cows were defined as those for which the infestation of flies appeared in the upper quartile more than 50% of the weeks and in the lower quartile less than 20% of the weeks. In contrast, a fly-resistant cow was defined as one for which the fly counts appeared in the lower quartile more than 50% of the weeks and in the upper quartile less than 20% of the weeks. In all, 8.3% of the cows were susceptible and 15% were resistant. These results may be used to selectively treat bulls or to treat the bulls and the most susceptible cows during the breeding season.

Different response of acetylcholinesterases in salt- and detergent-soluble fractions of honeybee haemolymph, head and thorax after exposure to diazinon.

Organophosphate pesticide diazinon is a specific inhibitor of acetylcholinesterase (AChE), which is a common neurotoxicity biomarker in environmental studies. In honeybees, AChE exists in two forms having different physiological roles, one existing as a soluble form and the other as membrane-bound. In most studies AChE activity has been analysed without paying considerable attention to different forms of AChE. In this study, we exposed honeybees Apis mellifera carnica for 10days to diazinon via oral exposure and analysed the total AChE activities in salt soluble (SS) and detergent soluble (DS) fractions. We assumed that SS fraction would preferentially contain the soluble AChE, but the DS fraction would contain only membrane AChE. On the contrary, our results showed that SS and DS fractions both contain soluble and membrane AChE and the latter has considerably higher activity. Despite this we obtained a differential response of AChE activity in SS and DS fractions when exposed to diazinon. The head/thorax AChE activity in DS fraction decreased, while the head/thorax AChE activity in SS fraction increased at sublethal concentrations. The AChE activity in honeybee hemolymph shown here for the first time is a salt soluble enzyme. Its activity remained unaltered after diazinon treatment. In conclusion, we provide evidence that varying results regarding AChE activity alterations upon stressor exposure are obtained when extracted through different procedures. In further environmental studies with honeybees this differential response of AChE activity should be given considerable attention because this affects the outcome of ecotoxicity study.

Protective effects of cerium oxide and yttrium oxide nanoparticles on reduction of oxidative stress induced by sub-acute exposure to diazinon in the rat pancreas.

Diazinon is a kind of organophosphorus (OP) compound that is broadly used against different species of insects and pests. Oxidative stress can occur at very early stages of diazinon exposure and the pancreas is one of the main target organs for toxicity by diazinon. The aim of this study was to evaluate the protective effects of cerium oxide nanoparticles (CeO2 NPs) and yttrium oxide nanoparticles (Y2O3 NPs) against the pancreatic damage from sub-acute exposure of diazinon. Diazinon at a dose of 70mg/kg/day was given through gavage to rats once a day. Along with diazinon, trace amounts of CeO2 NPs and Y2O3 NPs (35mg/kg and 45mg/kg per day, respectively) were administered by intraperitoneal injection once a day for 2 weeks. Animals weight and blood glucose were measured during the treatment, and oxidative stress biomarkers, diabetes physiology, function and viability of cells were investigated at the end of the treatment in serum and pancreas tissues. Apoptosis of islets was examined by the flow cytometry. The high blood glucose level and significant weight loss resulting from diazinon were modified as a result of the application of the NPs. A significant recovery in oxidative stress markers, pro-insulin, insulin, C-peptide, adenosine diphosphate/adenosine triphosphate (ATP/ADP) ratio, caspase-3 and -9 activities and apoptosis-necrosis in the islets was observed. In conclusion, administration of CeO2 NPs or Y2O3 NPs only or their combination with suitable and defined dose will help to overcome the consequences from oxidant agents.

Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum.

Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30nM), EFS-induced ileal contractions were increased significantly. In the same preparation, diazinon 3nM, significantly increased contractions induced by EFS, but did not affect the contractions caused by 5MFI. Contrarily, 1µM of diazinon significantly and reversibly inhibited the EFS-induced ileal contractions. Diazinon exhibited competitive and non-competitive inhibitions of 5MFI induced contractions. The control EC50 of 5MFI was 2.48µM with Rmax=1.88g. In the presence of diazinon, EC50 was 12.45µM, while Rmax was reduced to 0.43g. After washing, the EC50 and Rmax values were again closer to the control level (3.80µM and 1.04g). Diazinon 1µM did not inhibit Ascaris suum contractions caused by ACh, but it increased the Rmax. Diazinon in our study exhibits two opposite effects on the motor activity of the ileum. In low nanomolar concentrations the dominat is its effect on AChE and the stimulation of contractions. Furthermore, in concentrations that approach micromolar values diazinon has a direct inhibitory effect on muscarinic receptors. The direct inhibitory effect of diazinon on A. suum contractions was not found.

Effect of separate and combined exposure of selenium and diazinon on rat sperm motility by computer assisted semen analysis.

Effects of selenium (Se) and diazinon (DZN) on sperm motility parameters in rats were investigated. Male rats received a separate dose of Se (2mgkg-1 b.w., intraperitoneally, 5mgL-1, per os in drinking water), diazinon (20mgkg-1 b.w., intraperitoneally, 40mgL-1, per os in drinking water), and in combination (Se+DZN) with the same dosage as in the separate administration. 36h an intraperitoneal (i.p.) and after 90days of per oral (p.o.) exposure, thirteen parameters of sperm motility were evaluated using a Computer Assisted Sperm Analyzer (CASA). Almost all the evaluated sperm motility parameters significantly decreased in Se p.o. exposed groups. In the Se i.p. group decrease was noted only in beat cross frequency (BCF) and progressive motility. Significant decline in the sperm motility, progressive motility, BCF and increase in amplitude of lateral head displacement (ALH) were recorded after DZN i.p. administration. In DZN p.o. group, significant increase in ALH, velocity average path (VAP) and curvilinear velocity (VCL) but decrease in progressive motility and BCF was detected. Se+DZN i.p. administration caused a significant decrease in motility, progressive motility and BCF. Per oral administration of Se+DZN decreased all motility parameters except LIN, WOB and ALH. Sperm abnormalities increased in all experimental conditions. Se and DZN negatively affected sperm structure and function in separate doses or in combination. No protective effect of Se was observed.

Epidemiological and therapeutic studies of camel mange in Fafan zone, Eastern Ethiopia.

BACKGROUND: Camel mange is an economically important parasitic disease affecting productivity in camel rearing areas of the world if appropriate treatment is not instituted. METHODS: A cross-sectional and a controlled field trial were carried out to study the epidemiology of camel mange in Fafan zone, Eastern Ethiopia, and evaluate the efficacy of ivermectin and diazinon in the control of mange infestation in camels on the basis of clinical and parasitological evidence, respectively. Three groups of naturally infested camels and one group of healthy camels each composed of 6 individuals were enrolled: the two infested groups received either ivermectin or diazinon, and the other groups remained untreated. RESULTS: The overall prevalence rate of mange in camels in the study area was 31.5% and the only identified species was Sarcoptes scabiei. The prevalence rate was found to significantly vary (p < 0.05) in relation to body condition and herd size of camels. Both drugs showed significant variation (p < 0.05) on improving clinical and body condition scores. Clearance of mange lesions occurred with both drugs; however, re-infestation was observed in diazinon treated group. Ivermectin significantly improved (p < 0.05) both body condition and clinical scores whereas diazinon markedly improved only the later. CONCLUSION: In conclusion, camels in the study area harbored considerable level of S. scabiei which warrants institution of an integrated control approach by administration of ivermectin while also sanitating the animal environment.

The chemoprotective effects of L-carnitine against genotoxicity induced by diazinon in rat blood lymphocyte.

The purpose of this study was to assess the preventive effects of L-carnitine (LC) against DNA damage induced by diazinon (DZN) in rat blood lymphocytes. Animals were concurrently administered intraperitoneally with DZN in proper solvent (20 mg/kg body weight (b.w.)) and LC at three different doses (50, 100, and 150 mg/kg b.w.) for 30 consecutive days. The positive control group received DZN at the same dose without LC. Twenty-four hour after last injection, 0.5 ml blood of each rat was received and cultured in culture medium for 44 h. The lymphocyte cultures were mitogenically stimulated with cytochalasin B for the evaluation of the number of micronuclei (MNs) in cytokinesis-blocked binucleated cells. Incubation of lymphocytes with DZN induced additional genotoxicity and was shown by increase in MNs frequency in rat lymphocytes. LC at all doses had a protective effect and significantly reduced the MNs frequency in cultured lymphocytes (p < 0.0001-p < 0.05). The maximum effect was observed at 150 mg/kg that reduced the frequency of MN from 12.78 ± 0.24% for DZN group to 5.61 ± 0.17%. Our study revealed that LC has a potent antigenotoxic effect against DZN-induced toxicity in rats, which may be due to the scavenging of free radicals and increased antioxidant status. Since LC is a natural compound and is being safe, it is recommended as a daily supplement for body defense against side effects induced by chemical hazardous agents.

Effects of Haematobia irritans infestation on weight gain of Nelore calves assessed with different antiparasitic treatment schemes.

Effects of Haematobia irritans infestation on weight gain of 18 to 20 months old non-castrated Nelore calves, were investigated, under field conditions, using different antiparasitic treatments. Sixty animals were divided in three groups, with 20 bovines each: T01 (untreated control); T02 (treated with Cypermethrin 15 g+Chlorpyriphos 25 g+Citronellal 1 g, as a whole body spray, on days 0, 30, 60, 90 and 120 post-treatment); and T03 (treated on day zero with an ear tag impregnated with Diazinon 6g on the left ear). Counts of H. irritans were conducted on day 30, 60, 90, 120 and 150 post-treatment (DPT). On the same experimental dates, animals were individually weighed, seeking to evaluate the effects of parasitism on the development of animals in each group. From this study it is concluded that T03 had significantly higher efficacy (>90%, till 90 DPT), based on H. irritans fly counts, compared to T02 which showed little or no effect. At the specific conditions of the present study, an average of approximately 90 flies (mean difference of flycounts between groups T01 and T03) was associated with a difference of 20 kg/animal in 150 days.

Uso inadequado de organofosforados: uma prática de risco para bovinos no Sul do Rio Grande do Sul / Misuse of organophosphate: potential risk to cattle in Southern Brazil

Com o objetivo de determinar as causas para o súbito aumento no número de surtos de intoxicação por organofosforados foram analisados nove surtos da intoxicação diagnosticados em bovinos no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD/UFPel) entre novembro de 2013 e fevereiro de 2014. Em todos os surtos os animais foram tratados com concentrações entre duas e 151 vezes maiores que a concentração recomendada de diazinon para banho carrapaticida utilizado nas diferentes propriedades. Contribuíram, ainda, para o grande número de casos de intoxicação a via de adminstração pour on não recomendada para os produtos utilizados e o intenso calor registrado na época de ocorrência dos surtos.

In order to determine the cause of the sudden increase in the number of outbreaks of organophosphate poisoning, nine outbreaks diagnosed in cattle were analyzed at the Laboratório Regional de Diagnóstico, Faculdade de Veterinária, Universidade Federal de Pelotas (LRD/UFPel) between November 2013 and February 2014. In all outbreaks the animals were treated with concentration from two to 151 times higher than the concentration recommended of diazinon for tick treatment. The incorrect route of application, and the intense heat recorded at the time of the outbreaks also contributed to the large number of poisoning.

Safety prediction of topically exposed biocides using permeability coefficients and the desquamation rate at the stratum corneum.

Advances in the synthesis and utilization of new chemical compounds have led to improvements in our daily lives. However, new chemicals may be both beneficial and toxic. Thus, exposure to these new compounds should be restricted in an attempt to limit their potential toxicities. We predicted the safety of three biocides (p-cresol, diazinon and resmethrin) by comparing their skin permeability coefficients and desquamation rate (the counter flux of permeability coefficient for chemical compounds induced by skin turnover) following skin exposure. In vitro skin permeation experiments revealed that the permeability coefficients of diazinon and resmethrin were smaller than the desquamation rate; therefore, these biocides could not permeate the skin, which resulted in very low skin concentrations of these compounds. On the other hand, the skin concentration of p-cresol was high because of its higher permeability coefficient than the desquamation rate. Furthermore, low in vitro cell viability was reported for skin exposed to p-cresol. These results in the present study indicate that the method described herein is useful for predicting the toxicities of chemicals following their topical exposure.

Efficiency of partial treatment of cattle infested with horn fly using 40% diazinon / Eficiencia do tratamento parcial de bovinos infestados por mosca-dos-chifres utilizando diazinon 40%

The aim of this investigation was to evaluate the efficiency of partial treatment of animals infested with horn flies. Forty-five Guzerat cows between 4 and 7 years of age were divided into three groups (15 cows per group). The treatments were as follows: in groups G33 and G100, 33.3 and 100% of the cows were treated with one insecticide-impregnated ear tag/animal (40% diazinon), respectively, while in the group GC, the cows were not treated (control). The flies on the cervico-dorsal-lumbar region of the cows, in all three groups, were counted every 14 days. The experiment lasted from September 2006 to September 2009. Over this period, six four-month ear tag treatments, with intervals of one to two months, were conducted on both treated groups. The animals of group G33 had a higher infection than those of group G100, and the number of flies ranged from 12 to 27 (group G33) and from 3 to 11 (group G100). However, groups G33 and G100 had lower infection levels than group GC, which presented from 45 to 87 flies. Partial treatment of cattle infested with horn flies using 40% diazinon insecticide is an efficient alternative for controlling this ectoparasite.

Com objetivo de avaliar a eficiência do tratamento parcial de animais infestados por mosca-dos-chifres, foram utilizadas 45 vacas da raça Guzerá, com idade entre 4 e 7 anos, divididas em três grupos de 15 animais. Os animais dos grupos G33 (33,3% tratados) e G100 (100% tratados) receberam um brinco inseticida/animal, com diazinon 40%, e os do grupo GC não receberam tratamento (controle). A cada 14 dias foram realizadas contagens das moscas sobre a região cervico-dorso-lombar das vacas dos três grupos. O estudo foi realizado de setembro de 2006 a setembro de 2009. Neste período, seis tratamentos com quatro meses cada, e com intervalo de um a dois meses, foram realizados nos animais dos grupos G33 e G100. Os animais do grupo G33 apresentaram maior infestação que os do grupo G100, o número de mosca variou de 12 a 27 no grupo G33 e de 3 a 11 no grupo G100. No entanto, os grupos G33 e G100 apresentaram menores infestações que as observadas nos animais do grupo GC, que apresentou de 45 a 87 moscas. O tratamento parcial de bovinos infestados por mosca-dos-chifres com a utilização de inseticida diazinon 40% é uma alternativa eficiente no controle deste ectoparasita.

Simultaneous subchronic exposure to selenium and diazinon as possible risk factor for osteoporosis in adult male rats.

BACKGROUND: Osteoporosis and its main health outcome, fragility fractures, are large and escalating health problems. Skeletal damage may be the critical result of low-level prolonged exposure to several xenobiotics in the general population, but the mechanisms of their adverse effects are not clearly understood. The current study was aimed to investigate the possible ability of simultaneous subchronic peroral administration of selenium (Se) and diazinon (DZN) to induce changes in bone of adult male rats.In our study, twenty 1-month-old male Wistar rats were randomly divided into two experimental groups. In the first group, young males were exposed to 5 mg Na2SeO3/L and 40 mg of DZN/L in drinking water, for 90 days. Ten 1-month-old males without Se and DZN intoxication served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy. RESULTS: The body weight, femoral length and cortical bone thickness were significantly decreased in rats simultaneously exposed to Se and DZN (P < 0.05). These rats also displayed different microstructure in the middle part of the compact bone where vascular canals expanded into central area of substantia compacta. The canals occurred only near endosteal surfaces in rats from the control group. Additionally, a smaller number of primary and secondary osteons, as well as a few resorption lacunae were observed near endosteal surfaces in rats simultaneously administered to Se and DZN. The resorption lacunae as typical structures of bone resorption manifestation are connected with an early stage of osteoporosis. Histomorphometric analysis revealed that area, perimeter, maximum and minimum diameters of primary osteons' vascular canals were significantly increased (P < 0.05) in the Se-DZN-exposed rats. On the other hand, all measured variables of Haversian canals and secondary osteons were considerable reduced (P < 0.05) in these rats. CONCLUSIONS: Simultaneous subchronic peroral exposure to Se and DZN induces changes in macroscopic and microscopic structures of the femurs in adult male rats, and also it can be considered as possible risk factor for osteoporosis. The current study contributes to the knowledge on damaging impact of several xenobiotics on the bone.

Urinary determination of 2-isopropyl-4-methyl-6-hydroxypyrimidine in case of non fatal poisoning with diazinon.

We reported one non fatal case (42 month old boy) of intoxication with diazinon following accidental ingestion. Diazinon and three of its metabolites (2 common metabolites with other organophosphate pesticides: diethylphosphate and diethylthiophosphate; one specific metabolite: 2-isopropyl-4-methyl-6-hydroxypyrimidine) were determined in serum and in urine, respectively, using three liquid chromatography-tandem mass spectrometry methods. Diazinon was detected in serum while its metabolites were detected in urine. The concentrations of diazinon and its common metabolites were compared to concentrations previously described in literature in the same intoxication context and were discussed. The concentration of the specific metabolite was compared to concentrations highlighted in occupational exposure, because to the best of our knowledge, we reported here the first urinary concentration of this metabolite in an acute intoxication context.

Effects of oral exposure to diazinon on mice liver and kidney tissues: biometric analyses of histopathologic changes.

OBJECTIVE: To determine the sublethal toxic effects of diazinon on liver and kidney tissues of Swiss albino mice. STUDY DESIGN: Mice were exposed to different concentrations (30, 60, and 120 mg/kg) of diazinon through oral administration for 30 consecutive days. Biometric analyses (area measurements of histologic structures) of some histopathological changes were evaluated by measuring the areas of hepatocyte/nucleus in the liver and the areas of glomerulus and renal corpuscle in the kidney. Both glomerular area and renal corpuscle area statistically decreased from the low-dose group to high-dose group as compared to controls. RESULTS: In liver tissue vacuolization in hepatocytes, mononuclear cell infiltration, congestion, enlargement of the veins, and an increase in the number of Kupffer cells were found in the liver of exposed mice. In kidney tissue, mononuclear cell infiltration, glomerular degeneration, glomerular loss, and congestion were observed in diazinon-treated groups. CONCLUSION: Diazinon caused dose-related histopathological damage in liver and especially in kidney tissues of mice. This work indicates that it might cause adverse effects to nontarget organisms, including humans.

Intestinal rupture in a Mexican gray wolf (Canis lupus baileyi) in association with ingestion of a diazinon-impregnated cattle ear tag.

A free-ranging Mexican gray wolf (Canis lupus baileyi) suffered intestinal rupture following ingestion of an insecticidal cattle ear tag. Subsequent organophosphate toxicosis as a cause of the rupture was speculated. Insecticidal ear tags could represent a poisoning risk in canids and other wildlife scavengers.

Efficiency of partial treatment of cattle infested with horn fly using 40% diazinon.

The aim of this investigation was to evaluate the efficiency of partial treatment of animals infested with horn flies. Forty-five Guzerat cows between 4 and 7 years of age were divided into three groups (15 cows per group). The treatments were as follows: in groups G33 and G100, 33.3 and 100% of the cows were treated with one insecticide-impregnated ear tag/animal (40% diazinon), respectively, while in the group GC, the cows were not treated (control). The flies on the cervico-dorsal-lumbar region of the cows, in all three groups, were counted every 14 days. The experiment lasted from September 2006 to September 2009. Over this period, six four-month ear tag treatments, with intervals of one to two months, were conducted on both treated groups. The animals of group G33 had a higher infection than those of group G100, and the number of flies ranged from 12 to 27 (group G33) and from 3 to 11 (group G100). However, groups G33 and G100 had lower infection levels than group GC, which presented from 45 to 87 flies. Partial treatment of cattle infested with horn flies using 40% diazinon insecticide is an efficient alternative for controlling this ectoparasite.

Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice.

The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 µmol/kg/day) or cis-permethrin (90 µmol/kg/day) alone or in combination (100 µmol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon-permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident.

Involvement of TLR4 in diazinon-induced neurotoxicity in mice.

Our laboratory recently reported that Toll-like receptor (TLR) 4 may play a role in the neurotoxic effects in mice exposed to the environmental toxic chemical toluene. To investigate the role of TLR4 in hippocampal neurotrophin expression, C3H/HeN (TLR4 intact) and C3H/HeJ (TLR4 defective) male adult mice were administered diazinon (0, 0.05, 0.5 or 5 mg/kg) intraperitoneally once a week for three weeks. Twenty-four hours after the final diazinon injection, the hippocampus was collected from each mouse to detect mRNA expression of neurotrophins (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) by the real-time RT-PCR method. There was no difference between groups in neurotrophin expression in the C3H/HeN mice. However, the expression of NGF and BDNF mRNAs was suppressed significantly in the diazinon-injected C3H/HeJ mice compared with their control group. We also found an increased tendency of proinflammatory chemokine CCL3 mRNA and a marked increase in the proapoptotic gene Bax mRNA in the diazinon-injected C3H/HeJ mice. Our findings indicate that diazinon injection affects neurotrophin expression in the hippocampus in TLR4-defective mice but not in TLR4 intact mice. These results suggest that a defective TLR4 signaling pathway in the mouse hippocampus can be easily affected by diazinon administration.

Evaluation of developmental toxicity induced by anticholinesterase insecticide, diazinon in female rats.

Developmental toxicities, including birth defects, are significant public health problems. This study was planned to assess the cholinergic and developmental potentials of diazinon that is widely used as an organophosphate insecticide. Pregnant female Sprague-Dawley rats were given diazinon orally at doses of 0, 1.9, 3.8, and 7.6 mg/kg body weight (b.w.)/day on gestation days 6 to 15. Maternal brain acetylcholinesterase activities, measured on gestation day20, were significantly decreased at 3.8 and 7.6 mg/kg b.w./day, but fetal acetylcholinesterase activity was not altered. Maternal toxicities, as evidenced by cholinergic symptoms including diarrhea, tremors, weakness, salivation, and decreased activities, were observed at the 3.8 and 7.6 mg/kg b.w./day dose groups. Net gravid uterine weight was decreased at a dose of 7.6 mg/kg b.w./day. No maternal effects were apparent in the 1.9 mg/kg b.w./day dose group. Maternal toxicity at a dose of 3.8 mg/kg b.w./day did not induce fetotoxicity or teratogeneicity. However, 7.6 mg/kg b.w./day doses significantly resulted in fetal toxicity and malformations in addition to maternal toxicity in animals. In conclusion, teratogenic disorders only outlined by doses that produced marked maternal toxicity. Since the malformations were not morphologically related, they were considered to be secondary to maternal toxicity; hence, the malformations were not related to cholinesterase inhibition.