N318L Blocks the Interaction of Fluralaner but Not Broflanilide or Fipronil with the Insect GABA Receptor In Vivo.

Fluralaner is a novel insecticide targeting the ionotropic GABA receptor (GABAR) subunit, RDL. A recent study revealed that N316L, a substitution of asparagine (N) with leucine (L), in the second transmembrane (M2)-spanning region reduced the antagonist action of fluralaner on the housefly Musca domestica RDL (MdRDL) in vitro. To verify the impact of N316L in vivo, the corresponding mutation (N318L) in the fruitfly Drosophila melanogaster RDL (DmRDL) was constructed using CRISPR/Cas9 genome editing. The homozygous DmRDLN318L mutant showed a 9.87-fold resistance to fluralaner compared with w1118 while still being highly sensitive to broflanilide and fipronil, which is consistent with those findings observed in the electrophysiology assays of the homomeric DmRDLWT or DmRDLN318L channel. Moreover, DmRDLN318L led to malformed ovaries, stunted eggs, and sterility in homozygous females. These results highlighted N318 as a molecular site for fluralaner in vivo and in vitro and might elucidate the resistance mechanisms of insects against fluralaner.

Feasibility evaluation of a blended cover with activated carbon for in-situ stabilization of DDT in sediment.

Activated carbon (AC) sediment amendment is an in-situ remediation technology in which the applied AC immobilizes organic contaminant flux from sediments, thereby reducing contaminant bioavailability and associated risks. While various studies have demonstrated the feasibility of in-situ AC treatment, hesitation to apply this technology exists due to limited experience under field-specific scour conditions and hydrodynamic forces. To address this concern, we conducted a feasibility study for an AC-blended cover at the Lauritzen Channel of the United Heckathorn Superfund Site in Richmond, California, United States, which was contaminated with dichlorodiphenyltrichloroethane and its metabolites (DDx) as well as dieldrin. Vessel activities causing sediment disturbance were identified as key factors for remedy selection. A blended cover with AC and coarse materials was designed to withstand varied hydrodynamic conditions and AC stability was tested in a current flume. The cover comprised medium-size gravel (D50 = 15 mm, D90 = 19 mm) with 4 % granular AC by weight. Flume erosion studies showed minimal AC loss (1-2 % of total AC) under shear forces of 9-31 Pa, which was equivalent to or exceeded the estimated worst-case erosional conditions in the channel induced by a hypothetical, stationary tugboat propelling at high power thrust. The treatability performance of the engineered blended cover design was evaluated through mesocosm studies using site sediment and various cover options. Post-treatment assessments on days 5 and 145 showed rapid reductions in freely dissolved (Cfree) DDx and dieldrin in the blended cover layers and surface water. For example, by day 145, Cfree DDx was reduced by over 98 %, meeting US EPA remedial goals for the site. It is concluded that the combination of both stability and performance testing demonstrates that an engineered blended cover-AC design would be a feasible remedial option at the site, and that this testing approach can be applied to evaluate in-situ treatment in other sediment cleanup activities.

Developmental origins of Parkinson's disease risk: perinatal exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain.

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with an increased risk of Parkinson's disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 wk of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points-birth, 6, 12, and 36 wk old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of differential modification of cytosines with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late-life diseases, including PD.

Mode of action of dieldrin-induced liver tumors: application to human risk assessment.

Dieldrin is an organochlorine insecticide that was widely used until 1970 when its use was banned because of its liver carcinogenicity in mice. Several long-term rodent bioassays have reported dieldrin to induce liver tumors in in several strains of mice, but not in rats. This article reviews the available information on dieldrin liver effects and performs an analysis of mode of action (MOA) and human relevance of these liver findings. Scientific evidence strongly supports a MOA based on CAR activation, leading to alterations in gene expression, which result in increased hepatocellular proliferation, clonal expansion leading to altered hepatic foci, and ultimately the formation of hepatocellular adenomas and carcinomas. Associative events include increased liver weight, centrilobular hypertrophy, increased expression of Cyp2b10 and its resulting increased enzymatic activity. Other associative events include alterations of intercellular gap junction communication and oxidative stress. Alternative MOAs are evaluated and shown not to be related to dieldrin administration. Weight of evidence shows that dieldrin is not DNA reactive, it is not mutagenic, and it is not genotoxic in general. Furthermore, activation of other pertinent nuclear receptors, including PXR, PPARα, AhR, and estrogen are not related to dieldrin-induced liver tumors nor is there liver cytotoxicity. In previous studies, rats, dogs, and non-human primates did not show increased cell proliferation or production of pre-neoplastic or neoplastic lesions following dieldrin treatment. Thus, the evidence strongly indicates that dieldrin-induced mouse liver tumors are due to CAR activation and are specific to the mouse, which are qualitatively not relevant to human hepatocarcinogenesis. Thus, there is no carcinogenic risk to humans. This conclusion is also supported by a lack of positive epidemiologic findings for evidence of liver carcinogenicity. Based on current understanding of the mode of action of dieldrin-induced liver tumors in mice, the appropriate conclusion is that dieldrin is a mouse specific liver carcinogen and it does not pose a cancer risk to humans.

Developmental origins of Parkinson's disease risk: perinatal exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain.

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson's disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril (α-syn PFF) and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 weeks of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points - birth, 6 weeks, 12 weeks, and 36 weeks old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of DMCs with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late life diseases, including PD.

Developmental exposure to the Parkinson's disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice.

Parkinson's disease (PD) is the fastest-growing neurological disease worldwide, with increases outpacing aging and occurring most rapidly in recently industrialized areas, suggesting a role of environmental factors. Epidemiological, post-mortem, and mechanistic studies suggest that persistent organic pollutants, including the organochlorine pesticide dieldrin, increase PD risk. In mice, developmental dieldrin exposure causes male-specific exacerbation of neuronal susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and synucleinopathy. Specifically, in the α-synuclein (α-syn) pre-formed fibril (PFF) model, exposure leads to increased deficits in striatal dopamine (DA) turnover and motor deficits on the challenging beam. Here, we hypothesized that alterations in DA handling contribute to the observed changes and assessed vesicular monoamine transporter 2 (VMAT2) function and DA release in this dieldrin/PFF 2-hit model. Female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin or vehicle every 3 days by feeding, starting at 8 weeks of age and continuing throughout breeding, gestation, and lactation. Male offspring from independent litters underwent unilateral, intrastriatal injections of α-syn PFFs at 12 weeks of age, and vesicular 3H-DA uptake assays and fast-scan cyclic voltammetry were performed 4 months post-PFF injection. Dieldrin-induced an increase in DA release in striatal slices in PFF-injected animals, but no change in VMAT2 activity. These results suggest that developmental dieldrin exposure increases a compensatory response to synucleinopathy-triggered striatal DA loss. These findings are consistent with silent neurotoxicity, where developmental exposure to dieldrin primes the nigrostriatal striatal system to have an exacerbated response to synucleinopathy in the absence of observable changes in typical markers of nigrostriatal dysfunction and degeneration.

Optimization of Dieldrin Selection for the Genetic Sexing of Aedes albopictus.

The mass production of mosquitoes at an industrial scale requires efficient sex separation, which can be achieved through mechanical, genetic or artificial intelligence means. Compared with other methods, the genetic sexing approach offers the advantage of limiting costs and space by removing females at the larval stage. We recently developed a Genetic Sexing Strain (GSS) in Aedes albopictus based on the sex linkage of the rdlR allele, conferring resistance to dieldrin, to the male (M) locus. It has been previously reported that dieldrin ingested by larvae can be detected in adults and bioaccumulated in predators, raising the question of its use at a large scale. In this context, we performed several experiments aiming at optimizing dieldrin selection by decreasing both dieldrin concentration and exposure time while maintaining a stable percentage of contaminating females averaging 1%. We showed that the previously used dieldrin exposure induced an important toxicity as it killed 60% of resistant males at the larval stage. We lowered this toxicity by reducing the dose and/or the exposure time to recover nearly all resistant males. We then quantified the residues of dieldrin in resistant male adults and showed that dieldrin toxicity in larvae was positively correlated with dieldrin concentrations detected in adults. Interestingly, we showed that the use of reduced dieldrin exposure led to a dieldrin quantification in adult males that was below the quantity threshold of the Gas Chromatography-Mass Spectrometry detection method. Presented data show that dieldrin exposure can be adjusted to suppress toxicity in males while achieving efficient sexing and lowering the levels of dieldrin residues in adults to barely quantifiable levels.

Application of hollow fiber-protected liquid-phase microextraction combined with GC-MS in determining Endrin, Chlordane, and Dieldrin in rice samples.

This paper introduces a novel and minimized sample preparation technique based on hollow fiber-protected liquid-phase microextraction that can be used in joint with gas chromatography-mass spectrometry (GC-MS) detection to extract three organochlorine pesticides-Endrin, Chlordane, and Dieldrin-from rice samples. To that end, a single-walled carbon nanotube (SWCNT) and a proper ionic liquid (IL) were ultrasonically dispersed and injected into the lumen of hollow fiber as the extraction phase for preconcentrating and extracting the target analytes from the rice samples. The effects of the type of nanoparticles, ILs, and desorption solvent on the efficiency of extracting the analytes were investigated based on the one-factor-at-a-time (OFAT) approach. In addition, other parameters influencing the extraction procedure were optimized using an experimental design that decreased the number of experiments, reagent consumption, and costs. Under optimized conditions, the limits of detection and quantification in determining mentioned pesticides varied between 0.019-0.029 and 0.064-0.098 ng mL-1, respectively. The calibration graphs to measure Endrin, Chlordane, and Dieldrin were linear over the concentration range of 0.064-13.2, 0.098-16.7, and 0.092-11.4 ng mL-1, respectively. The relative standard deviations for inter-day and intra-day analysis were below 7.06 and 4.75% for the triplicate determination of three organochlorine pesticides. Besides, the relative recoveries and standard deviations of Endrin, Chlordane, and Dieldrin for analyzing several Iranian rice samples were between 86.0-92.9% and 4.5-5.8%, respectively. The results were compared with other similar works in literature, proving that the proposed method is efficient and useful for routine monitoring of organochlorine compounds in food samples.

A global review of the temporal and spatial patterns of DDT and dieldrin monitoring in raptors.

Concentrations of organochlorine pesticides have been extensively monitored in birds, particularly from higher trophic guilds such as raptors. While monitoring of raptors has been ongoing for decades, patterns from monitoring activities have never been summarised on a global scale. In this study, we undertake a review to better describe the monitoring of two widespread organochlorine pesticides monitored globally in raptors, DDT and dieldrin. We provide a historical retrospective on the monitoring effort of a global environmental issue. Sampling was heavily biased geographically to the global north, with more than 90 % of studies conducted in this socio-geographic region, most from Europe and North America. Although monitoring occurred from at least 114 species, most samples came from relatively few species, with three species (Eurasian Sparrowhawk Accipiter nisus, Bald Eagle Haliaeetus leucocephalus, and Peregrine Falcon Falco peregrinus) comprising 50 % of samples. The types of raptors sampled have changed over time, with avian and mammal specialists dominating samples until the 1970s, but more diverse dietary guilds monitored in later decades, and greater proportions of samples coming from generalist species. The three most sampled tissues (egg, liver, and plasma) comprised 84 % of all samples. Eggs were the earliest tissue examined and the only tissue sampled in all decades. The geographical bias in monitoring effort and relatively narrow species focus, suggests that patterns in these pesticides are unlikely to be fully representative of all global environments occupied by raptors. While DDT has been banned throughout most of the global north, it remains in use in the global south, yet monitoring effort in the south, does not match that of the north. While monitoring remains prevalent in the global north, contemporary monitoring is limited in the global south with less than 10 % of raptors sampled in Asia, Africa, and South America, over the last 3 decades.

Spatio-Temporal Dynamics of a Dieldrin Resistance Gene in Aedes albopictus and Culex quinquefasciatus Populations From Reunion Island.

The control of mosquito populations using insecticides is increasingly threatened by the spread of resistance mechanisms. Dieldrin resistance, conferred by point mutations in the Rdl gene encoding the γ-aminobutyric acid receptor, has been reported at high prevalence in mosquito populations in response to selective pressures. In this study, we monitored spatio-temporal dynamics of the resistance-conferring RdlR allele in Aedes (Stegomyia) albopictus (Skuse, 1895) and Culex (Culex) quinquefasciatus (Say, 1823) populations from Reunion Island. Specimens of both mosquito species were sampled over a 12-month period in three cities and in sites located at lower (<61 m) and higher (between 503 and 564 m) altitudes. Mosquitoes were genotyped using a molecular test detecting the alanine to serine substitution (A302S) in the Rdl gene. Overall, the RdlR frequencies were higher in Cx. quinquefasciatus than Ae. albopictus. For both mosquito species, the RdlR frequencies were significantly influenced by location and altitude with higher RdlR frequencies in the most urbanized areas and at lower altitudes. This study highlights environmental factors that influence the dynamics of insecticide resistance genes, which is critical for the management of insecticide resistance and the implementation of alternative and efficient vector control strategies.

Microbial Degradation of Aldrin and Dieldrin: Mechanisms and Biochemical Pathways.

As members of the organochlorine group of insecticides, aldrin and dieldrin are effective at protecting agriculture from insect pests. However, because of excessive use and a long half-life, they have contributed to the major pollution of the water/soil environments. Aldrin and dieldrin have been reported to be highly toxic to humans and other non-target organisms, and so their use has gradually been banned worldwide. Various methods have been tried to remove them from the environment, including xenon lamps, combustion, ion conversion, and microbial degradation. Microbial degradation is considered the most promising treatment method because of its advantages of economy, environmental protection, and convenience. To date, a few aldrin/dieldrin-degrading microorganisms have been isolated and identified, including Pseudomonas fluorescens, Trichoderma viride, Pleurotus ostreatus, Mucor racemosus, Burkholderia sp., Cupriavidus sp., Pseudonocardia sp., and a community of anaerobic microorganisms. Many aldrin/dieldrin resistance genes have been identified from insects and microorganisms, such as Rdl, bph, HCo-LGC-38, S2-RDLA302S , CSRDL1A, CSRDL2S, HaRdl-1, and HaRdl-2. Aldrin degradation includes three pathways: the oxidation pathway, the reduction pathway, and the hydroxylation pathway, with dieldrin as a major metabolite. Degradation of dieldrin includes four pathways: oxidation, reduction, hydroxylation, and hydrolysis, with 9-hydroxydieldrin and dihydroxydieldrin as major products. Many studies have investigated the toxicity and degradation of aldrin/dieldrin. However, few reviews have focused on the microbial degradation and biochemical mechanisms of aldrin/dieldrin. In this review paper, the microbial degradation and degradation mechanisms of aldrin/dieldrin are summarized in order to provide a theoretical and practical basis for the bioremediation of aldrin/dieldrin-polluted environment.

Status of Dieldrin in vegetable growing soils across a peri-urban agricultural area according to an adapted sampling strategy.

Since the fifties, organochlorine pesticides (OCPs) had been used in agriculture to protect vegetables. Two decades after their ban by the Stockholm convention in 2001, OCPs are still present in agricultural soils inducing vegetable contamination with concentrations above Maximum Residue Level (MRL). This is a major concern for a 5 km2 peri-urban vegetable growing valley located in the south west of France. In the present work, the sampling method was developed to clarify the spatial distribution of one OCP, Dieldrin, and its relationship with soil properties at the scale of study area. A total of 99 soil samples was collected for physicochemical analyses and Dieldrin concentrations. Results show Dieldrin concentrations in soils up to 204 µg kg-1. The horizontal distribution of this pesticide is heterogeneous at the study area scale but homogeneous in each reference plot studied. About 85% of the contamination was located in the top soil layers (0-40 cm depth), but Dieldrin may still be quantified at a depth of 80 cm. Among all soil physicochemical parameters analysed, SOM was the most significantly related (P < 10-4) with Dieldrin concentrations, once different grain size fractions were considered. Moreover, results indicate a 33 times higher Dieldrin concentration and/or extractability for coarse sand than for other grain size fractions. These results show that the developed sampling method is adapted for the study area scale as it helps understanding the factors influencing the spatial distribution of Dieldrin. Historical amendments are the predominant factor for the horizontal contamination and deep ploughing for the vertical contamination. Also, the variations of coarse sand repartition in soils prevents identification of relationships between SOM and Dieldrin contamination in bulk soil. Further investigation is required to explain these relationships but these results highlight why no clear relationship between OCPs and SOM was previously identified.

Determination of Median Lethal Concentration (LC50) for Endosulfan, Heptachlor and Dieldrin Pesticides to African Catfish, Clarias gariepinus and Their Impact on Its Behavioral Patterns and Histopathological Responses.

Pesticides such as endosulfan, heptachlor and dieldrin persist in aquatic environments as a result of their resistance to biodegradation. However, there is no adequate information about the toxicity of endosulfan, heptachlor and dieldrin to the aquatic organism, African catfish (Clarias gariepinus)-a high valued widely distributed commercially interesting species. The current experiment was performed with the aim to determine the median lethal concentration (LC50) of endosulfan, heptachlor and dieldrin to African catfish (Clarias gariepinus); their behavioral abnormalities and histopathological alterations in several vital organs. A total of 324 juvenile fish were exposed for 96 h to six concentrations of endosulfan and dieldrin at 0, 0.001, 0.002, 0.004, 0.008 and 0.016 ppm, and to heptachlor at concentrations of 0, 0.02, 0.04, 0.08, 0.16 and 0.32 ppm for dose-response tests. The study demonstrated that the species is highly susceptible to those contaminants showing a number of behavioral abnormalities and histopathological changes in gill, liver and muscle. The 96-h LC50 value of endosulfan, dieldrin and heptachlor for the African catfish was found as 0.004 (0.001-0.01) mg/L, 0.006 mg/L and 0.056 (0.006-0.144) mg/L, respectively. Abnormal behaviors such as erratic jerky swimming, frequent surfacing movement with gulping of air, secretion of mucus on the body and gills were observed in response to the increasing exposure concentrations. Histopathological alterations of liver, gill and muscle tissues were demonstrated as vacuolization in hepatocytes, congestion of red blood cells (RBCs) in hepatic portal vein; deformed secondary lamellae and disintegrated myotomes with disintegrated epidermis, respectively. These findings are important to monitor and responsibly manage pesticide use in and around C. gariepinus aquacultural areas.

Organochlorine pesticide dieldrin upregulate proximal promoter (PII) driven CYP19A1 gene expression and increases estrogen production in granulosa cells.

Organochlorine pesticides are highly persistent environmental pollutants, generally shown to act through estrogen receptor alpha and alter estrogen biosynthesis. However, the molecular mechanism of regulation of estrogen biosynthesis by these pesticides is not clear. Estrogen is main female fertility hormone regulated by rate-limiting enzyme aromatase. It is encoded by the CYP19A1 gene, which is expressed using specific promoters. In the present study, the attempt has been made to elucidate the effect of dieldrin on the promoter-specific CYP19A1 gene expression and estrogen hormone production in buffalo granulosa cells. The buffalo granulosa cells were cultured and treated with dieldrin in a dose (100,150 and 200 ng/mL) and time (6, 12, and 24 h) dependent manner, followed by analysis of CYP19A1, promoter-specific CYP19A1 transcript expression, and estrogen production. Results showed that dieldrin significantly increased the expression of the CYP19A1 gene after 6 and 12 h while its expression was decreased after 24 h. To understand the upregulation of CYP19A1 gene, promoters' specific CYP19A1 transcript analysis was done. The finding showed that dieldrin significantly increased the proximal promoter specific CYP19A1 transcript while there was no effect on distal promoter specific CYP19A1 transcripts. This specific-promoter activity was quantified by chromatin immunoprecipitation assay (ChIP). Results confirmed the involvement of the proximal promoter in the overexpression of CYP19A1 gene. Furthermore, a significant increase in estradiol-17ß level was also observed. Overall, the present study demonstrated the stimulatory effect of dieldrin on the CYP19A1 gene and will help to understand the toxicological role of dieldrin on the reproductive system.

A Pest or Otherwise? Encounter of Oryctes rhinoceros (Coleoptera: Scarabaeidae) with Persistent Organic Pollutants.

The potential use of invertebrates as bioreactors to treat environmental pollutants is promising and of great interest. Three types of the persistent organic pollutants (POPs), namely pentachlorophenol (PCP), PAHs (naphthalene and phenanthrene) and dieldrin (DLN), were spiked in soil and treated by using Oryctes rhinoceros larvae, a known pest of coconut trees in southeast Asia, and also the indicators of POP toxicity and the fate and degradability of the ingested POPs were assessed. The larvae were tested at various levels of the POPs and went through an acclimation process. Without acclimation, the tolerance limits of the larvae toward PCP, PAHs and DLN were 200, 100 and 0.1 mg/kg-soil, respectively, yet with acclimation, the tolerance levels increased to 800, 400 and 0.5 mg/kg-soil, respectively. Biodegradation rates of all the tested POPs were >90% by week 2, with <5% and nearly 0% remaining in the feces and body of the larvae, respectively. The results suggest that the use of the beetle larvae in soil POP decontamination is doable.

[Examination of Analytical Method for Mothproofing Agents to Revise the Official Methods Based on "Act on the Control of Household Products Containing Harmful Substances"].

In Japan, the use of mothproofing agents [dieldrin and 4,6-dichloro-7-(2,4,5-trichlorophenoxy)-2-trifluoromethylbenzimidazole; DTTB] in textiles is regulated by the Act on the Control of Household Products Containing Harmful Substances. Since official analytical methods for these agents have been in place for approximately 40 years, we developed an improved method in a previous study. In the present study, we validated this method. Accordingly, six laboratories analyzed the sample prepared at 3 µg/g (1/10 of the regulation value) and 30 µg/g (the regulation value). The high accuracy of the results for these samples in almost all the cases (accuracy: 70-120%, repeatability: <10%, reproducibility: <15%), confirmed the validity of the method. In addition, we examined three samples that were distributed before the introduction of the regulation. The analysis results for these samples showed little variation between laboratiories, indicating that our method is also applicable to actual samples. Meanwhile, the quantitative value was clearly lower in one laboratory than in the others. We presumed that the enhanced effect of the sample matrix (matrix effect) on the internal standards in GC-MS analysis was the main cause for this trend. Therefore, we examined the analytical method using polyethylene glycol 300 (PEG) as an analyte protectant. As PEG minimized the GC-MS response difference between the standard solution and the matrix-containing solution, GC-MS analysis with PEG would be useful for matrix effect measurements in this method.

Acute toxicity and biomarker responses in Gammarus locusta amphipods exposed to copper, cadmium, and the organochlorine insecticide dieldrin.

The toxicity of copper, cadmium, and dieldrin in adult Gammarus locusta (a marine amphipod) is currently unclear. Thus, G. locusta from the North Lake of Tunis were subjected to acute toxicity tests to assess LC50s at 48-96 h and to biomarker response tests through the assessment of catalase and acetylcholinesterase activities and malondialdehyde levels. The present study demonstrated the abilities of a chlorinated hydrocarbon pesticide (dieldrin) induce to oxidative stress and neurotoxicity. The comparison of metal toxicity showed that G. locusta was more sensitive to cadmium than copper. The three stressors caused significant inductions of all three biomarkers in a concentration-dependent manner. Catalase induction was dependent on exposure duration for all pollutants, while only copper led to increased malondialdehyde with longer exposure times. Catalase induction and malondialdehyde increase appeared to be sex dependent for all three pollutants. The neurotoxic effects of the pollutants were concentration dependent according to inhibition of acetylcholinesterase activity. In conclusion, catalase, malondialdehyde, and acetylcholinesterase are efficient biomarkers of copper, cadmium, and dieldrin in G. locusta.

Level of Organochlorine Pesticide in Prediabetic and Newly Diagnosed Diabetes Mellitus Patients with Varying Degree of Glucose Intolerance and Insulin Resistance among North Indian Population.

BACKGROUND: Organochlorine pesticides (OCPs) exposure may induce an endocrine disruption which may lead to the risk of developing diabetes through alteration and disturbance of glucose metabolism, insulin resistance, and destruction of ß-cells. The present study determines the recent trend of OCPs residue in blood samples and their association with the known risk factors responsible for developing the risk of diabetes among the North Indian population. METHODS: Blood sample of 300 patients (100 each of normal glucose tolerance [NGT], prediabetes and newly detected diabetes mellitus [DM]) between the age group of 30 to 70 years were collected. OCPs residue in whole blood samples was analyzed by using gas chromatography equipped with a 63Ni selective electron capture detector. RESULTS: Significantly higher levels of ß-hexachlorocyclohexane (HCH), dieldrin, and p,p'-dichloro-diphenyl-dichloroethylene (DDE) were found in the prediabetes and newly detected DM groups as compared to NGT group. Insulin resistance showed to be significantly positive correlation with ß-HCH and dieldrin. Also, fasting and postprandial glucose levels were significantly positively correlated with levels of ß-HCH, dieldrin, and p,p'-DDE. Further, when OCPs level was adjusted for age and body mass index (BMI), it was found that ß-HCH, dieldrin, and p,p'-DDE levels in blood increases the risk of diabetes by 2.70, 2.83, and 2.55 times respectively. Moreover, when we adjust OCPs level based on BMI categories (BMI <23, ≥23, and ≤25, and >25 kg/m2); ß-HCH and p,p'-DDE showed a significant risk of developing newly detected DM with BMI >25 and ≥23 and ≤25 kg/m2. CONCLUSION: The OCPs level present in the environment may be responsible for biological, metabolic, and endocrine disruptions within the human body which may increase the risk of developing newly detected DM. Hence, OCPs exposure can play a crucial role in the etiology of diabetes.

[Lessons from the Malaria Vector Control Program Based on Indoors Residual Spraying with DDT or Dieldrin in the Pilot Zone of Bobo-Dioulasso: Failure or Success?] / Les Leçons du Programme de Lutte Contre les Vecteurs du Paludisme Par Aspersions Intradomiciliaires de DDT ou de Dieldrine dans la Zone Pilote de Bobo-Dioulasso: Échec ou Succès?

During five years, from 1953, a village scale indoors residual spraying (IRS) was done in the pilot zone of Bobo-Dioulasso, Burkina Faso, with DDT or dieldrin (DLN) or even HCH with a conceptually both entomological and parasitological evaluation [18].Compared to the control area, DDT induced an approximatively 95% and 67% reduction in the landing rate of Anopheles gambiae, respectively inside and outside human houses but due to its irritant action, DDT greatly increased their exophagic behaviour. However, DLN had no impact on the landing rate of An. gambiae either indoors or outdoors due to the already noticed resistance of this species to this insecticide. The sporozoitic index of An. gambiae was reduced by 96% in the DDT treated areas and by 70% in the DLN treated area.DDT reduced the landing rates of Anopheles funestus by 98% and 91%, inside and outside treated houses respectively. With DLN, these reductions were 98% and 97%, respectively. The sporozoitic index of An. funestus was reduced by 95% in areas treated with DDT.Thus, vector control has reduced malaria transmission due to the two main vectors, An. gambiae and An. funestus, by some 99.8% in DDT treated villages compared to control villages. DLN reduced transmission from An. funestus by 99.9%, but almost not from An. gambiae . Overall, the implementation of vector control based on indoor residual spraying with DDT or DLN reduced by 99.9% the transmission of human Plasmodium in the villages of the pilot zone and therefore the program can be considered as entomologically successful.In children aged 2-9 years (target group for endemicity indices) the splenic index was 84.3% (n = 979) in the control area and 44.4% (n = 8920) in the treated areas (difference -47.3%), the plasmodial prevalence was 60.6% (n = 946) in the control zone and 38.0% (n = 7242) in the treated zones (difference - 37%) but the relatively high level of plasmodic or splenic index in treated villages showed that transmission was maintained at such a level that the program could be considered as a "semi-failure".Besides, the gametocytic indices remained at the same levels (3.28%, n = 946 in the control zone and 3.04%, n = 7242 in the treated zones) indicating the maintenance of the "reservoir of parasites" and the remaining possibilities of transmission.Compared to the control area, the index of new contamination was significantly lower in infants 0-3 months and 4 to 6 months in DDT treated villages but not in infants 7 to 12 months demonstrating that the control vector had some efficacy in the prevention of plasmodial infection but "all newborns were infected within one year" demonstrating that P. falciparum transmission was not completely stopped.In spite of its striking drop, the transmission was not fully stopped, and the programme was considered as a "semi-failure" or even a "failure" and inducing a complete shift in malaria control policy from vector control to mass drug chemotherapy (with several drugs, chloroquine, primaquine, pyriméthamine etc) without complete stop of transmission either. In fact, such vector control operations by DDT may have different analysis; in one side they can be considered an entomological success but, in another side, the actual reduction of plasmodic and splenic indices was not enough to be considered as successful. It was clear that both vector and parasite must be implemented in an integrated programme taking care of insecticide and drug resistance. Nevertheless, such programme, even not as successful as expected, could be considered as encouraging and not "disappointing" as it was. Important lessons can be learned from such large-scale field trial in spite of several methodological and operational issues.

[Analysis of Dieldrin and DTTB in Textiles].

Standard analytical methods for the detection of dieldrin and 4,6-dichloro-7-(2,4,5-trichlorophenoxy)-2-trifluoromethylbenzimidazole (DTTB) in textiles, which are regulated by Japanese law ("Act on the Control of Household Products Containing Harmful Substances"), have been in place for more than 30 years. In this study, we developed an improved analytical method, based on GC-MS, that uses safe reagents and can simultaneously detect dieldrin and DTTB analytes. In the standard (existing) analytical method, dimethyl sulfate, which is a potential carcinogen, is used to derivatize DTTB. In the developed method, phenyltrimethylammonium hydroxide, as an alternative reagent, was used to derivatize DTTB in good results. Dieldrin and the derivatized DTTBs gave highly linear calibration curves when analyzed by GC-MS. Moreover, we found that both analytes are adequately extracted from textiles by refluxing in hydrochloric acid and methanol. Furthermore, we established a purification method using the Bond Elut PRS column that effectively removed interfering substances in woolen products. Finally, we developed an improved analysis method by combining the above-mentioned techniques; the developed method exhibited a recovery rate of 94-104% and a relative standard deviation of less than 7% for both analytes. In addition, the limits of quantitation (dieldrin: 1.3 µg/g, DTTB: 0.72 µg/g) were sufficiently lower than the Japanese regulatory value of 30 µg/g.