Metabolite Of Malathion Research Articles

Exposure to non-persistent pesticides and sexual maturation of Spanish adolescent males

BackgroundSeveral non-persistent pesticides are endocrine disrupting chemicals and may impact on sexual maturation. ObjectiveTo examine the association between urinary biomarkers of non-persistent pesticides and sexual maturation in adolescent males in the Environment and Childhood (INMA) Project. MethodsThe metabolites of several pesticides were measured in spot urine samples collected from 201 boys aged 14–17 years, including: 3,5,6-trichloro-2-pyridinol (TCPy), metabolite of chlorpyrifos; 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), metabolite of diazinon; malathion diacid (MDA), metabolite of malathion; diethyl thiophosphate (DETP) and diethyl dithiophosphate, non-specific metabolites of organophosphates; 3-phenoxybenzoic acid (3-PBA) and dimethyl cyclopropane carboxylic acid, metabolites of pyrethroids; 1-naphthol (1-NPL), metabolite of carbaryl; and ethylene thiourea (ETU), metabolite of dithiocarbamate fungicides. Sexual maturation was assessed using Tanner stages, self-reported Pubertal Development Scale, and testicular volume (TV). Multivariate logistic regression was employed to examine associations between urinary pesticide metabolites and the odds of being in Tanner stage 5 of genital development (G5) or pubic hair growth (PH5); stage ≥4 of overall pubertal development, gonadarche, and adrenarche; or having mature TV (≥25 mL). ResultsDETP concentrations>75th percentile (P75) were associated with lower odds of being in stage G5 (OR = 0.27; 95% CI = 0.10–0.70), detectable TCPy with lower odds of gonadal stage≥4 (OR = 0.50; 95% CI = 0.26–0.96), and intermediate detectable MDA concentrations (<P75) with lower odds of adrenal stage≥4 (OR = 0.32; 95% CI = 0.11–0.94). Conversely, detectable concentrations of 1-NPL were associated with higher odds of adrenal stage≥4 (OR = 2.61; 95% CI = 1.30–5.24) but lower odds of mature TV (OR = 0.42; 95% CI = 0.19–0.90). ConclusionExposure to certain pesticides may be associated with delayed sexual maturity in adolescent males.

An ultrasensitive "mix-and-detect" kind of fluorescent biosensor for malaoxon detection using the AChE-ATCh-Ag-GO system.

Malaoxon, a highly toxic metabolite of malathion, can lead to severe harm or death if ingested. This study introduces a rapid and innovative fluorescent biosensor that relies on acetylcholinesterase (AChE) inhibition for detecting malaoxon using Ag-GO nanohybrid. The synthesized nanomaterials (GO, Ag-GO) were evaluated with multiple characterization methods to confirm their elemental composition, morphology, and crystalline structure. The fabricated biosensor works by utilizing AChE to catalyze the substrate acetylthiocholine (ATCh), which generates positively charged thiocholine (TCh) and triggers citrate-coated AgNP aggregation on the GO sheet, leading to an increase in fluorescence emission at 423 nm. However, the presence of malaoxon inhibits the AChE action and reduces the production of TCh, resulting in a decrease in fluorescence emission intensity. This mechanism allows the biosensor to detect a wide range of malaoxon concentrations with excellent linearity and low LOD and LOQ values of 0.001 pM to 1000 pM, 0.9 fM, and 3 fM, respectively. The biosensor also demonstrated superior inhibitory efficacy towards malaoxon compared to other OP pesticides, indicating its resistance to external influences. In practical sample testing, the biosensor displayed recoveries of over 98% with extremely low RSD% values. Based on the results obtained from the study, it can be concluded that the developed biosensor has the potential to be used in various real-world applications for detecting malaoxon in food, and water samples, with high sensitivity, accuracy, and reliability.

Preparation of chabazite based Fenton-like heterogeneous catalyst and its organic micropollutant removal performance

Natural chabazite (CHA) is used for the first time as a heterogeneous catalyst in Fenton-like oxidation. Pretreatment techniques (NH4+-exchange, steam treatment, and Fe-exchange) were applied to natural CHA to improve the available micropore and mesopore volume as well as to increase Fe-content. CHA samples were characterized by XRD, N2 adsorption, UV–Vis, SEM-EDX, ICP-OES, and MAS NMR to study the improvement after each pretreatment. Steam treatment at 675 °C and 20 kPa improved the mesopore volume of CHA, which enabled Fe3+ concentration to increase from 0.24 to 0.60 mmol Fe3+ g CHA−1 following the Fe-exchange. The Fe-exchanged CHA (Fe-CHA) was then tested for malathion oxidation. The effect of H2O2 and catalyst doses and pH on the degradation of malathion was investigated. Fenton-like oxidation was realized at a higher and wider pH range (pH 3–7) when compared to classical Fenton. A malathion removal between 20 and 81% was achieved depending on the initial malathion concentration (250–750 μg L−1), Fenton Reagents (H2O2 and Fe-CHA) concentrations (75–300 mg L−1 and 250–750 mg L−1, respectively) and pH (3–7). The metabolites of malathion were identified as malaoxon, desmethyl malaoxon and diethyl malate. A possible oxidation pathway was proposed, where desmethyl malaoxon and diethyl malate were identified as the secondary oxidation products. Moreover, the performance of Fe-CHA was compared with commercially available synthetic zeolites of Fe-Ultra-stable Y and Fe-ZSM-5. Fe-CHA is found to be comparably effective as these synthetic zeolites, as well as providing substantially smaller sludge production when compared to classical Fenton.

Inhibition of Oocyte Maturation by Malathion and Structurally Related Chemicals in Zebrafish (Danio rerio) After In Vitro and In Vivo Exposure.

Oogenesis is the process by which a primary oocyte develops into a fertilizable oocyte, making it critical to successful reproduction in fish. In zebrafish (Danio rerio), there are five stages of oogenesis. During the final step (oocyte maturation), the maturation-inducing hormone 17α,20β-dihydroxy-4-pregnen-3-one (MIH) activates the membrane progestin receptor, inducing germinal vesicle breakdown. Using in vitro assays, it has been shown that anthropogenic stressors can dysregulate MIH-induced oocyte maturation. However, it is unknown whether the in vitro assay is predictive of reproductive performance after in vivo exposure. We demonstrate that a known inhibitor of oocyte maturation, malathion, and a structurally related chemical, dimethoate, inhibit oocyte maturation. However, malaoxon and omethoate, which are metabolites of malathion and dimethoate, did not inhibit oocyte maturation. Malathion and dimethoate inhibited maturation to a similar magnitude when oocytes were exposed for 4 h in vitro or 10 days in vivo, suggesting that the in vitro zebrafish oocyte maturation assay might be predictive of alterations to reproductive performance. However, when adult zebrafish were exposed to malathion for 21 days, there was no alteration in fecundity or fertility in comparison with control fish. Our study supports the oocyte maturation assay as being predictive of the success of in vitro oocyte maturation after in vivo exposure, but it remains unclear whether inhibition of MIH-induced oocyte maturation in vitro correlates to decreases in reproductive performance. Environ Toxicol Chem 2022;41:1381-1389. © 2022 SETAC.

A glutathione S-transferase (BdGSTd9) participates in malathion resistance via directly depleting malathion and its toxic oxide malaoxon in Bactrocera dorsalis (Hendel).

The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with malaoxon and therefore enhance malathion resistance. BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and malaoxon. © 2020 Society of Chemical Industry.

A comparative study on degradation of complex malathion organophosphate using of Escherichia coli IES-02 and a novel carboxylesterase

Malathion organophosphates considered as the major constituent of herbicides, pesticides and insecticides. Extensively used in agricultural, horticultures and for numerous household applications contributes to precedence organic pollutants leading antagonistic effects on human health and environment. Therefore detoxification of malathion from contaminated site is of general interest. Simultaneously it is very emerging to isolated novel indigenous microbial strains from contaminated site with a record of pesticide application. In this study Escherichia coli IES-02 isolated from malathion contaminant effluent and the strain showed maximum efficiency in malathion degradation that utilized it as the sole source of carbon. Carboxylesterase (33.0, 30.0, 28.0 kDa) were purified (1685.71 U/mg) from Escherichia coli IES-02 showed significant results in malathion degradation approximately 81% within 20 min as compared with Escherichia coli IES-02 cells within 4 h (99.0 to 95.0%) into monocarboxylic acid and diacid derivatives. The generation time of Escherichia coli was also observed at 60 min with 0.1 ppm, 68 min with 0.5 ppm, 74.5 min with 2.0 ppm and 91.37 min with 50 ppm of malathion. The degradation rate and transformation metabolites were estimated by Gas Chromatography-Mass Spectrometry respectively. Malathion metabolites pathway proposed in this study which revealed the potential application against lethal environmental pollution.

Organic diet intervention significantly reduces urinary pesticide levels in U.S. children and adults

BackgroundPrevious diet intervention studies indicate that an organic diet can reduce urinary pesticide metabolite excretion; however, they have largely focused on organophosphate (OP) pesticides. Knowledge gaps exist regarding the impact of an organic diet on exposure to other pesticides, including pyrethroids and neonicotinoids, which are increasing in use in the United States and globally. ObjectiveTo investigate the impact of an organic diet intervention on levels of insecticides, herbicides, and fungicides or their metabolites in urine collected from adults and children. MethodsWe collected urine samples from four racially and geographically diverse families in the United States before and after an organic diet intervention (n = 16 participants and a total of 158 urine samples). ResultsWe observed significant reductions in urinary levels of thirteen pesticide metabolites and parent compounds representing OP, neonicotinoid, and pyrethroid insecticides and the herbicide 2,4-D following the introduction of an organic diet. The greatest reductions were observed for clothianidin (− 82.7%; 95% confidence interval [95% CI]: − 86.6%, − 77.6%; p < 0.01), malathion dicarboxylic acid (MDA), a metabolite of malathion (− 95.0%; 95% CI: − 97.0%, − 91.8%; p < 0.01), and 3,5,6-trichlor-2-pyridinol (TCPy), a metabolite of chlorpyrifos (− 60.7%; 95% CI: − 69.6%, − 49.2%; p < 0.01). Metabolites or parent compounds of the fungicides boscalid, iprodione, and thiabendazole and the neonicotinoid insecticide imidacloprid were not detected among participants in our study. ConclusionAn organic diet was associated with significant reductions in urinary excretion of several pesticide metabolites and parent compounds. This study adds to a growing body of literature indicating that an organic diet may reduce exposure to a range of pesticides in children and adults. Additional research is needed to evaluate dietary exposure to neonicotinoids, which are now the most widely used class of insecticides in the world.

Different Toxic Effects of Racemate, Enantiomers, and Metabolite of Malathion on HepG2 Cells Using High-Performance Liquid Chromatography-Quadrupole-Time-of-Flight-Based Metabolomics.

Commercial malathion is a racemic mixture that contains two enantiomers, and malathion has adverse effects on mammals. However, whether these two enantiomers have different effects on animals remains unclear. In this study, we tested the effect of racemate, enantiomers, and metabolite of malathion on the metabolomics profile of HepG2 cells. HepG2 cells showed distinct metabolic profiles when treated with rac-malathion, malaoxon, R-(+)-malathion, and S-(-)-malathion, and these differences were attributed to pathways in amino acid metabolism, oxidative stress, and inflammatory response. In addition, malathion treatment caused changes in amino acid levels, antioxidant activity, and expression of inflammatory genes in HepG2 cells. S-(-)-Malathion exhibited stronger metabolic perturbation than its enantiomer and racemate, consistent with the high level of cytotoxicity of S-(-)malathion. R-(+)-Malathion treatment caused significant oxidative stress in HepG2 cells but induced a weaker disturbance in the amino acid metabolism and a pro-inflammatory response compared to S-(-)-malathion and rac-malathion. Malaoxon caused more significant perturbation on antioxidase and a stronger antiapoptosis effect than its parent malathion. Our results provide insight into the risk assessment of malathion enantiomers and metabolites. We also demonstrate that a metabolomics approach can identify the discrepancy of the toxic effects and underlying mechanisms for enantiomers and metabolites of chiral pesticides.

In vitro selection of a single-stranded DNA molecular recognition element for the pesticide malathion.

Many large-scale applications of the organophosphate pesticide malathion have led to widespread environmental contamination. Concentrations are found in the environment well above those which are harmful to humans and environmental organisms. No current method of detection for this pesticide is rapid, cost-effective, and specific for malathion. Therefore, we utilized a stringent Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process to identify a Molecular Recognition Element (MRE) for malathion. This MRE was identified from a large ssDNA library and has an equilibrium dissociation constant (Kd) in the low-nanomolar range. Additionally, it has significant selectivity for malathion in comparison to various other pesticides and metabolites of malathion, which were used as negative targets of selection. The high affinity and selectivity of the ssDNA MRE for malathion is a product of the stringent SELEX selection scheme and will be useful for rapid, inexpensive, and specific detection of malathion in the environment.

Variation in the sensitivity of Callosobruchus (Coleoptera: Bruchidae) acetylcholinesterase to the organophosphate insecticide malaoxon: effect of species, geographical strain and food type

Bruchid beetles, Callosobruchus species, are serious pests of economically important grain legumes; their activity in stores is often controlled by the use of synthetic insecticides. Esterases are known to be involved in insecticide resistance in insects. However, there is a dearth of information on esterase activity in the genus Callosobruchus. In this study, the effect of species, geographical strain and food type on the variation in acetylcholinesterase (AChE) activity and its inhibition by malaoxon (malathion metabolite) was investigated using an in vitro spectrophotometric method. AChE activity varied significantly among species and strains and also among legume type used for rearing them. Generally, irrespective of species, strain or food type, the higher the AChE activity of a population, the higher is its inhibition by malaoxon. C. chinensis had the highest AChE activity of the species studied, and in the presence of malaoxon it had the lowest remaining AChE activity, while C. rhodesianus retained the highest activity. A first-hand knowledge of AChE activity in regional Callosobruchus in line with the prevailing food types should be of utmost importance to grain legume breeders, researchers on plant materials for bruchid control and pesticide manufacturer/applicators for a robust integrated management of these bruchids.

Does malaoxon play a role in the geno- and cytotoxic effects of malathion on human choriocarcinoma cells?

This investigation was undertaken to elucidate whether the active metabolite of malathion, malaoxon, has any role in exerting cyto- and genotoxic effects for human choriocarcinoma (JAR) cell line which is an acceptable model for human placental cells. Gas chromatography-mass spectrometry (GC-MS) analysis were separately performed on the cell compartment and supernatant cell culture medium after subjecting the cell line to different malathion concentrations (10–400 μg/mL) and for various incubation periods (0.5 to 24 hours). GC-MS analysis showed that the sonication performed for the disruption of the cells did not cause the chemical change of malathion. The uptake of malathion by the cells was relatively fast. However, the presence of malaoxon, even in trace amounts, could not be confirmed either in samples originating from disrupted cells or in the cell culture medium. Although the hydrolysis of malaoxon occurred in the culture medium, this degradation process could not be counted as a reason for the absence of malaoxon. Since both malathion and malaoxon standard compounds could be accurately detected and distinguished by the applied liquid-liquid extraction and GC-MS methods, one can conclude that, in the case of JAR cells, the parent compound, (i.e. malathion itself) is responsible for the observed in vitro cyto- and genotoxic effects. Our results indicate that the direct toxicity of malathion contributes to the complications of pregnancy observed for environmental malathion exposure.

Better than Eating Worms?: Children’s Dietary Exposure to OP Pesticides

Vol. 116, No. 4 EnvironewsOpen AccessBetter than Eating Worms?: Children’s Dietary Exposure to OP Pesticides Julia R. Barrett Julia R. Barrett Search for more papers by this author Published:1 April 2008https://doi.org/10.1289/ehp.116-a172aAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Widespread agricultural use of organophosphate (OP) pesticides frequently leads to low-level exposures in adults and children who eat conventionally grown foods. The frequently used one-time measurement of OP metabolites reveals only short-term exposures, thereby providing little evidence on long-term low-level exposures. A new article presents longitudinal evidence that foods grown in conventional fashion—that is, with the use of pesticides—may be a predominant source of exposure in children [EHP 116:537–542; Lu et al.].The article sprang from the Children’s Pesticide Exposure Study, which focused on two groups of children (3–11 years of age) in the Seattle and Atlanta areas from July 2003 to May 2004. For the present study, the researchers examined 23 children in Seattle (19 of whom completed the study) who normally consumed conventional diets. Parents tracked food consumption during the study and collected urine samples twice daily.During interventions over the course of the study, the children’s conventional diets were replaced with organic diets and the differences in urinary metabolites of OP pesticides were measured. The organic diets substituted conventionally produced grain, fruit, juice, and vegetables with those produced without pesticides; meat and dairy products rarely contain OP pesticides and were not substituted. During the summer and fall 2003 intervention periods (15 and 12 days, respectively), the children consumed their regular diets from days 1 to 3 and organic diets from days 4 to 8. After day 8, the children resumed their regular diets. There was no organic diet intervention during the winter and spring 2004 sampling periods.Urine samples were analyzed for metabolites of malathion, chlorpyrifos, diazinon, coumaphos, and methyl pirimiphos; only chlorpyrifos and malathion metabolites were detected frequently enough for statistical analysis. These metabolite levels fell to nearly or fully nondetectable levels within days of the children beginning an organic diet intervention and rose when the children returned to conventional diets.Given that OP pesticides were reported by parents not to have been used in the home and that urinary metabolites were clearly affected by diet, the researchers conclude that conventionally produced foods were the primary source of OP pesticide exposure for the children in this study. They also attribute higher dietary exposures to imported produce eaten in the winter and spring when domestic produce is not available. This finding is supported by a 2006 Environmental Protection Agency report showing that OP residues on imported produce have risen since 1996 even as residues on domestically grown produce have fallen.The authors caution, however, that their findings do not promote limiting fresh produce or eating only organic items, as it is unknown whether the observed exposures are harmful. Additionally, the study group did not represent the general population. However, the findings do provide a basis for more accurate assessment of exposure and associated efforts to determine the effects of OP pesticides on children’s health.For some families, food is likely the primary source of pesticide exposureFiguresReferencesRelatedDetails Vol. 116, No. 4 April 2008Metrics About Article Metrics Publication History Originally published1 April 2008Published in print1 April 2008 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Kinetic Analysis for Hydrolysis of Malathion by Carboxylesterase in Wheat Kernels

We previously found that malathion residue in wheat kernel sw as decomposed by wheat kernel carboxylesterase (CE) during sample preparation for pesticide residue analysis. The degradation of malathion in supernatant of wheat kernel homogenate was enzyme-kinetically analyzed to characterize the CE. Malathion α-monocarboxylic acid (MMCα), malathion β-monocarboxylic acid (MMCβ), malathion dicarboxylic acid (MDC) and desmethyl malathion (DMal) were identified by analysis using liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) after incubation at 36 ◦ Co f the reaction mixture of malathion in the supernatant of wheat kernel homogenate. Since small amounts of DMal and MMCβ were formed in boiled supernatant of wheat kernel homogenate, these compounds were nonenzymatically produced. Examination of the time course of enzymatic malathion degradation indicated that malathion was decomposed into MDC through both MMCα and MMCβ ,a nd the amount of MMCα formed was greater than that of MMCβ at maximum concentrations of both MMC isomers. MMCα and MMCβ were enzymatically decomposed into only MDC, which was the final metabolite of malathion because there was no further decomposition product. The order of degradation half-lives by wheat kernel CE (malathion < MMC β< MMCα )i sc onsistent with the intensity of their hydrophobicity. These results suggest that when malathion is degraded via MMC to MDC by wheat kernel CE, its enzymatic degradability and the decomposition products depends on their hydrophobicity.

Biological Monitoring of Exposure to Organophosphorus Insecticides in a Group of Horticultural Greenhouse Workers

Exposure to selected organophosphorus insecticides (OPs), malathion, diazinon and acephate, was evaluated in a group of horticultural greenhouse workers. This was achieved through measurements of the cumulative urinary excretion time courses of specific and non-specific biomarkers over a 24 h period following the onset of work exposure. For malathion, the absorbed daily doses were estimated from the 24 h cumulative urinary amounts of the specific mono- and di-carboxylic acid metabolites (the sum of MCA and DCA) through the use of a kinetic model. The observed 24 h urinary levels were also compared with a biological reference value (BRV) of 57 nmol kg(-1) of body weight established in a previous work on the basis of a human no-observed-effect level exposure dose. Excretion values were found to be 2.5% or less of the BRV, suggesting a negligible health risk. Both median and 95th percentile concentrations of DCA (n = 57 samples) were, however, slightly higher than the baseline values determined by the Centers for Disease Control and Prevention (CDC) in the US civilian population (MCA was not analyzed by the CDC). The cumulative urinary excretion time course of the methyl phosphoric (MP) derivatives, which are metabolites of malathion but also of several other OPs, was also determined. Though relatively low, the MP levels were from 3 to 31 times higher than would be expected on the basis of the malathion specific MCA and DCA excretions, indicating that MP excretions stem from sources other than malathion exposure. Accordingly, only the time courses of MCA and DCA excretion rate (nmol h(-1)) were compatible with the time of work exposure. Urinary biomarkers of exposure to diazinon and acephate were also measured. Urinary concentrations were essentially below or equal to the analytical limit of detection of 1 microg l(-1) for 2-isopropyl-4-methyl-6-hydroxypyrimidine (n = 54) and of 0.8 microg l(-1) for acephate and methamidophos (n = 59): values within the baseline range of the US civilian population, like the observed phosphoric metabolite concentrations. The workers under study thus appeared to be only slightly more exposed to malathion than the general population. However, their overall exposure to OPs, as measured by non-specific phosphoric metabolites, was similar to that of the general population, whose exposure occurs mainly through the ingestion of contaminated food. These results question the relevance of measuring non-specific phosphoric metabolites when attempting to assess low-dose occupational exposure to a specific OP.

OP Pesticides in Children’s Bodies: The Effects of a Conventional versus Organic Diet

Conventional agriculture includes the use of pesticides to control insects in vegetable, fruit, wheat, and other crops, so it’s no surprise that foods derived from these crops can therefore contain pesticide residues. What’s in question, though, is what these exposures amount to in terms of body burden. Risk-defining data are lacking, and scant data exist on diet-derived pesticides levels in children’s bodies. Now researchers from Seattle and Atlanta characterize the relationship between eating a diet of conventionally grown food products and the amount of organophosphorus (OP) pesticide residues that make it into children’s bodies [EHP 114:260–263]. According to a 1993 National Research Council report titled Pesticides in the Diets of Infants and Children, diet delivers the bulk of children’s exposure to pesticides. This exposure poses a greater health risk to children as compared to adults, because not only do children consume more food on a per-weight basis than adults and consequently have higher exposure, they also may be more vulnerable to the effects of toxicants because they are still developing. The researchers employed a longitudinal design in which 23 children aged 3 to 11 years accustomed to eating a conventional diet switched to organic foods and back again during a 15-day study period. For the first three days, the children consumed their regular conventional diets. During the next five days, they substituted organic equivalents of their usual plant-derived food items (including fresh produce, juice, processed fruits and vegetables, and grain-based products). For the last seven days, they resumed their conventional diets. Each day, for the entire 15-day period, parents collected a urine sample in the morning when the children woke and again at bedtime. The urine samples were analyzed for metabolites of several OP pesticides. The most commonly detected metabolites were MDA (a metabolite of malathion) and TCPY (a metabolite of chlorpyrifos). During both conventional phases, 60% of samples contained MDA, and 78% of samples contained TCPY. When children switched to organic foods, the percentage of samples containing MDA dropped to 22% and the proportion with TCPY fell to 50%. Average concentrations of MDA and TCPY also were significantly lower during the organic phase compared to the conventional phases. During the two conventional phases, mean urinary MDA concentrations were 2.9 and 4.4 micrograms per liter (μg/L) compared with 0.3 μg/L in the organic phase. The mean TCPY level decreased from 7.2 to 1.7 μg/L between the first and second phases, and rose to 5.8 μg/L when the children resumed their conventional diets. Metabolite levels varied widely among the samples, however. Recent research suggests that fractions of MDA and TCPY form as the parent compounds degrade in foods and the environment. Therefore, some proportion of the children’s exposure may have been to the metabolites themselves in the foods. The current study provides insight into how residual OP pesticides in food correspond with the absorbed dose, and the researchers conclude that a diet of organic foods protects children from exposure. They caution against applying results to the general population, however. Given that people from different backgrounds and living in different areas may have different and more significant OP exposures, it would be a mistake to assume that switching to an organic diet would eliminate all exposure to these pesticides. The study does support the National Research Council’s conclusion that dietary intake is a major source of OP pesticide exposure, but some children may receive even more exposure from the use of pesticides in the home, and further research is needed.

The pesticide malathion reduces survival and growth in developing zebrafish

Malathion is an organophosphorous pesticide widely used to control mosquitoes in urban areas and pests, such as boll weevils, in agricultural areas. Zebrafish, Danio rerio, are model organisms for developmental toxicology research because they are readily available, produce large numbers of clear embryos, and are sensitive to environmental changes. The nonlethal effects of malathion on developing zebrafish embryos, however, previously have not been analyzed quantitatively. We exposed zebrafish embryos to sublethal malathion concentrations to determine malathion's effects on a developing vertebrate. Zebrafish exposed to 0.5, 1.0, or 1.5 mg/L of malathion consistently elicited more rapid hatching from the chorion than zebrafish exposed to 2.0-, 2.5-, or 3.0-mg/L malathion concentrations. In addition, exposure to 2.0, 2.5, or 3.0 mg/L of malathion resulted in significantly shorter body length and eye diameters, indicating that malathion had teratogenic effects on zebrafish embryos. Malathion's action as an acetylcholinesterase inhibitor and the toxicity of the metabolites of malathion may be responsible for malathion's teratogenic effects on fish development.

Semen quality in relation to biomarkers of pesticide exposure.

We previously reported reduced sperm concentration and motility in fertile men in a U.S. agrarian area (Columbia, MO) relative to men from U.S. urban centers (Minneapolis, MN; Los Angeles, CA; New York, NY). In the present study we address the hypothesis that pesticides currently used in agriculture in the Midwest contributed to these differences in semen quality. We selected men in whom all semen parameters (concentration, percentage sperm with normal morphology, and percentage motile sperm) were low (cases) and men in whom all semen parameters were within normal limits (controls) within Missouri and Minnesota (sample sizes of 50 and 36, respectively) and measured metabolites of eight current-use pesticides in urine samples provided at the time of semen collection. All pesticide analyses were conducted blind with respect to center and case-control status. Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY)]; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively. Men from Missouri with high levels of alachlor or IMPY were significantly more likely to be cases than were men with low levels [odds ratios (ORs) = 30.0 and 16.7 for alachlor and IMPY, respectively], as were men with atrazine levels higher than the limit of detection (OR = 11.3). The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and metolachlor were also associated with poor semen quality in some analyses, whereas acetochlor levels were lower in cases than in controls (p = 0.04). No significant associations were seen for any pesticides within Minnesota, where levels of agricultural pesticides were low, or for the insect repellent DEET (N,N-diethyl-m-toluamide) or the malathion metabolite malathion dicarboxylic acid. These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduction in semen quality in fertile men from mid-Missouri we reported previously.

A Toxicokinetic Model of Malathion and Its Metabolites as a Tool to Assess Human Exposure and Risk through Measurements of Urinary Biomarkers

A toxicokinetic model is proposed to predict the time evolution of malathion and its metabolites, mono- and dicarboxylic acids (MCA, DCA) and phosphoric derivatives (dimethyl dithiophosphate [DMDTP], dimethyl thiophosphate [DMTP], and dimethyl phosphate [DMP]) in the human body and excreta, under a variety of exposure routes and scenarios. The biological determinants of the kinetics were established from published data on the in vivo time profiles of malathion and its metabolites in the blood and urine of human volunteers exposed by intravenous, oral, or dermal routes. In the model, body and excreta compartments were used to represent the time varying amounts of each of the following: malathion, MCA, DCA, DMDTP, DMTP, and DMP. The dynamic of intercompartment exchanges was described mathematically by a differential equation system that ensured conservation of mass at all times. The model parameters were determined by statistically adjusting the explicit solution of the differential equations to the experimental human data. Simulations provide a close approximation to kinetic data available in the published literature. When simulating a dermal exposure to malathion, the main route of entry for workers, the model predicts that it takes an average of 11.8 h to recover half of the absorbed dose of malathion eventually excreted in urine as metabolites, compared to 3.2 h following an intravenous injection and 4.0 h after oral administration. This shows that following a dermal exposure, the absorption rate governs the urinary excretion rate of malathion metabolites because the dermal absorption rate is much slower than biotransformation and renal clearance processes. The model served to establish biological reference values for malathion metabolites in urine since it allows links to be made between the absorbed dose of malathion and the time course of cumulative amounts of metabolites excreted in urine. From the no-observed-effect level (NOEL) of 0.61 micromol/kg/day derived from the data of Moeller and Rider (1962), the model predicts corresponding biological reference values for MCA, DCA, and phosphoric derivatives of 44, 13, and 62 nmol/kg, respectively, in 24-h urine samples. The latter were used to assess the health risk of workers exposed to malathion in botanical greenhouses, starting from urinary measurements of MCA and DCA metabolites.

Monitoring of pesticide applicators for potential dermal exposure to malathion and biomarkers in urine

Malathion was applied to roses in three Finnish greenhouses by hand held lance sprayers. The potential dermal exposure of applicators to this insecticide was measured. Total urine production of each applicator was also collected up to 24 h post application. In the urine samples the specific metabolite of malathion, malathion monocarboxylic acid (MMA), and the creatinine content were determined. The potential dermal exposure results show that during the application of malathion, the applicators’ lower limbs accounted, on average, for 48%, while the upper limbs accounted for 19% of the potential dermal exposure. Moreover, hands and chest and back and head regions accounted for 30 and 3%, respectively. Based on the urine measurements, it was observed that the excretion of MMA was very rapid reaching a maximum at about 6–7 h after the completion of the application. In the urine samples collected, MMA was found to be present in relatively small amounts.

Genotoxicity of Malaoxon: Induction of Oxidized and Methylated Bases and Protective Effect of α-Tocopherol

Abstract Malaoxon, the first and main metabolite of malathion, unlike its parent compound, can damage DNA in human lymphocytes, by mechanism(s) including oxidative action. Vitamin C may inhibit the DNA-damaging effect of malaoxon. To explore this effect further, we investigated the action of malaoxon on DNA in lymphocytes pretreated with a potent antioxidant, α-tocopherol (vitamin E), using the single-cell gel electrophoresis (comet assay). Addition of α-tocopherol to a final concentration of 20 and 80 μM reduced a dose-dependent DNA damaging effect of a 1-h incubation of human peripheral blood lymphocytes at 37°C with malaoxon at 25, 75, or 200 μM, measured as the increase in the comet tail moment of the lymphocytes. Lymphocytes treated with α-tocopherol displayed faster kinetics of removing damage to their DNA, and α-tocopherol abolished the cytotoxic effect of malaoxon at 200 μM. The protective action of α-tocopherol followed from its interaction with DNA or with malaoxon bound to DNA or lymphocytes rather than from chemical inactivation of malaoxon by it. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by malaoxon. Lymphocytes exposed to malaoxon and treated with formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, enzymes recognizing oxidized and methylated bases, displayed a greater extent of DNA damage than those not treated with these enzymes. The results suggest that hydrogen peroxide and reactive oxygen species may be involved in the formation of DNA lesions induced by malaoxon. Malaoxon can also methylate DNA bases, and α-tocopherol can be considered a protective agent against DNA damage in persons occupationally exposed to malathion/malaoxon.