Malathion exposure may increase infertility risk among US Adults: Results from the 2015-2016 NHANES.

BACKGROUND AND PURPOSE: Organophosphate pesticides such as malathion are the most widely used pesticides. Despite endocrine-disrupting effects, there is a paucity of information regarding chronic exposure to non-persistent organopesticides such as malathion. The purpose of this study is to describe the exposure burden among U.S. residents as well as possible impacts on fertility. METHODS: Population-based data collected by the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2016 were used to perform a retrospective analysis on urinary concentrations of malathion diacid. Samples were assessed from 1703 adult participants, statistically weighted to represent over 231 million individuals. General linear models were used to examine associations between exposure and reproductive health measures among pre-menopausal women. RESULTS: Detectable concentrations of malathion diacid were identified in 16.1 % (n = 254) of samples. Concentrations were higher among women who reported seeing a physician due to difficulties becoming pregnant (P < 0.001; r2 = 0.12) as well as among women who reported trying for at least a year to become pregnant (P < 0.001; r2 = 0.06). CONCLUSIONS: Exposure to malathion is associated with a history of reproductive health challenges among women.

Sex and adrenal hormones in association with insecticide biomarkers among adolescents living in ecuadorian agricultural communities.

BACKGROUND: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. METHODS: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17ß-estradiol, and cortisol. We used general linear models to assess linear (ß = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (ß2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. RESULTS: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (ßboys = 5.88% [1.21%, 10.78%], ßgirls = 4.10% [-0.02%, 8.39%]), and cortisol (ßboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (ß2boys = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (ß2boys = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (ßboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (ßboys = 3.90% [1.28%, 6.58%]) were positively associated with 17ß-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. CONCLUSIONS: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17ß-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

Urinary Pesticide Levels in Children and Adolescents Residing in Two Agricultural Communities in Mexico.

The use of pesticides in agricultural activities has increased significantly during the last decades. Several studies have reported the health damage that results from exposure to pesticides. In Mexico, hundreds of communities depend economically on agricultural activities. The participation of minors in this type of activity and their exposure to pesticides represents a potential public health problem. A cross-sectional study was conducted, in which urine samples (first-morning urine) were taken from children under 15 years of age in both communities. A total of 281 urine samples obtained in both communities were processed for the determination of pesticides with high-performance liquid chromatography together with tandem mass spectrometry. In 100% of the samples, at least two pesticides of the 17 reported in the total samples were detected. The presence of malathion, metoxuron, and glyphosate was remarkable in more than 70% of the cases. Substantial differences were detected regarding the other compounds. It is necessary to carry out long-term studies to determine the damage to health resulting from this constant exposure and to inform the health authorities about the problem in order to implement preventive measures.

Analysis of finit in urine sample using thin layer chromatography.

Finit is a common insecticide generally used to control a variety of insects in homes. Routinely it is analysed by Gas Liquid Chromatography (GLC) and High Performance Liquid Chromatography (HPLC). An attempt has been made to develop a new method for analysis of finit in urine samples using Thin Layer Chromatography (TLC) technique which is inexpensive, accurate and non-destructive. Finit was extracted from urine using solvent extraction methods and then identified on the TLC plates. For detection on developed plates, palladium chloride, silver nitrate, iodine vapour and bromophenol blue were used which successfully increased the sensitivity without dispensing with the simplicity of the method. The method developed is simple, inexpensive, accurate and non-destructive that allows for sensitive and reproducible analysis of finit.

Determination of no-observed effect level (NOEL)-biomarker equivalents to interpret biomonitoring data for organophosphorus pesticides in children.

BACKGROUND: Environmental exposure to organophosphorus pesticides has been characterized in various populations, but interpretation of these data from a health risk perspective remains an issue. The current paper proposes biological reference values to help interpret biomonitoring data related to an exposure to organophosphorus pesticides in children for which measurements of alkylphosphate metabolites are available. METHODS: Published models describing the kinetics of malathion and chlorpyrifos in humans were used to determine no-observed effect level - biomarker equivalents for methylphosphates and ethylphosphates, respectively. These were expressed in the form of cumulative urinary amounts of alkylphosphates over specified time periods corresponding to an absorbed no-observed effect level dose (derived from a published human exposure dose) and assuming various plausible exposure scenarios. Cumulative amounts of methylphosphate and ethylphosphate metabolites measured in the urine of a group of Quebec children were then compared to the proposed biological reference values. RESULTS: From a published no-observed effect level dose for malathion and chlorpyrifos, the model predicts corresponding oral biological reference values for methylphosphate and ethylphosphate derivatives of 106 and 52 nmol/kg of body weight, respectively, in 12-h nighttime urine collections, and dermal biological reference values of 40 and 32 nmol/kg of body weight. Out of the 442 available urine samples, only one presented a methylphosphate excretion exceeding the biological reference value established on the basis of a dermal exposure scenario and none of the methylphosphate and ethylphosphate excretion values were above the obtained oral biological reference values, which reflect the main exposure route in children. CONCLUSION: This study is a first step towards the development of biological guidelines for organophophorus pesticides using a toxicokinetic modeling approach, which can be used to provide a health-based interpretation of biomonitoring data in the general population.

Occupational behaviors and farmworkers' pesticide exposure: findings from a study in Monterey County, California.

BACKGROUND: We studied the relationship between behaviors promoted through the US Environmental Protection Agency Worker Protection Standard (WPS) and other programs and agricultural pesticide exposures in 73 strawberry fieldworkers employed in Monterey County, California. METHODS: Farmworkers' behaviors were assessed via self-report and organophosphorus (OP) pesticide exposure was measured using dimethyl alkylphosphate (DMAP) and malathion dicarboxylic acid (MDA) urinary metabolite levels. RESULTS: Wearing WPS-recommended clothing, wearing clean work clothes, and the combination of handwashing with soap and wearing gloves were associated with decreases in DMAP and MDA metabolite levels. Despite these protective behaviors, however, participants had significantly higher levels of exposure as compared with a national reference sample. CONCLUSIONS: Interventions that facilitate compliance with these behaviors may be effective in decreasing fieldworkers' pesticide exposures. However, further efforts are needed to reduce the exposure disparities experienced by farmworkers and decrease the potential for "take home" exposures to farmworkers' families.

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.

Simultaneous determination of malathion, permethrin, DEET (N,N-diethyl-m-toluamide), and their metabolites in rat plasma and urine using high performance liquid chromatography.

A method was developed for the separation and quantification of the insecticide malathion (O,O-dimethyl-S-(1,2-carbethoxyethyl) phosphorodithioate), its metabolite malaoxon (O,O-dimethyl-S-(1,2-carbethoxyethyl) phosphorothioate), the insecticide permethrin (3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid(3-phenoxyphenyl)methylester), two of its metabolites m-phenoxybenzyl alcohol and m-phenoxybenzoic acid, the insect repellent N,N-diethyl-m-toluamide (DEET), and its metabolites m-toluamide and m-toluic acid in rat plasma and urine. The method used high performance liquid chromatography (HPLC) with reversed phase C(18) column, and UV detection at 210 nm. The compounds were separated using gradient of 45--99% acetonitrile in water (pH 3.5) at a flow rate ranging between 0.5 and 2 ml/min in a period of 15 min. The retention times ranged from 7.4 to 12.3 min. The limits of detection ranged between 20 and 100 ng/ml, while limits of quantitation were 50-150 ng/ml. Average percentage recovery of five spiked plasma samples were 80.1+/-4.2, 75.2+/-4.6, 84.5+/-4.0, 84.3+/-3.4, 82.8+/-3.9, 83.9+/-5.5, 82.2+/-6.0, 83.1+/-4.3, and from urine 78.8+/-3.9, 76.4+/-4.9, 82.3+/-4.5, 82.5+/-3.9, 81.4+/-4.0, 83.9+/-4.3, 81.5+/-5.0, and 84.5+/-3.8 for, malathion, malaoxon, DEET, m-toluamide, m-toluic acid, permethrin, m-phenoxybenzyl alcohol, and m-phenoxybenzoic acid, respectively. The method was reproducible and linear over range between 100 and 1000 ng/ml. This method was applied to analyze the above chemicals and metabolites following combined dermal administration in rats.

Isotope dilution high-performance liquid chromatography/tandem mass spectrometry method for quantifying urinary metabolites of atrazine, malathion, and 2,4-dichlorophenoxyacetic acid.

We have developed an isotope dilution high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method for quantifying the urinary metabolites of the pesticides atrazine, malathion, and 2,4-dichlorophenoxyacetic acid (2,4-D). Urine samples are extracted with an organic solvent, and the organic fraction is concentrated. The concentrate is then analyzed using HPLC/MS/MS. The limits of detection for the metabolites are less than 0.5 microgram/L (parts per billion) in 10 mL of urine, with a high degree of accuracy and precision.

Dimethylphosphorus metabolites in serum and urine of persons poisoned by malathion or thiometon.

The urinary excretion rates of dimethyl-phosphate, -phosphorothioate and -phosphorodithioate were studied in six persons of whom four had ingested a concentrated solution of malathion and two of thiometon. The concentration decrease of single and total dimethylphosphorus metabolites was biphased, with a fast initial rate and a slow later rate. The excretion rate of total metabolites in the faster phase depended on the initial concentration in urine. At concentrations higher than 100 nmol/mg creatinine, the excretion half-times ranged from 7.5 to 15.4 h and at concentrations between 52 and 95 nmol/mg creatinine from 34.7 to 55.4 h. Non-metabolized malathion was detected only in one urine sample collected from one person immediately after hospitalization. Two persons poisoned with malathion were taken blood serum samples for the analysis of the parent pesticide and its metabolites on a daily basis after hospitalization. The parent pesticide was detectable in the serum only one day after the poisoning. The concentration of total malathion dimethylphosphorus metabolites in serum decreased very quickly within 1.5 days after hospitalization. The total metabolite elimination half-times were 4.1 and 4.7 h in the initial phase, and 53.3 and 69.3 days in the later slower elimination phase. There was no correlation between maximum concentrations of total metabolites measured in serum and/or urine on the day of admission to hospital and the initial depression of serum cholinesterase (BChE, EC 3.1.1.8) and erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7).

Malathion disposition in dermally and orally treated rats and its impact on the blood serum acetylcholine esterase and protein profile.

14C-methoxy-malathion with either pure or 50% E.C. formulated malathion were applied orally or dermally at one tenth of their LD50 to two batches of male albino rats. More than 90% of 14C was released with urine after 24 hours. The rest of 14C was detected in the feces, blood, intestines, liver and kidney in a descending order. No significant 14C was detected in other organs. Comparing the oral pure and formulated malathion treatments, there was no significant variation in the rate of disposition or excretion of 14C-malathion. However, the dermal treatment revealed that the 14C-formulated malathion was released faster than the pure one in urine in the first 24 hours; while the 14C-pure malathion showed relatively higher levels in the feces and blood in the first 24 hours. In a third batch of male albino rats, the effect of the same level of dermal treatment by either pure or 50% E.C. formulated malathion on serum acetylcholine-esterase (A. Ch. E.) activity and serum protein profile was studied. The serum A. Ch. E. activity was found to be inhibited to 40% activity after 6 to 24 hours for both treatments. However, after 96 hours the serum of the pure malathion treated rats showed full recovery of A.Ch.E. activity, while the formulated malathion treated showed only 60% activity. The SDS-PAGE analysis showed a differentiation in the serum protein bands of the 48 hours exposed rats to formulated malathion which was confirmed by the scanned gel profile. The FPLC integrated chromatograms proved an initiation of a new protein band accompanied with rearrangement of the albumin and pre-albumin bands. Thus it can be concluded that, the impact on the blood serum protein profile and A. Ch. E. activity can be used as reliable criteria to detect acute toxicity of malathion and other choline-esterase inhibitors in exposed field workers. Further research is needed to elucidate the specificity and sensitivity of such criteria as biomarkers for human exposure.

Selected pesticide residues and metabolites in urine from a survey of the U.S. general population.

Residues of toxic chemicals in human tissues and fluids can be important indicators of exposure. Urine collected from a subsample of the second National Health and Nutrition Examination Survey was analyzed for organochlorine, organophosphorus, and chlorophenoxy pesticides or their metabolites. Urine concentration was also measured. The most frequently occurring residue in urine was pentachlorophenol (PCP), found in quantifiable concentrations in 71.6% of the general population with an estimated geometric mean level of 6.3 ng/ml. Percent quantifiable levels of PCP were found to be highest among males. Quantifiable concentrations of 3,5,6-trichloro-2-pyridinol (5.8%), 2,4,5-trichlorophenol (3.4%), para-nitrophenol (2.4%), dicamba (1.4%), malathion dicarboxylic acid (0.5%), malathion alpha-monocarboxylic acid (1.1%), and 2,4-D (0.3%) were found, but at much lower frequencies. No quantifiable levels of 2,4,5-T or silvex were found. Preliminary analyses showed an apparent relationship between residue concentration and two measures of urine concentration (osmolality and creatinine). A large segment of the general population of the United States experienced exposure to certain pesticides, including some considered biodegradable, during the years 1976-1980.

Penetration, excretion and metabolism of 14C malathion in susceptible and resistant strains of Plutella xylostella.

1. The rate of penetration 14C malathion into the larvae of the diamondback moth, Plutella xylostella L., was found to be significantly different in an R-strain and S-strain. The rate of penetration was more rapid in the R-strain during the first hour after treatment. 2. The rate of metabolism in vivo and the rate of excretion were also higher in the R-strain compared with the S-strain. 3. The main metabolites produced in both strains were malathion dicarboxylic acid and desmethyl malathion. 4. The mechanism of insecticide resistance in Plutella xylostella L. is multifactorial, and involves a higher rate of penetration into the larvae of the R-strain, a higher activity of enzymes involved in its metabolism, and a higher level of excretion of the toxic compounds from the body of the R-strain compared with the S-strain.

Percutaneous absorption of malathion in the guinea-pig: effect of repeated topical application.

The effects of daily repeated topical application and of washing on the percutaneous absorption of malathion have been investigated in guinea-pigs. Skin absorption was determined indirectly by measurement of radioactivity excreted into the urine following topical administration of 14C-labelled malathion, with correction of these values for incomplete renal elimination. Malathion was applied at a concentration of 5 mg/cm2 every 24 hr to the same site on the post-auricular bald area for 15 days. Doses 1, 8 and 15 were radiolabelled. The effect of multiple application and washing was assessed by Newman-Keuls multiple range test for statistical significance. The percutaneous absorption of malathion was 2-3 times higher with washing than without. There was no significant increase (P greater than 0.05) in the percutaneous absorption of malathion with repeated application without washing. These studies suggest that the total penetration of malathion resulting from daily topical dosing without daily washing may be predicted from a single-dose application to the same unwashed site at an equivalent surface concentration, and also that repeated washing with soap and water may significantly decrease the barrier function of guinea-pig skin.

The rate of urinary excretion of phosalone residues in occupationally exposed persons.

The absorption of malathion and phosalone was followed in occupationally exposed workers by determination of residues excreted in the urine. Because of the high concentrations found in the morning urine samples, the rates of excretion of phosalone metabolites in the urine of a volunteer experimentally exposed to phosalone during one and then again during three subsequent working days were investigated. The urinary excretion of phosalone metabolites was most intense 4--5 hours after exposure. At the beginning of the next day, the metabolites were still well measureable in the urine. Blood and plasma cholinesterase activities were only slightly reduced during exposure. The analyses of 24-hour urine samples, or of urine samples taken 4--5 hours after exposure, are not suitable for the routine control of occupationally exposed persons because of sampling difficulties. Instead, analyses of samples taken immediately before and after work hours have to be performed. A systematic increase in the concentrations of pesticide residues in the morning urine should initiate more efficient and well-timed protection measures.

Organophosphorus pesticide poisonings in humans: determination of residues and metabolites in tissues and urine.

The analyses of four organophosphorus pesticide poisoning cases, three of which resulted in death, are reported. The case histories of the subjects, along with the analysis of tissues, urine, and blood for the levels of pesticides and metabolites are given. The pesticides involved include dicrotophos, chlorpyrifos, malathion, and parathion. The methods of analysis were adapted from previously published methods that provide a very rapid means of identification of organophosphorus pesticides in the tissues or in the blood of poisoned patients.