Association Between Organophosphate Pesticide Exposure and Thyroid Hormones in Pregnant Women.

BACKGROUND: Use of organophosphate pesticides (OPs) is widespread in China. Although animal studies suggested that OP exposure could affect thyroid function, little is explored in human populations. METHODS: We investigated levels of OP exposure in pregnant women and the relationship between OPs and thyroid hormones in Shandong, China. We enrolled 637 pregnant women from April 2011 to December 2013. OP exposure was assessed by a questionnaire administered to the pregnant women in the hospital and by analyses of urinary dialkylphosphate (DAP) metabolites of OPs in pregnant women (n = 413). We measured the concentration of five thyroid hormones in serum samples in pregnant women (n = 325) and analyzed the association between DAP metabolites of OPs and thyroid hormones (n = 325). RESULTS: Median levels of DAP metabolites were 9.81 µg/L for dimethylphosphate (DMP), 0.79 µg/L for dimethylthiophosphate (DMTP), 5.00 µg/L for diethylphosphate (DEP), and 0.78 µg/L for diethylthiophosphate (DETP), which were higher than those reported in developed countries. We found that the total DAP concentration (the sum of DMP, DMTP, DEP, and DETP) in urine was positively associated with free T4 levels (ß = 0.137; 95% confidence interval [CI] = 0.012, 0.263) and negatively associated with thyroid-stimulating hormone levels (ß = -0.145; 95% CI = -0.242, -0.048). CONCLUSIONS: The findings suggest that OP exposure may be associated with changes in thyroid function in pregnant women. Given that urinary OP levels in pregnant women in Shandong were much higher than those reported in developed countries, further studies on the effects of OP exposure on thyroid function in pregnant women in China are warranted.

Organophosphate pesticide exposure and dialkyl phosphate urinary metabolites among chili farmers in northeastern Thailand.

BACKGROUND: Chlorpyrifos and profenofos are organophosphate pesticides (OPPs), we studied exposure and urinary metabolites in an agricultural area in the northeastern of Thailand during the chili-growing season (March - April) in 2012. OBJECTIVE: This study was designed to assess pesticide exposure concentration through dermal and inhalation pathways and to find and depict a relationship between urinary metabolites and means of exposure. MATERIALS AND METHODS: To estimate the pesticides exposure concentration, dermal wipes (hand, face, and feet), dermal patches and air samples were collected from 38 chili farmers. The morning void of pre and post application urine samples was an indicator of biological monitoring in the study which derived from 39 chili farmers. RESULTS: Chlorpyrifos and profenofos residues were detected on dermal patches, face wipes, and hand wipe samples, while no significant residues were found on the feet. Using a personal air sampling technique, all air samples detected pesticide residues. However, significant correlation between dermal pesticide exposure concentration and inhalation was not found (p>0.05). For urinary metabolite levels, there was a relationship between the first pre application morning void and post application morning void (p < 0.05); similar to the association between the first pre application morning void and the second post application morning void (p < 0.05). The main relationship between pesticide exposure and urinary metabolite was found to have been relevant to dermal exposure (r= 0.405; p < 0.05). CONCLUSIONS: The results of this study could suggested that public health education training programs, including the use of appropriate personal protective equipment (PPE), should be offered for the chili growing farmers in order to improve their ability to properly use pesticides. KEY WORDS: pesticide exposure, chili farmers, urinary metabolites, organophosphate pesticides.

Development of a strategic approach for comprehensive detection of organophosphate pesticide metabolites in urine: Extrapolation of cadusafos and prothiofos metabolomics data of mice to humans.

OBJECTIVES: The comprehensive detection of environmental chemicals in biospecimens, an indispensable task in exposome research, is advancing. This study aimed to develop an exposomic approach to identify urinary metabolites of organophosphate (OP) pesticides, specifically cadusafos and prothiofos metabolites, as an example chemical group, using an original metabolome dataset generated from animal experiments. METHODS: Urine samples from 73 university students were analyzed using liquid chromatography-high-resolution mass spectrometry. The metabolome data, including the exact masses, retention time (tR ), and tandem mass spectra obtained from the human samples, were compared with the existing reference databases and with our original metabolome dataset for cadusafos and prothiofos, which was produced from mice to whom two doses of these OPs were orally administered. RESULTS: Using the existing databases, one chromatographic peak was annotated as 2,4-dichlorophenol, which could be a prothiofos metabolite. Using our original dataset, one peak was annotated as a putative cadusafos metabolite and three peaks as putative prothiofos metabolites. Of these, all three peaks suggestive of prothiofos metabolites, 2,4-dichlorophenol, 3,4,5-trihydroxy-6-(2,4-dichlorophenoxy) oxane-2-carboxylic acid, and (2,4-dichlorophenyl) hydrogen sulfate were confirmed as authentic compounds by comparing their peak data with both the original dataset and peak data of the standard reagents. The putative cadusafos metabolite was identified as a level C compound (metabolite candidate with limited plausibility). CONCLUSIONS: Our developed method successfully identified prothiofos metabolites that are usually not a target of biomonitoring studies. Our approach is extensively applicable to various environmental contaminants beyond OP pesticides.

A rapid, cost-effective method for analyzing organophosphorus pesticide metabolites in human urine for counter-terrorism response.

Organophosphorus (OP) pesticides are used as insecticides in agriculture and pest control and are often called "junior strength" nerve agents because they share the same mechanism of toxicity. OP pesticides are metabolized to dialkylphosphates and other metabolites, which are excreted in urine. In case of a terrorism incident involving widely available OP pesticides, an occurrence that may be likely given their widespread availability, a rapid, accurate, and cost-effective method for detecting exposure is required. We have evaluated several analytical methods to determine the most reliable and cost-effective methods for incident response. Our comparisons have included different internal standards (isotopically labeled standards versus chemically similar surrogate standards), different isolation techniques (some of which are automatable), and different analysis platforms. We found that isotopically labeled standards were a necessity to provide accurate quantification; the chemically similar surrogate was not suitable as an internal standard. The most sensitive and precise method uses isotopically labeled standards with gas chromatography-tandem mass spectrometry analysis. However, the most cost-effective method employed isotopically labeled standards with gas chromatography-single quadrupole-mass spectrometry using a less expensive mass selective detector. Because this method is lower in cost, it may be a more viable option for equipping multiple laboratories with chemical-terrorism response capabilities.

Exploring Associations Between Postural Balance and Levels of Urinary Organophosphorus Pesticide Metabolites.

OBJECTIVE: Apply a data-driven approach to explore associations between postural balance and pesticide exposure among Latino farmworkers and non-farmworkers. METHODS: Lasso-regularized, generalized linear models were used to examine associations between postural control measures in four experimental conditions (2 visual × 2 cognitive difficulty) and dialkylphosphate (DAP) urinary metabolite levels. RESULTS: Obtained models generally performed poorly at explaining postural control measures. However, when both visual and cognitive conditions were altered-the most challenging balance condition-models for some postural balance measures contained several DAP metabolites and had relatively better fits. CONCLUSIONS: The current results were equivocal regarding associations between postural control measures and DAP metabolite concentrations. However, farmworker status appears to be an important variable in understanding this association. Future work should use a posturally- and cognitively-challenging test condition to reveal any potential associations.

Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers: an analysis of recent studies in Washington State.

We examined findings from five organophosphorus pesticide biomonitoring studies conducted in Washington State between 1994 and 1999. We compared urinary dimethylthiophosphate (DMTP) concentrations for all study groups and composite dimethyl alkylphosphate (DMAP) concentrations for selected groups. Children of pesticide applicators had substantially higher metabolite levels than did Seattle children and farmworker children (median DMTP, 25 microg/L; p < 0.0001). Metabolite levels of children living in agricultural communities were elevated during periods of crop spraying. Median DMTP concentrations for Seattle children and farmworker children did not differ significantly (6.1 and 5.8 microg/L DMTP, respectively; p = 0.73); however, the DMAP concentrations were higher for Seattle children than for farmworker children (117 and 87 nmol/L DMAP, respectively; p = 0.007). DMTP concentrations of U.S. children 6-11 years of age (1999-2000 National Health and Nutrition Examination Survey population) were higher than those of Seattle children and farmworker children at the 75th, 90th, and 95th percentiles. DMTP concentrations for workers actively engaged in apple thinning were 50 times higher than DMTP concentrations for farmworkers sampled outside of peak exposure periods. We conclude that workers who have direct contact with pesticides should continue to be the focus of public health interventions and that elevated child exposures in agricultural communities may occur during active crop-spraying periods and from living with a pesticide applicator. Timing of sample collection is critical for the proper interpretation of pesticide biomarkers excreted relatively soon after exposure. We surmise that differences in dietary exposure can explain the similar exposures observed among farmworker children, children living in the Seattle metropolitan area, and children sampled nationally.

Biological monitoring of organophosphorus pesticide exposure among children of agricultural workers in central Washington State.

Children up to 6 years of age who lived with pesticide applicators were monitored for increased risk of pesticide exposure: 48 pesticide applicator and 14 reference families were recruited from an agricultural region of Washington State in June 1995. A total of 160 spot urine samples were collected from 88 children, including repeated measures 3-7 days apart. Samples were assayed by gas chromatography flame photometric detector for dimethylphosphate metabolites. Dimethylthiophosphate (DMTP) was the dominant metabolite. DMTP levels were significantly higher in applicator children than in reference children (p = 0.015), with median concentrations of 0.021 and 0.005 microg/ml, respectively; maximum concentrations were 0.44 and 0.10 microg/ml, respectively. Percentages of detectable samples were 47% for applicator children and 27% for reference children. A marginally significant trend of increasing concentration was observed with decreasing age among applicator children (p = 0.060), and younger children within these families had significantly higher concentrations when compared to their older siblings (p = 0.040). Applicator children living less than 200 feet from an orchard were associated with higher frequency of detectable DMTP levels than nonproximal applicator children (p =0.036). These results indicate that applicator children experienced higher organophosphorus pesticide exposures than did reference children in the same community and that proximity to spraying is an important contributor to such exposures. Trends related to age suggest that child activity is an important variable for exposure. It is unlikely that any of the observed exposures posed a hazard of acute intoxication. This study points to the need for a more detailed understanding of pesticide exposure pathways for children of agricultural workers.

Diethylphosphorus metabolites in serum and urine of persons poisoned by phosalone.

The presence and elimination rate of phosalone and its diethylphosphorus metabolites in blood serum and urine were studied in persons who had ingested a concentrated phosalone solution. Phosalone was detected only in serum samples. As it was rapidly hydrolysed and eliminated from the body, its diethylphosphorus metabolites were a more sensitive indicator of exposure. The concentration decrease of phosalone in serum and of total diethylphosphorus metabolites in serum and urine followed the kinetics of a biphasic reaction. The faster elimination half-times in serum, calculated for two persons, were 2.3 and 3.4 h for phosalone and 3.4 and 38.6 h for total diethylphosphorus metabolites. In the faster phase the average elimination half-time of total urinary metabolites in five persons was 25 +/- 17 h. The kinetic data for total urinary metabolites in a person occupationally exposed to phosalone indicated an early and very fast elimination phase (elimination half-time 1.3 h), which was overlooked in poisoned persons. The proportions of single metabolites in total urinary metabolites in poisoned persons depended on whether the total amount of diethylphosphorus metabolites was above 1000 or below 1000 nmol/mg creatinine. Diethylphosphorodithioate predominated at high and diethylphosphate at low concentrations of total metabolites. The correlation between the maximum concentrations of total metabolites, measured in urine of poisoned persons on the day of admission to hospital or a day later, and the initial depression of serum cholinesterase (EC 3.1.1.8) and erythrocyte acetylcholinesterase (EC 3.1.1.7) activities was poor (r = 0.6).

Chlorpyrifos metabolites in serum and urine of poisoned persons.

Concentrations of parent pesticide and corresponding diethylphosphorus metabolites in blood serum and urine were investigated in persons who had ingested a concentrated solution of organophosphorus pesticide chlorpyrifos. The organophosphate poisoning was indicated by a significant depression of blood cholinesterase (EC 3.1.1.7 and EC 3.1.1.8) activities. Blood and spot urine samples were collected daily after admission of the persons to hospital. Chlorpyrifos was detected only in serum samples in a period up to 15 days after poisoning. In the same samples chlorpyrifos oxygen analogue, chlorpyrifos oxon, was not detected. The presence of diethylphosphorothioate in all serum and urine samples confirmed that part of chlorpyrifos was hydrolysed before its oxidation. The maximum concentrations of chlorpyrifos in serum and of metabolites in serum and urine were measured on the day of admission. The decrease in concentrations followed the first-order kinetics with the initial rate constant faster and the later one slower. In the faster elimination phase chlorpyrifos was eliminated from serum twice as fast (t1/2 = 1.1-3.3 h) as the total diethylphosphorus metabolites (t1/2 = 2.2-5.5 h). The total urinary diethylphosphorus metabolites in six chlorpyrifos poisoned persons were excreted with an average elimination half-time of 6.10 +/- 2.25 h (mean +/- S.D.) in the faster and of 80.35 +/- 25.8 h in the slower elimination phase.

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).

The use of biological monitoring in the estimation of exposure during the application of pesticides.

In order to assess the occupational health risk to workers using pesticides, accurate data on exposure (including knowledge of the primary route of exposure) and on absorption are needed. In addition, a well-defined no-effect level (NOEL) derived from suitable animal data must be available. Biological monitoring, urinary metabolite excretion in particular, frequently is used to indicate whether a worker has been exposed. Interpretation of the toxicological significance of the observed urinary metabolite levels is often difficult because the relationship between these levels and toxic dose are generally unknown. Another complication is the apparent lack of correlation between patch data and urinary metabolite data. The usefulness of a metabolite to predict exposure depends on many things, including detailed knowledge of absorption and excretion characteristics of the parent compound and identification of the metabolites. These data, when combined with appropriate toxicology data, permit an analysis of the potential health risks associated with an occupational exposure to toxic chemicals. This paper will correlate data from a number of studies in which the dermal penetration of azinphosmethyl (AM) was measured in rats, rabbits, monkeys and man; and urinary alkyl phosphate metabolites were measured in orchardists exposed to AM. The feasibility of utilizing metabolite excretion to estimate exposure and ultimate risk will be discussed.

Exposure to the organophosphate diazinon: data from a human volunteer study with oral and dermal doses.

Biological monitoring of occupational exposure to diazinon is possible by the determination of blood cholinesterase activity and by the measurement of metabolites in urine. However, there is little data to aid in the interpretation of results. This study gave oral (11 microg kg(-1) (36 nmol kg(-1)) body weight) and occluded dermal (100 mg (329 micromol)) doses of diazinon to five volunteers and analysed blood and urine samples for plasma and erythrocyte cholinesterase and urinary dialkyl phosphate (DAP) metabolites of diazinon: diethyl phosphate (DEP) and diethyl thiophosphate (DETP). Following oral and dermal exposure, peak urinary DAP levels occurred at 2 and 12 h, respectively. The apparent urinary elimination half-lives of DAP metabolites following oral and dermal exposure were approximately 2 and 9 h, respectively. Approximately 60% of the oral dose and 1% of the dermal dose was excreted as urinary DAP metabolites, with 90% of the dermal dose being recovered from the skin surface. On a group basis, there was no statistically significant mean depression in plasma or erythrocyte cholinesterase when compared with pre-exposure levels for either dosing experiment. The observed elimination kinetics of diazinon metabolites suggest a biological monitoring strategy for occupational exposure to diazinon based on urine samples collected at the end of shift.

Urinary excretion of alkylphosphates in the general population (Italy).

Xenobiotic residues and their metabolites in biological fluids of the general population are an important indicator of exposure to toxic substances dispersed in the environment. Urine samples collected from 124 subjects living in SW Tuscany, Italy were analyzed for alkylphosphates (dimethylphosphate, dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate, diethyldithiophosphate), aspecific metabolites of organophosphorus insecticides. The compound most frequently found was dimethylthiophosphate which was detectable in 99% of the subjects analyzed, with a geometric mean of 70.7 nmol/g creatinine. The other substances were found in the following percentages of our population, at the following mean concentrations: dimethylphosphate, 87%, 62.8 nmol/g creat.; dimethyldithiophosphate, 48%, 21.1 nmol/g creat.; diethylphosphate, 81%, 27.4 nmol/g creat.; diethylthiophosphate, 73%, 22.8 nmol/g creat.; diethyldithiophosphate, 7%, 13.7 nmol/g creatinine. Subjects eating food (fruit, meat, vegetables) that was not their own produce showed higher urinary concentrations of nearly all the compounds. The other variables considered (sex, age, residence, alcohol, smoking, sampling period) seem to affect the percentages of positive values of the various substances but to different degrees. Age and source of foods were the most important variables for dimethylthiophosphate excretion when mean values were analyzed by Student's t-test and analysis of variance (ANOVA).

Method for the determination of dialkyl phosphates in urine by strong anion exchange disk extraction and in-vial derivatization.

A method for the determination of four dialkylphosphate metabolites in urine by strong anion exchange disk (SAX) was investigated. Calcium hydroxide was added to a 1-mL urine sample to reduce interference. The aliquot was passed through the SAX disk to accumulate dialkylphosphate metabolites on the disk. The retained dialkylphosphate metabolites were derivatized with methyl iodide in acetonitrile online, and the resulting methyl esters of dialkylphosphate metabolites were directly analyzed by capillary column gas chromatography with flame photometric detection. The recoveries of these dialkylphosphate metabolites were found to be stable. When the intact sample was diluted with deionized water at a 1:1 ratio, the recoveries were both increased and stabilized. The urine samples collected from eight fruit farmers showed that levels of dialkylphosphate metabolites in urine were significantly different before and after pesticide application, indicating the method established in this study is applicable for real sample analysis. Compared with previous studies, this method not only can greatly simplify sample preparation, but it can also significantly reduce the consumption of toxic solvents in sample preparation.

Diagnostic value of urinary dialkyl phosphate measurement in goats exposed to diazinon.

Recognition of exposure to diazinon, an organophosphate insecticide, was studied in goats. Urine and milk dialkyl phosphate concentrations (DETP; O,O-diethyl phosphorothionate) and blood cholinesterase activity (ChE) and diazinon concentrations were measured. Groups (n = 3 each) given (orally) diazinon at doses of 0.5 mg/kg for 7 days (small dose) or 5 mg/kg for 7 days (large dose) were compared with goats acutely exposed to single doses of 150 mg/kg (n = 1) or 700 mg/kg (n = 1). Clinical signs of intoxication occurred only in the goat given the 700 mg/kg dose. Urinary DETP concentrations were sensitive indicators of diazinon exposure and provided quantitative differences between small, large, and acute dosage exposures. Milk DETP concentrations were not detected. Cholinesterase measurement was useful only in the acute exposure studies. Whole blood diazinon concentrations were detected only in goats given the large dose for 7 days and acutely exposed. Measurement of urinary DETP was a sensitive aid for recognition of diazinon exposure.

Metabonomics analysis of urine and plasma from rats given long-term and low-dose dimethoate by ultra-performance liquid chromatography-mass spectrometry.

This study assessed the effects of long-term, low-dose dimethoate administration to rats by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Dimethoate (0.04, 0.12, and 0.36 mg/kg body weight/day) was administered daily to male Wistar rats through their drinking water for 24 weeks. Significant changes in serum clinical chemistry were observed in the middle- and high-dose groups. UPLC-MS revealed evident separate clustering among the different dose groups using global metabolic profiling by supervised partial least squares-discriminant analysis. Metabonomic analysis showed alterations in a number of metabolites (12 from urine and 13 from plasma), such as L-tyrosine, dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), citric acid, uric acid, suberic acid, glycylproline, allantoin, isovalerylglutamic acid and kinds of lipids. The results suggest that long-term, low-dose exposure to dimethoate can cause disturbances in liver function, antioxidant and nervous systems, as well as the metabolisms of lipids, glucose, fatty acids, amino acids, and collagen in rats. DMTP and DMDTP, which had the most significant changes among all other studied biomarkers, were considered as early, sensitive biomarkers of exposure to dimethoate. The other aforementioned proposed toxicity biomarkers in metabonomic analysis may be useful in the risk assessment of the toxic effects of dimethoate. Metabonomics as a systems toxicology approach was able to provide comprehensive information on the dynamic process of dimethoate induced toxicity. In addition, the results indicate that metabonomic approach could detect systemic toxic effects at an earlier stage compared to clinical chemistry. The combination of metabonomics and clinical chemistry made the toxicity of dimethoate on rats more comprehensive.

Improved analysis of dialkylphosphates in urine using strong anion exchange disk extraction and in-vial derivatization.

Determination of dialkylphosphates (DAPs) in urine is useful for assessing human exposure to organophosphates (OPs). An improved method for the determination of four DAPs based on a strong anion exchange (SAX) disk extraction and in-vial derivatization was presented in this study. The matrix effect of urine components such as chloride ion and phosphate ion by using a SAX disk to extract DAPs in urine analysis was carefully evaluated. It was observed that the chloride ion mainly affected the extraction of diethylphosphate (DEP), dimethylthiophosphate (DMTP), and diethylthiophosphate (DETP) in urine. The addition of silver hydroxide could significantly improve the extraction efficiencies of these three DAPs, but it decreases the extraction efficiencies of dimethyldithiophosphate (DMDTP) and diethyldithiophosphate (DEDTP). The LOD of this method for DMTP, DETP, DMDTP, and DEDTP are 5, 5, 11, and 5 microg/L, respectively. A pretreatment strategy for the determination of DMTP, DMDTP, DETP, and DEDTP in urine was proposed which can provide reliable and prompt determination of routine urine analysis.

Evaluation of skin and respiratory doses and urinary excretion of alkylphosphates in workers exposed to dimethoate during treatment of olive trees.

This article describes a study of exposure to dimethoate during spraying of olive trees in Viterbo province in central Italy. Airborne concentrations of dimethoate were in the range 1.5 to 56.7 nmol/m(3). Total skin contamination was in the range 228.4 to 3200.7 nmol/d and averaged 96.0% +/- 3.6% of the total potential dose. Cotton garments afforded less skin protection than waterproof ones, which were in turn associated with higher skin contamination than disposable Tyvek overalls. Total potential doses and estimated absorbed doses, including their maxima, were below the acceptable daily intake of dimethoate, which is 43.6 nmol/kg body weight (b.w.). Urinary excretion of alkylphosphates was significantly higher than in the general population, increasing with exposure and usually showing a peak in the urine sample collected after treatment. Metabolite concentrations were influenced by the type of individual protection used: minimum levels were associated with the closed cabin and maximum levels with absence of any respiratory or hand protection. Urinary alkylphosphates showed a good correlation with estimated absorbed doses and are confirmed as sensitive biologic indicators of exposure to phosphoric esters.

Biological monitoring of exposure to organophosphorus insecticides by assay of urinary alkylphosphates: influence of protective measures during manual operations with treated plants.

Biological monitoring was carried out by assaying urinary dimethylated alkylphosphates [dimethyldithiophosphate (DMDTP), dimethylthio-phosphate (DMTP), and dimethylphosphate (DMP)] in 11 workers exposed to chlorpyrifos-methyl and azinphosmethyl during operations in a previously sprayed peach orchard. The subjects were divided into groups on the basis of the protective clothing worn. The results were compared with those of a reference group of 99 subjects not occupationally exposed to organophosphorus insecticides. The hand-wash liquid of the workers was also analyzed to evaluate skin contamination. Significantly higher levels of urinary excretion of alkylphosphates were found in all groups than in unexposed controls (Student's t test). A good correlation was found between quantities of the active ingredients on the hands and urinary excretion of total dimethylated alkylphosphates (r = 0.788) and of DMTP (r = 0.749) and DMP (r = 0.790) alone. The correlation between azinphos-methyl on the hands and urinary excretion of DMDTP was poor (r = 0.069). Under the working conditions investigated, the main route of absorption seems to be via the skin. Respiratory absorption, however, also appears significant in view of the difference in urinary excretion of dimethylated alkylphosphates found between subjects with and without face masks.

Comparison of measurement of dialkyl phosphates in milk/urine and blood cholinesterase and insecticide concentrations in goats exposed to the organophosphate insecticide, imidan.

Recognition of exposure to imidan was assessed in goats by dialkyl phosphate concentrations, blood cholinesterase (ChE) determinations, and blood imidan concentrations. Groups of three goats received 5.0 mg imidan/kg/day (low dose) or 10 mg imidan/kg/day (high dose) for 7 days orally. One goat received no imidan and one goat received an acute single dose (200 mg/kg). The urine of all treated goats was examined for the excretory dialkyl phosphates, O,O-dimethyl phosphorodithioate (DMDTP) and O,O-dimethyl phosphorothionate (DMTP). The overall mean DMDTP urinary concentration was 19.1 ppm (10-mg/kg treatment group) and 7.2 ppm (5-mg/kg treatment group). These metabolites rapidly disappeared following removal of the treatment except in those goats clinically affected. Milk contained no identifiable concentrations of dialkyl phosphates. Cholinesterase depression was observed in all imidan-treated goats, and a dose effect was observed. No imidan was detected in whole blood of either the 5- or 10-mg/kg treatment groups. Low blood concentrations (ppb) of imidan were measured in the acute single-dose exposed goat. Both urinary DMDTP and blood ChE provided recognition of imidan exposure. DMDTP, however, was immediately present in urine after exposure and provided stronger support for organophosphate exposure than did blood ChE.