Identification of a Major Human Urinary Metabolite of Alachlor by LC-MS/MS

Driskell, William J.; Hill, Robert H.; Shealy, D. B.; Hull, R. D.; Hines, Cynthia J.

doi:10.1007/s001289900124

Cited by 26 publications

(19 citation statements)

References 4 publications

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“…Glutathione-derived mercapturate metabolites of alachlor and metolachlor have been identified as important human urinary metabolites after occupational exposures (Driskell et al, 1996;Driskell and Hill Jr., 1997). By analogy, acetochlor mercapturate (ACM) has been hypothesized to be a human urinary metabolite of acetochlor (Swan et al, 2003;Olsson et al, 2004;Curwin et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…By analogy, acetochlor mercapturate (ACM) has been hypothesized to be a human urinary metabolite of acetochlor (Swan et al, 2003;Olsson et al, 2004;Curwin et al, 2005). Human exposure to alachlor has also been estimated by quantifying the hydrolysis product of alachlorrelated metabolites, 2,6-diethylaniline, in urine (Driskell et al, 1996). The major portion of acetochlor metabolites in the urine may be similarly estimated by quantifying the hydrolysis product, 2-ethyl-6-methylaniline (EMA).…”

Section: Introductionmentioning

confidence: 99%

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Identification of human urinary metabolites of acetochlor in exposed herbicide applicators by high-performance liquid chromatography-tandem mass spectrometry

Barr

Hines

Olsson

et al. 2007

J Expo Sci Environ Epidemiol

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Acetochlor is a preemergent chloroacetanilide herbicide used to control annual grasses and small-seeded broadleaf weeds. It is the second most abundantly applied herbicide on corn crops in the United States; however, human metabolites associated with known exposure to acetochlor have not been positively identified and confirmed. We positively identified acetochlor mercapturate (ACM) as a metabolite of acetochlor in urine samples collected during a 24-h period from custom (commercial) applicators who had applied acetochlor on either the day of or the day before urine collection. Concentrations in applicator urine samples ranged from 0.5 to 449 mg/l (0.3-121 mg/g creatinine). We found that ACM accounted for as much as 42% of the total acetochlor-derived metabolites; however, as the exposure level decreased (based on total acetochlor metabolite level), ACM became a less abundant metabolite of acetochlor (o17%). Unmetabolized acetochlor was also measured in the urine samples analyzed. At high exposures (classified as 4100 mg/l), acetochlor accounted for about 0.8% of the total excreted acetochlor metabolites (B2% of the ACM concentrations). At lower exposures (classified as ACM o10 mg/l), ACM and acetochlor concentrations were similar. Additionally, we tentatively identified another acetochlor metabolite that appeared to be important at low levels of exposure.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of human urinary metabolites of acetochlor in exposed herbicide applicators by high-performance liquid chromatography-tandem mass spectrometry

Barr

Hines

Olsson

et al. 2007

J Expo Sci Environ Epidemiol

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“…In another study using radioactively dosed monkeys, alachlor mercapturate was found to be the major metabolite, accounting for about 40% of the metabolite concentration (Feng et al, 1994). We (Driskell et al, 1996) found that alachlor mercapturate made up between 25% and 62% of the total alachlor metabolite concentration in the human urine samples that we analyzed.…”

Section: Resultsmentioning

confidence: 75%

Identification of a Major Human Urinary Metabolite of Metolachlor by LC-MS/MS

Driskell

Hill

1997

Bulletin of Environmental Contamination and Toxicology

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Metolachlor is a preemergence herbicide commonly used on soybeans, corn, and other crops. Herbicides are the most used class of pesticides, and metolachlor is one of the top three herbicides, with 40 -60 million pounds used annually (EPA 21T-1005, 1991).Recently, we have been involved in studies of herbicide exposure that required us to develop procedures to measure metolachlor metabolites, alachlor metabolites, and other pesticide metabolites in urine. When we began the study, we found that neither alachlor nor metolachlor metabolism in humans was well understood although alachlor metabolism had been studied in monkeys (Carr et al. 1986). Therefore, to understand the metabolism of alachlor in humans, we analyzed for alachlor metabolites in the urine of occupationally exposed subjects.We were able to identify a major human metabolite of alachlor, alachlor mercapturate (Driskell et a1.,1996). Metolachlor metabolism has not been studied in humans, and only a few studies of its metabolism in animals have been done. In this study, we tested the hypothesis that metolachlor, which is structurally similar to alachlor, is metabolized to metolachlor mercapturate in humans as alachlor is metabolized to alachor mercapturate.We synthesized metolachlor mercapturate to use as a standard to determine whether the urine samples from subjects who had been occupationally exposed to metolachlor contained metolachlor mercapturate. MATERIALS AND METHODSTo test the hypothesis that metolachlor, like alachlor, is metabolized to a mercapturate, we followed this regimen: 1) We synthesized metolachlor mercapturate to use as a standard 2) developed an LC-MS/MS method for metolachlor mercapturate 3) developed a solid phase urinary extraction method for metolachlor mercapturate and 4) analyzed for metolachlor mercapturate in urine Correspondence to: W. J. Driskell 929

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“…Despite that, the same symptoms as those mentioned above occurred periodically during this period leading to numerous hospitalisations. Through the same period, several urinary pesticides analysis were performed using a liquid chromatography with tandem mass spectrometry detection method (LC-MS/MS) previously published [14,15]. Alachlor and/or metabolites (2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) and 2,6-diethylaniline (DEA)) were repeatedly detected in urinary samples.…”

Section: Casementioning

confidence: 99%