Urinary metabolite monitoring

Urinary Metabolite Monitoring 28 Salivary Monitoring 29 VALIDATION OF PASSIVE DOSIMETRY 30 Atrazine 30 Chlorpyrifos 31... 

To monitor the absorbed chlorpyrifos doses in human volunteers, urine was collected before and following a 4-hr activity period on the treated grass surface(re-entry). The urine was analyzed for 3,5,6-trichloropyridinol (3,5,6-TCP), the urinary metabolite of chlorpyrifos, and creatinine, which was determined to verify completeness of urine collection by each volunteer. 

Davies, J.E., Enos, H.F., Barquet, A., Morgade, C., and Danauskas, J.X. (1979) Developments in toxicology and environmental sciences pesticide monitoring studies. The epidemiologic and toxicologic potential of urinary metabolites, in Toxicology and Occupational Medicine, Deichman, W.B., Ed., pp. 369-380. 

Assessments of pyrethroid exposure levels by monitoring urinary metabolites of pyrethroids in large-sized general populations have been reported. 

A 29-year-old man presented with acute pancreatitis after a period of heavy cannabis smoking. Other causes of the disease were ruled out. The pancreatitis resolved itself after the cannabis was stopped and this was confirmed by urinary cannabinoid metabolite monitoring in the community. There were no previous reports of acute pancreatitis associated with cannabis use in the general population. Drugs of all types are related to the etiology of pancreatitis in approximately 1.4-2% of cases k Pancreatic toxicity. The dried leaf, smoked by a 19-year-old woman, was active. The subject was hospitalized with pancrea-titis . 

The major urinary metabolite of di(2-ethylhexyl) adipate, 2-ethylhexanoic acid, has been shown to be an appropriate marker for biological monitoring of dietary di(2-ethylhexyl) adipate intake (Loftus etal., 1993, 1994). A limited population study in the United Kingdom was undertaken to estimate the daily intake of di(2-ethylhexyl) adipate following intake of a mean dose of 5.4 mg di(2-ethylhexyl) adipate presented with food. The study involved the determination of the urinary metabolite, 2-ethyl-hexanoic acid (24-h mine sample) in 112 individuals from five geographical locations. A skewed distribution with a median value for the daily intake of 2.7 mg was determined (Loftus et al., 1994). This value is about one third of the indirectly estimated maximum intake of 8. 2 mg per day. The probability of a daily intake in excess of 8.2 mg in the limited population (112 individuals) was calculated to be 3% (Loftus etal, 1994). 

N-demethylase activity was monitored by the CBT, and 7-N-demethylase activity was monitored by the caffeine urinary metabolite ratio (CMR). PBB-exposed subjects had higher CBT values (p<0.02) than urban nonsmokers, but tire values were comparable to those of urban smokers. The correlation between serum PBB levels and the CBT value was poor (r ().2). The CMR value in PBB-exposed subjects was also higher than that of urban nonsmokers (p<0.05) there was no correlation between serum PBB levels and CMR values. Generally, smokers have higher CBT values than nonsmokers due to the presence of polycyclic aromatic hydrocarbons (PAH) in tobacco smoke, which induce CYPIA (Kotake et al. 1982). 

Chlorpyrifos provides an example of the utility of human pharmacokinetic models to estimate daily dose from biomonitoring data for a rapidly cleared pesticide. The urinary metabolite trichloro-2-pyridinol (TCP) is used in the NHANES study to monitor population exposure to chlorpyrifos (CDC 2005). Several epidemiologic studies have linked chlorpyrifos exposure to adverse birth outcomes through associations between urinary and blood biomarkers and have demonstrated maternal exposure and physiologic measurements in the neonate (Berkowitz et al. 2003, 2004 Whyatt et al. 2004 Needham 2005). 

Rasmussen BB, Bosen K (1996) Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase and N-acetyltransferase activity in humans. Ther Drug Monitor 18 254-262 Rostami-Hodjegan A, Nurminen S, Jackson PR, Tucker GT (1996) Caffeine urinary metabolic ratios as markers of enzyme activity a theoretical assessment. Pharmacogenetics 6 121-149... 

An example of the use of the radioactivity detector to monitor some alkylethoxylate urinary metabolites (9) is shown in figure 6. 

An Example of the Use of the Radioactivity Detector to Monitor Some Urinary Metabolite Derivatives... 

Saude and Sykes [97] studied the effects of preparation and storage on the stability of human urine for metabolomic studies. Urine samples were collected from healthy male and female subjects and prepared by four different procedures (raw, centrifuged, filtered, and containing the bacteriostatic preservative sodium azide) and analyzed by NMR. The samples were stored at three different conditions at room temperature (22°C), in a refrigerator (4°C), or in a deep-freezer (-80°C) and changes in concentrations of 55 metabolites were monitored every week for one month. The researchers concluded that samples should be stored in a deep freeze (-80°C) and the number of freeze-thaw cycles should be minimized as much as possible. Bacterial contamination of the urine had significant changes on urinary metabolites and could be controlled by either filtration (MS-based analyses) or by the addition of sodium azide (NMR-based analyses). 

The importance of gut microfloral populations on urine composition has been highlighted by a study in which axenic (germ free) rats were allowed to acclimatize in normal laboratory conditions and their urine biochemical makeup was monitored for 21 days [34]. The combined influence of gut microflora and parasitic infections on urinary metabolite profiles has also been elucidated [35]. 

GC and HPLC methods, not fully investigated, may be used for qualitative monitoring. It may be noted that exposure to certain chemicals, such as parathion, may also produce p-nitrophenol as a urinary metabolite. A screening test for nitrobenzene exposure may be performed by monitoring methe-moglobin in the blood. 

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