Urine excretion monitoring

Calculation of ID using biological monitoring techniques requires the knowledge of the pharmacokinetics of the parent pesticide in laboratory animals. This will allow the use of the parent or its urine metabolite(s) to calculate the total amount of the parent that had been absorbed through the skin of the test subject. The amount of the residue in the urine should be corrected for any molecular weight differences between the parent and its urine metabolite(s) and also corrected for daily urine excretion volumes based on creatinine analysis of the urine samples. 

Dopamine Low dose (0.5-3.0 xg/min per kg body weight) Stimulation of the dopamine D, receptors on intrarenal vessels Dilatation of renal arterioles leading to a selective increase in RBF Increases urine excretion of Na and water May increase GFR Constant i.v. infusion required Close patient monitoring required (in hospital treatment) May induce cardiac arrhythmias Greater risk of inducing arrhythmias... 

No detailed studies were located regarding excretion in humans following oral MBOCA exposure. After an acute occupational exposure to molten MBOCA, one worker complained of burning eyes and face. Hot, liquid MBOCA was sprayed over his face and some entered his mouth (Hosein and Van Roosmalen 1978). The worker s urine was monitored for MBOCA excretion over a 3-week period. MBOCA was found to be rapidly excreted during the first 18 hours following exposure, reaching a maximum concentration of 3.6 mg/L 6 hours later, (24 hours post-exposure), the urine MBOCA level was down to 0.03 mg/L. At 3 weeks, only trace amounts of MBOCA were detected in urine (Hosein and Van Roosmalen 1978). 

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

The use of the methods for monitoring metabolites of trichloroethylene in blood and urine is, however, rather limited since the levels of TCA in urine have been found to vary widely, even among individuals with equal exposure (Vesterberg and Astrand 1976). Moreover, exposure to other chlorinated hydrocarbons such as tetrachloroethane, tetrachloroethylene, and 1,1,1-trichloroethane would also be reflected in an increase in urinary excretion of TCA. In addition, there may be sex differences regarding the excretion of trichloroethylene metabolites in urine since one experiment shows that men secrete more trichloroethanol than women (Inoue et al. 1989). The use of the level of trichloroethylene adduction to blood proteins as a quantitative measure of exposure is also possible, although obtaining accurate results may be complicated by the fact that several metabolites of trichloroethylene may also form adducts (Stevens et al. 1992). 

Since collection of all urine from volunteers over a 24-h period may not be possible, creatinine analysis of the composite total urine sample is recommended. This will allow for a more scientific analysis and interpretation of the excretion pattern presented by the worker during the course of the monitoring. 

Besides alkylphosphates, OP metabolism gives rise to the production of other metabolites that can be used as exposure markers (Table 4). Unchanged OP compounds in blood or urine can also be measured to confirm exposure (Table 4), but this method is of limited use for routine biological monitoring of occupational exposure, as OP compounds are rapidly excreted in urine. Moreover, most OP pesticides are unstable, and, with a few exceptions, they are not detectable in biological specimens after a few hours. So far, the measurement of unchanged compounds in biological fluids has been performed primarily for research purposes and has limited practical applicability. 

Dithiocarbamates are chemically characterized by the presence of metals in the molecule (iron, manganese, zinc, etc.) therefore, the measurement of these metals in urine has been proposed as an alternative approach to monitor exposure. For instance, increased urinary excretion of manganese has been reported in workers exposed to mancozeb (Canossa et al., 1993). Available data are at present insufficient to confirm the possibility of using metals as biomarkers of human exposure to DTC. 

Diquat and paraquat are quaternary ammonium compounds largely used as contact herbicides and crop desiccants. When systemic absorption occurs, paraquat and diquat are rapidly distributed into the body. Paraquat primarily accumulates in the lungs and kidneys, while the highest diquat concentrations have been found in the gastrointestinal tract, liver, and kidneys (WHO, 1984). Urine is the principal route of excretion for both diquat and paraquat, which are primarily eliminated as unmodified compounds. Occupationally exposed workers can be monitored by measuring paraquat and diquat concentrations in urine samples (Table 6). Blood concentrations are useful to monitor acute poisoning cases. 

Some OC pesticides can induce the hepatic microsomal enzyme system (Kay, 1970). Tests measuring functions related to these enzymes, such as f.i. D-glucaric acid and 6-b-hydroxicortisol excretion in urine, can be applied to monitor occupational OC exposure. 

Dose- related increases in thiocyanate were observed, indicating that cyanide is liberated with the metabolism of acrylonitrile. In a study with human volunteers under controlled conditions, 2-cyanoethylmercapturic acid (CMA) was monitored in urine as an indication of exposure. On average, 22% of the absorbed acrylonitrile was metabolized to CMA however, considerable individual variability was observed. The CMA excretion ranged from 13% to 39% of the absorbed dose (Jakubowski et al. 1987). 

Aniline is rapidly and extensively metabolized following oral administration. In the pig and sheep, approximately 30% of a 50-mg/kg dose of 14C-labeled aniline was excreted in the urine, as measured by 14C activity, within 3 h after administration, whereas approximately 50% of the dose was excreted in rats. Within 24 h, more than half the administered dose was excreted by pigs and sheep and 96% of the dose was excreted by rats. Fecal radioactivity was low. A-acetylated metabolites accounted for most of the excretion—/V-acetyl-/>-aminophenyl glucuronide being the primary metabolite in sheep and pig urine and /V-acetyl-/>-aminophenyl sulfate being the primary metabolite in the rat (Kao et al. 1978). Biologic monitoring of workers exposed to aniline showed that /i-aminophenol constituted 15-55% of the parent compound in the urine the o- and ra-isomers were also formed (Piotrowski 1984). 

The activity of the renin-angiotensin system is reduced with age (Muhlberg and Platt 1999). The ability of the kidney to concentrate urine maximally after water deprivation decreases with age, as does the ability to excrete a water and salt load, particularly during the night. Nocturnal polyuria is common in the elderly (Lubran 1995). Diuretics are commonly used in the elderly. There is an increased risk for hypokalemia and hyponatremia from diuretics in the elderly (Passare et al. 2004). Electrolyte disturbances may also be caused by several types of drugs in the elderly and it is important to monitor serum electrolyte levels in the elderly. Treatment with... 

Metabolism in the rat is qualitatively similar to that in humans. Four male and four female Wistar rats were exposed individually to 14C-labeled HFC134a at 10,000 ppm for 1 h (Ellis et al. 1993). Atmospheres were monitored with a gas chromatograph. After exposure, urine and feces were collected at 6 h intervals up to 24 h and every 24 h for up to 5 d thereafter. Approximately 1% of the inhaled dose was recovered in urine, feces, and expired air of that 1%, approximately two-thirds was exhaled within 1 h postexposure as unchanged HFC-134a. Exhaled C02 was the primary metabolite and accounted for approximately 0.22% and 0.27% of the inhaled dose in males and females, respectively. Excretion in the urine and feces occurred within 24 h and accounted for 0.09% and 0.04% of the inhaled dose, respectively. The only metabolite identified in urine was trifluoroacetic acid. At sacrifice, 5 d postexposure, radioactivity was uniformly distributed among tissues and accounted for 0.14-0.15% of the inhaled dose. The average total metabolized dose in male and female rats was 0.37% of the inhaled dose. 

The gross appearance (macrostructure) of a kidney is recognizable to most people, even those who have no detailed knowledge of mammalian physiology. Furthermore, many people would be able to state that the role of the kidneys is to excrete waste materials in the urine. What is less likely to be so widely appreciated is the importance and complexity of action of the kidney in regulating the chemical composition and volume of the body fluids, a key aspect of homeostasis. Receiving approximately 25% of cardiac output per minute, the kidneys are adapted to monitoring blood pressure. 

Biological monitoring for exposure to phenol is possible by measuring blood or urine levels of the parent compound. However, it should be noted that phenol and metabolites of phenol may also come from other sources. For example, phenol is a metabolite of benzene and of protein metabolism. Urine samples taken from male workers employed in the distillation of high-temperature phenolic fractions of tar revealed a phenol excretion rate of 4.20 mg/hour compared to a control rate of 0.53 mg/hour for non-exposed workers (Bieniek 1994). Samples were taken 4 hours into the workers workday, but the worker exposure levels were not reported. 

A number of clinical tests are available to detect kidney damage. The clinician examining a patient or the toxicologist monitoring an animal toxicity stndy collects urine and blood samples. Indications of kidney damage (which, of course, for the human patient could be related to many factors other then chemical toxicity) include urinary excretion of excessive amonnts of proteins and glucose, and excessive levels in the blood of unexcreted waste products such as urea and creatine. A number of additional kidney function tests are available to help pin down the location of kidney dysfunction. 

Excretion of radioactivity in mice and rats was monitored for 48 hours following exposure to " C-labeled chloroform (Corley et al. 1990). In general, 92-99% of the total radioactivity was recovered in mice, and 58-98% was recovered in rats percentage of recovery decreased with increasing exposure. With increasing concentration, mice exhaled 80-85% of the total radioactivity recovered as " C-labeled carbon dioxide, 0.4-8% as " C-labeled chloroform, and 8-11 and 0.6-1.4% as urinary and fecal metabolites, respectively. Rats exhaled 48-85% of the total radioactivity as " C-labeled carbon dioxide, 2-42% as " C-labeled chloroform, and 8-11 and 0.1-0.6% in the urine and feces, respectively. A 4-fold increase in exposure concentration was followed by a 50- and 20-fold increase in the amount of exhaled, unmetabolized chloroform in mice and rats, respectively. 

Ekstrom T, Stahl A, Sigvardsson K, et al. 1986. Lipid peroxidation in vivo monitored as ethane exhalation and malondialdehyde excretion in urine after oral administration of chloroform. Acta Pharmacol Toxicol 58 289-296. 

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