Urine excretion pesticide metabolites, exposure

In addition to these calculated estimates of absorption, a specific estimate of absorbed dose can be made by measuring the metabolites of the pesticide in urine. For pesticides on which good data exist on metabolic excretion, it appears that this method is very sensitive. In a study conducted on orchardists (7), metabolites were detected in the urine samples of all workers, and a statistically significant correlation was found between the total 48 hour metabolite output and the total amount of pesticide sprayed. In contrast the same study indicated that the correlation between urinary output and the total spray time was not significant. This supports the point mentioned earlier that it seems reasonable to presume that exposure is related to the total amount available for contact, and that correlating exposure with the spray time may be misleading. 

Biomarkers of Exposure and Effect. Information regarding populations exposed specifically to 2-nitrophenol or 4-nitrophenol is not available. However, data derived from animal studies indicate that unchanged 2-nitrophenol or 4-nitrophenol or the sulfate and/or glucuronide conjugates monitored in the urine represent biomarkers of exposure. The same would probably occur in humans. This assumption is based on studies in populations exposed to the pesticide parathion, of which 4-nitrophenol is a metabolite. Individuals exposed to parathion excreted 4-nitrophenol and conjugates in the urine (Fatiadi 1984). 4-Nitrophenol is also a metabolite of pesticides other than parathion (Fatiadi 1984) and of nitrobenzene (Piotrowski 1967 Robinson et al. 1951b). However, because 2-nitrophenol and 4-nitrophenol and their metabolites are rapidly excreted in the urine, these biomarkers are only valuable in evaluating acute situations, as demonstrated by Arterberry et al. (1961) in humans exposed to parathion. Hence, the development of methods to detect alternative biomarkers, the presence of which in body fluid or tissues can be associated with chronic exposure levels of nitrophenol, would be useful. 

We return, consequently, to the problem of the excretion kinetics of pesticides, the complexity of which may render useless any search for a simple linear correlation between dose and urinary metabolites. Some experimenters have attempted to Investigate this area. Drevenkar et al. (20) studied the excretion of phosalone metabolites In one volunteer. Excretion reached a peak In 4-5 hr., but was not complete In 24 hr. Funckes et al. (42) exposed the hand and forearm of human volunteers to 2% parathlon dust. During exposure, the volunteers breathed pure air and placed their forearm and hand Into a plastic bag which contained the parathlon. This exposure lasted 2 hr. and was conducted at various temperatures. There was an Increased excretion of paranltrophenol with Increasing exposure temperature. More importantly, paranltrophenol could still be detected In the urine 40 hr. post exposure. In another human experiment, Kolmodln-Hedman et al. (43) applied methychlorophenoxy acetic acid (MCPA) to the thigh. Plasma MCPA reached a maximum in 12 hr. and MCPA appeared In the urine for 5 days with a maximum after about 48 hr. Given orally, urinary MCPA peaked in 1 hr. with about 40% of the dose excreted In 24 hr. In a rat experiment, seven different organophosphates at two different doses were fed to two rats per compound (21). The rats were removed from exposure after the third day and blood and urine collected for the next 10 days. 

Applicators, mixers, loaders, and others who mix, spray, or apply pesticides to crops face potential dermal and/or inhalation exposure when handling bulk quantities of the formulated active ingredients. Although the exposure periods are short and occur only a few times annually, an estimate of this exposure can be obtained by quantifying the excreted polar urinary metabolites. Atrazine is the most studied triazine for potential human exposure purposes, and, therefore, most of the reported methods address the determination of atrazine or atrazine and its metabolites in urine. To a lesser extent, methods are also reported for the analysis of atrazine in blood plasma and serum. 

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. 

In two cases of moderate intoxication from mevinphos, urinary excretion of dimethylphos-phate (a metabolite of mevinphos) was almost complete 50 hours after exposure/ Although a number of other organophosphorus pesticides also yield dimethyl phosphate, the presence of significant amounts of this metabolite in the urine may be useful in estimating the absorption of mevinphos. 

The major metabolic route for 2-nitrophenol and 4-nitrophenol is conjugation, with the resultant formation of either glucuronide or sulfate conjugates. Conjugates are more polar than the parent compounds and, therefore, are easier to excrete in the urine. Other possible routes of metabolism include reduction to amino compounds or oxidation to dihydric nitrophenols (catechols). In humans, the evidence is indirect and comes from studies of exposure to the pesticide parathion, of which 4-nitrophenol is a metabolite (Fatiadi 1984). 

The best, but sometimes more difficult, approach would be to measure the amount of pesticide or its metabolites in blood or target tissues (biological monitoring) taken periodically through the exposure period. To derive an accurate estimate of absorbed dose, knowledge of the pharmacokinetics of the pesticide would also be required. In some cases, the absorbed dose can be estimated from the amount of pesticide excreted in saliva, urine and/or feces. 

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