Urine toluene

Side chain oxidation of alkylbenzenes is important in certain metabolic processes One way m which the body rids itself of foreign substances is by oxidation m the liver to compounds that are more polar and hence more easily excreted m the urine Toluene for example is oxidized to benzoic acid by this process and is eliminated rather readily... 

In both humans and animals, toluene is rapidly excreted as both the unchanged compound in expired air and as a metabolite in the urine. Toluene is converted in the liver to water-soluble hippuric acid and conjugated cresols, which are then excreted in the urine. This conversion has been demonstrated in man and animals exposed via inhalation, although it is expected to occur for other exposure routes as well. Another excretion route for toluene is exhalation of the unchanged chemical. This excretion route might be expected to operate for all exposure routes but be more effective for exposures via inhalation. 

Radioactivity Analysis. Samples of urine, feces, and tissues were combusted to COo and analyzed for radioactivity (5). By using this method the recovery of radioactivity from samples spiked with C was 95 dt 5%. To determine the radioactivity expired as CO2, 5-ml aliquots of the solution used to trap the CO2 were added to 15 ml of a scintillation counting solution containing 4 grams 2,5-diphenyloxazole (PPO) and 0.1 grams l,4-bis-2(5-phenyloxazolyl)-benzene (POPOP) per liter of 1 1 toluene 2-methoxyethanol. Samples were counted for radioactivity in a Nuclear Chicago Mark II liquid scintillation counter. Counting eflSciency was corrected by the internal standard technique. 

The first spectrofluorimetric methods reported for the determination of nalidixic acid and its metabolites in biological fluids did not differentiate between nalidixic acid and hydroxynalidixic acid. The determination of free nalidixic acid and the hydroxy-metabolite in human urine plasma and feces was performed by extraction by toluene from acidified biological fluid and subsequent fluorimetric measurement at 325/375 nm of sample re-extracted into aqueous solution.(8) Conjugated nalidixic and hydroxynalidixic acids were determined by acid hydrolysis and then toluene extraction for fluorimetric measurement of the total drug. The conjugated nalidixic acid was then determined by difference. 

Indirect evidence for an effect of co-exposure to acetone on /2-hexane metabolism in humans has been described (Cardona et al. 1996). In this study, the relationship between free and total 2,5-hexanedione (2,5-hexanedione and 4,5-dihydroxy-2-hexanone, See Section 2.7) in urine and workplace air concentrations of /2-hexane, hexane isomers, acetone, and toluene was analyzed in a group of 87 workers. Median /2-hexane concentrations were 47 mg/m3 (range, 4-652 mg/m3 [13 ppm range, 1-185 ppm]) and median acetone concentrations (only 70 of the 87 workers were exposed) were 109 mg/m3 (range,... 

Kawai T, Yasugi T, Mizunuma K, et al. 1993. Comparative evaluation of blood and urine analysis as a tool for biological monitoring of -hexane and toluene. Int Arch Occp Environ Health 65 S123-S126. 

Zhao WY, Misumi J, Yasui T, et al. 1998. Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5-hexanedione concentration in the sciatic nerve, serum, and urine of rats. Int Arch Occup Environ Health 71 236-244. 

Toluene exposure does not result in the hematopoietic effects caused by benzene. The myelotoxic effects previously attributed to toluene are judged by more recent investigations to be the result of concurrent exposure to benzene present as a contaminant in toluene solutions. Most of the toluene absorbed from inhalation is metabolized to benzoic acid, conjugated with glycine in the liver to form hippuric acid, and excreted in the urine. The average amount of hippuric acid excreted in the urine by persons not exposed to toluene is approximately 0.7-1.0 g/1 of urine. ... 

Cresols can enter your body tissues quickly if you breathe air containing cresol gas or mist (droplets of cresol-containing liquid in the air), drink water or eat food that contains cresols, or allow your skin to come into contact with substances that contain cresols. If you live near a hazardous waste site, you might come into contact with cresols by drinking water, touching substances, or breathing in air that contains cresols. Cresols may also be formed in your body from other compounds, such as toluene and the amino acid tyrosine, which is present in most proteins. Most of the cresols that enter your body are quickly changed to other substances and leave your body in the urine within 1 day. More information on how cresols enter and leave your body can be found in Chapter 2. 

Samples of your urine can be tested for the presence of cresols, although this test is not routinely available in hospitals and clinics. This test will not tell you whether or not you will have any adverse health effects. The urine sample would have to be taken within 1 day of your exposure to be valid. Because cresols occur naturally in people, ant at levels that very from one individual to the next, results from tests for cresol exposure should be compared to values obtained from the same individual either before exposure or several days after exposure. Small changes might be caused by variation in daily diet. You should also be aware that an increased presence of cresols in the urine could indicate exposure to toluene, a related compound, rather than cresols. However, toluene exposure would also result in elevated urinary levels of hippuric acid cresol exposure would not. 

Cresols are formed from the commonly found amino acid tyrosine, and occur naturally in human and animal tissues, fluids, and urine. Cresols are also formed as minor metabolites of toluene, and an increased presence of cresol in the body could be due to exposure to this substance. Therefore, even the cresols themselves cannot be considered to be biomarkers of cresol exposure unless very high levels are found. There is some evidence that methemoglobinemia, reduced glutathione levels in red blood cells, and Heinz body formation are associated with oral exposure to cresols in humans (Chan et al. 1971 Cote et al. 1984), but these effects are too general and occur at too high doses to be useful as biomarkers of exposure to cresols. 

Biomarkers of Exposure and Effect. No biomarkers of exposure to cresols have been identified. In fact, even the cresols themselves cannot be considered specific biomarkers for cresol exposure because they are also formed as breakdown products of toluene and tyrosine. However, if toluene exposure could be ruled out, then a high level of cresols or metabolites in the blood or urine would strongly suggest cresol exposure. Distinguishing biomarkers of exposure to cresols would enable early detection of cresol exposure and provide the opportunity for early treatment. One possibility that can be further investigated is Heinz body formation in the blood of exposed humans (Chan et al. 1971 Cote et al. 1984). 

Exposure Levels in Humans. Cresols are naturally occurring substances that are present in human urine (Fiege and Bayer 1987), and data on this are available. Cresols may also be present as a result of the metabolic breakdown of other organic compounds, such as toluene (Needham et al. 1984). As such positive monitoring for cresols in humans does not necessarily mean exposure to them. The ability to rigorously establish cresol exposure levels in humans has yet to be demonstrated. 

Numerous methods for the determination of o-, m-, and p-cresol in urine have appeared in the literature, but none have been standardized. Cresol in urine is often measured to determine exposure to toluene or other aromatic compounds, of which cresol is a metabolite. The analytical methods summarized in Table 6-1 are sufficiently sensitive to detect the individual isomers of cresol at a concentration that may cause concern for human health. Humans normally excrete 16-29 mg of p-cresol daily as a result of the breakdown of tyrosine (Needham et al. 1984), and o-cresol is an indicator of toluene exposure (DeRosa et al. 1987). 

IC can also be used in detection of some acids. Zhao et al. [25] proposed a simple and eco-friendly ion chromatographic method for the determination of Hippuric acid (HA) in human urine (see Figure 12). Hippuric acid is a kind of metabolite of toluene in human body, therefore, HA is a physiological component of human urine if toluene was inhaled. The content of HA in human urine actually is confirmed as a diagnostic marker of exposure to toluene [26]. It has been reported that exposure to high concentrations of volatile organic compounds such as... 

Persson P, Dalene M, Skarping G, et al. 1993. Biological monitoring of occupational exposure to toluene diisocyanate measmement of toluenediamine in hydrolysed urine and plasma by gas chromatography-mass spectrometry. Br J Ind Med 50(12) 1111-1118. 

Amino acids in urine may be preserved by a bacteriostatic such as chloroform or toluene during the 24-h collection. Aliquots of urine should be stored subsequently at -20°C. Heat inactivation at 55°C for 20 min has proven to be effective in suppressing bacterial activity consequently, the sample can be shipped at room temperature. 

If possible, 24-h urine collections should be obtained. This is usually not possible in small infants or those who are physically or mentally handicapped, therefore a random urine sample (10-15 ml) is sufficient. The sample may be stabilised with toluene or chloroform, but thymol and acidification should be avoided. Samples may be sent by normal mail or alternatively deep-frozen on dry ice, and are then stored deep-frozen at -20°C prior to analysis. 

Take 100 pi of plasma/CSF sample, or 50 pi of urine sample in preparation. If smaller amounts of plasma/CSF are available, add water making a total volume of 100 pi, for urine add 50 pi of water. Add 50 pi of saturated NaHC03 solution, 500 pi of toluene and 50 pi of hexafluoroacetylaceton. Derivatise for 2 h at 80°C under continuous stirring. After derivatisation, allow the vials to cool and pipette 100 pi of the toluene layer (urine/plasma) or 300 pi of the toluene layer (CSF) into a clean tube and blow to dryness at 40°C using nitrogen. To derivatise the carboxylic groups of... 

To circumvent this bioactivation pathway, a more easily oxidizable C-H bond can be included in the molecule, such as a benzylic methyl group. Thus, toluene, is significantly less toxic than benzene since its major CYP metabolite is benzyl alcohol, which is converted to benzoic acid by ALDH. Benzoic acid is conjugated with glycine and eliminated in the urine as hippuric acid, which is much less toxic than the metabolites of benzene... 

During inhalation exposure of human volunteers to low levels of toluene (200-300 mg/mty, approximately 50% of the inhaled toluene was absorbed (Lbf et al., 1993). Such studies at low toluene exposure are complicated by the presence of toluene from other sources, in blood or in urine (Pierce et al., 1996). If the deuterated [ Hgjtoluene is used for exposure, this problem is avoided [but an isotope effect may reduce the rate of the metabolism of deuterated toluene compared to normal toluene, possibly by 30-50%]. When toluene is administered orally, it is virtually completely absorbed from the gastrointestinal tract (Baelum et al., 1993). 

Several authors have pointed out that the urinary excretion of hippurate is a poor indicator of exposure to toluene at 200 ppm [760 mg/m ] or lower (Jonai Sato, 1988 Too et al., 1991 Pierce et al., 1996). Therefore, data on ethnic differences in hippurate or cresol excretion in urine at these low exposure levels (e.g., Inoue et al., 1988) are of doubtful significance. Toluene level in expired air may be a more reliable parameter (Foo et al., 1991). Although at the level of the individual, data on urinary hippurate cannot be reliably used to estimate low toluene exposures, they can be used at the group level to establish whether at a certain location the toluene exposure remained below a particular threshold (Lauwerys, 1983). 

Tardif et al. (1992, 1993 a, 1997) have developed a physiologically based toxicokinetic model for toluene in rats (and humans—see Section 4.1.1). They determined the conditions under which interaction between toluene and xylene(s) occurred during inhalation exposure, leading to increased blood concentrations of these solvents, and decreased levels of the hippurates in urine. Similar metabolic interactions have been observed for toluene and benzene in rats (Purcell et al., 1990) toluene inhibited benzene metabolism more effectively than the reverse. Tardif et al. (1997) also studied the exposure of rats (and humans) to mixtures of toluene, we/a-xylene and ethylbenzene, using their physiologically based pharmacokinetic model the mutual inhibition constants for their metabolism were used for simulation of the human situation. 

The toxicokinetics of 2,4- and 2,6-toluenediisocyanates in 11 chronically exposed workers at two flexible foam polyurethane production plants have been reported. The toluene diisocyanate concentrations in air varied between 0.4 and 4 pg/m in one plant and in the other between 10 and 120 p-g/m. In one of the plants, the plasma 2,4-toluene diamine levels were 0.4-1 ng/mL before a 4-5-week holiday and 0.2-0.5 ng/mL afterwards. The corresponding plasma levels of 2,6-toluene diamine were 2-6 and 0.5-2 ng/mL, respectively. In the other plant, the plasma 2,4-toluene diamine concentrations were 2-23 ng/mL before the holiday and 0.5-6 ng/mL afterwards and those of 2,6-toluene diamine were 7-24 ng/mL before and 3-6 ng/mL afterwards. The plasma concentrations of 2,4-toluene diamine were 2-24 ng/mL before a 12-day holiday, and 1-14 ng/mL afterwards. The corresponding values for plasma 2,6-toluene diamine were 12-29 and 8-17 ng/mL, respectively. The urinary elimination rates for 2,4-toluene diamine before the holiday were 0.04-0.54 and 0.02-0.18 pg/li afterwards. The corresponding values for 2,6-toluene diamine were 0.18-0.76 pg/li before and 0.09-0.27 pg/h after the holiday. The half-life in urine ranged from 5.8 to 11 days for 2,4- and... 

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