Exposure to toluene increases the urinary excretion of D-glucaric acid.

Workers at a printing plant exposed to low concentrations of toluene (43-401 mg/m3, median 155 mg/m3) had increased urinary D-glucaric acid (3.55-5.12 mmol/mol creatinine) excretion at the end of the shift compared with controls (2.45-3.35 mmol/mol creatinine). No increase was found after the summer holiday (1.92-2.89 mmol/mol creatinine) but excretion had increased two weeks later (4.05-5.55 mmol/mol creatinine). These changes in the excretion of D-glucaric acid were not correlated to levels of exposure, to changes of urinary hippuric acid and o-cresol half lives (three to eight hours), nor to o-cresol/hippuric acid concentration ratios when measured at the end of daily exposure. Since a significant intra and interindividual variability of urinary D-glucaric acid was found in all groups, urinary D-glucaric acid excretion is suitable to monitor group but not individual exposure.     

Exposure to toluene and urinary hippuric acid excretion in a group of heliorotagravure printing workers

Summary The influence of a number of factors possibly affecting the relation between urinary hippuric acid excretion and the exposure level to toluene was studied in a population of heliorotagravure printers. It was observed that the hippuric acid excretion rates, after 4 h and 8 h from the onset of the exposure, were in better agreement with the average toluene concentrations in work room air than either the urinary metabolite concentrations alone or corrected for urine density. Apart from differences in exposure level, a substantial proportion of the interindividual variability in hippuric acid excretion could be explained by differences in energetical load during the exposure. It was thereby not possible to elucidate the full extent to which this factor influences the metabolite excretion.In good agreement with previous experimental findings, the hippuric acid excretion rate apparently does not depend on the time of urine sampling during the exposure, provided that at least 4 h have elapsed from the onset.     

Behaviour of urinary D-glucaric acid excretion in surgical patients and anaesthesiology staff acutely exposed to isoflurane and nitrous oxide.

Liver function abnormalities have been observed in humans exposed to anaesthetics inhalation. Furthermore, experimental studies have revealed changes in microsomal enzyme activity caused by inhalation of a variety of anaesthetics. The study was designed to assess liver microsomal enzyme function by means of a simple non-invasive test, i.e., measurement of urinary D-glucaric acid (UDGA) excretion. Three groups of selected subjects were examined: (i) 20 patients undergoing orthopaedic surgery receiving an anesthetic mixture, (ii) 18 workers of an Anesthesiology and Intensive Care Unit, occupationally exposed to anesthetics, (iii) 16 controls. Both in the patients and anesthesiology staff, the post-operative UDGA mean values were significantly increased compared to the pre-operative values. The study shows that the behaviour of UDGA excretion is similar in patients and in anaesthesiology staff. Although it is not possible to clarify the mechanism involved, this finding is regarded as a response of the liver to anaesthetics administration in patients and to both environmental pollution and occupational stress in hospital staff.     

Caffeine consumption and vegetarian diets affect D-glucaric acid excretion in man

The urinary excretion of D-glucaric acid (DGA) has been used as a nonspecific measure of the induction of hepatic enzymes associated with drug metabolism in man. A survey of 124 nonmedicated men (18–56 years of age), who kept a 5-day food, beverage, and drug intake record and collected their total urinary output for the last three days of the five, was conducted to assess the relationship between DGA excretion and various dietary factors. Eighteen nonmedicated healthy women collected the same data, but started on the eighth day from the commencement of menstruation. DGA was determined by an enzymatic assay and recorded as umoles D-glucaro-1,4-lactone/g creatinine. A positive association was found between total DGA excreted and the use of marijuana, caffeine, and tobacco products, the heaviest users excreting higher levels of urinary DGA than the moderate or low users of the same substance (P<0.05). Analysis of variance of mean DGA excretion also revealed differences (P<0.05) between females (17.0±3.7) and males (14.3±5.2); male vegetarians (17.4±5.5) and nonvegetarians (13.9±5.1); and female vegetarians (19.8±4.6) and nonvegetarians (16.2±3.1). Ethanol consumption did not relate to increased DGA excretion in either sex. Multiple regression analysis revealed that vegetarianism and caffeine consumption were the two strongest predictors of DGA excretion accounting for 32 percent of the total variance (P<0.005), while ethanol and marijuana consumption affected DGA the least. These results indicate that dietary and environmental factors may cause important changes in DGA excretion, and these changes may identify dietary inducers of hepatic enzymes associated with drug, xenobiotic and carcinogen biotransformations in humans.     

Toxicokinetics of toluene and urinary excretion of hippuric acid after human exposure to 2H8-toluene.

Nine male volunteers were exposed to 2H8-toluene (200 mg/m3 for two hours during a workload of 50 W) via inspiratory air with the aid of a breathing valve and mouthpiece. Labelled toluene was used to differentiate between hippuric acid originating from exposure to toluene and hippuric acid normally excreted in urine. The total uptake of toluene was 2.2 (standard deviation (SD) 0.2) mmol, or 50% of the amount inhaled. Four hours after the end of exposure 1.4 (SD 0.3) mmol or 65% of the total uptake had been excreted in urine as 2H-hippuric acid and 20 hours after the end of exposure the cumulative excretion of 2H-hippuric acid was 1.8 (SD 0.3) mmol, or 78% of the total uptake. By contrast the cumulative excretion of labelled plus unlabelled hippuric acid exceeded the total uptake of toluene already after four hours. The excretion rate of 2H-hippuric acid was highest, about 5 mumol/min, during exposure and the SD between the subjects was low. The background concentrations of unlabelled hippuric acid in urine were high, however, and there were large differences between subjects. These findings confirm earlier indications that for low exposure, urinary hippuric acid concentration cannot be used for biological monitoring of exposure to toluene.     

Exposure and urinary excretion of aluminum during welding

The exposure and urinary excretion of aluminum was studied among three previously unexposed volunteers and six welders exposed to welding fumes containing aluminum. The aluminum concentrations in air and urine were determined. The urinary aluminum concentrations rose rapidly in volunteers exposed only for 1 d and returned to the preexposure levels with an estimated half-time of about 8 h. The welders were monitored for one workweek. During the subsequent weekend a decrease in the urinary concentrations occurred in the three welders exposed for two years or less, but such a decrease was not observed among welders exposed for more than 15 years. The urinary concentrations of aluminum were dependent partly on the level of current exposure and partly on the duration of exposure. The data suggest that welders exposed to welding fumes containing aluminum may retain some of the inhaled metal fume for extended periods of time.     

Advances in evaluating liver response to operating theatre work: urinary D-glucaric acid as an index of effect

The contribution of operating theatre work to specific diseasesis still a controversial matter involving a variety of riskfactors. The concept that the liver plays a central role inanaesthetics biotransformation stimulated numerous studies aimedat establishing the occurrence of liver changes and at verifyingthe relationship between liver disease and anaesthetics. Theliver microsomal enzyme system has received particular attentionin order to clarify the mechanism involved in anaesthetics hepatotoxicityand an increased microsomal activity has been detected in experimentalconditions and in humans. In particular, a significant increasein the excretion of urinary D-glucaric acid (UDGA) in subjectsoccupationally exposed to anaesthetic mixture was observed.Nevertheless, few results exist about the relationship betweenUDGA increase and environmental anaesthetic concentration, andmechanisms responsible for UDGA increase still need to be clarified.Attention is focused, however, on the possibility of using UDGAas an index reflecting an adaptation effect (rather than aninjury effect), which may represent a more adequate approachfor evaluating any change related to working in the operatingtheatre.     

Urinary excretion of hippuric acid and m-methylhippuric acid after administration of toluene and m-xylene mixture to rats

Summary Male Wistar rats were injected intraperitoneally (i.p.) with toluene alone, m-xylene alone, and in combination with both of them. Urinary excretion of hippuric acid or m-methylhippuric acid of rats injected with solvents of various concentrations was investigated from the end of the injections up to 48 h later, at appropriate intervals. The amounts of increased excretion of HA and m-MHA in 0–24h urine samples of the rats given simultaneous injections of toluene and m-xylene were not lower than those of the rats given single injections of toluene alone or m-xylene alone, in the same amount. Data indicated that simultaneous administration of toluene and m-xylene did not significantly interfere with the metabolism of toluene or m-xylene.Read before the 50th Annual Meeting of Japan Industrial Health Association, Kurume, April 5, 1977The work was supported in part by grant No. 357188 of the Ministry of Education Agency     

Elevated urinary excretion of beta-aminoisobutyric acid and exposure to inorganic lead

beta-Aminoisobutyric acid (beta-AIB), a normal degradation product of thymine, a constituent of DNA and, to a lesser extent, of transfer RNA, is excreted in low levels in human urine. We found that a group of iron workers occupationally exposed to inorganic lead excreted high levels of urinary beta-AIB. Elevated urinary excretion of beta-AIB was also observed in marmosets, Callithrix jacchus, that received lead acetate in drinking water. Our results suggest that increased urinary excretion of beta-AIB could stem from damage to DNA on exposure to lead.     

Urinary hippuric acid and orthocresol excretion in man during experimental exposure to toluene.

It is not known whether urinary excretion of hippuric acid (HA) or orthocresol (O-Cr) is to be preferred for the biological monitoring of workers with occupational exposure to toluene. To study this, 42 printing trade workers with more than 10 years' exposure to a mixture of organic solvents including toluene (0-20 ppm) and 43 control subjects matched by age, smoking habits, and living accommodation were investigated. Each matched pair was randomised to an experimental exposure of either 100 ppm or 0 ppm toluene for 6.5 hours under controlled conditions in an exposure chamber. Urinary excretion of HA and O-Cr was determined by high pressure liquid chromatography from samples obtained before exposure, during the first three hours, and during the last 3.5 hours of exposure. No difference in HA and O-Cr excretion was found between printing trade workers and controls. The median O-Cr excretion increased 29 times during exposure, whereas the HA excretion increased only five times. Thus only 3% of the O-Cr excretion originated from other sources than toluene whereas the corresponding value for HA was 19%. Standardisation of the concentrations of HA and O-Cr in relation to urinary creatinine reduced the relative variation by 29% and 56% respectively. This was not reduced further by expressing the excretions as average excretion rates based on total volume of urine collected. Background urinary O-Cr excretion was three to four times higher among smokers than non-smokers, probably due to the content of O-Cr in cigarettes. The O-Cr excretion in unexposed smokers was, however, 10 times lower that that of the non-smokers during the end of the experimental exposure to 100 ppm toluene.