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Biomedical subjects

B Akesson

Publications and source records attributed to B Akesson.

At least 37 records · Page 2Linked to original sources

Suprathreshold intensity and annoyance reactions in experimental challenge to toluene and n-butyl acetate among subjects with long-term solvent exposure.

OBJECTIVES: This study explores reactions to low-level chemical challenge, aiming at the development of test procedures for assessing individual sensitivity to smells and chemicals. METHODS: Subjects with symptoms and neuropsychological test results compatible with toxic encephalopathy type 2A (TE-2A) and 2B (TE-2B) and unexposed referents (N=12 in each group) were challenged in an exposure chamber. Toluene exposure was started at 11 mg/m3, and it followed a geometric progression scale with a ratio of 2, until reaching 180 mg/m3. In a counterbalanced design, the subjects were similarly exposed to n-butyl acetate starting at a concentration of 14 mg/m3 and increasing to 228 mg/m3. At each exposure level, smell intensity was measured on a 7-step category scale. Mucous membrane irritation and annoyance reactions were rated on visual analogue scales. RESULTS: Both TE groups showed high sensitivity to the low-level solvent challenge, which provoked immediate annoyance and fatigue reactions. In particular the TE-2B group related smell intensity to various annoyance dimensions during exposure to n-butyl acetate, a pattern not observed during toluene exposure. The reference group clearly separated smell intensity and annoyance reactions in both exposure conditions. CONCLUSIONS: The reaction of the TE cases suggests that chemical sensitivity can be distinguished from normal annoyance reactions by the inability to differentiate between smell intensity and an experience of irritation from mucous membranes in air concentrations well below the trigeminal irritation threshold level. Fatigue coreactivity in challenges to single substances below the neurotoxic level may also be important.

Acetates↗

Determination of N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide in human urine and plasma.

A method for determination of N-methylsuccinimide (MSI) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in human urine and of MSI in human plasma was developed. MSI and 2-HMSI are metabolites of the widely used organic solvent N-methyl-2-pyrrolidone (NMP). MSI and 2-HMSI were purified from urine and plasma by C8 solid-phase extraction and analysed by gas chromatography-mass spectrometry in the negative-ion chemical ionisation mode. The intra-day precisions in urine were 2-6% for MSI (50 and 400 ng/ml) and 3-5% for 2-HMSI (1000 and 8000 ng/ml). For MSI in plasma it was 2% (60 and 1200 ng/ml). The between-day precisions in urine were 3-4% for MSI (100 and 1000 ng/ml) and 2-4% for 2-HMSI (10,000 and 18,000 ng/ml) and 3-4% for MSI in plasma (100 and 900 ng/ml). The recoveries from urine were 109-117% for MSI (50 and 400 ng/ml) and 81-89% for 2-HMSI (1000 and 8000 ng/ml). The recovery of MSI from plasma was 91-101% (50 and 500 ng/ml). The detection limits for MSI were 3 ng/ml in urine and 1 ng/ml in plasma and that of 2-HMSI in urine was 200 ng/ml. The method is applicable for analysis of urine and plasma samples from workers exposed to NMP.

Drug Stability↗

Determination of 5-hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide in human urine.

A method for simultaneous determination of 5-hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide in urine is described. These compounds are metabolites of N-methyl-2-pyrrolidone, a powerful and widely used organic solvent. 5-Hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide were purified from urine by adsorption to a C8 solid-phase extraction column and then elution by ethyl acetate-methanol (80:20). After evaporation, the samples were derivatised at 100 degrees C for 1 h by bis(trimethylsilyl)trifluoroacetamide. Ethyl acetate was then added and the samples were analysed by gas chromatography-mass spectrometry in the electron impact mode. The extraction recovery for 5-hydroxy-N-methylpyrrolidone was about 80% while that for 2-hydroxy-N-methylsuccinimide was about 30%. The intra-day precision for 5-hydroxy-N-methylpyrrolidone was 2-4% and the between-day precision 4-21% (4 and 60 microg/ml). The intra-day precision for 2-hydroxy-N-methylsuccinimide was 4-8% and the between-day precision 6-7% (2 and 20 microg/ml). The detection limit was 0.2 microg/ml urine for both compounds. The method is applicable for analysis of urine samples from workers exposed to N-methyl-2-pyrrolidone.

Air Pollutants, Occupational↗

Extracellular glutathione peroxidase and ascorbic acid in aqueous humor and serum of patients operated on for cataract.

Patients operated on for cataract (32 men/75 women, aged 50-93 years) were studied with respect to antioxidative agents in aqueous humor and serum. Extracellular glutathione peroxidase (eGSHPx) was demonstrated in aqueous humor for the first time by a radioimmunoassay, the concentration of eGSHPx being 0.66(0.18) mg/l (mean(S.D.)). The concentration of eGSHPx in serum was 3.81(0.84) mg/l, and its level in aqueous humor was 18(7)% of that level. Serum selenium had positive correlations with both serum eGSHPx (r = 0.34, P < 0.001) and aqueous humor eGSHPx (r = 0.25, P = 0.011). However, there was no relation between the concentrations of eGSHPx in aqueous humor and in serum, suggesting that the maintenance of eGSHPx levels in the two fluids is controlled by different mechanisms beside selenium status. There was an inverse correlation between age and serum eGSHPx but not with aqueous humor eGSHPx. The concentration of ascorbic acid in aqueous humor was 2.04(0.58) mmol/l, and it was closely correlated to the level of ascorbic acid in serum (0.052(0.032) mmol/l), r = 0.58 (P < 0.001). The ratio between the level of ascorbic acid in aqueous humor and that in serum was 39(17). There was no significant difference among patients with nuclear (n = 39), cortical (n = 20), posterior-subcapsular (n = 23) or mixed (n = 23) lens opacity with respect to levels of eGSHPx and ascorbic acid in serum and aqueous humor. Since serum ascorbic acid is related to ascorbic acid intake, its association to aqueous humor ascorbic acid indicates that dietary habits are important for maintaining that level which could play an important role in protecting ocular tissue against oxidative damage. The role of eGSHPx secreted into aqueous humor in the oxidant defence system needs further study.

Aged↗

The crystal structure of seleno-glutathione peroxidase from human plasma at 2.9 A resolution.

Glutathione peroxidase belongs to the family of selenoproteins and plays an important role in the defense mechanisms of mammals, birds and fish against oxidative damage by catalyzing the reduction of a variety of hydroperoxides, using glutathione as the reducing substrate. However, the physiological role of human plasma glutathione peroxidase remains unclear due to the low levels of reduced glutathione in human plasma and the low reactivity of this enzyme. The crystal structure of human plasma glutathione peroxidase was determined by Patterson search methods using a polyalanine model modified from the known structure of bovine erythrocyte glutathione peroxidase. The structure was refined to a crystallographic R-factor of 0.228 (R(free) = 0.335) with I > 2sigma(I) reflections in the resolution range of 8 to 2.9 A. The asymmetric unit contains a dimer. Tetramers are built up from dimers by crystallographic symmetry. The subunit structure of the plasma enzyme shows the typical structure motif of the thioredoxin fold consisting of a central beta-sheet and several flanking alpha-helices. The active site selenocysteine residue is situated in the loop between beta1 and alpha1 and is located in a pocket on the protein surface. The overall structure of the human plasma enzyme is similar to that of the bovine erythrocyte enzyme. The main differences in their subunit structures are an extended N terminus and the possible existence of a disulfide bridge in the plasma enzyme. Compared to the bovine erythrocyte enzyme, a number of residues in the active site are mutated or deleted in the plasma enzyme, including all the residues that were previously suggested to be involved in glutathione binding. The observed structural differences between the two enzymes suggest differences in substrate binding and specificity.

Amino Acid Sequence↗

Skin absorption of the industrial catalyst dimethylethylamine in vitro in guinea pig and human skin, and of gaseous dimethylethylamine in human volunteers.

OBJECTIVES: The aims of the study were three-fold: to assess the skin uptake of the industrial catalyst dimethylethylamine (DMEA) (a) in vitro from water solutions by fresh guinea-pig and human skin specimens, (b) in gaseous form in vivo in human volunteers, and (c) to estimate the relevance of the uptake as an occupational hazard. METHODS: Specimens from the in vitro and in vivo experiments were analysed by gas chromatography using a nitrogen-sensitive detector. DESIGN: DMEA, diluted with water or isotonic saline solution was applied to fresh human or guinea-pig skin, mounted in Teflon flow-through cells with a perfusion fluid flow rate of 1.5 ml/h, samples being collected at 2-h intervals for 48 h. Three healthy male volunteers each had their right forearm exposed (in a Plexiglass chamber) for 4 h to DMEA at each of three different levels (250, 500 and 1000 mg/m3 air). Urine was collected up to 24 h after the start of each experiment. RESULTS: DMEA penetrated both guinea-pig and human skin. The median steady-state flux and permeability coefficient (Kp) values, were 0.009 mg/cm2 x h and 0.001 cm/h, respectively, for guinea-pig skin, and 0.017 mg/cm2 x h and 0.003 cm/h, respectively, for human skin. The median uptake in the three volunteers at the different DMEA exposure levels (250, 500 or 1000 mg/m3) was 44, 64 and 88 micrograms, respectively. The median Kp for all experiments was 0.037 cm/h. CONCLUSION: Uptake of DMEA through the skin is of far less importance than simultaneous uptake via the airways. Thus, the amount of DMEA excreted in urine is a variable of limited use for the purposes of biological monitoring. Although a wide range of Kp values was obtained in the in vitro experiments, both for guinea-pig and human skin, there was no marked difference in median Kp values between the two types of skin. The Kp values were lower than those obtained for human forearm skin in vivo. However, future studies of other tertiary aliphatic amines may show the in vitro method to yield values predictive of those obtained in in vivo studies.

Adult↗

Experimental human exposure to N,N-dimethylbenzylamine: generation of a controlled atmosphere and biological monitoring.

The aim of the present study was to develop a method for generation of dimethylbenzylamine (DMBA) atmospheres in an exposure chamber and to investigate the possibility of using urinary DMBA metabolites for biological monitoring of exposure to DMBA. A DMBA atmosphere was generated by use of the gas-permeation principle. Six health male volunteers were exposed for 8 h to DMBA at air levels of 20, 45, and 80 microns/m3. Air levels of DMBA were analyzed by gas chromatography (GC). The total urinary amount of DMBA (U-SumDMBA; DMBA and metabolites that can be reduced to DMBA, e.g., DMBAO) was analyzed using GC-mass spectrometry (MS). The exposure chamber maintained very low (0-130 micrograms/m3) and steady concentrations for several weeks. DMBA uptake by inhalation was 76%. The amine was quickly distributed and biotransformed to nearly 100%. DMBA was eliminated in the urine with a half-time of 4.3 h. More than 50% was eliminated within 2 h of exposure. However, at all exposure levels the subjects continued to excrete DMBA the next morning. There was a significant correlation between the exposure to DMBA and the U-SumDMBA. Thus, U-SumDMBA may become an important biomarker for monitoring of industrial exposure to DMBA.

Adult↗

Experimental exposure of male volunteers to N-methyl-2-pyrrolidone (NMP): acute effects and pharmacokinetics of NMP in plasma and urine.

OBJECTIVES: To study the acute effects of exposure to the increasingly used solvent, N-methyl-2-pyrrolidone (NMP) in male volunteers. Further, to determine the NMP concentration in plasma and urine during and after the exposure. METHODS: Six male volunteers were exposed for eight hours on four different days to 0, 10, 25, and 50 mg/m3 NMP. Plasma was collected and urine was sampled during and after the exposure. Changes in nasal volume were measured by acoustic rhinometry and in airway resistance by spirometry. RESULTS: The eight-hour experimental exposure to 10, 25, and 50 mg/m3 did not induce discomfort to eyes or upper airways. Acute changes in nasal volume were not found, and no changes in the spirometric data could be registered. The elimination curves suggested a non-linear pattern and at the end of exposure showed mean (range) half lifes of NMP in plasma of about 4.0 (2.9-5.8) hours and in urine 4.5 (3.5-6.6) hours. The unmetabolised NMP found in urine samples collected during exposure and at the subsequent 44 hours corresponded to about 2% of the calculated absorbed dose. At the end of the exposure there was a close correlation between exposures and the plasma concentration and urinary excretion of NMP. CONCLUSIONS: NMP was absorbed through the respiratory tract and readily eliminated from the body, mainly by biotransformation to other compounds. Exposure to 10, 25, or 50 mg/m3 NMP did not cause nose, eye, or airway irritation. Thus, NMP is a mild irritant.

Acute Disease↗

Metachromatic cells and eosinophils in the nasal mucosa and N,N-dimethylbenzylamine exposure.

Six healthy non-atopic male volunteers participated in a dose-response study of N,N-dimethylbenzylamine (DMBA), which is a reactive chemical used in epoxy systems. The effects on the nasal mucosa after inhalation of 0, 20, 45, 80 and 120 microg/m3 were studied by means of symptom recordings, acoustic rhinometry, nasal lavages and nasal cytology processed for light microscopy of metachromatic cells (MC) and eosinophils (EOS). Although only minor symptoms were provoked, the numbers of MC and Eos tended to increase in a dose-response fashion after inhalation of the chemical. No signs of degranulation of the cells were found, as the levels of tryptase and eosinophil cationic protein in the nasal lavages remained low at all DMBA exposure levels. We therefore conclude that a reactive chemical such as DMBA can influence MC and Eos in the nasal mucosa even at low dose levels without causing significant clinical symptoms.

9,10-Dimethyl-1,2-benzanthracene↗

Major metabolic pathway for N-methyl-2-pyrrolidone in humans.

The aim was to study the metabolic pathway for N-methyl-2-pyrrolidone (NMP) in humans. Three healthy male volunteers were administered 100 mg NMP orally. All urine was collected during nine consecutive days. The identification and quantification of the metabolites were performed by gas chromatography/mass spectrometry (GC/MS). NMP, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP), N-methylsuccinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) were found in urine. The mean excreted fractions for NMP, 5-HNMP, MSI, and 2-HMSI were 0.8%, 44%, 0.4%, and 20%, respectively. There was no conjugation with glucoronic acid or sulfate or either 5-HNMP or 2-HMSI. One-third of the orally dosed NMP was not recovered in urine as either NMP, 5-HNMP, MSI, or 2-HMSI. The half-lives for 5-HNMP, MSI, and 2-HMSI in urine were approximately 4, 8, and 17 hr, respectively.

Administration, Oral↗

Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects.

Selenoprotein P, a selenium-rich plasma protein, is an index of selenium status in rats. Antibodies against human selenoprotein P were raised to study the protein and to develop a radioimmunoassay for it. A single collection of plasma from a healthy person in the United States contained 1.84 mumol selenium/L and was defined as containing 1 Unit (U) selenoprotein P/L. Removal of selenoprotein P from the reference plasma by an antibody column indicated that 0.81 mumol selenium/L, or 44% of the plasma selenium, was present as selenoprotein P. Work by others had determined that glutathione peroxidase accounted for 12% of plasma selenium. Stored plasma samples from selenium-deficient (Dechang County) and selenium-supplemented (Mianning County) populations in China were assayed for selenoprotein P. Boys aged 8-12 y had selenoprotein P concentrations of 0.10 +/- 0.04 U/L (n = 22) in Dechang and 0.39 +/- 0.17 U/L (n = 17) in Mianning. Supplementation with 100 micrograms selenium as selenate per day for 14 d raised those levels to 0.51 +/- 0.13 U/L in Dechang and to 0.76 +/- 0.27 U/L in Mianning. Similar results were obtained in men, and plasma selenium concentrations correlated with selenoprotein P concentrations. A study comparing indices of selenium status was conducted in the two counties. Selenoprotein P concentration in Dechang subjects (n = 79) was 36% of that in Mianning subjects (n = 117). For plasma glutathione peroxidase activity the value was 54%; for plasma selenium, 47%; and for whole blood selenium, 64%. We conclude that selenoprotein P is the major selenoprotein in human plasma and that its concentration is an index of selenium nutritional status that appears to be as sensitive as other indices in common use.

Adolescent↗

Interaction of the islet nitric oxide system with L-arginine-induced secretion of insulin and glucagon in mice.

1. Several recent in vitro studies have suggested that production of nitric oxide (NO) from the islet NO system may have an important regulatory influence on the secretion of insulin and glucagon. In the present paper we have investigated, mainly with an in vivo approach, the influence and specificity of the NO synthase (NOS) blocker NG-nitro-L-arginine methyl ester (L-NAME) on L-arginine-induced secretion of insulin and glucagon. 2. In freely fed mice, L-NAME pretreatment (1.2 mmol kg-1) influenced the dynamics of insulin and glucagon release following an equimolar dose of L-arginine, the specific substrate for NOS activity, in that the NOS inhibitor enhanced the insulin response but suppressed the glucagon responses. This was reflected in a large decrease in the plasma glucose levels of the L-NAME pretreated animals. 3. L-NAME pretreatment did not influence the insulin and glucagon secretory responses to the L-arginine-enantiomer D-arginine, which cannot serve as a substrate for NOS activity. 4. Replacing L-NAME pretreatment by pretreatment with D-arginine or L-arginine itself, which both carry the same cationic change and are devoid of NOS inhibitory properties, did not mimic the effects of L-NAME on L-arginine-induced hormone release. 5. Fasting the animals for 24 h totally abolished the L-NAME-induced potentiation of L-arginine stimulated insulin release suggesting that the sensitivity of the beta-cell secretory machinery to NO-production is greatly changed in the fasting state. However, the L-NAME-induced suppression of L-arginine stimulated glucagon release was unaffected by starvation. 6. In isolated islets from freely fed mice, L-arginine (5 mM) stimulated insulin release was greatly enhanced and glucagon release markedly suppressed by the presence of the NOS inhibitor L-NAME in the incubation medium. These effects were abolished in isolated islets taken from 24 h fasted mice. 7. Our present results, which showed that the NOS inhibitor L-NAME markedly enhances insulin release but suppresses glucagon release induced by L-arginine in the intact animal, give strong support to our previous hypothesis that the islet NO system is a negative modulator of insulin secretion and a positive modulator of glucagon secretion. Additionally, we observed that the importance of the beta-cell NO-production for secretory mechanisms, as evaluated by the effect of L-NAME on L-arginine-induced insulin release, was greatly changed after starvation, an effect less prominent with regard to glucagon release.

Animals↗

Biomarkers of exposure, antibodies, and respiratory symptoms in workers heating polyurethane glue.

OBJECTIVES: The pathogenic basis of respiratory disorders associated with isocyanates are still obscure. One reason for this is the lack of good estimates of human exposure. In this study exposure was estimated by measurement of isocyanate metabolites in biological samples. METHODS: In a factory using isocyanate based polyurethane (PUR) glue, isocyanate concentrations in air were measured by liquid chromatography. Samples from 174 employees were analysed for metabolites of 4,4'-methylene diphenyl diisocyanate (MDI) in plasma (P-MDX) and urine (U-MDX). After hydrolysis, 4,4'-methylenedianiline was measured by gas chromatography-mass spectrometry (GC-MS). The employees were screened for work related respiratory symptoms and tested for specific immunoglobulin E (IgE) and IgG antibodies directed against isocyanate conjugated to human serum albumin. RESULTS: The time weighted isocyanate concentrations in air were low (MDI < 0.2-7; hexamethylene diisocyanate (HDI) < 0.1-0.7; 2,6-toluene diisocyanate (TDI) < 0.1 microgram/m3). All subjects had detectable P-MDX and U-MDX. There were significant associations between the estimates of exposure to thermal degradation products of an MDI based glue and P-MDX (range < or = 0.10-5.5 micrograms/l); and U-MDX (< or = 0.04-5.0 micrograms/g creatinine); in cases of heavy exposure. P-MDX and U-MDX were associated with each other (r = 0.64; P = 0.0001), work related symptoms (P-MDX: P = 0.03; Mann-Whitney U test), and serum concentrations of MDI specific IgG antibodies (r = 0.26; P = 0.0007). Unexpectedly, high P-MDX and U-MDX concentrations were also encountered in workers cutting textile (P-MDX 2.4-4.5 micrograms/l; U-MDX 0.81-3.8 micrograms/g creatinine); the reason is still unknown. Equally unexpected, there were significant negative associations between P-MDX and liver function tests. CONCLUSIONS: The results clearly show the value of biomarkers for isocyanate exposure; in particular, P-MDX is useful. Further, these results show the risk connected with thermal degradation of PUR.

Adhesives↗

Changes in plasma insulin, enterostatin, and lipoprotein levels during an energy-restricted dietary regimen including a new oat-based liquid food.

The changes in plasma insulin, enterostatin, lipid, and glucose levels during weight reduction were studied in 32 subjects having a body mass index of 25-35. The 31 subjects who completed the study followed for 23 weeks an energy-restricted dietary regimen which included a new oat-based soup as the main meal once or twice daily. The intake of energy decreased from 8.9 to 6.2 MJ/day from 0 to 22 weeks, the energy percentage from fat decreased from 35 to 30%, and the intake of dietary fiber increased from 21 to 25 g/10 MJ. The body weight decreased from 83 to 78 kg after 6 weeks and to 77 kg after 23 weeks. Plasma glucose had decreased significantly from 5.4 to 5.2 mmol/l, and plasma insulin from 122 to 98 pmol/l after 23 weeks. In contrast, the plasma enterostatin concentration did not vary significantly over five sampling times, the mean values ranging from 25 to 30 nmol/l. Plasma cholesterol declined from 5.6 to 5.2 mmol/l, low-density lipoprotein cholesterol from 3.8 to 3.3, and plasma triglycerides from 1.5 to 1.3 mmol/l from 0 to 23 weeks. High-density lipoprotein cholesterol increased from 1.1 to 1.3 mmol/l. It is concluded that an energy-restricted regimen leading to lower plasma insulin, triglyceride, and low-density lipoprotein cholesterol levels did not significantly affect the plasma enterostatin concentration in overweight subjects. A new oat-based liquid food as a part of the dietary regimen was well tolerated.

Adult↗

Crystallization and preliminary X-ray diffraction analysis of glutathione peroxidase from human plasma.

The extracellular form of glutathione peroxidase from human plasma has been crystallized by the sitting-drop vapour-diffusion method. The crystals belong to tetragonal space group I4(1) with cell dimensions of a = b = 83.1 and c = 131.0 A. They diffract beyond 2.9 A resolution and have one dimer in the asymmetric unit. A self-rotation function analysis shows the possible (222) symmetry for the tetramers of this enzyme.

Journal Article↗

Thyroidal extracellular glutathione peroxidase: a potential regulator of thyroid-hormone synthesis.

Human thyrocytes were found to synthesize and secrete the selenoenzyme extracellular glutathione peroxidase (E-GPX), a process which was controlled by the Ca2+/phosphoinositol second-messenger cascade. The potential involvement of thyroidal E-GPX in the regulation of thyroid-hormone synthesis and in the protection of the thyrocyte from peroxidative damage is discussed.

8-Bromo Cyclic Adenosine Monophosphate↗

N,N-dimethylbenzylamine: occupational exposure, analysis and biological monitoring.

Dimethylbenzylamine (DMBA) is used in the production of epoxy resins. The aims of this study were to assess occupational exposure to DMBA and evaluate the usefulness of monitoring the urinary excretion of DMBA and DMBA metabolites as indicators of exposure to DMBA. A sensitive gas chromatographic method for analysis of DMBA in air and in urine has been developed. The detection limit for DMBA in air for a 60-l air sample collected in 10 ml absorption solution was 2 micrograms/m3 and in charcoal tubes, 0.3 micrograms/m3. The detection limit for DMBA in urine was 0.02 mg/l. Ten male workers manufacturing epoxy resin were monitored during a full shift in the working environment and urine samples were collected at the end of exposure. The mean exposure and the highest DMBA concentration observed in air were 18 micrograms/m3 (time-weighted average; range 3-48 micrograms/m3) and 91 micrograms/m3, respectively. The DMBA concentrations in the urine samples were below the detection limit. After reduction of the urine samples the DMBA concentrations (U-SumDMBA) ranged from 0.02 to 0.22 mg/l. There was significant correlation between the exposure to DMBA and the U-SumDMBA. This observation suggests that the U-SumDMBA in urine samples collected at the end of a shift is a useful indicator of occupational exposure to DMBA.

9,10-Dimethyl-1,2-benzanthracene↗