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Results for “Biomarker variability”

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PubMed2001

Validated biomarker responses influence medical surveillance of individuals exposed to genotoxic agents.

There is currently a vast armamentarium of biomarkers for evaluating human exposures to environmental carcinogens, the effects of such exposures and/or susceptibility to disease outcome. Before application, however, these biomarkers require validation in terms of truly reflecting what is claimed. Transitional epidemiological studies bridge the gap between laboratory and field. In a transitional study, a biomarker response is the dependent variable being evaluated, while the intended measure, i.e. exposure effect or susceptibility, is the independent variable. Once validated, biomarker responses provide valuable data for use in making human health risk assessments and as guides for individual medical surveillance programmes. An analysis of medical decision-making illustrates how biomarker responses that increase the relative risk of subsequent disease occurrence change the 'pre-test likelihood' of having the disease, thereby influencing interpretation of medical diagnostic tests and even the choice of tests to be performed. This argues that an individual's response using salidated biomarkers should be made part of the medical record.

Biomarkers↗

PubMed2004

Effects of cigarette smoking and exposure to cadmium and lead on phenotypic variability of hepatic CYP2A6 and renal function biomarkers in men.

Effects of cigarette smoking and exposure to dietary cadmium (Cd) and lead (Pb) on urinary biomarkers of renal function and phenotypic variability of cytochrome P450 2A6 (CYP2A6) were investigated in a group of 96 healthy Thai men with mean age of 36.7 year (19-57 years). In non-smokers, Cd burden increased with age (r = 0.47, P < 0.001). In current smokers, Cd burden increased with both age (r = 0.45, P = 0.01) and number of cigarettes smoked per day (r = 0.32, P = 0.05). Cd-linked renal tubular dysfunction was seen in both smokers and non-smokers, but Pb-linked glomerular dysfunction was seen in smokers only, possibly due to more recent exposure to high levels of Cd and Pb, as reflected by 30-50% higher serum Cd and Pb levels in smokers than non-smokers (P < 0.05). Exposure to dietary Cd and Pb appeared to be associated with mild tubular dysfunction whereas dietary exposure plus cigarette smoking was associated with tubular plus glomerular dysfunction. Hepatic CYP2A6 activity in non-smokers showed a positive association with Cd burden (adjusted beta = 0.38, P = 0.006), but it showed an inverse correlation with Pb (adjusted beta = -0.29, P = 0.003), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. In contrast, CYP2A6 activity in current smokers did not correlate with Cd or Pb, but it showed a positive correlation with serum ferritin levels (r = 0.45, P = 0.01). These finding suggest that Pb concentrations in the liver probably were too low to inhibit hepatic synthesis of heme and CYP2A6 and that the concurrent induction of hepatic CYP2A6 and ferritin was probably due to cigarette smoke constituents other than Cd and Pb.

Adult↗

PubMed2003

A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers.

BACKGROUND: Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk. METHODS: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided. RESULTS: Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P =.81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels. CONCLUSIONS: The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials.

Adult↗

PubMed2026

Longitudinal variability of lipoprotein(a) in youth-onset type 1 diabetes: implications for cardiovascular risk stratification.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor, traditionally considered stable across the lifespan, supporting a single lifetime measurement strategy. However, its longitudinal behaviour during childhood and adolescence remains poorly characterised, particularly in individuals with type 1 diabetes who face a markedly increased lifetime risk of coronary artery disease. We therefore aimed to characterise intra- and inter-individual trajectories of Lp(a) in a paediatric type 1 diabetes cohort and to assess the implications of Lp(a) variability for cardiovascular risk classification. METHODS: We conducted a retrospective single-centre cohort study of children and adolescents with type 1 diabetes attending Geneva University Hospitals between 2012 and 2023. Annual fasting Lp(a) concentrations were analysed longitudinally. Variability was assessed in participants with ≥ 2 measurements. Clinically relevant thresholds were used to evaluate cardiovascular risk reclassification. Paired Wilcoxon tests, Pearson and Kendall correlations, and Holm-adjusted p-values (P < 0.05) were applied. Analyses were conducted in R. RESULTS: A total of 286 participants contributed 1403 Lp(a) measurements, with observation periods varying across individuals (median 6.2 years, IQR 2.9-9.6) and between 1 and 13 measurements per participant. At baseline, 26% had elevated Lp(a) (≥ 300 mg/l). Among participants with serial measurements, 32% showed intraindividual fluctuations exceeding 50% of their individual maximum value. Reclassification across the 300 mg/l cardiovascular risk threshold occurred in 11.9% of participants. Lp(a) concentrations peaked between ages 10 and 13 years and declined thereafter. Modest seasonal variation was observed, with higher concentrations in autumn and winter (P < 0.05). CONCLUSIONS: In youth with type 1 diabetes, Lp(a) is not as stable as previously assumed, exhibiting clinically relevant variability over time. These findings challenge the current paradigm of a single lifetime Lp(a) measurement and suggest that repeated assessment, particularly during adolescence, may improve early cardiovascular risk stratification.

Humans↗

PubMed1998

Glutathione S-transferase M1 and P1 genotypes and urinary excretion of 1-hydroxypyrene in coke oven workers.

The objective of this study was to analyze the effect of the GSTM1 and GSTP1 genotypes on urinary 1-hydroxypyrene, a biomarker for exposure to polycyclic aromatic hydrocarbon. Urine samples were collected from coke oven workers at two time points (from 66 and 46 workers, respectively) and 1-hydroxypyrene was quantitated by HPLC chromatography. The genotype of GSTM1 and GSTP1 was determined by a PCR methods discriminating between GSTM1 present or absent and three different alleles for GSTP1. The mean value of urinary 1-hydroxypyrene was higher at both time points in coke oven workers with GSTM1 gene present compared to workers having the GSTM1 null genotype, but this difference was not statistically significant. The GSTM1 and GSTP1 genotypes were not significant parameters in a multiple regression analysis with urinary 1-hydroxypyrene as the dependent variable and with GSTM1, GSTP1, exposure group and smoking habit as explanatory variables. The biomarker 1-hydroxypyrene is not or only marginally influenced by the GSTM1 genotype. No systematic influence of the GSTP1 genotypes was found.

Adult↗

PubMed2005

Real-time telomerase activity measurements for detection of cancer.

Since the hallmark report of the PCR-based telomeric repeat amplification protocol (TRAP) in 1994, there has been a flurry of investigations of telomerase activity on normal, benign, premalignant and cancerous samples representative of the various stages of tumorigenesis. Basic research and technological advances in human genetics, biochemistry and model systems have brought much progress towards the understanding of human infectious, hereditary and somatically acquired diseases. The knowledge of carcinogenesis has increased very rapidly in the past few years, particularly with the development of automated molecular biologic analysis of tumors and preneoplastic lesions. Despite the wide variety of studies on the potential use of telomerase as a cancer biomarker, the variability of reported telomerase activity and the lack of a transferable detection method have prevented it from becoming a routine clinical application. Real-time PCR is a clinically transferable method and the advancement of real-time measurements of telomerase will facilitate moving telomerase activity and technologies towards clinical validation. It is expected that the next 5 years will see telomerase integrated into the initial detection and follow-up monitoring of cancer patients. The hope is that the use of telomerase will finally translate into a diagnostic to help realize longer survival and a better quality of life.

Biomarkers, Tumor↗

PubMed2003

B-type natriuretic peptide in ischemic heart disease.

B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-proBNP) are released from the heart in response to increased wall stress. Assays for these peptides are now commercially available, and measurement of BNP and N-proBNP is becoming commonplace in patients with suspected heart failure. BNP and N-proBNP facilitate diagnosis and risk stratification in patients with heart failure, and may help guide response to therapy. This review focuses on the emerging role of BNP and N-proBNP measurement in patients with acute coronary syndromes (ACS). Although experimental studies demonstrate rapid BNP release in response to cardiac ischemia, it is unlikely that BNP will be used to diagnose cardiac ischemia, because many other conditions are also associated with modest BNP elevation. In contrast, BNP holds tremendous promise as a prognostic marker in patients with ACS. Studies to date have shown consistently that higher BNP levels are associated with worse clinical outcomes, and that BNP provides unique information to clinical variables, other biomarkers, and left ventricular ejection fraction. Future studies are needed to identify the therapeutic implications of BNP elevation in patients with ACS.

Acute Disease↗

PubMed2004

Relative value of N-terminal probrain natriuretic peptide, TIMI risk score, ACC/AHA prognostic classification and other risk markers in patients with non-ST-elevation acute coronary syndromes.

AIMS: We prospectively studied the additive value of N-terminal probrain natriuretic peptide (NT-proBNP) in relation to the Thrombolysis in Myocardial Infarction (TIMI) risk score and the American College of Cardiology/American Heart Association (ACC/AHA) joint prognostic classification, and compared the predictive capacity of NT-proBNP, troponin T (TnT), C-reactive protein (hsCRP), myoglobin, and creatine kinase-MB (CK-MB) concentrations in a cohort of 1483 consecutive patients with non-ST-segment-elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: Centralised measurements of NT-proBNP, TnT, myoglobin, and hsCRP were performed 3 h (median) after admission. Adjusting by clinical, ECG variables, and biomarkers, NT-proBNP concentration was the strongest independent predictor of in-hospital (OR 1.7, 95% CI: 1.31-2.20, p < .001) and 180-day mortality (OR 1.67, 95% CI: 1.41-1.99, p < .001), and added significant prognostic information to the TIMI and ACC/AHA prognostic categories. NT-proBNP was not an independent predictor of risk of new myocardial infarction, even in the acute or long term. CONCLUSIONS: In NSTE-ACS, NT-proBNP adds substantial information to the TIMI risk score and the ACC/AHA classification. Compared to other biomarkers, NT-proBNP is the strongest independent predictor of in-hospital and 180-day mortality.

Aged↗

PubMed2002

The carbonyl content of specific plasma proteins is decreased by dietary copper deficiency in rats.

Copper (Cu) deficiency is associated with increased susceptibility of tissue homogenates or lipoproteins to oxidation in vitro. Plasma is easily sampled and contains both lipid and protein components that may be susceptible to oxidation, making it appropriate to investigate plasma oxidation variables as biomarkers of in vivo oxidative stress. Oxidation of plasma proteins may be discernible as an increased content of carbonyl (aldehyde or ketone) groups on the proteins. Weanling male Long-Evans rats were fed sucrose-based modified AIN-93G diets with (+Cu, 6.2 mg Cu/kg diet) or without (-Cu, 0.4 mg/kg) added Cu for 4 wk before killing. Plasma and RBC Cu,Zn-superoxide dismutase activities and liver Cu concentration were significantly decreased and relative heart weight was significantly increased, confirming the Cu-deficient status of the -Cu rats. Dinitrophenylhydrazine (DNP) derivatization followed by SDS-PAGE and Western blotting using commercial anti-DNP antibody demonstrated that several plasma proteins in +Cu control rats showed evidence of carbonyl groups. The carbonyl content of these bands was lower in -Cu rats, not greater as would have been expected with oxidative damage to these proteins. Although dietary Cu deficiency may increase susceptibility to oxidative stress, it does not lead to accumulation of oxidized plasma proteins in this animal model.

Aldehydes↗

PubMed2006

Survival outcomes of resected patients who demonstrate a pathologic complete response after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer.

A variety of strategies, using chemotherapy, radiation therapy, and surgical resection have been employed in the treatment of locally advanced esophageal cancer. No strategy has proven superior, and poor long-term survival is anticipated. A survival benefit has been suggested for patients who achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation therapy. We examined the collective results at three institutions of patients who achieved a pCR following neoadjuvant chemoradiation therapy. A retrospective, chart-based review was conducted. Kaplan-Meier calculations were used to determine overall and disease-free survival. Between 1995 and 2002, 229 patients were treated with neoadjuvant chemoradiation followed by surgery as a planned approach for locally advanced esophageal cancer. Forty-one patients (18%) demonstrated pCR and were the focus of this study. Histology was adenocarcinoma in 29, squamous in 10, and adenosquamous/undifferentiated in two patients. Forty patients were staged by endoscopic ultrasound prior to neoadjuvant therapy and all demonstrated a T-stage of 2 or higher, while 19 had evidence of nodal metastasis. Four patients died in the perioperative period. The remaining patients have been followed for an average of 46 months. Overall survival at 5 years was 56.4% and a median survival has not been reached. Esophageal cancer patients who demonstrate a pCR following neoadjuvant chemoradiation are a select subset who demonstrate excellent long-term survival. Identification of clinical variables or biomarkers predictive of pCR may therefore optimize treatment strategies of patients with locally advanced esophageal cancer.

Adenocarcinoma↗

PubMed2006

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment [ISRCTN08045231].

BACKGROUND: Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. METHODS/DESIGN: Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to approximately 25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. DISCUSSION: This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives.

Aged↗

PubMed2003

Chemical contaminants and biological indicators of mussel health during gametogenesis.

Mytilus edulis were collected intertidally from three locations in Halifax Harbor, Nova Scotia, on five occasions during spring and summer 2000. Bioindicators of health (lipid content), condition and gonad indices (CI and GI), and sex ratio, as well as vitellins, were compared with the bioaccumulation of polycyclic aromatic compounds (PACs) including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), coprostanol, and metals. Twice as many male as female mussels were collected from a downtown site (M8) close to numerous raw sewage effluents and a naval dockyard. Males from M8 had a high lipid content, and females had a delayed production of vitellins. These mussels also displayed the highest levels of PACs, coprostanol, Ag, and Sn. Coprostanol and silver are sewage markers in sediments, and their presence in mussels confirms exposure to sewage effluents. Female mussels were more abundant in an area outside the industrialized part of the harbor that had higher marine traffic (M14); displayed higher levels of vitellins in gonads; had similar time trends for CI and GI; and had some similar metals compared with mussels from M8. The lowest variability in biomarkers was observed at a site in a mostly residential arm of the harbor (M12), which was expected to be more pristine based on an earlier investigation. Compared to mussels in M14, the mussels of M12 had the lowest condition indices and PCB concentrations and low but similar levels of lipids, PACs, and coprostanol. They also displayed the highest concentrations of Cd, Cu, Pb, and Hg, and females had the highest gonad indices early in the season.

Animals↗

PubMed2001

Vitamin A, vitamin E and carotenoid status and metabolism during ageing: functional and nutritional consequences (VITAGE PROJECT).

Among the nutritional factors contributing to maintain health during ageing, fat-soluble vitamins (FSV) are crucial to protect against free radical-generated degenerative processes or impaired efficiency of the immune system. However, no sound scientific evidence is able to confirm specific dietary needs in vitamin A, vitamin E and carotenoids for the healthy elderly. VITAGE project aims at providing such evidence by undertaking studies on male volunteers from 3 European countries, aged between 20-75 years. Biomarkers and variables related to status, metabolism and functions will be measured either in steady-state conditions, or during dietary depletion and repletion in FSV. Original, yet already developed, methodologies will provide clear information about the physiological characteristics of vitamin A, vitamin E and carotenoids. Simultaneously, marketing opportunities for FSV-enriched dietetic foods, specifically designed for the elderly will be determined. The scientific and economical evidence obtained in this project will provide the basis to implement a EU nutritional policy towards the elderly and to develop a new sector of dietetic food products.

Adult↗

PubMed2006

Validity of human nails as a biomarker of arsenic and selenium exposure: A review.

Human nail clippings have been used in recent epidemiological studies as a routine bioindicator of arsenic and selenium exposure. To ensure sound application of this biomarker, however, it is important to consider properties and scientific knowledge pertaining to validation of this particular tool. In this review, the use of human nails to measure exposure to arsenic and selenium is discussed in the context of the biomarker validation framework. Literature related to both analytical procedures and intrinsic characteristics of the biomarker is reviewed. Specifically, the followings are addressed: sample collection and preparation methods, establishment of the exposure-biomarker relationship, intraindividual variability and reproducibility of measurements, and biomarker-disease investigations. Drawing from a rapidly growing body of literature, current knowledge of these biomarker validation steps is assessed. Therefore, this review brings attention to the important issue of biomarker validation, laying the framework for future studies measuring elemental composition of nails.

Arsenic↗

PubMed1990

The use of biomarkers in the prediction of survival in patients with pulmonary carcinoma.

Data on ten variables and 16 biomarkers were obtained on 119 patients with newly diagnosed pulmonary cancer. The prognostic value of 16 biomarkers (alpha-1-antitrypsin [AAT], adrenocorticotropic hormone [ACTH], alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], human chorionic gonadotropin [HCG], immune complexes, immunoglobulins, N-terminal peptide of proopiomelanocortin [NTERM], and tumor-associated antibody [TAA]) was tested by adding these to the model of age, gender, stage, morphology, Feinstein's classification of symptoms, Karnofsky scale, leukocyte count, recent weight loss, and liver enzymes. Using Cox's regression method and a forward stepwise procedure, seven biomarkers (ACTH, AAT, AFP, calcitonin, HCG, TAA, and prolactin) entered the model. Elevated levels of cortisol and TAA were associated with longer survival. The selection of biomarkers by stepwise regression needs to be interpreted with caution, especially since the Z scores were found to be dependent on the particular variables included in the model. Furthermore, when dichotomized on maximum of the normal laboratory values, HCG and AFP were infrequently (2%) elevated. The lack of correlation among the biomarkers supports the hypothesis of random derepression of the genome of cancer cells. Further studies in improved modeling and the formulation of a biomarker index could enhance our understanding of the biology of cancer.

Adenocarcinoma↗

PubMed2006

Exercise hemodynamic and neurohormone responses as sensitive biomarkers for diltiazem in rats.

PURPOSE: To investigate the potential of exercise hemodyanamic and neurohormone variables as sensitive biomarkers for pre-clinical evaluation of diltiazem (DTZ). METHODS: Sprague Dawley (SD) rats were randomly divided into 3 groups (n = 6 - 8 each), and each group received DTZ 10 mg/kg twice daily for 5 doses or saline followed by a treadmill exercise protocol for 7 min with speed set at 7 m/min at 3 % grade. The 3rd group received saline but no exercise. RESULTS: Exercise increased SBP from 108 +/- 2 to 131 +/- 3 mmHg, and HR from 437 +/- 6 to 503 +/- 6 bpm, and plasma epinephrine concentrations from 2.0 +/- 0.6 to 5.8 +/- 1.7 ng/mL in control rats (p < 0.05 for all variables), but had no significant effect on DBP (81 +/- 5 vs 87 +/- 6 mmHg) and plasma norepinephrine concentrations (1.5 +/- 0.2 vs 3.9 +/- 0.4 ng/mL). The hemodynamic responses to exercise were significantly attenuated by DTZ (p < 0.05), but the effect on neurohormone response was minimal (p > 0.05). CONCLUSION: Exercise hemodynamic and neurohormone responses are sensitive biomarkers which could be used for safety and efficacy evaluation of DTZ and perhaps also other calcium antagonists in pre-clinical animal models.

Animals↗

PubMed2005

Biomarker profiles and their relation to clinical variables in mild cognitive impairment.

The aim of the study was to compare clinical variables between MCI patients at different risk for Alzheimer's disease (AD) according to their biomarker profile. Fifty-four percent out of 39 MCI patients had a low Abeta42 and high tau in cerebrospinal fluid (CSF) (high-risk), 26% either a low CSF Abeta32 or high CSF tau (intermediate-risk) and 20% a normal CSF Abeta42 and tau (low-risk). Both high-and intermediate-risk subjects differed from the low-risk group in episodic memory, executive functions and the preclinical AD scale (PAS),which combines a set of clinical parameters. Subjects at high risk did not differ from subjects with an intermediate risk. Abeta42 levels correlated with the MTA and PAS scores, tau levels with episodic memory. These correlations suggest that the biomarkers are not independent when compared to the other AD markers. Longitudinal studies are necessary to interpret the correlations between biomarkers, imaging, and neuropsychological markers.

Aged↗

PubMed2006

Exposure assessment at the workplace: implications of biological variability.

Biological monitoring (BM) and biomarkers are widely applied in occupational toxicology. BM is mainly aimed at (i) defining the existence of an occupational exposure; (ii) quantifying the level of internal dose; (iii) verifying that exposure limits (BEI((R)), BAT, BLV) are respected. As compared to ambient monitoring, BM is more expensive and complex. Several biomarkers are available for the same chemical and the meaning of the marker may depend on the sampling time. Therefore, practical issues, including cost and selection of an adequate sampling strategy, should be dealt with when planning a BM program for specific purposes. In addition, several biological and analytical sources of variability may influence biomarker levels, thus making the interpretation of BM data a difficult task. However, we should recognize that the main aim of BM is not to reduce, but to explain biological variance. The decreasing trend in occupational exposure levels highlighted the specificity problems of traditional biomarkers of exposure and prompted the research to the development of new biomarkers, e.g. unchanged volatile compounds in urine, minor metabolites, DNA and protein adducts. Depending on the scope and context (research or routine) different requirements of biomarkers can be envisaged in terms of validation and acceptable variability.

Air Pollutants, Occupational↗