Useful Biomarkers Of Exposure Research Articles

Interspecies Differences in 6PPD-Quinone Toxicity Across Seven Fish Species: Metabolite Identification and Semiquantification.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a recently identified contaminant that originates from the oxidation of the tire antidegradant 6PPD. 6PPD-Q is acutely toxic to select salmonids at environmentally relevant concentrations, while other fish species display tolerance to concentrations that surpass those measured in the environment. The reasons for these marked differences in sensitivity are presently unknown. The objective of this research was to explore potential toxicokinetic drivers of species sensitivity by characterizing biliary metabolites of 6PPD-Q in sensitive and tolerant fishes. For the first time, we identified an O-glucuronide metabolite of 6PPD-Q using high-resolution mass spectrometry. The semiquantified levels of this metabolite in tolerant species or life stages, including white sturgeon (Acipenser transmontanus), chinook salmon (Oncorhynchus tshawytscha), westslope cutthroat trout (Oncorhynchus clarkii lewisi), and nonfry life stages of Atlantic salmon (Salmo salar), were greater than those in sensitive species, including coho salmon (Oncorhynchus kisutch), brook trout (Salvelinus fontinalis), and rainbow trout (Oncorhynchus mykiss), suggesting that tolerant species might detoxify 6PPD-Q more effectively. Thus, we hypothesize that differences in species sensitivity are a result of differences in basal expression of biotransformation enzyme across various fish species. Moreover, the semiquantification of 6PPD-Q metabolites in bile extracted from wild-caught fish might be a useful biomarker of exposure to 6PPD-Q, thereby being valuable to environmental monitoring and risk assessment.

Urinary Biomarkers of Exposure to Volatile Organic Compounds from the Population Assessment of Tobacco and Health Study Wave 1 (2013-2014).

Volatile organic compounds (VOCs) are ubiquitous in the environment. In the United States (U.S.), tobacco smoke is the major non-occupational source of exposure to many harmful VOCs. Exposure to VOCs can be assessed by measuring their urinary metabolites (VOCMs). The Population Assessment of Tobacco and Health (PATH) Study is a U.S. national longitudinal study of tobacco use in the adult and youth civilian non-institutionalized population. We measured 20 VOCMs in urine specimens from a subsample of adults in Wave 1 (W1) (2013–2014) to characterize VOC exposures among tobacco product users and non-users. We calculated weighted geometric means (GMs) and percentiles of each VOCM for exclusive combustible product users (smokers), exclusive electronic cigarette (e-cigarette) users, exclusive smokeless product users, and tobacco product never users. We produced linear regression models for six VOCMs with sex, age, race, and tobacco user group as predictor variables. Creatinine-ratioed levels of VOCMs from exposure to acrolein, crotonaldehyde, isoprene, acrylonitrile, and 1,3-butadiene were significantly higher in smokers than in never users. Small differences of VOCM levels among exclusive e-cigarette users and smokeless users were observed when compared to never users. Smokers showed higher VOCM concentrations than e-cigarette, smokeless, and never users. Urinary VOC metabolites are useful biomarkers of exposure to harmful VOCs.

Cluster analysis of urinary tobacco biomarkers among U.S. adults: Population Assessment of Tobacco and Health (PATH) biomarker study (2013–2014)

Tobacco use delivers nicotine, tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons (PAHs), which are metabolized and excreted in urine offering useful biomarkers of exposure. Previous studies compared individual toxicants across tobacco users. Based on a group of biomarkers, cluster analysis was used to define tobacco toxicant exposure profiles. Clusters with distinct exposure profiles, were determined and described, based on levels of urinary biomarkers of exposure to nicotine, TSNAs, VOCs, and PAHs among a national sample of current, established, adult tobacco users, and examine the association of use behavior and cluster membership. The PATH Biomarker Wave 1 data were analyzed. Current established tobacco users with complete urinary biomarker data were included (N = 6724). User groups included cigarette smokers, users of electronic cigarette (ECIG), smokeless tobacco (SLT), and dual and poly tobacco users. Cluster analysis, pairwise comparisons, and multinomial logistic regression were conducted. Cigarette smokers were primarily in clusters with high biomarker concentrations across all groups, but actual concentrations were associated with smoking quantity. A cluster with high TSNAs but low levels of PAHs and VOCs was heavily populated by SLT users. Exclusive ECIG users, depending on use frequency, were predominantly in clusters with low biomarker concentrations, except for one cluster that had relatively high TSNAs. Clusters heavily populated by dual and poly tobacco users were the same as those heavily populated by cigarette smokers. Ten exposure profiles (clusters) were determined and linked to tobacco use behavior. Findings could inform future research and policy initiatives.

Human immune response to Phlebotomus sergenti salivary gland antigens in a leishmaniasis-endemic focus in Iran

ABSTRACT Salivary proteins specific antibodies have been shown to be useful biomarkers of exposure to sand fly bites. This study aimed to investigate the level, duration, and dynamics of the human immune response against the SGL of Phlebotomus sergenti Parrot, 1917 (Diptera: Psychodidae), and to assess the immunoreactivity of human sera with SGL components in an endemic area of anthroponotic cutaneous leishmaniasis (ACL) in Iran. The study was carried out in 2-phase; longitudinal and cross-sectional. Sand flies were collected monthly from indoors and outdoors. In the longitudinal study, sera from healthy volunteers were collected monthly, and in the cross-sectional study, sera from healthy volunteers and patients with ACL lesion/s, were collected for immunoassay studies. The level of anti-P. sergenti saliva IgG was detected using the ELISA. Immunoreactivity of individual human sera with saliva components was also assessed by western blotting. Phlebotomus sergenti was the predominant sand fly species in the study area. The maximum and minimum percentages of IgG responses were seen in October (66%) and March (29%), respectively. Additionally, the cross-sectional study showed that 59.3% of the healthy volunteers and 80% of the patients were IgG positive. The antibody response against P. sergenti salivary gland was high during the sand fly active season and declined by the end of the activity of the vectors. Antibody response against the SGL components of P. sergenti was transient and individual-specific. Some individuals shared a strong reaction against certain individual antigens, which could be considered as vector exposure markers for further investigation. List of abbreviations ELISA: Enzyme-Linked Immunosorbent Assay; SDS PAGE: Sodium Dodecyl Sulfate–Polyacrylamide Gel Electrophoresis; SGL: Salivary Gland Lysate; ACL: Anthroponotic Cutaneous Leishmaniasis; PBS: Phosphate Buffered Saline; BCA: Bicinchoninic Acid; PBS-T: Phosphate Buffered Saline Tween; FBS: Fetal Bovine Serum; HRP: Horseradish Peroxidase; TMB: 3,3′,5,5′-Tetramethylbenzidine; PVDF: Polyvinylidene Difluoride; SGA: Salivary Gland Antigens; OD: Optical Density; KDa: Kilodalton; VL: Visceral Leishmaniasis; CL: Cutaneous Leishmaniasis; SGs: Salivary glands

Association between pre/perinatal exposure to POPs and children's anogenital distance at age 4 years: A study from the INMA-Asturias cohort.

Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children. Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n=155) and in cord blood serum (n=229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex. In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (ß=-0.041, 95% confidence interval [CI]: -0.074, -0.008, second tertile), PCB-153 (ß=-0.052, 95% CI: -0.085, -0.020, second tertile), PCB-180 ß=-0.065, 95% CI: -0.096, -0.035, second tertile; ß=-0.042, 95% CI: -0.073, -0.011, third tertile), PBDE-209 (ß=-0.031, 95% CI: -0.058, -0.006), cord serum concentrations of PCB-153 (ß=-0.029, 95% CI: -0.059, -0.000, second tertile; ß=-0.047, 95% CI: -0.085, -0.008, third tertile), and PCB-180 (ß=-0.041, 95% CI: -0.078, -0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (ß=0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4'-DDT (ß=0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4'-DDE (ß=0.040, 95% CI: 0.011, 0.069, third tertile). Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females.

Effects of the organochlorine p,p’-DDT on MCF-7 cells: Investigating metabolic and immune modulatory transcriptomic changes

The organochlorine pesticide dichloro-diphenyl-trichloroethane (DDT) is persistent in the environment and leads to adverse human health effects. High levels in breast milk pose a threat to both breast tissue and nursing infants. The objectives of this study were to investigate DDT-induced transcriptomic alterations in enzymes and transporters involved in xenobiotic metabolism, immune responses, oxidative stress markers, and cell growth in a human breast cancer cell line. MCF-7 cells were exposed to both environmentally-relevant and previously-tested concentrations of p,p’-DDT in a short-term experiment. Significant up-regulation of metabolizing enzymes and transporters (ACHE, GSTO1, NQO1 and ABCC2) and oxidative stress markers (CXCL8, HMOX-1, NFE2L2 and TNF) was clearly observed. Conversely, UGT1A6, AHR and cell growth genes (FGF2 and VEGFA) were severely down-regulated. Identification of these genes helps to identify mechanisms of p,p’-DDT action within cells and may be considered as useful biomarkers for exposure to DDT contamination.

Do Post-breast Cancer Diagnosis Toenail Trace Element Concentrations Reflect Prediagnostic Concentrations?

Exposure to trace elements may affect health, including breast cancer risk. Trace element levels in toenails are potentially useful biomarkers of exposure, but their reliability is not established. We assessed the reproducibility of toenail element concentrations over time and whether concentrations change following a breast cancer diagnosis. We assessed trace element levels in toenails collected at two time points from 221 women (111 with and 110 without an intervening breast cancer diagnosis). We measured levels of arsenic, cadmium, chromium, cobalt, copper, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, tin, vanadium, and zinc using inductively coupled plasma mass spectrometry in samples collected at baseline and 4-10 years later. We compared trace element concentrations over time using Spearman's rank correlation coefficient (R). We used linear models to examine the magnitude and direction of changes and the influence of a breast cancer diagnosis. Overall, we observed positive correlations (R = 0.18-0.71) between paired samples for all trace elements. However, nickel (R = -0.02) and antimony (R = 0.12) were not correlated among cases. We observed decreases in cadmium, chromium, mercury, manganese, molybdenum, nickel, and lead between baseline and follow-up, but case status was unrelated to these changes. The declines are consistent with decreases over calendar time rather than age time. Toenail trace element concentrations were correlated over time, but many elements showed systematic decreases by calendar year. Aside from nickel and antimony, postdiagnostic toenail levels correlated with prediagnostic levels, providing support for using postdiagnostic toenail samples in retrospective studies.

Metabolite profiles of striped marsh frog (Limnodynastes peronii) larvae exposed to the anti-androgenic fungicides vinclozolin and propiconazole are consistent with altered steroidogenesis and oxidative stress

Amphibians use wetlands in urban and agricultural landscapes for breeding, growth and development. Fungicides and other pesticides used in these areas have therefore been identified as potential threats that could contribute towards amphibian population declines. However, relatively little is known about how such chemicals influence sensitive early life-stages or how short episodic exposures influence sub-lethal physiological and metabolic pathways. The present study applied untargeted metabolomics to evaluate effects in early post-hatch amphibian larvae exposed to the anti-androgenic fungicides vinclozolin and propiconazole. Recently hatched (Gosner developmental stage 25) striped marsh frog (Limnodynastes peronii) larvae were exposed for 96 h to vinclozolin at 17.5, 174.8 and 1748.6 nM and propiconazole at 5.8, 58.4 and 584.4 nM. Nuclear Magnetic Resonance (NMR) spectroscopy was performed on polar metabolites obtained from whole-body extracts. Both fungicides altered metabolite profiles compared to control animals at all concentrations tested, and there were notable differences between the two chemicals. Overall responses were consistent with altered steroidogenesis and/or cholesterol metabolism, with inconsistent responses between the two fungicides likely reflecting minor differences in the mechanisms of action of these chemicals. Broad down-regulation of the tricarboxylic acid (TCA) cycle was also observed and is indicative of oxidative stress. Interestingly, formic acid was significantly increased in larvae exposed to vinclozolin but not propiconazole, suggesting this metabolite may serve as a useful biomarker of exposure to androgen-receptor binding anti-androgenic contaminants. This study demonstrates the power of untargeted metabolomics for distinguishing between similarly acting, but distinct, pollutants and for unraveling non-endocrine responses resulting from exposure to known endocrine active contaminants.

Documenting the kinetic time course of lambda-cyhalothrin metabolites in orally exposed volunteers for the interpretation of biomonitoring data

Lambda-cyhalothrin is a pyrethroid pesticide largely used in agriculture. Exposure assessment can be performed by measuring key urinary metabolites. For a proper use of biomonitoring data, it is however important to gain information on the toxicokinetics of these key biomarkers of exposure. A human volunteer study was performed to document the plasma and urinary time courses of major lambda-cyhalothrin metabolites. Seven volunteers ingested 0.025mgkg−1 body weight of lambda-cyhalothrin. Blood samples were withdrawn prior to dosing and at fixed time periods over the 72 h-period following ingestion and complete urine voids were collected pre-exposure and at pre-established intervals over 84h post-dosing. The cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were quantified in these samples. Plasma concentrations of CFMP and 3-PBA increased rapidly after ingestion, with average peak values at 3.1 and 4.0h post-dosing, respectively; subsequent elimination phase showed a rapid decay with a mean half-life (t½) of ≈5.3 and 6.4h for CFMP and 3-PBA, respectively. Urinary rate time courses displayed a profile similar to the plasma concentration-time curves with corresponding mean t½ of ≈4.2 and 5.9h. In the 84-h period post-treatment, on average 21% of lambda-cyhalothrin dose were excreted in urine as CFMP as compared to 30% as 3-PBA. Overall, CFMP and 3-PBA metabolites were confirmed to be major metabolites of lambda-cyhalothrin and exhibited similar kinetics with short half-lives; they thus both appear as useful biomarkers of exposure to lambda-cyhalothrin in humans.

Temporal variability of blood lead, mercury, and cadmium levels in elderly panel study (2008-2014).

Biological measurements have been employed as useful biomarkers for exposure. Because of its property of reflecting toxicokinetic differences, however, within-subject variability leads to biased results in epidemiologic studies. We examined the variability of lead (Pb), mercury (Hg), and cadmium (Cd) levels in blood samples from 1429 participants among 1677 elderly individuals aged over 60 years who lived in an urban area from August 2008 to April 2015. The geometric means of blood Pb, Hg, Cd were 1.92μg/dL, 2.48μg/L, and 1.33μg/L, and the intra-class correlations (ICCs) were 0.81, 0.71, and 0.83, respectively. The mean values of Pb and Hg levels in this study were lower than the results from single spot samples in other national biomonitoring surveys in Korea, with the exception of Cd was higher than those in other studies. Moreover, the predicted exceedances over the guidance levels for Pb, Hg, and Cd were 1.9%, 4.2%, and 0.3%, respectively. Korean elderly were exposed to high levels of Pb, Hg and Cd. Especially, those who had high levels of Cd were continuously exposed to Cd during study period with the 6 collection intervals. Therefore, factors affecting environmental Cd exposure should be further studied in the future.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well-designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

Separate and Joint Effects of Polycyclic Aromatic Hydrocarbons (PAH)and Polychlorinated Biphenyls (PCB) on Aromatase CYP19A Transcription Level in Atlantic Tomcod (Microgradus tomcod)

Ovarian cytochrome 19A (CYP19A) expression is recognized as a useful biomarker for exposure of fish to environmental contaminants such as PAHs and PCBs. In this study, a laboratory approach using Atlantic tomcod (Microgradus tomcod) from the Hudson River was used to evaluate the additive and interactive effects of a PAH (benzo[a]pyrine) and a PCB mixture (Aroclor 1242) with respect to their effects on various metrics of reproduction. The experimental design was a two-way factorial with each treatment at 0, 0.1 and 1 ppm and replicated three times. Fish embryos were subjected to a short term aqueous exposure (DMSO as vehicle) whereas larvae were exposed via repeated feedings of contaminated prey (Artemia). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to evaluate the mRNA expression level of the ovarian aromatase CYP19A as a biomarker to assess reproductive stress in Microgadus tomcod. When tested alone, expression of aromatase CYP19A was significantly up regulated at the higher level of PCBs but no effect was observed from benzo-a-pyrene (B[a]P). In the PCB/PAH combined treatment, both low-PCB with both low/high levels of PAH and high-PCB with both low/high levels of PAH treatment groups had no significant effect on aromatase CYP19A transcript levels compared with the control group. Gonadosomatic Index (GSI) of reproductively mature females showed that only the high-PCB treatment group exhibited significant gonadal loss. The results confirm the expectation that transcription of both PCB and PAH responsive genes are upregulated since they both exert their toxic effects through the aryl hydrocarbons receptor (AHR) pathway

Normative concentrations of urine thiocyanate in cassava eating communities in Nigeria

Exposure to cyanide is a major public health problem where highly cyanogenic cassava foods are consumed. Thiocyanate (SCN), the biomarker of exposure to cyanide is present in several foods, and produced endogenously. Concentrations of urine SCN were measured in endemic and non-endemic areas of ataxic polyneuropathy in Nigeria. Cassava food consumption in the endemic area was twice that of non-endemic areas. Geometrical mean (95% CI) urine SCN was 20 µmol/l (18–24) for no consumption of cassava foods, 56 µmol/l (49–64) for daily consumption, 56 µmol/l (48–65) for twice daily consumption and 85 µmol/l (62–117) for thrice daily consumption. 95th percentile reference limit was 125 µmol/l for no consumption of cassava food, but 360 µmol/l for thrice daily consumption. Urine SCN is a useful biomarker of exposure to cyanide from cassava foods. There is strong ecological association of exposure to cyanide and endemicity of ataxic polyneuropathy.

Genotoxicity of copper oxide and silver nanoparticles in the mussel Mytilus galloprovincialis

Though there is some information on cytotoxicity of copper nanoparticles and silver nanoparticles on human cell lines, there is no information on their genotoxic and cytotoxic behaviour in bivalve molluscs. The aim of this study was to investigate the genotoxic impact of copper oxide and silver nanoparticles using mussels Mytilus galloprovincialis. Mussels were exposed to 10 μg L−1 of CuO nanoparticles and Cu2+ and Ag nanoparticles and Ag+ for 15 days to assess genotoxic effects in hemocytes using the comet assay. The results obtained indicated that copper and silver forms (nanoparticles and ionic) induced DNA damage in hemolymph cells and a time-response effect was evident when compared to unexposed mussels. Ionic forms presented higher genotoxicity than nanoparticles, suggesting different mechanisms of action that may be mediated through oxidative stress. DNA strand breaks proved to be a useful biomarker of exposure to genotoxic effects of CuO and Ag nanoparticles in marine molluscs.

Histopathology alterations and lipid peroxidation as biomarkers of hydrocarbon-induced stress in earthworm, Eudrilus eugeniae

This study investigated the biomarker responses of the earthworm, Eudrilus eugeniae, exposed to sublethal concentrations of benzene, toluene and xylene (BTX) for a time span of 28days. Lipid peroxidation (LPO) and histopathological alterations were examined. Toxicological evaluations of BTX were carried out against E. eugeniae. On the basis of the 96-h LC(50) value, xylene (1.212mg/kg) was found to be the most toxic followed by toluene (1.335mg/kg) and benzene (1.896mg/kg) was the least toxic. The exposure of earthworms to sublethal concentrations (1/10th and 1/100th of 96h LC(50)) of BTX premixed with the substrate (loamy and humus soil) induced pathological changes in the clitella such as severe lesion, necrosis and dark brown pigments. The result of the lipid peroxidation assay showed a significant increase in oxidative damage with LPO values ranging from 2.58-7.8nM/g in exposed animals when compared to 0.07nM/g in the control group. The findings from this study suggest the use of LPO and histopathology as useful biomarkers of exposure for early detection of petroleum related stress in terrestrial ecosystems.

Plastics and carcinogenesis: The example of vinyl chloride.

The manufacture, use and disposal of various plastics can pose numerous health risks, including the risk of cancer. A model example of carcinogenic risk from plastics is provided by polyvinyl chloride, since it is composed of the known human carcinogen vinyl chloride (VC). In recent years, much has been learned about the molecular biological pathways of VC carcinogenesis. This has led to molecular epidemiologic studies of VC carcinogenesis in exposed human populations which have identified useful biomarkers of exposure, effect and susceptibility for VC. These studies have in turn provided the basis for new molecular approaches for the prevention and treatment of VC cancers. This model could have much wider applicability for many other carcinogenic exposures and many other human cancers.

Factors affecting variability in the urinary biomarker 1,6-hexamethylene diamine in workers exposed to 1,6-hexamethylene diisocyanate

Although urinary 1,6-hexamethylene diamine (HDA) is a useful biomarker of exposure to 1,6-hexamethylene diisocyanate (HDI), a large degree of unexplained intra- and inter-individual variability exists between estimated HDI exposure and urine HDA levels. We investigated the effect of individual and workplace factors on urine HDA levels using quantitative dermal and inhalation exposure data derived from a survey of automotive spray painters exposed to HDI. Painters' dermal and breathing-zone HDI-exposures were monitored over an entire workday for up to three separate workdays, spaced approximately one month apart. One urine sample was collected before the start of work with HDI-containing paints, and multiple samples were collected throughout the workday. Using mixed effects multiple linear regression modeling, coverall use resulted in significantly lower HDA levels (p = 0.12), and weekday contributed to significant variability in HDA levels (p = 0.056). We also investigated differences in urine HDA levels stratified by dichotomous and classification covariates using analysis of variance. Use of coveralls (p = 0.05), respirator type worn (p = 0.06), smoker status (p = 0.12), paint-booth type (p = 0.02), and more than one painter at the shop (p = 0.10) were all found to significantly affect urine HDA levels adjusted for creatinine concentration. Coverall use remained significant (p = 0.10), even after adjusting for respirator type. These results indicate that the variation in urine HDA level is mainly due to workplace factors and that appropriate dermal and inhalation protection is required to prevent HDI exposure.

Trace elements in nails as biomarkers in clinical research

The importance of trace elements in relation to human health has been increasingly recognized. Accurate and adequate quantification of trace elements are crucial in clinical research. This review was to discuss the rationale of using nail trace elements as biomarkers in clinical studies. For most trace elements, dietary instruments cannot appropriately capture the intakes because of the minimal amounts and wide variations in the same foods grown in different area as well as the nondietary exposures. Therefore, biomarkers may be essential in studying trace elements. Although there are notable differences among trace elements in the availability of biomarkers, increasing evidence supports that nails, particularly toenail concentrations of most trace elements, are useful biomarkers of exposure in which a single sample is assumed to represent long-term exposure. Compared with other potential biomarkers of trace elements, nail measurement has certain advantages in clinical research.

Modulation of ethoxyresorufin O-deethylase and glutathione S-transferase activities in Nile tilapia (Oreochromis niloticus) by polycyclic aromatic hydrocarbons containing two to four rings: implications in biomonitoring aquatic pollution

Despite ubiquity of polycyclic aromatic hydrocarbons (PAHs) in the tropical environments, little information is available concerning responses of tropical fish to PAHs and associated toxicity. In the present study, effects of five PAHs containing two to four aromatic rings on hepatic CYP1A dependent ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST) and serum sorbitol dehydrogenase (SDH) activities in Nile tilapia, a potential fish species for biomonitoring pollution in tropical waters, were evaluated. Results showed that EROD activities were induced by the PAHs containing four aromatic rings (pyrene and chrysene) in a dose dependent manner. However PAHs with two to three aromatic rings (naphthalene, phenanthrene and fluoranthene) caused no effect or inhibition of EROD activities depending on the dose and the duration. Fluoranthene was the most potent inhibitor. SDH results demonstrated that high doses of fluoranthene induced hepatic damage. GST activity was induced by the lowest dose of phenanthrene, fluoranthene and chrysene but high doses had no effect. The results indicate that induction of EROD enzyme in Nile tilapia is a useful biomarker of exposure to PAHs such as pyrene and chrysene. However EROD inhibiting PAHs such as fluoranthene in the natural environment may modulate the EROD inducing potential of other PAHs thereby influencing PAH exposure assessments.

Low air levels of benzene: Correlation between biomarkers of exposure and genotoxic effects

This study was aimed to identify useful biomarkers of exposure and effect in workers exposed to low levels of benzene, and to evaluate any correlations existing between these parameters. Benzene exposure was measured in 33 petrochemical industry operators (PIO), 28 service station attendants (SSA), 21 gasoline pump maintenance workers (GPMW) and 51 non-exposed controls by GC-FID analysis. Samples were collected with personal passive samplers (Radiello ®). End-shift urine samples were collected for t, t-muconic acid ( t, t-MA) determination by HPLC and for S-phenylmercapturic acid ( S-PMA) measurement by HPLC–MS/MS. The alkaline version of the comet assay and, in a subgroup of 19 SSA and 16 control subjects, chromosomal aberrations (CA) and glutathione (GSH) levels were measured in peripheral blood lymphocytes. Personal benzene exposure was significantly higher in PIO, SSA and GPMW as compared to controls. The urinary excretion of the two metabolites showed a significant increase in SSA ( p = 0.0258 and p = 0.0001, for t, t-MA and S-PMA, respectively) and in PIO ( p = 0.0013 and p = 0.0001, for t, t-MA and S-PMA, respectively) as compared with the control group, while no such increase was observed for GPMW, for whom occupational exposure was not continuous and occurred on specific working days only. Significant increases of DNA damage were found by the comet assay for tail moment (TM) and tail length (TL) in SSA ( p < 0.0001 and p = 0.008, for TM and TL, respectively) and PIO ( p < 0.0001 and p < 0.0001, for TM and TL, respectively) when compared with controls. The PIO group also displayed a significant increase in the number of cells with comet ( p < 0.0001). Smoking habits did not appear to interfere with these results in any of the groups. No difference was found in percentage of CA between exposed workers and controls. Significant correlations were found, in all groups, between benzene exposure and the more representative comet parameter TM ( r = 0.509, p = 0.007; r = 0.525, p = 0.017 and r = 0.420, p = 0.046 in SSA, GPMW, and PIO, respectively). A trend of negative correlation was observed between DNA damage and either GSH or urine S-PMA for exposed workers. In summary, in present study urinary S-PMA and DNA damage by the comet assay were both sensitive to exposure to low levels of benzene, and GSH seems to play an important defence role against benzene-dependent DNA damage.