1-OHP In Urine Research Articles

Biomonitoring of polycyclic aromatic hydrocarbons in firefighters at fire training facilities and in employees at respiratory protection and hose workshops.

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic to humans and are formed by incomplete combustion. PAHs are always present during firefighting operations, and fire department members can be exposed to them in the workplace. In this study, we analyzed 1-hydroxypyrene (1-OHP) in 36 urine samples from nine firefighters, collected before and after fire training sessions, and 32 urine samples from eight employees at respiratory protection and hose workshops. To assess breakthrough PAH exposure through personal protective equipment and potential dermal uptake, some of the workshop employees wore cotton garments under their regular workwear. Cotton samples were then examined for the presence of 17 semi-volatile and low-volatility PAHs. After firefighting exercises, we observed approximately a fivefold increase in mean 1-OHP concentrations in samples from firefighters, from 0.24 μg/L to 1.17 μg/L (maximum: 5.31 μg/L). In contrast, 1-OHP levels in workshop employees were found to be low, with the majority of urine samples yielding concentrations below the limit of quantification (LOQ: 0.05 μg/L, maximum: 0.11 μg/L). Similarly, low PAH levels were found on the workshop employees' cotton undergarments, with maximum concentrations of 250 and 205 ng/g for pyrene and benzo[a]pyrene, respectively. In conclusion, significant increases in 1-OHP in urine were observed in firefighters after training sessions, whereas work-related exposure remained low among workshop employees.

Genetic Instability among Hitnü People Living in Colombian Crude-Oil Exploitation Areas.

Oil exploitation, drilling, transportation, and processing in refineries produces a complex mixture of chemical compounds, including polycyclic aromatic hydrocarbons (PAHs), which may affect the health of populations living in the zone of influence of mining activities (PZOI). Thus, to better understand the effects of oil exploitation activities on cytogenetic endpoint frequency, we conducted a biomonitoring study in the Hitnü indigenous populations from eastern Colombia by using the cytokinesis micronucleus cytome assay (CBMN-cyt). PAH exposure was also measured by determine urine 1-hydroxypyrene (1-OHP) using HPLC. We also evaluated the relationship between DNA damage and 1-OHP levels in the oil exploitation area, as well as the modulating effects of community health factors, such as Chagas infection; nutritional status; and consumption of traditional hallucinogens, tobacco, and wine from traditional palms. The frequencies of the CBMN-cyt assay parameters were comparable between PZOI and Hitnü populations outside the zone of influence of mining activities (POZOI); however, a non-significant incremental trend among individuals from the PZOI for most of the DNA damage parameters was also observed. In agreement with these observations, levels of 1-OHP were also identified as a risk factor for increased MN frequency (PR = 1.20) compared to POZOI (PR = 0.7). Proximity to oil exploitation areas also constituted a risk factor for elevated frequencies of nucleoplasmic bridges (NPBs) and APOP-type cell death. Our results suggest that genetic instability and its potential effects among Hitnü individuals from PZOI and POZOI could be modulated by the combination of multiple factors, including the levels of 1-OHP in urine, malnutrition, and some traditional consumption practices.

The Influence of Air Pollution on the Development of Allergic Inflammation in the Airways in Krakow’s Atopic and Non-Atopic Residents

Until now, the simultaneous influence of air pollution assessed by measuring the objective marker of exposition (1-hydroxypirene, 1-OHP) and atopy on the development of allergic airway diseases has not been studied. The aim of this study was to determine the pathomechanism of the allergic response to PM2.5 in atopic and non-atopic patients. We investigated the changes in peripheral blood basophil activity of patients after stimulation with the birch pollen allergen alone, the allergen combined with PM2.5 (BP), PM2.5 alone, a concentration of 1-OHP in urine, and a distance of residence from the main road in 30 persons. Activation by dust alone was positive for all concentrations in 83% of atopic and 75% of non-atopic assays. In the group of people with atopy, the simultaneous activation of BP gave a higher percentage of active basophils compared to the sum of activation with dust and birch pollen alone (B + P) for all concentrations. The difference between BP and B + P was 117.5 (p = 0.02) at a PM concentration of 100 μg. Such a relationship was not observed in the control group. The correlation coefficient between the distance of residence from major roads and urinary 1-OHP was 0.62. A Pearson correlation analysis of quantitative variables was performed, and positive correlation results were obtained in the atopy group between BP and 1-OH-P. Exposure to birch pollen and PM2.5 has a synergistic effect in sensitized individuals. The higher the exposure to pollutants, the higher the synergistic basophil response to the allergen and PM in atopic patients.

GSTs polymorphisms are associated with epigenetic silencing of CDKN2A gene in esophageal squamous cell carcinoma.

Esophageal cancer is the eighth most common cancer and the sixth most frequent cause of cancer mortality worldwide. Exposure to polycyclic aromatic hydrocarbons formed by incomplete combustion of organic matter is an important risk factor. Genetic polymorphisms in genes encoding PAH-metabolizing enzymes like glutathione S-transferases (GSTM1, GSTP1, GSTT1) which conjugate glutathione to PAHs for reduction of oxidative stress may affect an individual's response to PAH exposure. Genomic DNA from 50 esophageal squamous cell carcinoma patients extracted from peripheral blood. PCR-RFLP technique was employed to determine GSTM1, GSTT1, and GSTP1 polymorphisms. Aberrant promoter methylation of CDKN2A was applied by methylation-specific PCR technique. Concentration of urinary 1-hydroxypyrene was determined using a HPLC system. About 38.7% showed the null GSTM1 genotype (54% cases and 13% controls), 23.7% showed GSTT1 null genotype (30% cases and 13% controls), and 62.5% were GSTP1 A/A genotype (66% cases and 56% controls). Polymorphic variants of GSTM1 and GSTT1 were significantly associated with aberrant methylation of CDKN2A gene. The null state of GSTT1 was significantly associated with high concentrations of 1-OHP in urea (p < 0.01). There was significant association between methylated states of CDKN2A and high concentrations of 1-OHP in urine (p < 0.01). We identified significant association between polymorphism of GSTs genes and epigenetic silencing of tumor suppressor gene CDKN2A in esophageal squamous cell carcinoma.

Comparison of Polycyclic Aromatic Hydrocarbons Exposure Across Occupations Using Urinary Metabolite 1-Hydroxypyrene.

Polycyclic aromatic hydrocarbons (PAHs) are well-known carcinogens causing lung and skin cancers in exposed workers. Certain occupations, such as coke production, have been associated with high PAH exposure; however, the number of occupations tested to date remains small. Here, we sought to compare PAH exposure across a wide range of occupations based on levels of 1-hydroxypyrene (1-OHP), the urinary exposure surrogate of PAHs. We collected urine 1-OHP data from the Korean National Environmental Health Survey (KoNEHS), a nationwide biomonitoring survey. We developed a linear regression model, controlling for sex, age, smoking, and survey cycle, and obtained resulting residuals. Then, we computed the fraction of exceeding the third quartile (Q3) level of residuals for each occupation, which is employed as a relative exposure indicator across occupations. A total of 15 125 measurements derived from three cycles of KoNEHS were used for analysis. The overall geometric means (GMs) and geometric standard deviation (GSD) of urine 1-OHP levels were 0.16 µg g-1 creatinine and 3.07, respectively. Among the sub-major occupational groups, 'construction and mining related elementary occupations' showed the highest fraction (0.45) of exceeding the Q3 level of residuals. Among the minor occupational groups, 'deliverers' showed a high fraction (0.42) of exceeding the Q3 level of residuals, which indicates rapidly growing occupations to be addressed. Our results provide ancillary information regarding PAH exposure across occupations, especially for occupations for which PAH exposure has not been well characterized.

Effects of smoking on concentration of urinary 8-hydroxydeoxyguanosine in coke oven workers

Objective: To explore the influence of smoking and polycyclic aromatic hydrocarbons (PAHs) on urinary 8-hydroxydeoxyguanosine (8-OHdG) in coke oven workers and investigate their dose-dependent relationships. Methods: A total of 436 workers exposed to coke oven emissions (COEs) and 132 controls were recruited in this study. Questionnaires were completed in a personal interview. Then their urine samples were also collected and the concentrations of urinary four OH-PAHs and 8-OHdG were determined by high performance liquid chromatography (HPLC) which was used to evaluate the levels of occupational PAHs internal exposure among workers and the DNA damage. Results: The differences of concentrations of urinary 2-NAP (2-hydroxynathalene) , 2-FLU (2-hydroxyfluorene) , 9-PHE (9-hydroxyphenanthrene) , 1-OHP (1-hydroxypyrene) between exposure group and control group were statistically significant (P<0.05) . In exposure group and control group, the level of 8-OHdG in heavy smoking workers were significantly higher than that in other groups (P<0.05) . Multivariate logistic regression analysis revealed high levels of urinary 8-OHdG were associated with a significantly increased risk of having higher urinary1-hydroxypyrene levels[OR=1.43 (95%CI: 1.06-1.94) , P<0.01] and heavy smoking [OR=1.44 (95%CI: 1.08-1.91) , P<0.01], respectively. Trend test showed that linear dose response relationship between smoking, 1-OHP in urine and higher concentrations of 8-OHdG (P<0.05) . Smoking could significant modify the effects of urinary 1-hydroxypyrene, while co-exposure to both heavy smoking and high urinary 1-hydroxypyrene levels[OR=5.64 (95%CI: 2.15-14.80) , P<0.05]. Conclusion: Urinary 1-hydroxypyrene is a useful biomarker for evaluating total PAHs exposure, coke oven workers with heavy smoking present more serious DNA oxditive damage.

Polycyclic aromatic hydrocarbons exposure, oxidative stress, and asthma in children.

Polycyclic aromatic hydrocarbons (PAHs) are known for their carcinogenic and teratogenic properties. However, little is known about the effect of PAH on our immune and respiratory systems. Hence, we investigated associations (1) between PAH exposure and IgE levels and asthma in children and (2) between PAH exposure and the oxidative stress marker 8OHdG potentially involved in disease pathogenesis stratifying by (3) sex-based differences. A total of 453 kindergarten children were recruited and provided samples. Urine biomarker of PAH exposure (1-OHP levels) was measured by UPLC-MS/MS and a marker of oxidative stress (8OHdG) was measured by ELISA. Serum IgE were assessed and information on asthma was collected. Associations between 1-OHP levels, 8OHdG, IgE and asthma were analyzed by multivariate linear and logistic regression. A mediation analysis was conducted to evaluate whether the risk of increased IgE and asthma related to PAH exposure is explained by 8OHdG changes. Urine 1-OHP levels were positively related to 8OHdG levels (per ln-unit: β = 0.30kU/l, p = 0.002). Similar results were also found for 1-OHP levels with IgE levels (per ln-unit: β = 0.27 kU/l, p = 0.027). 1-OHP levels (per ln-unit) were significantly associated with asthma, with an OR (95% CI) of 1.42 (1.18-1.70). In addition, 1-OHP levels were associated with asthma. It is estimated that 35% of the effect of PAH exposure on asthma is mediated by 8OHdG levels. Exposure to PAH may enhance oxidative stress and may induce asthma. The effect of PAH exposure on asthma may be mediated by oxidative stress.

The Relations between Polycyclic Aromatic Hydrocarbons Exposure and 1-OHP Levels as a Biomarker of the Exposure.

Polycyclic aromatic hydrocarbons (PAHs) are the products of incomplete combustion or pyrolysis of various organic materials. Their ubiquity in the environment leads to measurable levels of exposure. However, the exposure varies strongly between different regions in Europe. Some PAHs with four or more rings are suspected to be human carcinogens. Therefore, the occupational and/or environmental exposure to PAHs may cause a significant health risk. The aim of the study was to evaluate current levels of PAH exposure in defined groups of workers. The industrial sites selected in this survey involved PAHs originating from coal tar pitch, carbon black, bitumen, and rubber fumes. Based on the historical data, the sites were expected to exhibit quantifiable levels of exposure to PAHs. The total study population consisted of 139 persons: 108 workers (85 males and 23 females) workers were occupationally exposed in aluminium production, the production of graphite electrodes, road construction, or the rubber forming industry and 31 control individuals in two groups. The highest concentrations – 8-hour time-weighted average (TWA) levels (sum of 16 components according to the EPA list), as expected, were found in the aluminium production plant (55.15 µg.m−3) and production of graphite electrodes (54.25 µg.m−3). The lowest concentrations were found in personal air samples of road construction workers (1.93 µg.m−3). The concentrations of 1-hydroxypyrene as a pyrene metabolite (1-OHP) in the urine of the exposed group of workers were found in levels 0.74 µmol.mol−1 creatinine before the exposure and 2.27 µmol.mol−1 creatinine after the exposure (arithmetic mean values). 1-OHP concentrations in post-shift urine samples were highly correlated with the total airborne PAHs concentrations and pyrene concentrations in air. The correlation coefficients (rS) between 1-OHP concentration and pyrene or total PAHs in air were 0.710 and 0.752 (p < 0.05). This statistical analysis confirmed the effect of the occupational exposure to PAHs and pyrene on body burden in workers. However, a modifying effect of gender, smoking habits, dietary intake, genetically modified metabolism, and the use of medication on the toxicokinetics of pyrene was not determined as significant. Based on the results a strong correlation between the concentration of 1-OHP in urine as an exposure biomarker and the concentration of pyrene or PAH was affirmed.

Molecularly imprinted titania microbeads for extraction of the metabolite 1-hydroxypyrene from urine prior to its determination by HPLC

The authors describe a method for the extraction of 1-hydroxypyrene (1-OHP) from urine by using a molecularly imprinted TiO2 gel, and the determination of 1-OHP by HPLC. This method was applied to determine levels of 1-OHP in urine of patients in order to estimate the degree of exposure to polycyclic aromatic hydrocarbons. The molecularly imprinted TiO2 gel (MITiG) was prepared by polycondensation of titanium(IV) butoxide in the presence of the template 1-OHP. The gel was deposited in the form of a thin film on a quartz support, and the 1-OHP template was eluted. The resulting MITiG binds 1-OHP much better than chemically related species. The MITiG was then applied to prepare micro beads (with a typical diameter of 500–600 μm) to enlarge the specific surface. These beads were used to extract 1-OHP from urine. Following elution of 1-OHP with ethanol, it was quantified by HPLC with fluorescence detection at excitation/emission wavelengths of 242/388 nm. The method is accurate, cheaper and faster than the often used enzyme-based method.

Human sperm aneuploidy after exposure to polycyclic aromatic hydrocarbons.

The purpose of this cross-sectional study was to investigate whether environmental exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with sperm aneuploidy. A sample of 181 men who attended an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20-300×106 spermatozoa mL-1 or slight oligozoospermia (semen concentration of 15-20×106 spermatozoa mL-1; <a href=

Association of Urinary 1-OHP Concentration with Childhood Asthma

Background: Polycyclic aromatic hydrocarbons (PAHs) are known for their carcinogenic, mutagenic, and teratogenic properties. However, little is known about the effect of PAH on the development of asthma in children. Aims: To address the effect of PAH exposure on the development of sensitization and asthma by objective urine biomarker (1-OHP) at different ages. Methods: A total of 453 children from the Taiwan Childhood Environment and Allergic diseases Study (TCEAS) cohort with urine samples were recruited. Urine 1-OHP levels at age 3 and 6, as an indicator of exposure, were measured by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). At age 3 and 6, information on serum IgE levels and the development of asthma was collected. The association between 1-OHP levels at different stages and IgE levels and asthma was evaluated by multivariate linear regression and logistic regression. Results: The geometric mean levels of 1-OHP at age 3 were higher than those at age 6 (5.71 vs 4.74µg/g creatinine). 1-OHP levels at age 3 positively correlated with serum IgE levels (per ln-unit: ß=55.81 KU/l, p=0.04). Interestingly, analyses stratified by gender revealed that 1-OHP levels positively correlated with IgE only in girls (per ln-unit: ß=131.63 KU/l, p=0.02). Urine 1-OHP levels at age 3 significantly associated with asthma at age 3 and age 6 with OR(95% CI) of 3.18(1.87-5.42) and 2.54(1.45-4.44) for the highest tertile compared with lowest tertile. However, 1-OHP levels at age 6 did not reach statistical significance. Conclusions: Exposure to PAH at young age is associated with the development of sensitization and asthma in children.

Influence of genetic polymorphisms on biomarkers of exposure and effects in children living in Upper Silesia

This article is a follow-up to our previous molecular epidemiology studies on the DNA damage in children from the Upper Silesia region of Poland. It is expected that metabolic and DNA repair gene polymorphisms may modulate individual susceptibility to environmental exposure. In this study, we investigate the association between polymorphisms of metabolising (CYP2D, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) and DNA repair (XPD, XRCC1, XRCC3) genes and selected biomarkers of exposure and effect such as levels of 1-hydroxypyrene (1-OHP) and urinary mutagenicity, aromatic DNA adducts, sister chromatid exchange (SCE) and micronuclei (MN) in 74 children. Both 1-OHP concentration and urinary mutagenicity tested by TA98+S9 were significantly higher in individuals with EPHX1 (exon 4) Arg/Arg genotype than in individuals with other genotype. The EPHX1 (exon 3) significantly affected urinary mutagenicity tested with strain YG1024+S9. The urinary mutagenicity in individuals with Tyr/Tyr homozygotes was lower than in individuals with Tyr/His and His/His (1057±685 vs. 1432±1003 revertants/mol creatinine). XRCC3 Met/Met genotype was associated with significantly higher levels of 1-OHP in urine compared with only The/Met genotype. The PAH-DNA adduct levels in the subgroup with GSTM1 null genotype was 2-fold higher than in individuals with GSTM1 active (7.06±5.12 vs. 13.14±9.81 adduct/10(8) nucleotides). The mean level of aromatic DNA adducts in children with deletion of the GSTT1 gene was significantly higher compared with individuals with that gene present (8.03±6.23 vs. 14.66±10.70 adduct/10(8) nucleotides). Also the carriers of the XPD Lys/Lys genotype showed higher levels of DNA adducts than heterozygotes (13.16±9.70 vs. 6.81±5.86 adducts/10(8) nucleotides). Children carrying the XRCC3-241 Met/Met genotype exhibited a higher number of SCE in peripheral blood lymphocytes than carriers of Thr/Met allele (8.15±0.86 vs. 7.62±0.79 SCE/cell). It was also observed that children with the GSTP1 slow conjugator had significantly elevated MN in peripheral blood lymphocytes compared with fast conjugator (4.23±3.49 vs. 6.56±5.00 MN/1000 cells).

High human exposure to pyrene (polycyclic aromatic hydrocarbon) in Kinshasa, a capital of the Democratic Republic of Congo

BackgroundData on human exposure to chemicals in Africa are scarce. A biomonitoring study was conducted in a representative sample of the population in Kinshasa (Democratic Republic of Congo) to document exposure to polycyclic aromatics hydrocarbons.Methods1-hydroxypyrene (1-OHP) was measured by HPLC fluorescence in spot urine samples from 220 individuals (50.5% women), aged 6–70 years living in the urban area and from 50 additional subjects from the sub-rural area of Kinshasa. Data were compiled as geometric means and selected percentiles, expressed without (μg/L) or with creatinine adjustment (μg/g cr). Multiple regression analyses were applied to factors (creatinine, grilled meat habits and smoking habits) influencing 1-OHP (stepwise procedure, criteria: probability F to enter ≤ 0.05 and probability F to remove ≥ 0.10).ResultsAccording to the regression models, creatinine, grilled meat habits and smoking habits contribute to explain 45% of the variation in population’s urinary 1-OHP by the environmental exposure. Overall, living in urban area of Kinshasa was associated with increased levels of 1-OHP in urine as compared to a population living in the sub-rural area [GM: 1.8 μg/L (n = 220) versus 1.4 μg/L (n = 50), p < 0.01] as well as compared to the reference values from databases involving American or German populations.ConclusionThis study reveals the high pyrene (PAH) exposure of the Kinshasa population. However, more work, with a rigorous design in the exposed population (monitoring of air concentrations and identifying other sources of pyrene –PAH exposure), is needed to establish further documentation.

Urinary 1-hydroxypyrene concentration from Mexican children living in the southeastern region in Mexico

Biomass combustion indoors has been associated with generation of various pollutants, such as carbon monoxide, formaldehyde, respirable particles, toluene, benzene and polycyclic aromatic hydrocarbons (PAHs), among others. In this context, the aim of this study was to evaluate the urinary 1-hydroxypyrene (as a biomarker exposure to PAHs) levels in children living in three states in Mexico. We evaluated children living in communities that use biomass fuels to cook and to heat homes in the next states: Chiapas, Oaxaca and Quintana Roo. We found similar levels of 1-OHP in urine of children living in the three studied states, with mean levels of 3.5 ± 1.0; 4.5 ± 2.8 and 4.4 ± 2.5 μg/L (geometric mean ± standard deviation), respectively for Chiapas, Oaxaca and Quintana Roo. In conclusion, our data indicate high exposure levels to PAHs in children living in the states studied in this work.

Direct analysis of urinary 1-hydroxypyrene using extractive electrospray ionization ion trap tandem mass spectrometry

Fast detection (0.5 min) of 1-hydroxypyrene (1-OHP) in urine and hydrolyzed urine without pre-treatment has been successfully achieved by using extractive electrospray ionization ion trap tandem mass spectrometry (EESI-MS/MS) under optimized EESI and MS/MS conditions. Experimental results indicated that for MS/MS analysis the operating parameter of activation Q (AQ) was critical for 1-OHP fragmentation in collision induced dissociation (CID) experiments, and in the EESI process the primary ESI solvent was a key factor for extractive ionization of urinary 1-OHP. The limit of detection (LOD) and limit of quantification (LOQ) were 0.75 and 2.25 μM for both urine and hydrolyzed urine samples. A five-point working curve ranging from 2.29 to 22.91 μM for 1-OHP in urine or hydrolyzed urine was obtained (R2 = 0.9941 for urine and R2 = 0.9983 for hydrolyzed urine), and the relative standard deviations (RSD, n = 6) were 2.6–9.7% and 1.5–6.4%, respectively. The developed EESI-MS/MS method was validated by detecting 1-OHP in both urine and hydrolyzed urine samples. Recoveries were determined to >50% and 0.5 min was taken for each measurement, indicating that the proposed method is a promising strategy for high throughput analysis of urinary 1-OHP required for health risk assessment of exposure to polycyclic aromatic hydrocarbons (PAHs).

Association between a biomarker of exposure to polycyclic aromatic hydrocarbons and semen quality

Growing evidence supports the reproductive and developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) from prenatal and postnatal exposure, but the results of epidemiological studies regarding harmful effects of PAHs exposure on male reproductive system still remain limited and inconclusive. The aim of the present study was to investigate the relationship between 1-hydroxypyrene, a biomarker of polycyclic aromatic hydrocarbons exposure and semen quality. The study population consisted of 277 men attending an infertility clinic for diagnostic purposes and having normal semen concentration of 20-300 mln/ml or slight oligozoospermia (semen concentration: 15-20 mln/ml) (WHO 1999). All the men were healthy and under 45 years of age. All participants were interviewed and provided a semen sample. The interview included questions concerning demographics, socio-economic status, medical history related to past diseases which may have an impact on semen quality, lifestyle factors and occupational information. Concentrations of 1-hydroxypyrene (1-OHP) in the urine samples were analyzed using high performance liquid chromatography (HPLC). A positive association was found between the level of 1-OHP in urine and sperm neck abnormalities as well as the percentage of static sperm cells (p = 0.001, p = 0.018, respectively). Additionally, exposure to PAHs measured by 1-OHP in urine decreased semen volume and the percentage of motile sperm cells (p = 0.014, p = 0.0001, respectively). Presented findings indicate that the environmental level of PAHs exposure adversely affects male semen quality. The future large-scale studies should incorporate different biomarkers to generate a more accurate and full assessment of the effects of PAHs exposure on male fertility.

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model

A physiologically based toxicokinetic (PBTK) model can predict blood and urine concentrations, given a certain exposure scenario of inhalation, dermal and/or oral exposure. The recently developed PBTK-model IndusChemFate is a unified model that mimics the uptake, distribution, metabolism and elimination of a chemical in a reference human of 70 kg. Prediction of the uptake by inhalation is governed by pulmonary exchange to blood. Oral uptake is simulated as a bolus dose that is taken up at a first-order rate. Dermal uptake is estimated by the use of a novel dermal physiologically based module that considers dermal deposition rate and duration of deposition. Moreover, evaporation during skin contact is fully accounted for and related to the volatility of the substance. Partitioning of the chemical and metabolite(s) over blood and tissues is estimated by a Quantitative Structure-Property Relationship (QSPR) algorithm. The aim of this study was to test the generic PBTK-model by comparing measured urinary levels of 1-hydroxypyrene in various inhalation and dermal exposure scenarios with the result of model simulations. In the last three decades, numerous biomonitoring studies of PAH-exposed humans were published that used the bioindicator 1-hydroxypyrene (1-OH-pyrene) in urine. Longitudinal studies that encompass both dosimetry and biomonitoring with repeated sampling in time were selected to test the accuracy of the PBTK-model by comparing the reported concentrations of 1-OHP in urine with the model-predicted values. Two controlled human volunteer studies and three field studies of workers exposed to polycyclic aromatic hydrocarbons (PAH) were included. The urinary pyrene-metabolite levels of a controlled human inhalation study, a transdermal uptake study of bitumen fume, efficacy of respirator use in electrode paste workers, cokery workers in shale oil industry and a longitudinal study of five coke liquefaction workers were compared to the PBTK-predicted values. The simulations showed that the model-predicted concentrations of urinary pyrene and metabolites over time, as well as peak-concentrations and total excreted amount in different exposure scenarios of inhalation and transdermal exposure were in all comparisons within an order of magnitude. The model predicts that only a very small fraction is excreted in urine as parent pyrene and as free 1-OH-pyrene. The predominant urinary metabolite is 1-OH-pyrene-glucuronide. Enterohepatic circulation of 1-OH-pyrene-glucuronide seems the reason of the delayed release from the body. It appeared that urinary excretion of pyrene and pyrene-metabolites in humans is predictable with the PBTK-model. The model outcomes have a satisfying accuracy for early testing, in so-called 1st tier simulations and in range finding. This newly developed generic PBTK-model IndusChemFate is a tool that can be used to do early explorations of the significance of uptake of pyrene in the human body following industrial or environmental exposure scenarios. And it can be used to optimize the sampling time and urine sampling frequency of a biomonitoring program.

Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar [polycyclic aromatic hydrocarbons (PAH)] and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis. We evaluated dermal absorption of PAH as well as the genotoxic and apoptotic effects of GT in 20 patients with psoriasis, by determining numbers of chromosomal abnormalities in peripheral lymphocytes, and levels of 1-hydroxypyrene (1-OHP), p53 protein and soluble FasL (sFasL) in urine and/or blood, before and after GT. Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GT. Compared with pre-treatment levels, there was a significant increase in urine 1-OHP, indicating a high degree of dermal absorption of PAH (P < 0.01). We also found a significant increase in the number of chromosomal abnormalities in peripheral blood lymphocytes (P < 0.001), suggesting that GT is genotoxic; significantly increased p53 protein in plasma (P < 0.05), an indicator of cell response to DNA damage; and significantly increased sFasL in serum (P < 0.01), an indicator of apoptosis. The PASI score was significantly decreased after GT (P < 0.001), confirming clinical benefit of this treatment. Our results demonstrate high dermal absorption of PAH during GT and provide evidence that GT promotes genotoxicity and apoptosis.

Urinary Excretion of Malondialdehyde and 1-Hydroxypyrene in Restaurant Workers

SAB2-O-03 Introduction: Restaurant workers may have the risk for occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in cooking oil fume. Urinary malondialdehyde (MDA) and 1-hydroxypyrene (1-OHP) are biologic markers of oxidative damage and PAHs metabolism, respectively. We attempted to evaluate the relationship between MDA and 1-OHP in urine for restaurant workers in this study. Methods: We studied 314 nonsmoker workers of Chinese-type restaurants who had been employed for at least 1 year in northern Taiwan. All participants were asked to answer a questionnaire that inquired their type of job, lifestyle, and health condition. After subjects completed the questionnaires during their annual physical examinations, a single urine sample was collected. The annual physical examinations were arranged during the work shifts. All workers were asked to wash their hands prior to urine collection to avoid environmental contamination. All urine samples were analyzed for 1-OHP and MDA by high-performance liquid chromatograph. Result: For male kitchen workers, median MDA and 1-OHP concentrations (μmol/mol creatinine) were 287.4 and 2.0, respectively. These levels were significantly higher than those for male banquet workers: 216.4 μmol/mol creatinine (P = 0.024) and 0.4 μmol/mol creatinine (P = 0.01), respectively. There was a significantly positive correlation between individual urinary MDA concentrations and 1-OHP concentrations, after adjusting several potential confounders. Discussion and Conclusions: Kitchen workers may have the high risk for occupational exposure to polycyclic aromatic hydrocarbons in cooking oil fume. We need further studies to confirm this finding.

Argyrophil nucleolar organizer regions as biomarker of effect for polycyclic aromatic hydrocarbon exposure

To study whether the argyrophil nucleolar organizer regions (AgNOR) in T lymphocytes of peripheral blood in coke-oven workers can be used as a biomarker of effect for polycyclic aromatic hydrocarbon (PAH) exposure. Fifty-two male coke-oven workers were divided into three groups according to exposure levels of coke oven emissions: high-exposure, middle-exposure and low-exposure workers. Additionally 10 men without occupational PAH exposure were chosen as control group. Peripheral blood T lymphocytes were cultured, spread on slides and stained with silver nitrate. The ratio of AgNOR area vs. nuclear area (I/S) in T lymphocytes was analyzed. Urinary 1-hydroxypyrene (1-OHP) was measured as the internal dose of PAH exposure. Mean urinary 1-OHP level in high-exposure group (16.56 +/- 2.77 micromol/mol Cr) was significantly higher than those in low-exposure group (3.30 +/- 2.77 micromol/mol Cr, P < 0.001) and control group (3.04 +/- 1.58 micromol/mol Cr, P < 0.01). The mean I/S of AgNOR in T lymphocytes in high-exposure group (0.056 +/- 0.010) was significantly lower than those in middle-exposure group (0.065 +/- 0.013, P < 0.05), low-exposure group (0.067 +/- 0.008, P < 0.01) and control group (0.076 +/- 0.007, P < 0.001). It was also found that I/S of AgNOR were significantly decreased in middle-exposure group and low-exposure group in comparison with control group (P < 0.01, P < 0.05). The occupational exposure to PAH resulted in increase of 1-OHP in urine and decrease of AgNOR in T lymphocytes. PAH exposure might lead to damage T lymphocytes function and AgNOR may be considered as a biomarker of effect for PAH exposure.