Use of Physiologically-Based Pharmacokinetic Modeling to Simulate the Profiles of 3-Hydroxybenzo(a)pyrene in Workers Exposed to Polycyclic Aromatic Hydrocarbons

Biomathematical modeling has become an important tool to assess xenobiotic exposure in humans. In the present study, we have used a human physiologically-based pharmacokinetic (PBPK) model and an simple compartmental toxicokinetic model of benzo(a)pyrene (BaP) kinetics and its 3-hydroxybenzo(a)pyrene (3-OHBaP) metabolite to reproduce the time-course of this biomarker of exposure in the urine of industrially exposed workers and in turn predict the most plausible exposure scenarios. The models were constructed from in vivo experimental data in rats and then extrapolated from animals to humans after assessing and adjusting the most sensitive model parameters as well as species specific physiological parameters. Repeated urinary voids from workers exposed to polycyclic aromatic hydrocarbons (PAHs) have been collected over the course of a typical workweek and during subsequent days off work; urinary concentrations of 3-OHBaP were then determined. Based on the information obtained for each worker (BaP air concentration, daily shift hours, tasks, protective equipment), the time courses of 3-OHBaP in the urine of the different workers have been simulated using the PBPK and toxicokinetic models, considering the various possible exposure routes, oral, dermal and inhalation. Both models were equally able to closely reproduce the observed time course of 3-OHBaP in the urine of workers and predicted similar exposure scenarios. Simulations of various scenarios suggest that the workers under study were exposed mainly by the dermal route. Comparison of measured air concentration levels of BaP with simulated values needed to obtain a good approximation of observed time course further pointed out that inhalation was not the main route of exposure for most of the studied workers. Both kinetic models appear as a useful tool to interpret biomonitoring data of PAH exposure on the basis of 3-OHBaP levels.     

Development of a urinary biomarker for exposure to the organophosphate propetamphos: data from an oral and dermal human volunteer study.

Propetamphos is a member of the vinyl phosphate group of insecticides and is mainly used for sheep dipping. There have been no published metabolic studies on the effect of propetamphos in man to date, although the present authors have published the identification of a metabolite. The present paper presents data from a human volunteer study investigating the toxicokinetics of the organophosphorus pesticide propetamphos following oral and dermal exposure. Five volunteers ingested a propetamphos dose of 10 micrograms kg-1 (35 nmol kg-1) body weight. Following a washout of 4 weeks, a 100 mg (356 mumol) dermal dose of propetamphos was applied, occluded to 80 cm2 of the inner forearm, for 8 h to the same five volunteers. In a pilot study (several weeks before the main study), one volunteer also received an occluded dermal dose of 50 mg (178 mumol) propetamphos. Unabsorbed propetamphos on the skin was washed off after 8 h and collected. Blood and urine samples were collected over 30 and 54 h for the oral and dermal exposures respectively. Blood samples were analysed for plasma and erythrocyte cholinesterase. Urine samples were analysed for a urinary metabolite of propetamphos: methylethylphosphoramidothioate (MEPT). Following oral and dermal exposure, peak urinary MEPT levels occurred at 1 and 10-12 h respectively. The apparent urinary elimination half-lives of MEPT had means of 1.7 h (oral exposure) and 3.8 h (dermal exposure). Approximately 40% of the oral dose and 1% of the dermal dose were recovered as urinary MEPT or metabolites, which could be hydrolysed to MEPT. Approximately 90% of the dermal dose was recovered from the skin washings. Data from a volunteer showed that a doubling of the dermal dose resulted in approximately double the concentration of total MEPT. Alkaline hydrolysis of urine samples increased the level of MEPT detected after both oral and dermal doses. The increase was greater and statistically significant (p < 0.001, paired t-test) for the dermal dose. This increase in MEPT suggests the presence of other MEPT-containing metabolites or conjugates. The difference in the increase between oral and dermal doses raises the question of a difference in metabolism between the two routes. No individual showed a significant depression compared with their pre-exposure levels of erythrocyte acetyl cholinesterase or plasma cholinesterase activity for either dosing route. However, on a group basis, there was a statistically significant mean depression in plasma cholinesterase activity at 8 and 24 h for oral exposure, with a maximum mean depression of 7% from pre-exposure levels at 8 h. Hydrolysis of urine samples had the effect of reducing the interindividual coefficient of variation (CV) for total excretion of MEPT following both oral (CV reduced from 36 to 8%) and dermal (CV reduced from 40 to 17%) exposure. The ability to detect and follow the elimination of low doses of propetamphos by measurement of 'total' (after hydrolysis) urinary MEPT suggests it is a suitable biomarker of propetamphos exposure. The comparatively short elimination half-lives suggest a strategy for biological monitoring of occupational exposure based on samples collected at the end of the shift.     

Development of a urinary biomarker for exposure to the organophosphate propetamphos: data from an oral and dermal human volunteer study

Propetamphos is a member of the vinyl phosphate group of insecticides and is mainly used for sheep dipping. There have been no published metabolic studies on the effect of propetamphos in man to date, although the present authors have published the identification of a metabolite. The present paper presents data from a human volunteer study investigating the toxicokinetics of the organophosphorus pesticide propetamphos following oral and dermal exposure. Five volunteers ingested a propetamphos dose of 10 μg kg^-1 (35nmol kg^-1) body weight. Following a washout of 4 weeks, a 100mg (356 μmol) dermal dose of propetamphos was applied, occluded to 80cm² of the inner forearm, for 8 h to the same five volunteers. In a pilot study (several weeks before the main study), one volunteer also received an occluded dermal dose of 50 mg (178 μmol) propetamphos. Unabsorbed propetamphos on the skin was washed off after 8 h and collected. Blood and urine samples were collected over 30 and 54 h for the oral and dermal exposures respectively. Blood samples were analysed for plasma and erythrocyte cholinesterase. Urine samples were analysed for a urinary metabolite of propetamphos: methylethylphosphoramidothioate (MEPT). Following oral and dermal exposure, peak urinary MEPT levels occurred at 1 and 10-12 h respectively. The apparent urinary elimination half-lives of MEPT had means of 1.7h (oral exposure) and 3.8 h (dermal exposure). Approximately 40% of the oral dose and 1% of the dermal dose were recovered as urinary MEPT or metabolites, which could be hydrolysed to MEPT. Approximately 90% of the dermal dose was recovered from the skin washings. Data from a volunteer showed that a doubling of the dermal dose resulted in approximately double the concentration of total MEPT. Alkaline hydrolysis of urine samples increased the level of MEPT detected after both oral and dermal doses. The increase was greater and statistically significant (p < 0.001, paired t-test) for the dermal dose. This increase in MEPT suggests the presence of other MEPT-containing metabolites or conjugates. The difference in the increase between oral and dermal doses raises the question of a difference in metabolism between the two routes. No individual showed a significant depression compared with their pre-exposure levels of erythrocyte acetyl cholinesterase or plasma cholinesterase activity for either dosing route. However, on a group basis, there was a statistically significant mean depression in plasma cholinesterase activity at 8 and 24 h for oral exposure, with a maximum mean depression of 7% from pre-exposure levels at 8 h. Hydrolysis of urine samples had the effect of reducing the interindividual coefficient of variation (CV) for total excretion of MEPT following both oral (CV reduced from 36 to 8%) and dermal (CV reduced from 40 to 17%) exposure. The ability to detect and follow the elimination of low doses of propetamphos by measurement of 'total' (after hydrolysis) urinary MEPT suggests it is a suitable biomarker of propetamphos exposure. The comparatively short elimination half-lives suggest a strategy for biological monitoring of occupational exposure based on samples collected at the end of the shift.     

A Tiered Approach for Assessing Dermal Exposure to Constituents in Latex Paint

Latex paint is commonly used by professional and consumer painters. Potential inhalation exposure to chemical vapors from paint has been studied extensively. Potential dermal exposure is not as well studied and existing exposure evaluation methods assume the paint remains wet for the duration of skin contact. However, latex paint may dry quickly and this limits the bioavailability of paint constituents due to the decreased diffusion through a dry film. This study presents a tiered in silico (i.e., computer modeling) approach to evaluate potential dermal exposure to nonvolatile substances using a technique that begins with exposure to a wet paint film and transitions to a dry film. Experiments were performed to help quantify a key parameter, latex paint drying time, and the experimental results were used in a case study to demonstrate the tiered approach. The predicted dermal penetration ranged from 100% of the applied substance for a simple conservative approach to 5% of the applied substance for the refined wet/dry film approach. Assuming the paint film was partially wiped further reduced the predicted penetration to 2%. This study addresses only latex paint but the tiered approach could be modified to evaluate other products.     

Human exposure and risk assessment of chromafenozide during treatment in rice fields

The potential dermal and respiratory exposure and risk assessments for an applicator were performed with chromafenozide in rice fields in Korea. Three experienced farmers of approximately the same height (168–170 cm) and weight (65–73 kg) were employed to perform the experiment. Dermal patches, gloves, socks, and masks were used to monitor the potential dermal exposure (PDE), and personal air samplers with XAD-2 resins were used to monitor the potential inhalation exposure. During the mixing/loading process of chromafenozide (2.5%, EC), the average hand exposure amount was 3.7 mg and the ratio to the applied amount was 1.85 ×10^?2%. For spraying process, the potential dermal exposure amount was 98.3 (74.5–112.8) mg, corresponding to 0.492% of the total exposure amount. The major exposure parts were thigh (0.37%) and shin (0.10%), and the left body (55.0%) was more than that of the right body (45.0%). The inhalation exposure amount was only 39.9 mg. For risk assessment, the mean of PDE (384.0 mg/day) and the mean of absorbable quantity of exposure (3.99 mg/day) were calculated. The value of margin of safety (MOS) ranged from 1.12 to 1.69, all MOS were >1, indicating the exposure level of chromafenozide was safe during application in rice fields.     

Qualitative Profiling and Quantification of Neonicotinoid Metabolites in Human Urine by Liquid Chromatography Coupled with Mass Spectrometry

Neonicotinoid pesticides have been widely applied for the production of fruits and vegetables, and occasionally detected in conventionally grown produce. Thus oral exposure to neonicotinoid pesticides may exist in the general population; however, neonicotinoid metabolites in human body fluids have not been investigated comprehensively. The purpose of this study is the qualitative profiling and quantitative analysis of neonicotinoid metabolites in the human spot urine by liquid chromatography coupled with mass spectrometry (LC/MS). Human urine samples were collected from three patients suspected of subacute exposure to neonicotinoid pesticides. A qualitative profiling of urinary metabolites was performed using liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) with a database of nominal molecular weights of 57 known metabolites of three neonicotinoid pesticides (acetamiprid, Imidacloprid, and clothianidin), as well as the parent compounds. Then a quantitative analysis of selected urinary metabolites was performed using liquid chromatography/tandem mass spectrometry (LC/MS/MS) with a standard pesticide and metabolite, which were detected by the qualitative profiling. The result of qualitative profiling showed that seven metabolites, i.e. an acetamiprid metabolite, N-desmethyl-acetamiprid; three Imidacloprid metabolites, 5-hydroxy-Imidacloprid, 4,5-dihydroxy-imidacloprid, 4,5-dehydro-Imidacloprid; a common metabolite of acetamiprid and Imidacloprid, N-(6-chloronicotinoyl)-glycine; and two clothianidin metabolites, N-desmethyl-clothianidin, N-(2-(methylsulfanyl)thiazole-5-carboxyl)-glycine, as well as acetamiprid, were detected in the urine of three cases. The result of the quantitative analysis showed N-desmethyl-acetamiprid was determined in the urine of one case, which had been collected on the first visit, at a concentration of 3.2 ng/mL. This is the first report on the qualitative and quantitative detection of N-desmethyl-acetamiprid in the human urine. The results suggest that the one case with detection of N-desmethyl-acetamiprid was exposed to acetamiprid through the consumption of contaminated foods. Urinary N-desmethyl-acetamiprid, as well as 5-hydroxy-Imidacloprid and N-desmethyl-clothianidin, may be a good biomarker for neonicotinoid exposure in humans and warrants further investigation.     

Human Exposure Pathways of Heavy Metals in a Lead-Zinc Mining Area,Jiangsu Province,China

Heavy metal pollution is becoming a serious issue in developing countries such as China, and the public is increasingly aware of its adverse health impacts in recent years. We assessed the potential health risks in a lead-zinc mining area and attempted to identify the key exposure pathways. We evaluated the spatial distributions of personal exposure using indigenous exposure factors and field monitoring results of water, soil, food, and indoor and outdoor air samples. The risks posed by 10 metals and the contribution of inhalation, ingestion and dermal contact pathways to these risks were estimated. Human hair samples were also analyzed to indicate the exposure level in the human body. Our results show that heavy metal pollution may pose high potential health risks to local residents, especially in the village closest to the mine (V1), mainly due to Pb, Cd and Hg. Correspondingly, the residents in V1 had higher Pb (8.14 mg/kg) levels in hair than those in the other two villages. Most of the estimated risks came from soil, the intake of self-produced vegetables and indoor air inhalation. This study highlights the importance of site-specific multipathway health risk assessments in studying heavy-metal exposures in China.     

Animal models to test respiratory allergy of low molecular weight chemicals: a guidance

At present, there are no widely applied or fully validated test methods to identify respiratory LMW allergens, i.e. compounds that are considered capable of inducing allergic asthma. Most tests have been investigated using strong respiratory allergens. Moreover, they are meant to detect the potential of a chemical to induce respiratory sensitisation at relatively high doses. Consequently, the sensitivity of the tests is not well-known, and they do not provide information on low doses such as generally found in occupational situations, and on threshold levels to be used in risk assessment. In addition, the various test methods use different application routes, i.e. intradermal, topical or inhalation exposure, and different parameters. Therefore standardised and validated dose-response test methods are urgently required in order to be able to identify respiratory allergens and to recommend safe exposure levels for consumers and workers. In the present paper, methods or testing strategies are described to detect respiratory sensitisation and/or allergy. Overall, assays that utilize only an induction phase may serve as indicators of respiratory sensitisation potential whereas assays that use both an induction and an elicitation or challenge phase may provide information on potency and presence of thresholds. The dermal route as sensitisation route has the advantage of the respiratory tract not being exposed to the allergen prior to challenge which facilitates the distinction between irritant and allergic effects.     

Glycophorin A mutant frequency in radiation workers at the nuclear power plants and a hospital

We studied to assess the validity of the glycophorin A (GPA) mutant assay as a biological marker of the cumulative effects of chronic low doses of ionizing radiation. In 144 nuclear power plants workers and 32 hospital workers, information on confounding factors, such as age and cigarette smoking, was obtained through a self-administered questionnaire. The information on physical exposure doses was obtained from the registries for radiation exposure monitoring and control at each facility. The range of cumulative exposure doses were 0-12.02cGy. GPA mutant assay was performed by the BR6 method with modification using a FACScan flow cytometer. Potential confounders, such as, age and cigarette smoking habits showed increasing trends with GPA variants, but were not of statistical significance. The hospital workers showed higher frequency of the GPA NO variant than nuclear power plant workers. Significant dose-response relationships were found between cumulative exposure to radiation and variants levels by simple and multiple linear regression models. The slope of regression equation of the dose-response of nuclear power plants workers was much smaller than that of hospital workers. These findings suggest that there may be dose-rate effects. In a population exposed to chronic low-dose radiation, the GPA assay shows potential to be used as an effective biologic marker for assessing the cumulative exposure dose although it could not be able to see a dose relation below 10cGy of cumulative exposure dose.     

Biological monitoring of benzene exposure during maintenance work in crude oil cargo tanks

We investigated the association between the individual concentrations of benzene in the breathing zone and the concentrations of benzene in the blood and urine among workers maintaining crude oil cargo tanks. Benzene exposure was measured during three consecutive 12h work days among 13 tank workers and 9 unexposed referents (catering section). Blood and urine samples were collected pre-shift on the first day, post-shift on the third day, and pre-next shift on the following morning. The workers used half-mask air-purifying respirators, but not all workers used these systematically. The individual geometric mean benzene exposure in the breathing zone of tank workers over 3 days was 0.15 ppm (range 0.01-0.62 ppm). The tank workers' post-shift geometric mean benzene concentrations were 12.3 nmol/l in blood and 27.0 nmol/l in urine versus 0.7 nmol/l for both blood and urine among the referents. Benzene in the work atmosphere was highly correlated with the internal concentration of benzene both in post-shift blood (r=0.87, P<0.001) and post-shift urine (r=0.90, P<0.001), indicating that the varying use of respirators did not explain much of the variability in absorbed benzene. The results showed that, despite low benzene exposure in this work atmosphere and the use of personal protective equipment to a varying degree, the tank workers had a significant uptake of benzene that correlated highly with benzene exposure. The internal concentration of benzene was higher than expected considering the measured individual benzene exposure, probably due to an extended work schedule of 12h and physical strain during tank work. Control measures should be improved for processes, which impose a potential for increased absorption of benzene upon the workers.     

Secondary indoor air pollution and passive smoking associated with cannabis smoking using electric cigarette device–demonstrative in silico study

With electronic (e)-liquids containing cannabis components easily available, many anecdotal examples of cannabis vaping using electronic cigarette devices have been reported. For electronic cigarette cannabis vaping, there are potential risks of secondary indoor air pollution from vapers. However, quantitative and accurate prediction of the inhalation and dermal exposure of a passive smoker in the same room is difficult to achieve due to the ethical constraints on subject experiments. The numerical method, i.e., in silico method, is a powerful tool to complement these experiments with real humans. In this study, we adopted a computer-simulated person that has been validated from multiple perspectives for prediction accuracy. We then conducted an in silico study to elucidate secondary indoor air pollution and passive smoking associated with cannabis vaping using an electronic cigarette device in an indoor environment. The aerosols exhaled by a cannabis vaper were confirmed to be a secondary emission source in an indoor environment; non-smokers were exposed to these aerosols via respiratory and dermal pathways. Tetrahydrocannabinol was used as a model chemical compound for the exposure study. Its uptake by the non-smoker through inhalation and dermal exposure under a worst-case scenario was estimated to be 5.9% and 2.6% of the exhaled quantity from an e-cigarette cannabis user, respectively.     

alpha-Fluoro beta alanine in urine of workers occupationally exposed to 5 fluorouracil in a 5 fluorouracil producing factory

Because of possible harmful health effects increased attention is being paid to the occupational exposure to cytostatic drugs of workers in hospitals and industry. In this study a biomarker for exposure to 5-fluorouracil (5FU) based on GC-MSMS was applied to study the occupational exposure of four workers in a pharmaceutical factory producing 5FU. The four workers all excreted-fluoro--alanine (FBAL), a metabolite of 5FU, via the urine (range excretion rates: 0-88 9 g per 8h). This is in accordance with the presence of 5FU and/or its precursor ethoxyfluorouracil (EFU) in stationary and personal air wipe samples taken from the the workplace.     

alpha-Fluoro beta alanine in urine of workers occupationally exposed to 5 fluorouracil in a 5 fluorouracil producing factory

Because of possible harmful health effects increased attention is being paid to the occupational exposure to cytostatic drugs of workers in hospitals and industry. In this study a biomarker for exposure to 5-fluorouracil (5FU) based on GC-MSMS was applied to study the occupational exposure of four workers in a pharmaceutical factory producing 5FU. The four workers all excreted-fluoro--alanine (FBAL), a metabolite of 5FU, via the urine (range excretion rates: 0-88 9 g per 8h). This is in accordance with the presence of 5FU and/or its precursor ethoxyfluorouracil (EFU) in stationary and personal air wipe samples taken from the the workplace.     

Biological monitoring among benzene-exposed workers in Bangalore city, India.

Environmental and biological monitoring was carried out in the winter season of 2004 for 30 gasoline station workers (study subjects) and 30 office workers (controls) of Bangalore city, India. Personal air sampling was carried out in the breathing zone of workers using an Anasorb CSC sorbent tube (SKC 226-01) fitted to the low-flow personal samplers (PCXR4 and pocket pump Model No. 210-1002) at a flow rate of 200 ml min(-1) during the shift work of 8 h. The benzene content adsorbed in the sorbent tube (SKC 226-01) was desorbed with 1 ml of benzene-free carbon disulfide on a developing vibrator and later analysed by Trace GC fitted with MXT-624 column and flame ionization detector. The mean time weighted average benzene concentration found among study and controls was 1.10+/-1.08 and 0.070+/-0.035 mg m(-3), respectively. Biological monitoring for benzene exposure was performed by measuring trans,trans muconic acid (t,t-MA) in the end shift urine samples using HPLC-UV technique. End-shift urine samples (1 ml) were adjusted to pH 7-9 with phosphate buffer pH 7.4 passed through the preconditioned Q-SAX anion-exchange cartridge and the (t,t-MA) is extracted with 10% acetic acid and later analysed by HPLC-UV detection The mean t,t-MA found among study and controls were 563.16+/-281.81 and 266.88+/-110.65 microg g(-1) creatinine. About 50% of the study subjects (15) have higher t,t-MA values than the biological exposure index of the American Conference of Government Industrial Hygienist (ACGIH). Correlation is significant at 5% level (p<0.05) between personal air benzene concentration and urinary t,t-MA in the study group. Based on these findings, the t,t-MA can be used as a biomarker for benzene exposure.     

Urinary 1-hydroxypyrene as a biomarker of exposure to polycyclic aromatic hydrocarbons: biological monitoring strategies and methodology for determining biological exposure indices for various work environments

This article reviews the published studies on urinary 1-hydroxypyrene (1-OHP) as a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs) in work environments. Sampling and analysis strategies as well as a methodology for determining biological exposure indices (BEIs) of 1-OHP in urine for different work environments are proposed for the biological monitoring of occupational exposure to PAHs. Owing to the kinetics of absorption of pyrene by different exposure routes and excretion of 1-OHP in urine, in general, 1-OHP urinary excretion levels increase during the course of a workday, reaching maximum values 3-9 h after the end of work. When the contribution of dermal exposure is important, post-shift 1-OHP excretion can however be lower than pre-shift levels in the case where a worker has been exposed occupationally to PAHs on the day prior to sampling. In addition, 1-OHP excretion levels in either pre-shift, post-shift or evening samples increase during the course of a work-week, levelling off after three consecutive days of work. Consequently, ideally, for a first characterization of a work environment and for an indication of the major exposure route, considering a 5-day work-week (Monday to Friday), the best sampling strategy would be to collect all micturitions over 24 h starting on Monday morning. Alternatively, collection of pre-shift, post-shift and evening urine samples on the first day of the work-week and at the end of the work-week is recommended. For routine monitoring, pre-shift samples on Monday and post-shift samples on Friday should be collected when pulmonary exposure is the main route of exposure. On the other hand, pre-shift samples on Monday and Friday should be collected when the contribution of skin uptake is important. The difference between beginning and end of work-week excretion will give an indication of the average exposure over the workweek. Pre-shift samples on the first day of the work-week will indicate background values, and, hence, reflect general environment exposure and body burden of pyrene and/or its metabolites. On the other hand, since PAH profile can vary substantially in different work sites, a single BEI cannot apply to all workplaces. A simple equation was therefore developed to establish BEIs for workers exposed to PAHs in different work environments by using a BEI already established for a given work environment and by introducing a correction factor corresponding to the ratio of the airborne concentration of the sum of benzo(a)pyrene (BaP) equivalent to that of pyrene. The sum of BaP equivalent concentrations represents the sum of carcinogenic PAH concentrations expressed as BaP using toxic equivalent factors. Based on a previously estimated BEI of 2.3 μmol 1-OHP mol^-1 creatinine for coke-oven workers, BEIs of 4.4, 8.0 and 9.8 μmol 1-OHP mol^-1 creatinine were respectively calculated for vertical pin Söderberg workers, anode workers and pre-bake workers of aluminium plants and a BEI of 1.2 μmol 1-OHP mol^-1 creatinine was estimated for iron foundry workers. This approach will allow the potential risk of cancer in individuals occupationally exposed to PAHs to be assessed better.     

The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure

We investigated the association between biomarkers of dermal exposure, naphthyl-keratin adducts (NKA), and urine naphthalene biomarker levels in 105 workers routinely exposed to jet-fuel. A moderate correlation was observed between NKA and urine naphthalene levels (p?=?0.061). The NKA, post-exposure breath naphthalene, and male gender were associated with an increase, while CYP2E1*6 DD and GSTT1-plus (++/+-) genotypes were associated with a decrease in urine naphthalene level (p?相似文献   

Toxicity of CdSe Nanoparticles in Caco-2 Cell Cultures

Background  

Potential routes of nanomaterial exposure include inhalation, dermal contact, and ingestion. Toxicology of inhalation of ultra-fine particles has been extensively studied; however, risks of nanomaterial exposure via ingestion are currently almost unknown. Using enterocyte-like Caco-2 cells as a small intestine epithelial model, the possible toxicity of CdSe quantum dot (QD) exposure via ingestion was investigated. Effect of simulated gastric fluid treatment on CdSe QD cytotoxicity was also studied.     

Assessment of occupational exposure to PAHs in an Estonian coke oven plant- correlation of total external exposure to internal dose measured as 1-hydroxypyrene concentration

The exposure of cokery workers to polynuclear aromatic hydrocarbons at an Estonian oil shale processing plant was assessed by using occupational hygiene and biomonitoring measurements which were carried out twice, in midwinter and in the autumn. To assess the external dose of polynuclear aromatic hydrocarbons, pyrene and benzo[a]pyrene concentrations were measured from the breathing zone of workers during a workshift. Skin contamination with pyrene and benzo[a]pyrene was assessed by skin wipe sampling before and after the workshift. As a biomarker of overall exposure to polynuclear aromatic hydrocarbons, and as an integral of all absorption routes of pyrene, 1-hydroxypyrene concentration was measured from post shift urine samples. Of the personal air samples, 18% exceeded the Finnish threshold limit value of benzo[a]pyrene (10 μg m^-3). Mean value (two separate measurements together) for benzo[a]pyrene was 5.7 μg m^-3 and for pyrene, 8.1 μg m^-3. Based on skin wipe sample analyses, the skin contamination was also obvious. The mean value of benzo[a]pyrene in the samples collected after the shift was 1.2 ng cm^-2. Benzo[a]pyrene was not found in control samples. The mean value of urinary 1-hydroxypyrene concentration was 6.0 μmol mol^-1 creatinine for the exposed workers and 0.5 μmol mol^-1 creatinine for the controls. This study undoubtedly shows the usefulness of 1-hydroxypyrene as an indicator of internal dose of polynuclear aromatic hydrocarbons. It can be concluded that the cokery workers at the Kohtla-Järve plant are exposed to high concentrations of polynuclear aromatic compounds, and the exposure level is considerably higher during the winter measurements.     

Personal exposure to different levels of benzene and its relationships to the urinary metabolites S-phenylmercapturic acid and trans,trans-muconic acid

This report is part of an extensive study to verify the validity, specificity, and sensitivity of biomarkers of benzene at low exposures and assess their relationships with personal exposure and genetic damage. The study population was selected from benzene-exposed workers in Tianjin, China, based on historical exposure data. The recruitment of 130 exposed workers from glue-making or shoe-making plants and 51 unexposed subjects from nearby food factories was based on personal exposure measurements conducted for 3-4 weeks prior to collection of biological samples. In this report we investigated correlation of urinary benzene metabolites, S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) with personal exposure levels on the day of urine collection and studied the effect of dose on the biotransformation of benzene to these key metabolites. Urinary S-PMA and t,t-MA were determined simultaneously by liquid chromatography-tandem mass spectrometry analyses. Both S-PMA and t,t-MA, but specifically the former, correlated well with personal benzene exposure over a broad range of exposure (0.06-122 ppm). There was good correlation in the subgroup that had been exposed to <1 ppm benzene with both metabolites (P-trend <0.0001 for S-PMA and 0.006 for t,t-MA). Furthermore, the levels of S-PMA were significantly higher in the subgroup exposed to <0.25 ppm than that in unexposed subjects (n=17; P=0.001). There is inter-individual variation in the rate of conversion of benzene into urinary metabolites. The percentage of biotransformation of benzene to urinary S-PMA ranged from 0.005 to 0.3% and that to urinary t,t-MA ranged from 0.6 to approximately 20%. The percentage of benzene biotransformed into S-PMA and t,t-MA decreased with increasing concentration of benzene, especially conversion of benzene into t,t-MA. It appears that women excreted more metabolites than men for the same levels of benzene exposures. Our data suggest that S-PMA is superior to t,t-MA as a biomarker for low levels of benzene exposure.