Relationship between urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites and reproductive hormones in polyvinyl chloride production workers.

OBJECTIVES: We investigated the relationship between urinary metabolites of di(2-ethylhexyl) phthalate (DEHP) and reproductive hormones in workers of polyvinyl chloride (PVC) production plants. After exposure, most of the DEHP is rapidly metabolised to mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), which may be associated with reproductive hormone interruption and testicular toxicity. Some studies report that urinary concentrations of phthalate metabolites for plastics workers are significantly higher than for the general population. However, little is known about the disruption of reproductive hormones for DEHP exposure workers. METHODS: This cross-sectional study of 82 male workers measured the biomarkers for their reproductive hormones and their exposure to DEHP. Relationships between urinary concentrations of DEHP metabolites were estimated using multivariate linear regression and quartile analysis models. RESULTS: The geometric means of urinary creatinine-adjusted (µg/g-Cre) concentrations of MEHP, MEOHP and MEHHP during the post-shift period were 23.9, 66.9 and 84.6, respectively. In multiple regression models adjusted for potential confounders, there were significant positive associations between urinary concentrations of DEHP metabolites and estradiol (E2) (p<0.01), and in the ratio of E2 to testosterone (p<0.05). Moreover, quartile analysis showed significant positive relationships between the total urinary concentration of DEHP metabolites and E2 (ptrend=0.024), and in the ratio of E2 to testosterone (ptrend=0.031). CONCLUSIONS: Relationships between reproductive hormones and the total urinary concentration of DEHP metabolites in male PVC production workers were significantly positive. This indicated that aromatase activity had increased in male workers exposed to DEHP, which is consistent with animal studies.

Cancer risk of incremental exposure to polycyclic aromatic hydrocarbons in electrocautery smoke for mastectomy personnel.

BACKGROUND: Electrocautery applications in surgical operations produce evasive odorous smoke in the cleanest operation rooms. Because of the incomplete combustion of electrical current in the tissues and blood vessels during electrocautery applications, electrocautery smoke (ES) containing significant unknown chemicals and biological forms is released. The potential hazards and cancer risk should be further investigated from the perspective of the occupational health of surgical staff. METHODS: The particle number concentration and the concentration of polycyclic aromatic hydrocarbons (PAHs) in ES were thoroughly investigated in 10 mastectomies to estimate the cancer risk for surgical staff. The particle number concentration and gaseous/particle PAHs at the surgeons' and anesthetic technologists' (AT) breathing heights were measured with a particle counter and filter/adsorbent samplers. PAHs were soxhlet-extracted, cleaned, and analyzed by gas chromatography/mass spectrometry. RESULTS: Abundant submicron particles and high PAH concentrations were found in ES during regular surgical mastectomies. Most particles in ES were in the size range of 0.3 to 0.5 µm, which may potentially penetrate through the medical masks into human respiration. The average particle/gaseous phase PAH concentrations at the surgeon's breathing height were 131 and 1,415 ng/m³, respectively, which is 20 to 30 times higher than those in regular outdoor environments. By using a toxicity equivalency factor, the cancer risk for the surgeons and anesthetic technologists was calculated to be 117 × 10(-6) and 270 × 10(-6), respectively; the higher cancer risk for anesthetic technologists arises due to the longer working hours in operation rooms. CONCLUSIONS: The carcinogenic effects of PAHs in ES on the occupational health of surgical staff should not be neglected. The use of an effective ES evacuator or smoke removal apparatus is strongly suggested to diminish the ES hazards to surgical staff.

Study of urinary mercapturic acids as biomarkers of human acrylonitrile exposure.

Exposure to the vinyl monomer acrylonitrile (AN) is primarily occupational. AN is also found in cigarette smoke. AN can be detoxified to form N-acetyl-S-(2-cyanoethyl)-cysteine (CEMA) or activated to 2-cyanoethylene oxide (CEO) and detoxified to form N-acetyl-S-(1-cyano-2-hydroxyethyl)-cysteine (CHEMA) and N-acetyl-S-(2-hydroxyethyl)-cysteine (HEMA). These urinary mercapturic acids (MAs) are considered to be potential biomarkers of AN exposure. This study assessed personal AN exposure, urinary MAs (CEMA, CHEMA, and HEMA), and cotinine (a biomarker of cigarette smoke) in 80 AN-exposed and 23 non-exposed factory workers from urine samples provided before and after work shifts. Unambiguous linear correlations were observed between levels of urinary CEMA and CHEMA with personal AN exposures, indicating their potential as chemically-specific biomarkers for AN exposures. AN exposure was the dominant factor in MA formation for AN-exposed workers, whereas urinary cotinine used as a biomarker showed that cigarette smoke exposure was the primary factor for non-exposed workers. The CHEMA/CEMA and (CHEMA+HEMA)/CEMA ratios in this human study differ from those in similar studies of AN-treated rats and mice in literature, suggesting a possible dose- and species-dependent effect in AN metabolic activation and detoxification.

Novel active personal nanoparticle sampler for the exposure assessment of nanoparticles in workplaces.

A novel active personal nanoparticle sampler (PENS), which enables the collection of both respirable particulate mass (RPM) and nanoparticles (NPs) simultaneously, was developed to meet the critical demand for personal sampling of engineered nanomaterials (ENMs) in workplaces. The PENS consists of a respirable cyclone and a micro-orifice impactor with the cutoff aerodynamic diameter (d(pa50)) of 4 µm and 100 nm, respectively. The micro-orifice impactor has a fixed micro-orifice plate (137 nozzles of 55 µm in the inner diameter) and a rotating, silicone oil-coated Teflon filter substrate at 1 rpm to achieve a uniform particle deposition and avoid solid particle bounce. A final filter is used after the impactor to collect the NPs. Calibration results show that the d(pa50) of the respirable cyclone and the micro-orifice impactor are 3.92 ± 0.22 µm and 101.4 ± 0.1 nm, respectively. The d(pa50) at the loaded micro-Al(2)O(3) mass of 0.36-3.18 mg is shifted to 102.9-101.2 nm, respectively, while it is shifted to 98.9-97.8 nm at the loaded nano-TiO(2) mass of 0.92-1.78 mg, respectively. That is, the shift of d(pa50) due to solid particle loading is small if the PENS is not overloaded. Both NPs and RPM concentrations were found to agree well with those of the IOSH respirable cyclone and MOUDI. By using the present PENS, the collected samples can be further analyzed for chemical species concentrations besides gravimetric analysis to determine the actual exposure concentrations of ENMs in both RPM and NPs fractions in workplaces, which are often influenced by the background or incident pollution sources.

Simultaneous quantitation of urinary cotinine and acrylonitrile-derived mercapturic acids with ultraperformance liquid chromatography-tandem mass spectrometry.

Acrylonitrile (AN), a widely used industrial chemical also found in tobacco smoke, has been classified as a possible human carcinogen (group 2B) by the International Agency for Research on Cancer. AN can be detoxified by glutathione S-transferase (GST) to form glutathione (GSH) conjugates in vivo. It can be metabolically activated by cytochrome P450 2E1 to form 2-cyanoethylene oxide, which can also be detoxified by GST to generate GSH conjugates. The GSH conjugates can be further metabolized to mercapturic acids (MAs), namely, N-acetyl-S-(2-cyanoethyl)cysteine (CEMA), N-acetyl-S-(2-hydroxyethyl)cysteine (HEMA), and N-acetyl-S-(1-cyano-2-hydroxyethyl)cysteine (CHEMA). This study developed an ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method to quantitatively profile the major AN urinary metabolites (CEMA, HEMA, and CHEMA) to assess AN exposure, as well as analyze urinary cotinine (COT) as an indicator for tobacco smoke exposure. The limits of quantitation were 0.1, 0.1, 1.0, and 0.05 µg/L for HEMA, CEMA, CHEMA, and COT, respectively. This method was applied to analyze the three AN-derived MAs in 36 volunteers with no prior occupational AN exposure. Data analysis showed significant correlations between the level of COT and the levels of these MAs, suggesting them as biomarkers for exposure to low levels of AN. The results demonstrate that a highly specific and sensitive UPLC-MS/MS method has been successfully developed to quantitatively profile the major urinary metabolites of AN in humans to assess low AN exposure.

Biological monitoring for occupational acrylamide exposure from acrylamide production workers.

OBJECTIVE: We conducted a repeated-measurement study to (1) investigate the correlation between occupational exposure to airborne acrylamide (AA) and the time-dependent behavior of urinary AAMA, GAMA2, and GAMA3 and (2) calculate the estimated biological exposure index at the permissible exposure limit (PEL) level of 30 µg/m(3). METHODS: Forty-four workers were recruited--8 were AA-exposed and 36 were controls. Pre- and post-shift urine samples were collected from the exposed group in parallel with personal sampling for 8 consecutive days and only 1 day for the control group and analyzed using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI-MS/MS). RESULTS: Post-shift urinary AAMA level was significantly associated with personal AA exposure (p < 0.001), indicating that urinary AAMA was a better AA exposure biomarker. The estimated urinary excretion of AAMA was 3.0 mg/g creatinine for nonsmoking workers exposed to the PEL of 30 µg/m(3). The median GAMA (the sum of GAMA2 and GAMA3)/AAMA ratio for exposed workers was 0.03 (range, 0.005-0.14), relatively lower than that of the nonoccupational group. CONCLUSIONS: Although sample size in this study was small, the repeated-measurement data provide useful reference for future studies related to biological monitoring of occupational exposure to AA.

Exposure assessment of airborne acrylamide for occupationally exposed workers by using an isotope-dilution gas chromatography coupled with mass spectrometry.

OBJECTIVES: To develop a highly sensitive analytical method for very low acrylamide (AA) exposure and to conduct an occupational exposure assessment by the developed method. METHODS: Seventy-five air samples from four plants were collected and analyzed using an isotope-dilution gas chromatography coupled with mass spectrometry (GC/MS). RESULTS: This isotope-dilution GC-MS method is sufficiently sensitive for assessing very low AA level as 4.37 ng m(-3), which is 10- to 7500-fold lower than the current analytical method. Field study showed that most airborne AA was gaseous rather than particulate. The personal exposure levels in workers ranged from 4.37 x 10(-3) microg m(-3) to 94.90 microg m(-3) with a mean of 12.08 microg m(-3). Fifty percent of personal 8-h time-weighted average (TWA) concentrations in the AA production plant exceeded the threshold limit value of 30 microg m(-3) set by American Conference of Governmental Industrial Hygienists. CONCLUSIONS: The field study indicated that 8-h TWA concentrations in workers varied by two orders of magnitude. The highly sensitive method can be used in future health risk assessment of AA exposure, such as those in fast-food restaurants.

Reduced adiponectin:leptin ratio associated with inhalation exposure to vinyl chloride monomer.

The hepatic toxicity of vinyl chloride monomer (VCM) has often been reported, but few studies have assessed insulin resistance or adipose tissue dysfunction. We analyzed the chronic health effects of moderate exposure to VCM on factory workers in Taiwan. Data were collected from personal air samples, urine samples, and immunohistochemical (IHC) examinations of 122 recruited voluntary participants. Air samples were analyzed to assess personal levels of exposure to VCM and ethylene dichloride (EDC). Urine samples were collected from each worker before they started and after they finished their daily shift. Urinary thiodiglycolic acid (TDGA) levels were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). IHC examinations included liver function and serum adipokine level tests for insulin resistance. Consequently, the participants included for the final analysis were 113. After confounders had been adjusted for, the airborne VCM concentration significantly (P = 0.043) correlated with pre-shift urinary TDGA levels (ß = 0.194). A multivariate analysis showed a significant (P = 0.013) inverse correlation between the adiponectin:leptin ratio and the airborne VCM concentration (ß = -0.283), which means that exposure to VCM might increase the risk of insulin resistance and adiponectin abnormalities. We hypothesized that pre-shift urinary TDGA levels can be used as exposure biomarkers for the exposure of workers to VCM.

Measurements of ultrafine particle concentrations and size distribution in an iron foundry.

The number and surface area concentration of ultrafine particles in an iron foundry is of interest as freshly generated ultrafine particles are produced by metal melting, pouring and molding processes. This study measured the number and surface area concentrations of ultrafine particles and their size distributions in an iron foundry using a scanning mobility particle sizer (SMPS). The 10-100 nm ultrafine particle number concentrations (NC(0.01-0.1)) and surface area concentrations (SC(0.01-0.1)) measured at the iron foundry were 2.07 x 10(4) to 2.82 x 10(5)particles cm(-3) and 67.56 to 2.13 x 10(3)microm(2)cm(-3), respectively. The concentrations changed dramatically depending on on-site manufacturing conditions. The NC(0.01-0.1) levels in the iron foundry were approximately 4.5 times higher on average compared with those in the outdoor ambient environment. These measurement results indicate that the presence of extra particles in the workplace air is within the ultrafine range. Additionally, the analytical results suggest that the number mode diameter can be used to estimate the SC(0.01-0.1) levels using the NC(0.01-0.1) levels. Moreover, the ultrafine particle number mode diameter was found to be about 46.1 nm in the iron foundry.

Exposure assessment of organic solvents for aircraft paint stripping and spraying workers.

The main objective of this study is to investigate the personal or area exposure of organic solvents during paint stripping and paint spraying. Three aircraft paint stripping/spraying workplaces in Taiwan were selected, and the Council of Labor Affairs and NIOSH recommended sampling/analytical methods used in this study. Activated charcoal tubes were used to investigate the personal and area exposure concentration of organic solvents in paint stripping and paint spraying operations. During aircraft paint stripping, experiment results show that methylene chloride personal exposure concentration at the ground area, 42.01+/-31.86 ppm, is higher than that at the working platform 4 M high above the ground, 20.41+/-11.43 ppm. Exposure concentration of methylene chloride in the initial paint stripping operation stage of every workplace is over the PEL (50 ppm) set by the Taiwan Council of Labor Affairs. Corrective actions are needed. During paint spraying, concentrations of all organic solvents were found to be below the PEL of OSHA.

Occupational bladder cancer in a 4,4 -methylenebis(2-chloroaniline) (MBOCA)-exposed worker.

A 52-year-old male chemical worker was admitted to the hospital with a history of paroxysmal microscopic hematuria for about 2 years and nocturia with gross hematuria about five times per night for 2 months. He was a nonsmoker and denied a history of any other bladder carcinogen exposure except for occasional pesticide application during agricultural work. Intravenous urogram imaging showed a mass occupying half of the bladder capacity. Cystoscopy revealed a mass over the left dome of the bladder. Cystoscopic biopsy revealed a grade 3 invasive transitional cell carcinoma with marked necrosis. From 1987 until hospital admission in 2001, the patient had worked in a company that produced the 4,4 -methylenebis(2-chloroaniline) (MBOCA) curing agent. He did not wear any personal protective equipment during work. Ambient air MBOCA levels in the purification process area (0.23-0.41 mg/m3) exceeded the U.S. Occupational Safety and Health Administration's permissible exposure level. Urinary MBOCA levels (267.9-15701.1 microg/g creatinine) far exceeded the California Occupational Safety and Health Administration's reference value of 100 microg/L. This patient worked in the purification process with occupational exposure to MBOCA for 14 years. According to the environmental and biologic monitoring data and latency period, and excluding other potential bladder carcinogen exposure, this worker was diagnosed as having occupational bladder cancer due to high exposure to MBOCA through inhalation or dermal absorption in the purification area. This case finding supports that MBOCA is a potential human carcinogen. Safe use of skin-protective equipment and respirators is required to prevent workers from MBOCA exposure.

Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate (DEHP) for PVC production workers, using personal air sampling and urinary metabolite monitoring.

Because of troubling reports of high urinary metabolite levels and adverse reproductive health effects in workers exposed to di(2-ethylhexyl)phthalate (DEHP) in occupational settings, concern about exposure to DEHP in occupational settings is increasing. However, the contributions of different routes of exposure to DEHP are unclear. We used personal air sampling and biomonitoring to determine the contribution of inhalation exposure to the body burden of DEHP in the workplace. Eighty-nine workers (high-exposure group: 66 raw-materials workers; low-exposure group: 23 administrative workers) were recruited from three polyvinyl chloride (PVC) factories. Urinary levels of mono(2-ethylhexyl) phthalate (MEHP), (mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were measured in pre-shift and post-shift samples. The geometric means of airborne concentrations of DEHP were 5.3 µg/m3 (low-exposure group) and 32.7 µg/m3 (high-exposure group) (P<0.01). Correlation analysis showed a consistently significant association between airborne DEHP concentration and urinary DEHP metabolite levels in the high-exposure group. Calculating daily DEHP intake based on total urinary metabolite levels showed that the geometric means of total daily urinary metabolite levels of DEHP were 9.2 µg/kg/day (low-exposure group) and 15.5 µg/kg/day (high-exposure group) (P<0.01). A quartile analysis of all workers showed a significant trend toward an association between the individual contribution of inhalation exposure to DEHP and urinary DEHP metabolite levels, for which the mean inhalation contribution was 46.7% in the highest quartile. We conclude that inhalation-absorbed airborne DEHP significantly increased the total body burden of DEHP in these occupationally exposed workers.

The modifying effect of CYP2E1, GST, and mEH genotypes on the formation of hemoglobin adducts of acrylamide and glycidamide in workers exposed to acrylamide.

This study assesses the association of acrylamide (AA) and glycidamide (GA) hemoglobin adducts (AAVal and GAVal) and their ratios with genetic polymorphisms of the metabolic enzymes cytochrome P450 2E1 (CYP2E1), exon 3 and 4 of microsomal epoxide hydrolase (mEH3 and mEH4), glutathione transferase theta (GSTT1), and mu (GSTM1) or/and the combinations of these polymorphisms, involved in the activation and detoxification of AA in humans. Fifty-one AA-exposed workers and 34 controls were recruited and provided a post-shift blood sample. AAVal and GAVal were determined simultaneously using isotope-dilution liquid chromatography-electronspray ionization/tandem mass spectrometry (LC-ESI-MS/MS). Genetic polymorphisms of CYP2E1, mEH3 and 4, GSTT1, and GSTM1 were also analyzed. Our results reveal that the GAVal/AAVal ratio, potentially reflecting the proportion of AA metabolized to GA, ranged from 0.13 to 0.45 with a mean at 0.27. Multivariate regression analysis demonstrates that the joint effect of CYP2E1, GSTM1, and mEH4 genotypes was significantly associated with AAVal and GAVal levels after adjustment for AA exposures. These results suggest that mEH4 and the combined genotypes of CYP2E1, GSTM1 and mEH4 may be associated with the formation of AAVal and GAVal. Further studies may be needed to shed light on the roles that phase I and II enzymes play in AA metabolism.

Association of CYP2E1, GST and mEH genetic polymorphisms with urinary acrylamide metabolites in workers exposed to acrylamide.

This study elucidates the association of acrylamide metabolites, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (GAMA2), and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA3) in urine with genetic polymorphisms of the metabolic enzymes cytochrome P450 2E1 (CYP2E1), microsomal epoxide hydrolase (mEH) in exon 3 and exon 4, glutathione transferase theta (GSTT1) and mu (GSTM1), involved in the activation and detoxification of acrylamide (AA) in humans. Eighty-five workers were recruited, including 51 AA-exposed workers and 34 administrative staffs serve as controls. Personal air sampling was performed for the exposed workers. Each subject provided pre- and post-shift urine samples and blood samples. Urinary AAMA, GAMA2 and GAMA3 levels were simultaneously quantified using liquid chromatography-electronspray ionization/tandem mass spectrometry (LC-ESI-MS/MS). CYP2E1, mEH (in exon 3 and exon 4), GSTT1, and GSTM1 were analyzed using polymerase chain reaction (PCR). Our results reveal that AA personal exposures ranged from 4.37 × 10⁻³ to 113.61 µg/m³ with a mean at 15.36 µg/m³. The AAMA, GAMA2, and GAMA3 levels in the exposed group significantly exceeded those in controls. The GAMAs (the sum of GAMA2 and GAMA3)/AAMA ratios, potentially reflecting the proportion of AA metabolized to glycidamide (GA), varied from 0.003 to 0.456, and indicate high inter-individual variability in the metabolism of AA to GA in this study population. Multivariate regression analysis demonstrates that GSTM1 genotypes significantly modify the excretion of urinary AAMA and the GAMAs/AAMA ratio, exon 4 of mEH was significantly associated with the urinary GAMAs levels after adjustment for AA exposures. These results suggest that mEH and/or GSTM1 may be associated with the formation of urinary AAMA and GAMAs. Further study may be needed to shed light on the role of both enzymes in AA metabolism.

Simultaneous analysis of urinary 4,4'-methylenebis(2-chloroaniline) and N-acetyl 4,4'-methylenebis(2-chloroaniline) using solid-phase extraction and liquid chromatography/tandem mass spectrometry.

Analysis of 4,4'-methylenebis(2-cholroaniline) (MOCA) or its metabolites in urine has been considered as the appropriate method to assess MOCA exposures through inhalation and skin absorption. MOCA and its metabolite, N-acetyl 4,4'-methylenebis(2-chloroaniline) (acetyl-MOCA), are analyzed using methods either limited by sensitivity or sample preparation. Therefore, a solid-phase extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed to simultaneously analyze MOCA and acetyl-MOCA in urine to serve as biomarkers for MOCA exposure. Protein was precipitated by using acetonitrile, and SPE were applied to clean up samples to eliminate the matrix effect and to improve the recovery. The limit of quantitation of this method was at 1.0 ng/mL for MOCA and 0.03 ng/mL for acetyl-MOCA (signal-to-noise (S/N) ratio = 10). Urinary MOCA and acetyl-MOCA levels in MOCA-exposed workers were analyzed and quantitated to be 191.9 +/- 373.2 (mean +/- standard deviation (SD)) and 11.79 +/- 23.8 ng/mL (N = 54) with the median values 38.6 and 1.8 ng/mL, respectively. MOCA concentrations are significantly correlated with their corresponding acetyl-MOCA levels in urine (Spearman correlation coefficient r = 0.916, p < 0.001). These results show that this method has been successfully developed and provides high-throughput potential to analyze MOCA and acetyl-MOCA to serve as exposure biomarkers for future study of the potential health effects associated with MOCA exposures.

Bladder cancer screening and monitoring of 4,4'-methylenebis(2-chloroaniline) exposure among workers in Taiwan.

OBJECTIVES: Transitional cell carcinoma of the urinary bladder is associated with occupational exposure to 4,4'-methylenebis(2-chloroaniline) (MBOCA). A program to monitor MBOCA levels in the work environment and to screen for bladder cancer was performed at four MBOCA manufacturing factories. METHODS: The U.S. Occupational Safety and Health Administration analytic method No. 24 was adopted in this study to measure air MBOCA concentrations. A total of 70 MBOCA-exposed workers and another 92 nonexposed workers were recruited for screening. Urine occult blood tests, urine cytology, tests for the urine tumor marker nuclear matrix protein, and abdominal ultrasonography were performed in all patients. Intravenous urography and cystoscopy were used to confirm the presence of bladder cancer. RESULTS: The air concentration of MBOCA was greatest in the purification area (0.23 to 0.41 mg/m3), followed by the washing area (less than 0.02 to 0.08 mg/m3) and neutralization area (less than 0.05 to 0.06 mg/m3). This study identified a current worker with proved bladder cancer. In addition, we also identified 1 worker with suspected malignant cells on urine cytology and 1 worker with atypical cytology combined with gross hematuria. Although the prevalence of atypical urinary cells and the nuclear matrix protein 22 tumor marker was not significantly different between the MBOCA-exposed workers and nonexposed workers as a whole or when grouped by sex, the prevalence of positive occult blood was marginally significantly (P = 0.055) greater in male exposed workers (18%) than in male nonexposed workers (7%). CONCLUSIONS: The findings of this study support the conclusions from other studies that MBOCA is potentially carcinogenic to humans. Control measures are needed to prevent overexposure from inhalation and skin absorption.

Analysis of 7-methylguanine using isotope dilution and gas chromatography/electron-capture negative chemical ionization mass spectrometry.

This paper presents results obtained for in vivo endogenous and exogenous 7-methylguanine (7-MG) analyzed using a method incorporating gas chromatography with electron-capture negative chemical ionization mass spectrometry and isotope dilution (GC/EC-ID-MS). 13C4-Labeled 7-MG was synthesized to serve as an internal standard to improve accuracy of quantitation, and was used to analyze 7-MG in livers of control mice and dacarbazine-treated mice. The results confirm that 7-MG in tissue DNA can be measured using this GC/EC-ID-MS method with excellent sensitivity and specificity. Administration of 0, 30, and 60 mg/kg dacarbazine to mice led to dose-dependent increases in the formation of 7-MG. The results indicate that this method could be applied to the analysis of endogenous and exogenous 7-MG in human tissues for future molecular epidemiology studies on potential health effects caused by methylating agents.