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Background Epidemiological evidence has linked fine particulate matter (PM2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM2.5 in spontaneously hypertensive (SH) rats. Results SH rats were exposed to S-, K-, Si-, and Fe-dominated PM2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 μg/m3 for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM2.5 exposure (p 2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p 2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM2.5 exposure. Conclusions Chronic exposure to low-level PM2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension.

Photoresist materials are indispensable in photolithography, a process used in semiconductor fabrication. The work process and potential hazards in semiconductor production have raised concerns as to adverse health effects. We therefore performed a health risk assessment of occupational exposure to positive photoresists in a single optoelectronic semiconductor factory in Taiwan. Positive photoresists are widely used in the optoelectronic semiconductor industry for photolithography. Occupational exposure was estimated using the Stoffenmanager® model. Bayesian modeling incorporated available personal air sampling data. We examined the composition and by-products of the photoresists according to descriptions published in the literature and patents; the main compositions assessed were propylene glycol methyl ether acetate (PGMEA), novolac resin, photoactive compound, phenol, cresol, benzene, toluene, and xylene. Reference concentrations for each compound were reassessed and updated if necessary. Calculated hazard quotients were greater than 1 for benzene, phenol, xylene, and PGMEA, indicating that they have the potential for exposures that exceed reference levels. The information from our health risk assessment suggests that benzene and phenol have a higher level of risk than is currently acknowledged. Undertaking our form of risk assessment in the workplace design phase could identify compounds of major concern, allow for the early implementation of control measures and monitoring strategies, and thereby reduce the level of exposure to health risks that workers face throughout their career.

Addressing occupational health and safety concerns early in the design stage anticipates hazards and enables health professionals to recommend control measures that can best protect workers’ health. This method is a well-established tool in public health. Importantly, its success depends on a comprehensive exposure assessment that incorporates previous exposure data and outcomes. Traditional methods for characterizing similar occupational exposure scenarios rely on expert judgment or qualitative descriptions of relevant exposure data, which often include undisclosed underlying assumptions about specific exposure conditions. Thus, improved methods for predicting exposure modeling estimates based on available data are needed. This study proposes that cluster analysis can be used to quantify the relevance of existing exposure scenarios that are similar to a new scenario. We demonstrate how this method improves exposure predictions. Exposure data and contextual information of the scenarios were collected from past exposure assessment reports. Prior distributions for the exposure distribution parameters were specified using Stoffenmanager® 8 predictions. Gower distance and k-Medoids clustering algorithm analyses grouped existing scenarios into clusters based on similarity. The information was used in a Bayesian model to specify the degree of correlation between similar scenarios and the scenarios to be assessed. Using the distance metric to characterize the degree of similarity, the performance of the Bayesian model was improved in terms of the average bias of model estimates and measured data, reducing from 0.77 (SD: 2.0) to 0.49 (SD: 1.8). Nevertheless, underestimation of exposures still occurred for some rare scenarios, which tended to be those with highly variable exposure data. In conclusion, the cluster analysis approach may enable transparent selection of similar exposure scenarios for factoring into design-phase assessments and thereby improve exposure modeling estimates.

Data concerning the effects of prenatal exposures to nonylphenol (NP) and oxidative stress on neonatal birth outcomes from human studies are limited. A total of 146 pregnant women were studied (1) to investigate the association between prenatal NP exposure and maternal oxidative/nitrative stress biomarkers of DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua)) and lipid peroxidation (8-iso-prostaglandin F2α (8-isoPF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) and (2) to explore the associations among oxidative stress biomarkers, NP exposure, and neonatal birth outcomes, including gestational age, birth weight, length, Ponderal index, and head and chest circumferences. NP significantly increased the 8-OHdG and 8-NO2Gua levels. All infants born to mothers with urinary 8-OHdG levels above the median exhibited a significantly shorter gestational duration (Badjusted = -4.72 days; 95% CI: -8.08 to -1.36 days). No clear association was found between NP levels and birth outcomes. Prenatal 8-OHdG levels might be a novel biomarker for monitoring fetal health related to NP exposure.

Maleic acid (MA), an intermediate reagent used in many industrial products, instigated public health concerns in Taiwan when it was used to adulterate an array of starch-based delicacies to improve texture and storage time. Established studies reported that exposure to high concentrations of MA induce renal injury; little is known whether oxidative stress is induced at a relative low dose. This study aims to investigate the effect of oral single dose exposure of MA on the status of oxidative stress and inflammation. Single dose of MA at 0, 6 and 60 mg/kg (control, low- and high-dose groups, respectively) were orally administered to adult male and female rats. Urine samples were collected and analyzed to measure 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-IsoPGF2α), 8-nitroguanine (8-NO2Gua) and N-acetyl-S-(tetrahydro-5-hydroxy-2-pentyl-3-furanyl)-L-cysteine (HNE-MA) using LC-MS/MS. Results revealed that oral consumption of MA induced oxidative DNA damage and lipid peroxidation, as demonstrated by the statistically significant increases in urinary levels of 8-NO2Gua, 8-OHdG, and 8-isoPGF2α, in high-dosed male rats within 12 h of oral gavage (p < 0.05). Additionally, increases in concentration of these biomarkers persist for days after consumption; male rats appear to be more sensitive to oxidative burden compared to their counterparts. The aforementioned findings could help elucidate the mechanisms through which nephrotoxicity occur.

We evaluated the reliability of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and determined its ability to predict functional outcomes in stroke survivors. The rehabilitation effect on 8-OHdG and functional outcomes were also assessed. Sixty-one stroke patients received a 4-week rehabilitation. Urinary 8-OHdG levels were determined by liquid chromatography–tandem mass spectrometry. The test-retest reliability of 8-OHdG was good (interclass correlation coefficient = 0.76). Upper-limb motor function and muscle power determined by the Fugl-Meyer Assessment (FMA) and Medical Research Council (MRC) scales before rehabilitation showed significant negative correlation with 8-OHdG (r = −0.38, r = −0.30; p < 0.05). After rehabilitation, we found a fair and significant correlation between 8-OHdG and FMA (r = −0.34) and 8-OHdG and pain (r = 0.26, p < 0.05). Baseline 8-OHdG was significantly correlated with post-treatment FMA, MRC, and pain scores (r = −0.34, −0.31, and 0.25; p < 0.05), indicating its ability to predict functional outcomes. 8-OHdG levels were significantly decreased, and functional outcomes were improved after rehabilitation. The exploratory study findings conclude that 8-OHdG is a reliable and promising biomarker of oxidative stress and could be a valid predictor of functional outcomes in patients. Monitoring of behavioral indicators along with biomarkers may have crucial benefits in translational stroke research.

Perfluoroalkyl substances (PFASs) can cross the placenta, enter fetal circulation, and were found to correlate with adverse fetal growth. However, determinants of cord blood PFASs are not fully characterized. The study aimed to explore the association between PFASs and neonatal-maternal factors within a Taiwanese birth cohort. We selected subjects from Taiwan Birth Panel Study, which enrolled 486 infant-mother pairs in 2004-2005. We collected cord blood and analyzed perfluorooctanoic acid (PFOA), perfluorooctanyl sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) using a simple protein precipitation and an ultra-high performance liquid chromatography/tandem mass spectrometry. We retrieved information pertaining to maternal socio-demographics, lifestyle- and dietary-related factors through structured questionnaires during the postpartum hospital stay. A total of 439 subjects, with 90% response rate, have completed serum analysis and questionnaire survey. The median concentrations for PFOA, PFOS, PFNA, and PFUA in cord blood were 1.86, 5.67, 3.00, and 13.5ngmL(-1), respectively. After adjusting for potential confounders, multiple linear regression models revealed that log10-PFOA was positively associated with maternal age (β=0.011) and negatively associated with multiparity (β=-0.044). Log10-PFOS was negatively correlated with birth weight (β=-0.011) and higher maternal education (senior high school: β=-0.067; university: β=-0.088). Log10-PFUA tended to negatively associate with gender, male infants (β=-0.075), and using cosmetics during pregnancy (β=-0.065). Interestingly, presence of cockroaches in the home was positively associated with log10-PFOA (β=0.041) and 1og10-PFNA (β=0.123). In conclusion, this study demonstrated several factors to correlate with cord blood PFASs and further investigation are still needed for confirmation of exposure routes.

Introduction Environmental tobacco smoke (ETS) is a hazardous component of indoor air, and may increase the risk of respiratory diseases, atherosclerosis and otitis media in children. In this study, we explored the relationship between time inside the house, ETS exposure and urinary cotinine level, and also determined the association of time inside the house on asthma phenotypes when children exposed to ETS. Methods A total of 222 asthmatic children and 205 non-asthmatic controls were recruited in the Genetic and Biomarker study for Childhood Asthma (GBCA). Structured questionnaires and time–location pattern questionnaires were administered by face-to-face interview. Urinary cotinine was measured by liquid chromatography tandem mass spectrometry (LC/MS/MS). The level of household ETS exposure was assessed using the cotinine/creatinine ratio (CCR). Results In general, urinary cotinine and CCR were higher in subjects exposed to household ETS than those who never had ETS at home. A significant positive relationship was found between average time inside the house and urinary CCR in asthmatic children with current ETS at home (β=0.278, p=0.02). After adjustment for age and gender, average time inside the house was positively related to severe wheeze in asthmatic children with household ETS within 1 month (OR: 1.26, 95%: 1.02–1.64). Conclusions Our study suggests that the major source of ETS exposure for children is due to longer period of exposures among children living with adult smokers at home. Home-smoking restrictions that effectively prevent children from being exposed to ETS would be worthwhile.

BackgroundA new engineering intervention measure, an embracing air curtain device (EACD), was used to increase the capture efficiency of cooker hoods and reduce cooking oil fume (COF) exposure in Chinese restaurants.MethodsAn EACD was installed in six Chinese restaurants where the cooks complained of COF exposure. Before- and after-installation measurements were taken to compare changes in particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) in kitchen air, and changes in levels of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The association between PM and PAHs in air and 8-OHdG and MDA in urine was evaluated by linear mixed-effects regression analysis.ResultsResults showed that geometric mean kitchen air levels of PM10, PM2.5, PM1.0and total particulate PAHs were significantly reduced after the EACDs were introduced. Urinary levels of 8-OHdG and MDA in cooks were also significantly lower after EACD instalment. PM2.5, PM1.0and benzo(a)pyrene (BaP) levels were positively associated with urinary 8-OHdG levels after adjusting for key personal covariates. Urinary MDA levels in cooks were also positively associated with BaP levels after adjusting for key personal covariates.ConclusionThis study demonstrates that the EACD is effective for reducing COF and oxidative stress levels in cooks working in Chinese kitchens.

Little is known about the exposure profiles of melamine in children. We evaluated the association of clinical findings, exposure patterns and biomarkers with nephrolithiasis in children with potential exposure to melamine.A case-control study was conducted in children aged 0-16 years with potential exposure to contaminated dairy products. Cases were defined as nephrolithiasis detected by renal ultrasonography. On the basis of different brands of contaminated dairy products consumed, subjects were classified into high exposure, low exposure and control groups with estimated melamine exposure levels of higher than 2.5 ppm, 0.05-2.5 ppm and lower than detection limits0.05 ppm. We measured urine melamine for those with nephrolithiasis and age-matched and gender-matched controls within the subset of the study population.The duration of consumption of contaminated products was longer in children with nephrolithiasis in the high exposure group than in controls (median (IQR) 12.0 (3.3-24.0) vs 6.0 (4.0-7.0) months; p = 0.048). High melamine exposure levels were significantly associated with nephrolithiasis (OR 61.04 (95% CI 12.73 to 292.84)). The risk was found to increase with estimate melamine exposure levels (p for trend0.001). Two among 10 affected subjects with nephrolithiasis showed elevated urine melamine levels. In comparison, levels of all 20 controls were lower than the detection limit.The risk of melamine-associated nephrolithiasis was related to duration of consumption of contaminated products and estimated melamine exposure levels. Though urine melamine was not a sensitive test, it might serve as an exposure biomarker in melamine-associated nephrolithiasis.

This study evaluates oxidative DNA damage in workers who are exposed to cooking oil fumes (COFs) in Chinese restaurants. The study participants were 387 nonsmoking Chinese restaurant workers, 202 kitchen staff, and 185 service staff at 23 Chinese restaurants in Taiwan. Airborne particulate matter and particulate polycyclic aromatic hydrocarbon levels were monitored in kitchens and dining areas. Urinary 1-hydroxypyrene (1-OHP) was used as an internal dose of exposure to COFs, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was used as an oxidative DNA damage marker. The relationship between workers' 8-OHdG and 1-OHP levels was estimated using linear mixed-effects models. Airborne particulate matter and polycyclic aromatic hydrocarbons levels in kitchens significantly exceeded those in dining areas. The kitchen staff's geometric mean levels of urinary 8-OHdG (7.9 μg/g creatinine) and 1-OHP (4.5 μg/g creatinine) were significantly higher than those of the service staff, which were 5.4 and 2.7 μg/g creatinine, respectively. Urinary 1-OHP level, work in kitchens, gender, and work hours per day were four significant predictors of urinary 8-OHdG levels after adjustments are made for covariates. Oxidative DNA damage was associated with exposure of Chinese restaurant workers to COFs. Female restaurant workers had a greater oxidative stress response to COFs than male restaurant workers, providing additional evidence of the link between lung cancer in Chinese women and exposure to COFs. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3351–7)

Objectives: To assess internal dose and oxidative stress in male restaurant workers exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking oil fumes (COFs) in Chinese restaurants. Methods: The study participants included 288 male restaurant workers (171 kitchen and 117 service staff) in Chinese restaurants in Taiwan. Airborne particulate PAHs were measured over 12 h on each of two consecutive work days and then identified using high performance liquid chromatography. Urinary 1-hydroxypyrene (1-OHP) measurements were used to indicate COF exposure, and urinary malondialdehyde (MDA) was adopted as an oxidative stress marker. Multiple regression models were used to assess the relationship between MDA and 1-OHP levels after adjusting for key personal covariates. Results: Summed particulate PAH levels in kitchens (median 23.9 ng/m3) were significantly higher than those in dining areas (median 4.9 ng/m3). For non-smoking kitchen staff, mean MDA and 1-OHP levels were 344.2 (SD 243.7) and 6.0 (SD 8.0) μmol/mol creatinine, respectively. These levels were significantly higher than those for non-smoking service staff, which were 244.2 (SD 164.4) and 2.4 (SD 4.3) μmol/mol creatinine, respectively. Urinary 1-OHP levels were significantly associated with work in kitchens (p

To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Clinical outcome study in an adult medical intensive care unit (ICU). 85 consecutive septic patients (59 men, 26 women). Patient characteristics and the clinical course were examined. Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality was 25.9% (22/85) and hospital mortality 38.8% (33/85). Survivors' APACHE II scores on days 1 and 3 and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. This is a preliminary study. Excretion of urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, and the APACHE II score were correlated with the outcome of critically septic patients in medical ICU.

Background Oxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke. Methods In this nested case–control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography–tandem mass spectrometry, including 8-iso-prostaglandin F 2α (8-iso-PGF 2α ), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine. Results The levels of urinary 8-iso-PGF 2α in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23–4.36) μg/g creatinine versus 0.71 (1.34–3.02) μg/g creatinine, p=0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF 2α entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06–1.85; p=0.005] with a significant increasing trend across its quartiles (p for trend=0.016). After adding urinary 8-iso-PGF 2α , the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006–0.045; p=0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6–35.1%; p=0.011). In contrast, the relationships were non-significant among the other three biomarkers. Conclusions Our findings demonstrated that urinary 8-iso-PGF 2α could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.

Background and Purpose— The increasing availability of robot-assisted therapy (RT), which provides quantifiable, reproducible, interactive, and intensive practice, holds promise for stroke rehabilitation, but data on its dose–response relation are scanty. This study used 2 different intensities of RT to examine the treatment effects of RT and the effect on outcomes of the severity of initial motor deficits. Methods— Fifty-four patients with stroke were randomized to a 4-week intervention of higher-intensity RT, lower-intensity RT, or control treatment. The primary outcome, the Fugl-Meyer Assessment, was administered at baseline, midterm, and posttreatment. Secondary outcomes included the Medical Research Council scale, the Motor Activity Log, and the physical domains of the Stroke Impact Scale. Results— The higher-intensity RT group showed significantly greater improvements on the Fugl-Meyer Assessment than the lower-intensity RT and control treatment groups at midterm ( P =0.003 and P =0.02) and at posttreatment ( P =0.04 and P =0.02). Within-group gains on the secondary outcomes were significant, but the differences among the 3 groups did not reach significance. Recovery rates of the higher-intensity RT group were higher than those of the lower-intensity RT group, particularly on the Fugl-Meyer Assessment. Scatterplots with curve fitting showed that patients with moderate motor deficits gained more improvements than those with severe or mild deficits after the higher-intensity RT. Conclusions— This study demonstrated the higher treatment intensity provided by RT was associated with better motor outcome for patients with stroke, which may shape further stroke rehabilitation. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00917605.

Background and Aims:Environmental tobacco smoke (ETS) is an important exposure of indoor air, and may increase the risk of respiratory disease in children. The level of household ETS exposure may b...

Background and Aims: The evidence of exposure to environmental tobacco smoke (ETS) on children’s growth and obesity is limited and not sufficient to conclude a definitive relationship. The aim of t...

OBJECTIVE The aim of this study was to examine whether infant metabolic gene polymorphisms modify the effect of maternal environmental tobacco smoke (ETS) on neonatal neurobehavior. METHODS We conducted a birth cohort study of 87 nonsmoking women who delivered single births of normal birth weight. We enrolled the women before delivery, interviewed them using a structured questionnaire, and collected umbilical cord blood. Umbilical cord cotinine, a blood indicator of prenatal ETS exposure, was analyzed. The Neonatal Neurobehavioral Examination-Chinese Version (NNE-C) was administrated within 5 days after delivery to examine neonatal neurobehavior. Four infant metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1, and GSTM1, were identified. RESULTS Maternal ETS exposure during pregnancy was not related to neonatal neurobehavior when infant genetic polymorphisms were not considered. However, maternal ETS exposure did cause adverse effects in neonates with the absent type of GSTM1. Adverse effects were seen on the total NNE-C (β = -2.55; p = .02) and on primitive reflexes (β = -1.70; p = .004), especially in grasp reflexes (β = -.36; p = .011) and tonic neck reflexes (β = -.36; p = .049). In addition, there was a significant interaction between maternal ETS exposure and infant GSTM1 genotype on neonate grasp reflexes (p for interaction = .019). CONCLUSIONS These data indicate that weaker responses in neonatal primitive reflexes in infants with the absent type GSTM1 were related to maternal ETS exposure during pregnancy.

Objectives: The object of this study was to assess the modulating effects of genetic polymorphisms of glycine N-methyltransferase (GNMT) genotypes on 1-hydroxypyrene (1-OHP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urine from coke-oven workers, consistently exposed to polycyclic aromatic hydrocarbons (PAHs). Methods: The study participants included 289 coke-oven workers from a steel company in Taiwan. Personal air samples, spot urine samples, peripheral blood samples, and questionnaires were used to quantify PAH exposure, oxidative DNA damage, GNMT gene polymorphisms, demographic data, and environmental pollutants. Results: Urinary 1-OHP level, GNMT STRP1 genotype, and worksite were significant predictors of urinary 8-OHdG levels after adjustments were made for covariates. Conclusions: This study suggests that GNMT STRP1 could modulate urinary 1-OHP and 8-OHdG levels in coke-oven workers exposed to PAHs.

Background and Objectives. Robot-assisted therapy (RT) is a current promising intervention in stroke rehabilitation, but more research is warranted for examining its efficacy and the dose–benefit relation. The authors investigated the effects of higher intensity versus lower intensity RT on movements of forearm pronation–supination and wrist flexion–extension relative to conventional rehabilitation (CR) in patients poststroke for a mean of 21 months. Methods. In this pilot study, 18 patients with initial mean Fugl-Meyer Assessment (FMA) of 37 to 44 for the upper extremity were randomized to higher intensity RT, lower intensity RT, or CR intervention for 4 weeks. The dose of the higher intensity RT was twice the number of repetitions in the lower intensity RT. Outcome measures at pretreatment and posttreatment were administered to patients to evaluate beneficial and adverse effects of interventions. Primary outcomes were the FMA and Medical Research Council scale. Results. There were significant differences in motor function ( P = .04) and daily performance ( P = .03) among the 3 groups. The higher intensity RT group showed better improvement in motor function, muscle strength, performance of daily activities, and bimanual ability than the other 2 groups. The intensive RT intervention did not induce higher levels of an oxidative DNA biomarker. Conclusions. Higher intensity of RT that assists forearm and wrist movements may lead to greater improvement in motor ability and functional performance in stroke patients. A sample size of only 20 to 25 in each arm of a larger randomized controlled trial is needed to confirm the findings for similar subjects.

Although the 2008 outbreak of nephrolithiasis in children due to melamine-contaminated infant formula has subsided, it remains uncertain whether the present tolerable daily intake (TDI) of melamine provides sufficient protection for young children. To conduct a safety assessment for melamine in infant formula, we established a dose-response relationship based on 13 nephrolithiasis cases selected from 932 children, all of whom were under 5 years of age and had potentially been exposed to contaminated milk in China or Taiwan. According to the children's exposure history, distributions of individual daily melamine intake (mg/kg BW/day) were reconstructed using Monte Carlo simulations to account for uncertainties in exposure duration and melamine concentrations in the contaminated milk. Based on the simulated individual average daily intake (AVDI) of melamine, subjects were further classified into four separate AVDI groups: high, medium, low and a reference group. A statistical logistic model was then fitted for the dose-response relationship between nephrolithiasis incidence and daily melamine intakes using Markov chain Monte Carlo (MCMC) simulations. Based on the background exposure, spontaneous rate, and mode of action (MOA) of nephrolithiasis in children, the simulated lower bounds of the 95% CIs daily melamine intake ranged from 0.008 to 0.03 mg/kg BW/day corresponding to an additional risks of 0.1% is proposed as a plausible TDI, which is approximately an order lower than the current WHO-suggested TDI level of 0.2 mg/kg BW/day. More stringent regulations on melamine levels in infant formula should be considered to protect young children fully.

Introduction: Maternal environmental tobacco smoke (ETS) has been identified as a key risk factor for problem behavior in children, but the role of genetic susceptibility is not clear. The purpose of this study was to examine the metabolic genetic modification effect of exposure to ETS in nonsmoking mothers on child behavior at 2 years of age. Methods: A prospective cohort study was conducted among 191 mothers who gave births between 2004 and 2005 and their infants in Taiwan. The mothers completed a questionnaire before delivery in which they provided information on exposure to ETS during pregnancy. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1, and GSTM1 were isolated from both maternal and infant DNA samples. Children's behavior problems at 2 years of age were reported by their mothers using the Child Behavior Checklist/1.5-5. Multiple linear models were used to estimate the effects of ETS and genotype on child behavior. Results: Maternal ETS exposure was associated with the anxious score. The ETS-exposed group with both the CYP1A1 MspI and the CYP1A1 Ile462 Val variants had higher scores, as reflected in total CBCL score as well as scores on the internalizing scale and its emotional subdomain, the anxious scale, and the externalizing scale and its aggressive subdomain. Conclusions: Child behavioral problems may be associated with prenatal ETS exposure, and this effect may be modified by infant CYP1A1 MspI and CYP1A1 Ile462 Val genes.

The adverse impact of smoking on respiratory diseases and birth outcomes in children is well-known. However, the influence of smoke exposure including environmental tobacco smoke (ETS) and maternal smoking during pregnancy on atopic dermatitis (AD) is not clear. The purpose of this study was to evaluate the effect of gestational smoke exposure on the development of AD in the offspring on the basis of the maternal and cord blood cotinine. We recruited 261 mother and newborn pairs in 2004. Cord blood and information on perinatal factors of children were gathered at birth. At 2 yr of age, information about development of AD and environmental exposures were collected. We compared AD with non-AD children for the concentration of cotinine in cord and maternal blood measured by high performance liquid chromatography-mass spectrometry. Multiple logistic regressions were performed to estimate the relationship of cotinine levels and AD. About 150 mother and child pairs completed the follow-up study and specimen collection with 38 (25.3%) children developing AD. Two (1.3%) out of 150 mothers smoked during pregnancy, while 38 (25.3%) mothers reported having ETS exposure. Cotinine levels in cord blood and maternal blood were highly correlated (r = 0.71, p0.001). The risk of AD was found to increase with maternal and cord blood cotinine levels in a dose-response manner (p for trend = 0.01). Children exposed to high levels (75th percentile) had a significantly increased risk of AD. Smoke exposure during pregnancy might increase the risk of AD in children. Avoidance of prenatal smoke exposure may be warranted for early prevention.

Maternal exposure to environmental tobacco smoke (ETS) has been reported to be associated with children's neurobehavioral development but there was no studies investigating the genetic susceptibilities to maternal ETS exposure on children's neurodevelopment. The aim of the study was to explore the modification effect of metabolic gene polymorphisms to cord blood cotinine on children's neurodevelopment at the 2 years of age. This study is one investigation of the Taiwan Birth Panel Study and a total of 145 pregnant women and their neonates were recruited between April 2004 and January 2005. We interviewed them by a structured questionnaire after delivery and collected umbilical cord blood at birth. Cotinine in umbilical cord blood as an indicator of environmental tobacco smoke was analyzed by using HPLC–MS/MS and the detection limited of this method was 0.05 ng/mL. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were identified. The Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) was used for assessing children's neurodevelopment at the 2 years of age accompanying with the measurement of Home Observation for Measurement of the Environment scale. We used multiple linear regression models to estimate the effects of cord blood cotinine and gene modification. Cotinine levels were significantly negatively associated with developmental quotients (DQs) of the whole test, and cognitive, language, fine-motor and social subtests of the CDIIT. Lower cognitive and language DQs were found in exposed group with absent type of GSTT1. In addition, the lowest scores in fine-motor and whole test DQs were detected in exposed group with CYP1A1 Ile462Val variant type and GSTT1 absent type. It can be concluded that CYP1A1 Ile462Val and GSTT1 metabolic genes can modify the effect of cord blood cotinine on early child neurodevelopment especially for language and fine motor development.

Oxidative DNA damage may play an important role in the human carcinogenic process. Recently, we reported a case of bladder cancer among 4, 4'-methylenebis (2-chloroaniline) (MBOCA)-exposed workers. By measuring the plasma level of 8-hydroxydeoxyguanosine (8-OHdG), we investigated the association between oxidative DNA damage and MBOCA exposure. In addition, we examined the effects of different confounders on the plasma level of 8-OHdG. We undertook a cross-sectional survey at four MBOCA-producing factories in Taiwan (158 subjects). Plasma 8-OHdG levels and urinary MBOCA concentrations were measured by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Personal characteristics were collected by questionnaire. The workers were classified according to their job titles as exposed (n=57) or unexposed (n=101) groups as well as classified according to urinary MBOCA levels as high urinary MBOCA (20 microg/g creatinine) (n=45) or low urinary MBOCA (n=108) groups. Neither the MBOCA-exposed workers nor the high urinary MBOCA workers had a significant increase in the mean plasma 8-OHdG level, even after adjustment for potential confounders. Age and gender were significantly positively correlated with plasma 8-OHdG levels. Smokers among high urinary MBOCA workers also had significantly higher 8-OHdG levels than non-smokers among high urinary MBOCA workers. Our study provides evidence that smoking rather than MBOCA exposure induces elevation of plasma 8-OHdG levels among workers exposed to MBOCA, indicating that oxidative DNA damage does not play an important role in the carcinogenic processes of MBOCA.

Objectives Our aim is to analyze the association between polycyclic aromatic hydrocarbon (PAH) exposure and the temporal change of urinary 1-hydroxypyrene (1-OHP). Methods Two personal air samples, eight spot urine samples, and questionnaires were used to collect PAH exposure, urinary 1-OHP, demographic data, and environmental pollutants. Results Topside-oven workers had significantly higher levels of PAH exposure and 1-OHP than side-oven workers. Urinary 1-OHP was a biomarker for PAH exposure. In topside-oven workers, the trend of 1-OHP increased sharply and reached the top in the sixth day after work and declined dramatically on days off. In side-oven workers, such a trend was not found, and those who smoked showed a slight increase in urinary 1-OHP levels on days off. Conclusions We suggest that the pattern of temporal change of urinary 1-OHP levels is different between topside-oven and side-oven workers.

Background Both active cigarette smoking and human papillomavirus (HPV) infection are known risk factors for cervical intraepithelial neoplasm (CIN). The association between second-hand smoke (SHS) and CIN has not been conclusively determined. We conducted a community-based case–control study to estimate the relationship between SHS and CIN. Methods Potential study subjects were selected through Pap smear screening in Kaohsiung County, Taiwan. A total of 171 subjects with either their first case of inflammation (benign epithelial lesion) or ≥CIN1 by biopsy confirmation were assigned to a case group; 513 normal subjects with negative findings by Pap smears or biopsies were assigned to a control group. Results Non-smoking women exposed to more than 20 pack-years of cigarette smoke had a significantly greater risk of developing ≥CIN2 than unexposed non-smokers (adjusted OR=7.2, 95% CI=2.5–20.6). Among the women without HPV infections, the greater the severity of disease found in the groups (normal, inflammation, CIN1, to ≥CIN2), the more likely it was for the women to be exposed to SHS, a significant increasing trend ( p =0.037). Conclusions In addition to HPV infection and active cigarette smoking, exposure to SHS is a major risk factor for CIN among Taiwanese women.

The occupational exposure limits (OELs) in Taiwan was promulgated in 1974 and has been revised five times since then. Many of the OELs were adopted from the most recent ACGIH TLVs and US OSHA PELs. A total of 483 chemicals were listed in the current Taiwan OELs Standard. The procedures of OELs development in Taiwan include the IOSH organized a recommended exposure limits (RELs) Committee to select the target chemicals and to recommend the RELs through literature review based on the health effects in the first stage, then, the CLA put policy needs, economical and technical feasibility into consideration and set up the final OELs at the second stage. A standard operation manual of RELs Committee has been developed. Based on our experience, several issues including the participation of representatives from a comprehensive spectrum, communication/education and training/enforcement, continuous collection of the local exposure data and health hazard information, use of health risk assessment, consideration of economic, and technical feasibility, as well as the globalization and information and experience sharing are critical in developing the appropriate OELs. Three examples including benzene, crystalline silica, and 2-methoxy ethanol are given to demonstrate the operation of system.

The formation of N-(2-hydroxyethyl)valine (HEV) in hemoglobin has been considered as a biomarker to assess exogenous and endogenous exposures to ethylene oxide (EO) and/or ethylene (ET). Factors associated with daily exposures to such compounds might significantly affect the formation of HEV. Tobacco smoke containing EO elicited a significant increase in the levels of HEV amongst smokers, although other factors related to lifestyles may warrant further studies. The objective of this study was to specifically analyze HEV using a modified Edman degradation technique in order to study the association between lifestyle related factors (smoking, second-hand smoke exposure, tea and alcohol consumption) and HEV formation in vivo. Total of 148 Taiwanese volunteers with no history of occupational exposure to either EO or ET were recruited in this study. The HEV levels for smokers (204 +/- 151 pmol HEV/g globin, n = 70 ) were greater than those for non-smokers (57 +/- 46 pmol HEV/g globin, n = 78), HEV level increasing with the number of cigarettes smoked by subjects per day with a rate of 8.8 pmol HEV/g globin per cigarettes per day. Further analysis revealed that the rate of HEV formation in our study subjects was significantly associated with the number of daily cigarettes smoked (P0.001), but was not associated with tea or alcohol consumption, second-hand smoke exposure, subject age, or subject gender. These results suggest that the significantly higher levels of HEV for smokers than for non-smokers were mainly due to subject exposure to EO contained in cigarette smoke.

Many sites of contamination due to inappropriate disposal of hazardous materials or wastes have been found. These sites have the potential of damaging the environment and human health and thus need to be evaluated as to whether and what actions should be initiated. In the decision on whether a contaminated site should be subject to management, the knowledge concerning important parameters that would influence the decision will be beneficial to planning of data collection to support the decision. This paper presents a case study of contaminated site located in northern Taiwan, where the groundwater is contaminated by chlorinated hydrocarbons including trichloroethylene (TCE) and tetrachloroethylene (PCE). A site-specific multimedia risk assessment is performed to estimate the total risk resulting from the contamination. In addition, Monte Carlo simulation, rank correlation coefficients, and decision criteria are combined to develop a methodology for assessing the important of parameters in terms of their influence on the decision. It is found that TCE concentration, vegetable yield, deposition interception fraction of vegetables, and plant surface loss constant, are the four parameters important to the decision-making of the case problem.

Objectives N, N-dimethylformamide (DMF) is a common organic solvent massively used industrially. Exposure of DMF was reported to cause liver function damages and adverse health effects. DMF exposures in workplaces have been of great concern. Therefore, the objective of this study was to assess health risk due to occupational exposures to DMF in artificial leather industry. Methods Personal samples at pre-shift and post-shift were collected to assess exposures for each individual study subject in artificial leather factories in this study. Air-monitoring samples were collected through SKC 226-01 coconut charcoal sorbent tubes, and followed by determination of DMF concentrations with Agilent 6890 GC-FID. Pre-shift and post-shift bio-monitoring samples were collected separately. Then urinary N-methylformamide (NMF) concentrations were determined by Agilent 6890 GC-FID. Results The personal DMF exposures were analysed, and all data complied with the current PELs. However, hazard indexes (HI) were assessed by using either the reference concentration (RfC) published by U.S. EPA IRIS database, or the RfC generated from Benchmark dose modeling an animal dataset by using BMD 2.1.1 version software. Eighty of the 106 study subjects with HI value greater than 1. Conclusions These results demonstrate that long-term occupational DMF exposures may cause liver damages or other lung non-cancer effects although complied with the current regulations.

H.C. Wu, Y J Cheng, G.A. Liang, H.F. Huang, K.Y. Wu, S.Y Chiang 1 School of Post Baccalaureate Chinese Medicine, China Medical University, 2 Department of Radiation Therapy and Oncology, China Medical University Hospital, 3 Institute of Chinese Medical Science, 4 Institute of Environmental Health and Occupational Medicine, National Health research Institute, Kaohsiung, 5 Department of Occupational Safety and Health

Background Cigarette smoking cannot fully explain the epidemiologic characteristics of chronic obstructive pulmonary disease (COPD) in women, particularly for those who rarely smoke, but COPD risk is not less than men. The aim of our study is to investigate the relationship between second-hand smoke (SHS) exposure and chronic bronchitis in Taiwanese women. Methods We used Taiwan's National Health Insurance Bureau claims data in 1999, and cross-checked using criteria set by the American Thoracic Society; there were 33 women with chronic bronchitis, 182 with probable chronic bronchitis, and 205 with no chronic bronchitis during our interview time between 2000 and 2005. We measured second-hand smoke (SHS) exposure by self-reported measures (household users and duration of exposure), and validated this by measuring urinary cotinine levels of a subset subjects. Classification of chronic bronchitis was also based on spirometry defined according to the GOLD guidelines to get the severity of COPD. Results Women who smoked and women who had been exposed to a lifetime of SHS were 24.81-fold (95% CI: 5.78-106.38) and 3.65-fold (95% CI: 1.19-11.26) more likely to have chronic bronchitis, respectively, than those who had not been exposed to SHS. In addition, there was a significant increasing trend between the severity of COPD and exposure years of SHS (p < 0.01). The population attributable risk percentages of chronic bronchitis for smokers and those exposed to SHS were 23.2 and 47.3% respectively. Conclusions These findings indicate that, besides cigarette smoking, exposure to SHS is a major risk factor for chronic bronchitis in Taiwanese women.

Melamine, a widely used chemical found in many products in daily use, became a public health concern due to melamine-associated urinary stone formation in children. In adults, it is still unknown whether low-dose melamine exposure may also cause urolithiasis. To address this question, we studied 211 Taiwanese patients diagnosed with calcium urolithiasis and 211 age- and gender-matched controls. All patients completed a detailed questionnaire and provided blood and urine samples for biochemical analysis. Urinary melamine concentrations were measured by triple-quadrupole liquid chromatography tandem mass spectrometry. Compared with those whose urinary melamine levels were below the detection limit of the method, patients with urinary melamine levels of up to 3.11 ng/ml and those with levels of ≥3.12 ng/ml had 3.01- and 7.64-fold increased risk, respectively, of calcium urolithiasis after adjusting for educational level, fluid intake, cigarette smoking, betel quid chewing, alcohol drinking, urinary uric acid, calcium, creatinine, and estimated creatinine clearance rate. The population attributable risk of calcium urolithiasis averaged 50% when melamine was detected in the urine, after considering other covariates. MALDI-TOF mass spectrometry detected melamine in the stones of nine representative patients who had measurable urinary melamine levels. Thus, low-dose melamine exposure can play an important role in calcium urolithiasis in Taiwanese adults.

Background The Taiwan Birth Panel Study (TBPS) is a prospective follow-up study to investigate the development of child health and disease in relation to in-utero and/or early childhood environmental exposures. The rationale behind the establishment of such a cohort includes the magnitude of potential environmental exposures, the timing of exposure window, fatal and children's susceptibility to toxicants, early exposure delayed effects, and low-level or unknown neurodevelopmental toxicants. Methods A total of 486 mother-infant paired was enrolled from April 2004 to January 2005 in this study. Maternal blood before delivery, placenta and umbilical cord blood at birth, and mothers' urine after delivery were collected. The follow-up was scheduled at birth, 4, 6 months, and 1, 2, 3 and 5 years. The children's blood, urine, hair, and saliva were collected at 2 years of age and children's urine was collected at 5 years of age as well. The study has been approved by the ethical committee of National Taiwan University Hospital. All the subjects signed the inform consent on entering the study and each of the follow up. Results Through this prospective birth cohort, the main health outcomes were focused on child growth, neurodevelopment, behaviour problem and atopic diseases. We investigated the main prenatal and postnatal factors including smoking, heavy metals, perfluorinated chemicals, and non-persistent pesticides under the consideration of interaction of the environment and genes. Conclusions This cohort study bridges knowledge gaps and answers unsolved issues in the low-level, prenatal or postnatal, and multiple exposures, genetic effect modification, and the initiation and progression of "environmentally-related childhood diseases."