Exposure Characterization of Haloacetic Acids in Humans for Exposure and Risk Assessment Applications: An Exploratory Study.

Disinfected water is the major source of haloacetic acids (HAAs) in humans, but their inter- and intra-individual variability for exposure and risk assessment applications is under-researched. Thus, we measured HAAs in cross-sectional and longitudinal urine and water specimens from 17 individuals. Five regulated HAAs-mono, di, and trichloroacetic acid (MCAA, DCAA, and TCAA) and mono- and dibromoacetic acid (MBAA and DBAA)-and one unregulated HAA-bromochloroacetic acid (BCAA)-were measured. Urinary DCAA, MBAA, DBAA, and BCAA levels were always below the limits of detection (LOD). Measured levels and interindividual variability of urinary MCAA were higher than urinary TCAA. Longitudinal urinary specimens showed MCAA levels peaked in after-shower specimens, while TCAA levels remain unchanged. Correlation between urinary MCAA and TCAA was moderate but statistically significant. The prevalence of MCAA and TCAA in urine suggest they can be considered as biomarkers of HAA. Peak urinary MCAA in post-shower specimens suggest MCAA captures short-term exposure via dermal and/or inhalation, while urinary TCAA captures long-term exposure via ingestion. However, further research is warranted in a large pool of participants to test the reliability of MCAA as exposure biomarker.

Total organic halogen (TOX) in human urine: A halogen-specific method for human exposure studies.

Disinfection by-products (DBPs) are a complex mixture of compounds unintentionally formed as a result of disinfection processes used to treat drinking water. Effects of long-term exposure to DBPs are mostly unknown and were the subject of recent epidemiological studies. However, most bioanalytical methods focus on a select few DBPs. In this study, a new comprehensive bioanalytical method has been developed that can quantify mixtures of organic halogenated compounds, including DBPs, in human urine as total organic chlorine (TOCl), total organic bromine (TOBr), and total organic iodine (TOI). The optimized method consists of urine dilution, adsorption to activated carbon, pyrolysis of activated carbon, absorption of gases in an aqueous solution, and halide analysis with ion chromatography and inductively coupled plasma-mass spectrometry. Spike recoveries for TOCl, TOBr, and TOI measurements ranged between 78% and 99%. Average TOCl, TOBr, and TOI concentrations in five urine samples from volunteers who consumed tap water were 1850, 82, and 21.0µg/L as X-, respectively. Volunteers who consumed spring water (control) had TOCl, TOBr, and TOI average concentrations in urine of 1090, 88, and 10.3µg/L as X-, respectively. TOCl and TOI in the urine samples from tap water consumers were higher than the control. However, TOBr was slightly lower in tap water urine samples compared to mineral water urine samples, indicating other sources of environmental exposure other than drinking water. A larger sample population that consumes tap water from different cities and mineral water is needed to determine TOCl, TOBr, and TOI exposure from drinking water.

Quantification of N-methylmalonamic acid in urine as metabolite of the biocides methylisothiazolinone and chloromethylisothiazolinone using gas chromatography-tandem mass spectrometry.

Methylisothiazolinone and the mixture of chloromethylisothiazolinone/methylisothiazolinone (MCI/MI, 3:1) are widespread biocides used in cosmetic and household products. Due to their skin permeability, they might be taken up by the general population via use of products containing these biocides. As both compounds are known skin sensitizers, the use of these products is under discussion by regulatory agencies. In order to evaluate the possible uptake of MI and/or MCI/MI by human biomonitoring, we have developed and validated a highly sensitive and specific GC/MS/MS-method for the quantification of N-methylmalonamic acid (NMMA), a known metabolite of MI and MCI in urine of rats. After freeze-drying of urine, the analyte is derivatised with pentafluorobenzyl bromide in anhydrous solution and the PFB-derivative is extracted into n-hexane. After concentration, the derivative is finally quantified by GC/MS/MS in EI-mode using 13C3-NMMA as internal standard. The limit of quantification for NMMA was 0.5ngmL-1 urine. Precision within and between-series was determined to range between 3.7-10.9% using native and spiked quality control samples. Accuracy ranged between 89 and 114%. In a pilot study we applied this method to spot urine samples of 63 persons not knowingly exposed to MI and/or MCI/MI. NMMA was quantifiable in every urine sample analysed, with no significant difference in urinary levels between male and female participants. The median (95th percentile) levels for urinary NMMA were 3.6 (7.4) ngmg-1 creatinine and 2.9 (9.1) ngmg-1 creatinine for males (n=32) and females (n=31), respectively. In a volunteer experiment, a relation of exposure to MI and/or MCI/MI and subsequent NMMA-excretion was shown. Our method is the first to report human urinary background levels of NMMA. However, the possibility of formation and urinary excretion of NMMA within physiological processes cannot be ruled out.

Environmental and personal determinants of the uptake of disinfection by-products during swimming.

BACKGROUND: Trihalomethanes (THMs) in exhaled breath and trichloroacetic acid (TCAA) in urine are internal dose biomarkers of exposure to disinfection by-products (DBPs) in swimming pools. OBJECTIVE: We assessed how these biomarkers reflect the levels of a battery of DBPs in pool water and trichloramine in air, and evaluated personal determinants. METHODS: A total of 116 adults swam during 40min in a chlorinated indoor pool. We measured chloroform, bromodichloromethane, dibromochloromethane and bromoform in exhaled breath and TCAA in urine before and after swimming, trichloramine in air and several DBPs in water. Personal determinants included sex, age, body mass index (BMI), distance swum, energy expenditure, heart rate and 12 polymorphisms in GSTT1, GSTZ1 and CYP2E1 genes. RESULTS: Median level of exhaled total THMs and creatinine adjusted urine TCAA increased from 0.5 to 14.4µg/m(3) and from 2.5 to 5.8µmol/mol after swimming, respectively. The increase in exhaled brominated THMs was correlated with brominated THMs, haloacetic acids, haloacetonitriles, haloketones, chloramines, total organic carbon and total organic halogen in water and trichloramine in air. Such correlations were not detected for exhaled chloroform, total THMs or urine TCAA. Exhaled THM increased more in men, urine TCAA increased more in women, and both were affected by exercise intensity. Genetic variants were associated with differential increases in exposure biomarkers. CONCLUSION: Our findings suggest that, although affected by sex, physical activity and polymorphisms in key metabolizing enzymes, brominated THMs in exhaled breath could be used as a non-invasive DBP exposure biomarker in swimming pools with bromide-containing source waters. This warrants confirmation with new studies.

Commercial Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Testing is Not Vulnerable to Incidental Alcohol Exposure in Pregnant Women.

BACKGROUND: Ethyl Glucoronide (EtG) and Ethyl Sulfate (EtS) have shown promise as biomarkers for alcohol and may be sensitive enough for use with pregnant women in whom even low-level alcohol use is important. However, there have been reports of over-sensitivity of EtG and EtS to incidental exposure to sources such as alcohol-based hand sanitizer. Further, few studies have evaluated these biomarkers among pregnant women, in whom the dynamics of these metabolites may differ. OBJECTIVES: This study evaluated whether commercial EtG-EtS testing was vulnerable to high levels of environmental exposure to alcohol in pregnant women. METHODS: Two separate samples of five nurses-one pregnant and the other postpartum, all of whom reported high levels of alcohol-based hand sanitizer use-provided urine samples before and 4-8 hours after rinsing with alcohol-based mouthwash and using hand sanitizer. The five pregnant nurses provided urine samples before, during, and after an 8-hour nursing shift, during which they repeatedly cleansed with alcohol-based hand sanitizer (mean 33.8 uses). The five postpartum nurses used hand sanitizer repeatedly between baseline and follow-up urine samples. RESULTS: No urine samples were positive for EtG-EtS at baseline or follow-up, despite use of mouthwash and-in the pregnant sample-heavy use of hand sanitizer (mean of 33.8 uses) throughout the 8-hour shift. CONCLUSIONS/IMPORTANCE: Current, commercially available EtG-EtS testing does not appear vulnerable to even heavy exposure to incidental sources of alcohol among pregnant and postpartum women.

Predictors of urinary trichloroacetic acid and baseline blood trihalomethanes concentrations among men in China.

Urinary trichloroacetic acid (TCAA) and baseline blood trihalomethanes (THMs) have been measured as biomarkers of exposure to drinking water disinfection by-products (DBPs) that have been associated with increased risk of cancers and adverse reproductive outcomes. This study aimed to identify predictors of urinary TCAA and baseline blood THMs among men in China. Urine samples, blood samples, and information on socio-demographic factors and water-use activities were collected from 2216 men who participated in a cross-sectional study of exposure to drinking water DBPs and reproductive health during 2011 to 2012. Urinary TCAA and baseline blood THMs including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were analyzed. Multivariable linear regression was used to evaluate predictors of urinary TCAA and baseline blood THM concentrations. Tap water consumption was significantly associated with creatinine-adjusted urinary TCAA concentration (ß = 0.23 µg/g creatinine per log10 unit; 95% CI: 0.12, 0.35). Men with surface water source had 0.13 (95% CI: 0.00, 0.27) higher mean creatinine-adjusted urinary TCAA concentrations than those with ground water source. Smoking was associated with lower concentration of creatinine-adjusted urinary TCAA. Age was significantly associated with baseline blood Br-THM (sum of BDCM, DBCM, and TBM) concentration (ß = 0.01 ng/L per unit; 95% CI: 0.00, 0.02). Increased household income was associated with decreased concentrations of baseline blood BDCM and Br-THMs. Our results suggest that tap water consumption, water source, smoking, age, and household income as the primary determinants of exposure to drinking water DBPs should be considered in exposure assessment.

Dermal and pulmonary absorption of ethanol from alcohol-based hand rub.

BACKGROUND: Ethanol intoxication of healthcare workers (HCWs) using alcohol-based hand rubs (ABHRs) in the workplace is a potentially serious issue. This study quantified the level of ethanol absorption among HCWs after hygienic hand disinfection. METHODS: Eighty-six HCWs from Nancy University Hospital were tested before and after a 4-h shift. Participants used ABHR containing 70% ethanol. Levels of ethanol, acetaldehyde and acetate in blood and urine were determined using gas chromatography. A breathalyzer was used to measure the level of ethanol in expired air. RESULTS: Ethanol [mean concentration 0.076 (standard deviation 0.05) mg/L] was detected in the expired air of 28 HCWs 1-2 min post exposure. Ethanol, acetaldehyde and acetate were undetectable in blood after a 4-h shift, and urine tests were negative in all participants. CONCLUSION: Ethanol exposure from ABHR, particularly inhalation of vapours, resulted in positive breathalyzer readings 1-2 min after exposure. Dermal absorption of ethanol was not detected. Pulmonary absorption was detected but was below toxic levels.

Ethyl glucuronide, ethyl sulfate, and ethanol in urine after sustained exposure to an ethanol-based hand sanitizer.

To assess the degree of ethanol absorption and subsequent formation of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) following sustained application of hand sanitizer, 11 volunteers cleansed their hands with Purell(™) hand sanitizer (62% ethanol) every 5 min for 10 h on three consecutive days. Urine specimens were obtained at the beginning and end of each day of the study, and on the morning of the fourth day. Urinary creatinine, ethanol, EtG, and EtS concentrations were measured. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (73 and 37 ng/mL). None of the pre-study specimens had detectable ethanol. The maximum EtG and EtS concentrations over the course of the study were 2001 and 84 ng/mL, respectively, and nearly all EtG- and EtS-positive urine specimens were collected at the conclusion of the individual study days. Only two specimens had detectable EtG at the beginning of any study day (96 and 139 ng/mL), and only one specimen had detectable EtS at the beginning of a study day (64 ng/mL), in addition to the two with detectable EtS prior to the study. Creatinine-adjusted maximum EtG and EtS concentrations were 1998 and 94 µg/g creatinine, respectively. In patients being monitored for ethanol use by urinary EtG concentrations, currently accepted EtG cutoffs do not distinguish between ethanol consumption and incidental exposures, particularly when urine specimens are obtained shortly after sustained use of ethanolcontaining hand sanitizer. Our data suggest that EtS may be an important complementary biomarker in distinguishing ethanol consumption from dermal exposure.

Urinary trichloroacetic acid levels and semen quality: a hospital-based cross-sectional study in Wuhan, China.

Toxicological studies indicate an association between exposure to disinfection by-products (DBPs) and impaired male reproductive health in animals. However, epidemiological evidence in humans is still limited. We conducted a hospital-based cross-sectional study to investigate the effect of exposure to DBPs on semen quality in humans. Between May 2008 and July 2008, we recruited 418 male partners in sub-fertile couples seeking infertility medical instruction or assisted reproduction services from the Tongji Hospital in Wuhan, China. Major semen parameters analyzed included sperm concentration, motility, and morphology. Exposure to DBPs was estimated by their urinary creatinine-adjusted trichloroacetic (TCAA) concentrations that were measured with the gas chromatography/electron capture detection method. We used linear regression to assess the relationship between exposure to DBPs and semen quality. According to the World Health Organization criteria (<20 million/mL for sperm concentration and <50% motile for sperm motility) and threshold value recommended by Guzick (<9% for sperm morphology), there were 265 men with all parameters at or above the reference values, 33 men below the reference sperm concentration, 151 men below the reference sperm motility, and 6 men below the reference sperm morphology. The mean (median) urinary creatinine-adjusted TCAA concentration was 9.2 (5.1) µg/g creatinine. Linear regression analyses indicated no significant association of sperm concentration, sperm count, and sperm morphology with urinary TCAA levels. Compared with those in the lowest quartile of creatinine-adjusted urinary TCAA concentrations, subjects in the second and third quartiles had a decrease of 5.1% (95% CI: 0.6%, 9.7%) and 4.7% (95% CI: 0.2%, 9.2%) in percent motility, respectively. However, these associations were not significant after adjustment for age, abstinence time, and smoking status. The present study provides suggestive but inconclusive evidence of the relationship between decreased sperm motility and increased urinary TCAA levels. The effect of exposure to DBPs on human male reproductive health in Chinese populations still warrants further investigations.

[Diagnosis of formaldehyde allergy]. / Diagnostika sensibilizatsii k formal'degidu.

Exposure to small-dose environmental agents is a risk factor of immunopathological reactions. The levels of formaldehyde-specific IgE were comparatively analyzed in 50 children of whom 25 live in the area exposed to formaldehyde. Children with varying respiratory allergic reactions comprised a study group. To identify allergen-specific IgE, the authors used a method that determined formaldehyde antibodies by using the tested allergen (formaldehyde on the paper). There were significant group-specific differences in the levels of formaldehyde antibodies (3.8 times higher in the study group than in the controls). Combined therapy substantially reduced specific IgE whose levels returned to the levels observed in the controls. The findings may recommend the use of this test for the diagnosis of immune-depended abnormalities and the evaluation of their effective treatment.

Quantitative analysis of tribromsalan in blood and urine.

Tribromsalan can be quantitatively measured in whole blood and urine by a technique involving extraction with ethyl acetate, treatment with silica gel, separation by TLC, and quantitative measurement by fluorescent spectrophotometry. This method has a sensitivity down to 125 ng (25 ppb in 5.0 ml of sample) of free tribromsalan and shows an average 90% recovery of tribromsalan in blood and urine with standard deviations of 9.7 and 7.4%, respectively.