Biomonitoring of benzene exposure by trace analyses of phenylguanine

Summary From preliminary experiments it was known that radiolabelled benzene and some of its metabolites during its metabolic activation process produce different in vitro DNA-phenyladducts in mitoplasts [5, 11].As we reported previously [9] at least one of these adducts, N-7-phenylguanine, is excreted in the urine of rats in measurable amounts, probably through an excision-repair mechanism after an inhalation experiment. Now we found, after i.p. application of benzene in the urine of rats, a compound separated by cation-exchange chromatography that behaves like a synthezised N-7-phenylguanine reference substance with respect to its retention index and the UV-absorption. This finding could be confirmed by HPLC-measurements with reversed-phase carrier materials. Silylation and gaschromatographic/mass spectrometric (GC/MS) separation of the fraction, which contains the phenylguanine, revealed that these fractions contain further phenyl adducts. Furthermore we studied the time-dependent excretion of the DNA-base adduct. Surprisingly the excretion dropped to zero on the fourth day and showed a new increase thereafter.     

Cotinine determination by immunoassays may be influenced by other nicotine metabolites

Polyclonal rabbit anticotinine antiserum, which can be used for biomonitoring nicotine uptake by the determination of cotinine in body fluids, was checked by a competitive ELISA for its cross-reactivity with nine nicotine metabolites. The highest percentage of relative crossreactivity (about 30%) was observed with trans-3-hydroxycotinine, a metabolite which is known to be excreted in 3-fold higher amounts than cotinine in the urine of human smokers. Therefore, it is possible that cotinine determinations performed by immunochemical methods — especially in urine — may yield overestimated cotinine concentrations.     

Blood lead levels and risk factors in young children in France, 2008–2009

BackgroundThe exposure of children to lead has decreased in recent years, thanks notably to the banning of leaded gasoline. However, lead exposure remains a matter of public health concern, because no toxicity threshold has been observed, cognitive effects having been demonstrated even at low levels. It is therefore important to update exposure assessments. A national study was conducted, in 2008–2009, to determine the blood lead level (BLL) distribution in children between the ages of six months and six years in France. We also assessed the contribution of environmental factors.MethodsThis cross-sectional survey included 3831 children recruited at hospitals. Two-stage probability sampling was carried out, with stratification by hospital and French region. Sociodemographic characteristics were recorded, and blood samples and environmental data were collected by questionnaire. Generalized linear model and quantile regression were used to quantify the association between BLL and environmental risk factors.ResultsThe geometric mean BLL was 14.9 μg/l (95% confidence interval (CI) = [14.5–15.4]) and 0.09% of the children (95% CI = [0.03–0.15]) had BLLs exceeding 100 μg/l, 1.5% (95% CI = [0.9–2.1] exceeding 50 μg/l. Only slight differences were observed between French regions. Environmental factors significantly associated with BLL were the consumption of tap water in homes with lead service connections, peeling paint or recent renovations in old housing, hand-mouth behavior, passive smoking and having a mother born in a country where lead is often used.ConclusionsIn children between the ages of one and six years in France, lead exposure has decreased over the last 15 years as in the US and other European countries. Nevertheless still 76,000 children have BLL over 50 μg/l and prevention policies must be pursued, especially keeping in mind there is no known toxicity threshold.     

Arsenic exposure and tobacco consumption: Biomarkers and risk assessment

Arsenic is measurable in tobacco and cigarette mainstream smoke (MSS). Whether arsenic has an independent role in diseases associated with tobacco consumption is not known. Epidemiology and biomonitoring data and probabilistic risk assessment (PRA) methods were used to investigate this potential association. Analysis of data from the National Health and Nutrition Examination Survey (NHANES) showed that urine arsenic concentrations in tobacco consumers were not different or were lower than levels in non-consumers of tobacco. Additionally, urine arsenic levels from NHANES tobacco consumers were five-times or more lower than levels reported in epidemiology studies to be associated with adverse health effects. Results of PRA indicated that mean non-cancer hazard estimates and mean incremental lifetime cancer risk estimates were within accepted ranges. Taken together, these results suggest that arsenic may not be independently associated with tobacco consumption or diseases related to tobacco consumption.     

Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature

Introduction: Phthalates, a class of commonly used compounds with widespread human exposure, have been described as obesogens, or chemicals that disrupt lipid metabolism and produce metabolic changes leading to increased risk of type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). This communication provides a systematic review of the available epidemiologic evidence on associations between phthalate ester metabolites in urine or blood and various health endpoints related to overweight/obesity, DM or CVD. Methods: We followed the current methodological guidelines for systematic reviews to identify, retrieve and summarize the relevant epidemiological literature on the relation between phthalates and overweight/obesity, DM, CVD or related biomarkers. Each eligible paper was summarized with respect to methods and results with particular attention to study design and exposure assessment. As quantitative meta-analysis was not feasible, the study results were assessed qualitatively for inter- and intra-study consistency. Results: We identified 26 publications of epidemiologic studies that assessed associations between either urinary or serum phthalate metabolites and outcomes of interest. These studies represented 18 independent data sources. We found no inter- or intra-study consistency for any phthalate metabolite for any of the indicators of overweight/obesity, DM or CVD in children or adults. Most reported associations were not statistically significantly different from the null, some were positive, and others were inverse. All studies except two used cross-sectional analyses and for this reason could not be used to test causal hypotheses. Conclusion: The current epidemiological data do not support or refute the hypothesis that phthalates act as obesogens in humans.     

Biomarkers for monitoring transfluthrin exposure: Urinary excretion kinetics of transfluthrin metabolites in rats

The urinary excretion kinetics of a fluorine-containing pyrethroid transfluthrin [(2,3,5,6-tetrafluorophenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate], which is widely used recently as mosquito repellents, was examined in rats to search for urinary metabolites suitable as biomarkers for monitoring transfluthrin exposure of the general population. After a single dose of 26, 64, 160 or 400 mg/kg body weight of transfluthrin had been administered intraperitoneally to male Sprague-Dawley rats, their urine was collected periodically for one week. Three major urinary transfluthrin metabolites were measured: 2,3,5,6-tetrafluorobenzyl alcohol, 2,3,5,6-tetrafluorobenzoic acid and 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid. The kinetics was evaluated by moment analysis of the urinary excretion rate of the metabolites versus time curves.The urinary excretion amounts of these three metabolites were estimated to be proportional to the absorption amounts of transfluthrin over a wide exposure range. Urinary 2,3,5,6-tetrafluorobenzoic acid was considered to be an optimal biomarker for monitoring transfluthrin exposure.     

Demographic and dietary predictors of urinary bisphenol A concentrations in adults in Israel

Background

To date, there is scarce data on levels of exposure to bisphenol A (BPA) in the general population in Israel and the region. The goal of the current study was to measure urinary levels of BPA in the general adult population in Israel and to determine the demographic and dietary predictors of exposure.

Methods

We recruited 249 individuals (ages 20–74) from five different regions in Israel. We collected urine samples and questionnaire data including detailed dietary data and analyzed urine samples for BPA concentrations.

Results

Eighty nine percent of the study population had urinary BPA concentrations equal to or above the level of quantification (0.3 μg/L). Median creatinine adjusted BPA urinary concentrations in the study population (2.3 μg/g) were slightly higher than those reported for the general population in the US (1.76 μg/g) and Canada (1.47 μg/g), and were comparable to those reported for the general population in Belgium (2.25 μg/g) and Korea (2.09 μg/g). BPA concentrations were higher in Jews compared to Arab and Druze (prevalence ratio (PR) = 2.34; 95%CI 1.56–3.49), in individuals with higher education (PR = 1.70, 1.11–2.62), in individuals consuming mushrooms (PR = 2.08, 1.07–4.05), and in smokers (PR = 1.43, 1.00–2.05).

Conclusions

We found that the general adult population in Israel is widely exposed to BPA. Our findings on higher BPA levels in Jews compared to Arabs and Druze and in individuals with higher education highlights the fact that predictors of BPA exposure vary across populations.     

Urinary concentrations of acrylamide (AA) and N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and associations with demographic factors in the South Korean population

Acrylamide (AA) and N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) are important urinary biomarkers of acrylamide exposure in human biomonitoring, because AA is classified as a probable carcinogen in humans.     

Urinary nickel as bioindicator of workers' Ni exposure in a galvanizing plant in Brazil

Objectives: We measured urinary nickel (U-Ni) in ten workers (97 samples) from a galvanizing plant that uses nickel sulfate, and in ten control subjects (55 samples) to examine the association between occupational exposure to airborne Ni and Ni absorption. Methods: Samples from the exposed group were taken before and after the work shift on 5 successive workdays. At the same time airborne Ni (A-Ni) was measured using personal samplers. Ni levels in biological material and in the airborne were determined by a graphite furnace atomic absorption spectrometry validated method. In the control group the urine samples were collected twice a day, in the before and after the work shift, on 3 successive days. Results: Ni exposure low to moderate was detected in all the examined places in the plant, the airborne levels varying between 2.8 and 116.7 μg/m³ and the urine levels, from samples taken postshift, between 4.5 and 43.2 μg/g creatinine (mean 14.7 μg/g creatinine). Significant differences in U-Ni creatinine were seen between the exposed and control groups (Student's t test, P ≤ 0.01). A significant correlation between U-Ni and A-Ni (r = 0.96; P ≤ 0.001) was detected. No statistical difference was observed in U-Ni collected from exposed workers in the 5 successive days, but significant difference was observed between pre- and postshift samples. Conclusions: Urinary nickel may be used as a reliable internal dose bioindicator in biological monitoring of workers exposed to Ni sulfate in galvanizing plants regardless of the day of the workweek on which the samples are collected. Received: 28 January 1999 / Accepted: 10 July 1999     

Biomonitoring of aromatic amines V: acetylation and deacetylation in the metabolic activation of aromatic amines as determined by haemoglobin binding

Aromatic amines are metabolically activated by N-oxidation of either the amine or the acetamide as a first step and esterification of the resulting N-hydroxyl derivatives as a second step. Both pathways may lead to DNA-adducts and subsequently to DNA lesions and mutations. Since the accumulation of non-acetylated adducts has been associated with tumour initiating properties, the balance between acetylation and deacetylation may greatly influence the biological effect. Hydrolysable haemoglobin adducts representing the bioavailability of N-hydroxylamines and the corresponding nitroso-derivatives were analysed following oral administration to female Wistar rats of two arylamine-acetamide couples: 4-aminobiphenyl and 2-aminofluorene, and two arylamine-acetamide-diacetamide triples: benzidine and 3,3′-dichlorobenzidine. The results show that the mono-acetamides are readily deacetylated in vivo whereas the diacetamides are not. A dynamic equilibrium is indicated to exist between acetylation and deacetylation, which depends on substrate specificity, and the role of deacetylation is emphasised. In addition, acetylation polymorphism was studied with 4-chloroaniline and 3,3′-dichlorobenzidine in slow acetylating A/J and rapid acetylating C57BL/6J mice. The slow acetylator genotype was associated with significantly higher haemoglobin-adduct levels for both arylamines. The results provide additional support for the use of haemoglobin adducts in biomonitoring as a dosimeter for the biologically active dose of arylamines/arylacetamides. Moreover, biomonitoring of haemoglobin adducts may provide information about an individual's susceptibility to the toxic and carcinogenic effects of these chemicals. Received: 19 January 1998 / Accepted: 7 April 1998