Individual and combined effects of mycotoxins from typical indoor moulds.

The mycotoxins patulin, gliotoxin and sterigmatocystin can be produced by common indoor moulds and enter the human body via inhalation of mycotoxin containing spores and particulates. There are various studies about the individual effects of these mycotoxins, but a lack of knowledge about their effects in mixtures. The aim of this study was to evaluate combined effects on the singe celled organism Tetrahymena pyriformis. Using the MIXTOX model (EU project NOMIRACLE) synergistic or antagonistic effects with dose level deviation or dose ratio dependent deviation were analyzed. The most toxic compound gliotoxin (EC50 0.37 µM) and patulin (EC50 9.3 µM) as shown by the MIXTOX model acted synergistic, caused by similar mode of actions. Within the combination with sterigmatocystin (maximum inhibition of 45% at 12.5 µM) antagonistic effects were observed with switch to synergism if the toxicity of the mixture is mainly caused by sterigmatocystin. In the end the MIXTOX model was applicable for the prediction of combined effects of toxic compounds.

Cumulative risk assessment of chemical exposures in urban environments.

We performed a cumulative risk assessment for people living in a hypothetical urban environment, called Urbania. The main aims of the study were to demonstrate how a cumulative risk assessment for a middle-sized European city can be performed and to identify the bottlenecks in terms of data availability and knowledge gaps. The assessment focused on five air pollutants (i.e., PM10, benzene, toluene, nonane and naphthalene) and six food pesticides (i.e., acetamiprid, carbendazim, chlorpyrifos, diazinon, imidacloprid and permethrin). Exposure predictions showed that PM10, benzene and naphthalene exposure frequently exceeded the standards, and that the indoor environment contributed more than the outdoor environment. Effect predictions showed that mixture and interaction effects were generally limited. However, model calculations indicated potential synergistic effects between naphthalene and benzene and between chlorpyrifos, diazinon and toluene. PM10 dominated the health impact expressed in Disability Adjusted Life Years (DALYs). We conclude that measures to reduce the health impact of environmental pollution should focus on the improvement of indoor air quality and the reduction of PM10 emissions. Cumulative risk assessment can be improved by (1) the development of person-oriented exposure models that can simulate the cumulative exposure history of individuals, (2) a better mechanistic understanding of the effects of cumulative stressors, and (3) the development of instruments to prioritize stressors for inclusion in cumulative risk assessments.

Maternal immune status in pregnancy is related to offspring's immune responses and atopy risk.

BACKGROUND: The influence of maternal immune responses in pregnancy on children's immune competence and the development of atopic diseases later in life are poorly understood. To determine potential maternal effects on the maturation of children's immune system and resulting disease risks, we analysed immune responses in mother-child pairs in a prospective birth cohort study. METHODS: Within the Lifestyle and Environmental factors and their Influence on Newborns Allergy risk (LINA) study, concentrations of Th1/Th2/Th17 and inflammatory cytokines/chemokines as well as IgE were measured in phytohemagglutinin and lipopolysaccharide stimulated maternal blood in the 34th week of gestation and in corresponding children's blood at birth and 1 year after (n = 353 mother-child pairs). Information on atopic outcomes during the first year of life was obtained from questionnaires. RESULTS: Concentrations of inflammatory markers, excepting TNF-α, were manifold higher in cord blood samples compared with maternal blood. Th1/Th2 cytokines were lower in children's blood with a Th2 bias at birth. Maternal inflammatory parameters (MCP-1, IL-10, TNF-α) in pregnancy showed an association with corresponding cytokines blood levels in children at the age of one. High maternal IgE concentrations in pregnancy were associated with increased children's IgE at birth and at the age of one, whereas children's atopic dermatitis (AD) was determined by maternal AD. CONCLUSIONS: Maternal inflammatory cytokines during pregnancy correlate with children's corresponding cytokines at the age of one but are not related to IgE or AD. While maternal IgE predicts children's IgE, AD in children is only associated with maternal disease.

Measuring and modeling of binary mixture effects of pharmaceuticals and nickel on cell viability/cytotoxicity in the human hepatoma derived cell line HepG2.

The interaction of drugs and non-therapeutic xenobiotics constitutes a central role in human health risk assessment. Still, available data are rare. Two different models have been established to predict mixture toxicity from single dose data, namely, the concentration addition (CA) and independent action (IA) model. However, chemicals can also act synergistic or antagonistic or in dose level deviation, or in a dose ratio dependent deviation. In the present study we used the MIXTOX model (EU project ENV4-CT97-0507), which incorporates these algorithms, to assess effects of the binary mixtures in the human hepatoma cell line HepG2. These cells possess a liver-like enzyme pattern and a variety of xenobiotic-metabolizing enzymes (phases I and II). We tested binary mixtures of the metal nickel, the anti-inflammatory drug diclofenac, and the antibiotic agent irgasan and compared the experimental data to the mathematical models. Cell viability was determined by three different methods the MTT-, AlamarBlue(R) and NRU assay. The compounds were tested separately and in combinations. We could show that the metal nickel is the dominant component in the mixture, affecting an antagonism at low-dose levels and a synergism at high-dose levels in combination with diclofenac or irgasan, when using the NRU and the AlamarBlue assay. The dose-response surface of irgasan and diclofenac indicated a concentration addition. The experimental data could be described by the algorithms with a regression of up to 90%, revealing the HepG2 cell line and the MIXTOX model as valuable tool for risk assessment of binary mixtures for cytotoxic endpoints. However the model failed to predict a specific mode of action, the CYP1A1 enzyme activity.

Fatty acids in colostrum from mothers of children at high risk of atopy in relation to clinical and laboratory signs of allergy in the first year of life.

BACKGROUND: It remains controversial whether fatty acid (FA) composition of breast milk relates to development of atopy in the infant. This study evaluates FA in colostrum from mothers of children at high risk of atopy in association with atopy at the age of 1 year. METHODS: The FA of colostrum were analyzed for 218 children (60 with low birth weight between 1500 and 2500 g, 84 with a history of maternal atopy, and 74 with an elevated cord blood immunoglobulin (Ig)E of >0.9 IU/ml). Total lipids were extracted, methylated and separated by gas-liquid chromatography. Laboratory screening for allergic sensitization and clinical examination took place within the Leipzig Allergy Risk Children's Study (LARS). RESULTS: Low birth weight was correlated with low percentage levels of 20:2n-6, 22:2n-6, and 22:3n-3 (r = 0.14, P < 0.05; r = 0.14, P < 0.05 and r = 0.20, P < 0.01, respectively) and low gestational age at birth was correlated with low 22:3n-3 (r = 0.15, P < 0.05). There was no association between FA and atopic eczema at the age of 1 year. However, high linoleic acid (LA, 18:2n-6) was linked to high specific IgE against cow's milk protein (P < 0.05), and low docosapentaenoic acid (DPA, 22:5n-3) was associated with elevated total serum IgE (P < 0.05) at the age of 1 year, respectively. CONCLUSIONS: The polyunsaturated fatty acid composition of colostrum in a high risk newborn population shows associations with atopic sensitization at the age of 1 year and may be predictive for later atopic disease.

Seasonal cycle of VOCs in apartments.

To assess the adverse health effects of volatile organic compounds (VOCs), epidemiological studies combine the health outcome of individuals with their concomitant VOC exposure. While the latter is representative of the studied period, health effects might also be the result of long-term exposure or emerge in consequence of a peak pollution throughout the year. To address these problems, additional information about the spatiotemporal distribution of VOCs is necessary. The present paper aims at elucidating the spatial and temporal variation of VOC concentrations in Leipzig, Germany. The analysis is based on 1499 indoor and 222 outdoor measurements taken in the period between 1994 and 2001. All data were collected in the frame of epidemiological studies (Diez et al., 1999; Fritz et al., 1998; Schulz et al., 1999). The analysis comprised concentrations of 30 VOCs belonging to the groups of alkanes, cycloalkanes, aromatics, volatile halogenated hydrocarbons, and terpenes. We found that the VOC load in indoor air is, on average, 10 times higher than outdoors. For the studied period there was a clear downward tendency for all VOCs in apartments in Leipzig, except for terpenes which show an upward trend in the period 1996-99. In indoor air we observe an annual cycle for the total VOC concentration as well as the sum concentrations of the above called groups. Highest concentrations occur during the winter months, approximately three times higher than the summer burden. We summarize this finding in a seasonal model, which is fitted to our measurements. Based on the model we develop a procedure for seasonal adjustment, which enables to roughly estimate the annual peak concentration utilizing one monthly observation.

The influence of maternal exposure to volatile organic compounds on the cytokine secretion profile of neonatal T cells.

Indoor VOC (volatile organic compound) exposure has been shown to be correlated with airway symptoms and allergic manifestations in children. An investigation was conducted within an ongoing birth cohort study (LISA: Lifestyle-Immune System-Allergy) of the association between maternal exposure to VOCs and immune status at birth, in particular the cytokine secretion profile of cord-blood T cells. In a randomly selected group of 85 neonates, cytokine-producing cord-blood T cells were analyzed using intracellular cytokine detection. VOC exposure was measured in children's dwellings by passive sampling, while parents were asked to complete questionnaires about possible sources of VOC exposure. Adjusted odds ratios (ORs) were calculated by logistic regression based on categorized quartiles. A positive association was found between elevated percentages of interleukin-4-producing (IL-4) type 2 T cells and exposure to naphthalene (OR = 2.9) and methylcyclopentane (OR = 3.3). Exposure to tetrachloroethylene was associated with reduced percentages of interferon-gamma-producing (IFN-gamma) type 1 T cells (OR = 2.9). In addition, smoking during pregnancy was correlated with a higher indoor air concentration of naphthalene (OR = 3.8), new carpets in infants' bedrooms with elevated methylcyclopentane concentrations (OR = 4.1), and home renovation with a higher trichloroethylene burden (OR = 4.9). Our data suggest that maternal exposure to VOC may have an influence on the immune status of the newborn child.

T cell reactivity in neonates from an East and a West German city--results of the LISA study.

BACKGROUND: Within an ongoing birth cohort study (LISA) the cytokine production of cord blood T cells was compared between neonates from Leipzig (East Germany) and Munich (West Germany). The aim of this study was to analyse regional differences and influencing factors of the immune status. METHODS: Cytokine production was measured in a randomly selected subgroup of 158 children from the LISA (Life style - Immune system - Allergy) cohort by intracellular cytokine staining. Information on family "atopy" history (FAH) and home characteristics was obtained from questionnaires. RESULTS: Reduced numbers of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) producing T cells were found in association with biparental FAH and housing renovation during pregnancy. In addition, cytokine production was influenced by season. In Munich, the frequency of biparental FAH and of renovation measures during pregnancy was significantly higher as compared to Leipzig. Neonates from Munich showed significantly decreased amounts of IFN-gamma and TNF-alpha and elevated levels of interleukin-4 (IL-4) producing T cells. Differences in cytokine production between Munich and Leipzig were influenced by season (IL-4) and housing renovation (IFN-gamma, TNF-alpha). CONCLUSIONS: Since differences in the T cell cytokine production of neonates in Munich and Leipzig are independent from FAH our findings may provide evidence for the impact of environmental factors upon the fetal immune system.

Helicobacter pylori prevalences and risk factors among school beginners in a German urban center and its rural county.

In 1998, the Helicobacter pylori [(13)C]urea breath test was offered to all school beginners (birth cohort 1991/1992) in the city of Leipzig and in Leipzig County, Germany, to determine the colonization prevalence and potential transmission pathways of the bacterium. A total of 3,347 school beginners participated in the test, and 2,888 parents completed the detailed, self-administered questionnaire. The H. pylori prevalence was 6.5% [95% confidence interval (CI), 5.3-7.6] in the city and 5.7% (CI, 4.2-7.0) in the county. Using cluster analysis (WARD's method, Euclidean distances), we identified different sets of variables (confirmed by multivariate logistic regression analyses [odds ratios (ORs)] that are signficantly associated with H. pylori positivity. Among city children, the risk is significantly increased with contact to a pet hamster (OR = 2.4; 95% CI, 1.2-4.7; p < 0.015) and travels to Asian countries (OR = 3.7; 95% CI, 1.6-8.7; p < 0.002). Among county children, H. pylori positivity increased significantly with drinking of water from nonmunicipal sources (OR = 16.4; 95% CI, 3.1-88.5; p < 0.001), more than 3 children living in a household (OR = 4.2; 95% CI, 1.2-14.6; p < 0.02), and contact with pet hamsters (OR = 2.4; 95% CI, 1.0-5.7; p < 0.04). These data suggest that, in a general population sample, indirect fecal-oral transmission and living conditions are important risk factors in the spread of H. pylori infection. However, clinical symptoms do not necessarily indicate H. pylori positivity.

Helicobacter pylori prevalence in Leipzig's 1998 school entries: methodology and first results.

The non-invasive, stable-isotope-aided Helicobacter pylori (H. pylori) tests--breath and equivalent urine tests--were offered on a voluntary basis as part of the mandatory school entry medical examination to the 1998 school entry cohort of the City of Leipzig (480,000 residents). Parents of participating subjects were asked to fill out a detailed epidemiologic questionnaire. The response rate was 94% (n = 2228 of 2369 school starters born in 1991/92). Parent-completed questionnaires were returned by 1890 (80%) children. The overall H. pylori positive prevalence was 7.2%. The prevalence among children with a test and a parent-completed questionnaire was 6.5%. Prevalences among subsequently tested family members of the positive tested children was 65, 60 and 39% for mothers, fathers and siblings respectively. Though studies have shown that the direct transmission of the bacterium (oral-oral and fecal-oral) is a dominant pathway of infection, the questionnaire analyses indicate associations between H. pylori colonisation and living as well as environmental conditions.

Ozone-monitoring in Mendoza, Argentina: initial results.

A series of continuous ambient tropospheric ozone measurements were taken in Mendoza, Argentina, for a period of one year starting in November 1995. The data obtained were analyzed in terms of diurnal and annual variation. Indications were found of the strong impact of the mountain-valley circulation system, which ventilates and considerably cleans the air in Mendoza. The data are discussed in comparison with air pollution in the German city of Leipzig. In Mendoza, the high concentration of precursors and the strong solar radiation contribute to high levels of ozone. In fact, monitoring reveals considerably lower concentrations than in Leipzig, owing to the diluting effect of local meteorology. The low-level jet is mainly active during the summer. It lowers the peak mid-day ozone concentration and produces a temporary concentration increase at night. The Environmental Protection Agency standard of a maximum one-hour mean concentration of 0.250 mg ozone/m3 (125 ppb) is never reached, and the World Health Organization standard of 0.113 mg ozone/m3 (56.5 ppb) is only rarely exceeded during winter.

[Computer-assisted evaluation of emission data]. / Zur rechnergestützten Auswertung von Immissionsmessdaten.

To estimate the hygienic relevance of a given air pollution situation the knowledge of the quantiles of an ensemble of measuring data is very important. A computer programme to determine the quantiles is presented. In addition to the usual method of ranking data it allows the calculation by use of the Weibull distribution function, which is important in the case of a small data set. First results of practising on this software are discussed.