Risk assessment of pyrrolizidine alkaloids in food of plant and animal origin.

Acute liver toxicity, specifically in the form of hepatic veno-occlusive disease (HVOD), is known from reports on human poisonings following ingestions of 1,2-unsaturated pyrrolizidine alkaloids (PAs) containing herbs. Recently PA exposure via common foods contaminated via PA-producing plants raised concern, especially regarding the potential of genotoxicity and carcinogenicity. The health risks related to the estimated exposures to PAs from food were assessed. With respect to common foods, herbal teas and teas are the main sources through which consumers can be exposed to PAs. For high long-term consumption of these foods a possible health concern has been revealed in the assessment of chronic risks referring to a BMDL10 of 237 µg/kg bw per day recently established by EFSA based on model averaging for data on riddelliine. However, acute health damage from acute or short-term intake of PAs via common food is considered to be unlikely. Food supplements on the basis of PA-producing plants may significantly contribute to PA exposures and their intake is associated with risks of acute and chronic toxicity. However, no health risks have to be expected from the consumption of food supplements based on oil-based preparations of PA-producing plants, which were described to be free of PAs.

Copper and zinc content in wild game shot with lead or non-lead ammunition - implications for consumer health protection.

The aim of this study was to examine the contamination of game meat with copper and zinc and establish whether the use of alternative (non-lead) ammunition can lead to higher or unsafe levels of copper and zinc in the meat of roe deer, wild boar and red deer. The research project "Safety of game meat obtained through hunting" (LEMISI) was conducted in Germany with the purpose of examining the entry of lead as well as copper and zinc into the meat of hunted game when using either lead or non-lead ammunition. The outcome of this study shows that the usage of both lead-based ammunition and alternative non-lead ammunition results in the entry of copper and zinc into the edible parts of the game. Using non-lead ammunition does not entail dangerously elevated levels of copper and zinc, so replacing lead ammunition with alternative ammunition does not introduce a further health problem with regard to these metals. The levels of copper and zinc in game meat found in this study are in the range found in previous studies of game. The content of copper and zinc in game meat is also comparable to those regularly detected in meat and its products from livestock (pig, cattle, sheep) for which the mean human consumption rate is much higher. From the viewpoint of consumer health protection, the use of non-lead ammunition does not pose an additional hazard through copper and zinc contamination. A health risk due to the presence of copper and zinc in game meat at typical levels of consumer exposure is unlikely for both types of ammunition.

Estimation of dietary intake of bis(2-ethylhexyl)phthalate (DEHP) by consumption of food in the German population.

In the study presented here, we evaluated the exposure of the German population aged 14-80 years to bis(2-ethylhexyl)phthalate (DEHP) from consumption of food by means of deterministic and probabilistic estimations. The study was performed on the basis of an extensive review of literature from around the world reporting measured data on DEHP in food, as well as official German food control data. Only data from individual measurements were considered and used for fitting of distributions. A wide range of concentrations in non-representative samples are reported in the literature. On the basis of the available DEHP concentration data, 37 food categories were characterized which covered all major food classes. Food consumption data were taken from the diet history interviews of the German National Nutrition Survey II (Nationale Verzehrsstudie II) which was performed in 2005/2006 in a representative study population of 15,371 and is the most recent data source of this kind in Germany. Average DEHP intake was estimated deterministically using data on measured concentrations in food (medians and means) and food consumption (means). A total dietary exposure to DEHP of 3.6 (median based) and 9.3µg/kg of BW per day (based on mean values) was estimated deterministically. In addition, distributions of both concentrations and consumption figures were fitted using the @RISK best fit tool for further probabilistic estimations. This approach resulted in estimates within the same range: the estimated median DEHP intake in the whole population (both non-consumers and consumers of the foods considered) was 10.2, the arithmetic mean 14.0 and the 95th percentile 28.6µg/kg of BW per day. The respective estimates for consumers only were 12.4, 18.7 and 36.5µg/kg of BW per day. These results demonstrate that the probabilistic approach is able to estimate broader ranges of exposure even when using data representing an average intake. Moreover, it reflects the uncertainties of the estimation due to insufficient analytical data on concentrations of DEHP in food.

Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review.

This review assessed the efficacy of isoflavone supplements to reduce vasomotor symptoms in menopausal women by reviewing all published randomized controlled trials. Systematic literature searches were carried out in 70 databases. Randomized and placebo controlled studies were included if they investigated the treatment of isoflavone supplements derived from soy or red clover on vasomotor symptoms in peri- or postmenopausal women for at least 12 wks. Data were analyzed concerning outcome and methodological quality of the study. Twenty-three trials met the inclusion criteria, thereof 17 investigated soy isoflavones and 6 red clover isoflavones. Without exception, selected trials examining the effect of red clover isoflavones were already assessed in several meta-analyses and were therefore excluded from this evaluation. As the soy isoflavone studies were very heterogeneous concerning interventions and outcome measures, meta-analysis could not be performed and trials were systematically assessed in a structured approach. Included soy isoflavone studies had numerous quality deficiencies and did not consistently show a reduction of flushes after treatment with soy isoflavones. Therefore, there is no conclusive evidence, but only some indication of a benefit of soy isoflavones on hot flush frequency or severity.

Can the use of HEPA cleaners in homes of asthmatic children and adolescents sensitized to cat and dog allergens decrease bronchial hyperresponsiveness and allergen contents in solid dust?

BACKGROUND: Exposure and sensitization to pet allergens are associated with allergic asthma in children. Conflicting data have emerged regarding the potential benefit of air cleaners with respect to a reduction of indoor pet allergens and bronchial hyperresponsiveness (BHR). METHODS: In a randomized controlled trial 36 asthmatic children with sensitization to cat and/or dog and significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g of carpet dust) were included in order to study the effect of high-efficiency particulate arresting (HEPA) air cleaners placed in the living room and bedroom compared with the effect of sham air cleaners. Patients were allocated to two groups: group 1 exposed to active filters and group 2 exposed to sham filters. At month 0, after 6 months and after 12 months, pulmonary function testing and cold air challenge were performed, serum eosinophil cationic protein (ECP) and specific IgE to seven aeroallergens were determined, and carpet dust samples and filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were determined in filters and bulk dust samples. RESULTS: Thirty patients completed the study. After 6 and 12 months, there was no significant change in delta FEV(1) after cold air challenge, or in the use of medication and serum ECP levels. However, there was a trend in the active group towards an improvement of bronchial hyperresponsiveness, whereas the sham filter group showed a deterioration of BHR. CONCLUSION: Although HEPA air cleaners retained airborne pet allergens, no effect on disease activity or allergen concentrations in bulk dust samples was observed in this study.

Quantification of Campylobacter on the surface and in the muscle of chicken legs at retail.

The objective of this study was to determine the prevalence and numbers of Campylobacter on the skin and in the muscle of chicken legs at retail to examine the external and internal contamination for an exposure assessment. Furthermore, the study assessed seasonal influence on Campylobacter contamination in chicken legs. Of the 140 examined skin samples, 66% were positive, and the internal contamination of 115 sampled chicken legs was 27%. The enumeration of Campylobacter on the surface of positive chicken legs revealed a median of 2.4 log CFU/g of skin, and the quantification of Campylobacter in the muscle gave results mainly under the detection limit of the most-probable-number method (<0.3 MPN Campylobacter per g). The external contamination was significantly higher than the internal. In both skin and muscle samples, Campylobacter jejuni had a much higher incidence than Campylobacter coli. However, with regard to the specification of Campylobacter on the surface of chicken legs, C. coli was isolated at higher colony counts than C. jejuni. During the 1-year study, two peaks of Campylobacter contamination occurred, one in the early springtime (February and March, 100 and 90%, respectively) and the second during the warmer months in the summer (July and August, both 90%). Furthermore, a positive correlation between prevalence and numbers of Campylobacter on chicken legs was observed.

No association of histamine- N-methyltransferase polymorphism with asthma or bronchial hyperresponsiveness in two German pediatric populations.

Histamine plays an important role in the allergic inflammation. Histamin N-Methyltransferase (HNMT) catalyses the major pathway of histamine metabolism in the human lung. A common functional single nucleotide polymorphism (SNP) within the HNMT gene (C314T) was recently related to asthma. We tested this SNP for associations with asthma and asthma associated traits in two German pediatric populations (1. MAS-cohort, n=888, 85 children with asthma; 2. asthmatic children from Freiburg, n=176). Non-asthmatic (n=515) and non-atopic (n=211) children from the MAS-cohort were used as controls. For genotyping melting curve analyses (Light Cycler System) were applied. In contrast to a previous study, no association of the HNMT 314T allele with asthma, bronchial hyperresponsiveness (BHR) or other asthma related phenotypes could be observed in either study population. We conclude that this SNP might not play a major role in the pathogenesis of asthma or BHR in German children.

Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study.

BACKGROUND: Among many published studies of specific IgE response or atopy, only a few showed positive marginal effects for 6 potentially functional single nucleotide polymorphisms (SNPs; C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene). SNPs were commonly considered individually, and therefore the true effect could be masked by other genes or environmental factors. OBJECTIVE: We tested the relationship between these 6 SNPs and sensitization to food, mite, cat, and outdoor allergens in unrelated German children drawn from the Multicenter Atopy Study. Gene-gene and gene-environment interactions were also evaluated. METHODS: Multiple logistic regression models were used for the analyses of 4 sensitization outcomes. RESULTS: The variant C-1055T was significantly associated with increased risk of sensitization to food and outdoor allergens, with odds ratios of 3.49 (95% CI, 1.52-8.02) and 2.27 (95% CI, 1.04-4.94), respectively. The effects of the TT genotype on food sensitization appear to depend on variants in the IL4RA gene, in which marginally significant interaction terms were observed. Significant evidence supported an interaction between exposure to maternal smoking and variant Gln551Arg on risk of cat sensitization. In addition, we found that the effect of variant C-590T on sensitization to mite depended on Der p 1 allergen levels in carpet dust samples. CONCLUSIONS: These findings not only suggested that variants in the IL4, IL13, and IL4RA genes play an important role in controlling specific IgE response but also strengthened our understanding of gene-gene and gene-environment interaction on the development of specific sensitization in this study population.

Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study.

BACKGROUND: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent. OBJECTIVE: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study. METHODS: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background. RESULTS: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined. CONCLUSION: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.

Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children.

BACKGROUND: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16) gene maps to this region. CC16 is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16 gene (A38G) was previously associated with asthma. OBJECTIVE: We evaluated the role of the CC16 SNP in pediatric asthma and asthma severity in 2 German study populations. METHODS: The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the present study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1 was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied. RESULTS: No association of the CC16*38A allele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC(20)FEV(1) values were significantly lower in individuals homozygous or heterozygous for the CC16*38A allele compared with those in subjects with the CC16*38GG genotype (P <.05 and P <.03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1 after exercise when homozygous for the CC16*38A allele compared with that seen in asthmatic patients with the *38AG or *38GG genotype (P <.04 and P =.006, respectively). CONCLUSION: We conclude that the CC16*A38G SNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children.

The development of childhood asthma: lessons from the German Multicentre Allergy Study (MAS).

Epidemiological surveys have indicated that there has been a notable increase in the prevalence of both asthma and other allergic symptoms in children and young adults. Since it seems unlikely that genetic factors would contribute to the rising trend, environmental factors might play a major part in the development of childhood asthma. In a prospective birth-cohort study, we assessed the relevance of different exposures such as mite and cat allergen exposure, environmental tobacco smoke (ETS) exposure, early infectious diseases and vaccinations for the development of childhood asthma up to the age of 10 years. Data up to 7 years of age have been evaluated. Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available for 939 children (72%). Assessments included repeated measurements of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months and 3 years of age and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial responsiveness was determined in 645 children. At age 7, the prevalence of wheezing in the past 12 months was 10% (94 out of 938), and 6.1% (57 out of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze and increased bronchial responsiveness. However, no relationship between early indoor allergen exposure and the prevalence of asthma, wheeze and bronchial responsiveness was seen. During the first 3 years of life, intra-uterine tobacco and consistent ETS exposure have an adjuvant effect on allergic sensitisation that is transient and restricted to children with a genetic predisposition for allergy. Children sensitised to any allergen early in life and sensitised to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio (OR) = 10.12; 95% confidence interval (CI) = 3.81-26.88). Children with repeated episodes (> or =2) of runny nose before the age of 1 year were less likely to develop asthma by the age of 7 years (OR = 0.52; 95% CI = 0.29-0.92). Our data do not support the hypothesis that exposure to environmental allergens directly causes asthma in childhood but that induction of specific IgE responses and the development of childhood asthma are determined by independent factors. Indoor allergen avoidance is recommended as first line treatment in secondary and tertiary prevention; however, conclusions should be drawn with caution about the possible effect of primary preventative measures. Since allergic asthma seems to be a Th2-disease, immunomodulating factors such as early childhood infections, LPS-exposure or other factors influencing gene-environment interaction and individual susceptibility seem to be relevant for the development of childhood asthma.

Placebo-controlled study of the mite allergen-reducing effect of tannic acid plus benzyl benzoate on carpets in homes of children with house dust mite sensitization and asthma.

We studied the effect of a spray containing 1% benzyl benzoate, an acaricide, and 1% tannic acid ('Lowal'; a protein-denaturing substance), on concentrations of major allergens from house dust mite (HDM) species Dermatophagoides pteronyssinus and D. farinae (Der p 1 and Der f 1, respectively) in carpets. In a double-blind, placebo-controlled study with crossover design, 30 homes of children with HDM sensitization and asthma were included. All houses showed > or = 400 ng/g of Der p 1 + Der f 1 in carpet dust. The first treatment was performed on day 0 (group 1 active treatment, n = 15; group 2 placebo treatment, n = 15). After 2 and 8 weeks, dust samples were collected for quantification of mite allergens. After a 2-week washout period, the second treatment was performed (group 1 placebo treatment; group 2 active treatment). Again, carpet dust was collected after 2 and 8 weeks. Twenty-two of 30 families completed the trial: 14/15 in group 1 and eight of 15 in group 2. On day 0, there was no significant difference in mite allergen exposure between group 1 and group 2 (1,498 vs. 2,239 ng/g of Der p 1 + Der f 1, respectively). In group 1, the geometric mean for the difference of mite allergen concentration comparing day 0 and week 6 was 196 ng/g (95% CI: -7,161 and 8,401) for the first treatment (active) and 15 ng/g (95% CI: -1,079 and 1,292) for the second treatment (control). In group 2, the difference was 66 ng/g (95% CI: -398 and 1,515) for the first treatment (control) and 609 ng/g (95% CI: 186 and 9,264) for the second treatment (active). Comparing placebo and active treatment in total, there was a significant decrease following placebo treatment after 14 days (p = 0.026). After 8 weeks, active treatment was superior to placebo treatment (p = 0.049), but the allergen reduction achieved was < 20% (median 1,500 ng/g on day 0 vs. 1,250 ng/g after 8 weeks). We conclude that the slight mite allergen reduction on carpets achieved by the treatment with 'Lowal' is unlikely to achieve worthwhile clinical benefit either in the treatment of mite-sensitive patients or in primary or secondary prophylaxis.