Birgitta Kütting

Determination of haemoglobin adducts of acrylamide and glycidamide in smoking and non-smoking persons of the general population

Acrylamide (AA) is a food-borne toxicant suspected to be carcinogenic to humans. It is formed in the heating process of starch-containing food. Currently, there is a great discussion about the possible human health risks connected with the dietary uptake of acrylamide. Haemoglobin adducts of acrylamide and its oxidative metabolite glycidamide are both markers of biochemical effect. However, because glycidamide has a higher carcinogenic potency than acrylamide itself, the glycidamide adduct might mirror the genotoxicity better than acrylamide adducts. In order to gain more information about the human metabolism of acrylamide, we investigated a small group of persons for the effective internal doses of acrylamide and glycidamide using haemoglobin adducts as parameters of biochemical effect. The collective was subdivided into non-smokers (n=13) and smokers (n=16) by determining the smoking-specific acrylonitrile haemoglobin adduct (N-cyanoethylvaline, CEV). The mean values for the adducts of acrylamide (N-2-carbamoylethylvaline, AAVal) and glycidamide (N-(R,S)-2-hydroxy-2-carbamoylethylvaline, GAVal) in nonsmokers was 19 pmol/g globin AAVal (range 7-31 pmol/g globin) and 17 pmol/g globin GAVal (range 9-23 pmol/g globin). For smokers mean levels of AAVal were 80 pmol/g globin (range: 25-199 pmol/g globin) and those of GAVal were 53 pmol/g globin (range: 22-119 pmol/g globin). Metabolism to glycidamide turned out to be significantly more effective in non-smokers than in the higher exposed smokers. Compared with studies in rats, the metabolic conversion of acrylamide to glycidamide as measured by haemoglobin adducts seems to occur to a similar extent in humans as in rats. Risk estimations on acrylamide based on experimental data obtained in rats obviously did not overestimate the cancer risk for the general population. Furthermore, our results might indicate that the dose-response curve for acrylamide is not linear. This would be in line with the results of animal experiments on rodents.

Effectiveness of skin protection measures in prevention of occupational hand eczema: results of a prospective randomized controlled trial over a follow-up period of 1 year

Background  We recently found a very low adherence to a generally recommended skin protection regimen in a sample of 1355 metalworkers.

UV-induced skin cancer at workplace and evidence-based prevention

PurposeThe present review is aimed at providing an overview of skin cancer with particular focus on occupational concern and giving evidence-based recommendation for effective prevention at workplace.MethodsWe performed a systematic search of literature using PubMed and the Cochrane Library.ResultsOutcome of preventive strategies depends either on efficacy of the strategy itself but also on acceptance and implementation of protective means among the persons at possible risk for hazardous health effects. Epidemiological studies have reported significantly more non-melanoma skin cancer in men than in women. Life-style choices and difference in immunosuppression play a major role in this gender disparity. Tumor biology of skin cancer is diverging: severe blistering sunburns corresponding to intermittent intense UV exposures are associated with an increased risk for both melanoma and basal cell carcinoma (BCC); whereas the risk of squamous cell carcinoma (SCC) and actinic keratoses (AK) is strongly associated with chronic UV exposure. Several clinical trials give evidence that long-term use of sunscreen prevents the appearance of non-melanotic skin cancer such as AK and SCC, but not of BCC. All technical and organizing measures aimed at reducing UV exposure at workplace belong to first-line prevention; however, there is much room for improvement. The efficacy of personal protection means (second-line strategy) strongly depends on the workers’ compliance which is quite low at workplace.ConclusionEvidence-based data confirming the benefit of sun protective strategies are scarce, general recommendations are mainly based on the avoidance of UV radiation being identified as potential risk factor for non-melanoma skin cancer in epidemiological studies. Occupational screenings should include regular interventions aimed at enhancing a clear understanding of risk factors for individuals and finally improving the acceptance and maintenance for UV-protective means at workplace.

Current acceptance and implementation of preventive strategies for occupational hand eczema in 1355 metalworkers in Germany

Summary Background The effectiveness of a skin care programme is based mainly on the effectiveness of the products used and the frequency and diligence of the application of skin care products.

Acrylamide as environmental noxious agent: a health risk assessment for the general population based on the internal acrylamide burden.

The present population-based cross-sectional study in 1008 volunteers was aimed at quantifying the internal burden of acrylamide (AM) in the general population using hemoglobin adduct levels as biomarker of exposure. Based on these adduct levels the risk of (AM) related hazardous health effects in the general population is assessed. Hemoglobin adducts of acrylamide were detected in 999 out of 1008 analyzed blood samples (99.1%). Smoking can be regarded as a main source of overall acrylamide intake in persons without occupational exposure to acrylamide but a second main influence factor, i.e. food intake, is of environmental importance. Due to the sizable study population the 95th percentile differentiated in smokers and non-smokers are actually the best available reference values for an internal environmental acrylamide burden. Based on our data neurotoxicity and reproductive toxicity due to acrylamide are not likely to occur in the general population except very high consumers. However, carcinogenicity and mutagenicity are possible hazardous health effects for the general population.

Allergenicity of natural rubber latex gloves.

The concentrations of proteins, allergens and rubber chemicals are essential parameters of the allergenicity of NRL gloves. To date, a standardized method has been given only for analysis of the protein concentration (DIN EN 455‐3), and not for the concentrations of allergens and rubber chemicals. In the present study, we investigated 11 brands of surgical gloves currently available on the German market. Additionally 1 glove, not subjected to final leaching procedures, was added for comparison purposes. Protein concentrations were analysed by different methods in different laboratories. Allergen concentrations were assayed by prick tests in NRL‐allergic volunteers and by RAST inhibition methods. Rubber chemicals were analysed by HPTLC and GC. The protein concentrations analysed by the Lowry method in the 2 laboratories gave concordant results, but the correlations between protein and allergen concentrations were low. The protein concentration analysed by HPLC correlated with the allergen concentration, and gave better information on the allergenicity of the gloves. The development of standardized methods for allergen analysis in the assessment routine is necessary, due to significant discrepancy between protein and allergen levels of some gloves. Thiurams were not found in any of the gloves, though carbamates were present in all gloves tested. Our data indicate that washing procedures have little or no effect on the concentration of rubber chemicals.

An overview of skin scores used for quantifying hand eczema: a critical update according to the criteria of evidence-based medicine

The present review gives an overview of the enormous variety of skin scores used for assessing severity in patients suffering from hand eczema. In order to evaluate the validity and practical relevance of different scoring systems according to the criteria of evidence‐based medicine, in May 2009 we performed a systematic search of the literature using PubMed and the Cochrane Library. A total of 69 articles reporting on 45 different methods for quantifying hand eczema were identified. The panel of methods varied from pure subjective categories to more or less quantitative scoring systems. Furthermore, by focusing on skin scores used in clinical trials in which the results led to the licensing of a systemic or topical drug for treatment of hand eczema, a panel of different scoring systems was identified. In addition to morphological pattern, some scoring systems included subjective complaints, which might cause an individual bias by overestimation of self‐reports. Inter‐ and intraobserver reliability was rarely reported except for three scores. Among these validated scores interobserver reliability was reported for three scores, but only one of the three included reliability within observers (repeatability). Advantages and disadvantages of the different scoring systems are critically discussed. Depending on different indications and particular settings (e.g. occupational screening vs. clinical examinations, evaluating progress of treatment in everyday clinical practice or for research purposes) scoring systems have to fulfil diverging demands. We draw the conclusion that a standardized diagnostic procedure for assessing the severity of hand eczema would facilitate the comparability of outcome of clinical trials. However, scoring systems used for occupational screening have to fulfil different demands compared with scoring systems used for licensing of drugs. This striking difference might be explained by the skin condition, which is generally supposed to be much better in subjects at medical check‐ups at the workplace.

Monoarylamines in the general population--a cross-sectional population-based study including 1004 Bavarian subjects.

AIM The population-based cross-sectional study including 1004 Bavarian volunteers aged 3 up to 84 years (median: 42 years) was aimed to quantify the internal burden of monocyclic arylamines in the general population and to yield reference values. MATERIAL AND METHODS Participants were asked to complete a questionnaire, to give a venous blood sample and a urinary sample. The selected monoarylamines (aniline, o-anisidine, all isomers of toluidine, single and double chlorinated anilines) represent main sources of potential environmental exposure. The venous blood sample was taken to determine the smoking-specific acrylonitrile-adduct N-cyanoethylvaline. RESULTS Detectable levels of aniline were found in the urine of 93.9% of the participants, whereas 3-chloroaniline was only detected in 16% of the samples. The influence of smoking on the urinary arylamine concentration was weak. Only for o-toluidine, m-toluidine and o-anisidine values were significantly higher in smokers. Therefore, while the 95th percentile based on the total sample (n=1004) is the best reference value for all other arylamines (i.e. p-toluidine, 3-chloroaniline, 4-chloroaniline, 3,4-dichloroaniline) we suggest separate reference values for smokers and non-smokers for the former three compounds. A statistically significant difference in urinary arylamine concentration between men and women was observed for 3,5-dichloroaniline, o-anisidine and aniline (p<0.001). Therefore we suggest gender-specific reference values for dichloroaniline and aniline; for o-anisidine we suggest gender- and smoking-specific reference values. The observation of o-toluidine in 178 urinary samples in concentration above the limit of quantification raises concern regarding human carcinogenicity. CONCLUSION This study supports the notion of further relevant sources of o-toluidine exposure except smoking and occupation. Compared to other environmental risk factors (e.g. environmental tobacco smoke) the risk of o-toluidine-induced cancer seems to be extremely low for the general population.

Influence of Diet on Exposure to Acrylamide – Reflections on the Validity of a Questionnaire

Aim: This pilot study attempts to assess how far the standardized questionnaires are a valid tool to detect the food-related burden of acrylamide. Acrylamide is a toxic substance classified by the International Agency of Research on Cancer, as well as the Deutsche Forschungsgemeinschaft, as a probable human carcinogen. Methods: A venous blood sample was taken in order to determine the smoking-specific acrylnitrile adduct N-cyanoethylvaline and the acrylamide adduct N-2-carbamoylethylvaline in a female study population expecting delivery soon. A standardized questionnaire was used to determine the consumption of acrylamide-contaminated food. The results of our questionnaire were transferred to a linear evaluation system. Finally, anamnestic data of the questionnaire were correlated to objective parameters such as blood levels of hemoglobin adducts of acrylamide and acrylonitrile. Results: A positive correlation between the acrylamide intake and the levels of hemoglobin adducts in our study population was not proven. Conclusions: Evaluation of food-related exposure to acrylamide is difficult due to several reasons. Firstly, the validity of anamnestic data strongly depends on the patient’s ability to remember precisely all consumed food (quality as well as quantity) over a 3-month period. In addition, the contamination of acrylamide in food varies from one product to another; even the contamination of the same product is variable. Therefore, the missing correlation between the questionnaire and hemoglobin adduct rates is rather due to restricted validity of anamnestic data.

How to quantify skin impairment in primary and secondary prevention? HEROS: a proposal of a hand eczema score for occupational screenings

Background  Skin scoring systems have to meet specific demands depending on their particular settings and indications, e.g. occupational screenings vs. clinical examinations, evaluating progress of treatment or supervision of preventive strategies. Until now, most scoring systems have been developed for severe cases of hand eczema. A validated quantitative scoring system for early hand eczema is still missing.