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Hans Drexler

Publications and source records attributed to Hans Drexler.

At least 19 recordsLinked to original sources
PubMed2006

Occurrence and daily variation of phthalate metabolites in the urine of an adult population.

Phthalates like di-(2-ethylhexyl) phthalate (DEHP) are commonly used as plasticizers and their metabolites are suspect of especially reproductive toxicity. The aim of our study was to assess phthalate exposure in adults by measuring urinary phthalate metabolite levels and to explore individual temporal variability. Urine samples were collected by 27 women and 23 men aged 14-60 years during 8 consecutive days. We quantified four monoesters, four oxidative DEHP metabolites, and two secondary metabolites of di-isononyl phthalate (DiNP) by a LC/LC-MS/MS method. If we analyzed all 399 available samples independent of classification, the highest median values of primary metabolites in this study were found for mono-n-butyl phthalate (MnBP: 49.6 microg/l), followed by mono-isobutyl phthalate (MiBP: 44.9 microg/l), mono-benzyl phthalate (MBzP: 7.2 microg/l), and mono-2-ethylhexyl phthalate (MEHP: 4.9 microg/l). The median concentrations of the oxidized metabolites of DEHP were 8.3 microg/l for mono-(2-carboxymethylhexyl) phthalate (2cx-MMHP), 19.2 microg/l for mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), 14.7 microg/l for mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 26.2 microg/l for mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The concentrations of the two DiNP secondary metabolites mono (oxoisononyl) phthalate (oxo-MiNP) and mono(hydroxyisononyl) phthalate (OH-MiNP) ranged from <LOD to 304 microg/l (median: 3.0 microg/l, 2.9 microg/g creatinine) and <LOD to 698 microg/l (median: 5.5 microg/l, 5.2 microg/g creatinine), respectively. Phthalate metabolite levels did not consistently differ by sex or age. There was substantial day-to-day variation of urinary levels with considerable within-subject variability. Intraclass correlation coefficients adjusted for sex and age ranged between 0.21 and 0.48 for unadjusted metabolite levels and between 0.20 and 0.57 for creatinine-adjusted levels. The secondary metabolites of DiNP were detectable in nearly all samples and were therefore sensitive biomarkers of DiNP exposure. Our results of within-subject variability suggest that exposure assessment should not be based on a single urine measurement.

Adolescent↗
PubMed2006

Dermal absorption of aromatic amines in workers with different skin lesions: a report on 4 cases.

There are only few studies about the relationship of skin lesions and the percutaneous uptake of hazardous substances in exposed workers. Several aromatic amines are well known carcinogens for humans and/or animals. This case report emphasizes the relevance of dermal absorption of the aromatic amine ortho-toluidine considering four workers with different skin status (healthy, erythematous and burned skin as well as dishydrotic eczema) during the vulcanisation process of rubber products in a components supplier plant for automobile industry. The results of our case report show that dermal absorption of o-toluidine through damaged epidermal barrier is significantly higher than through healthy skin.

Journal Article↗
PubMed2006

Is occupational exposure to solvents associated with an increased risk for developing systemic scleroderma?

BACKGROUND: Our study was aimed to investigate in a German collective if there are any hints for an increased occupational or environmental risk to develop systemic sclerosis, especially, focussing on work-related exposure to solvents. Moreover, we tried to evaluate the feasibility of a sampling method addressing support groups. METHODS: A standardised questionnaire was published in two journals subscribed by members of two different support groups and all members were asked to complete the questionnaire and to return it anonymously. The subjects were not informed on the scientific hypotheses, nor did they know who of them belonged to the case group (scleroderma) or to the control group (multiple sclerosis). RESULTS: 175 questionnaires could be included in the statistical analysis. As expected, a female predominance was in our collective. In the male subpopulation, the occupational exposure to solvents was higher in the case group than in the control-group (70% versus 45.8%). Based only on the male subgroup, a tendency for an association between occupational exposure to solvents and the risk to develop systemic sclerosis was found. CONCLUSION: According to our experience in this case-control-study exposure misclassification, qualitative or quantitative, was an eminent problem. Within such a setting, it is generally very difficult to establish an exact dose-response relationship due to incomplete, imprecise or missing data concerning duration of exposure, frequency of use and kind of solvent. Additionally, a well-known problem in studies based on self-reported questionnaires is the so-called volunteer bias. Unfortunately, but similar to other studies assessing epidemiologic factors in such a rare disease, our study was of limited power, especially in the subgroups defined by gender.

Journal Article↗
PubMed2006

Penetration of beta-naphthylamine and o-toluidine through human skin in vitro.

Several aromatic amines (AAs) are known to be carcinogens for humans. AAs are considered to be substantially absorbed through the skin. However, the database for dermal absorption of AAs in general is limited and no specific studies on dermal absorption of beta-naphthylamine (BNA) and o-toluidine (OT) have been published. In the present study using diffusion cells, we investigated dermal penetration of BNA and OT through human skin. We have demonstrated that both AAs penetrate through human skin fast (lag time: approximately 1.2 vs. 0.8 h) and in high percentages (54 vs. 50%, respectively, of the applied dose within 24 h). A skin notation is therefore justified for these substances.

2-Naphthylamine↗
PubMed2005

Excretion of mercapturic acids of acrylamide and glycidamide in human urine after single oral administration of deuterium-labelled acrylamide.

We investigated the human metabolism of AA to the mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R/S)-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L: -cysteine (GAMA) which are derived from AA itself and from its oxidative genotoxic metabolite glycidamide (GA), respectively. A healthy male volunteer received a single dose of about 1 mg deuterium-labelled acrylamide (d(3)-AA), representing 13 microg/kg body weight, in drinking water. Urine samples before dosing and within 46 h after the dose were analysed for d(3)-AAMA and d(3)-GAMA by LC-ESI-MS/MS. A first phase of increase in urinary concentration was found to last 18 h with a broad plateau between 8 and 18 h for AAMA, and 22 h for GAMA. Elimination half-lives of both AAMA and GAMA were estimated to be approximately 3.5 h for the first phase and more than 10 h up to few days for the second phase. Total recovery in urine after 24 h was about 51% as the sum of AAMA and GAMA and hereby well in accordance with former studies in rats. After 2 days AAMA, accounting for altogether 52% of the total AA dose, was the major metabolite of AA in humans. GAMA, accounting for 5%, appeared as a minor metabolite of AA. In humans we found a urinary ratio of 0.1 for GAMA/AAMA compared to previously reported values of 0.2 for rats and 0.5 for mice. Therefore, the metabolic fate of AA in humans was more similar to that in rats than in mice as already demonstrated in terms of the haemoglobin adducts. Consequently a genotoxic potency of AA mediated by GA could be supposed to be comparable in rats and humans.

Acetylcysteine↗
PubMed2005

Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors.

Each year thousands of healthy volunteers undergo apheresis procedures to donate blood components and safe lives. However, many disposables used in apheresis contain di(2-ethylhexyl)phthalate (DEHP). This way, donors are exposed to DEHP, which is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. We quantified the DEHP exposure of six plasma donors, six discontinuous-flow platelet donors and six continuous-flow platelet donors by determining three specific metabolites in urine (5OH-MEHP: mono(2-ethyl-5-hydroxyhexyl)phthalate; 5oxo-MEHP: mono(2-ethyl-5-oxo-hexyl)phthalate and MEHP: mono(2-ethylhexyl)phthalate). We found maximum concentrations in urine samples after the discontinuous-flow plateletpheresis procedure with 826 microg/l for 5OH-MEHP, 774 microg/l for 5oxo-MEHP and 266 microg/l for MEHP (mean of the six volunteers). Metabolite excretions were found to be significantly (p<0.0001) higher for both plateletpheresis techniques compared to plasmapheresis and controls. Continuous-flow plateletpheresis led to significantly higher (p<0.0001) excretions than discontinuous-flow plateletpheresis. Mean absolute DEHP exposures were 1.2 mg for discontinuous- and 2.1 mg for continuous-flow plateletpheresis. Exposure for plasmapheresis (0.37 mg) was in the range of the controls (0.41 mg). Mean DEHP doses for both plateletpheresis techniques (18.1 and 32.3 microg/kg/day) were close to or exceeded the reference dose (RfD) of the US EPA and tolerable daily intake (TDI) value of the EU on the day of the apheresis. Therefore, margins of safety might be insufficient to protect especially young men and women in their reproductive age from effects on reproductivity. At present, discontinuous-flow devices should be preferred to avert conceivable health risks from plateletpheresis donors. Strategies to avoid DEHP exposure of donors during apheresis need to be developed.

Adult↗
PubMed2005

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.

Acrylamide↗
PubMed2005

Secondary prevention of allergic symptoms in a dairy farmer by use of a milking robot.

BACKGROUND: Animal-derived allergens include lipocalins which play an increasing role in occupational respiratory sensitizations. The prevention of sensitization in stock farming is often difficult due to intense exposure, with traditional milking still requiring close animal contact. Complete avoidance of allergen exposure is only possible if stock farming is abandoned. This is, however, often not feasible in small dairy plants because of the resulting loss of income. CASE PRESENTATION: In a 37-year-old female farmer daily asthmatic complaints appeared, associated with cow dust-derived allergen exposure by milking with a conventional device. Respiratory symptoms increased during a period of 12 years. Allergic bronchial asthma was diagnosed, caused by sensitization against cow dust-derived allergens, as demonstrated by positive skin prick test and by detection of IgE antibodies. In a separate specific inhalation challenge test using a 10% extract of cow dust-derived allergens a 330% increase of airway resistance was detected. To enable further dairy farming, a milking robot was installed in 1999, i.e., an automatic milking system. The novel milking technique reduced the daily exposure from over 2 hours to approximately 10 min. The clinical course after the installation of the milking robot was favourable, with less frequent allergic and asthmatic symptoms. Furthermore, asthma medication could be reduced. Improvement was noted also in terms of lung-function and decreased total serum IgE. CONCLUSION: The case presented and the evidence from the literature indicates that the strategy of exposure minimization to allergens at workplaces can be an effective alternative to total elimination. In farmers with cow dust allergy a milking robot is an appropriate technical measure to minimize allergen-exposure.

Journal Article↗
PubMed2005

Current external and internal exposure to naphthalene of workers occupationally exposed to polycyclic aromatic hydrocarbons in different industries.

OBJECTIVES: External and internal exposure to naphthalene was examined in the most important industries that are typically concerned with polycyclic aromatic hydrocarbon (PAH)-induced diseases (cancer). Furthermore, a control collective from the general population was investigated. METHODS: External naphthalene was determined by personal air sampling (n = 205). The internal exposure was examined by urinary metabolites 1-naphthol and 2-naphthol (n = 277). RESULTS: Highest median concentrations of naphthalene in air were found in converter infeed (93.2 microg/m3) and coal-tar distillation (35.8 microg/m3). Moderate and low levels were determined in coking plants (14.5 microg/m3) and in the production of refractories (6.1 microg/m3) and graphite electrodes (0.7 microg/m3). Biological monitoring revealed concentrations of the sum of both metabolites [(1+2)-NOL] in smokers to be increased by 1.6-6.4 times compared with that in non-smokers at the same workplaces. Among non-smokers we found high median (1+2)-NOL levels in converter bricklayers (120.1 microg/l), in coal-tar distillation workers (56.0 microg/l) and in coking plant workers (29.5 microg/l). (1+2)-NOL concentrations around 10 microg/l were found in the production of refractories and graphite electrodes. There was a rough coherency between external and internal naphthalene exposure. In the controls, median (1+2)-NOL concentrations were 10.9 microg/l in non-smokers' urine and 40.3 microg/l in smokers' urine samples. CONCLUSIONS: Actual conditions of occupational hygiene at the workplaces investigated in this comprehensive study are better than those that current limit values of 50,000 microg/m3 (TLV, TRK) seem to induce. It has become obvious that tobacco smoking is a crucial confounding factor in biological monitoring of naphthalene-exposed humans, making interpretation of occupationally increased naphthol excretions very difficult at low exposure levels.

Adult↗
PubMed2005

Exposure of nursery school children and their parents and teachers to di-n-butylphthalate and butylbenzylphthalate.

OBJECTIVES: Some phthalates, among them di-n-butylphthalate (DnBP) and butylbenzylphthalate (BBzP), are known reproductive and developmental toxicants in animals and suspected endocrine disruptors in humans. Children are probably the most susceptible to these effects. To obtain an estimate of internal exposure to DnBP and BBzP we compared the excretion of their metabolites in the urine of nursery school children with that of their teachers and parents. METHODS: We measured the urinary mono-ester metabolites of DnBP, mono-n-butylphthalate (MnBP), and BBzP, monobenzylphthalate (MBzP), in first-morning voids of 36 children (median age 4.7 years) and 19 adults (37.4 years). RESULTS: In all samples both metabolites were detected. Urinary MnBP concentrations (in microgrammes per litre) of the children and adults were 139 and 91.8 (median), respectively. MBzP concentrations were 22.1 microg/l and 12.7 microg/l (median), respectively. Concentrations in microgrammes per gramme creatinine for MnBP were 161 for the children and 91.8 for the adults (median). The maximum concentration found for children (2249 microg/g) was approximately 15-times higher than that for adults (149 microg/g). This maximum value for children was attributed to medication that contained DnBP. If this child was excluded, the maximum concentration was 517 microg/g. MBzP concentrations for children and adults were 37.0 microg/g and 9.8 microg/g (median), respectively. The maximum concentration found for children (193 microg/g) was approximately seven-times higher than that for adults (26.7 microg/g). Creatinine-adjusted concentrations were significantly higher for children for both MBzP and MnBP (P<0.0001). MnBP and MBzP exposures were found to correlate statistically significantly within the children's cohort (r=0.723, P<0.001). Within the children's cohort we found elevated MnBP exposure to be caused by augmented use of skin-care products (P<0.05). CONCLUSION: We have shown that the internal exposure to MnBP and MBzP in children is approximately two- to four-times higher than in adults. Correlation of internal MnBP with MBzP exposure points to common sources of exposure for both phthalates. DnBP exposure seems, at least in part, to be connected with the use of body/skin care products and certain medications.

Adult↗
PubMed2005

Transepidermal water loss and incidence of hand dermatitis in a prospectively followed cohort of apprentice nurses.

The purpose of the study was to evaluate the incidence of hand dermatitis, the impact of potential risk factors and the efficacy of skin bioengineering in a prospectively followed cohort of apprentice nurses. 104 participants were prospectively followed for 3 years. Before the start of training, after about 1 year and in the third year of occupational exposure, a standardized questionnaire was distributed, and a clinical examination with skin bioengineering of the dorsum of hand and forearm was performed. The 12-month period prevalence of self-reported symptoms of hand dermatitis was 36.5%[95%-confidence interval (CI) 27.3-46.6] at intermediate follow-up and 43.3% (95%-CI 33.6-53.3) at the final examination. Apprentices with self-reported symptoms at the final examination showed a significant increase of transepidermal water loss (TEWL) at the dorsal hand from 10.15 g/m2h to 13.55 g/m2h. TEWL at this site did, at the initial examination, not differ significantly between persons who later reported symptoms of hand dermatitis at the final examination and those who did not (10.50 g/m2h versus 10.15 g/m2h, respectively). Our results do not support the notion that an increased basal TEWL is a good indicator for hand dermatitis risk.

Adult↗
PubMed2005

Transcutaneous penetration of toluene in rat skin a microdialysis study.

Percutaneous absorption of lipophilic substances has major implications for therapeutical use or toxicological effects. We, therefore, using dermal microdialysis, measured local toluene concentrations and assessed the effects of duration of exposure, skin barrier disruption and the use of skin-care products. Three microdialysis membranes (3000 kDa) were inserted intradermally at a length of 2 cm in the abdominal skin of 82 anaesthetized male Wistar rats. They were perfused with albumin solution (5%) at 10 microl/min. A skin area of 1.5 x 0.6 cm above the membranes was exposed to toluene (100%, 200 microl) for 15 or 240 min. Dialysate was sampled at 20-min intervals. Using GC-FPD (gas charomotography flame photometric detector), it was analysed for toluene. In addition, the effects of tape stripping and pretreatment with topical products were assessed. In each of the 12 permutations of exposure time, pretreatments and tape stripping, five to eight animals were investigated. Maximum toluene concentrations were reached at 60 min after exposure (3.07 +/- 0.40 microg/ml, 15 min; 5.38 +/- 0.92 microg/ml, 240 min). In 15-min exposure experiments, dermal toluene concentrations decreased slowly to reach baseline values after 240 min. After 240-min exposure, a plateau of approximately 6 microg/ml was reached after 60 min. Neither tape stripping nor the pretreatment with barrier cream induced a significant change on dermal toluene concentrations. The slow kinetics of toluene penetration results in a steep concentration gradient in the skin with very-high local toluene concentrations and a delayed wash out, which might be relevant not only toxicologically, but also therapeutically.

Administration, Cutaneous↗
PubMed2004

Is the permeability coefficient Kp a reliable tool in percutaneous absorption studies?

In percutaneous absorption studies the potency of penetration of chemical substances is often described by the permeability coefficient Kp. The experimentally determined Kp is characterized according to Fick's first law of diffusion by the ratio of flux and the concentration of the test compound (Kp=Flux/C). This equation implies that in percutaneous absorption studies Kp is theoretically a more reliable parameter than flux taking the concentration into consideration, and should remain constant for each compound independent from the grade of dilution. In our study we evaluated the course of the percutaneous absorption parameters flux and Kp of neat and of 50% aqueous solution of 2-butoxyethanol (BE). An infinite dose of neat and 50% aqueous solution of non-radiolabeled BE were applied on excised human skin from two donors in static diffusion cells in parallel (for each test setting n=21). The flux of 50% aqueous BE (0.704+/-0.152 mg/cm2/h) was about 15-fold higher than that of neat BE (0.045+/-0.014 mg/cm2/h). The comparison of the Kp values of both test settings showed with a factor of about 31 (Kp=1.563 x 10(-3) cm/h) much higher values for 50% aqueous BE and Kp=0.050 x 10(-3) cm/h for neat BE. Although the flux does not consider the chemical concentration, it showed a smaller difference in both test settings as Kp; however, the flux remains a non-specific parameter for the description of percutaneous absorption. The results of our experiments showed that the permeability coefficient Kp was not able to adjust the flux of BE to the concentration. This is in agreement with the evaluation of Kp from BE data described in the literature.

Adult↗
PubMed2004

Internal exposure of nursery-school children and their parents and teachers to di(2-ethylhexyl)phthalate (DEHP).

Di(2-ethylhexyl)phthalate (DEHP) is the main plasticizer for polyvinyl chloride (PVC) products. It has become widely spread in our environment and among people. DEHP is suspected to be responsible for endocrine-disruptor-like effects in mankind. Children are probably most susceptible to these endocrine effects. In this study we determined the internal exposure of nursery school children (aged 2-6 years) to DEHP and compared it to their parents' and teachers' exposure. The DEHP-metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP) were determined in first morning urine. The sum of the three DEHP metabolites in children's and in adults' urine was 90.0 and 59.1 micrograms/l respectively (median values; p = 0.074). Concentrations of the secondary metabolites 5OH-MEHP (median: 49.6 vs. 32.1 micrograms/l; p = 0.038) and 5oxo-MEHP (median: 33.8 vs. 19.6 micrograms/l; p = 0.015) were significantly higher in children than in adults. MEHP concentrations were low both in adults and children (median: 6.6 micrograms/l vs. 9.0 micrograms/l). Creatinine adjusted values should more accurately reflect the dose taken up with respect to body weight when comparing children with adults. Total creatinine adjusted DEHP metabolites in urine were significantly higher in children than in adults (median values: 98.8 vs. 50.9 micrograms/g creatinine; p < 0.0001). This also applied to the concentrations of both secondary metabolites 5OH-MEHP (55.8 vs. 28.1 micrograms/g creatinine; p < 0.0001) and 5oxo-MEHP (38.3 vs. 17.2 micrograms/g creatinine; p < 0.0001). Creatinine corrected concentrations for the monoester MEHP in children and adults were very similar (8.7 vs. 8.6 micrograms/g creatinine; p = 0.908). Based on the sum of the three determined metabolites we estimated the DEHP dose (in microgram/kg body-weight) taken up by children to be about twice as high as the dose taken up by adults. Routes of the ubiquitous exposure to DEHP remain indistinct. In children's urine the mean relative ratios of MEHP to 5OH-MEHP to 5oxo-MEHP were 1 to 7.1 to 4.9, in adults they were 1 to 3.4 to 2.1. This might indicate an enhanced oxidative metabolism in children. To date no information on the biological activity and toxicity of oxidative metabolites of DEHP is available. Since these are the major metabolites of DEHP toxicological data on these metabolites is urgently needed.

Adult↗
PubMed2004

Evidence for increased internal exposure to lower chlorinated polychlorinated biphenyls (PCB) in pupils attending a contaminated school.

External and internal exposure to six WHO-indicator congeners of polychlorinated biphenyls (PCB 28, 52, 101, 138, 153, 180) as well as subjective health complaints of a group of 377 pupils attending a PCB-contaminated school were compared with a control group of 218 pupils attending a non-contaminated school. Indoor air of the contaminated school revealed total PCB concentrations (sum of six indicator congeners times 5) ranging between 690 and 20,800 ng/m3 (median 2044 ng/m3). The lower chlorinated congeners PCB 28, 52, 101 were the prevailing contaminants (median 33, 293, and 66 ng/m3). Using improved analytical procedures at least one of the lower chlorinated congeners could be detected in 95% of the blood samples of pupils attending the contaminated school. Median concentrations for PCB 28, 52, 101, and for the sum of lower chlorinated congeners were 6, 9, 5, and 22 ng/l blood plasma, respectively, whereas the corresponding values in the control group were all < 1 ng/l. In contrast, no significant differences were found for the higher chlorinated congeners (PCB 138, 153, 180) which were detected in 1-2 orders of magnitude higher concentrations in both groups. Due to the dietary intake of these congeners similar total PCB levels were found (95th percentile 1070 and 1010 ng/l plasma in participants of the contaminated and control school). Using the Giessen Subjective Complaint List for Children and Adolescents no statistically significant differences in health complaints were observed between both groups of children. It is concluded that exposure of pupils to PCB in indoor air of the contaminated school caused increased blood concentrations of lower chlorinated congeners. Compared to background levels the detected excess body burden was very low indicating no additional health risk. Exposure was not associated to any specific subjective complaints.

Adolescent↗
PubMed2004

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.

Acrylamide↗
PubMed2004

Student health policy of a German medical school--results of a cross sectional study concerning students' immunity to vaccine-preventable diseases.

Medical students come into contact with infectious materials early in their medical education. Aim of this study was to assess medical students' immunity to vaccine-preventable diseases and to ensure immunity against hepatitis B. An occupational health medical was offered to all medical students with special emphasis on preclinical students. The examination included a check of the certificates of vaccination and serological tests concerning hepatitis B virus, hepatitis C virus and, on request, HIV. A lecture on occupational risks and general precautions was given to the students. In 7 of 804 tested students serological markers of a previous hepatitis B infection were discovered, fortunately none of the students was infectious. No case of infection with the hepatitis C virus (n=804) or HIV (n=700 tested voluntary) was identified. For 52 percent of the students vaccination against hepatitis B was necessary to guarantee protective immunity. Documented protection against other vaccine-preventable diseases as tetanus (71%), diphtheria (67%), poliomyelitis (56%), pertussis (2%), measles (32%), mumps (24%) and rubella (25%) was also insufficient. As a result a vaccination against hepatitis B in childhood without documented response doesn't guarantee a sufficient protection. An occupational health medical at the beginning of preclinical training seems to be an adequate method of making medical students aware of occupational risks, immunization policies and the importance of occupational medicine.

Adult↗