Thomas Eikmann

Health effects of particles in ambient air

UNLABELLED A summary of a critical review by a working group of the German commission on Air Pollution Prevention of VDI and DIN of the actual data on exposure and health effects (excluding cancer) of fine particulate air pollution is presented. EXPOSURE Typical ambient particle concentrations for PM10 (PM2.5) in Germany are in the range of 10-45 (10-30) microg/m3 as annual mean and 50-200 (40-150) microg/m3 as maximum daily mean. The ratio of PM2.5/PM10 generally amounts between 0.7 and 0.9. HEALTH EFFECTS During the past 10 years many new epidemiological and toxicological studies on health effects of particulate matter (PM) have been published. In summary, long-term exposure against PM for years or decades is associated with elevated total, cardiovascular, and infant mortality. With respect to morbidity, respiratory symptoms, lung growth, and function of the immune system are affected. Short-term studies show consistant associations of exposure to daily concentrations of PM with mortality and morbidity on the same day or the subsequent days. Patients with asthma, COPD, pneumonia, and other respiratory diseases as well as patients with cardio-vascular diseases and diabetes are especially affected. The strongest associations are found for PM2.5 followed by PM10, with no indication of a threshold value for the health effects. The data base for ultra fine particles is too small for final conclusions. The available toxicological data support the epidemiological findings and give hints as to the mechanisms of the effects. CONCLUSION The working group concludes that a further reduction of the limit values proposed for 2005 will substantially reduce health risks due to particulate air pollution. Because of the strong correlation of PM10 with PM2.5 at most German sites there is no specific need for limit values of PM2.5 for Germany in addition to those of PM10.

ADDITIONAL COSTS FOR PREVENTING THE SPREAD OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS AND A STRATEGY FOR REDUCING THESE COSTS ON A SURGICAL WARD

OBJECTIVE To determine the added costs of hygienic measures (barrier precautions, isolation, and decontamination) required for MRSA carriers in German hospitals and possible strategies for cost reduction. DESIGN On a septic surgical ward caring for 35% of all MRSA cases in a university hospital (1,182 beds), additional costs for personnel time and materials were calculated and medical charts of all MRSA cases admitted to the ward during 1 year were analyzed retrospectively. Twelve of the wards 13 beds were located in rooms with at least 2 beds. PATIENTS Four hundred ninety-eight MRSA carrier hospital-days (of 20 MRSA cases) could be assessed. All patients (80% men, 50% older than 74.5 years) had broken skin. RESULTS In 95% of the cases, microbiological findings suggested transmission of MRSA during the current or a previous stay on this ward. The study found total avoidable costs of approximately 142,794.01 euros in 1 year, averaging 371.95 euros for one MRSA patient hospital-day and 9,261.56 euros per MRSA case. The most expensive single measure was blocked beds in multibed rooms (305.75 euros/day), which accounted for 82% of the extra costs. Costs most likely were underestimated. CONCLUSIONS Daily additional case costs amounted to 96% of social security payments. Blocked beds in multibed rooms accounted for more than 80% of these excess costs. Isolation has been scientifically validated and is required by law in Germany. Building an adequate number of single-bed rooms should help prevent spread and would greatly lower the added costs of infection.

Urinary di(2-ethylhexyl)phthalate (DEHP)--metabolites and male human markers of reproductive function.

INTRODUCTION Phthalates are suspected to act as endocrine modulators in humans and exert reproductive toxicity. The general population is exposed to phthalates through nutrition, consumer products, medications and medical devices. The aim of the present study is to explore whether internal phthalate exposure represented by metabolites of di(2-ethylhexyl) phthalate (DEHP) can be related to human markers of reproductive function (i.e. semen concentration, motility and morphology). METHODS We recruited 349 men who were part of subfertile couples and were referred for fertility work-up between April 2004 and November 2005. Semen analysis was performed according to recommendations of the World Health Organization (WHO). Parameters were dichotomized based on 1999 WHO reference values for sperm concentration (<20million/ml) and motility (<50% sperm with progressive motility), as well as Tygerberg strict criteria for morphology (<4% normal forms). We analyzed internal DEHP exposure in single spot urine samples by determining its secondary metabolites mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP), mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and 5carboxy-mono(2-ethylhexyl)phthalate (5cx-MEPP) next to the monoester metabolite mono(2-ethylhexyl)phthalate (MEHP). Logistic regression was performed for the three semen parameters (concentration, motility, and normal morphology) to estimate their dependence on the sum of the four DEHP metabolites (DEHP-4) under consideration. Adjustment was performed for age, duration of abstinence, and smoking status. RESULTS DEHP metabolites of n=349 men (age: median=34ys) were analysed. Median concentrations [microg/l] were MEHP (n=337) 4.35, 5OH-MEHP (n=341) 12.66, 5oxo-MEHP (n=341) 9.02, and 5cx- MEPP (n=292) 14.53. Semen parameters of n=349 men were analysed by logistic regression. Semen concentration (<20mio/ml: 35%) or sperm motility (WHO A+B <50%=20%) were not found to be associated statistically significantly with the sum the DEHP metabolites (DEHP-4). DISCUSSION Metabolites of DEHP and other phthalates analyzed in urine are very specific for determining recent internal phthalate exposure. According to our evaluation human reproductive parameters from semen analyses do not show significant associations with concentrations of DEHP metabolites determined in spot urine sampled at the day of andrological examination.

Ranking and frequency of somatic symptoms in residents near composting sites with odor annoyance

The presented study reports the prevalence of somatic symptoms in three study samples living in the vicinity of composting plants. Microorganisms were measured in the air of the residential areas closest to the plants at the same time an epidemiological investigation was performed in the neighborhood near (150 to 1,500 m) to three plants and in corresponding control residential areas of the same district. Nine hundred and seventy-nine residents were questioned about the odor annoyance in their vicinity. An instrument measuring somatic complaints (SOMS 2 acc. Rief et al., 2001) was used to determine the unexplained somatic symptoms of the past two years and a gender-independent Total Complaint Index (TCI) was calculated. The percentages of study population reporting somatic symptoms were higher in all six samples in comparison with the German population (Rief et al., 2001) and in samples living near composting sites compared to the corresponding control samples. The study sample living close to site A (exposed to bioaerosols and odor annoyance) had the highest rates of complaints. A difference could be seen in comparison to the corresponding control sample (TCI: p[Anear vs. Acontrol] = 0.001; Mann-Whitney). In this group breathlessness was reported more than twice as often as in the other three samples. Out of the five most frequently reported symptoms four corresponded to the five complaints the German population reports most frequently in all groups. Nausea was the fifth most reported symptom in both samples reporting annoying residential odors (Anear and Bnear). The type of somatic symptoms reported most often was influenced little by environmental odors and medically relevant bioaerosol concentrations, except for nausea in context with annoying residential odors. As expected frequency of reporting general somatic symptoms was influenced by the perceived environment near the three composting sites. Concerning the sum of bodily complaints (TCI) though, this was only significant in the group exposed to medically relevant concentrations of residential outdoor bioaerosols, which was accompanied by high rates for breathlessness. The SOMS2 was able to mirror measurable, medically relevant environmental exposures in study groups and showed fewer changes concerning annoying or presumed environmental exposures.

Testing of chelating agents and vitamins against lead toxicity using mammalian cell cultures

Mammalian cell cultures were used to determine the capacity of antidotes to modify (a) lead uptake, (b) lead toxicity and (c) lead release from cells. The following chelating agents were tested: Na, Ca-ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), nitriloacetic acid, ethylene glycol-bis(aminoethyl)tetraacetic acid (EGTA), D,L-mercaptosuccinic acid (MSA), meso-2,3-dimercaptopropanesuccinic acid (MSA), D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS), penicillamine (PA), N-acetylpenicillamine (NAPA), and diethylcarbodithioate (DDTC). The following vitamins were tested: thiamine (B1), riboflavine (B2), pyridoxine (B6), cobalamin (B12) and ascorbic acid (C). Inhibition of lead uptake was produced by EDTA, EGTA, DMSA, DMPS, MSA, PA, NAPA and vitamins B1, B6 and C, vitamins B2 and B12 being ineffective. The same compounds reduced lead cytotoxicity. Interestingly DDTC and DTPA increased lead uptake, but did not exacerbate lead toxicity. Significant release of lead from preloaded cells was caused by DTPA, NAPA, DMPS and PA, while the other chelators were ineffective.

Influences on human internal exposure to environmental platinum

Different influences on internal exposure to platinum are investigated and for the first time weighted in environmentally exposed subjects as far as individual internal platinum concentrations are concerned. Detailed medical and environmental histories as well as oral cavity status were assessed in 84 dermatological patients, and internal platinum exposure was determined by analyzing platinum in urine using adsorptive voltammetry (AV). Platinum concentrations ranged from <0.9 (detection limit) to 65.5 ng Pt/l urine. Influence of different types and age of alloy restorations and therefore relevance of the exposure pathway due to solubilization of platinum in saliva could be demonstrated. No platinum-related health effects (contact stomatitis, asthma or kidney conditions) were observed. Analysis of covariance showed the number of noble dental alloy restorations (P<0.0001) and to a lesser extent age (P=0.0017) to independently influence internal platinum exposure. Even though spread of environmental platinum has increased, internal platinum exposure is low in subjects without assessable medical or dental devices (usually <4.5 ng/l urine) and not related to adverse health effects. For the first time, detailed individual information on possible exposure pathways to platinum were considered in an analysis of relevant influential factors: Car traffic exposure and dermatological condition showed no association with internal platinum exposure. Uptake from platinum containing noble metal dental alloy restorations (NMDAR) is of greatest relevance, surmounting the influence of each year of lifetime on platinum body load by more than 10-fold.

Low dose effects of fibrous and non-fibrous mineral dusts on the proliferation of mammalian cells in vitro

This report presents preliminary results of studies on the growth stimulating properties of mineral dusts. The studies were carried out with Syrian hamster diploid embryonic fibroblasts and Chinese hamster fibroblasts, line B14F28. Toxicity testing was done by the determination of the plating efficiency as a measure of growth and viability. The following dusts were used: the modified UICC asbestos fibres amosite, (AFF) crocidolite (KFF), chrysotile (KFF): in addition glass fibre (GFF), corundum and quartz DQ12. Concentrations > 2 microg/cm2 of AFF, CFF, KFF and GFF depressed the plating efficiency of B14F28 cells in a dose-dependent manner, but all of the fibres and corundum increased colony sizes at concentrations of 0.16-0.33 microg/cm2, in the case of corundum, AFF, KFF, and CFF also at up to 0.66 or 1.32 microg/cm2. DQ12 did not enhance colony growth. The stimulation of proliferation could be demonstrated both in terms of colony size (diameter) and cell numbers. The factor(s) responsible for proliferation stimulation reside in the supernatant, since the medium of dust-treated cell cultures was able to stimulate colony growth after removal of the dusts by filtration. The results indicate the induction of growth factors (cytokines) by low concentrations of the mineral dusts. Experiments concerning the effect of dusts on embryonic golden hamster fibroblasts yielded similar results. The plating efficiency was inhibited by concentrations of GFF and CFF > 0.25 microg cm2 and by AFF, KFF, GFF and corundum at concentrations > 5 microg/cm2, but colony counts were significantly increased by AFF, KFF and corundum at concentrations of 0.25-3 microg/cm2. This biological reaction which was observed in different cell types appears to be especially relevant in the context of environmental exposure where low dust concentrations prevail.

Interdisciplinary diagnostics in environmental medicine – findings and follow-up in patients with chronic medically unexplained health complaints

PROBLEM In patients attributing their chronic, medically unexplained complaints to environmental factors the greatest challenge is to overcome their disabling belief in toxicogenic explanations. METHOD Patients presenting with health complaints that they attributed to environmental causes in an environmental outpatient department (EOPD) within a university medical center in Germany were studied. An interdisciplinary review of previously diagnosed medical conditions, current clinical consultations, personal risk communication and therapeutic advice is presented. Additionally, patient contentedness, complaint development, and belief in environmental attribution in a follow-up interview are given. RESULTS The open, prospective study comprises 51 patients reporting more than one complaint. Symptoms had lasted for more than 3 years in 63% of the cases. Seventy percent attributed their complaints to more than one environmental cause. The clinical diagnostic procedure reduced the number of prediagnosed clinical conditions by 50%. Numerous foregoing environmental laboratory analyses had overestimated toxicologically relevant findings. These were not confirmed in 80% (8/10) of the cases. In 8% (n = 4) of the patients a relevant environmental or occupational medical condition was found. A mental or behavioral condition was not considered to have first priority in explaining all complaints in 43% (22/51) of the patients. Among these, mostly respiratory or skin-related diseases were found. All patients contacted participated in a follow-up study after a minimum of 21 months. Sixty-seven percent reported having felt that they were taken seriously, 38% felt better after the beginning of the study, and 45% were no longer certain about the importance of the environmental attribution. Since 83% of the patients with a preceding residential diagnosis of MCS or SBS still believed in environmental causes of their complaints in the follow-up study, we conclude that these prediagnoses appear to be a risk for persisting attribution of the environmental factor. About one third (37%) of these patients with complaints that had not been medically explained by an organic condition during interdisciplinary diagnostics had meanwhile consulted a psychotherapist. CONCLUSIONS Interdisciplinary diagnostics and scientifically based risk assessment in a specialized clinical center were effective and mostly well accepted by the patients and resulted in reduced attribution of complaints to environmental conditions. No indication was found that patients with complaints not medically explained by organic conditions were managed less successfully by this approach. Considering the high costs that these patients have previously caused, it appears valuable to apply an interdisciplinary diagnostic strategy.

Assessment of somatic complaints in environmental health

In patients attributing their health complaints to environmental factors (EnvPat) evidence based medical diagnostics usually do not confirm environmental and somatic causes of symptoms. Many symptoms remain unexplained. Aim of the study was the systematic assessment of medically unexplained physical symptoms (MUPS) in EnvPat and comparison to symptom rates reported by subjects of an environmental study exposed to environmental odors (EnvExp). This specific exposure was chosen, as odors are associated by an unclear mechanism with physical symptoms. By this we aimed to enlighten the open question as to likeliness that MUPS of EnvPat are caused by hitherto unrevealed environmental exposures or result from somatization. MUPS were measured with SOMS-2 in EnvPat n=92, patients presenting in a university environmental outpatients clinic, and different study groups exposed to environmental odors (EnvExp). These were: (1) subjects exposed to annoying odors and medically relevant concentrations of bioaerosols, such as airborne microorganisms (EnvExp-1, n=74), and (2) subjects exposed to odors alone (EnvExp-2, n=282) as well as unexposed controls (Controls, n=235). Logistic regression and analysis of variance were applied to analyze rates of single complaints and the sum index of complaints (SOMS-CoIx). In EnvPat rates of MUPS were highest - significant (p<0.05) adjusted OR in 23 of 25 MUPS compared to controls - and highest SOMS-CoIx (mean 15.3 (S.D. +/-9.3). Rates of MUPS were lower in environmentally exposed subjects with difference in the two strata: while EnvExp-1 differed in several complaints, i.e., nausea and SOMS-CoIx (mean 7.2, S.D. +/-6.9) from controls (p<0.05), EnvExp-2 (SOMS-CoIx mean 4.8, S.D. +/-5.2) showed relevant differences only in two single complaints and not in the SOMS-CoIx from controls, SOMS-CoIx mean 3.9, S.D. +/-5.0. This remained when adjusting for age, gender, and school education. Rates of MUPS in environmental patients were clearly higher than in subjects with actual environmental exposure, making it unlikely that their symptoms are due to undetected environmental factors. MUPS of EnvPat show similarities to psychosomatic patients. In the environmental survey symptom assessment by SOMS-2 was sensitive to different environmental scenarios, i.e., higher rates of physical complaints were only found in subjects with hazardous residential bioaerosols pollution as well as an annoying odor exposure and interestingly not in subjects exposed to annoying odors alone. This underlines that questionnaire data of somatic complaints need to be interpreted on the basis of exposure assessment in order to unjustly attribute health complaints to annoyance.

Clinical Environmental Medicine

INTRODUCTION Clinical environmental medicine deals with environmental effects on human health in individual patients. Patients seek medical advice for problems of many different kinds that may be due to environmental exposures; such exposures must be considered carefully along with other potential causes. An environmental medical assessment should include thorough medical history-taking and physical examination, the formulation of a differential diagnosis, and (whenever indicated) human biomonitoring, site inspections, and ambient monitoring. METHODS This review of clinically relevant environment-related health disturbances is based on a selective evaluation of the pertinent literature and of own experiences. RESULTS Overall, relevant environmental exposures can be identified in up to 15% of patients who attribute their health complaints to environmental factors. (Clinical disorders are more common and more severe in these patients.) 40% to 75% are found to suffer from other physical and/or emotional conditions without any specific environmental aspect, i.e., without any apparent or verifiable exposure. DISCUSSION Despite the relative rarity of verifiable environmentally related health disturbances, these must be clearly identified and delimited to avoid further harmful exposures. Environmental medical counseling should include risk assessment and behavior recommendations for all patients who attribute their medical problems to their environment. Physicians performing specific environmental-medical diagnostic procedures must be aware of their limitations in order to avoid performing tests whose results have no therapeutic consequences and are thus of no help to either the physician or the patient.