Liquid release as a source of potential drug exposure during the handling of intravenous infusions in nursing.

PURPOSE: This study aims at experimentally determining the incidence and extent of liquid releases onto the operator's hands and into the work environment during common nursing operations involving infusions. METHODS: A sequence of operations related to the preparation and administration of infusions was conducted by three subjects for 15 times each using fluorescein marked infusion solutions and two different infusion sets (standard set vs. safety-optimized set). Unintended release of liquid was quantified by glove and surface wipe sampling and HPLC/FD analysis of the samples. Operations concerning the disposal of infusions were also part of the study. RESULTS: In over 90% of the simulations, a release of infusion solution was observed in a standard workflow, comprising priming and decapping the infusion set, connecting it to a peripheral intravenous (IV) cannula, and detaching it again. Based on median values (229 vs. 26 µl), the release of infusion solution was about ninefold higher when using the non-optimized standard infusion set. During decapping, a hand contamination was found in a majority of cases. CONCLUSIONS: The handling of infusions may involve a risk of nurses' exposure to active agents by release of infusion solution into the work environment. According to our results with different infusion sets, exposure risks can be reduced technically and by appropriate handling. Nevertheless, hand contaminations found for both sets emphasize the necessity for additional measures such as more consistent use of protective gloves.

Saliva as a matrix for human biomonitoring in occupational and environmental medicine.

PURPOSE: Human biomonitoring (HBM) implies the assessment of internal exposure to hazardous substances by measuring the substances, their metabolites or reaction products, as well as effect parameters in human body fluids. Along with blood, plasma and urine, saliva is of increasing interest as an alternative matrix for HBM. METHODS: This paper reviews studies that measure salivary background levels of hazardous substances, elevated levels after environmental or occupational exposure, as well as references which deal with physiological and toxicokinetic behaviour of saliva and salivary parameters, respectively. RESULTS: The studies revealed that the determination of biomarkers in saliva is a promising approach for HBM, even if only few substances showed a satisfying correlation with exposure data or established biomonitoring matrices such as blood, plasma and urine. Saliva has been proven to be particularly suitable for substances of low molecular weight such as organic solvents, selected pesticides, cotinine, and for some specific trace elements. Besides several advantages, serious problems and limitations were identified. Above all, the complex interactions between substance properties, sampling procedure, sample preparation, measurement techniques or individual factors, and the salivary analyte level are discussed. CONCLUSIONS: A major conclusion of the review is that more scientific studies are needed in order to systematically collect data on parameters, influencing salivary analyte levels. Crucially required is a harmonisation of the sampling as well as the sample preparation techniques and procedures, which is indispensable to achieve an overall comparability and interpretability of salivary biomarker levels.

Biomonitoring in wearers of permethrin impregnated battle dress uniforms in Afghanistan and Germany.

OBJECTIVES: To analyse differences in uptake of the insecticide permethrin in wearers of non-impregnated and permethrin impregnated battle dress uniforms (BDU) in Afghanistan and Germany. METHODS: In two separate studies, in April 2003-January 2004 (study I, n=549) and in February-April 2005 (study II, n=195), healthy female and male members of the German Federal Armed Forces were equipped with permethrin impregnated BDU (two sub-cohorts in Germany and one in Afghanistan) while members equipped with non-impregnated uniforms served as a control group. Human biomonitoring was conducted before, during and after wearing the uniforms by measuring permethrin metabolites in urine samples via GC-MS. RESULTS: Subjects of the Afghan and German control groups had permethrin levels in the range of the German general population. In contrast, subjects wearing impregnated BDU had about 200-fold higher exposure levels. Within this group, subjects located in Afghanistan and smokers had significantly higher exposure levels. Internal exposure decreased with increasing duration of use of impregnated BDU. CONCLUSIONS: There is no evidence for a higher background permethrin contamination in military bases located in Afghanistan compared to Germany. Daily use of permethrin impregnated BDU is associated with significantly higher permethrin uptake compared to the general population. Hand-mouth contact by smoking can increase uptake which also seems to be influenced by the duration of use of impregnated BDU.

Renal excretion of 1,2-dihydroxynaphthalene (DHN) in firefighting instructors after exposure to polycyclic aromatic hydrocarbons (PAHs) during live fire training.

Exposure of firefighting instructors to polycyclic aromatic hydrocarbons (PAHs) such as naphthalene is unavoidable during live fire training. The study aimed to investigate naphthalene uptake by measuring the urinary excretion of the naphthalene metabolite 1,2-dihydroxynaphthalene (DHN), to describe the DHN elimination kinetics and to evaluate the results by comparison to further biomarkers of PAH exposure. N = 6 male non-smoking firefighting instructors completed five training sessions each in a residential fire simulation unit under respiratory protection. All participants provided two urine samples before and another seven samples within an 18-h-interval after each session. DHN was detected by gas chromatography/tandem mass spectrometry (GC-MS/MS) in all samples (n = 237) with median concentrations ranging from 3.3 µg/g crea. (range 0.9-10.2) before exposure to 134.2 µg/g crea. (43.4-380.4) post exposure. Maximum elimination found 3.3 h (median) after onset of exposure decreased with a mean half-life of 6.6 h to 27.1 µg/g crea. (15.7-139.5) 18 h after training. DHN sensitively indicated a presumed dermal naphthalene intake during training, showing similar elimination kinetics like other naphthalene metabolites. Internal exposure of the participants transiently exceeded exposures determined for non-smokers in the general population, but was lower than at other workplaces with PAH exposure. Despite limited uptake, accumulation is possible with daily exposure.

Comparison of experimentally determined and mathematically predicted percutaneous penetration rates of chemicals.

The aim of the study was to evaluate the predictive potential of three different mathematical models for the percutaneous penetration of industrial solvents with respect to our experimental data. Percutaneous penetration rates (fluxes) from diffusion cell experiments of 11 chemicals were compared with fluxes predicted by mathematical models. The chemicals considered were three glycol ethers (2-butoxyethanol, diethylene glycol monobutyl ether and 1-ethoxy-2-propanol), three alcohols (ethanol, isopropanol and methanol), two glycols (ethylene glycol and 1,2-propanediol), one aromatic hydrocarbon (toluene) and two aromatic amines (aniline and o-toluidine). For the mathematical prediction of fluxes, models described by Fiserova-Bergerova et al. (Am J Ind Med 17:617-635 1990), Guy and Potts (Am J Ind Med 23:711-719 1993) and Wilschut et al. (Chemosphere 30:1275-1296 1995) were used. The molecular weights, octanol-water partition coefficients (LogP) and water solubilities of the compounds were obtained from a database for modelling. The fit between the mathematically predicted and experimentally determined fluxes was poor (R(2) = 0.04-0.29; linear regression). The flux differences ranged up to a factor of 412. For 4 compounds, the Guy and Potts model showed a closer fit with the experimental flux than the other models. The Wilschut et al. model showed a lower flux difference for 4 compounds as compared to experimental data than the models of Fiserova-Bergerova et al. and Guy and Potts. The Fiserova-Bergerova et al. model showed for 3 compounds a lower flux difference to experimental data than the other models. This study demonstrates large differences between mathematically predicted and experimentally determined fluxes. The percutaneous penetration as determined in diffusion cell experiments may be considerably overestimated as well as underestimated by mathematical models. Although the number of compounds in our comparison study is small, the results point out that none of the mathematical model has significant advantages.

Internal exposure of firefighting instructors to polycyclic aromatic hydrocarbons (PAH) during live fire training.

Firefighting instructors in live fire training are inevitably exposed to emissions containing, carcinogenic PAH. The study investigated PAH uptake in a group of firefighting instructors during short-term exposure in live fire training by urinary biomonitoring. Six firefighting instructors (non-smokers) completed five 2 h-training sessions each in a carbonaceous-fired simulation unit using self-containing breathing apparatuses (SCBA). Complying with a minimum time interval of six days between the individual training sessions, the participants provided urine samples before and immediately after, as well as 1, 3, 6, 9, 11, and 18 h after each training session. Samples were analyzed for 10 mono-hydroxylated metabolites of the PAH naphthalene, fluorene, phenanthrene and pyrene using gas chromatography/tandem mass spectrometry. A significant effect of the training sessions on the time course of internal exposure was found (p < 0.0001). The concentration of all parameters clearly increased at the latest 3 h after end of training. After peaking, the concentrations dropped with half-lives between 3.5 and 9.3 h but did not reach the initial levels within 18 h again. Compared to pre-training levels, the increase in metabolite excretion was between 546-933 %. During peak excretion reference values for hydroxynaphthalene (35 µg/L, sum of 1- and 2-isomer) and 1-hydroxypyrene (0.30 µg/L) were exceeded in 64 % (maximum: 381.3 µg/L) and 73 % of the samples (maximum: 1.88 µg/g crea.), respectively. Live fire training is associated with an additional uptake of PAH. Due to the consequent use of SCBA, dermal absorption is assumed as major exposure route. Further measures to reduce PAH exposure should be considered, in particular since higher internal loads caused by accumulation effects are to be expected with daily or more frequent training.

Occupational exposure to polycyclic aromatic hydrocarbons and DNA damage by industry: a nationwide study in Germany.

Exposure to polycyclic aromatic hydrocarbons (PAH) and DNA damage were analyzed in coke oven (n = 37), refractory (n = 96), graphite electrode (n = 26), and converter workers (n = 12), whereas construction workers (n = 48) served as referents. PAH exposure was assessed by personal air sampling during shift and biological monitoring in urine post shift (1-hydroxypyrene, 1-OHP and 1-, 2 + 9-, 3-, 4-hydroxyphenanthrenes, SigmaOHPHE). DNA damage was measured by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and DNA strand breaks in blood post shift. Median 1-OHP and SigmaOHPHE were highest in converter workers (13.5 and 37.2 microg/g crea). The industrial setting contributed to the metabolite concentrations rather than the air-borne concentration alone. Other routes of uptake, probably dermal, influenced associations between air-borne concentrations and levels of PAH metabolites in urine making biomonitoring results preferred parameters to assess exposure to PAH. DNA damage in terms of 8-oxo-dGuo and DNA strand breaks was higher in exposed workers compared to referents ranking highest for graphite-electrode production. The type of industry contributed to genotoxic DNA damage and DNA damage was not unequivocally associated to PAH on the individual level most likely due to potential contributions of co-exposures.

Urine tropenol ester levels in workers handling tiotropium bromide synthesis: implications for exposure prevention and biomonitoring.

Tropenol ester is a highly toxic anticholinergic substance and an intermediate used in industrial production of the bronchodilator tiotropium bromide. The aim of this study was to systematically test workers involved in its production for tropenol ester in urine to identify any exposure pathways and define additional preventive measures. Twelve workers performing tasks involving potential exposure to tropenol ester were repeatedly monitored at the end of each production cycle. Medical exams revealed no symptoms of acute poisoning with tropenol ester, but biological monitoring of urine showed 36 positive findings in 79 samples, with tropenol ester concentrations ranging between the detection limit of 54 pg/mL and 2160 pg/mL. We managed to establish the cause of only one positive finding, which was a hole in a protective glove, whereas the rest most likely occurred due to human error. Because of this, the plant decided to modify the production process by replacing tropenol ester with a safer intermediate. While it is the safest course of action, there where it cannot be taken, biological monitoring can be very helpful in raising awareness about exposure to toxic substances, including the new ones that have not been studied for their adverse potential.

Risk assessment of Bundeswehr (German Federal Armed Forces) permethrin-impregnated battle dress uniforms (BDU).

In an age when vector-borne diseases are emerging worldwide, personal protective measures are essential for shielding soldiers and other exposed persons from arthropod attack. The development of permethrin-impregnated clothing has been one recent advance in protecting persons at-risk. However, to date risk assessment has not been performed related to wearing permethrin-impregnated clothing over longer time periods. Therefore, this paper describes relevant toxicological aspects of permethrin and estimates the extent of dermal permethrin uptake by soldiers wearing impregnated uniforms by determining urine metabolites of permethrin. The exposure monitoring conducted in wearers of untreated uniforms did not show any signs of increased permethrin uptake and was similar to that of the general population in Germany. By contrast, studies involving the soldiers wearing permethrin-impregnated uniforms identified far higher internal exposure, the amounts of urine metabolites clearly above the reference value for the background exposure of the German population at large. Comparing the median excretion values, an approximately 200 times higher exposure can be assumed. The excretion levels of the subject with the maximum amount of metabolites correspond to an internal exposure of around 5-6microg/kg body weight and day thereby considering that biomonitoring could not take all urine metabolites and other elimination routes into account. Based on an oral absorption rate of 50%, the internal dose of 5-6microg/kg body weight and day would correspond to an oral uptake of permethrin which is around 20% of the ADI value of 50microg/kg body weight and day. In addition, based on these data and using a dermal absorption rate of 2% the permethrin dose reaching the skin was estimated to be 250microg/kg body weight and day. Considering a standard body weight and the area covered by the uniform, an exposure level of about 1.25microg permethrin/cm(2) skin and day can be calculated. Clinical subjective symptoms were recorded by means of a self-reporting questionnaire which has been developed and used for this specific purpose in environmental outpatient departments in both groups (wearers of impregnated versus non-impregnated uniforms). Only minor sensory impairments were identified in one of the studies (Kabul/Afghanistan) which may represent skin paraesthesiae. Based on these results, it can be assumed that the normal use of permethrin-treated uniforms does not affect human health to a clinical relevant extent. We recommend that the release rate of permethrin from the textile material should be strictly monitored by means of a quality assurance method. It should comply with standards to which the results of this study may contribute.

[Influence of rescue service personnel's shift work on psycho-physical parameters]. / Einfluss der Schichtarbeit im Rettungsdienst auf psychophysische Parameter.

BACKGROUND: The aim of the investigation was to receive information about the interaction between psycho-physical parameters as a function of the strain by shift work for rescue service personnel. MATERIAL AND METHODS: We examined 26 persons, who are active in the rescue service. The investigations always took place in the morning between 7.00 and 8.00 o'clock, either after 3 days off (n = 26), after 3 night shifts (n = 14) or in the morning of the third day shift (n = 14). The investigations included measurements of blood pressure, heart rate variability, and salivary cortisol. Additionally, standardized questionnaires (WHO-5, EBF 72/3) were used. RESULTS: A significant rise of the quotient LF/HF--as indicator for a sympathetic dominance--could be proven by means of a simple three minute arithmetic task at every investigation (after 3 days off from 0.81 to 2.30; p < 0.001). By means of the EBF a clear impairment could be demonstrated after 3 night shifts. Fatigue and somatic complaints were the main outcomes. In our study a more impaired well-being was associated with a more pronounced decrease of salivary cortisol (r = 0.538; p < 0.05) as well as lower blood pressure values (r = 0.547; p < 0.05), and a lower LF/HF quotient (r = 0.836; p < 0.01), indicating lower sympathetic and/or increased vagale activation, after three night shifts. CONCLUSIONS: After three night shifts a lower sympathetic activation seems to negatively affect the well-being. Due to the provable specific strain night- and shift-workers should be a priority target group for prevention and workplace health promotion.

Urinary excretion of heptanones, heptanoles and 2,5-heptanedione after controlled acute exposure of volunteers to n-heptane.

A lack of well-established parameters and assessment values currently impairs biomonitoring of n-heptane exposure. Using controlled inhalation experiments, we collected information on urinary n-heptane metabolite concentrations and the time course of metabolite excretion. Relationships between external and internal exposure were analysed to investigate the suitability of selected metabolites to reflect n-heptane uptake. Twenty healthy, non-smoking males (aged 19-38 years, median 25.5) were exposed for 3 h to 167, 333 and 500 ppm n-heptane, each. Spot urine samples of the volunteers, collected before exposure and during the following 24 h, were analysed for heptane-2-one, 3-one, 4-one, 2,5-dione, 1-ol, 2-ol, 3-ol, and 4-ol using headspace solid phase dynamic extraction gas chromatography/mass spectrometry (HS-SPDE-GC/MS). Starting from median pre-exposure concentrations between <0.5 (3-one) and 82.9 µg/L (4-one), exposure increased the concentrations for all parameters except for 4-one. Median post-exposure concentrations ranged up to 840.4 µg/L (2-ol) and decreased with half-lifes <3 h after exposure. Non-parametric correlation analyses (n = 47, p < 0.05) revealed weak to moderate associations of volume related metabolite excretion with external exposure for 2-one, 3-one and 2,5-dione (R = 0.332-0.753). Heptanol excretion was moderately associated with exposure (R ≥ 0.509) only after creatinine adjustment. Lacking association with external exposure impedes the use of 4-one as heptane biomarker, whereas 2-ol and 3-ol turned out to be sensitive indicators of exposure if creatinine correction is applied. By providing fundamental data on a panel of eight potential heptane metabolites, our study can help to promote biological monitoring of n-heptane exposure.

Dose-response modeling of occupational exposure to polycyclic aromatic hydrocarbons with biomarkers of exposure and effect.

In regulatory toxicology, the dose-response relationship between occupational exposure and biomarkers is of importance in setting threshold values. We analyzed the relationships between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and various biomarkers of internal exposure and DNA damage with data from 284 highly exposed male workers. Personal exposure to phenanthrene and other PAHs was measured during shift and correlated with the sum of 1-, 2+9-, 3-, and 4-hydroxyphenanthrenes in post-shift urine. PAHs and hydroxyphenanthrenes were associated with DNA damage assessed in WBC as 8-oxo-7,8-dihydro-2'-deoxyguanosine/10(6) dGuo and strand breaks by Comet assay as Olive tail moment. Hydroxyphenanthrenes correlated with phenanthrene (Spearman r(s) = 0.70; P < 0.0001). No correlations could be found between strand breaks and exposure (r(s) = 0.01, P < 0.0001 for PAHs; r(s) = -0.03, P = 0.68 for hydroxyphenanthrenes). Correlations with 8-oxo-7,8-dihydro-2'-deoxyguanosine/10(6) dGuo were weakly negative (r(s) = -0.22, P = 0.004 for PAHs) or flat (r(s) = -0.08, P = 0.31 for hydroxyphenanthrenes). Linear splines were applied to assess the relationships between the log-transformed variables. All regression models were adjusted for smoking and type of industry. For hydroxyphenanthrenes, 51.7% of the variance could be explained by phenanthrene and other predictors. Up to 0.77 microg/m(3) phenanthrene, no association could be found with hydroxyphenanthrenes. Above that point, hydroxyphenanthrenes increased by a factor of 1.47 under a doubling of phenanthrene exposure (slope, 0.56; 95% confidence interval, 0.47-0.64). Hydroxyphenanthrenes may be recommended as biomarker of occupational PAH exposure, whereas biomarkers of DNA damage in blood did not show a dose-response relation to PAH exposure.

Biological monitoring of welders exposed to aluminium.

To evaluate an adequate strategy for biological monitoring of aluminium (Al), a group of 62 Al welders (age in 1999: 23-51 years, median 35 years) was surveyed annually from 1999 to 2003 by determination of pre- and post-shift Al in urine and plasma. Biomonitoring was supplemented by personal air measurements of the total dust concentration. The welders' internal exposure was compared to the exposure of 60 non-exposed assembly workers (age in 1999: 21-51 years, median: 36 years) who were surveyed in 1999, 2001 and 2003. Having a nearly constant dust exposure, median concentrations of Al in urine (Al in plasma) of the welders decreased from 40.1 microg/g to 19.8 microg/g creatinine (8.7 to 4.6 microg/l). For the control group the median levels of Al in urine (plasma) ranged from 4.8 microg/g to 5.2 microg/g creatinine (2.4-4.3 microg/l) indicating a higher sensitivity for the marker Al in urine. No systematic differences have been found between pre- and post-shift internal exposure. This might be caused by the slow elimination kinetics and low systemic bioavailability of Al. A correlation analysis did not yield close relationships between dust exposure, Al in plasma and Al in urine underlining the importance of biomonitoring for assessment of Al exposure.

External and internal exposure to polycyclic aromatic hydrocarbons (PAH) among workers in the production of fire-proof materials - proposal of a biological monitoring guidance value.

In 1999, we introduced the German polycyclic aromatic hydrocarbons (PAH) study. The study was designed as a nation-wide investigation on workers exposed to PAH. One aim of the study was to establish biological monitoring guidance values (BMGVs) for different branches. Here, we report on the production of fire-proof materials. This branch of industry is typically confronted with high exposure to PAH and with PAH-induced occupational (cancer) diseases. One hundred and thirty-five employees participated in the course of seven sampling dates in four different plants in Germany. External exposure was determined by personal air monitoring of the 16 EPA-PAH. Human biological monitoring was accomplished by the determination of 1-hydroxypyrene and monohydroxyphenanthrenes in post-shift spot urine samples. Concentrations of PAH in the air of the workplaces ranged up to 1102.6microg/m(3). Maximum benzo[a]pyrene concentration was 38.2microg/m(3). The internal PAH exposure of workers was much higher compared with that of the general population. Median concentration for 1-hydroxypyrene was 6.4microg/g creatinine (maximum 279.6, 90th percentile 23.9microg/g creatinine) and for the sum of monohydroxyphenanthrene metabolites 13.3microg/g creatinine (maximum 313.4, 90th percentile 70.8microg/g creatinine). The following BMGVs for the non-smokers of this branch of industry are proposed: for 1-hydroxypyrene 18microg/g creatinine and for the sum of hydroxyphenanthrenes 77microg/g creatinine in urine measured at the end of the shift.

Biomonitoring and evaluation of permethrin uptake in forestry workers using permethrin-treated tick-proof pants.

We conducted a randomized case-control trial to analyze uptake of the insecticide/arcaricide permethrin in wearers of permethrin-impregnated and non-impregnated pants in German forestry. Eighty-two male workers were each equipped for a 16-week period with permethrin-treated (test group) or with non-treated work pants (control group). Pants with or without lining to protect against cuts, obtained from two different distributors, were worn in each group. Urinary permethrin metabolite levels were measured by GC-MS/MS before, during and after wearing of the pants. Permethrin uptake was calculated using additional questionnaire data. In the control group, metabolite levels in the range of environmental background exposure (median: ~0.5 µg/l) were measured. Subjects wearing impregnated pants showed consistently significantly higher exposure levels even before the first use of the pants with a maximum after 1 week of wearing the pants (median: ~12.5 µg/l). Significant differences in internal exposure were found depending on which of the distributors the pants came from. Metabolite levels decreased probably due to permethrin losses associated with laundering the pants. Calculated permethrin uptake is below the value corresponding to the WHO-proposed acceptable daily intake. Based on our data, a marginally increased cancer risk compared with the general population cannot be excluded when wearing impregnated pants over a working-lifetime period.

Occupational exposure to polycyclic aromatic hydrocarbons in German industries: association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms.

A cross-sectional study was conducted in 170 German workers exposed to polycyclic aromatic hydrocarbons (PAH) to investigate the role of 11 polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, GSTM1, GSTT1, and GSTP1 in the association between occupational exposure to PAH and urinary PAH metabolites. Polymorphisms were genotyped with real-time PCR. Exposure to 16 PAH was measured by personal air sampling. Urinary concentrations of 1-hydroxypyrene (1-OHP) and the sum of 1-, 2+9-, 3-, and 4-hydroxyphenanthrenes (OHPhe) were determined post-shift. Urinary 1-OHP and OHPhe correlated significantly with exogenous pyrene (Spearman r=0.52, p<0.0001) and phenanthrene (Spearman r=0.72, p<0.0001), respectively. ANCOVA was applied to investigate potential predictors of the metabolite levels. Current smoking and type of industry turned out to be predictors of 1-OHP but not of OHPhe. CYP1A1 3801TC carriers showed 1.6-fold higher OHPhe levels than 3801TT carriers (p=0.03). EPHX1 113HH was associated with higher and 139RR with lower metabolite levels when compared with the corresponding reference genotypes (113YY; 139HH). In comparison to GSTP1 114AA, carriers of the V allele had 1.5-fold higher 1-OHP (p=0.03) and 2-fold higher OHPhe concentrations (p=0.001). OHPhe turned out to be also a suitable biomarker of occupational PAH exposure. The association with ambient PAH exposure and the influence of polymorphisms was more pronounced for OHPhe.

Acute exposure to 50ppm toluene does not increase sleepiness.

The Pupillographic Sleepiness Test (PST) is a new neurophysiological method to assess sleepiness. In an exposure study to a constant exposure level of 50ppm toluene on 20 healthy men, our aim was to find out, if increased sleepiness could be seen with PST. PST was performed before and after 4.5h of exposure. General complaints were assessed with the Swedish Performance Evaluation System (SPES) self-assessment questionnaire, once before and during exposure. Values obtained during exposure were related to pre-exposure values. Parametric cross-over analysis of logarithmic Pupillary Unrest Index (PUI) values did not show an effect of toluene exposure. In a nonparametric cross-over analysis of SPES-scores a significant increase of the scores of unpleasant smell and irritation to the throat, but not of tiredness was found. In conclusion, acute exposure to 50ppm toluene, corresponding to the German threshold limit value, did not increase sleepiness.

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.

Uptake and elimination of permethrin related to the use of permethrin treated clothing for forestry workers.

Wearing of permethrin treated clothing usually implicates an uptake of permethrin by the user. Aim of our study was to examine the kinetics of internal permethrin exposure in volunteers during and after a single 8h-use of treated clothing as well as factors potentially influencing permethrin uptake. 28 male volunteers (age: 20-34 years) were equipped with permethrin treated jackets and pants from two different suppliers. The clothing was worn for 8h, simulating differing external conditions, including comfort conditions as well as conditions of increased temperature and humidity without and with additional physical workload. Internal permethrin exposure was monitored by determination of permethrin metabolites (DCCA and 3-PBA) in a set of 12 urine samples, covering a period of 504 h from the beginning of the wearing interval. Time-concentration curves showed an increase of internal exposure associated with wearing of the clothing (individual maximum: 109.5 µg/L) followed by a first-order like decay (mean half-life: 38.5 h). Metabolite excretion was affected by the make of clothing, which could be explained by differing permethrin contents of the garment. Furthermore, internal exposure increased with increasing temperature/humidity and additional physical workload. Assuming dermal uptake of permethrin, this may be ascribed to an alteration of the barrier function of the skin.

Protective efficacy of permethrin-treated trousers against tick infestation in forestry workers.

INTRODUCTION AND OBJECTIVE: Prevention of tick borne diseases in forestry workers is essentially based on the use of appropriate clothing. The objective of this pragmatic, randomized, controlled trial was to assess the potential benefit of permethrin-treated working trousers for the prevention of tick infestation during forestry work. MATERIALS AND METHODS: N=164 male forestry workers were equipped for a period of 16 weeks with permethrin-treated (intervention group-I) or untreated work trousers (control group-II). Subgroups, according to the use of trousers with (I-1, II-1) or without cut protection lining (I-2, II-2) were constituted. Tick infestation (quantity of ticks on the body surface) was assessed by questionnaire after 16 workdays. Control and intervention groups were compared by calculating the infestation rate (percentage of subjects with ticks) and the average number of ticks per workday. RESULTS: The infestation rate in the intervention group was significantly lower than in the control group (36.6 vs. 63.4%, p=0.001; Fisher-test). Further analysis revealed a significant reduction of tick infestation by permethrin treatment only for subjects wearing trousers without the cut protection lining (I-2: 34.2 vs. II-2: 80.0%, p<0.001), while users of cut protection trousers did not benefit from such treated trousers (I-1: 38.6 vs. II-1: 47.6%, n.s.). Similar results were found for comparisons based on the average number of ticks per workday. CONCLUSIONS: The use of permethrin-treated trousers does not completely prevent tick infestations. Improvement of tick protection has been shown only for some applications, but not in general. Additional prevention measures are therefore still indispensable.