Influence of artificial sebum on the dermal absorption of chemicals in excised human skin: A proof-of-concept study.

In an initial diffusion cell study, the influence of artificial sebum on dermal penetration and intradermal reservoir of ethanol and toluene was investigated in comparison with the effects of a skin cream (o/w- and w/o-emulsion) and untreated (control) skin. Human skin was exposed to neat ethanol and toluene for 4h, respectively. During the experiments, the penetration of the compounds was assessed in the receptor fluid. The amounts of the test compounds in the skin were determined at the end of exposure. In the control experiments, 42% of the total resorbed ethanol amounts were found in the intradermal reservoir after 4h, whereas 82% of the toluene amounts were found in the skin compartments. The treatment with artificial sebum showed no significant differences in dermal absorption of both test compounds compared to control skin. In contrast, the treatment with skin cream increased the percutaneous penetration (p<0.001) and the intradermal reservoir of ethanol ~2-fold but not of toluene. In all exposure scenarios, a relevant intradermal reservoir was formed. The results indicate that sebum does not influence the percutaneous penetration and the intradermal reservoir of epidermally applied chemicals, whereas the application of skin creams may increase the dermal penetration of the compounds.

Evaluation of the effect of skin cleaning procedures on the dermal absorption of chemicals.

To reduce the internal exposure, skin decontamination is the most important measure after dermal contact to chemicals. However, no harmonized skin cleaning procedure for experimental ex vivo studies is published. In our study, the impact of two skin cleaning techniques on dermal penetration kinetics and intradermal deposition of 1,4-dioxane, 5% hydrofluoric acid (HF, detected in terms of fluoride ions), and anisole was evaluated to develop a reliable ex vivo skin cleaning method using the diffusion cell technique. After exposure (duration: 3 min (HF); 1h (1,4-dioxane and anisole)) of excised human skin (n=6-8) decontamination was performed by (I) water-soaked cotton swabs or (II) direct application of water on the exposure area. The effect of skin cleaning was investigated by analysing the concentration time course of chemicals in the receptor fluid of diffusion cells and by determining the deposition in skin. Both skin cleaning procedures reduced the amount of fluoride in the skin compartments (p<0.05) and the receptor fluid (p<0.1). However, the effect of cleaning on the dermal absorption of the organic test compounds was not significant. The results demonstrate the suitability of the applied ex vivo protocol for investigating the effectiveness of skin cleaning measures following dermal exposure. In addition, data reveal that the determination of test compounds in both, skin compartments as well as receptor fluid as equivalent for the systemic uptake needs to be considered in studies assessing the effectiveness of skin decontamination procedures.

Percutaneous absorption of aromatic amines and the risk assessment resulting from the dermal pathway.

Aromatic amines (AA) are compounds of different carcinogenic potency causing occupational bladder cancer. The percutaneous absorption of AA is mostly appraised to be high. Many AA are, therefore, assigned with skin notations. However, for the assessment of the dermal exposure route only little data are available. Additionally, in many studies the skin penetration data for AA are provided as absorbed percentage of applied dose or permeability coefficients, which are less useful in risk assessment. In this overview, the toxicological relevance of percutaneous absorption of AA was evaluated and a percutaneous penetration ranking for some AA is proposed. A continuous skin exposure of hands to AA for a few minutes can exceed the inhalative exposure over 8 hours at occupational threshold limit values in the workplace air. The health risk resulting from the percutaneous absorption of AA can be considerable. Also the dermal exposure to azo dyes, which can be metabolized to AA, should be considered with caution.

Studies on percutaneous penetration of chemicals - Impact of storage conditions for excised human skin.

According to international guidelines skin penetration experiments can be carried out using freshly excised or frozen stored skin. However, this recommendation refers to data obtained in experiments with human cadaver skin. In our study, the percutaneous penetration of the occupationally relevant chemicals anisole, cyclohexanone and 1,4-dioxane was investigated for freshly excised as well as for 4 and 30 days at -20°C stored human skin using the diffusion cell technique. As indicator for the impairment of skin barrier by freezing cholesterol dissolution was determined in the solvents in exposure chambers of diffusion cells. Considering the percutaneously penetrated amounts, the following ranking was determined: 1,4-dioxane>anisole>cyclohexanone (decline to a factor of 5.9). The differences of fluxes between freshly excised and frozen stored skin (4 and 30 days) were not significant (p>0.05). Cholesterol dissolved from the skin indicates no significant differences between freshly excised and frozen stored skin. This study shows that freezing of human skin for up to 30 days does not alter the skin barrier function and the permeability of chemicals.

Potential of the octanol-water partition coefficient (logP) to predict the dermal penetration behaviour of amphiphilic compounds in aqueous solutions.

Aqueous amphiphilic compounds may exhibit enhanced skin penetration compared with neat compounds. Conventional models do not predict this percutaneous penetration behaviour. We investigated the potential of the octanol-water partition coefficient (logP) to predict dermal fluxes for eight compounds applied neat and as 50% aqueous solutions in diffusion cell experiments using human skin. Data for seven other compounds were accessed from literature. In total, seven glycol ethers, three alcohols, two glycols, and three other chemicals were considered. Of these 15 compounds, 10 penetrated faster through the skin as aqueous solutions than as neat compounds. The other five compounds exhibited larger fluxes as neat applications. For 13 of the 15 compounds, a consistent relationship was identified between the percutaneous penetration behaviour and the logP. Compared with the neat applications, positive logP were associated with larger fluxes for eight of the diluted compounds, and negative logP were associated with smaller fluxes for five of the diluted compounds. Our study demonstrates that decreases or enhancements in dermal penetration upon aqueous dilution can be predicted for many compounds from the sign of logP (i.e., positive or negative). This approach may be suitable as a first approximation in risk assessments of dermal exposure.

Influence of dietary factors, age and nickel contact dermatitis on nickel excretion.

BACKGROUND: Nickel is a frequently detected cause of allergic contact dermatitis. Ingestion of nickel may lead to flares of nickel contact dermatitis. METHODS: We examined nickel excretion in the urine of 164 female patients with and without nickel contact dermatitis. The associations between age, atopic dermatitis, nickel contact dermatitis and nickel exposure through nutrition (e.g. dietary supplements) and by patch tests were investigated prospectively. Nickel was measured with atomic absorption spectrometry with two different standardized methods. RESULTS: A nickel detection limit of 0.2 µg/l was exceeded by all samples. The 95th percentiles of urine nickel concentration were 3.77 µg/l (age 18-30 years) and 3.98 µg/l (age 31-46 years). Bivariate analyses pointed to significantly increased nickel excretion with increasing age, ingestion of dietary supplements, drinking of stagnant tap water, and consumption of nickel-rich food. In the multivariate analysis, age and dietary supplements remained significant predictors of high nickel excretion. A non-significant increase in the median concentration of nickel was observed after the administration of conventional nickel patch tests. Patients with atopic eczema showed urine nickel concentrations similar to those in non-atopic controls. CONCLUSIONS: The 95th percentile of nickel excretion in our study population markedly exceeded the actual reference value of 3 µg/l. Age and consumption of dietary supplements are the most important predictors. The use of stagnant tap water and consumption of nickel-rich food contribute to the total load. These factors should be explicitly mentioned when allergic patients on a low-nickel diet are counselled. In contrast, existing nickel contact sensitization was not more frequent in subjects with higher nickel excretion. Nickel patch testing may cause transient minor systemic nickel exposure. The findings of this study extend our understanding and management of factors associated with nickel allergy.

External quality assessment of human biomonitoring in the range of environmental exposure levels.

The number of human biomonitoring (HBM) applications for identifying and assessing the chemical exposure of the general population from the environment has distinctly increased during the last decade. An appropriate external quality assessment of the applied methods is essential to assure the accuracy and the comparability of HBM results. The international programme of the German External Quality Assessment Scheme (G-EQUAS) provides proficiency testing for most of the HBM parameters, which are commonly used for the assessment of the human exposure to chemicals. Since 1992, G-EQUAS provides intercomparison runs for biological monitoring parameters in the environmental exposure range twice a year, with a successive increase of parameter numbers. In round no. 45 (2010) 18 metals in blood, plasma and urine und 36 organic parameters in urine and plasma were provided. Additionally analyses of 4 haemoglobin adducts were offered. For each parameter, two samples with different concentrations of the biomarker were sent to the participants. The target values as well as the tolerance ranges were estimated on the basis of the results from reference laboratories. The successful participation was certified, if the participant's results were within the tolerance ranges for both samples. The number of participants ranged from 3 to 37 international laboratories according to the individual parameter. The highest interest was observed for the detection of metals in blood, serum and urine, whereas only a few of the participants took part in the analyses of organophosphate metabolites and haemoglobin adducts. The rate of a successful participation ranged from 38 to 100%. Poor success rates were found for organophosphate metabolites, 1-naphthol and cotinine in urine. A training effect was observed for a group of laboratories which participated regularly in the analysis of organochlorinated compounds in serum.

Biological reference values for chemical compounds in the work area (BARs): an approach for evaluating biomonitoring data.

Biological monitoring is a routine method that has been applied in occupational medical practice for many years. A requirement for its application is the availability of criteria suitable for evaluating biomonitoring data. Health-based threshold values are particularly useful as a criterion, yet only for substances for which effect thresholds can reliably be determined. For substances for which the concept of health-based threshold values is not applicable, the Working Group Setting of Threshold Limit Values in Biological Materials of the DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has recently established "Biologische Arbeitsstoff-Referenzwerte" (BARs, Biological Reference Values for Chemical Compounds in the Work Area) as an approach for evaluating biomonitoring data. The BAR represents the upper reference concentration of a biomarker in the general adult population without occupational exposure to the agent. It is derived from biomonitoring data of a sample of a defined population group. In general, a BAR corresponds to the 95th percentile of the sample distribution. Ideally, national environmental surveys including human biomonitoring results are used as basis for deriving BARs. The influence of age, sex, social status, residential area and life style factors on background exposure is considered in the evaluation of these values. Because tobacco smoking is the most frequent influencing factor, several BARs have been determined for non-smokers only. To date, BARs for 17 substances or substance groups are listed in the List of MAK and BAT Values 2011. BARs for another five substances have been discussed, but have not been established because of the insufficient scientific database. Establishing the BARs aims to facilitate the evaluation of human exposure to chemical compounds for which no health-based threshold values can be derived but an adequate assessment of exposure is required due to their toxicity. The application of BARs does not permit a toxicological evaluation, but does allow the occurrence and the extent of occupational exposure to hazardous substances to be proved.

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.

Dermal uptake and excretion of 4,4'-methylenedianiline during rotor blade production in helicopter industry--an intervention study.

OBJECTIVES: Workers using composite materials by fibre reinforced laminate technology are exposed to 4,4'-methylenedianiline (MDA), a liver toxicant and suspected human carcinogen, during the production of rotor blades in helicopter industry. The aim of the study presented here was to assess the internal dose of MDA and the suitability of various personal protection measures at the workplace. METHODS: Ambient monitoring and biological monitoring was carried out by analysing MDA in air and urine samples in seven workers of a highly specialized workplace (rotor blade production). Three different concepts of personal protection measures were applied to study the route of uptake and to evaluate strategies in decreasing workplace exposure. In addition, elimination kinetics of MDA was studied in three workers who were exposed to MDA on three consecutive working days. RESULTS: Ambient monitoring consistently provided air levels at or below the limit of quantification of 0.1 µg m(-3). Nevertheless, MDA was detected in 89% of all post-shift urine samples and median concentration was 4.2 µg l(-1). MDA in urine were >20 times higher than expected on data from ambient monitoring alone. A significant decrease in exposure could be achieved when workers have worn MDA-protective overalls in combination with MDA-protective gloves and a splash protection shield (from 9.8 µg l(-1) down to 3.7 µg l(-1)). The results show that MDA is taken up primarily via the skin at the workplaces under study. The excretion of MDA in urine was observed to be delayed after dermal exposure. CONCLUSIONS: Exposure assessment of MDA should be carried out by biological monitoring rather than ambient monitoring. For this purpose, urine samples midweek or at the end of the week should be used based on the observed delay in the excretion of MDA after dermal absorption. Uptake of MDA via the skin could not be completely avoided even if state-of-the-art personal protection measures were applied.

Lead--still a health threat for marksmen.

OBJECT: Indoor shooting is a popular recreational activity all over the world. It is also a known source of exposure to lead fumes and dusts for the general, i.e. the non-occupationally exposed population. This study aimed at reporting the lead levels in blood of indoor shooters in Germany in association with personal behaviour at shooting ranges. METHODS: Seven marksmen were examined via self-administered questionnaires. Lead level in blood (BLL) as well as airborne lead concentration (personal air sampling (PAS)) were detected. RESULTS: All measured blood lead levels (median: 290 microglead/L; range: 240-450 microglead/L) exceeded the values of the German general population (50 microg/L). Shooters sweeping the range after training seemed especially exposed (PAS: 7.14 mglead/m3). CONCLUSION: While extensive public effort is undertaken to prevent the general population from environmental lead exposure this short report gives reason to keep recreational shooting in mind when facing elevated blood lead levels or clinical symptoms possibly associated with lead intoxication.

Biological tolerance values: change in a paradigm concept from assessment of a single value to use of an average.

Since 1981 biological tolerance values for occupational exposure (BAT values) have been published in the List of MAK and BAT Values of the Deutsche Forschungsgemeinschaft (DFG). In 2007 the list includes threshold limit values for more than 90 substances. The BAT value was defined as the maximum permissible quantity of a chemical substance or its metabolites or the maximum permissible deviation from the norm of biological parameters induced by these substances. The biological limit values derived by other commissions (ACGIH, SCOEL) are to be understood as averages, which may well be exceeded individually, in contrast to the BAT values that were defined as ceiling values and thus did not allow an excess of values in the individual employee. The DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has now revised the concept of biological limit values. The BAT value describes the concentration of a chemical substance, of its metabolites or of an effect indicator in appropriate biological material derived by occupational medical and toxicological criteria, at which the health of an employee is usually not affected, even after repeated or long-term exposure. In this case, derivation of the BAT value is based on the average internal exposures. With this redefinition of the German BAT value, it will be possible to better harmonize the values with those provided by other commissions, which are also based on an average concept.

Enhancement of percutaneous penetration of aniline and o-toluidine in vitro using skin barrier creams.

Aniline (ANI) and the human carcinogen o-toluidine (OT) are released at the workplace during the production and processing of rubber. Recently, we showed in rubber industry workers that a frequent use of skin barrier creams (SBC) increased the internal exposure of ANI and OT. In the present study, diffusion cells were used to investigate the effects of two SBC and one skin care cream (SCC) on percutaneous penetration of neat ANI and OT as well as of OT from a mixture with a workplace specific lubricant. The experiments were carried out with untreated and with skin creams treated human skin. A considerable percutaneous penetration enhancement of test compounds was observed for treated skin compared with untreated skin; the highest enhancement (mean factors 6.2-12.3) was found for SBC (based on oil in water emulsion) treated skin. The lowest penetration enhancement showed SCC treated skin (mean factors 4.2-9.7). The in vitro data support our findings in workers that the percutaneous absorption of aromatic amines significantly increases in presence of skin creams. The efficacy of skin creams to protect the percutaneous penetration of aromatic amines is not confirmed by our own experiments.

Discrepancies between different rat models for the assessment of percutaneous penetration of hazardous substances.

By regulatory authorities the rat is considered to be a suitable animal model to predict the percutaneous absorption of hazardous substances in humans. In our study, the percutaneous penetration of 2-butoxyethanol (BE) and toluene was compared in different rat models. Intradermal microdialysis and static diffusion cells were used in in vivo and in vitro experiments with haired Wistar and hairless Lewis rats. Microdialysis experiments showed a steady-state penetration for BE and a penetration maximum for toluene in both rat strains at approximately 60 min after beginning of exposure. However, in diffusion cell experiments the penetration of the test compounds in both rat strains increased until the end of exposure (4 h). Additionally, in microdialysis experiments BE penetrated in hairless rats in a higher amount than in haired rats (factor: 1.4; P < 0.01), for toluene it was just the opposite (factor: 1.9; P < 0.001). In diffusion cell experiments, the penetrated amounts of both compounds were higher in hairless rats compared to haired rats. The fluxes for BE were in diffusion cell experiments at a factor of 14.5 (haired rat) and 18.1 (hairless rat) higher than in microdialysis experiments, the difference factor for toluene was 2.6 (haired rat) and 12.9 (hairless rat). The lag times indicate a significantly faster penetration in microdialysis experiments compared with diffusion cell experiments (P < 0.001). There are great differences in percutaneous penetration behaviour between the techniques and the rat strains. The diffusion cell method has difficulties to describe the percutaneous penetration kinetics, whereas microdialysis describes it more reliable. Due to these differences the reliability of a conversion factor for the transfer of percutaneous absorption data from rat to human skin, as proposed in the literature, is questionable.

Percutaneous absorption and metabolism of 2-butoxyethanol in human volunteers: a microdialysis study.

We determined percutaneous absorption kinetics of 2-butoxyethanol (BE) in volunteers using microdialysis. Four male volunteers were dermally exposed twice to 90% and 50% aqueous solutions (v/v) of BE for 4.5h. To determine percutaneous absorption kinetics the concentration of BE was measured in the dialysate samples collected at 30 min-intervals throughout exposure. The systemic absorption, which is needed to determine recovery of the BE in the dialysate, was estimated from the concentration of the main metabolite of BE, free butoxyacetic acid (BAA) in urine. A pseudo steady-state percutaneous absorption was reached approximately at 2h of exposure for both BE concentrations. The maximum dermal flux of 50% BE was higher than that of 90% BE (2.8+/-0.4, 1.9+/-0.6 mg cm(-2)h(-1), respectively). The more diluted BE solution showed shorter lag time: 25 min versus 39 min. The amount of BAA was determined in the pooled dialysate samples collected at 4 and 4.5h. The dermal metabolism seems to be low, the BAA amount ranged from 0.03% to 1.9% of the BE in the same dialysate. Our study demonstrates applicability of microdialysis technique for assessment of percutaneous absorption kinetics and dermal metabolism without interference from the systemic compartment.

Monitoring of chromium and nickel in biological fluids of grinders grinding stainless steel.

OBJECTIVE: Stainless steel (SS) welders usually spend some of their working time grinding, to finish and smoothen the welding groove. The aim of this study was to investigate possible relations between the concentrations of nickel (Ni) and chromium (Cr) in the work atmosphere generated by grinders grinding SS, and to compare the air levels to the levels of Cr and Ni in their biological fluids. Hereby, it might be possible to identify the contribution of grinding to the levels of Cr and Ni in biological fluids in SS welders. Also the airborne levels of Cr and Ni in SS grinders were compared to corresponding levels in SS welders. METHOD/DESIGN: The subjects examined in this study were selected among SS grinders not performing welding. Nine grinders were monitored for 1 workweek, measuring Cr and Ni in air, blood and urine. They were questioned about their exposure to Cr and Ni during their working careers. RESULTS: Air levels of total Cr up to 95 microg/m(3) and Ni levels up to 25 microg/m(3) were measured. Chromium(VI) (Cr(VI)) was detectable only in five air samples; the levels in the remaining samples were below the detection limit. The levels of Cr in blood and urine were also low. The levels of Ni in urine were close to those for MMA and MIG/MAG SS welders. In spite of high levels of total Cr and Ni observed in air, the levels found in biological fluids were low. The Cr levels in more than 50% of the whole blood and red cell samples and about 1/3 of the Cr-plasma levels were below the detection limits. The mean blood levels for Cr were 0.43, 0.60 and 0.35 microg/l, in whole blood, plasma and red cells, respectively. The mean levels for Cr in the urine was 1.6, 1.4 and 1.4 microg/g creatinine for the first void, just before and just after work. For Ni the mean blood levels were 0.87 microg/l in whole blood and 0.68 microg/l in plasma. The mean levels and ranges of Ni from the first void, just before and after work in urine were 3.79 microg/g creatinine, 3.39 and 4.56, respectively. The Cr concentrations found in whole blood, plasma and red cells were approximately the same as those found in the unexposed controls and among TIG SS welders, while the urinary levels were somewhat higher, but still lower than in the welders applying other welding techniques. The mean levels of Ni in the urine of grinders were higher than those of welders, except for SS welders welding the MIG/MAG-method. CONCLUSION: SS Grinding seems not to contribute significantly to the uptake of Cr, which may be explained by the fact that most of Cr in the air is present in the metallic (0-valent) or trivalent form, and hardly any as Cr(VI), and therefore hardly being taken up in the airways. The grinders' uptake of Ni seems to take place to the same extent as in SS welders.

Aluminosis--detection of an almost forgotten disease with HRCT.

The aim of this study was to investigate whether it is possible to detect high-resolution computed tomography (HRCT) findings in aluminium powder workers, which are consistent with early stages of aluminosis.62 male workers from 8 departments of two plants producing aluminium (Al) powder were investigated using a standardized questionnaire, physical examination, lung function analysis, biological monitoring of Al in plasma and urine, chest X-ray, HRCT and immunological tests. Chronic bronchitis was observed in 15 (24.2%) of the workers, and four workers (6.5%) reported shortness of breath during exercise. HRCT findings in 15 workers (24.2%) were characterized by ill-defined centrilobular nodular opacities. Workers with ill-defined centrilobular nodular opacities had a lower vital capacity than workers who had no such HRCT-findings (90.9 % pred. vs. 101.8 % pred., p = 0.01). Biological monitoring in plasma and urine revealed higher internal exposure to Al in affected workers (33.5 microg/l plasma to 15.4 microg/l plasma, p = 0.01) and (340.5 microg/g creat. to 135.1 microg/g creat., p = 0.007). Years of exposure and concentration of aluminum in urine and plasma appear to be the best predictors for HRCT findings. Age and decreased vital capacity show borderline significance.We conclude that aluminosis is still relevant in occupational medicine. With HRCT it is possible to detect early stages of aluminosis and biological monitoring can be used to define workers at high risk.

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.

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.

Monitoring of chromium and nickel in biological fluids of stainless steel welders using the flux-cored-wire (FCW) welding method.

OBJECTIVE: This study was undertaken to investigate the exposure to chromium (Cr) and nickel (Ni) in flux-cored wire (FCW) welders welding on stainless steel (SS). METHOD/DESIGN: Seven FCW welders were monitored for 3 days to 1 workweek, measuring Cr and Ni in air, blood, and urine. The welders were questioned about exposure to Cr and Ni during their whole working careers, with emphasis on the week of monitoring, about the use of personal protective equipment and their smoking habits. RESULTS: The air concentrations were mean 200 microg/m(3) (range 2.4-2,744) for total Cr, 11.3 microg/m(3) (<0.2-151.3) for Cr(VI), and 50.4 microg/m(3) (<2.0-416.7) for Ni during the workdays for the five welders who were monitored with air measurements. The levels of Cr and Ni in biological fluids varied between different workplaces. For Cr in whole blood, plasma, and erythrocytes, the mean levels after work were 1.25 (<0.4-8.3) and 1.68 (<0.2-8.0) and 0.9 (<0.4-7.2) microg/l, respectively. For Ni most of the measurements in whole blood and plasma were below the detection limits, the mean levels after work being 0.84 (<0.8-3.3) and 0.57 microg/l (<0.4-1.7), respectively. Mean levels for Cr and Ni in the urine after work were 3.96 (0.34-40.7) and 2.50 (0.56-5.0) microg/g creatinine, respectively. CONCLUSION: Correlations between the Cr(VI) levels measured in air and the levels of total Cr in the measured biological fluids were found. The results seem to support the view that monitoring of Cr in the urine may be versatile for indirect monitoring of the Cr(VI) air level in FCW welders. The results seem to suggest that external and internal exposure to Cr and Ni in FCW welders welding SS is low in general.