M. Jakubowski, Institute of Occupational Medicine, Lodz, Poland.
The concept of biological monitoring (BM) has gained special interest of individual scientists and international organizations. Biological monitoring of exposure thus far has been applied to environmental and occupational toxicology as well as epidemiological studies aiming at evaluating the dose-response relationship between internal exposure and adverse effects of exposure to chemicals.
Presently, BM plays not more than a complementary role in industrial hygiene practice. There are several reasons for that. Firstly, this kind of role used to be commonly accepted as something obvious. Then BM was thought to be more expensive than environmental monitoring (EM), ethical reasons suggested that a worker cannot serve as an individual sampler, and the collection of blood samples has not been generally approved. Moreover, it is not clear whether BM belongs to occupational hygiene or occupational medicine. Consequently, BM recommendations are not considered legal standard as in the case with EM in most countries.
Today, when the analytical problems have almost ceased due to new laboratory techniques and quality assurance systems, the methods for interpretation of results have become the most important issue. And these are much more difficult to understand by the legislative bodies than in the case of environmental monitoring where the rules are relatively simple.
J. Cocker, J. Morton, B. Smith, Health & Safety Laboratory, Sheffield, United Kingdom; J. Wheeler, Health & Safety Executive, Liverpool, United Kingdom.
Introduction: Data submitted for regulatory approval of CCA wood preservatives showed inhalation exposure was low but there was significant skin exposure, through handling freshly-treated wet timber, etc. The biological monitoring data submitted used different methods, measuring different species (forms) of urinary arsenic, and there were few data for urinary chromium. The UK Advisory Committee on Pesticides required new data for reassurance of low exposure to arsenic and chromium. There are currently no UK biological monitoring guidance values for these. The work reported here describes a study to supply the necessary data.
Method: The study attempted to collect four urine samples at six-monthly intervals from all UK workers using CCA. We wrote to the managers on each site and the workers they identified. Volunteers were sent collection bottles, packaging, instructions, and a short questionnaire about smoking status and recent consumption of seafood. Urine samples were analysed for inorganic arsenic and methylated metabolites by hydride generation ICP-MS and for chromium by graphite furnace AAS.
Interim Results: Of 450 site managers, 159 agreed to give us the names of workers. Information packs and consent forms were sent to 437 workers and we received 200, 159, and 123 samples the first, second, and third rounds of sample collection. The mean, median, and maximum values for arsenic were 23, 17, and 170 mmol/mol creatinine, respectively. The mean, median, and maximum values for chromium were 2.0, 0.9, and 28 mmol/mol, respectively. There was no statistically significant difference between values for smokers and nonsmokers, or for recent seafood consumption.
The continuing study shows the relative urinary concentrations of arsenic and chromium are generally below published biological monitoring guidance values (ACGIH, MAK Commission). The study also shows the utility of biological monitoring as a tool for remote assessment of exposure, and a new role in post-regulation surveillance.
K. Czarnocki, E. Czarnocka, T. Baum, Lublin University of Technology, Lublin, Poland.
WITHDRAWN
B. Edwards, M. Genter, P. Succop, G. Talaska, University of Cincinnati, Cincinnati, OH.
There is wide individual variation in responses to organic solvent exposure. Factors that contribute to this variability are largely unknown. We tested the hypothesis that eating higher fat content meals increases blood lipid levels and results in higher blood levels of lipophilic organic solvents. We investigated the effects of diet and blood lipid levels with solvents having different octanol:water partition coefficients.
Blood was drawn from 11 male and 9 female volunteers on two separate days, before and after low or high fat content meals were served. The subjects, of varying body types, were between the ages of 19–29 and acted as their own controls. A fasting blood sample was taken each day as the baseline for the blood sample taken 4 to 5 hours after the meal was consumed. Three solvents, chloroform, isobutanol, and methanol, were introduced in vitro to 1 mL aliquots of whole blood and allowed to equilibrate at 37°C for five minutes. Solvent concentrations in the headspace were then measured using gas chromatography.
Average blood lipid levels increased from 117.3 to 119.7, and 80.1 to 160.3 mg/dL for low and high fat meals, respectively. Headspace chloroform concentrations decreased as blood lipid levels increased. Headspace isobutanol and methanol concentrations slightly increased as blood lipid levels increased. This was not expected for isobutanol. Solvent headspace concentrations and blood lipid levels were all significantly correlated with chloroform having the highest correlation coefficient and lowest p value (r = -0.38; p = 0.001).
Headspace chloroform concentrations decreased when individuals consumed the high fat versus the low fat meal (paired t-test, p = 0.002). No differences in headspace concentrations were observed for isobutanol and methanol with respect to diet. Thus, data to date suggest that diet may contribute to uptake of a lipophilic solvent and in this way may influence solvent-related narcotic effects.
L. Saarinen, M. Hakkola, K. Pekari, Finnish Institute of Occupational Health, Helsinki, Finland.
Road tanker drivers exposed to reformulated gasoline vapors during work were studied during the work week. The relationships between airborne ethers, methyl tert-butyl ether (MTBE) and methyl tert-amyl ether (MTAE), and pre- and post-shift urinary MTBE, MTAE, and metabolites tert-butyl alcohol (TBA) and tert-amyl alcohol (TAA) were followed.
The airborne gasoline components were measured with diffusive samplers in the drivers’ breathing zones (n = 29). The spot urine samples were collected after the work shifts and before the next work shifts. The samples were analyzed with gas chromatographs equipped with FID and ion-specific detectors. One-way repeated-measures analysis of variance was applied to the data.
The mean of urinary concentrations in the post-shift samples (n = 29) was 145 nmol/l for MTBE and 10 nmol/l for MTAE. The corresponding concentrations of the metabolites were 553 nmol/l for TBA and 58 nmol/l for TAA. The means of the corresponding concentrations in the pre-shift urine samples (n = 24) were 21 nmol/l for MTBE, and 4.5 nmol/l for MTAE. The pre-next shift metabolite concentrations were 354 nmol/l for TBA and 25 nmol/l for TAA. The correlation coefficients between the TWA 8-hour MTBE concentrations and the urinary MTBE and TBA were 0.86 and 0.90 for the post-shift spot samples, and 0.69 and 0.76 for the pre-shift spot samples. The correlation coefficients between airborne MTAE and post-shift urinary MTAE and TAA were 0.76 and 0.80, respectively. The correlation between MTAE in air and the pre-shift urinary concentrations of MTAE and TAA were 0.22 and 0.58. The daily correlation coefficients varied between 0.48–0.99 for post-shift and -0.81–0.97 for pre-shift samples.
There was a strong linear correlation between the ambient and urinary concentrations. The urinary tert-ethers and tert-alcohols could be measured concurrently and used as biological indicators of exposure to reformulated gasoline vapor.
A. Ibrahim, JD Medical, Santa Monica, CA; J. Dahlgren, University of California at Los Angeles, Los Angeles, CA.
Purpose: To assess serum levels of PFOA, PFOS, OF (organic fluorine), IOF (inorganic fluorine), TF (total fluorine) in occupational and nonoccupational populations reported in the literatures.
Methods: We carried out a systematic retrospective review of biological monitoring articles and reports to the EPA of serum/blood levels of PFOA, PFOS, OF, and IOF. We classified studies by year of publication, year study was conducted, population understudy, country of origin, and job category. We calculated the weighted mean ((mean * n)/N) for each compound and compared the results.
Inclusion Criteria: Articles reporting serum levels of PFOA and related compounds in medical journals between 1979–2003.
Results: 17 studies were identified including case series. For PFOA, three studies were in an occupational setting (n = 859, weighted mean = 2718.735 bbp). For PFOS, two were from general population, from Japan (n = 36, weighted mean was 2.9662 ppb), and the USA (n = 106, range 81.5–6.7 ppb). For PFHS, one study was from Japan (n = 13, weighted mean = 0.769 ppb). For TF, two studies were in general population (n = 291, weighted mean = 7.130 ppb). For OF, two from occupational population(n = 65, weighted mean = 3.693 ppb) and three in general population (n = 349). IOF were in two occupational settings, n = 57, 12 in general population (n = 295, weighted mean = 2.905 ppb). There is a 50 to 100 folds increase in the PFOA and PFOS in plant workers. Using t-test, there are higher levels in the U.S. population vs. the Japanese population and higher levels in occupational setting vs, nonoccupational settings (p = .001)
Conclusions: PFAS compounds are widespread in the general population in detectable levels and extremely higher in occupational population. While the undesirable health effects are still understudied, workers and employers should be counseled and occupational health providers informed. Further studies are needed to investigate the underlying biological mechanisms.
H. Maibach, University of California-San Francisco, San Francisco, CA.
A prominent dermatotoxicologic myth suggests that workers may readily remove skin surface applied chemicals (from routine exposure or accidental spills, or after chemical warfare or terrorist exposure).
This presentation will document the evidence-based data in this experimental field suggesting that, for practical purposes, this approach is currently myth and not fact.
Then, new techniques for ascertaining stratum corneum mass (a protein method) will be illustrated. This method, combined with in vitro stratum corneum assays, should permit screening of more efficient skin decontaminating systems.
D. Bello, S. Woskie, University of Masachusetts Lowell, Lowell, MA; R. Strecher, NIOSH, Cincinnati, OH; M. Stowe, J. Sparer, Y. Liu, Yale University School of Medicine, New Haven, CT.
Isocyanates may cause contact dermatitis and skin irritation or sensitization leading to asthma. Dermal exposure to aliphatic isocyanates in auto body shops is very common. However, little is known about the efficiency of available commercial products in decontaminating isocyanates. This experimental study evaluated decontamination efficiency of aliphatic isocyanates for six skin (ZEP®, GOJO®, STOKO® painters hand cleaners, STOKO® Culpran® barrier cream, CLI-DTAM™ safe solvent, and polypropylene glycol PPG) and seven surface (water, 10% soap/water, isopropanol, isopropanol/tergitol/water 5/20/75, CLI-ammonia, Pine-Sol® general purpose cleaner, generic ammonia-based cleaner) decontaminants used in or recommended for the auto body industry. The two major decontamination mechanisms were studied separately for each decontaminant: (1) destruction of free isocyanate groups via chemical reactions with active hydrogen components of decontaminant was studied via measuring reaction kinetics in a vial; (2) decontamination efficiency by physical and mechanical removal processes was evaluated from triplicate isocyanate spikes on 10-cm diameter aluminum foil. Two model isocyanates, butyl isocyanate and Bayer’s N3300 isocyanurate each at 1 x 10-3 N, were used for the reaction kinetic study. N3300, spiked at 0.33 and 3.3 µg NCO/in2, was used to study the efficiency of mechanical removal processes. Isocyanates were quantified using NIOSH method 5525 and high performance liquid chromatography. Considerable differences were observed among surface and skin decontaminants in their rate of isocyanate consumption, of which those containing free amine groups performed the best and PPG the worst. Overall, Pine-Sol® and CLI-ammonia solutions were the most efficient surface decontaminants, operating primarily via chemical reaction with the isocyanate group. All tested skin decontaminants performed similarly, accomplishing decontamination primarily via mechanical processes and removing up to 80% of isocyanates in one wiping. Limitations of these skin decontaminants are discussed and alternatives presented. In vivo testing and evaluation are needed to further assess the efficiency and identify related determinants.
J. DeHaven, C. Beighley, M. Kashon, S. Soderholm, NIOSH, Morgantown, WV.
Dermal exposure to toxic chemicals is associated with health risks. Intuitively, health risks should be reduced by skin decontamination. As a preliminary step in studies of decontamination, we have looked at the modulation of skin barrier integrity by selected cleansers. Using the standard in vitro tritiated water barrier assay in a flow-through diffusion cell system, we evaluated five cleansers and two controls (water, no treatment). We chose cleansers (none containing abrasives) from the many readily-available or specifically marketed for decontamination. Cleansers were: 10% (v/v) Ivory Liquid®, 100% Safe Solvent®, 100% D-TAM®, 100% GoJo Smooth Orange®, 0.5% Clorox®. They were used with mild scrubbing (Q-tip) and according to the printed instructions of the manufacturer or, for Clorox®, per U.S. Army recommendations. Dorsal skin from three aged (29–36 mo) female hairless guinea pigs was stored, full-thickness, at -85°C for 130–260 days. Each dermatomed skin produced 14 skin disks. Disks were weighed, randomized to one of 14 cells, and tested for barrier integrity (tritiated water assay #1). Then intact disks (typical result 0.1% penetration) were exposed to acetone to simulate application of a contaminating chemical. Following 2 hours rest, 2 disks from each animal were randomized to each cleanser treatment (cleanser and 2 water rinses within 5 minutes). After 2 more hours, cells were re-tested for barrier integrity (tritiated water assay #2). Acetone alone did not perturb barrier function. None of the cleansers destroyed barrier integrity, i.e., all <0.35% penetration. Analysis of covariance using skin disk weight as the covariate indicated a significant effect of treatment (p = 0.018). Pair-wise comparisons of each cleanser vs. water using Dunnett’s test showed evidence that the two most lipophilic cleansers significantly increased tritiated water penetration (p<0.05), suggesting that lipophilic cleansers might reduce barrier function in this test system.
E. Chao, B. Serda, P. Egeghy, S. Rappaport, L. Nylander-French, University of North Carolina-Chapel Hill, Chapel Hill, NC.
JP-8 is the major fuel used by the U.S. Air Force and the North Atlantic Treaty Organization and it has been recognized as a major source of chemical exposure among fuel-cell maintenance workers. Inhalation is believed to be the primary route of JP-8 exposure but dermal exposure is common and unavoidable since workers wear cotton overalls during work to avoid the formation of static electricity. Furthermore, the low vapor pressure and slower rate of evaporation of JP-8 compared to its predecessor JP-4 provides an opportunity for increased dermal exposure. To our knowledge, dermal exposure assessment has not yet been performed on JP-8 exposed workers. The goal of this study was to use a non-invasive tape-stripping technique coupled with GC/MS method to assess dermal exposure to JP-8 on U.S. Air Force fuel-cell maintenance workers and to investigate the importance of dermal exposure route to total body burden. Subjects (n = 124) were volunteers from active duty Air Force personnel who routinely worked with or were exposed to JP-8. Demographic, medical history including skin condition, job and work task, environmental, and use of protective equipment-related information was collected using questionnaires. Our results showed that measured dermal exposure to naphthalene (as the marker to JP-8 exposure) was significantly correlated to breath and urine naphthalene and naphthalene metabolite concentrations. Multiple linear regression models showed that breath naphthalene and urinary 2-naphthol concentrations, time duration of JP-8 exposure, and skin irritation were significant factors to explain dermal exposure to naphthalene. We concluded that dermal exposure is an important route for JP-8 exposure and it has a great contribution to total body burden in this exposed population.
J. Cocker, P. Akrill, D. Bagon, M. Roff, N. Warren, Health & Safety Laboratory, Sheffield, United Kingdom.
This study is part of the EU project RISKOFDERM and looked at exposure to N-methyl pyrrolidone (NMP) during graffiti removal and dipping for paint stripping or degreasing.
Potential dermal exposure was assessed with 11 patches outside and 1 inside normal workwear (OECD). Cotton gloves over the protective gloves were used to assess hand exposure. Patches and gloves were extracted in methanol and analysed by GC-MS. Air sampling used pumped Tenax sorption tubes and were analysed by automated thermal desorption with capillary GC-FID detection.
Workers were asked to give urine samples before and after work, and again the next morning. Urine was analysed for 5-hydroxy-N-methyl pyrrolidone (5-HNMP) by GC-MS. Forty-one (23 graffiti, 18 dipping) sets of pads and air samples were taken and 28 workers provided 81 urine samples.
Airborne NMP concentrations were low; graffiti removal 0.01–30 mg.m-3; dipping 0.01–6 mg.m-3. Potential dermal exposure to the body was low for all tasks, but hand exposure was significant for wiping (14–550 µg.cm-2.min-1) and dipping (0.001–250 µg.cm-2.min-1). All graffiti removal workers had detectable levels of 5-HNMP in their urine. Post-shift results ranged from 0.7 mmol.mol-1 to 27 mmol.mol-1 (mean = 6). For semi-automated dipping only 3 out of 10 workers had detectable levels of 5-HNMP in their urine. In contrast, all four workers performing manual dipping had detectable levels of 5-HNMP in their urine (range 0.72 to 47.4, GM 3.76 mmol.mol-1).
PBPK modelling showed that inhalation exposures cannot account for the urinary 5-HNMP in some groups of workers. Dermal exposure of the hands is the most significant route of exposure to NMP during graffiti removal and dipping activities. Careful selection and use of gloves is important to control exposure. Biological monitoring is useful in assessing overall exposure and the effectiveness of controls.
C. Chen, H. Ahlers, M. Boeniger, NIOSH, Cincinnati, OH.
Skin notations (SNs) are the primary mechanism to warn of potential health hazards from skin exposures at the workplace. In theory, the SN is established based on the potential contribution of a chemical substance to causing systemic toxicity by way of dermal absorption. However, the SN assignment has not always strictly followed this principle, and inconsistent criteria have been used in the process, partly due to the limited availability of data reporting skin exposures and consequent health effects. To reduce the misuse and enhance clarity, SNs need to be assigned following standardized criteria using scientifically reliable information.
Based on the prevailing methods of evaluating health effects resulting from skin exposure and the abundance of pertinent data, we designed a strategy to improve SNs by accommodating both the conventional concept of the skin as a route of absorption contributing to systemic toxicity and the concern of the skin itself being a target organ. In this design, SNs are structured into three distinct classes for use independently or in conjunction to indicate: (1) hazards of systemic toxicity due to dermal absorption; (2) hazards of direct effect(s) on skin including primary irritation, corrosion, and compromised skin barrier integrity; and (3) hazards of allergic contact dermatitis in exposed workers or sensitization of mucous membranes due to skin exposure. For a chemical to receive one of these labels, the evaluation for assignment must consider data demonstrating the presence of adverse effect(s) from skin exposure, including reports of clinical/field observations, results of animal studies following scientifically validated protocols, and data from alternative methods such as in vitro bioassays and estimation algorithms based on quantitative structure-activity relationships. This presentation will introduce the transformation of these methods into operational criteria for application in the SN assignment.
Posted May 30, 2004