Inhalation and dermal exposure to biocidal products during foam and spray applications.

OBJECTIVES: Foaming and spraying are common application techniques for biocidal products. In the past, inhalation and dermal exposure during spraying have been investigated extensively. Currently, however, no exposure data are available for foaming, hindering a reliable risk assessment for foam applications of biocidal products. The focus of this project was the quantification of inhalation and potential dermal exposure to non-volatile active substances during the foam application of biocidal products in occupational settings. In some settings, exposure during spray application was measured for comparative purposes. METHODS: The inhalation and dermal exposure of operators were investigated during the application of benzalkonium chlorides and pyrethroids by foaming and spraying, considering both small- and large-scale application devices. Inhalation exposure was measured by personal air sampling; potential dermal exposure was measured using coveralls and gloves. RESULTS: Potential dermal exposure was substantially higher than inhalation exposure. Changing from spraying to foaming reduced inhalation exposure to airborne non-volatile active substances, but had no relevant effect on potential dermal exposure. However, for potential dermal exposure, considerable differences were observed between the application device categories. CONCLUSIONS: To our knowledge, this study presents the first comparative exposure data for the foam and spray application of biocidal products in occupational settings with detailed contextual information. The results indicate a reduction of inhalation exposure with foam application compared to spray application. However, special attention is necessary for dermal exposure, which is not reduced by this intervention.

Aerosol formation during foam application of non-volatile biocidal substances.

The application of biocidal products by foam is considered an alternative to droplet spraying when disinfecting surfaces or fighting infestations. Inhalation exposure to aerosols containing the biocidal substances cannot be ruled out during foaming. In contrast to droplet spraying, very little is known about aerosol source strength during foaming. In this study, the formation of inhalable aerosols was quantified according to the aerosol release fractions of the active substance. The aerosol release fraction is defined as the mass of active substance transferred into inhalable airborne particles during foaming, normalised to the total amount of active substance released through the foam nozzle. Aerosol release fractions were measured in control chamber experiments where common foaming technologies were operated according to their typical conditions of use. These investigations include foams generated mechanically by actively mixing air with a foaming liquid as well as systems that use a blowing agent for foam formation. The values of the aerosol release fraction ranged from 3.4 × 10-6 to 5.7 × 10-3 (average values). For foaming processes based on mixing air and the foaming liquid, the release fractions could be correlated to the process and foam parameters such as foam exit velocity, nozzle dimensions, and foam expansion ratio.

Inhalation and dermal exposure of workers during timber impregnation with creosote and subsequent processing of impregnated wood.

OBJECTIVES: Coal tar creosote oils are used as highly effective wood protectants for, e.g., railway sleepers, utility poles and marine pilings. For impregnation of wood, the hot creosote oil is mostly applied in vacuum processes and by hot-and-cold dipping. From the perspective of an occupational hygienist, creosote tar oils are problematic because they have a number of hazardous properties, including carcinogenicity. We have studied inhalation and dermal exposure in six and four impregnation plants, respectively, in Germany. Some plants were visited repeatedly, for up to five measurement campaigns conducted over several years. Inhalation and dermal exposure resulting from vacuum impregnation and from hot-and-cold dipping, as well as secondary exposure resulting from assembly of impregnated railway sleepers have been measured. Accompanying, human biomonitoring of the employees has been performed. METHODS: Inhalation exposure was measured using personal air samplers, collecting particles and vapours simultaneously. Dermal exposure was investigated by whole body dosimetry using disposable chemical protective coveralls and split leather gloves. 18 polycyclic aromatic hydrocarbons (PAHs) have been determined separately by high performance liquid chromatography (HPLC) or gas chromatography-mass spectrometry (GC-MS), respectively. For human biomonitoring 1-hydroxypyrene (1-OHP) in urine related to creatinine has been measured using HPLC. Both, pre- and post-shift values have been determined for this metabolite. RESULTS: Dermal exposure towards pyrene and the sum of the determined 18 PAHs as well as inhalation exposure to naphthalene, pyrene and the sum of the determined 18 PAHs are presented in this paper. The plants performing vacuum impregnation have employed different constructive, technical and organisational measures, and some measures have also changed between the different measurement campaigns. We have found that cooling the vacuum impregnation vessel before unloading can reduce inhalation exposure to about one-third. However, our data shows that installation of structural or technical risk management measures (RMM) did not always reduce the exposure as intended, and can even lead to increased exposure in adverse constellations. Dermal exposure was strongly affected by differences in the working procedures. Measurements performed during assembly of impregnated railway sleepers indicate that secondary exposure leads to lower inhalation, but similar dermal exposure compared to the impregnation processes. Also 1-OHP excretion rates are similar after impregnation process and after assembly of impregnated railway sleepers. CONCLUSION: Our recent data underlines that efficient reduction of the exposure resulting from impregnation with creosote requires sophisticated risk reduction strategies. Structural measures such as the enclosure of the loading area and technical measures like local exhaust ventilation shall be coordinated carefully with organisational measures and provision of personal protective equipment. The data presented here represents a broad bandwidth of current workplace situations in the creosote oil processing industry and is therefore suitable for risk assessment in related plants as well as under regulatory frameworks like the European Biocides Regulation. Each plant in this investigation was unique. Together they represent the whole width of this branch in Germany. Additionally, the number of plants and exposed workers is limited and relative low. Therefore, a comprehensive consideration and statistical analysis were not feasible.

Dermal and Inhalation Exposure of Workers during Control of Oak Processionary Moth (OPM) by Spray Applications.

BACKGROUND: The caterpillars of the oak processionary moth (OPM) form stinging hairs, which release an irritant poison. They cause skin and eye irritation and sometimes even breathing difficulties and allergic reactions. OPM is mainly controlled by spraying insecticides. Insecticides applied for protection of human health must be authorized under the Biocidal Products Regulation (BPR) (EU) No 528/2012. In order to assess safety of professional use, which is a key requirement for the authorization, a risk assessment based on exposure estimation has to be performed. However, no exposure data specific for OPM control was available until now. Existing models for agricultural spray applications such as Agricultural Operator Exposure Model cover different spray patterns and equipment and were therefore considered too unreliable for assessment of OPM control. METHODS: We have studied dermal and inhalation exposure of certified pest control operators resulting from spraying DimilinTM 80 WG suspensions with vehicle-mounted spraying (VMS) and with handheld spraying (HHS) devices for control of OPM. Exposure resulting from these applications, from weighing and portioning of the granular product and from cleaning of contaminated spraying devices was studied. Dermal exposure was investigated by whole body dosimetry using disposable chemical protective coveralls and cotton gloves as samplers. Inhalation exposure was measured using personal air samplers. The active substance diflubenzuron was quantified by gas chromatography-mass spectrometry with positive chemical ionization and by high-performance liquid chromatography for dermal and inhalation measurements, respectively. RESULTS: The exposure was dominated by the dermal pathway. HHS results in considerably higher operator exposure than VMS. Comparison with data from typical agricultural spraying applications revealed that OPM control results in much higher exposure of operators for both, vehicle-mounted and handheld equipment. CONCLUSIONS: Comprehensive data on potential dermal and inhalation exposure is presented in this article, along with typical figures for handled and applied amounts of product and respective task durations. This data is suitable for risk assessments in regulatory frameworks such as the European BPR.

Suitability of several naphthalene metabolites for their application in biomonitoring studies.

Naphthalene occurs together with polycyclic aromatic hydrocarbons (PAHs) at industrial workplaces and is ubiquitous in the environment. For biological monitoring of naphthalene exposures, up to now mainly 1- and 2-naphthol in urine have been used. Recently, we proposed 1,2-dihydroxynaphthalene (1,2-DHN) and the 1- and 2-naphthylmercapturic acid (1- and 2-NMA) as new urinary biomarkers to characterise a naphthalene exposure. In this study, in a collective of nine occupationally exposed workers handling with creosote the naphthalene metabolites 1,2-DHN, 1- and 2-NMA as well as 1- and 2-naphthol were analysed in order to evaluate the suitability of the different parameters for their application in biomonitoring studies. Additionally, air sampling was conducted to characterise the exposure in task related exposure situations at different workplaces. In the analysed 51 urine samples, 1,2-DHN was the main metabolite with concentrations ranging from 2.3 to 886 µg/g creatinine (crea) (median 34 µg/g crea). For the sum of 1- and 2-naphthol, concentrations in the range of 2.6-174 µg/g crea (median 15 µg/g crea) were observed. 1-NMA concentrations were in the range of < LOD-2.4 µg/g crea (61% > LOD), while 2-NMA was not detected in the analysed urine samples. The biomarkers 1,2-DHN, 1- and 2-naphthol as well as 1-NMA showed significant correlations, which pointed out to naphthalene as the common exposure source. The poor correlations between naphthalene in the air and the biomarkers in urine may be a result of the varying exposure situations and may indicate not solely inhalative, but additional dermal uptake. 1,2-DHN was the most sensitive and, together with 1-NMA, the most specific parameter of the biological monitoring of naphthalene exposure at workplaces. Further studies with this parameter are needed for individuals at different workplaces as well as for persons of the general population without occupational PAH exposure to characterise 1,2-DHN levels as well as to establish their relationship with the naphthalene exposure.

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.

Allocation of reliable analytical procedures for human biomonitoring published by the DFG Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area.

In 1955 the Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) was founded by the Deutsche Forschungsgemeinschaft (DFG). The Commission is responsible for analysing health risks by chemical exposure at the workplace and for advising public authorities accordingly. Within the Commission, the working group "Analyses of Hazardous Substances in Biological Materials" (AiBM) deals with the development of procedures to analyse chemical substances in biological materials. Most of these detailed, ready-to-use protocols for human biomonitoring, do not only enable the monitoring of occupational exposure, but also the determination of the background exposure in the general population. The AiBM working group applies a multi-stage process to develop and evaluate human biomonitoring methods. As a matter of special importance, every method is tested by at least one examiner to ensure reproducibility of the analytical procedure and of the reliability data. Submitted methods and examination reports are discussed within the working group. The positively proved methods, if satisfactory, are adopted for publication. Otherwise, they are given back to the author with the demand for revision. In case of fundamental drawbacks, methods are rejected. The adopted methods are published in German and in English at regular intervals. Since 1985 the working group has published 129 analytical methods (plus 11 methods for markers of susceptibility) in 12 issues of the English edition. The detection limits of eighty methods allow the analyses of background exposure for one or more parameters. About forty methods were specially designed for the application in population studies. Particularly relevant method examples are the determination of the metabolites of organophosphate pesticides, pyrethroides and phthalates in urine as well as the determination of perfluorinated compounds and polychlorinated biphenyls in serum.

Uranyl nitrilotriacetate, a stabilized salt of uranium, is genotoxic in nontransformed human colon cells and in the human colon adenoma cell line LT97.

Previous uranium mining in the "Wismut" region in Germany enhanced environmental distribution of heavy metals and radionuclides. Carryover effects may now lead to contamination of locally produced foods. Compounds of "Wismut" origin are probably genotoxic via their irradiating components (radon) or by interacting directly with cellular macromolecules. To assess possible hazards, we investigated the genotoxic effects of uranyl nitrilotriacetate (U-NTA) in human colon tumor cells (HT29 clone 19A), adenoma cells (LT97), and nontransformed primary colon cells. These are target cells of oral exposure to environmentally contaminated foods and represent different cellular stages during colorectal carcinogenesis. Colon cells were incubated with U-NTA. Cell survival, cytotoxicity, cellular glutathione (GSH) levels, genotoxicity, and DNA repair capacity (comet assay), as well as gene- and chromosome-specific damage combination of comet assay and fluorescence in situ hybridization [FISH], 24-color FISH) were determined. U-NTA inhibited growth of HT29 clone 19A cells (75-2000 microM, 72 h) and increased GSH (125-2000 microM, 24 h). U-NTA was genotoxic (1000 microM, 30 min) but did not inhibit the repair of DNA damage caused by hydrogen peroxide (H(2)O(2)), 4-hydroxynonenal, and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]-pyridine. U-NTA was also genotoxic in LT97 cells and primary colon cells, where it additionally increased migration of TP53 into the comet tail. In LT97 cells, 0.5-2mM U-NTA increased chromosomal aberrations in chromosomes 5, 12, and 17, which harbor the tumor-related genes APC, KRAS, and TP53. It may be concluded that uranium compounds could increase alimentary genotoxic exposure in humans if they reach the food chain in sufficient amounts.

Expression of glutathione S-transferases (GSTs) in human colon cells and inducibility of GSTM2 by butyrate.

The glutathione S-transferases (GSTs) are a multigene family of enzymes largely involved in the detoxification of chemicals. In animals, enhanced expression is mediated by products of gut fermentation. Of these, butyrate induces GSTP1 protein expression and GST activity in the human colon tumor cell line HT29. The aim of the following investigations was to further elucidate butyrate-modulated induction of additional colonic GSTs in HT29 and to determine baseline expression in non-transformed cells, isolated from human colorectal tissue. We measured five GST protein subunits (GSTA1/2-composed of GST A1-1, A1-2 and A2-2-GSTM1, GSTM2, GSTP1, GSTT1) by western blot, GST activity using 1-chloro-2,4-dinitrobenzene as substrate and GSTM2 mRNA expression with RT-PCR. GSTP1, followed by GSTT1, were major subunits in all colon cells. Cells isolated from colon tissue were identified to be colonocytes and colon fibroblasts, both of which also expressed substantial levels of GSTM1 and GSTM2. The inter-individual variation of GST subunits in coloncytes of 15 individuals was marked, with total GST protein per 106 cells differing by more than a factor of four. In HT29, butyrate significantly enhanced GSTA1/2 (3.5-fold), GSTM2 (not detectable in controls), GSTP1 (1.5-fold) and GST activity (1.4-fold), but not GSTM1 or GSTT1. GSTM2 mRNA expression was significantly induced after 24 ( approximately 14-fold) and 72 h treatment ( approximately 8-fold). In colon fibroblasts, butyrate (4 mM, 72 h) also induced GSTM2 protein (1.7-fold) and GST activity (1.4-fold). Colonocytes were too short lived to be used for inducibility studies. In conclusion, GSTs are expressed with high inter-individual variability in human colonocytes. This points to large differences in cellular susceptibility to xenobiotics. However, butyrate, an important luminal component produced from fermentation of dietary fibers, is an efficient inducer of GSTs and especially of GSTM2. This indicates that butyrate may act chemoprotectively by increasing detoxification capabilities in the colon mucosa.