Evaluation of propylene glycol methyl ether as a potential challenge agent for leak detection of liquid and headspace from closed system drug transfer devices using Fourier transform infrared spectroscopy.

Choosing an appropriate surrogate of hazardous drugs for use in testing Closed System Drug-Transfer Devices (CSTDs) is a challenging endeavor with many factors that must be considered. It was suggested that the compound propylene glycol methyl ether (PGME) may meet many of the criteria we considered important in a suitable surrogate. Criteria included sufficient volatility to evaporate from aqueous liquid leaks efficiently, a Henry's constant which produced sufficient vapor phase concentrations to make headspace leaks detectable, and suitability for detection using a low-cost detection system. We evaluated the measurement of vapors from solutions containing PGME released inside a closed chamber. We present data used to quantify limits of detection, limits of quantification, bias, precision, and accuracy of Fourier Transform Infrared Spectroscopy (FTIR) measurements of vapors from 2.5 M PGME solutions. The effects of ethanol as a component of the PGME solution were also evaluated. Liquid drops of PGME solutions and headspace vapors above PGME solutions were released to simulate leaks from CSTDs. Using a calibration apparatus, an instrumental limit of detection (LOD) of 0.25 ppmv and a limit of quantitation (LOQ) of 0.8 ppmv were determined for PGME vapor. A LOD of 1.1 µL and a LOQ of 3.5 µL were determined for liquid aliquots of 2.5 M PGME solution released in a closed chamber. Accurate quantitation of liquid leaks required complete evaporation of droplets. With the upper end of the useable quantitation range limited by slow evaporation of relatively large droplets and the lower end defined by the method LOQ, the method evaluated in this research had a narrow quantitative range for liquid droplets. Displacement of 45 mL of vial headspace containing PGME vapor is the largest amount expected when using the draft NIOSH testing protocol. Release of an unfiltered 45 mL headspace aliquot within the NIOSH chamber was calculated to produce a concentration of 0.8 ppmv based on the Henry's constant, which is right at the instrumental LOQ. Therefore, the sensitivity of the method was not adequate to determine leaks of PGME vapor from a headspace release through an air filtering CSTD when using the draft NIOSH testing protocols with an FTIR analyzer.

A field-portable colorimetric method for the measurement of peracetic acid vapors: a comparison of glass and plastic impingers.

A method for measuring peracetic acid vapors in air using impinger sampling and field-portable colorimetric analysis is presented. The capture efficiency of aqueous media in glass and plastic impingers was evaluated when used for peracetic acid vapor sampling. Measurement of peracetic acid was done using an N,N-diethyl-p-phenylenediamine colorimetric method with a field-portable spectrometer. The linearity of the N,N-diethyl-p-phenylenediamine method was determined for peracetic acid both in solution and captured from vapor phase using glass or plastic impingers. The Limits of Detection for the glass and plastic impingers were 0.24 mg/m3 and 0.28 mg/m3, respectively, for a 15 L air sample. The Limits of Quantitation were 0.79 mg/m3 and 0.92 mg/m3 for the glass and plastic impingers, respectively. Both metrics were below the American Conference of Governmental Industrial Hygienists Threshold Limit Value Short-Term Exposure Limit of 1.24 mg/m3 (0.4 ppmv) during a 15-min period. The impinger sampling method presented herein allows for an easy-to-use and rapid in-field measurement that can be used for evaluating occupational exposure to peracetic acid.

Source apportionment and quantification of liquid and headspace leaks from closed system drug-transfer devices via Selected Ion Flow Tube Mass Spectrometry (SIFT-MS).

A system to differentiate and quantify liquid and headspace vapor leaks from closed system drug-transfer devices (CSTDs) is presented. CSTDs are designed to reduce or eliminate hazardous drug (HD) exposure risk when compounding and administering HDs. CSTDs may leak liquid, headspace, or a mixture of the two. The amount of HD contained in liquid and headspace leaks may be substantially different. Use of a test solution containing two VOCs with differences in ratios of VOC concentrations in the headspace and liquid enables source apportionment of leaked material. SIFT-MS was used to detect VOCs from liquid and headspace leaks in the vapor phase. Included in this report is a novel method to determine the origin and magnitude of leaks from CSTDs. A limit of leak detection of 24 µL of headspace vapor and 0.14 µL of test liquid were found using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS).

Controlled generation of peracetic acid atmospheres for the evaluation of chemical samplers.

A system for controlled generation of peracetic acid (PAA) atmospheres used to test and evaluate sampling and measurement devices was developed and characterized. Stable atmospheric conditions were maintained in a dynamic flow system for hours while multiple sensors were simultaneously exposed to equivalent atmospheres of PAA vapors. Atmospheres characterized by a range of PAA concentrations at a controlled flow rate, temperature, and humidity were generated. Presented herein is a system for vaporization of PAA solutions to generate controlled atmospheres with less than 3% relative standard deviation (RSD) of the PAA concentrations over time.

Communities near toluene diisocyanate sources: an investigation of exposure and health.

Toluene diisocyanate (TDI) is a well-known cause of occupational asthma, but we know little about the potential for exposure and health effects among residents who live near facilities that release TDI. In the mid-1990's, the North Carolina Department of Health and Human Services and the Agency for Toxic Substances and Disease Registry investigated exposures to TDI and health outcomes in one community, which left some unanswered questions. This cross-sectional study evaluated the potential associations between living near a TDI source and the prevalence of three variables: asthma or asthma-like respiratory symptoms, antibodies specific to TDI, and verifiable levels of TDI in residential air. Results among North Carolina residents living near such facilities (five target communities) were compared with the results from residents living further away (five comparison communities). Overall, the prevalence of reporting either asthma or asthma-like respiratory symptoms was higher (odds ratio = 1.60; 95% confidence interval = 0.97-2.54) among residents in target communities than those in comparison communities. However, this difference was not statistically significant. Symptom prevalence varied greatly among the community populations. The prevalence of respiratory symptoms was higher near facilities with historically higher TDI emissions. Among the 351 participants who provided blood samples, only one had immunoglobulin G specific antibodies to TDI. This participant lived in a target area and may have had non-occupational exposure. TDI was detected at an extremely low level (1 ppt) in one of the 45 air samples from target communities. One ppt is one-tenth the EPA reference concentration. Overall, air sample and antibody test results are not consistent with recent or ongoing exposure to TDI.

Skin exposure to aliphatic polyisocyanates in the auto body repair and refinishing industry: II. A quantitative assessment.

BACKGROUND: Skin exposure to isocyanates, in addition to respiratory exposures, may contribute to sensitization and asthma. Quantitative skin exposure data are scarce and quantitative methods limited. METHODS: As part of the Survey of Painters and Repairers of Autobodies by Yale study, a method to sample and quantify human isocyanate skin exposure was developed (based on NIOSH 5525 method) and used to evaluate aliphatic isocyanate skin exposure in 81 auto body shop painters and body technicians. Wipe samples were collected from unprotected skin and from under PPE (gloves, clothing and respirator) using a polypropylene glycol-impregnated wipe. Hexamethylene diisocyanate (HDI), its polyisocyanates [HDI-derived polyisocyanates (pHDI)], isophorone diisocyanate (IPDI) and its polyisocyanates and IPDI-derived polyisocyanates (pIPDI) were quantified separately and also expressed as the total free isocyanate groups (total NCO). RESULTS: For unprotected skin areas, 49 samples were collected for spray painting, 13 for mixing, 27 for paint-related tasks (e.g. sanding and compounding) and 53 for non-paint-related tasks. Forty-three samples were also collected under PPE. The geometric mean (GM) [geometric standard deviation (GSD)] total NCO concentrations (ng NCO cm(-2)) for unprotected skin (hands, face and forearms) was 1.9 (10.9) and range 0.0-64.4. pHDI species were the major contributor to the total NCO content. Levels were very variable, with the highest concentrations measured for clear coating and paint mixing tasks. Isocyanate skin exposure was also commonly detected under PPE, with 92% of samples above the limit of detection. Levels were very variable with the overall GM (GSD) total NCO (ng NCO cm(-2)) under PPE 1.0 (5.2) and range (0.0-47.0) and similar under the different PPE (glove, respirator and clothing). The highest concentrations were detected for mixing and spraying tasks, 6.9 (5.3) and 1.0 (5.2), respectively. Levels under PPE were generally lower than unpaired samples obtained with no PPE, but not statistically significant. Total isocyanate GM load on exposed skin and under PPE was commonly 100-300 ng NCO per sample, except for higher levels on exposed forearms during spraying (GM 5.9 mug NCO). CONCLUSIONS: A quantitative method was developed for skin sampling of isocyanates. Using this method, the study demonstrates that skin exposure to aliphatic polyisocyanates during painting, mixing and paint-related tasks in auto body shop workers is common and also commonly detected under routine PPE.

Skin exposure to isocyanates: reasons for concern.

OBJECTIVE: Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. DATA SOURCES: We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. DATA EXTRACTION: We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords "isocyanate," "asthma," "skin," "sensitization," and other synonymous terms, and our own extensive collection of isocyanate publications. DATA SYNTHESIS: Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. CONCLUSIONS: Integrated animal and human research is needed to better understand the role of skin exposure in human isocyanate asthma and to improve diagnosis and prevention. In spite of substantial research needs, sufficient evidence already exists to justify greater emphasis on the potential risks of isocyanate skin exposure and the importance of preventing such exposures at work and during consumer use of certain isocyanate products.

An FTIR investigation of isocyanate skin absorption using in vitro guinea pig skin.

Isocyanates may cause contact dermatitis, sensitization and asthma. Dermal exposure to aliphatic and aromatic isocyanates can occur in various exposure settings. The fate of isocyanates on skin is an important unanswered question. Do they react and bind to the outer layer of skin or do they penetrate through the epidermis as unreacted compounds? Knowing the kinetics of these processes is important in developing dermal exposure sampling or decontamination strategies, as well as understanding potential health implications such exposure may have. In this paper the residence time of model isocyanates on hairless guinea pig skin was investigated in vitro using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometry. Model isocyanates tested were octyl isocyanate, polymeric hexamethylene diisocyanate isocyanurate (pHDI), polymeric isophorone diisocyanate isocyanurate (pIPDI) and methylenediphenyl diisocyanate (MDI). Isocyanates in ethyl acetate (30 microL) were spiked directly on the skin to give 0.2-1.8 micromol NCO cm(-2) (NCO = -N=C=O), and absorbance of the isocyanate group and other chemical groups of the molecule were monitored over time. The ATR-FTIR findings showed that polymeric isocyanates pHDI and pIPDI may remain on the skin as unreacted species for many hours, with only 15-20% of the total isocyanate group disappearing in one hour, while smaller compounds octyl isocyanate and MDI rapidly disappear from the skin surface (80+% in 30 min). Isocyanates most likely leave the skin surface by diffusion predominantly, with minimal reaction with surface proteins. The significance of these findings and their implications for dermal exposure sampling and isocyanate skin decontamination are discussed.

A laboratory investigation of the effectiveness of various skin and surface decontaminants for aliphatic polyisocyanates.

Isocyanates may cause contact dermatitis and respiratory sensitization leading to asthma. Dermal exposure to aliphatic isocyanates in auto body shops is very common. However, little is known about the effectiveness of available commercial products used for decontaminating aliphatic polyisocyanates. This experimental study evaluated the decontamination effectiveness of aliphatic polyisocyanates for several skin and surface decontaminants available for use in the auto body industry. The efficiency of two major decontamination mechanisms, namely (i) consumption of free isocyanate groups via chemical reactions with active hydrogen components of the decontaminant and (ii) physical removal processes such as dissolution were studied separately for each decontaminant. Considerable differences were observed among surface decontaminants in their rate of isocyanate consumption, of which those containing free amine groups performed the best. Overall, Pine-Sol(R) MEA containing monoethanolamine was the most efficient surface decontaminant, operating primarily via chemical reaction with the isocyanate group. Polypropylene glycol (PPG) had the highest physical removal efficiency and the lowest reaction rate with isocyanates. All tested skin decontaminants performed similarly, accomplishing decontamination primarily via physical processes and removing 70-80% of isocyanates in one wiping. Limitations of these skin decontaminants are discussed and alternatives presented. In vitro testing using animal skins and in vivo testing with field workers are being conducted to further assess the efficiency and identify related determinants.

Polyisocyanates in occupational environments: a critical review of exposure limits and metrics.

BACKGROUND: Determination of polyisocyanates is important because they are a major contributor of exposure to the isocyanate functional group in many workplace environments and are capable of inducing sensitization and asthma. However, with multiple different measurement metrics in use, comparison of isocyanate exposure data between studies and development of occupational exposure limits (OELs) for polyisocyanates is difficult. METHODS: An analysis of existing problems in the measurement and regulation of isocyanates is presented based on the published analytical, toxicological, and regulatory literature, and the authors' own analytical data and experience with isocyanates. RESULTS: This analysis supports a need for standardization of isocyanate measurement metrics and provides a framework for the development of an OEL for polyisocyanates. CONCLUSIONS: The total isocyanate group (microg NCO/m(3)) is recommended as the most feasible and practical metric (unit) by which to express polyisocyanate exposures for research, control, and regulatory purposes. The establishment of a comprehensive isocyanate OEL that simplifies the current agent-by-agent approach and expands coverage to polyisocyanates is also recommended.