Dry Sampling for Isocyanates Measurement of the Potential Exposure to Isocyanate Monomers and Oligomers during Automotive Spray Paint Applications: A Comparison of Two Sampling Methods By Gary Oishi
Isocyanates are the reactive component used in making polyurethane materials. Simple polyurethanes (PU) are made by reacting an isocyanate and polyol. Other forms of PU materials can be made with active hydrogen-containing compounds such as alcohols, carboxylic acids, and amines, yielding products with various characteristics. 
Isocyanates are used in numerous commercial and residential applications such as paints, coatings, and insulating foams, leading to potential exposures for many workers. The most common interactions people have with isocyanates are through exposure to paints, coatings, and insulating foams, and from polyurethane foams found in furniture. However, these materials are cured prior to use. Consequently, when these same materials are applied or thermally degraded, there is a risk for exposure not only to the monomer but also the oligomers. Exposures During Spray Painting Why the concern? We know isocyanates are highly reactive, powerful irritants and sensitizers to the mucous membranes of the respiratory tract, eyes, and skin. Exposures can develop into and manifest as occupational asthma or—as a worst case—even lead to death.
Numerous sampling approaches exist for isocyanates, from solution-type samplers that utilize impingers to dry-type filter samplers and even combinations of the two. The R&D team at Millipore Sigma recently undertook a study to determine whether typical sampling methods resulted in an underestimation of exposure during automotive spray-painting operations. We examined two dry-type samplers since this platform type is commonly used. Comparison sampling was performed using a 37 mm cassette (ORBO-80) containing the derivatizing reagent 1-(2-pyridyl)piperazine (1,2-PP) coated on a glass fiber filter as described in OSHA methods 42 and 47. The samples were field desorbed as described in the methods. The other sampler type was a Denuder + 13 mm cassette dry filter sampler (ASSET EZ4-NCO), which contains two glass-fiber filters coated with the derivatizing agent dibutylamine (DBA).
The automotive clear coat used in our study is commercially available and recommended by a local auto body repair shop. The two components of the coating (clear coat and activator) were mixed per the manufacturer’s instructions and thinned. The clear coat contained a mixture of both hexamethylene diisocyanate (HDI) and Isophorone Diisocyante (IPDI). A high-volume, low-pressure (HVLP) spray gun was used to apply the coating to a car hood in a ventilated spray booth. Both personal and area samples were collected simultaneously for 15 minutes.
Figure 1. Our study examined whether typical sampling methods resulted in an underestimation of exposure during automotive spray-painting operations.
The ORBO-80 sampler analysis was performed by liquid chromatography-ultraviolet (LC-UV) following OSHA 42/47 using the 1,2-PP derivatives of hexamethylene diisocyanate (HDI). Additional peaks were noticed in the chromatography but retention time identification was not possible because of the non-existence of references. A major unknown was later identified as the 1-2PP derivative of an oligomer (HDI-isocyanurate) by liquid chromatography-mass spectrometry (LC/MS). The current OSHA 42/47 method would not work even if standards are available as it was noticed during sample analysis that some of the unknown compounds were not stable.
The ASSET sampler analysis was performed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) using DBA-isocyanate derivative Certified Reference Material (CRM) standards and deuterated internal standards, with both monomers and oligomers available to provide direct quantitation. Having the oligomer standards eliminated the estimation most methods base their calculations upon.
Personal sample results are in in Table 1.
Table 1: Concentrations of Isocyanates (µg/m3) Observed in the Breathing Zone
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Concentrations found were higher and, in addition, two additional isocyanates were detected on the operator’s left side. This difference may have been caused by the booth air flow movement, which was from the operator’s right to left.

Area sample results are shown in Table 2.
Table 2. Concentrations of Isocyanates (µg/m3) Inside the Spray Booth
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In comparison to the area samples, there appears to be an underestimation of the HDI monomer by the 37 mm 1,2-PP filter cassette technique.
The results of the ASSET area samplers reported for the oligomers (highlighted in yellow) show higher levels. In particular, the higher levels of oligomers compared to the monomers are indicated in red font. Collection Pathways How can we explain a possible reason for the underestimation of just the monomer found between these two dry sampling techniques? 
The difference is the collection pathways are different. The coated filter in the ORBO-80 cassette acts as both particle and vapor collector. The ASSET sampler is constructed with two collection areas (one for particle and one for vapor) and uses a derivatization reagent, which is less prone to reagent depletion because the dynamic of the denuder + cassette-based sampler design (ASSET) is that it constantly refreshes the reagent. This is one reason OSHA recommends field desorption of dry-type samplers to be done immediately (with the exception of the ASSET sampler). 
This experiment has demonstrated that there can be an underestimation of the isocyanate monomer, and also that a potential for exposure exists when testing for oligomers using a method that is monomer specific. These results may not be true for all applications, but the results of not looking for oligomers are very different than looking for them and not detecting any.
In short, don’t ignore the potential of oligomer exposures.
Health Effects of Oligomer Exposures

The OSHA National Emphasis Program (NEP) for isocyanates (PDF) lists in Appendix B only monomeric forms. However, oligomeric isocyanate species have also been shown to produce respiratory issues. In a 2016 document on Toluene Diisocyanate Reference Exposure Levels (PDF), the California Office of Environmental Health Hazard Assessment (OEHHA) references studies that "show that TDI monomer and prepolymers share many of the same pulmonary effects, including inducing sensitization and occupational asthma with repeated exposure. This suggests some commonality in the mechanisms of sensitization, possibly related to N=C=O binding carrier proteins (Bello et al., 2004; Redlich et al., 2007)."
GARY OISHI is currently an R&D chemist in the Environmental Air Monitoring group at Millipore Sigma in Bellefonte, Pa., where he helps develop new products and testing methodologies in air monitoring. In his twenty-plus-year career in analytical chemistry, he has been involved with the identification of micro- and macro-contaminations in failure analysis, deformulation, forensic, and industrial hygiene sample testing. He can be reached at gary.oishi@sial.com.