Editorial

Diisocyanates offer fascinating and versatile chemistries that form the basis for a wide variety of polyurethane applications. These very same chemistries also make the safety of diisocyanates much debated and drive the need to handle them with care, both in the workplace (direct exposure) and in the broader context of the human environment (indirect exposure). As such, from both an Industrial Hygiene (IH) and Product Stewardship (PS) perspective, access to science-based information is critical to management of these materials.

In the workplace, the main concern is direct exposure to isocyanate (NCO) groups and the associated potential for those exposed to become sensitized and develop occupational respiratory diseases like asthma. In addition, in the workplace as well as in the general environment, the presence of NCO-derived diamines could constitute a source of indirect exposure to substances with a high-health hazard profile.

This special issue covers both diisocyanates and their corresponding diamines, addresses aspects of exposure and health, and includes an extensive review of work dedicated toward elucidating how diisocyanate chemistry and biochemistry drive their absorption-distribution-metabolism-excretion (ADME) and, ultimately, toxicity characteristics.

Much work has been done over an extensive period of time on diisocyanate sensitization, yet it is surprising and sobering to realize how much is still not understood and how many important questions remain unanswered. For instance, on the one hand, diisocyanate-induced asthma presents itself as a chronic disease, which would indicate that cumulative exposure is the determining factor. On the other hand, peak exposure is invariably considered as an important factor, suggesting a different approach to address and resolve practical exposure problems. The quantitative-weight-of-evidence studies included in this issue indicate that the currently available data are not sufficient to discriminate between the two exposure modes. This observation points out the great need for better and targeted data from well-designed and detailed field assessments of real exposure profiles and the associated adverse health effects. We are pleased having received such contributions, which support the ultimate goal of better managing exposure and reducing the occurrence of diisocyanate-induced asthma.

In most every regulatory framework, any NCO-containing substance is considered a sensitizer. The reactivity of the NCO-group makes isocyanates test positive in most screening tests; however, validated tests for evaluating sensitization via the respiratory route are lacking. We present in this issue an article about the sensitization potential of polymeric diisocyanate-based prepolymers by the dermal route, which we believe to be novel in both design and findings. The results of testing diisocyanate-based prepolymers show that the picture is much more complex and that factors other than the mere presence of an NCO-group may determine sensitization potency or, surprisingly, the absence thereof. These results can inform the designing of substances with, at the same time, adequate reactive properties and reduced health hazard potential.

In the workplace as well as the broader environment, there is always an implicit concern when diisocyanates come into contact or react with the most prevalent constituent of the human body, water. Be this as part of a specific process or intended use (e.g., polyurethane production) or unintentional (e.g., spills), both instances require the attention from an IH or PS perspective since the potential formation of the corresponding diamines is always a factor to be considered. For aromatic diamines in particular, the toxicological consequences can be significant. As an example of an intended use, the potential formation and emission of methylene dianiline (MDA) was investigated during application of do-it-yourself (DIY) MDI (methylenediphenyl diisocyanate)-based products. To support PS activities in case of unintentional releases, the aquatic exposure and acute toxicity potential of the already mentioned polymeric diisocyanate prepolymers form the subject of an additional publication. And since Toxicology and Industrial Health is also dedicated to publishing “negative results” from scientifically rigorous experiments, the results of three in vitro genotoxicity screening tests conducted with the 2,4’-MDA isomer are included in this special issue.

The special issue opens with the already mentioned overview of the ADME of aromatic diisocyanates. This review summarizes more than two decades of work and illustrates how reactive chemistry and a combination of in vitro and in vivo (bio)chemical investigations provide the basis for understanding the toxic effects of aromatic NCO-groups at the portal of entry and their non-availability on a systemic basis.

The aim of this special issue is to present both a comprehensive and compelling overview of diisocyanate toxicology that can inform both IH and PS professionals as well as regulators.

Wishing you pleasant and informative reading.