In terms of bonding, isocyanates are closely related to carbon dioxide (CO2) and carbodiimides (C(NR)2). The C−N=C=O unit that defines isocyanates is planar, and the N=C=O linkage is nearly linear. In phenyl isocyanate, the C=N and C=O distances are respectively 1.195 and 1.173 Å. The C−N=C angle is 134.9° and the N=C=O angle is 173.1°.<ref>Template:Cite journal</ref>
These reactions proceed via the intermediacy of a carbamoyl chloride (Template:Chem2). Owing to the hazardous nature of phosgene, the production of isocyanates requires special precautions.<ref name=Ullmann/> A laboratory-safe variation masks the phosgene as oxalyl chloride.<ref>Smith (2020), March's Organic Chemistry, rxn. 16-7.</ref> Also, oxalyl chloride can be used to form acyl isocyanates from primary amides, which phosgene typically dehydrates to nitriles instead.Template:Sfn
Another route to isocyanates entails addition of isocyanic acid to alkenes. Complementarily, alkyl isocyanates form by displacement reactions involving alkyl halides and alkali metal cyanates.Template:Sfn
An isocyanate is also the immediate product of the Hofmann rearrangement, but typically hydrolyzes under reaction conditions.<ref>Template:Citation</ref>
where R and R' are alkyl or aryl groups.
If a diisocyanate is treated with a compound containing two or more hydroxyl groups, such as a diol or a polyol, polymer chains are formed, which are known as polyurethanes.
This reaction is exploited in tandem with the production of polyurethane to give polyurethane foams. The carbon dioxide functions as a blowing agent.<ref name="Coleman2019">Template:Cite book</ref>
MDI is commonly used in the manufacture of rigid foams and surface coating.<ref name=Ullmann>Template:Ullmann</ref> Polyurethane foam boards are used in construction for insulation. TDI is commonly used in applications where flexible foams are used, such as furniture and bedding. Both MDI and TDI are used in the making of adhesives and sealants due to weather-resistant properties. Isocyanates, both MDI and TDI are widely used in as spraying applications of insulation due to the speed and flexibility of applications. Foams can be sprayed into structures and harden in place or retain some flexibility as required by the application.<ref>Template:Cite web</ref> HDI is commonly utilized in high-performance surface-coating applications, including automotive paints.
The risks of isocyanates was brought to the world's attention with the 1984 Bhopal disaster, which caused the death of nearly 4000 people from the accidental release of methyl isocyanate. In 2008, the same chemical was involved in an explosion at a pesticide manufacturing plant in West Virginia.<ref>Template:Cite web</ref>
Since they are used in spraying applications, the properties of their aerosols have attracted attention.<ref name=":4">Template:Cite web</ref><ref name=":5">Template:Cite web</ref> In the U.S., OSHA conducted a National Emphasis Program on isocyanates starting in 2013 to make employers and workers more aware of the health risks.<ref>Template:Cite web</ref>
Polyurethanes have variable curing times, and the presence of free isocyanates in foams vary accordingly.<ref name="CPWR">Template:Cite journal</ref>
Isocyanates can present respiratory hazards as particulates, vapors or aerosols. Autobody shop workers are a very commonly examined population for isocyanate exposure as they are repeatedly exposed when spray painting automobiles<ref name=":9">Template:Cite journal</ref> and can be exposed when installing truck bed liners.<ref name=":10">Template:Cite web</ref><ref>Template:Cite journal</ref> Hypersensitivity pneumonitis has slower onset and features chronic inflammation that can be seen on imaging of the lungs. Occupational asthma is a worrisome outcome of respiratory sensitization to isocyanates as it can be acutely fatal.<ref>Template:Cite journal</ref> Diagnosis of occupational asthma is generally performed using pulmonary function testing (PFT) and performed by pulmonology or occupational medicine physicians.<ref>Template:Cite web</ref> Occupational asthma is much like asthma in that it causes episodic shortness of breath and wheezing. Both the dose and duration of exposure to isocyanates can lead to respiratory sensitization.<ref>Template:Cite journal</ref> Dermal exposures to isocyanates can sensitize an exposed person to respiratory disease.
Dermal exposures can occur via mixing, spraying coatings or applying and spreading coatings manually. Dermal exposures to isocyanates is known to lead to respiratory sensitization.<ref>Template:Cite journal</ref> Even when the right personal protective equipment (PPE) is used, exposures can occur to body areas not completely covered.<ref>Template:Cite journal</ref> Isocyanates can also permeate improper PPE, necessitating frequent changes of both disposable gloves and suits if they become over exposed.
Methyl isocyanate (MIC) is highly flammable.<ref>Template:Cite web</ref> MDI and TDI are much less flammable.<ref>Template:Cite web</ref> Flammability of materials is a consideration in furniture design.<ref>Template:Cite web</ref> The specific flammability hazard is noted on the safety data sheet (SDS) for specific isocyanates.
Industrial science attempts to minimize the hazards of isocyanates through multiple techniques. The EPA has sponsored ongoing research on polyurethane production without isocyanates.<ref>Template:Cite news</ref><ref>Template:Cite web</ref> Where isocyanates are unavoidable but interchangeable, substituting a less hazardous isocyanate may control hazards. Ventilation and automation can also minimizes worker exposure to the isocyanates used.<ref name=":4" /><ref name="auto">Template:Cite web</ref>
If human workers must enter isocyanate-contaminated regions, personal protective equipment (PPE) can reduce their intake. In general, workers wear eye protection<ref name="auto"/> and gloves and coveralls to reduce dermal exposure<ref>Template:Cite journal</ref><ref>Template:Cite web</ref><ref name=":5" /><ref>Template:Cite web</ref> For some autobody paint and clear-coat spraying applications, a full-face mask is required.<ref name=":9" /><ref name=":10" />
The US Occupational Safety and Health Administration (OSHA) requires frequent training to ensure isocyanate hazards are appropriately minimized.<ref>Template:Cite web</ref> Moreover, OSHA requires standardized isocyanate concentration measurements to avoid violating occupational exposure limits. In the case of MDI, OSHA expects sampling with glass-fiber filters at standard air flow rates, and then liquid chromatography.<ref>Template:Cite web</ref>
Combined industrial hygiene and medical surveillance can significantly reduce occupational asthma incidence.<ref>Template:Cite journal</ref> Biological tests exist to identify isocyanate exposure;<ref>Template:Cite journal</ref> the US Navy uses regular pulmonary function testing and screening questionnaires.<ref name=":6">Template:Cite web</ref>
Emergency management is a complex process of preparation and should be considered in a setting where a release of bulk chemicals may threaten the well-being of the public. In the Bhopal disaster, an uncontrolled MIC release killed thousands, affected hundreds of thousands more, and spurred the development of modern disaster preparation.<ref>Template:Cite journal</ref>
Exposure limits can be expressed as ceiling limits, a maximal value, short-term exposure limits (STEL), a 15-minute exposure limit or an 8-hour time-weighted average limit (TWA). Below is a sampling, not exhaustive, as less common isocyanates also have specific limits within the United States, and in some regions there are limits on total isocyanate, which recognizes some of the uncertainty regarding the safety of mixtures of chemicals as compared to pure chemical exposures. For example, while there is no OEL for HDI, NIOSH has a REL of 5 ppb for an 8-hour TWA and a ceiling limit of 20 ppb, consistent with the recommendations for MDI.<ref>Template:Cite web</ref>
The Occupational Safety and Health Administration (OSHA) is the regulatory body covering worker safety. OSHA puts forth permissible exposure limit (PEL) 20 ppb for MDI and detailed technical guidance on exposure assessment.<ref name=":6" />
The National Institutes of Health (NIOSH) is the agency responsible for providing the research and recommendations regarding workplace safety, while OSHA is more of an enforcement body. NIOSH is responsible for producing the science that can result in recommended exposure limits (REL), which can be lower than the PEL. OSHA is tasked with enforcement and defending the enforceable limits (PELs). In 1992, when OSHA reduced the PEL for TDI to the NIOSH REL, the PEL reduction was challenged in court, and the reduction was reversed.<ref name=":7">Template:Cite journal</ref>
The Environmental Protection Agency (EPA) is also involved in the regulation of isocyanates with regard to the environment and also non-worker persons that might be exposed.<ref>Template:Cite web</ref>
The European Chemicals Agency (ECHA) provides regulatory oversight of chemicals used within the European Union.<ref>Template:Cite web</ref> ECHA has been implementing policy aimed at limiting worker exposure through elimination by lower allowable concentrations in products and mandatory worker training, an administrative control.<ref>Template:Cite web</ref> Within the European Union, many nations set their own occupational exposure limits for isocyanates.
The IARC evaluates the hazard data on chemicals and assigns a rating on the risk of carcinogenesis. In the case of TDI, the final evaluation is possibly carcinogenic to humans (Group 2B).<ref>Template:Cite web</ref> For MDI, the final evaluation is not classifiable as to its carcinogenicity to humans (Group 3).<ref>Template:Cite web</ref>
The International Isocyanate Institute is an international industry consortium that seeks promote the safe utilization of isocyanates by promulgating best practices.<ref>Template:Cite web</ref>
