Lab safety alert: a real case of isocyanate exposure

Abstract

Real-world laboratory exposure to isocyanates highlights the severe dermal risks posed by these reactive chemicals. A real lab accident reveals the underestimated danger of isocyanates. First-aid actions and key safety insights are shared to reinforce best practices in the laboratory.

Polyurethanes (PUs) are a widely used class of polymers and rank sixth in global polymer production, with a market volume of 21.3 million tons in 2022. One of the key advantages of polyurethanes is that, by carefully selecting the monomer structure and functionality, a broad range of thermomechanical properties can be achieved. These properties range from thermoplastic polyurethanes, which are used as fibers in textiles to provide elasticity in clothing, to polyurethane foams, which, for example, are used as insulators, making their use essential for various industries, including construction, automotive, textiles, and healthcare.^1,2

Conventional PUs are polymerized through a simple process involving poly(isocyanates) and polyols.³ However, the production of PUs raises environmental and human health concerns because isocyanates are among the most hazardous chemicals listed under the REACH (Registration, Evaluation, Authorisation, and Restriction of Chemicals) regulation due to their high reactivity and significant risks to both human health and the environment (Fig. 1). Exposure to these chemicals has been linked to respiratory sensitization, occupational asthma, chemical burns from skin contact, and long-term ecological damage from improper disposal.^4,5 The Bhopal tragedy remains one of the most devastating industrial disasters involving isocyanates, underscoring their severe risks. This catastrophic event remains a stark reminder of the severe risks associated with these chemicals, emphasizing the critical need for stringent safety measures.^6,7 Now, four decades later, Bhopal is not just a historical tragedy but an important warning that chemical safety must never be compromised.

Fig. 1 Substance info card: hexamethylene diisocyanate. Adapted from REACH website.¹¹

In recognition of the severe risks, regulatory bodies such as the European Commission have imposed strict limits on isocyanate exposure, and special training is required in industrial sectors where operators handle reagents containing more than 0.1% free isocyanates.⁸ Non-isocyanate polyurethanes (NIPUs) have emerged as greener alternatives over the past decade. Despite this, the use of NIPUs on an industrial scale remains limited, and isocyanate-based PUs continue to be the prevalent method for producing these versatile materials.^9,10

As a scientific researcher in chemistry, dealing with chemicals of varying degrees of hazard is unavoidable. Although the risks associated with certain chemicals, particularly isocyanates, are well known, what would happen if a small amount—less than 1 mL—were accidentally spilled on your skin? What kind of harm could it cause? Unfortunately, a real case occurred in the Catalysis and Sustainable Polymers group, when a student accidentally spilled less than 1 mL of hexamethylene diisocyanate (HDI) onto her face and neck. The consequences were serious.

Drawing from a recent example shared by Sébastián Vidal's group regarding the issues caused by injecting a tiny amount of dichloromethane into the skin,¹² we aimed to raise awareness about the potential consequences of using isocyanates and the importance of acting quickly after such an accident. Preventing accidents is the best approach. However, once an accident occurs, we believe it provides valuable information that should be shared with the scientific community.

On the morning of Wednesday, October 23, 2024, advisors and the security team were alerted to a chemical accident involving a PhD researcher who had recently joined the group as part of a collaborative project with the Spanish chemical industry on enhancing the barrier properties of water-dispersed polyurethane-based polymers. During a PU synthesis, she was transferring 3 mL of HDI into a Schlenk flask containing polyol and catalyst. After successfully injecting 2 mL, as she was attempting to inject the remaining amount, the needle detached from the syringe adapter, causing the chemical to splash onto her neck and face.

Fortunately, following the safety protocols, she was wearing the mandatory personal protective equipment (PPE)¹³ (Fig. 2). However, the fume hood sash was not positioned correctly; it was not fully closed as it should have been. While this can make chemical manipulation easier, which is why such scenes are viewed with relative frequency in chemistry laboratories, an open fume hood drastically increases the risk of injuries in case of a chemical spill and fails to protect the researcher from toxic vapors.

Fig. 2 Protective goggles following the accident. Yellow arrows indicate the marks left by HDI contact with the polycarbonate lenses. These images emphasize the necessity and importance of wearing PPE.

After the accident, she immediately removed her gloves and goggles, rushed to the sink, and instinctively rinsed her face with water. A colleague in the lab quickly retrieved Diphoterine® from the first aid kit and helped her apply it to the affected areas, using two entire flasks of 500 mL to wash her eyes, face, and neck. Diphoterine®^14–16 is a hypertonic and amphoteric aqueous solution that can be used after spilling many chemicals, except hydrofluoric acid (HF), strong oxidizers like peroxides, dichromates, certain heavy metal compounds, and highly lipophilic chemicals.

Despite being dressed in full laboratory safety gear, including a lab coat, chemical-resistant gloves, and safety goggles, she experienced a burning sensation that spread from her cheek to her neck. Although she felt no irritation in her eyes, she felt a burning sensation in her throat, possibly from inhaling the vapors. Concerned about her symptoms, she was taken to a nearby hospital that specializes in work-related injuries. The hospital, located about 2 km away, was reached in approximately 10 minutes by car. At the hospital, her vitals were checked, and an X-ray of her lungs was taken to rule out any further complications. Although the X-ray results were normal, the doctor recommended rest and allowed the burns to heal naturally. She felt well enough to go home with the assistance of a team member.

Meanwhile, some team members reviewed the MSDS (Fig. 3) for HDI to confirm if the necessary precautions for skin exposure were taken. The document identifies HDI as toxic if inhaled, a respiratory sensitizer, and capable of causing severe skin and eye irritation or burns. According to the MSDS, if the skin is exposed to HDI, it should be washed with plenty of water.

Fig. 3 Part of safety data sheet of hexamethylene diisocyanate.¹⁷

By evening, she noticed small black spots forming on her chin, neck, and cheeks (Fig. 4a). These spots grew larger over the next few days, turning into dry, peeling skin. On Saturday evening (the third day after the accident), she began feeling discomfort in her left eyelid. By the next morning, her eyelid had become blackened and swollen (Fig. 5a), despite wearing Class 1A safety goggles (spectacles with side protection) at the time of the incident.

Fig. 4 Burn marks on the neck: (a) day 1, (b) one week, (c) two weeks, (d) one month, (e) two months.

Fig. 5 Isocyanate vapor effect on the eye: (a) day 5, (b) one week, (c) two weeks, (d) one month, (e) two months.

The burn wounds worsened in the following 24 hours, with the skin on her neck, chin, and the corners of her eyelids chapping due to dryness and movement, causing additional wounds (Fig. 4b and 5b).

She was taken to a general hospital, where she was prescribed ointments for the burns and advised to use an aloe vera-based moisturizer for the burn marks. The delayed progression of the injury may be attributed to the penetration of HDI or the formation of 1,6-hexane-diamine from HDI hydrolysis, which, after entering the skin, led to slow tissue necrosis and the appearance of dark spots. It took two weeks for her wounds to begin healing, and her skin is now gradually returning to its original state. However, she remains under close observation. Regular medical evaluations are being periodically conducted to ensure her recovery progresses without complications (Fig. 4 and 5).

Several factors could have contributed to the eye injury. Firstly, eye protection is designed to guard against three primary hazards: impact, chemical splashes, and radiation. While Class 1A to 2A safety goggles provide effective protection against impact, they are not suitable for shielding against chemical splashes. Class 2B safety goggles, which feature sealed sides, are recommended for such cases.¹⁸

Considering this, multiple factors could have led to the eyelid burn: (1) residual HDI on her forehead or surrounding areas may have been inadvertently transferred to her eyelid during the initial rinsing with water; (2) chemical vapors could have caused irritation or burns, particularly on the delicate eyelid skin, due to an open fume hood sash; (3) microdroplet exposure might have occurred through the open areas of the safety goggles, as they were not fully sealed like Class 2B goggles.

Lessons learned and the importance of sharing this incident with the scientific community

While, ideally, policies should focus on preventing accidents in the laboratory, it is true that accidents can still happen. It is important to consider what we can learn from these incidents and what steps we can take to minimize the chances of a similar event occurring again. If an accident does occur, we must know what actions to take to minimize the damage caused. A detailed analysis of the incident revealed that the primary causes were improper use of the fume hood, which was not fully closed, and incorrect syringe and needle handling,¹⁹ likely due to excessive pressure or clogging.

As an initial mitigation plan, we decided to encourage group members to: (1) check the MSDS for all chemicals before starting an experiment and have a colleague verify the information to ensure safe handling and preparedness; (2) appropriately close the fume hoods;²⁰ (3) re-assure that the needle is properly connected to the syringe prior to any liquid transference, (4) perform transferences of liquid chemicals slowly and steadily to prevent sudden pressure changes; (5) check for cracks in glassware before use and following a collective review we identified additional contributing factors beyond the improper use of the fume hood including (a) the use of goggles that, although present, were not fully secure against splashes, (b) the arbitrary selection of needle gauge by team members, and (c) the absence of a Luer lock on the syringe, which may have played a role in the incident.

As a group, we critically evaluated the response to the incident. While it is commonly believed that rinsing the skin or eyes with water is the best immediate response to a chemical spill, our analysis suggests that a different approach could have mitigated the severity of the accident. Remaining calm and adhering to safety training protocols is essential in such situations. Based on our findings, an effective decontamination strategy should involve the immediate application of a suitable neutralizing agent (like Diphoterine®), followed by the use of an emergency shower to ensure thorough removal of hazardous substances. Rinsing in a sink is often inadequate for chemical decontamination, as it requires manually directing water flow, increasing the risk of cross-contamination. However, for corrosive chemicals like HDI, which may come into contact with the face or other body areas that cannot be sufficiently rinsed in a sink, the immediate use of a safety shower is imperative. This ensures proper decontamination, reduces further exposure, and enhances overall laboratory safety.

Safety showers need to be used with the removal of all clothing to avoid cross-contamination and allow proper and abundant rinsing of all the skin, with abundant water–skin contact. Such action would help remove the hydrophilic hexamethylene diamine formed as a product of HDI hydrolysis in the skin. It is crucial to consider that water is not always the appropriate response for all chemical accidents. It is important to make a correct choice of decontamination method based on the chemical involved. There is no unique and universal procedure for chemical exposures.

Conclusions and outlook

Laboratory protocols should incorporate structured safety documentation, including dedicated sections in lab journals for identifying potential risks such as fire hazards, gas releases, and thermal runaways. These sections should guide researchers in systematically planning preventive measures, control strategies, and containment actions for both the chemicals used and the specific experimental procedures. Implementing mandatory safety forms before commencing any experiment ensures a thorough risk assessment and enhances preparedness. By integrating comprehensive training with enforced safety documentation, laboratories can minimize accidents, safeguard personnel, and cultivate a strong culture of safety and accountability.²¹

This step is especially critical for highly reactive chemicals like HDI, which can rapidly penetrate the skin. Effectively managing such incidents requires a well-thought-out approach. It should be emphasized that academic research laboratories generally have a high turnover of people, with around 70–90% of the members being temporary employees who spend 3–5 years in the group, along with a constant rotation of research activities. For example, in the Catalysis and Sustainable Group, 4–6 people leave the group, new members join each year, and new projects require the use of new chemicals. These factors create additional challenges, as safety protocols must be updated regularly to account for the new hazards of chemicals being introduced.

Acknowledgements

G.P. acknowledges funding from the EU Horizon 2020 program (Marie Skłodowska-Curie grant No. 101154935). L.P.F. acknowledges support from ADAGIO and Horizon 2020 (Marie Skłodowska-Curie grant No. 101034379). M.X. acknowledges the Gipuzkoa Fellows Programme (G75067454). M.X. and H.S. acknowledge PID2022-138199NB-I00 funded by MCIU/AEI/10.13039/501100011033.

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