In the occupational environment, many efforts are made to identify potential skin sensitizers used in production through available testing and proper risk and hazard communication. Unfortunately, despite these efforts, this toxicological endpoint remains a qualitative assessment, with the resulting conclusion that industrial hygiene procedures should focus on reducing peak exposures. But what does this qualitative assessment entail? How does the toxicological characterization take place? Why is it so difficult to predict if an individual will react with a skin sensitization, and how can sensitization be prevented? How should workers protect their skin? How can workers identify a reaction, and what should they do if they experience one? Why hasn’t industry already adopted a standard approach to handling sensitizers? In this article, we provide a brief overview of the industry approach where dose-related reactions can be highly variable among individual workers. 

A benchmarking summary of how companies consider skin sensitization potential in the pharmaceutical industry appears in Table 1. Companies A, B, and C directly integrate the sensitization hazard into the exposure limit or occupational exposure band. In contrast, companies D, E, F, and G either include a sensitization or skin notation on the OEB (without including it in the OEL calculation) or directly calculate surface limits instead of considering it via the inhalation route.  Many companies, especially in the chemical and pharmaceutical industry, have integrated the sensitization aspect into hazard or control banding systems (similar to Companies A, B, and C in Table 1). In that case, a higher level of containment is automatically required, as the sensitizing products are placed in a band with a range of very low exposure limits. Some may even be considered highly potent compounds, with OELs of less than 10 µg/m3. But in some industries, using costly high level containment can impose great constraints on production and is not really a feasible option. This has been our experience in the agrochemical and cosmetics industries, where lower margins on products result in lower investment in controls. In these industries, the choice of protective measures easily becomes personal protective equipment. The problem with this solution is of course that the PPE needs to be removed at some point and the risk of skin contact or inhalation from a suit contaminated with product still remains. Therefore, the only true way to reduce the risk is containment of the process.  It is also possible to simply use the hazard phrases or skin notations to alert occupational health and safety professionals to the need for special measures during the risk assessment. (This is the approach favored by Companies E, F, and G in Table 1.) In this case, one would consider using a higher level of containment regardless of the OEL value. Theoretically, relying on hazard phrases in this manner is appropriate only when the hazard phrases have been validated. In practice, many field practitioners do not have an in-house toxicologist to validate hazard information for all products, and most EHS professionals must make decisions based on the data they have available. Because the quality as well as quantity of available data can drastically vary, the following indications may help to gauge the reliability of your data. Hazard phrases present on a safety data sheet are generally more conservative and less reliable; they could be validated by looking at positive toxicity studies publicly available in the European Chemical Agency’s database of registered substances or obtained by the compound’s supplier. Alternatively, even stronger supporting data come from epidemiology; in the case of a commercial active pharmaceutical ingredient, sensitization reactions could be listed in the labelling information under adverse events noted in the clinical or post-marketing authorization phases. Nevertheless, based on reliable epidemiological data, the sensitization risk may be included in the calculation of OELs; in cases where a high frequency of people exhibit sensitization reactions, the OEL can be decreased with a qualitative adjustment. A good example is beta lactams (a type of antibiotic drug). Beta lactams are used clinically at high doses, which would lead to a rather high OEL value when considering the clinical dose in the OEL calculation. A qualitative OEL adjustment could help to avoid cases of sensitization in the production of beta lactams by reducing the OEL and therefore requiring a more rigorous risk assessment in some companies.  In summary, because of the variability of the toxicity data available to identify skin sensitizers, the inability to identify a general induction/elicitation threshold in workers, and industry’s broad strategy of communicating (validated) skin sensitization potential with differential approaches (exposure banding, surface target values, GHS hazard or skin notation statements), dermal sensitization should be considered as a qualitative assessment and peak exposures should be avoided. For this reason, it is important for the IH practitioner to consider the company’s chosen strategy for identifying potential skin sensitizers when developing a containment strategy and selecting PPE at the workplace. OTHER CONSIDERATIONS FOR THE IH PRACTITIONER  Of course, the number one goal for any health and safety specialist is to prevent exposure as much as possible. When considering the hierarchy of controls, this would mean either substituting for a non-sensitizing product or using technical controls to contain the product as much as possible.  Nevertheless, there are several important points that should be considered: Remember to assess all potential routes of exposure. Do not forget to evaluate the potential for dermal contact. What could be the potential concentration of product on the skin, and how easily could it be absorbed? Air sampling results do not directly relate to surface contamination. This is a crucial point for the exposure assessment when working with dermal sensitizers. Even if air sampling results are very low, it is important to consider where else the worker may come into contact with the product. For example, in the case of powder handling, was the surrounding area cleaned well between the batches or campaigns? Does the next worker risk being exposed when turning a knob or handle or using the same tools as another worker? Surface monitoring, or “wipe samples,” can be used to answer these questions.  Dermal contact can also occur via cross- contamination of areas or services that aren’t directly related. If someone from maintenance is using improperly decontaminated tools from production, they too might risk being exposed.  Peak exposures should be avoided, regardless of the OEL. Concentration of the product on the skin is more important than the surface area covered.  Other special considerations during the risk assessment include the use of surfactants in the process or requirements for wet work or handling of aggressive chemicals (such as caustics), which can break the skin’s barrier. Surfactants, for example, can reduce the effective limits three to ten times lower than usual, according to the 2016 study in the Journal of Dermatology.  Sometimes products are not classified as sensitizers, and unfortunately, the first cases are seen without warning in production. When this happens, it is essential to alert the internal toxicologist or regulatory specialist by reporting potential or confirmed sensitization cases to management and to conduct an investigation regarding the employees’ potential exposures from work and home. Such an investigation should consider whether the employee uses soaps with fragrances or known sensitizing agents (at work or at home) or wears powdered gloves (the employee could be allergic to the powder or glove material). When multiple cases of confirmed skin sensitization are reported, a more stringent containment strategy to decrease employee exposure to the compound must be considered.   SAMANTHA CONNELL, MSPH, CIH, is an industrial hygienist at Lonza in Visp, Switzerland. SELENE ARAYA, PhD, is a toxicologist at Lonza in Basel, Switzerland. Acknowledgment: The authors would like to thank Ester Lovsin Barle, PhD, MScTox, ERT, for her contribution of industry research. Send feedback to The Synergist.