Workers’ safety is a fundamental concern in any industry. Employees in pharmaceutical and chemical manufacturing sectors may be exposed to drug substances or chemicals that pose potential health risks in the workplace. Therefore, to protect employees from potential health hazards in the workplace, it is crucial to establish and adhere to safety limits, among this the Occupational Exposure Limit (OEL) is one of the primary benchmarks.
But what exactly is an OEL?
OEL is a “health-based limit” derived solely from health-related data: human data, animal data and certain physicochemical properties of the substances. It is an upper limit on the acceptable concentration of hazardous substance in workplace air for a particular material or class of materials.
OELs refer to the permissible or recommended concentrations of hazardous substances in the workplace environment. These levels are established to protect workers from the potential health risks associated with exposure to various chemicals, physical agents, or biological agents during their work, as these exposures can lead to a wide range of acute and chronic health problems, from respiratory issues to cancer.
By establishing OELs, organizations can limit worker exposure to such hazards, reducing the risk of occupational illnesses and injuries, as required by law.
When it comes to particularly hazardous chemicals some regulatory agencies, such as the Occupational Safety and Health Administration (OSHA) in the United States, have already established OELs. Compliance with these OELs is often a legal requirement, and failing to meet them can result in fines and other penalties. When such limits do not exist, “in house” OELs, specifically for therapeutic substances and their intermediates, should be derived to ensure workers safety in the workplaces.
The OEL can also be used in the framework of risk assessment:
In fact, OELs provide a basis for risk assessment. By setting exposure limits, companies can assess the risks associated with specific tasks or job roles. This information is invaluable for developing safety protocols and personal protective equipment (PPE) requirements. It enables employers to make informed decisions to mitigate risks effectively. In fact, OELs may apply to ceiling, short-term exposure limits (STELs), or time-weighted average (TWA) limits depending by the hazardous properties of the compound.
Now, let’s analyse key factors in the establishment of OELs!
- Toxicological studies: These are a cornerstone of OEL determination. Scientists analyse data on the toxicity of manufactured substances, to identify any potential health effects associated with exposure. In fact, the OEL is a “health-based limit” derived solely from health-related data (both human and animal data) and taking into account certain physicochemical properties of the substances that are being evaluated.
- Epidemiological Data: Observational studies of workers exposed to the same hazardous substance we are deriving an OEL for, can provide valuable insights into the relationship between exposure levels and health outcomes.
- Expert Judgment: In cases where data are limited or uncertain, expert judgment plays a pivotal role.
How is the OEL derived?
The determination of OELs is a systematic and data-driven process. Generally, the following formula has to be applied:
As we can see, some of the values in the above reported formula bear resemblance to those used in deriving the PDE formula. Notably, the PoD, body weight, uncertainty factors and TF are shared between the two formulas, even if with some differences. For a more in-depth exploration of these shared values, please click here to review our previous article. In this discussion, our focus will be on examining the distinctions. In particular:
-The weight adjustments are different in respect to the PDE formula, as the working population is more homogeneous and do not include children. Usually a weight of 60-70 kg is warranted;
-The UF1, representing the difference in population is also different, as in case of workers the population is more homogeneous. Thus, alower value is used;
-The MF value represents the quality of whole database taken into consideration for the evaluation, and can have a value ranging from 1 to 10. This factor is crucial, as it takes an experienced professional to correctly evaluate the quality of data.
-The V represents the volume of air inhaled during an 8-hour workday. In fact, OELs are generally established in relation to a reference period of a typical 8-hour working day, i.e. as 8-hour time weighted average (TWA) exposure limits. Further, they are generally set on the basis of a nominal 40-hour working week and for a working lifetime of 40 years (48 weeks/year; 5 days/week; i.e. 9600 days or 76,800 hours).
What if toxicological data is not available?
In case of pharmaceuticals characterized by having few toxicological data, or low quality and not reliable toxicological data in the open literature, OELs can be calculated starting from the lowest therapeutic dose (LDT), applying the following formula:
What if I have to derive an OEL for a data-poor substances?
Sometimes, especially when dealing with isolated synthesis intermediates, we can encounter chemicals with extremely poor data and, in this case, it is not possible to generate a reliable OEL. This situation usually applies also to new chemical entities. In such cases, it is possible to apply a weight of evidence (WoE) approach using (Q)SAR or read-across techniques for determining a provisional OEL.
Another approach can consist in establishing occupational exposure bands (OEBs), based on the intrinsic hazard properties, mechanism of action, and predicted potency. Compound-specific data together with expert judgment are used to assign an occupational exposure band (OEB), that is the range of airborne concentration levels expected to be protective of the worker’s health.
You have your OEL. What now?
The OEL is not a static value, but rather dynamic. It evolves and adjusts according to new scientific discoveries, as new data become available. This adaptability is essential for protecting worker safety. Obviously, this can go in both directions: an OEL value can become more or less restrictive.
A proactive approach ensures that workers are protected from the latest workplace hazards.
How can we help you?
At ToxHub, we offer comprehensive expertise to assist our clients in the determination of OELs. With our expertise in regulatory compliance and risk assessment, we offer tailored high-quality solutions to navigate the complexities of establishing OELs, even for data-poor substances.
Feel free to reach out to us with any inquiries. We’re here to help!
Article Issued by Chiara Gazerro