Should I panic when an OEL or ADE changes?

In the field of occupational and product toxicology for the pharmaceutical industry, it is quite common to see the numerical value for an occupational exposure limit (OEL) or acceptable daily exposure (ADE) change over the course of product development. These changes can occur for several reasons. These reasons can include:

New data or newly "discovered" data. With the world of the internet, new data and new studies get published all the time. According to the National Science Foundation, in 2018, there were over 2.5 million scientific and engineering articles published. In addition, search engines, such as Google, are revised 500 to 600 times per year with minor changes, and 3 to 5 times per year with major changes. The major changes can dramatically impact the indexing of scientific articles that were previous hidden from view in the search engines. To make matters more difficult, search engine companies do not announce their changes or tell anyone what has changed. It can be like one day your search results will be one set and the next day your search results will be significantly different for the same search query.
Longer studies and/or more human experience. The longer the drug has been on the market, the greater the variability in the number of patients that have used the drug. This provides the occupational and product quality toxicologist with greater certainty that all the adverse effects have been identified and reduces the uncertainty.
New regulatory guidance documents or industry best practices. The field of occupational and product toxicology continues to evolve. New studies are performed or case histories are published that necessitate the need to change an OEL and/or ADE.

In most cases, as the data gets more comprehensive, the numerical OEL and/or ADE value goes higher in value and the exposure control band assignment goes down (i.e. from an exposure control band 3 to an exposure control band 2); however, while rare, occasionally the numerical OEL or ADE will decrease in value such that the OHC goes up (i.e. OHC from 2 to 3). In these cases it is often a challenging risk communication issue for the EHS professional because employees will be asking questions such as “Was I over-exposed?” or “Will I be harmed?” This is where it is important that an environmental, health and safety professional in the pharmaceutical industry have a strong understanding of the underlying concepts and assumptions behind occupational exposure limits. These concepts include the following:

Most OEL and/or ADE values assume long-term exposure. With the exception of short-term exposure limits (STELs) and ceiling limits, OELs assume that a worker will be potentially exposed to a compound for 8-hours per day, 5-days per week, for an entire working lifetime (approximately 40 years). ADE values assume that the patient will be expose to the drug for an entire lifetime.

OEL and/or ADE values are not bright lines between safe and unsafe. The majority of OELs and ADEs use the uncertainty factor (now called adjustment factors) method for determining the OEL or ADE value. In most cases these OEL and/or ADE values are protective over a wide range of airborne concentrations.

The starting point for determining an OEL or ADE is at the very bottom of the dose-response curve. When using the adjustment factor method for determining an OEL the occupational toxicologist is typically tasked with finding what is called the “point of departure (PoD).” As defined by the EPA, “A 'point of departure' (POD) marks the beginning of extrapolation to lower doses. The POD is an estimated dose (usually expressed in human-equivalent terms) near the lower end of the observed range, without significant extrapolation to lower doses.” In other words, the PoD is near the very bottom of the dose-response curve where the slightest response was observed. Once the PoD is selected, then the occupational toxicologists applies the adjustment factors to even further lower the acceptable dose.

OELs assume that there was no benefit from personal protective equipment worn. The numerical value of the OEL is based solely on the inherent toxicology of the compound and makes no adjustment for respiratory protection worn or engineering controls used (that’s part of the risk assessment process).

So if the numerical OEL goes down, or your OHC goes up, should you panic? Well the answer is no; but you should gain an understanding as to why the OEL or OHC has changed and make the appropriate adjustments to your operations and activities.

As always, if you have any questions regarding potent compound safety or occupational toxicology, please contact us at Affygility Solutions.