Can you add a short-term exposure limit (STEL) or ceiling limit to the monograph?
Unfortunately, in most cases the answer is “no.” In general, establishing compound-specific ceiling limits or short-term exposure limits (STELs) for active pharmaceutical ingredients (API) is not necessary or not practical, since the underlying toxicology data for the API is lacking the high-‐dose, short-‐term data. There are exceptions to this statement for compounds that have highly irritating, narcosis, or other acute effects. As indicated in the Introduction to TLV/BEI Guidelines by the American Conference of Governmental Industrial Hygienists (ACGIH, 2015), STELs are described as follows:
“A 15-‐minute TWA exposure that should not be exceeded at any time during a workday, even if the 8-‐hour TWA is within the TLV–TWA. The TLV–STEL is the concentration to which it is believed that workers can be exposed continuously for a short period of time without suffering from 1) irritation, 2) chronic or irreversible tissue damage, 3) dose-‐rate-‐dependent toxic effects, or 4) narcosis of sufficient degree to increase the likelihood of accidental injury, impaired self-‐ rescue, or materially reduced work efficiency. The TLV–STEL will not necessarily protect against these effects if the daily TLV–TWA is exceeded. The TLV–STEL usually supplements the TLV–TWA where there are recognized acute effects from a substance whose toxic effects are primarily of a chronic nature; however, the TLV–STEL may be a separate, independent exposure guideline. Exposures above the TLV–TWA up to the TLV–STEL should be less than 15 minutes, should occur less than four times per day, and there should be at least 60 minutes between successive exposures in this range. An averaging period other than 15 minutes may be recommended when this is warranted by observed biological effects.”
Additionally, in the ACGIH guide, ceiling limits are described as: “The concentration that should not be exceeded during any part of the working exposure.”
The key point in the both above descriptions is that both STELs and ceiling limits are applicable when the compound has an acute health effect, not a chronic effect. The vast majority of OELs for active pharmaceutical ingredients are based on repeat‐dose, chronic exposures and on an eight-‐hour exposure period. So, an alternate approach, in the case where a compound-‐specific STEL or ceiling limit does not exist, is to follow the “excursion limit” concept (also called “the 3 by 5 rule”), as presented ACGIH guidebook. Excursion limits are described as:
“Excursion Limits. For many substances with a TLV–TWA, there is no TLV-STEL. Nevertheless, excursions above the TLV–TWA should be controlled, even where the 8-‐hour TLV–TWA is within recommended limits. Excursion limits apply to those TLV–TWAs that do not have TLV–STELs."
Excursions in worker exposure levels may exceed 3 times the TLV– TWA for no more than a total of 30 minutes during a workday, and under no circumstances should they exceed 5 times the TLV–TWA, provided that the TLV–TWA is not exceeded. The approach here is that the maximum recommended excursion should be related to the variability generally observed in actual industrial processes.” The approach above is that no more than 3 times the OEL for a total of 30 minutes during a workday, and under no circumstances should exposures exceed 5 times the OEL.