Does the occupational exposure limit (OEL) or acceptable daily exposure (ADE) value change based on the formulation?
No. The OEL or ADE of a specific compound is based solely on the toxicology of the compound. The toxicology of the compound does not change. However; if the formulation changes, the probability of exposure may change. The best way to understand this is to consider the following equation:
Risk = Hazard × Probability of exposure.
Again, the hazard of the compound is based solely on the toxicology of the active pharmaceutical ingredient (API). The probability of exposure is based on many factors. These factors include, but not limited to the following:
- Scale of the process (mg to kg);
- Physical state (dry solid, liquid, solution, wet cake, etc.);
- Amount of energy imparted on the process;
- Engineering controls used;
- Frequency of exposure;
- Duration of exposure;
- Percentage of the API in the formulation; and
- Many others.
If you think about it, changing the OEL based on the formulation would create the following issues:
- There would be an endless number of OEL values for the same compound. Regulatory agencies always present exposure limit values (PEL, TLV, MAK, etc.) as a single number.
- There would need to be an air monitoring method for the formulation "mixture." Sure, you could try either a "total dust" monitoring method or a particle counter, but numerous studies in the pharmaceutical industry indicate these don't work well (either not sensitive enough or the particle size distribution of the formulation doesn't match up well with the particle range of the counter).
- There is the incorrect assumption that the formulation becomes airborne as a homogenous mixture. This is incorrect because what become airborne depends on many factors such as particle size, moisture content, electrostatic properties and more.
As an example, let use finger nail polish remover. One of the ingredients in finger polish remover is acetone. The ACGIH TLV-TWA for acetone is 250 ppm. However, the amount of acetone in finger polish remover is less than 60%; therefore, the probability of exposure and the over risk is reduced, but the TLV-TWA for acetone still is 250 ppm.
The proper way to adjust for formulations is to perform a risk assessment and keep the OEL value constant and adjust the "probability" of exposure based on the factors first stated.
For more insight, please view the following video: