Friday, September 3, 2010

Revision of Isopropylbenzene status from Class 3 to Class 2

Keyoor has forwarded an interesting information. The jumping of chemicals from one list to another will continue. The information says that ICH is revising the status of Isopropylbenzene to Class 2 from existing Class 3 ! This is somewhat a demotion of Isopropylbenzene which was previously in the safer Class 3. It also means that there will be an upper specification limit to Isopropylbenzene and which must be continuously monitord and controlled.

Although I could not verify the source of this information, but I am sure Keyoor's information is correct and precise. Please read the following text which is copy-paste version:

Due to new toxicity studies in rats and mice, the solvent Isopropylbenzene is meant to be categorised as Class 2 instead of Class 3. A corresponding ICH draft guideline has been published and released for commenting by the public.
The ICH Guideline Q3C defining the limits for residual solvents as impurities in active pharmaceutical ingredients (APIs) and finished medicinal products as well as the methods for establishing their exposure limits has already been revised four times. The revisions concern among others provisions for calculating the PDEs (PDE = permissible daily exposure, denoting the maximum amount of a solvent that may be taken in with a medicinal product) for the solvents N-Methylpyrrolidone and Tetrahydrofuran. Now the guideline is about to be revised once more, the reason being that new toxicological data have been collected on the solvent Isopropylbenzene (called "Cumene" in the guideline). Hitherto, this substance has been categorised as Class 3, i.e. as a solvent with low toxicity. In general, these solvents have PDE values of 50 mg per day or more. Recent toxicity studies conducted in rats and mice clearly showed a heightened carcinogenic potential so that it has become necessary to assign Isopropylbenzene to the higher Class 2 and to calculate the PDE accordingly.
On 26 March 2010, the ICH Draft Consensus Guideline "Impurities: Guideline for Residual Solvents - PDE for Cumene" was published (Step 2 in the ICH process) and has since been available for commenting by the public. This guideline now requires the calculation of the PDE for Isopropylbenzene according to the rules for Class 2 solvents. After two further steps in the ICH process, this guideline will be integrated into the core document, which will then bear the name ICH Q3C(R5).
This new regulation might require manufacturers of APIs and medicinal products using Isopropylbenzene to make a considerable effort in changing their registration dossier (e. g. as a consequence of changes to the manufacturing process, the analytical methods etc.).

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