(adopted October 2010, revised July 2011) -- Download in PDF format >>
AHPA recommends that herbal extracts marketed in the U.S. limit any contained residual solvents to the levels established by the current International Conference on Harmonization’s (ICH’s) document, Impurities: Guideline for Residual Solvents, except that this guidance does not apply to the ICHlimit of 50 mg per day for the class 3 solvent ethanol when it is present in liquid extracts formulated to contain ethanol, or for the class 3 solvent acetic acid when it is present in liquid extracts formulatedto contain acetic acid or vinegar.
With regard to this guidance, solvents identified in the cited ICH document as class 1 solvents (benzene;* carbon tetrachloride;* 1,2-dichloroethane;* 1,1-dichloroethene; and 1,1,1-trichloroethane), which are considered by ICH as unacceptably toxic or an environmental hazard, are not appropriate for use, and should not be used, in the manufacture of herbal extracts.
With regard to this guidance, solvents identified in the cited ICH document as class 2 solvents, which are considered by ICH to be inherently toxic, are listed in the table below with the ICH recommended upper limits for Permissible Daily Exposures (PDE) and concentration limits given in ppm assuming a 10 gram daily dose.
Class 2 Solvent
With regard to this guidance, solvents identified in the cited ICH document as class 3 solvents, which are considered by ICH as having low toxic potential, should be limited to 50 mg/day,† which equates to 5000 ppm or 0.5% in 10 grams. Their use should be limited by good manufacturing practice (GMP) or other quality based requirements. They are identified as the following:
| Class 3 Solvents
† This limit does not apply for ethanol when it is present in liquid extracts formulated to contain ethanol or for acetic acid when it is present in liquid extracts formulated to contain acetic acid or vinegar.
Adherence to this AHPA guidance does not infer compliance with California Proposition 65. Several of these solvents are listed by the State of California as chemicals known to the State to cause cancer or reproductive toxicity, including, as of the date of the last revision of this guidance, at least those solvents marked with an asterisk (*). The listing of ethanol with regard to California Proposition 65 refers only to its presence in alcoholic beverages.