Test, control, and reference substances

Test, control, and reference substance mixtures with carrier.156... 

Analytical chemistry is a critical component of worker safety, re-entry, and other related studies intended to assess the risk to humans during and subsequent to pesticide applications. The analytical aspect takes on added significance when such studies are intended for submission to the U.S. Environmental Protection Agency and/or other regulatory authorities and are thus required to be conducted according to the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Good Laboratory Practice (GLP) Standards, or their equivalent. This presentation will address test, control, and reference substance characterization, use-dilution (tank mix) verification, and specimen (exposure matrix sample) analyses from the perspective of GLP Standards requirements. 

It is largely without debate that the term "reference substance" includes those chemical and biological materials that are used as standards in a study (i.e., those materials used for response comparison purposes, such as analytical reference standards). Normally, one thinks of reference substances as just referring to specimen (sometimes referred to as "matrix samples") analyses, but the characterization of test, control, and reference substances (see... 

Test, control, and reference substances used in worker safety and reentry testing also must be verified for their shelf-life stability prior to (or concomitantly with) use in a particular study. This means assuring stability... 

The GLP requirements for mixtures with carrier (40 CFR 160.113) were originally intended to address problems associated with the incorporation of test and control substances into feed, water, and other media for toxicology studies however, now these same requirements pertain to all other GLP-required studies, including those pertaining to re-entry and worker safety. The requirement involves (1) substantiation of test, control, and reference substance concentration through periodic analyses (2) verification of homogeneity and (3) determination of stability and, if applicable, also solubility. All of these requirements usually require chemical analysis, although bioassay may be necessary for microbial pesticides. 

These three analytical phases pertain to worker safety and re-entry testing as much as to other types of GLP studies, and, from a scientific soundness perspective, the method cycle also applies to test, control, and reference substance characterization (and mixtures with carriers). 

The EPA GLPs include a paragraph under Subpart G ( 160.135) that deals with physical and chemical characterization studies. This paragraph states that all provisions of GLP standards apply to certain specific physical and chemical characterization studies of test, control, and reference substances. These studies are listed. It also states that certain specified paragraphs do not apply to studies other than those listed. 

Receipt, identification, storage, handling, mixing, and method of sampling of the test, control, and reference substances. 

To assure that test, control, and reference substances or mixtures have been appropriately tested for identity, strength, purity, stability, and uniformity, as applicable... 

Receipt and storage of the test, control, and reference substances. 

The test, control, and reference substances identified by name, chemical abstracts service (CAS) number or code number, strength, purity, and composition, or other appropriate characteristics. 

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