Europe, chemical testing

Some plants accumulate alkaloids with very different chemical structures which are nevertheless related biosynthetically. In some cases the biosynthetic route may be branched, but in some it is rather clear that the more complicated structures arise from the simpler molecules. The latter condition is encountered in lupines. While the majority of alkaloids are of a coupled quinolizidine structure, two uncommon alkaloids, lupinine and epilupinine, are of a simple quinolizidine structure. The idea that lupinine is a precursor of sparteine, i.e., a bisquinolizidine, was first proven by experiments in which radioactive lupinine was fed to the plants and radioactive sparteine and its derivatives were isolated (Schuette, 1960 Nowacki et al.y 1961). In this study, varieties of Lupinus luteus from Palestine, Portugal, and central Europe were tested. There were plants that produced only one major alkaloid, either sparteine or lupinine however, the hybrid plants which produced sparteine also produced a small amount of lupinine. Consequently, it was a typical example of intermediate inheritance. The F2... 

Requirements for labelling of containers for supply may differ from those for conveyance. Key features of a supply label are to identify the substance (the chemical name in most cases) and any hazards and safety precuations. In Europe the classification, packaging and labelling of dangerous substances is covered by Directive 67/548/EEC as amended. This requires labels to identify appropriate risk and safety phrases (Tables 12.2 and 12.3) depending upon product properties. A substance is considered dangerous if in Part lA of an approved list or if it exhibits hazardous properties as defined in Schedule 1 for supply, or Schedule 2 for conveyance as shown in Tables 12.4 and 12.5. Substances not tested should be labelled Caution — substance not yet fully tested . Criteria for risk phrases are provided, e.g. as in Table 12.6 for toxic compounds. 

Within Europe there are thousands of organizations concerned with analytical measurement. However, within the broad field of testing, chemical measurement has generally been poorly represented. EURACHEM was established to address this concern by enabling analytical laboratories to work together, across international boundaries, on analytical measurement issues. EURACHEM s uniqueness as an organization comes from its primary concern, which is the analytical quality of chemical measurement. 

At the same time, the public s faith in science and technology was eroding. Radioactive fallout from atomic bomb tests was poisoning cows milk, and the thalidomide antinausea medicine prescribed to pregnant women in Europe had caused severe birth defects in 8000 children. Above all, the enormous growth of the chemical industry and pollution after World War II put public pressure on Congress to clean up the nation s air and water. 

The duration of such toxicity tests varies. In the USA, the FDA usually recommends a period of up to 2 years, whereas in Europe the recommended duration is usually much shorter. Chronic toxicity studies of biopharmaceuticals can also be complicated by their likely stimulation of an immune response in the recipient animals. In the context of new chemical entities (NCEs, i.e. low molecular weight traditional chemicals), not only can the drug itself exhibit a toxic effect, but so potentially can drug breakdown products. As proteins are degraded to amino acids, any potentially toxicity associated with protein-based drugs is typically associated with the protein itself and not degradation products. 

Finally, the different approaches to followup notification and testing impose additional requirements upon substances in Europe that do not apply to the same chemicals when they are marketed in the U.S. In the short term, at least, this discrepancy may well work to the advantage of companies doing business in this country (whether U.S.- or foreign-based). But, over time this also could lead European companies to seek changes ("harmonization" ) which either make the EEC requirements less stringent or incorporate an EEC-type of followup scheme into TSCA.(39)... 

Jimidar, M., Van Ael, W., De Smet, M., and Cockaerts, R (2002). Method validation and robustness testing of an enantioselective CE method for chemical quality control. LC-GC Europe (April), 230-241. 

The cnrrent registration procedure for new substances in Europe (high information reqnirements even for small quantities), together with the absence of binding test reqnirements for existing substances, represents a hindrance for substance innovation in the area of high-volume, established industrial chemicals. 

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