Toxicity testing requirements, summary

As provided in the Botanical Guidance, clinical studies have been permitted for many botanical preparations prior to a complete set of conventional animal toxicity testing. The decisions were not difficult for submissions with substantial and well-documented history of past human use. But some other applicants had not presented an adequate summary of the past human experiences and had failed even to document well-known toxicity of the herbal ingredients. Between these two extremes, how to adjust the requirements of animal toxicity data and substitute that with large quantity but poor quality of human experiences is another big challenge to the regulatory agency in the review of botanical applications. 

Notifications or applications for clinical trials are supported by summaries or full reports on the preclinical pharmacology and safety assessment. The kind of safety data (e.g. the type and duration of toxicity tests), which are expected at this time, should correspond to the intended route and duration of application. Data on process details and on the quality of the product are not always required. But it must be kept in mind that clinical trials can only render useful results for the later product registration, if the quality characteristics of the tested product and its method of production are the essentially same as for the final product. If available, clinical data from trials in other countries must also be provided. Protocols for the intended clinical trials are an essential part of the application. 

Table 2.3 Summary of variability in toxicity resulting from testing single chemicals in aquatic toxicity tests (at least six data are required)21.

It is important to distinguish between assessment and measurement endpoints (Gaudet 1994). An assessment endpoint is an environmental value that has to be protected. If the risk assessment process results in an unacceptable risk for the defined environmental value, then risk reduction measures (e.g. remediation of site) are required. A measurement endpoint is a measurable environmental characteristic, such as the quantitative summary of the results of a toxicity test or a biological survey (Suter 1993). If assessment and measurement endpoints are not the same, it is necessary to constitute a quantitative relationship between these to enable the extrapolation of measured effects to the threatened environmental characteristic. 

The use of dispersants remains a controversial issue and special permission is required in most jurisdictions. In some jurisdictions, their use is banned. In Canada, special permission is required from Environment Canada, through the Regional Environmental Emergencies Team (REET) or regional response team. Similarly, in the United States, special permission is required from the U.S. Environmental Protection Agency (U.S. EPA) and in waters near shore, permission is also required from the state. In both countries, products must pass standard test procedures for toxicity and effectiveness before they can be used. Only about live of approximately 30 proposed products are approved for use in a typical year. In summary, around the world, there is a mixed usage of dispersants. Dispersants have not been used much in North America in the past 10 years and in Europe, only three countries occasionally use dispersants. 

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