Guidelines and Guidance Documents

A WHO/IPCS criteria document on human exposure assessment presents the concepts, rationale, and statistical and procedural methodologies for human exposure assessment, but does not give detailed guidance on technical issues regarding instrumental and laboratory methods (WHO/IPCS 2000). 

The International Programme on Chemical Safety (IPCS) has undertaken a project to harmonize approaches to the assessment of risk from exposure to chemicals through increased understanding. The project focuses on specific issues and attempts to achieve agreement on basic principles. Among the project s focus areas are exposure assessment and terminology for exposure assessment and risk assessment. The status for the activities of the harmonization project is published in a newsletter (WHO/IPCS 2007). 

Under this project, an IPCS Harmonization Project Document on the Principles of Characterizing and Applying Human Exposure has been published (WHO/IPCS 2005). This document sets out the characteristics of exposure assessment models that should be described to aid in model selection by exposure assessors. The document summarizes current practice in exposure modeling and principles for evaluating exposure models, but does not provide a comprehensive list of existing exposure models. The focus of the document is on the discussion of general properties of exposure models and how they should be described. The characteristics of different modeling frameworks are examined, and 10 principles are recommended for characterization, evaluation, and use of exposure models in order to help model users select and apply the most appropriate models. The report also discusses issues such as validation, input data needs, time resolution, and extrapolation of the model results to different populations and scenarios. 

Also under the IPCS harmonization project, a working group is preparing a harmonized set of principles for the treatment of uncertainty in exposure assessment. The document will review the types of uncertainty analyses used in exposure assessments, evaluate their effectiveness in giving decision-makers the types of information they need, and derive a set of principles for uncertainty analysis (WHO/IPCS 2006). 

OECD has not published any guidelines for exposure assessment for workers or consumers. 

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In order to understand the use and intent of the various immunotoxicology regulatory guidelines and guidance documents, the difference between two concepts familiar to toxicologists should be emphasized. Hazard, identification refers to a method which is essentially qualitative that is, it is designed to detect the ability of a test article to produce a certain (in the context of toxicology) adverse effect, without reference to exposure issues. Risk assessment, on the other hand, takes into consideration method, dose, and duration of exposure, condition(s) of the exposed population, and concurrent... 

It has always been agreed that safety assessment of GM plants should be carried out on a case by case basis. For that reason the various official guidelines and guidance documents have emphasised principles rather than laid down hard and fast mles to cover all cases. Early discussions of... 

Table 1 EU Clinical Trials Directive Principal Elements of Articles and Primary Applicable Draft Guidelines or Guidance Documents (December 2003) for Implementation...

The ICH have issued guidelines on how to organise the data in the modules. These guidance documents, which are shown in Table 6.3, deal primarily with how the information should be organised, whereas advice on how to generate the data is provided in the quality, safety and efficacy guidelines that were discussed in the previous chapters. We shall now look at the stmcture of the modules in a little more detail, starting with the basic data modules. 

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

Finally, in the risk characterization step, the PEC/PNEC quotient that defines the risk of the substance in the environment is calculated. If the quotient (PEC/PNEC) is less than 1, the substance do not present risk to the environment. More information is available in the European Commission Technical Guidance Document on Risk Assessment [3] and in the United States Environmental Protection Agency s Guidelines for Ecological Risk Assessment [6]. 

In addition to the regulations under 21 CFR, the FDA publishes Guidance for Industry and documents called Points to Consider (PTCs) as guidelines and recommendations to industry to adopt as part of the compliance program. 

US-EPA has formed the Risk Assessment Forum, a standing committee of senior US-EPA scientists, to promote US-EPA consensus on difficult and controversial risk assessment issues and to ensure that this consensus is incorporated into appropriate US-EPA risk assessment guidance. To fulhil this purpose, the Forum assembles US-EPA risk assessment experts in a formal process to study and report on issues from a US-EPA scientific perspective. Major Fomm guidance documents are developed in accordance with the US-EPA s regulatory and policy development process and become US-EPA pohcy upon approval by the Administrator or the Deputy Administrator. The Risk Assessment Forum products include risk assessment guidelines, technical panel reports on special risk assessment issues, and peer consultation and peer review workshops addressing controversial risk assessment topics. 

The guidance document offers a comparison of TG 420 (Fixed Dose Method), TG 423 (Acute Toxic Class Method), and TG 425 (Up-and-Down Procedure). The purpose of this Guidance Document is to provide information to assist with the choice of the most appropriate Guideline to enable particular data requirements to be met while reducing the number of animals used and animal suffering. The Guidance Document also contains additional information on the conduct and interpretation of test guidelines 420, 423, and 425. 

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