General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine: Annex II. Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines a : Acute Toxicity Test

General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine
(2000; 80 pages) [French] [Spanish]

Table of Contents

	Acknowledgements
	Foreword
	Introduction
		Definitions
		General Considerations
		Purpose of the Guidelines
		Use of the Guidelines
	1. Methodologies for Research and Evaluation of Herbal Medicines
		1.1 Definitions
		1.2 Botanical Verification and Quality Considerations
		1.3 Research and Evaluation of Safety and Efficacy
	2. Methodologies for Research and Evaluation of Traditional Procedure-Based Therapies
		2.1 Types of Traditional Procedure-Based Therapies
		2.2 Evaluation of Safety and Efficacy
	3. Clinical Research
		3.1 General Considerations
		3.2 Literature Review
		3.3 Selection of Study Design
	4. Other Issues and Considerations
		4.1 Pragmatic Research Issues
		4.2 Ethics
		4.3 Education and Training
		4.4 Surveillance Systems
	References
	Annexes
		Note
	Annex I. Guidelines for the Assessment of Herbal Medicines^a
		Introduction
		Assessment of Quality
		Assessment of Safety
		Assessment of Efficacy
		Intended Use
		Utilization of these Guidelines
	Annex II. Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines^a
		Definition of Terms
		Guidelines for Toxicity Investigation of Herbal Medicines
		Acute Toxicity Test
		Long-Term Toxicity Test
	Annex III. Report of a WHO Consultation on Traditional Medicine and AIDS: Clinical Evaluation of Traditional Medicines and Natural Products^a
		Preclinical Considerations
		Clinical Considerations
		Recommendations
	Annex IV. Definition of Levels of Evidence and Grading of Recommendation^a
		Levels of Evidence
		Grading of Recommendations
	Annex V. Guidelines for Levels and Kinds of Evidence to Support Claims for Therapeutic Goods^a
		Claims Based on Evidence of Traditional Use
		What Kinds of Claims Does the Evidence Support?
		Registrable Diseases List
		Claims Based on Evidence of Traditional Use
	Annex VI. Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products^a
		Ethical Principles
	Annex VII. Guidance for Industry: Significant Scientific Agreement in the Review of Health Claims for Conventional Foods and Dietary Supplements^a
		Identifying Data for Review
	Annex VIII. Guideline for Good Clinical Practice^a
		Clinical Trial Protocol and Protocol Amendment(s)
	Annex IX. WHO QOL (Quality of Life) User Manual: Facet Definitions and Response Scales^a
		Introduction
		Overall Quality of Life and Health
		Domain I - Physical Domain
		Domain II - Psychological
		Domain III - Level of Independence
		Domain IV - Social Relationships
		Domain V - Environment
		Domain VI - Spirituality/Religion/Personal Beliefs
		Response Scales
	Annex X. Participants in the WHO Consultation on Methodologies for Research and Evaluation of Traditional Medicine

Acute Toxicity Test

Animal species

Some regulatory agencies require that at least two species be used, one of them to be selected from rodents and the other from non-rodents.

Sex

In at least one of the species, males and females should be used.

Number of animals

In the case of rodents, each group should consist of at least five animals per sex. In the case of non-rodents, each group should consist of at least two animals per sex.

Route of administration

Ordinarily, the oral route is sufficient as this is the normal route of clinical administration. However, some regulatory agencies suggest in addition a parenteral route of administration.

In cases where it is proposed to administer the herbal preparation to a human subject by the parenteral route, it may be sufficient to use this route alone for animal testing.

Dose levels

A sufficient number of dose levels should be used in rodents to determine the approximate lethal dose. In non-rodents, sufficient dose levels should be used for the observation of overt toxic signs.

Frequency of administration

The test substance should be administered in one or more doses during a 24-hour period.

Observation

Toxic signs and the severity, onset, progression and reversibility of the signs should be observed and recorded in relation to dose and time. As a general rule, the animals should be observed for at least seven to fourteen days.

Animals dying during the observation period, as well as rodents surviving to the end of the observation period should be autopsied.

If necessary, a histopathological examination should be conducted on any organ or tissue showing macroscopic changes at autopsy.