----------------------------------------------------------------------------------------------------------------- STUDY on the ASSESSMENT OF PLANTS/HERBS, PLANT/HERB EXTRACTS AND THEIR NATURALLY OR SYNTHETICALLY PRODUCED COMPONENTS AS “ADDITIVES” FOR USE IN ANIMAL PRODUCTION CFT/EFSA/FEEDAP/2005/01 Authors: Ch. Franz, Vienna (editor-in-chief) R. Bauer, Graz R. Carle, Hohenheim D. Tedesco, Milano A. Tubaro, Trieste (pharm/tox) K. Zitterl-Eglseer, Wien Co-workers: K. Barker-Benfield, Vienna S. Galletti, Milano L. Garavaglia, Milano A. Tava, Milano K. Schütz, Hohenheim U. Schweiggert, Hohenheim E.-M. Wenzig, Graz 1 ----------------------------------------------------------------------------------------------------------------- TABLE OF CONTENTS Foreword 3 Assessment of plants/herbs and extracts Introduction 5 Monographs of the following species: Achillea millefolium L. 9 Allium sp. 18 Aloe vera 43 Astragalus gummifer 53 Borago officinalis 61 Calendula officinalis 74 Echinacea 88 Eucalyptus officinalis 97 Foeniculum vulgare 107 Gaultheria procumbens 116 Gentiana lutea L 123 Lavandula sp. 133 Macleaya/Sanguinaria 140 Matricaria recutita 155 Mentha piperita 170 Origanum sp 182 Petroselinum crispum 194 Pimpinella anisum 201 Ribes nigrum 210 Rosmarinus officinalis 218 Salvia officinalis 230 Silybum marianum 237 Thymus vulgaris 250 Uncaria tomentosa 259 Urtica sp. 269 Valeriana officinalis 277 Conclusion 287 References 292 List of Acronyms 294 Index of Authors 297 2 Foreword ----------------------------------------------------------------------------------------------------------------- FOREWORD In September 2003 the European Parliament and the Council of the European Union adopted the Regulation No. 1831/2003 on additives for use in animal nutrition. The purpose of this regulation is to establish a Community procedure for authorising the placing on the market and use of feed additives and to lay down rules for the supervision and labelling of feed additives and premixtures in order to provide the basis for the assurance of a high level of protection of human health, animal health and welfare, environment, and “users and consumers” interests in relation to feed additives, whilst ensuring the effective functioning of the internal market. Any person seeking an authorisation for a feed additive or for a new use should submit an application to the European Commission and the European Food Safety Authority (EFSA), as provided by Article 7 of Regulation No. 1831/2003 at least one year before the expiry date of the previous authorisation for additives with a limited authorisation period, and within a maximum of seven years after the 18th October 2004, date of entry into force of this Regulation for additives authorised without a time limit or pursuant Directive 82/471/EEC. The guidelines for the applicants to prepare the dossier for the authorisation of additives in animal nutrition are provided according to Directive 2001/79/EC, until specific guidelines following Regulation No. 1831/2003 will be established by the Panel on Additives and Products of Substances used in Animal Feed (FEEDAP) of the European Food Safety Authority (EFSA). Under the current regulation detailed guidelines for some family of products are completely missing, that it is the case of the plants/herbs, plant/herb extracts and their naturally or synthetically produced components. For this reason it is one of the priorities of the FEEDAP Panel to implement guidelines/guidance for these types of compounds. It has been observed that plant/herbs and their extracts are increasingly being used (and informally marketed) not only as sensory additives, but also for other purposes not covered by the legislation, notably better growth or feed conversion, improved meat quality, and for prophylactic purposes. There are strong indications that such use will further increase as replacement additives for the antibiotic growth promoters whose use will be prohibited by the end of 2005. Nowadays, a compiled list of these compounds or extracts does not exists although the European Federation of Animal Feed Additive Manufacturers (FEFANA) notes that some 280 plant extracts and a further 1700 chemically defined compounds have been used within Member States as sensory additives in animal feeds. The results of this study will be used by EFSA, in consultation with the European Commission, Member States and other stakeholders, to provide input for the development of guidance/guidelines documents for the authorisation of plants/herbs, plant/herb extracts and their naturally or synthetically produced components for use in animal nutrition. Claudia Roncancio Peña FEEDAP Panel 3 Foreword ----------------------------------------------------------------------------------------------------------------- 4 Introduction ----------------------------------------------------------------------------------------------------------------- ASSESSMENT OF PLANTS/HERBS, PLANT/HERB EXTRACTS AND THEIR NATURALLY OR SYNTHETICALLY PRODUCED COMPONENTS AS “ADDITIVES” FOR USE IN ANIMAL NUTRITION CFT/EFSA/FEEDAP/2005/01 INTRODUCTION The last two decades have seen a substantial increase in use of herbs/botanicals and their products not only as herbal medicinal products and for food supplements, but also in the field of animal nutrition. The use of herbal feed additives, which include essential oils and (exotic) herbal mixtures, is extensively promoted by the producers, but the scientific background underpinning their use often is limited. Consequently an adequate knowledge of quality control (content of active substance(s) stability), efficacy and safety is often lacking. A critical examination of bioactive plant products has to cover analytical aspects, absorption, bioavailability and molecular functionality in addition to feeding experiments and technology development. Finally, quality assurance management (analytical methods) is considered an absolute prerequisite. Presently herbs/botanicals are used by the feed industry only as sensory additives, functional group “flavouring compounds”. These are defined by Annex I of Regulation (EC) No 1831/2003 as “substances the inclusion of which in feedingstuffs increases smell or palatability”. This regulation foresees the evaluation of all herbal products and their derived extracts currently on the market and notified to the European Commission. This is to be completed by 2010. BACKGROUND The challenge that food suppliers face is to accept the consequences of consumers’ demands and aspirations and to become more proactive in developing scientific approaches to meet these demands. In this context, sustainable farming must be guided by the following principles: - animal friendly - scientifically proven to respect the welfare of livestock and to enhance their physiological condition through nutrition - consumer friendly – 100% natural, traceable, no risk of pathogenic cross-resistance, non-GM products, no harmful effects on humans - environmentally friendly – products that actively reduce the environmental impact of intensive livestock production through the reduction of both atmospheric emissions and non-organic effluents. In-feed antibiotics have been used for growth promotion and prophylaxis against enteric pathogens for the last 50 years. However, recognition that the continuing use of antibiotics for growth promotion contributed to a growing resistance among human pathogens has resulted in these additives have been withdrawn stepwise since 1994. This withdrawal was completed in 2006 and the use of antibiotics for growth promotion is now prohibited in the EU member states. Proposed alternatives to in-feed antibiotics are extremely diverse and include organic acids, pre- and pro-biotics, enzymes and especially herbs and herbal products/botanicals. For most of the ever-evolving area of feed additives, the flavour and appetizing substances based on plants/plant extracts represent a real alternative both for the European feed industry and the livestock production. Although the understanding of their modes of action is a prerequisite for their optimal application and use, in terms of efficacy, at the moment, a full understanding of these aspects in animals is not achieved yet. For example, phytocompounds act along the animal’s digestive tract to improve appetite, bacterial modulation, and are able to induce a number of very positive benefits on well being (Kamel, 2001). The antimicrobial properties of 5 Introduction ----------------------------------------------------------------------------------------------------------------- plant extracts and herbs can be dose-dependently bacteriostatic and/or bactericidal. In addition, several investigations have been performed concerning the changes in digestive physiology and digestion at weaning (Zabielski et al., 1999), the microbiology of the gut (Jensen, 1998) and the implementation of test models in poultry (Hess, 2002). Herbs and herbal products/botanicals represent a large array of nutraceuticals, which are defined as “any non-toxic feed component that has scientifically proven health benefits including disease prevention or treatment” (Boothe, 1997). Many classes of plant products have been shown to have antimicrobial activity including phenolics, quinones, flavones, tannins, coumarins, several compounds of essential oils (mono- and sesquiterpenes, phenylpropanoids) and isothiocyanates. One perceived advantage is that many of these plant products occur in complex mixtures and not only as single compounds, hence resistance is less