Michael H. Henry, Ph.D.
Division of Animal Feeds
Center for Veterinary Medicine
Food and Drug Administration
Phone: 240-453-6861
E-mail: Mike.Henry@fda.hhs.gov

Presentation for Risk Management Agency
August 23, 2006 in Austin, Texas

Slide 2

Introduction

• CVM Responsibilities
• CVM Authority
• Action, Guidance and Advisory Levels and Tolerances
• Mycotoxins and Regulatory Limits
• Use of Contaminated Grains
• Blending
• Special Provisions
• Export Requirements

Slide 3

CVM Responsibilities

• The Center for Veterinary Medicine (CVM) is a consumer protection organization. We foster public and animal health by approving safe and effective products for animals and by enforcing other applicable provisions of the Federal Food, Drug, and Cosmetic Act and other authorities.
• Within CVM, the Division of Animal Feeds is responsible for ensuring that animal feeds are safe and wholesome.

Slide 4

CVM Authority

• Federal Food, Drug, and Cosmetic Act
  
  • SEC. 402. [21 U.S.C. 342] A food shall be deemed to be adulterated
    • (a)(1) If it bears or contains any poisonous or deleterious substance which may render it injurious to health; …

Slide 5

CVM Authority

• Federal Food, Drug, and Cosmetic Act
  • TOLERANCES FOR POISONOUS INGREDIENTS IN FOOD
    • SEC. 406. [21 U.S.C. 346] paraphrasing -- When any poisonous or deleterious substance cannot be avoided by good manufacturing practice, the Secretary shall promulgate regulations limiting the quantity therein or thereon to such extent as he finds necessary for the protection of public health…
      

Slide 6

CVM Authority

• Federal Food, Drug, and Cosmetic Act
  • TOLERANCES FOR POISONOUS INGREDIENTS IN FOOD
    • SEC. 406 (continued) …In determining the quantity of such added substance to be tolerated in or on different articles of food the Secretary shall take into account the extent to which the use of such substance is required or cannot be avoided in the production of each such article, and the other ways in which the consumer may be affected by the same or other poisonous or deleterious substances.

Slide 7

Action, Guidance and Advisory Levels and Tolerances

• Tolerances represent limits above which the product is adulterated as a matter of law. FDA can take legal action to remove products from the market without having to prove them unsafe.
• Action, guidance, and advisory levels are not binding on the Agency.
• Where no action, guidance or advisory level or tolerance exists, FDA may consider taking regulatory action against the product at levels it deems to be unsafe.
  

Slide 8

Mycotoxins are a Potential Risk to both Humans and Livestock

Slide 9

Mycotoxins and Regulatory Limits

• Mycotoxins
  • Secondary metabolites of certain species of fungi (molds)
  • Approx. 300 listed mycotoxins
  • Genera of toxigenic fungi:
    • Aspergillus, Penicillium and Fusarium
  • Mycotoxins of greatest importance worldwide:
    • aflatoxins, trichothecenes, fumonisins, zearalenone, ochratoxin A and ergot alkaloids

Slide 10

Mycotoxins and Regulatory Limits

• CVM focuses on 5 major mycotoxins in the U.S.:
• Action levels – aflatoxins  -- Compliance Policy Guidance Manual Section 683.100
• Guidance levels – fumonisins
• Advisory levels – vomitoxin (DON)
• No action, guidance or advisory levels for ochratoxin A or zearalenone have been established by the FDA in animal feeds (these 2 mycotoxins are handled on a case-by-case basis.

Slide 11

Aflatoxins

• produced by Aspergillus sp. ( A. flavus and A. parasiticus)
• common feed substrates such as corn, cottonseed, peanuts, and sorghum.
• occur most commonly in warm, humid regions of the south and central regions of the U.S.
• high levels of aflatoxins are associated with above-average temperature and below-average rainfall (micro-climate)

Slide 12

Aflatoxins

• four major aflatoxins in feed: B1, B2, G1 & G2 (B1 + B2 + G1 + G2 = total aflatoxins)
• one major aflatoxin in milk: M1
• inhibits protein synthesis, one of the most potent carcinogens - interacts with DNA
• young animals more susceptible than adults
• monogastric animals more susceptible than ruminants
  

Slide 13

Action levels for total aflatoxins in livestock feed

Class of Animals	Feed	Aflatoxin Level
Finishing beef cattle	Corn and peanut products	300 ppb
Beef cattle, swine or poultry	Cottonseed meal	300 ppb
Finishing swine over 100 lb.	Corn and peanut products	200 ppb
Breeding cattle, breeding swine and mature poultry	Corn and peanut products	100 ppb
Immature animals	Animal feeds and ingredients, excluding cottonseed meal	20 ppb
Dairy animals, animals not listed above, or unknown use	Animal feeds and ingredients	20 ppb

Slide 14

Fumonisins

• produced by Fusarium sp. (F. verticillioides)
• found worldwide, mainly in corn and particularly corn screenings
• high levels associated with hot and dry weather, followed by periods of high humidity
• three major fumonisins in feed are B1, B2 & B3 (B1 + B2 + B3 = total fumonisins)
• most susceptible species are horses (equine leukoencephalomalacia) and rabbits
• suspected carcinogens
  

Slide 15

Guidance levels for total fumonisins in animal feeds

Slide 16

Vomitoxin

• produced by members of genus Fusarium (especially F. graminearum)
• commonly found on wheat, barley, rye and oats
• reported most frequently in cool, temperate regions (northern U.S. and Canada)
• member of the trichothecene family of mycotoxins
• inhibitor of protein synthesis, affecting GI tract and immune system
• swine most susceptible -- causing vomiting and feed refusal

Slide 17

Advisory levels for vomitoxin (DON) in livestock feed

Slide 18

Ochratoxin A

• Produced by Aspergillus sp. (A. ochraceus) and Penicillium sp. (P. viridicatum)
• Highest levels usually found in cereal grains (corn, barley, wheat and rye)
• At least nine ochratoxins identified, but ochratoxin A is the most common and has the greatest toxicological significance
• Nephrotoxic and a suspected carcinogen
• No FDA action, advisory or guidance levels established for ochratoxin A in US feed

Slide 19

Zearalenone

• Produced by Fusarium sp. (primarily F. graminearum)
• Common substrates are corn, wheat, barley, occasionally oats
• Production favored by high humidity and low temperatures
• Estrogenic mycotoxin, swine most susceptible – vulvar swelling in gilts
• Toxicity related to reproductive system
• No FDA action, advisory or guidance levels established for zearalenone in US feed

Slide 20

Use of Contaminated Grains

• Action, guidance and advisory levels were established, in part, to protect public health.
• Grains with mycotoxin(s) that exceed the appropriate action, advisory or guidance levels may be considered by CVM as adulterated.
• Grains with mycotoxin(s) exceeding the highest action, advisory or guidance levels may be considered by CVM as unfit for use in animal feed.
  

Slide 21

FDA Compliance Policy Guide on Blending

• Sec. 555.200 Adulterated Food Mixed with Good Food (CPG 7120.14)
• BACKGROUND:
• The Commissioner of Food and Drugs responded on March 15, 1974, to a suggested plan involving the deliberate addition of fish which may contain excessive mercury residues to other fish which contain lower levels of mercury. The plan was expected to yield a product whose average mercury content fell below the FDA guideline. In that response the Commissioner expressed our policy regarding the deliberate mixing of adulterated food with good food.
• POLICY:
• In our opinion, the deliberate mixing of adulterated food with good food renders the finished product adulterated under the Federal Food, Drug, and Cosmetic Act, regardless of the final concentration of contaminant in the finished food. We, therefore, cannot agree to a plan which incorporates this concept.
• Issued: 10/1/80
  

Slide 22

Summary of FDA's Blending Policy

• Blending of “clean” grain with adulterated grain is generally not permitted and the final product resulting from blending is unlawful, regardless of the level of the contaminant.
• Exception: CVM may permit “blending” under special provisions

Slide 23

Special Provisions

• CVM has made a special provision for the States with extraordinary situations concerning aflatoxins in corn.
• States may make a written request to CVM for permission to blend corn for up to a year (a limited period of time) to meet the FDA aflatoxin action levels for certain animals (feedlot cattle, mature poultry, finishing swine, etc.)
• States must demonstrate that an extraordinary situation exists (e.g., unusual drought conditions).
• Permission is granted to the State and the State is responsible for ensuring the activity is conducted safely.
• To date, CVM has not permitted blending of corn with > 500 ppb total aflatoxins.
• FDA aflatoxin action levels are still applicable.
  

Slide 24

Extraordinary Situations

High Temperature and Low Rainfall

Slide 25

Export Requirements*

• Federal Food, Drug and Cosmetic Act
  • Imports and Exports
    • SEC. 801 [21 U.S.C. 381] (e)(1) A food, drug, device or cosmetic intended for export shall not be deemed to be adulterated or misbranded under this Act if it
    • (A) accords to the specifications of the foreign purchaser
    • (B) is not in conflict with the laws of the country to which it is intended for export
    • (C) is labeled on the outside of the shipping package that is intended for export, and
    • (D) is not sold or offered for sale in domestic commerce

*For export at the time of production. Product was not offered for sale in the U.S.

Slide 26

Acknowledgements

• Randall Lovell, DVM, Ph.D.
• Karen Ekelman, Ph.D.
• Office of Surveillance and Compliance