By John Nickum
By John Nickum
When I first saw the acronym, GRAS, 25 years ago, in reference to actions taken by the Center for Veterinary Medicine (CVM), US Food and Drug Administration (FDA), I could only think in terms of “grass”, a vernacular term for marijuana. (I hasten to add, I was not a user.) I wondered why CVM might be involved with this kind of substance. Prior to that time, I had never heard of an acronym use to designate a feed ingredient as “Generally Recognized as Safe”. I suspect that many readers still are not familiar with the acronym, GRAS; and wonder why I am choosing to discuss it now. The answer is that the CVM recently updated (01/13/2015) information on animal feeds ingredients, some of which are used in fish feeds and are “Generally Recognized as Safe”.
A very important point that readers must keep in mind is that a substance is not GRAS, rather it is a particular use of a substance that is GRAS. Even use in the same way in a different species may not be Generally Recognized as Safe.
As I browsed the information in the recent announcement, it reminded me of discussions that took place roughly 25 years ago when my duties as National Aquaculture Coordinator for the US Fish and Wildlife Service (USFWS) included liaison activities with FDA CVM. One substance on the current GRAS list for feeds, canthaxanthin, did surprise me a little. It is recognized as safe when used as an additive in feeds for breeder hens to support the development of chicks; however, there have been intense disagreements about the use of canthaxanthin and/or astaxanthin in fish feeds.
Some consumer groups have insisted that fish, especially trout and salmon, reared on feeds containing these substances must be labeled as “color added”. Fish culturists have argued that these substances occur naturally in food items consumed by fish and produce pink-colored flesh through natural metabolic processes. My cynical opinion is that although consumer groups do much good, they are also prone to mistaken, belief-driven “crusades” that are not based on scientifically valid evidence. FDA CVM requires consensus from experts, based on scientifically valid evidence that a substance is safe before classifying it as GRAS; essentially the same level of evidence required for drug approval.
The presence of antibiotics, such as, Penicillin G potassium, or a probiotics, Bacillus cereus, in the GRAS list for animal feeds was also a bit surprising. There is much current controversy in medical circles about any routine use of any antibiotic with animals that could possibly lead to drug resistant bacteria.
One definition that can be applied to a substance and result in it being classified as a “drug” is that the substance is being used to control an infection and it changes the physiology of the animal being treated. Years ago, (1990s) this definition produced some heated arguments as to whether or not, ice could be classified as a drug. The course of some diseases can be altered by decreasing the water temperature in which fish are held. If ice was used for this purpose, would it be considered a “drug”?
The term GRAS is not used in conjunction with drugs. The similar term is, GRAS/E. A drug must be considered to be “effective” in addition to being recognized as safe. Again, it is important to emphasize that “safe and effective” is always conditional on following the specific directions for the species and the intended purpose. Most animal drugs are “approved”, rather than GRAS/E. They have gone through rigorous testing and review protocols and must be found to be efficacious (i.e. they actually provide the disease control that is claimed), safe for the animal receiving them, safe for the human administering them, and safe for the environment. As stated previously, approvals are always very specific. Drugs carry specific instructions limiting their use to the purposes, species, situation, and manner of administration. Any deviation from the instructions printed on the label, makes the user subject to potential “enforcement action”. Although unapproved uses are not always detected and prosecuted; it is extremely “unwise” to violate FDA regulations.
The FDA Center for Veterinary Medicine maintains a very complete website that provides information on substances currently on the GRAS and GRAS/E lists, as well as drugs on the approved list. The Aquatic Animal Drug Approval Partnership (AADAP) program co-located at the Bozeman (MT) Fish Technology Center also maintains fully up-to-date information on drugs approved for use on aquatic animals.
Perhaps a special benefit of the AADAP program for aquaculturists is that the biological scientists at the AADAP center are experienced fish culturists who understand exactly the situations that readers might present to them.
Readers who may want specific information from the FDA CVM or the AADAP program are advised to simply enter these names as search terms for an online search. An array of sites will appear. Choose the site most appropriate for each reader’s need.
— John C. Nickum
The FDA GRAS notification can be accessed from the following site: http://www.fda.gov/AnimalVeterinary/Products/AnimalFoodFeeds/GenerallyRecognizedasSafeGRASNotifications/ucm243845.htm.