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Guidance for Industry  
 
Concerns Related to the use of Clove Oil as 
an Anesthetic for Fish  
 
(This version of the guidance replaces the version that was made available in June 
11, 2002. This guidance document has been revised to clarify our position on the 
use of clove oil as an anesthetic for fish.) 
 
This level 2 guidance document provides information regarding the use of clove oil and 
its components as an anesthetic for fish. 
 
Comments and suggestions regarding this guidance document should be submitted to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Room 1061, Rockville, MD 20852.    Submit electronic comments to 
http://www.regulations.gov.  All comments should be identified with the exact title of the 
document.  
For questions regarding information about regulatory discretion, contact Scott Melton, 
Center for Veterinary Medicine (HFV-232), Food and Drug Administration, 7519 
Standish Place, Rockville, MD  20855, 240-276-8666, email:  scott.melton@fda.hhs.gov  
 
. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine 
April 24, 2007    
Concerns Related to the use Clove Oil as an Anesthetic for Fish  
 
 
This document represents the Agencys current thinking on concerns related to the use of clove oil as 
an anesthetic for fish.  It does not create or confer any rights for or on any person and does not 
operate to bind the Food and Drug Administration (FDA) or the public.  An alternative approach may 
be used as long as it satisfies the requirements of the applicable statute and regulations.  If you want to 
discuss an alternative approach, contact the FDA staff responsible for implementing this guidance.  If 
you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of 
this guidance. 
 
Introduction 
The Food and Drug Administration's Center for Veterinary Medicine (FDA/CVM) has 
had many inquiries regarding the use of clove oil, and/or the active components of clove 
oil, as an anesthetic for use in fish.  This guidance document provides information 
regarding CVMs position for the use of clove oil and its components as an anesthetic for 
fish. 
Background 
Current scientific information suggests that clove oil is actually a mixture of different 
compounds.  Some of the ingredients of clove oil include eugenol, isoeugenol and 
methyleugenol.  Although clove oil is generally 85 to 95% eugenol, the remaining 
components may vary.  Isoeugenol is the compound considered by some aquaculturists to 
have the best anesthetic effect.  However, neither clove oil nor any individual active 
ingredient of clove oil (including eugenol, isoeugenol, or methyleugenol) is the subject of 
an FDA approved new animal drug application.  
Although clove oil and some of its components are generally recognized as safe (GRAS) 
for use in dental cement or as food additives, neither clove oil nor any of its components 
are GRAS for use as an anesthetic for fish. 
The only new animal drug approved for use as an anesthetic in fish as of the date of 
publication of this guidance document, is MS-222 (Finquel or Tricaine-S), also known 
as tricaine methanesulfonate.  This drug has a 21-day withdrawal time.  The conditions of 
use for this drug can be viewed at http://www.accessdata.fda.gov/scripts/animaldrugsatfda. 
Safety Concerns over the Use of Clove Oil and its Components in Fish 
Historically, clove oil and isoeugenol have been used in foods and eugenol has been used 
in animal foods.  However, concerns regarding this class of chemical compounds led to 
the nomination of eugenol, isoeugenol, and methyleugenol for investigation under the 
National Toxicology Program (NTP).  The NTP conducts studies in nominated drugs and 
chemicals to determine their potential to cause cancer.  Studies have been completed for 
eugenol, isoeugenol, and methyleugenol.  NTP determined that eugenol is an equivocal 
carcinogen and methyleugenol is carcinogenic to rodents.  While the in-life studies are  complete for isoeugenol, the NTP has not yet reached a conclusion regarding its 
carcinogenicity.  The status of toxicology studies conducted on these compounds can be 
found on the NTP website at http://ntp-server.niehs.nih.gov/.  A search for 'eugenol' 
brings up all the related test results. 
Because some clove oil products may contain or include either methyleugenol or 
isoeugenol, or both, CVM is concerned that the use of clove oil or its components in fish 
may adversely affect human food safety and animal food safety.  This concern especially 
applies to the use of Clove Oil or any of its components in fish intended for use in human 
or animal food, and from use in those fish that may be released into public waters where 
they would be available as food for other aquatic species, or could be caught and end up 
in the human food supply. In addition, because clove oil and its components have not 
been evaluated for target animal safety, CVM is also concerned that the use of any of 
these compounds may adversely affect fish, including endangered aquatic species.  
This guidance is intended to remind producers that neither clove oil nor any of its 
components are the subject of an approved new animal drug application and, because of 
safety concerns, should not be used as an anesthetic in fish.  For more information on 
drugs that are acceptable for use as an anesthetic for fish, contact Scott Melton, at (240) 
276-8666.