Contains Nonbinding Recommendations 
  
  
 
 
Frequently Asked Questions About 
GRAS for Substances Intended for 
Use in Human or Animal Food: 
Guidance for Industry  
 
Additional copies are available from: 
Office of Food Additive Safety (HFS-200) 
Center for Food Safety and Applied Nutrition 
Food and Drug Administration 
5001 Campus Drive 
College Park, MD  20740 
(Tel) 240-402-1200 
http://www.fda.gov/FoodGuidances 
and 
 Division of Animal Feeds (HFV-220) 
Office of Surveillance and Compliance  
Center for Veterinary Medicine 
Food and Drug Administration 
7519 Standish Place 
Rockville, MD 20855 
(Tel) 240-402-7077 
http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/de
fault.htm 
 
You may submit written comments regarding this guidance at any time.  Submit written 
comments on the guidance to the Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.  All comments should be 
identified with the title of the guidance document. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Food Safety and Applied Nutrition 
Center for Veterinary Medicine 
October 2016 
    Contains Nonbinding Recommendations 
Table of Contents  
 
 
Table of Contents 
I.  Introduction 
II.  Frequently Asked Questions 
1.  What does "GRAS" mean? 
2.  What are the criteria for eligibility for classification as GRAS? 
3.  How are the criteria for eligibility for classification as GRAS similar to the criteria 
for FDAs approval of a food additive? 
4.  How are the criteria for eligibility for classification as GRAS through scientific 
procedures different from the criteria for FDAs approval of a food additive? 
5.  If an ingredient is GRAS for one use, is it GRAS for all uses? 
6.  Is a substance that is used to impart color eligible for classification as GRAS? 
7.  Is a substance that is used as a dietary ingredient in a human dietary supplement 
eligible for classification as GRAS? 
8.  Must FDA approve GRAS substances? 
9.  What is GRAS affirmation? 
10.  What is the GRAS notification procedure? 
11.  If I choose to submit a GRAS notice, how do I do so? 
12.  Where do I send my GRAS notice? 
13.  If I submit a GRAS notice, how long will it take for me to receive a response from 
FDA? 
14.  If I submit a GRAS notice about a substance intended for use in human or animal 
food, must I wait until I receive a response from CFSAN or CVM before I market that 
substance? 
15.  Does FDA have a list of substances that are used in food on the basis of the 
GRAS provision? 
16.  Can the use of a substance be GRAS even if it is not listed by FDA? 
III.  How to Contact FDA With Questions About GRAS 
IV.  References 
 
  2  Contains Nonbinding Recommendations 
Frequently Asked Questions About 
GRAS for Substances Intended for 
Use in Human or Animal Food: 
1
Guidance for Industry
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or we) 
on this topic.  It does not establish any rights for any person and is not binding on FDA or the 
public.  You can use an alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
for this guidance as listed on the title page.  
 
I.  Introduction  
This list of frequently asked questions (FAQ) is intended to be a convenient place to find 
answers to common questions about the food substance classification known as "generally 
recognized as safe" or "GRAS." This FAQ addresses common questions about the regulatory 
process and regulatory considerations regarding whether the use of a substance in human or 
animal food is GRAS.   
Our Center for Food Safety and Applied Nutrition (CFSAN) provides additional information 
about GRAS substances intended for use in human food on CFSANs Web site entitled 
Generally Recognized as Safe (GRAS). Our Center for Veterinary Medicine (CVM) provides 
additional information about GRAS substances intended for use in animal food on CVMs Web 
site entitled Generally Recognized as Safe (GRAS) Notification Program. To contact CFSAN 
or CVM to obtain more information about whether the intended use of a substance in human 
food or animal food is GRAS, see section III. 
This guidance updates and replaces a previous guidance, entitled Frequently Asked Questions 
About GRAS, that CFSAN issued in December 2004. This updated guidance refers to the 
provisions of a final rule that we published on August 17, 2016 (81 Fed. Reg. 54960) and 
addresses substances used in human food as well as substances used in animal food. This 
guidance also includes an editorial change, relative to the guidance issued on October 17, 
2016, to clarify the response to Question 14.  
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe our current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  
                                                
1 This guidance has been jointly prepared by the Office of Food Additive Safety in the Center for Food 
Safety and Applied Nutrition and the Division of Animal Feeds in the Office of Surveillance and 
Compliance in the Center for Veterinary Medicine at the U.S. Food and Drug Administration.   
  3  Contains Nonbinding Recommendations 
The use of the word should in FDA guidances means that something is suggested or 
recommended, but not required.  
II.  Frequently Asked Questions  
1. What does "GRAS" mean? 
"GRAS" is an acronym for the phrase Generally Recognized as Safe. Under sections 201(s) 
and 409 of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), any substance that is 
intentionally added to food is a food additive, that is subject to premarket review and approval 
by FDA, unless the substance is generally recognized, among qualified experts, as having been 
adequately shown to be safe under the conditions of its intended use, or unless the use of the 
substance is otherwise excepted from the definition of a food additive.2 Sections 201(s) and 409 
were enacted in 1958 as part of the Food Additives Amendment to the FD&C Act.  FDA has 
several lists of substances that are used in food on the basis of the GRAS provision (see 
Question 15).  
2. What are the criteria for eligibility for classification as GRAS? 
Under section 201(s) of the FD&C Act, and FDA's implementing regulations in Title 21 of the 
Code of Federal Regulations (21 CFR), the use of a food substance may be GRAS either 
through scientific procedures or, for a substance used in food before 1958, through experience 
based on common use in food. Table 1 provides regulatory citations for key regulations 
implementing the GRAS provisions of the FD&C Act for substances intended for use in human 
food.  Table 2 provides regulatory citations for key regulations implementing the GRAS 
provisions of the FD&C Act for substances intended for use in animal food. 
Table 1.Key Regulatory Text Regarding Whether the Intended Use of a Substance in 
Human Food is GRAS 
Regulatory Citation  Regulatory Text 
21 CFR 170.3(f)  Common use in food means a substantial history of consumption of a 
substance for food use by a significant number of consumers. 
21 CFR 170.3(h)  Scientific procedures include the application of scientific data (including, 
as appropriate, data from human, animal, analytical, or other scientific 
studies), information, and methods, whether published or unpublished, 
as well as the application of scientific principles, appropriate to establish 
the safety of a substance under the conditions of its intended use. 
21 CFR 170.30  Eligibility for Classification as Generally Recognized as Safe (GRAS) 
                                                
2 For example, substances whose use meets the definition of a pesticide, a dietary ingredient of a dietary 
supplement, a color additive, a new animal drug, or a substance used in accordance with a sanction or 
approval granted prior to September 6, 1958, are excepted from the definition of food additive. 
  4  Contains Nonbinding Recommendations 
Regulatory Citation  Regulatory Text 
21 CFR 170.30(a)  General recognition of safety may be based only on the views of experts 
qualified by scientific training and experience to evaluate the safety of 
substances directly or indirectly added to food. The basis of such views 
may be either (1) scientific procedures or (2) in the case of a substance 
used in food prior to January 1, 1958, through experience based on 
common use in food.  General recognition of safety requires common 
knowledge throughout the scientific community knowledgeable about the 
safety of substances directly or indirectly added to food that there is 
reasonable certainty that the substance is not harmful under the 
conditions of its intended use (see  170.3(i)). 
21 CFR 170.30(b)  General recognition of safety based upon scientific procedures shall 
require the same quantity and quality of scientific evidence as is required 
to obtain approval of a food additive.  General recognition of safety 
through scientific procedures shall be based upon the application of 
generally available and accepted scientific data, information, or 
methods, which ordinarily are published, as well as the application of 
scientific principles, and may be corroborated by the application of 
unpublished scientific data, information, or methods.   
21 CFR 170.30(c)(1)  (1) General recognition of safety through experience based on common 
use in food prior to January 1, 1958, may be achieved without the 
quantity or quality of scientific procedures required for approval of a food 
additive.  General recognition of safety through experience based on 
common use in food prior to January 1, 1958, shall be based solely on 
food use of the substance prior to January 1, 1958, and shall ordinarily 
be based upon generally available data and information. An ingredient 
not in common use in food prior to January 1, 1958, may achieve 
general recognition of safety only through scientific procedures. 
21 CFR 170.30(c)(2)  (c)(2)  A substance used in food prior to January 1, 1958, may be 
generally recognized as safe through experience based on its common 
use in food when that use occurred exclusively or primarily outside of the 
United States if the information about the experience establishes that the 
substance is safe under the conditions of its intended use within the 
meaning of section 201(u) of the FD&C Act (see also  170.3(i)). 
Common use in food prior to January 1, 1958, that occurred outside of 
the United States shall be documented by published or other information 
and shall be corroborated by information from a second, independent 
source that confirms the history and circumstances of use of the 
substance.   The information used to document and to corroborate the 
history and circumstances of use of the substance must be generally 
available; that is, it must be widely available in the country in which the 
history of use has occurred and readily available to interested qualified 
experts in the United States.  A person who concludes that a use of a 
substance is GRAS through experience based on its common use in 
food outside of the United States should notify FDA of that view in 
accordance with subpart E of this part. 
 
Table 2.Key Regulatory Text Regarding Whether the Intended Use of a Substance in 
Food for Animals is GRAS 
  5  Contains Nonbinding Recommendations 
Regulatory Citation  Regulatory Text 
21 CFR 570.3(f)  Common use in food means a substantial history of consumption of a 
substance by a significant number of animals of the species to which the 
substance is intended to be fed (and, for food-producing animals fed 
with such substance, also means a substantial history of consumption by 
humans consuming human foods derived from those food-producing 
animals), prior to January 1, 1958. 
21 CFR 570.3(h)  Scientific procedures include the application of scientific data (including, 
as appropriate, data from human, animal, analytical, or other scientific 
studies), information, and methods, whether published or unpublished, 
as well as the application of scientific principles, appropriate to establish 
the safety of a substance under the conditions of its intended use. 
21 CFR 570.30  Eligibility for Classification as Generally Recognized as Safe (GRAS) 
21 CFR 570.30(a)  General recognition of safety may be based only on the views of experts 
qualified by scientific training and experience to evaluate the safety of 
substances directly or indirectly added to food. The basis of such views 
may be either (1) scientific procedures or (2) in the case of a substance 
used in food prior to January 1, 1958, through experience based on 
common use in food. General recognition of safety requires common 
knowledge throughout the scientific community knowledgeable about the 
safety of substances directly or indirectly added to food that there is 
reasonable certainty that the substance is not harmful to either the target 
animal or to humans consuming human food derived from food-
producing animals under the conditions of its intended use (see  
570.3(i)). 
21 CFR 570.30(b)  General recognition of safety based upon scientific procedures shall 
require the same quantity and quality of scientific evidence as is required 
to obtain approval of a food additive.    General recognition of safety 
through scientific procedures shall address safety for both the target 
animal and for humans consuming human food derived from food-
producing animals and shall be based upon the application of generally 
available and accepted scientific data, information, or methods, which 
ordinarily are published, as well as the application of scientific principles, 
and may be corroborated by the application of unpublished scientific 
data, information, or methods. 
21 CFR 570.30(c)(1)  (c)(1) General recognition of safety through experience based on 
common use in food prior to January 1, 1958, shall address safety for 
both the target animal and for humans consuming human food derived 
from food-producing animals and may be achieved without the quantity 
or quality of scientific procedures required for approval of a food 
additive.  General recognition of safety through experience based on 
common use in food prior to January 1, 1958, shall be based solely on 
food use of the substance in the same animal species prior to January 1, 
1958, and shall ordinarily be based upon generally available data and 
information.  An ingredient not in common use in food prior to January 1, 
1958, may achieve general recognition of safety only through scientific 
procedures. 
  6  Contains Nonbinding Recommendations 
Regulatory Citation  Regulatory Text 
21 CFR 570.30(c)(2)  (2) A substance used in food prior to January 1, 1958, may be generally 
recognized as safe through experience based on its common use in food 
when that use occurred exclusively or primarily outside of the United 
States if the information about the experience establishes that the 
substance is safe under the conditions of its intended use within the 
meaning of section 201(u) of the Federal Food, Drug, and Cosmetic Act 
(see also  570.3(i)) for both the target animal and for humans 
consuming human food derived from food-producing animals.  Common 
use in food prior to January 1, 1958, that occurred outside of the United 
States shall be documented by published or other information and shall 
be corroborated by information from a second, independent source that 
confirms the history and circumstances of use of the substance.  The 
information used to document and to corroborate the history and 
circumstances of use of the substance must be generally available; that 
is, it must be widely available in the country in which the history of use 
has occurred and readily available to interested qualified experts in the 
United States.  A person who concludes that a use of a substance is 
GRAS through experience based on its common use in food outside of 
the United States should notify FDA of that view in accordance with 
subpart E of this part. 
 
 
3. How are the criteria for eligibility for classification as GRAS 
similar to the criteria for FDAs approval of a food additive? 
Regardless of whether the use of a substance is a food additive use or is GRAS, there must be 
evidence that the substance is safe under the conditions of its intended use. FDA has defined 
"safe" (21 CFR 170.3(i) and 21 CFR 570.3(i)) as a reasonable certainty in the minds of 
competent scientists that the substance is not harmful under the conditions of its intended use. 
The specific data and information that demonstrate safety depend on the characteristics of the 
substance, the estimated dietary exposure3, the population that will consume the substance, 
and other relevant considerations. 
4. How are the criteria for eligibility for classification as GRAS 
through scientific procedures different from the criteria for FDAs 
approval of a food additive? 
The difference between the criteria for eligibility for classification as GRAS through scientific 
procedures (21 CFR 170.30(b) and 21 CFR 570.30(b)) and FDAs approval of a food additive 
(21 CFR 171.1 and 21 CFR 571.1) relates to who has access to the data and information and 
who has reviewed those data and information.  For a substance to be GRAS under the 
conditions of its intended use, the data and information relied on to establish the safety of the 
use of the substance must be generally available (e.g., through publication in the scientific 
literature) and there must be a basis for a person to conclude that the substance is generally 
                                                
3 For a substance intended for use in animal food, the data and information address exposure to the 
target animal and to humans consuming human food derived from food-producing animals.  
  7  Contains Nonbinding Recommendations 
recognized, among qualified experts, to be safe under the conditions of its intended use.  In 
contrast, for FDAs approval of a food additive privately held data and information about the 
substance under the conditions of its intended use are sent by the sponsor to FDA and FDA 
reviews those data and information to determine whether they demonstrate that the substance 
is safe under the conditions of its intended use. 
5. If an ingredient is GRAS for one use, is it GRAS for all uses? 
Not necessarily. Under section 201(s) of the FD&C Act, it is the use of a substance, rather than 
the substance itself, that is eligible for classification as GRAS (81 Fed. Reg. 54960 at 54963; 
August 17, 2016). An evaluation of the safety of the use of an ingredient includes information 
about the characteristics of the substance, the estimated dietary exposure under the intended 
conditions of use, and the population that will consume the substance. Dietary exposure to a 
substance depends on the food categories in which it will be used and the level of use in each 
of those food categories. For information about how CFSAN estimates human dietary exposure 
to a food substance, see CFSAN's document entitled "Estimating Dietary Intake of Substances 
in Food" (Ref. 1).  
Some uses of a human food substance are intended for a narrowly defined population.  For 
example, some human food substances are intended for consumption by newborn infants who 
consume infant formula as the sole item of the diet; in such a circumstance, there may be 
special considerations associated with that population but not with general use of the food 
substance.  Likewise, some substances intended for use in animal food are intended for specific 
animal species (such as cattle or swine), or for a specific life stage of an animal species; a 
substance that is safe for use in one animal species may not be safe for use in another species 
or in the same species at a different stage of life.   
6. Is a substance that is used to impart color eligible for 
classification as GRAS? 
The short answer is "No." Under section 201(s) of the FD&C Act, the GRAS provision applies to 
the definition of a food additive. There is no corresponding provision in the definition (in section 
201(t) of the FD&C Act) of a color additive. 
However, under section 201(t)(1) and 21 CFR 70.3(f), the term color additive means a material 
that is a dye, pigment, or other substance made by a process of synthesis or similar artifice, or 
extracted, isolated, or otherwise derived from a vegetable, animal, mineral, or other source, and 
that is capable (alone or through reaction with another substance) of imparting color when 
added or applied to a food; except that such term does not include any material which FDA, by 
regulation, determines is used (or intended to be used) solely for a purpose or purposes other 
than coloring. Under 21 CFR 70.3(g), a material that otherwise meets the definition of color 
additive can be exempt from that definition on the basis that it is used or intended to be used 
solely for a purpose or purposes other than coloring, as long as the material is used in a way 
that any color imparted is clearly unimportant insofar as the appearance, value, marketability, or 
consumer acceptability is concerned. Given the construct of section 201(t)(1) of the Act and 21 
CFR 70.3(f) and (g), the use of a substance that is capable of imparting color may constitute 
use as both a color additive and as a food additive or GRAS substance. For example, beta-
carotene is both approved for use as a color additive (21 CFR 73.95) and affirmed as GRAS for 
use as a nutrient in human food (21 CFR 184.1245); in some food products, beta-carotene may 
be safely and lawfully used for both purposes. 
  8  Contains Nonbinding Recommendations 
7. Is a substance that is used as a dietary ingredient in a human4 
dietary supplement eligible for classification as GRAS? 
Under section 201(s) of the FD&C Act, a substance that is GRAS under the conditions of its 
intended use is excluded from the definition of a food additive. In addition, under section 201(s) 
of the FD&C Act the term "food additive" does not include a dietary ingredient5 used or intended 
for use in a dietary supplement as defined in section 201(ff) of the FD&C Act. In other words, 
because dietary ingredients intended for use in dietary supplements are already excepted from 
the food additive definition, their GRAS status for that use is irrelevant because they are already 
exempt from the food additive approval requirement. However, some dietary ingredients that 
may be used in a dietary supplement may also be GRAS for use in a conventional food (e.g., 
vitamin C; calcium carbonate). In addition, a substance that is not a dietary ingredient as 
defined in section 201(ff)(1) of the FD&C Act must be approved as a food additive when used in 
a dietary supplement (e.g., as a coating, filler, or binder) unless the substance is GRAS for that 
use or otherwise excepted from the definition of a food additive. 
8. Must FDA approve GRAS substances? 
No. If the use of a food substance is GRAS, it is not subject to FDAs premarket review and 
approval as a food additive.  
9. What is GRAS affirmation? 
GRAS affirmation is a process that FDA developed in the 1970s. In response to concerns raised 
by new information on cyclamate salts, then-President Nixon directed FDA to re-examine the 
safety of substances considered to be GRAS. FDA announced that the agency would evaluate, 
by contemporary standards of the time, the available safety information regarding substances 
considered to be GRAS. If the re-evaluations confirmed that the uses were GRAS, FDA 
promulgated new GRAS regulations, affirming those findings. FDA also established procedures 
whereby an individual could voluntarily petition FDA to review the GRAS status of substances 
that would not have been considered as part of the agency's GRAS review. 
In a final rule that FDA published on August 17, 2016 (81 Fed. Reg. 54960), FDA removed that 
voluntary process from its regulations and replaced it with a voluntary GRAS notification 
procedure. See Question 10. 
10.  What is the GRAS notification procedure? 
The GRAS notification procedure is a voluntary procedure under which any person may notify 
FDA of a conclusion that a substance is GRAS under the conditions of its intended use in 
human food (21 CFR part 170, subpart E) or animal food (21 CFR part 570, subpart E). 
Although the GRAS notification procedure is voluntary, FDA strongly encourages any person 
                                                
4 Note that FDA previously published a notice in the Federal Register explaining its conclusion that the 
Dietary Supplement Health and Education Act of 1994 (which established the exception from the 
definition of food additive in section 201(s) of the FD&C Act for a dietary ingredient of a dietary 
supplement) does not apply to products intended for use in animals (61 Fed. Reg. 17706; April 22, 1996).  
5 Dietary ingredient is defined in section 201(ff)(1) of the FD&C Act and generally includes vitamins, 
minerals, herbs and other botanicals, amino acids, dietary substances, and concentrates, metabolites, 
constituents, extracts, and combinations of dietary ingredients in the other categories.   
  9  Contains Nonbinding Recommendations 
who intends to market a food substance on the basis of the GRAS provision to submit a GRAS 
notice to FDA. 
A GRAS notice has seven required parts as shown in Table 3 for a substance intended for use 
in human food and as shown in Table 4 for a substance intended for use in animal food. 
Table 3.The Seven Required Parts of a GRAS Notice for a Substance Intended for Use 
in Human Food 
Regulatory  Part of a  Title 
Citation  GRAS 
Notice 
170.225  Part 1  Signed statements and certification 
170.230  Part 2  Identity, method of manufacture, specifications, and physical or technical 
effect 
170.235  Part 3  Dietary exposure 
170.240  Part 4  Self-limiting levels of use 
170.245  Part 5  Experience based on common use in food before 1958 
170.250  Part 6  Narrative 
170.255  Part 7  List of supporting data and information in your GRAS notice 
 
 
Table 4.The Seven Required Parts of a GRAS Notice for a Substance Intended for Use 
in Animal Food 
Regulatory  Part of a  Title 
Citation  GRAS 
Notice 
570.225  Part 1  Signed statements and certification 
570.230  Part 2  Identity, method of manufacture, specifications, and physical or technical 
effect 
570.235  Part 3  Target animal and human exposures 
570.240  Part 4  Self-limiting levels of use 
570.245  Part 5  Experience based on common use in food before 1958 
570.250  Part 6  Narrative 
570.255  Part 7  List of supporting data and information in your GRAS notice 
 
11.  If I choose to submit a GRAS notice, how do I do so? 
For a substance intended for use in human food, follow the procedure in 21 CFR part 170, 
subpart E for submission of a GRAS notice to CFSAN.  
For a substance intended for use in animal food, follow the procedure in 21 CFR part 570, 
subpart E for submission of a GRAS notice to CVM.  
12.  Where do I send my GRAS notice? 
For a substance intended for use in human food, send your GRAS notice to the Office of Food 
Additive Safety (HFS-200), Center for Food Safety and Applied Nutrition, Food and Drug 
Administration, 5001 Campus Drive, College Park, MD 20740. For electronic submission of your 
GRAS notice, see Ref. 2. 
  10  Contains Nonbinding Recommendations 
For a substance intended for use in animal food, send your GRAS notice to the Division of 
Animal Feeds (HFV- 220), Center for Veterinary Medicine, Food and Drug Administration, 7519 
Standish Pl., Rockville, MD 20855. For electronic submission of your GRAS notice, eSubmitter 
is available for use (http://www.fda.gov/ForIndustry/FDAeSubmitter/default.htm). 
13.  If I submit a GRAS notice, how long will it take for me to 
receive a response from FDA? 
The GRAS notification procedure requires that FDA respond to a GRAS notice within 180 days, 
with an option to extend the 180-day timeframe by 90 days on an as needed basis. 
14.  If I submit a GRAS notice about a substance intended for 
use in human or animal food, must I wait until I receive a response 
from CFSAN or CVM before I market that substance? 
No. If you are correct in concluding that a substance is GRAS under the conditions of its 
intended use, there is no requirement under section 409 of the FD&C Act for FDA review and 
approval for that use of the substance. Your decision to submit a GRAS notice to CFSAN or 
CVM is voluntary, and the response to a GRAS notice from CFSAN or CVM is not an approval. 
You may market a substance that is GRAS under the conditions of its intended use without 
informing CFSAN or CVM or, if CFSAN or CVM is so informed, while the applicable Center is 
evaluating your GRAS notice. (See Response 114, 81 Fed. Reg. 54960 at 55022). We 
recognize, however, that some firms prefer to know that the applicable FDA Center has 
evaluated a submitted GRAS notice, without raising safety or legal issues, before marketing. 
15.  Does FDA have a list of substances that are used in food 
on the basis of the GRAS provision? 
FDAs regulations in 21 CFR include several lists of substances that are used in food on the 
basis of the GRAS provision (see Table 5 and Table 6). Importantly, these lists are not all-
inclusive. Because the use of a GRAS substance is not subject to premarket review and 
approval by FDA, it is impracticable to list all substances that are used in food on the basis of 
the GRAS provision. 
CFSANs Web site entitled Generally Recognized as Safe (GRAS), and CVMs Web site 
entitled Generally Recognized as Safe (GRAS) Notification Program, each contain a list of 
substances that have been the subject of a GRAS notice to FDA, whether to CFSAN (for 
intended use in human food) or to CVM (for intended use in animal food). You can access these 
lists, along with the response from CFSAN or CVM to the notifier, from CFSANs Web site and 
CVMs Web site (Ref. 3 and Ref. 4).      
  11  Contains Nonbinding Recommendations 
Table 5.Lists of Substances Intended for Use in Human Food on the Basis of the GRAS 
Provision 
List  Description 
21 CFR part 182  Contains the remnants of a list that FDA established in its human food 
regulations shortly after passage of the 1958 Food Additives 
Amendment. The list is organized according to the intended use of these 
substances. As part of CFSANs comprehensive review of GRAS 
substances in the 1970s, CFSAN affirmed that the use of some of the 
ingredients on this original GRAS list are GRAS, and moved the affirmed 
uses of the substance to 21 CFR Part 184. 
21 CFR part 184  Contains a list of substances that CFSAN affirmed as GRAS as direct 
human food ingredients for general or specific uses. This list derives 
from CFSANs 1970s comprehensive review of GRAS substances and 
from petitions that CFSAN received to affirm the GRAS status of 
particular uses of some food ingredients. 
21 CFR part 186  Contains a list of substances that CFSAN affirmed as GRAS for certain 
indirect food uses (e.g., in the manufacture of paper and paperboard that 
contact human food). 
 
 
Table 6.Lists of Substances Intended for Use in Animal Food on the Basis of the GRAS 
Provision 
List  Description 
21 CFR part 582  Contains the remnants of a list that FDA established in its animal food 
regulations shortly after passage of the 1958 Food Additives 
Amendment. The list is organized according to the intended use of these 
substances.  
21 CFR part 584  Contains a list of substances that CVM affirmed as GRAS as direct 
animal food ingredients for general or specific uses. This list derives 
from petitions that CVM received to affirm the GRAS status of particular 
uses of some food ingredients. 
 
 
 
16.  Can the use of a substance be GRAS even if it is not listed 
by FDA? 
Yes. Because the use of a substance that is GRAS is not subject to premarket review and 
approval by FDA, it is impracticable to list all substances that are used in food on the basis of 
the GRAS provision (21 CFR 182.1(a) and 21 CFR 582.1(a)). The use of a substance is GRAS 
because of widespread knowledge among the community of qualified experts, not because of a 
listing or other administrative activity. 
III.  How to Contact FDA With Questions About GRAS  
You may contact CFSAN: 
  By contacting Dr. Paulette Gaynor at (240)402-1192 
  12  Contains Nonbinding Recommendations 
  By email to premarkt@fda.hhs.gov 
  By mail sent to the following address: 
FDA/CFSAN 
Office of Food Additive Safety 
5001 Campus Drive 
College Park, MD  20740 
 
You may contact CVM: 
  By contacting Mr. Geoffrey Wong at (240)402-5838 
  By email to AskCVM@fda.hhs.gov 
  By mail sent to the following address: 
FDA/CVM 
Office of Surveillance and Compliance, Division of Animal Feeds (HFV-220) 
7519 Standish Pl.  
Rockville, MD 20855 
 
 IV.  References   
1.  FDA, Guidance for Industry: Estimating Dietary Intake of Substances in Food, 
(http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformati
on/ucm074725.htm), 2006.    
2.  FDA, Guidance for Industry:  Providing Regulatory Submissions in Electronic or Paper 
Format to the Office of Food Additive Safety; Draft Guidance, 
(http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformati
on/IngredientsAdditivesGRASPackaging/ucm2021277.htm), 2010.   
3.  GRAS Notice Inventory, 
(http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.h
tm).   
4.  Current Animal Food GRAS Notices Inventory, 
(http://www.fda.gov/AnimalVeterinary/Products/AnimalFoodFeeds/GenerallyRecognized
asSafeGRASNotifications/ucm243845.htm) 
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