22 REGULATORY AFFAIRS ARTICLE
Edible oil extraction solvents:
FDA regulatory considerations
P.J. Wakelyn and P.J. Wan
Edible oils and fats are produced either by
solvent or mechanical extraction of oilseeds
or oil-bearing plant and animal materials or
by heat rendering of animal tissues. When a
solvent is used to extract edible oil from oil-
bearing materials in the United States, fed-
eral and state workplace, environmental, and
food safety regulations have to be complied
with.
If solvent extraction is used, trace amounts
of the extraction solvent potentially can be
detected in the finished oil. In the United
States, the U.S. Food and Drug Administration
(FDA) regulates all aspects of food, includ-
ing food ingredients and labeling. A sub-
stance that is added to food is subject to
premarket approval by FDA unless its use is
generally recognized as safe (GRAS) by qual-
ified experts. Oilseed extraction solvents and
food processing substances, to be legally
used in the United States, must have been
subject to an approval by the FDA or the U.S.
Department of Agriculture (USDA) during
19381958 for this use [prior sanction;
Federal Food, Drug and Cosmetic A c t
(FFDCA) section 201(s)(4)]; be GRAS for
this use by FDA (GRAS affirmation; 21
CFR 170.35); or be used in accordance with
food additive regulations promulgated by
the FDA [21 CFR 170.3(h)(I)]. Food addi-
tives generally fall into two broad categories:
(1) those added directly to food (21 CFR
172), and (2) those that are added indirectly
to food through contact with packaging mate-
rials, processing equipment, or other food-
contact materials (21 CFR 174178). (The
Code of Federal Regulations [CFR] can be
accessed on-line at netlink: www.gpoac-
cess.gov/cfr/index.html).
Many prior sanctions (21 CFR 181) and
GRAS determinations (21 CFR 182, 184,
186) are not codified in the FDA regulations.
However, extracting solvents used in food
manufacturing, such as n-hexane or iso-
hexane/hexane isomers, have been labeled
as food additives; incidental additives (i.e.,
additives that are present in a food at sig-
nificant levels and do not have any techni-
cal or functional effect in that food); sol-
vent, defoaming agent, component of a sec-
ondary direct food and color additives (21
CFR 173); or minor constituent, depend-
ing on the application. Incidental additives
can be processing aids (i.e., substances
that are added to a food during processing
but removed from the food before it is pack-
aged). Most food-processing substances,
including solvents, can be regarded as inci-
dental additives and thus are exempt from
label declaration in the finished food prod-
uct. Even if exempt from label declaration,
all extraction solvents must be used in accor-
dance with the FDA good manufacturing
practices (GMP; 21 CFR 100).
Since vegetable oil and other human
food-grade oils undergo refining, bleaching,
deodorization (steam distillation), and some-
times other purification processes as part of
the manufacturing process before being used
as a food product, they should not contain
any detectable amount of the extraction sol-
vent if proper manufacturing practices are
followed. Refining removes nonglyceride
materials (e.g., phospholipids, color, and
trace metals) and free fatty acids; bleaching
with acid-activated bleaching earth or clay
(e.g., bentonite) removes color- p r o d u c i n g
substances; and deodorization, the last major
processing step in edible oils refining removes
volatile compounds (undesirable ingredients
occurring in natural oil and those that may
be imparted by prior unit processes or even
storage, many of which are associated with
undesirable flavors and odors). Most com-
mercial deodorizers operate at temperatures
of 245275C (475525F) under a nega-
tive pressure of 210 mm Hg. It is generally
recognized that no n-hexane residue remains
in the finished oil after processing owing
to its high volatility. In addition, animal-feed-
ing studies with expeller and solvent-extracted
meals have not indicated any adverse health
effects related to the extraction solvent. The
same should be true for isohexane, acetone,
and other volatile organic solvents that can
be used for edible oil extraction.
inform January 2004 Volume 15 (1)
Commercial hexane, containing about
5085% n-hexane (the rest is hexane iso-
mers that also make up commercial iso-
hexane), has been in major use since the
1940s as an oilseed-extraction solvent. As
with many other food-processing substances,
there is no FDA regulation specifically list-
ing n-hexane as GRAS (21 CFR 182, 184,
186) or as subject to a prior sanction approval
(21 C F R 181). Isohexane/hexane isomers
also are not specifically listed as GRAS or
as prior sanctioned. However, under FDA
regulations n-hexane has been cleared as a
solvent for use in many products: in the man-
ufacture of the food additive fish protein iso-
late (residue not more that 5 ppm) (21 CFR
172.340); a solvent for use in manufactur-
ing modified hop extract used in beer brew-
ing (residue not more than 25 ppm) (21 CFR
172.560); an extraction solvent (residue not
more than 25 ppm) for the color additives;
Tagetes (Aztec marigold) meal and extract
(21 CFR 73.295); carrot oil (73.300), color
endosperm oil (73.315), paprika oleoresin
(73.345), or annatto extract (73.30); a com-
ponent of resinous and polymeric coatings
(21 CFR 175.320) and of adhesives for food
packaging (21 CFR 175.105); and a defoam-
ing agent for use in coatings that are used in
producing, packaging, processing, prepar-
ing, treating, transporting, or holding foods
(21 C F R 176.200). The FDA sets a toler-
ance for n-hexane residues for the food addi-
tive modified cottonseed products (defatted
cottonseed flour) of 60 ppm (21 C F R
172.894); sets a tolerance for secondary
direct food additives (21 C F R 173), and
allows 25 ppm as n-hexane residue in the
extraction of spice oleoresins and a residue
not to exceed 2.2 wt% n-hexane in hops
extract [21 CFR 173.270 (a) and (b)]. Also,
n-hexane has been cleared as a minor con-
stituent (not more than 5 ppm) of a cocoa
butter substitute, a direct food additive that
has been affirmed by FDA as GRAS for food
use (21 CFR 184.1259).
In Europe the maximum residue limit
(MRL) for n-hexane in vegetable oils has
inform January 2004 Volume 15 (1)
been established as 5 ppm n-hexane [European
Union (EU) Community Directive
88/344/EECC of 13 June 1988; Official J.
E u r. Commun. L157, 24 June 1988, pp.
00280033]. There is no MRL for iso-
hexane/hexane isomers.
For determining GRAS status in the
United States, the following options may be
considered by the users of solvents for extrac-
tion of edible oil:
1. GRAS affirmation : This is a full-approval
process by FDA (21 CFR 170.35). It is very
involved and can take a long time. (GRAS
substances are listed in 21 CFR 182; direct
food substances affirmed as GRAS in part
184; and indirect food substances affirmed
as GRAS in part 186.)
2. FEMA GRAS (independent third-party
d e t e r m i n a t i o n ): The Flavor and Extract
ManufacturersAssociation (FEMA) has
conducted a program since 1958 using a panel
of expert pharmacologists and toxicologists
to determine substances that are GRAS. (This
is considered an industry/government part-
nership with FDA.) This panel uses all avail-
able data, including experience based on
common uses in food. This safety assess-
ment program (FEMA GRAS) is widely
accepted. A number of papers published in
the journal Food Technology since 1961 list
the substances that the panel has determined
to be GRAS and the average maximum lev-
els in parts per million (ppm) at which each
has been reported to be GRAS for different
categories of food. The FDA has not incor-
porated these substances in their regulations
but does recognize the findings of the Expert
Panel of FEMA as GRAS substances. n-
Hexane and isohexane/hexane isomers are
not FEMA GRAS.
3 . GRAS self-determination: This is a
decision by the manufacturer to market the
product as meeting FDAs criteria for GRAS
status (i.e., determined by a company by
reviewing all available data to make a strong
case).
4. GRAS notification : FDA issued a pro-
posed rule (April 17, 1997; 62 FR 18938)
that would establish a notification procedure
whereby any person may notify FDA of a
determination by that person that a particu-
lar use of a substance is GRAS. Although the
proposed notification procedure is not yet
final, FDA has already received and reviewed
several notices (netlink: www.cfsan.fda.
gov/~rdb/opa-gras.html). FDA/CFSAN
(Center for Food Safety and Applied Nutrition)
has indicated in several cases that FDA does
not question the notifiers GRAS determi-
nation. As described in the GRAS proposal,
the agency is evaluating whether each sub-
mitted notice provides a sufficient basis
for a GRAS determination and whether infor-
mation in the notice or otherwise available
to FDA raises issues that lead the agency
to question whether use of the substance is
GRAS. Following this evaluation, FDA
responds to the notifier by letter.
In general, FDAs response has been in
one of three categories:
n The agency does not question the basis
for the notifiers GRAS determination.
n The agency concludes that the notice does
not provide a sufficient basis for a GRAS
determination (e.g., because the notice
does not include appropriate data and
information or because the available data
and information raise questions about the
safety of the notified substance).
n The response letter states that the agency
has, at the notifiers request, ceased to
evaluate the GRAS notice.
In the GRAS notification proposal, FDA
announced its intention to maintain an
Inventory of GRAS Notices and the agencys
response to those notices. Importantly, the
Inventory of GRAS Notices includes all
GRAS notices, regardless of whether the
notice is pending at FDA or has come to clo-
sure, and regardless of the nature of FDAs
response.
In summary, GRAS status may be deter-
mined by a company or an industry (GRAS
self-determination or GRAS notification),
by an independent scientific organization
REGULATORY AFFAIRS ARTICLE 23
(e.g., FEMA GRAS), or by the FDA
(GRAS Affirmation). The FFDCA (21 U.S.
Code 321 et seq.) does not provide for the
FDA to approve all ingredients used in food,
and the FDA explicitly recognizes that its
published GRAS list is not meant to be a
complete listing of all substances that are in
fact GRAS food substances. Although there
is no requirement to inform the FDA of a
GRAS self-determination or to request FDA
review or approval on the matter, the FDA
has established a voluntary GRAS affirma-
tion program under which such advice will
be provided by the agency. Solvents that do
not have prior sanction, a GRAS determi-
nation, or an established tolerance probably
should be evaluated for compliance under
food safety requirements, if a facility is con-
sidering changing its extracting solvent or
using any solvent for the extraction of the
various biological materials for specialty
markets.
Suggested reading
Appropriate background reading for this
topic containing relevant references to the
scientific literature may be found in the fol-
lowing work:
P.J. Wakelyn, Regulatory Considerations
for Oilseed Processors and Oil Refiners,
Chapter 16, Introduction to Fats and Oils
Technology,2nd edn., edited by P.J. Wan, D.
OBrien, and W. Farr,
AOCS Press, Champaign,
2000, pp. 302325.
P.J. Wakelyn is senior sci -
entist, environmental
health and safety, for the
National Cotton Council,
Washington, D.C., USA.
P.J. Wan is a chemical
engineer for food and
feed processing re s e a rch
with the USDA S o u t h -
ern Regional Researc h
C e n t e r, New Orleans,
Louisiana, USA.