[Federal Register Volume 59, Number 238 (Tuesday, December 13, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-30585]
[[Page Unknown]]
[Federal Register: December 13, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 94F-0152]
Roquette America, Inc.; Filing of Food Additive Petition
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing that
Roquette America, Inc., has filed a petition proposing that the food
additive regulations be amended to permit the manufacture of mannitol
by fermentation of sugars or sugar alcohols such as glucose, sucrose,
fructose, or sorbitol by the action of the yeast Zygosaccharomyces
rouxii.
DATES: Written comments on the petitioner's environmental assessment by
January 12, 1995.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr.,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Rosalie M. Angeles, Center for Food
Safety and Applied Nutrition (HFS-207), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-418-3107.
SUPPLEMENTARY INFORMATION: Under the Federal Food, Drug, and Cosmetic
Act (sec. 409(b)(5) (21 U.S.C. 348(b)(5))), notice is given that a food
additive petition (FAP 4A4412) has been filed by Roquette America,
Inc., c/o Keller and Heckman, 1001 G St. NW., Washington, DC 20001. The
petition proposes that the food additive regulations in Sec. 180.25
Mannitol (21 CFR 180.25) be amended to permit the manufacture of
mannitol by fermentation of sugars or sugar alcohols such as glucose,
sucrose, fructose, or sorbitol by the action of the yeast
Zygosaccharomyces rouxii.
As part of FDA's comprehensive safety review of substances on the
list of substances generally recognized as safe (GRAS), the safety of
mannitol as a food ingredient was evaluated in 1972 by the Select
Committee on GRAS Substances (SCOGS) from the Life Sciences Research
Office of the Federation of American Societies for Experimental Biology
(FASEB). SCOGS concluded that mannitol was safe when used in food at
current or reasonably expected future levels. In the Federal Register
of July 26, 1973 (38 FR 20046), FDA proposed to affirm the GRAS status
of mannitol that was manufactured by the process then known to the
agency.
In response to the proposal, the agency received a comment stating
that mannitol was also commonly manufactured by a process different
from that set out in the proposed GRAS affirmation. The agency also
received information raising questions about the safety of mannitol.
Data from studies on mannitol demonstrated a significant (but not dose
related) incidence of benign thymomas, and an abnormal growth of thymus
gland tissue, in female rats fed mannitol.
As a result of these findings, the agency concluded that additional
data were necessary to evaluate the safety of mannitol. Thus, in the
Federal Register of September 23, 1974 (39 FR 34178), the agency
declined to affirm the use of mannitol as GRAS and, instead,
established an interim food additive regulation for use of mannitol at
existing levels. The interim regulation, Sec. 121.4005 (21 CFR
121.4005) (redesignated as Sec. 180.25 (21 CFR 180.25)) required that
mannitol be manufactured by either the process FDA had proposed to
affirm as GRAS or the process described in the comment.
Following the publication of the interim food additive regulation,
the agency received data that showed an increased combined incidence of
medullary hyperplasia and pheochromocytoma of the adrenal glands in
Fischer rats fed a diet of 10 percent mannitol. No such mannitol-
treatment effect, however, was observed in Sprague-Dawley and Wistar
rats.
In 1985, FASEB, under contract with FDA, established an ad hoc
Expert Panel on Sugar Alcohols and Lactose to study certain effects
that had been observed in animal experiments in which the test animals
were fed sugar alcohols and lactose. In a report submitted to FDA in
1986, ``Health Aspects of Sugar Alcohols and Lactose,'' FASEB concluded
that there was a statistically significant increased incidence of
adrenal medullary hyperplasia and pheochromocytoma in rats fed high
levels of sugar alcohols, including mannitol. The report further
concluded that the existing data provided no satisfactory mechanistic
explanations of these adrenal medullary lesions, which are commonly
found in aged rats maintained on standard laboratory diets.
FDA is continuing to evaluate the FASEB report on sugar alcohols,
including mannitol, as well as other data from animal studies of these
substances to determine whether any regulatory action is appropriate
for any or all of the sugar alcohols. During this period of continuing
evaluation, mannitol continues to be listed, on an interim basis, for
food use.
Roquette America's petition to amend the interim food additive
regulation on mannitol, if granted, would not change the allowed uses
of mannitol; it would simply permit a new method of manufacture of the
additive. The subject regulation on mannitol specifies manufacturing
procedures that do not include the fermentation process used in
Roquette's production of mannitol. To permit a new manufacturing
method, Roquette's petition proposes to amend the interim food additive
regulation (Sec. 180.25) to provide for the use of Zygosaccharomyces
rouxii in the fermentation process of producing mannitol from sugars
and sugar alcohols.
The potential environmental impact of this action is being
reviewed. To encourage public participation consistent with regulations
promulgated under the National Environmental Policy Act (40 CFR
1501.4(b)), the agency is placing the environmental assessment
submitted with the petition that is the subject of this notice on
public display at the Dockets Management Branch (address above) for
public review and comment. Interested persons may, on or before January
12, 1995, submit to the Dockets Management Branch (address above)
written comments. Two copies of any comments are to be submitted,
except that individuals may submit one copy. Comments are to be
identified with the docket number found in brackets in the heading of
this document. Received comments may be seen in the office above
between 9 a.m. and 4 p.m., Monday through Friday. FDA will also place
on public display any amendments to, or comments on, the petitioner's
environmental assessment without further announcement in the Federal
Register. If, based on its review, the agency finds that an
environmental impact statement is not required and this petition
results in a regulation, the notice of availability of the agency's
finding of no significant impact and the evidence supporting that
finding will be published with the regulation in the Federal Register
in accordance with 21 CFR 25.40(c).
Dated: November 28, 1994.
Alan M. Rulis,
Acting Director, Office of Premarket Approval, Center for Food Safety
and Applied Nutrition.
[FR Doc. 94-30585 Filed 12-12-94; 8:45 am]
BILLING CODE 4160-01-F