[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