Roquette America, Inc.; Filing of Food Additive Petition

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]

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