[Federal Register Volume 64, Number 163 (Tuesday, August 24, 1999)]
[Rules and Regulations]
[Pages 46130-46132]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-21850]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 176

[Docket No. 98F-0871]


Indirect Food Additives: Paper and Paperboard Components

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the food 
additive regulations to provide for the safe use of polyethylene glycol 
monoisotridecyl ether sulfate, sodium salt as a component of coatings 
on paper and paperboard intended for use in contact with dry food. This 
action is in response to a petition filed by Servo Deldon BV.

DATES: This regulation is effective August 24, 1999; submit written 
objections and requests for a hearing by September 23, 1999.

ADDRESSES: Submit written objections to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Mark A. Hepp, Center for Food Safety 
and Applied Nutrition (HFS-215), Food and Drug Administration, 200 C 
St. SW., Washington, DC 20204, 202-418-3098.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of October 13, 1998, (63 FR 54717), FDA announced that a food 
additive petition (FAP 8B4630) had been filed by Servo Deldon BV, c/o 
Keller and Heckman LLP, 1001 G St. NW., suite 500 West, Washington, DC 
20001. The petition proposed to amend the food additive regulations in 
Sec. 176.180 Components of paper and paperboard in contact with dry 
food (21 CFR 176.180) to provide for the safe use of polyethylene 
glycol monoisotridecyl ether sulfate, sodium salt as a component of 
coatings on paper and paperboard intended for use in contact with dry 
food.
     In its evaluation of the safety of this additive, FDA has reviewed 
the safety of the additive itself and the chemical impurities that may 
be present in the additive resulting from its manufacturing process. 
Although the additive itself has not been shown to cause cancer, it has 
been found to contain minute amounts of unreacted 1,4-dioxane and 
ethylene oxide, carcinogenic impurities resulting from the manufacture 
of the additive. Residual amounts of reactants and manufacturing aids, 
such as 1,4-dioxane and ethylene oxide, are commonly found as 
contaminants in chemical products, including food additives.

I. Determination of Safety

     Under the general safety standard of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 348(c)(3)(A)), a food additive cannot 
be approved for a particular use unless a fair evaluation of the data 
available to FDA establishes that the additive is safe for that use. 
FDA's food additive regulations (21 CFR 170.3(i)) define safe as a `` 
reasonable certainty in the minds of competent scientists that the 
substance is not harmful under the intended conditions of use.''
    The food additives anticancer, or Delaney, clause of the act (21 
U.S.C. 348(c)(3)(A)) provides that no food additive shall be deemed 
safe if it is found to induce cancer when ingested by man or animal. 
Importantly, however, the Delaney clause applies to the additive itself 
and not to impurities in the additive. That is, where an additive 
itself has not been shown to cause cancer, but contains a carcinogenic 
impurity, the additive is properly evaluated under the general safety 
standard using risk assessment procedures to determine whether there is 
a reasonable certainty that no harm will result from the intended use 
of the additive (Scott v. FDA, 728 F.2d 322 (6th Cir. 1984)).

[[Page 46131]]

II. Safety of Petitioned Use of the Additive

     FDA estimates that the petitioned use of the additive, 
polyethylene glycol monoisotridecyl ether sulfate, sodium salt as a 
surfactant in coatings for paper and paperboard in contact with dry 
foods, will result in exposure to no greater than 50 parts per billion 
(ppb) of the additive in the daily diet (3 kilogram (kg)) or an 
estimated daily intake (EDI) of 0.15 milligrams per person per day (mg/
p/d) (Ref. 1).
     FDA does not ordinarily consider chronic toxicological studies to 
be necessary to determine the safety of an additive whose use will 
result in such low exposure levels (Ref. 2), and the agency has not 
required such testing here. However, the agency has reviewed the 
available toxicological data on the additive and concludes that the 
estimated small dietary exposure resulting from the petitioned use of 
the additive is safe.
     FDA has evaluated the safety of this additive under the general 
safety standard, considering all available data and using risk 
assessment procedures to estimate the upper-bound limit of lifetime 
human risk presented by 1,4-dioxane and ethylene oxide, the 
carcinogenic chemicals that may be present as impurities in the 
additive. This risk evaluation of 1,4-dioxane and ethylene oxide has 
two aspects: (1) Assessment of the exposure to the impurities from the 
petitioned use of the additive and (2) extrapolation of the risk 
observed in the animal bioassays to the conditions of exposure to 
humans.

A. 1,4-Dioxane

     FDA has estimated the exposure to 1,4-dioxane from the petitioned 
use of the additive as a surfactant in coatings for paper and 
paperboard in contact with dry foods to be no more than 0.2 ppb of the 
daily diet (3 kg) or 0.6 micrograms per person per day (g/p/d) 
(Ref. 1). The agency used data from a carcinogenesis bioassay on 1,4-
dioxane, conducted by the National Cancer Institute (Ref. 3), to 
estimate the upper-bound limit of lifetime human risk from exposure to 
this chemical resulting from the petitioned use of the additive. The 
authors reported that the test material caused a significantly 
increased incidence of squamous cell carcinomas and hepatocellular 
tumors in female rats. Based on the agency's estimate that exposure to 
1,4-dioxane will not exceed 0.6 g/p/d, FDA estimates that the 
upper-bound limit of lifetime human risk from the petitioned use of the 
subject additive is 2.1 x 10-8 (or 2.1 in 100 million) (Ref. 
4). Because of the numerous conservative assumptions used in 
calculating the exposure estimate, the actual lifetime-averaged 
individual exposure to 1,4-dioxane is likely to be substantially less 
than the estimated exposure, and therefore, the probable lifetime human 
risk would be less than the upper-bound limit of lifetime human risk. 
Thus, the agency concludes that there is reasonable certainty that no 
harm from exposure to 1,4-dioxane would result from the petitioned use 
of the additive.

 B. Ethylene Oxide

     FDA has estimated the exposure to ethylene oxide from the 
petitioned use of the additive as a surfactant in coatings for paper 
and paperboard in contact with dry foods to be no more than 3.9 parts 
per trillion in the daily diet (3 kg) or 12 nanograms per person per 
day (ng/p/d) (Ref. 1). The agency used data from a carcinogenesis 
bioassay on ethylene oxide conducted by the Institute of Hygiene, 
University of Mainz, Germany (Ref. 5), to estimate the upper-bound 
limit of lifetime human risk from exposure to ethylene oxide resulting 
from the petitioned use of the additive. The authors reported that the 
test material caused significantly increased incidence of squamous cell 
carcinomas of the forestomach and carcinomas in situ of the glandular 
stomach in female rats. Based on the agency's estimate that exposure to 
ethylene oxide will not exceed 12 ng/p/d, FDA estimates that the upper-
bound limit of lifetime human risk from the petitioned use of the 
subject additive is 2.24 x 10-8 (or 2.24 in 100 million)) 
(Ref. 4). Because of the numerous conservative assumptions used in 
calculating the exposure estimate, the actual lifetime-averaged 
individual exposure to ethylene oxide is likely to be substantially 
less than the estimated exposure, and therefore, the probable lifetime 
human risk would be less than the upper-bound limit of lifetime human 
risk. Thus, the agency concludes that there is reasonable certainty 
that no harm from exposure to ethylene oxide would result from the 
petitioned use of the additive.

 C. Need for Specifications

     The agency has also considered whether specifications are 
necessary to control the amount of 1,4-dioxane and ethylene oxide as 
impurities in the additive. The agency finds that specifications are 
not necessary for the following reasons: (1) Because of the low level 
at which 1,4-dioxane and ethylene oxide may be expected to remain as 
impurities following production of the additive, the agency would not 
expect the impurities to become components of food at other than 
extremely small levels; and (2) the upper-bound limits of lifetime risk 
from exposure to 1,4-dioxane and ethylene oxide is very low, 2.1 in 100 
million and 2.24 in 100 million, respectively.

 III. Conclusion

     FDA has evaluated the data in the petition and other relevant 
material. Based on this information, the agency concludes that the 
proposed use of the additive in adhesives is safe, that the additive 
will achieve its intended technical effect, and therefore, that the 
regulations in Sec. 176.180 should be amended as set forth below in 
this document.
     In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition 
and the documents that FDA considered and relied upon in reaching its 
decision to approve the petition are available for inspection at the 
Center for Food Safety and Applied Nutrition by appointment with the 
information contact person listed previously. As provided in 
Sec. 171.1(h), the agency will delete from the documents any materials 
that are not available for public disclosure before making the 
documents available for inspection.

 IV. Environmental Impact

     The agency has previously considered the environmental effects of 
this rule as announced in the notice of filing for FAP 8B4630 (October 
13, 1998, 63 FR 54717). No new information or comments have been 
received that would affect the agency's previous determination that 
there is no significant impact on the human environment and that an 
environmental impact statement is not required.

 V. Paperwork Reduction Act of 1995

     This final rule contains no collection of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

 VI. Objections

     Any person who will be adversely affected by this regulation may 
at any time on or before September 23, 1999, file with the Dockets 
Management Branch (address above) written objections thereto. Each 
objection shall be separately numbered, and each numbered objection 
shall specify with particularity the provisions of the regulation to 
which objection is made and the grounds for the objection. Each 
numbered objection on which a hearing is requested shall specifically 
so state. Failure to request a hearing for any

[[Page 46132]]

particular objection shall constitute a waiver of the right to a 
hearing on that objection. Each numbered objection for which a hearing 
is requested shall include a detailed description and analysis of the 
specific factual information intended to be presented in support of the 
objection in the event that a hearing is held. Failure to include such 
a description and analysis for any particular objection shall 
constitute a waiver of the right to a hearing on the objection. Three 
copies of all documents shall be submitted and shall be identified with 
the docket number found in brackets in the heading of this document. 
Any objections received in response to the regulation may be seen in 
the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through 
Friday.

 VII. References

     The following references have been placed on display in the 
Dockets Management Branch (address above) and may be seen by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday.
     1. Memoranda, dated January 13, 1999, and March 8, 1999, from 
the Chemistry Review Team, FDA, to the file concerning FAP 8B4630 
(MATS No. 1011), Servo Delden BV, concerning the use of polyethylene 
glycol monoisotridecyl ether sulfate sodium salt as a surfactant in 
coatings in food-contact paper and paperboard,
     2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in 
``Chemical Safety Regulation and Compliance,'' edited by F. 
Homburger and J. K. Marquis, published by S. Karger, New York, NY, 
pp. 24-33, 1985.
    3. ``Bioassay of 1,4-Dioxane for Possible Carcinogenicity,'' 
National Cancer Institute, NCI-CG-TR-80, 1978.
    4. Memorandum, dated January 25, 1999, from the Indirect 
Additives Branch, FDA, to the Executive Secretary, Quantitative Risk 
Assessment Committee, FDA, concerning estimation of upper-bound 
lifetime risk from ethylene oxide and 1,4-dioxane in polyethylene 
glycol monoisotridecyl ether sulfate, sodium salt (PGMES): food 
additive petition No. 8B4630 (Servo Delden BV).
     5. Dunkelberg, H., ``Carcinogenicity of Ethylene Oxide and 1,2-
propylene Oxide Upon Intragastric Administration to Rats,''British 
Journal of Cancer, 46: pp. 924-933, 1982.

 List of Subjects in 21 CFR Part 176

     Food additives, Food packaging.
     Therefore, under the Federal Food, Drug, and Cosmetic Act and 
under authority delegated to the Commissioner of Food and Drugs, 21 CFR 
part 176 is amended as follows:

PART 176--INDIRECT FOOD ADDITIVES: PAPER AND PAPERBOARD COMPONENTS

     1. The authority citation for 21 CFR part 176 continues to read as 
follows:
    Authority: 21 U.S.C. 321, 342, 346, 348, 379e.
     2. Section 176.180 is amended in the table in paragraph (b)(2) by 
alphabetically adding an entry under the headings ``Lists of 
Substances'' and ``Limitations'' to read as follows:


Sec. 176.180   Components of paper and paperboard in contact with dry 
food.

* * * * *
    (b) * * *
    (2) * * *

 
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          List of Substances                      Limitations
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  *                    *                    *                    *
                   *                    *                    *
Polyethylene glycol monoisotridecyl    For use only as a surfactant at
 ether sulfate, sodium salt (CAS Reg.   levels not to exceed 3 percent
 No. 150413-26-6).                      in latex formulations used in
                                        pigment binders for paper and
                                        paperboard.
  *                    *                    *                    *
                   *                    *                    *
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    Dated: August 5, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-21850 Filed 8-23-99; 8:45 am]
BILLING CODE 4160-01-F