[Federal Register Volume 61, Number 99 (Tuesday, May 21, 1996)]
[Rules and Regulations]
[Pages 25392-25395]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-12762]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 176

[Docket No. 92F-0313]


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 diethanolamine as a 
boiler water additive in paper mill boilers used in the manufacture of 
paper and paperboard intended for use in contact with aqueous and fatty 
food. This action is in response to a food additive petition filed by 
Betz Laboratories, Inc.

DATES: Effective May 21, 1996; written objections and requests for a 
hearing by June 20, 1996.

ADDRESSES: Submit written objections to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm 1-23, 
Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Diane E. Robertson, Center for Food 
Safety and Applied Nutrition (HFS-216), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-418-3089.


[[Page 25393]]



SUPPLEMENTARY INFORMATION:

I. Background

     In a notice published in the Federal Register of September 14, 
1992 (57 FR 41944), FDA announced that a food additive petition (FAP 
2B4329) had been filed by Betz Laboratories, Inc., 4636 Somerton Rd., 
Trevose, PA 19053-6783. The petition proposed to amend the food 
additive regulations in Sec. 176.170 Components of paper and paperboard 
in contact with aqueous and fatty foods (21 CFR 176.170) to provide for 
the safe use of diethanolamine as a boiler water additive in paper mill 
boilers.
    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 may 
contain minute amounts of 1,4-dioxane and ethylene oxide, which are 
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.

II. Determination of Safety

    Under the so-called ``general safety clause'' 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 the 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 
clause using risk assessment procedures to determine whether there is a 
reasonable certainty that no harm will result from the proposed use of 
the additive, Scott v. FDA, 728 F.2d 322 (6th Cir. 1984).

III. Safety of Petitioned Use of the Additive

    FDA estimates that the petitioned use of the additive, 
diethanolamine, will result in exposure to no greater than 5 parts per 
billion (ppb) of the additive in the daily diet (3 kilograms (kg)) or 
an estimated daily intake (EDI) of 15 micrograms per person per day 
(/person/day) (Ref. 1) and that the cumulative dietary 
concentration of the additive from all regulated uses is conservatively 
58 ppb in the daily diet or an EDI of 170 /person/day.
    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 a small 
increase in dietary exposure is safe.
    FDA has evaluated the safety of this additive under the general 
safety clause, considering all available data and using risk assessment 
procedures to estimate the upper-bound limit of risk presented by 1,4-
dioxane and ethylene oxide, 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 worst-case 
exposure to these impurities from the proposed use of the additive; and 
(2) extrapolation of the risk observed in the animal bioassays to the 
conditions of probable exposure to humans.

 A. 1,4-Dioxane

    FDA has estimated the hypothetical worst-case exposure to 1,4-
dioxane from the petitioned use of the additive in the manufacture of 
paper to be 0.6 part per quadrillion (ppq) of the daily diet (3 kg), or 
2 picograms (pg)/person/day (Ref. 3). The agency used data from a 
carcinogenesis bioassay on 1,4-dioxane conducted by the National Cancer 
Institute (Ref. 4), to estimate the upper-bound limit of lifetime human 
risk from exposure to this chemical resulting from the proposed use of 
the additive (Ref. 4). The results of the bioassay on 1,4-dioxane 
demonstrated that the material was carcinogenic for female rats under 
the conditions of the study. The test material caused significantly 
increased incidence of squamous cell carcinomas and hepatocellular 
tumors in female rats.
    Based on the estimated worst-case exposure to 1,4-dioxane of 2 pg/
person/day, FDA estimates that the upper-bound limit of lifetime human 
risk from the use of the subject additive is 6.9 x 10-14, or 6.9 
in 100 trillion (Ref. 5). Because of the numerous conservative 
assumptions used in calculating the exposure estimate, the actual 
lifetime-averaged individual exposure to 1,4-dioxane is expected to be 
substantially less than the worst-case exposure, and therefore, the 
upper-bound limit of risk would be less. Thus, the agency concludes 
that there is a reasonable certainty that no harm from exposure to 1,4-
dioxane would result from the proposed use of the additive.

 B. Ethylene Oxide

    FDA has estimated the hypothetical worst-case exposure to ethylene 
oxide from the petitioned use of the additive in the manufacture of 
paper to be 0.6 ppq of the daily diet (3 kg), or 2 pg/person/day (Ref. 
3). The agency used data from a carcinogenesis bioassay on ethylene 
oxide conducted for the Institute of Hygiene, University of Mainz, 
Germany to estimate the upper-bound limit of lifetime human risk from 
exposure to ethylene oxide resulting from the proposed use of the 
additive (Ref. 6). The results of the bioassay on ethylene oxide 
demonstrated that the material was carcinogenic for female rats under 
the conditions of the study. The test material caused significantly 
increased incidence of squamous cell carcinomas of the forestomach and 
carcinomas in situ of the glandular stomach.
    Based on the estimated worst-case exposure to ethylene oxide of 2 
pg/person/day, FDA estimates that the upper-bound limit of lifetime 
human risk from the use of the subject additive is 3.7 x 10-12, or 
3.7 in 1 trillion (Ref. 5). Because of the numerous conservative 
assumptions used in calculating the exposure estimate, actual lifetime-
averaged individual exposure to ethylene oxide is likely to be 
substantially less than the worst-case exposure, and therefore, the 
upper-bound limit of risk would be less. Thus, the agency concludes 
that there is a reasonable certainty that no harm from exposure to 
ethylene oxide would result from the proposed 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 present 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 these impurities to

[[Page 25394]]

become components of food at other than extremely small levels; and (2) 
the upper-bound limits of lifetime risk from exposure to these 
impurities, even under worst-case assumptions, are very low, less than 
6.9 in 100 trillion for 1,4-dioxane and less than 3.7 in 1 trillion for 
ethylene oxide, respectively.

IV. Conclusion

    FDA has evaluated the data in the petition and other relevant 
material and concludes that the proposed use of the additive in paper 
mill boilers used in the manufacture of paper and paperboard products 
intended for use in contact with aqueous and fatty food is safe. Based 
on this information, the agency has also concluded that the additive 
will have the intended technical effect. Therefore, Sec. 176.170 should 
be amended as set forth below.
    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 above. As provided in 21 CFR 
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.

V. Environmental Impact

    The agency has carefully considered the potential environmental 
effects of this action. FDA has concluded that the action will not have 
a significant impact on the human environment, and that an 
environmental impact statement is not required. The agency's finding of 
no significant impact and the evidence supporting that finding, 
contained in an environmental assessment, may be seen in the Dockets 
Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
through Friday.

 VI. Objections

    Any person who will be adversely affected by this regulation may at 
any time on or before June 20,1996, 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 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. Memorandum dated September 8, 1993, from the Chemistry Review 
Branch (HFS-247), to the Indirect Additives Branch (HFS-216) 
concerning ``FAP 2B4329 (MATS No. 654; M 2.1). Submission of 6/5/92; 
Betz Laboratories. Diethanolamine in papermill boilers.''
    2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in 
Chemical Safety Regulation and Compliance, edited by F. Homburger 
and J. K. Marquis, S. Karger, New York, NY, pp. 24-33, 1985.
    3. Memorandum dated April 28, 1994, from the Chemistry Review 
Branch (HFS-247) to the Indirect Additives Branch (HFS-216) 
concerning ``FAP 2B4329 (MATS No. 654; M 2.4): Diethanolamine. Paper 
mill boiler additive. Betz Laboratories-Submission of 4/8/94.''
    4. ``Bioassay of 1,4-Dioxane for Possible Carcinogenicity,'' 
National Cancer Institute, NCI-CG-TR-80, 1978.
    5. Memorandum, Report of the Quantitative Risk Assessment 
Committee, October 28, 1994.
    6. Dunkelberg, H., ``Carcinogenicity of Ethylene Oxide and 1,2-
Propylene Oxide Upon Intragastric Administration to Rats,'' British 
Journal of Cancer, 46:924, 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: Secs. 201, 402, 406, 409, 721 of the Federal Food, 
Drug, and Cosmetic Act (21 U.S.C. 321, 342, 346, 348, 379e).

    2. Section 176.170 is amended in the table in paragraph (a)(5) by 
revising the entry for ``Diethanolamine'' under the heading 
``Limitations'' to read as follows:


Sec. 176.170  Components of paper and paperboard in contact with 
aqueous and fatty foods.

 * * * * *
     (a) * * *
     (5) * * *

                                                                        
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          List of Substances                      Limitations           
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  *                    *                    *                    *      
                   *                    *                    *          
Diethanolamine.......................  For use only:                    
                                       1. As an adjuvant to control pulp
                                        absorbency and pitch content in 
                                        the manufacture of paper and    
                                        paperboard prior to the sheet-  
                                        forming operation.              
                                       2. In paper mill boilers.        
  *                    *                    *                    *      
                   *                    *                    *          
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[[Page 25395]]


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    Dated: May 15, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-12762 Filed 5-20-96; 8:45 am]
BILLING CODE 4160-01-F