[Federal Register Volume 61, Number 163 (Wednesday, August 21, 1996)]
[Rules and Regulations]
[Pages 43156-43158]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-21229]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 178

[Docket No. 92F-0475]


Indirect Food Additives: Adjuvants, Production Aids, and 
Sanitizers

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 phosphorylated tall 
oil fatty acids as pigment dispersants in polymeric films intended for 
use in contact with food. This action is in response to a petition 
filed by SCM Chemicals.

DATES: Effective August 21, 1996; written objections and requests for a 
hearing September 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: Vir D. Anand, Center for Food Safety 
and Applied Nutrition (HFS-216), Food and Drug Administration, 200 C 
St. SW., Washington, DC 20204, 202-418-3081.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of February 9, 1993 (58 FR 7789), FDA announced that a food 
additive petition (FAP 3B4350) had been filed by SCM Chemicals, c/o 
1001 G St. NW., suite 500 West, Washington, DC 20001 (formerly, 1100 G 
St. NW., Washington, DC 20001). The petition proposed to amend the food 
additive regulations to add a new Sec. 178.3725 Pigment dispersants (21 
CFR 178.3725) to provide for the safe use of phosphorylated tall oil 
fatty acids as pigment dispersants in polymeric films intended for use 
in contact with food.
    In the FDA evaluation of the safety of this food additive, the 
agency 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 
dimethyl hydrogen phosphite, which is a carcinogenic impurity resulting 
from the manufacture of the additive. Residual amounts of reactants and 
manufacturing aids, such as dimethyl hydrogen phosphite, are commonly 
found as contaminants in chemical products, including food additives.

I. Determination of Safety

    Under the so-called ``general safety clause'' section 409(c)(A) of 
the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 
348(c)(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 additive anticancer, or Delaney, clause of the act section 
409(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).

II. Safety of Petitioned Use of the Additive

    FDA estimates that the petitioned use of the additive, 
phosphorylated tall oil fatty acids, will result in exposure to no 
greater than 2.3 parts per billion (ppb) of the additive in the daily 
diet (3 kilogram (kg)) or an estimated daily intake (EDI) of 7 
microgram per person per day (g/person/day) (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 to this additive 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 
dimethyl hydrogen phosphite, the carcinogenic chemical that may be 
present as an impurity in the additive. The risk evaluation of dimethyl 
hydrogen phosphite has two aspects: (1) Assessment of the worst-case 
exposure to the impurity from the proposed use of the additive; and (2) 
extrapolation of the risk observed in the animal bioassay to the 
conditions of probable exposure to humans.

A.  Dimethyl Hydrogen Phosphite

     FDA has estimated the hypothetical worst-case exposure to dimethyl 
hydrogen phosphite from the petitioned use of the additive as a pigment 
dispersant in polymeric films to be 0.009 ppb in the daily diet (3 kg), 
or 27 nanograms/person/day (Ref. 1). The Cancer Assessment Committee 
(CAC) of the Center for Food Safety and Applied Nutrition (CFSAN) 
reviewed data from a 103- week carcinogenic bioassay on dimethyl 
hydrogen phosphite in F344/N rats and B6C3F1 mice conducted by the 
National Toxicology Program (NTP). The results of the bioassay on 
dimethyl hydrogen phosphite demonstrated that the material induced lung 
and forestomach neoplasms in male rats when administered by gavage in 
corn oil. The agency used the data reviewed by the CAC to estimate the 
upper-bound limit of lifetime human risk from exposure to this chemical 
resulting from the proposed use of the additive.
    Based on the estimated worst-case exposure to dimethyl hydrogen 
phosphite of 7 g/person/day, FDA's CFSAN estimates that a 
worst-case upper-bound limit of lifetime human risk from the use of the 
subject additive is 1.4 x 10-9, or 1.4 in one billion (Refs. 4 and 
5). Because of the numerous conservative assumptions used in 
calculating the exposure estimate, the actual lifetime-averaged 
individual exposure to dimethyl hydrogen phosphite is likely to be 
substantially less than the worst-case exposure, and therefore, the 
upper-bound lifetime human risk would be less. Thus, the agency 
concludes that there is reasonable certainty that no harm from exposure 
to dimethyl hydrogen phosphite would result from the proposed use of 
the additive.

[[Page 43157]]

B. -Need for Specifications

    The agency has also considered whether specifications are necessary 
to control the amount of dimethyl hydrogen phosphite present as an 
impurity in the additive. The agency finds that specifications are not 
necessary for the following reasons: (1) Because of the low level at 
which dimethyl hydrogen phosphite may be expected to remain as an 
impurity following production of the additive, the agency would not 
expect the impurity to become a component of food at other than 
extremely low levels; and (2) the upper-bound limit of lifetime human 
risk from exposure to the impurity, even under worst-case assumptions, 
is very low, less than 1.4 in a billion.

III. Conclusion

    FDA has evaluated the data in the petition and other relevant 
material and concludes that the proposed use of the additive as a 
pigment dispersant in polymeric films intended for use in contact with 
food is safe. Based on this information, the agency has also concluded 
that the additive will achieve its intended technical effect. 
Therefore, the agency concludes that a new Sec. 178.3725 should be 
added to part 178 (21 CFR part 178) 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 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 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.

V. Objections

    Any person who will be adversely affected by this regulation may at 
any time on or before September 20, 1996, file with the Dockets 
Management Branch (address above) written objection 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 objection 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.

VI. 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 from the Chemistry Review Branch (HFS-247) to the 
Indirect Additives Branch (HFS-216) concerning FAP 3B4350: Dietary 
Concentrations of the Additive and the Impurity (dimethyl hydrogen 
phosphite), April 28, 1994.
    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. ``Toxicology and Carcinogenesis Studies of Dimethyl Hydrogen 
Phosphite,'' National Toxicology Program, Technical Report, #287, 
November 1985.
    4. Memorandum from Executive Secretary, Cancer Assessment 
Committee (HFS-227) to Chairman, Cancer Assessment Committee, and 
Chairman, Quantitative Risk Assessment Committee: ``Tentative, 
Worst-case Risk Assessment for Dimethyl Hydrogen Phosphite,'' 
January 4, 1996.
    5. Memorandum from Executive Secretary, Cancer Assessment 
Committee (HFS-227) to Chairman, Cancer Assessment Committee, and 
Chairmen, Quantitative Risk Assessment Committee: ``Risk Assessment 
for Dimethyl Hydrogen Phosphite (DMHP),'' June 26, 1996.

List of Subjects in 21 CFR Part 178

    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 
178 is amended as follows:

PART 178--INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND 
SANITIZERS

    1. The authority citation for 21 CFR part 178 continues to read as 
follows:
    Authority: Secs. 201, 402, 409, 721 of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 321, 342, 348, 379e).

    2. New Sec. 178.3725 is added to subpart D to read as follows:


Sec. 178.3725  Pigment dispersants.

    Subject to the provisions of this regulation, the substances listed 
in this section may be safely used as pigment dispersants in food-
contact materials.

                                                                        
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              Substances                          Limitations           
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Phosphorylated tall oil fatty acids    For use only at levels not to    
 (CAS Reg. No. 68604-99-9), prepared    exceed 1.0 percent by weight of 
 by the reaction of dimethyl hydrogen   the pigment. The pigmented      
 phosphite with tall oil fatty acids.   polymeric films may contact all 
                                        food under conditions of use D, 
                                        E, F, and G described in Table 2
                                        of Sec.  176.170(c) of this     
                                        chapter.                        
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[[Page 43158]]



    Dated: August 13, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-21229 Filed 8-20-96; 8:45 am]
BILLING CODE 4160-01-F