[Federal Register Volume 62, Number 10 (Wednesday, January 15, 1997)]
[Rules and Regulations]
[Pages 2011-2014]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-1021]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 175 and 178

[Docket No. 91F-0356]


Indirect Food Additives: Adhesives and Components of Coatings; 
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 2,2'-
ethylidenebis(4,6-di-tert-butylphenyl)fluorophosphonite as an 
antioxidant in adhesives and in the preparation of polymers intended 
for contact with food. This action responds to a petition filed by 
Ethyl Corp.

DATES: Effective January 15, 1997; written objections and requests for 
a hearing by February 14, 1997.

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: Daniel N. Harrison, Center for Food 
Safety and Applied Nutrition (HFS-216), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-418-3084.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of September 30, 1991 (56 FR 49484), FDA announced that a food 
additive petition (FAP 1B4281) had been filed on behalf

[[Page 2012]]

of Ethyl Corp., c/o 1150 17th St. NW., Washington, DC 20036. The 
petition proposed to amend the food additive regulations in 
Sec. 175.105 Adhesives (21 CFR 175.105) and Sec. 178.2010 Antioxidants 
and/or stabilizers for polymers (21 CFR 178.2010) to provide for the 
safe use of 2,2'-ethylidenebis(4,6-di-tert-
butylphenyl)fluorophosphonite as an antioxidant in adhesives and in the 
preparation of polymers intended for contact with food.
    Subsequent to the filing of the petition, Ethyl Corp. was 
reorganized to form Albemarle Corp., an independent corporation. As a 
result of this reorganization, FDA was informed that Albemarle Corp. 
(c/o Lowell Harmison, Gallery House, 2022 R St. NW., Washington, DC 
20009) is now the petitioner of record for this food additive petition.
    In FDA's evaluation of the safety of 2,2'-ethylidenebis(4,6-di-
tert-butylphenyl)fluorophosphonite (CAS Reg. No. 118337-09-0), the 
agency reviewed the safety of the additive, including impurities that 
might be present in the additive. Although the additive itself has not 
been shown to cause cancer, it may contain minute amounts of methylene 
chloride, which is a carcinogenic impurity resulting from the 
manufacture of the additive. Residual amounts of reactants and 
manufacturing aids, such as methylene chloride, are commonly found as 
contaminants in chemical products, including food additives.

I. 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).

II. Safety of the Petitioned Use of the Additive

    FDA estimates that the petitioned uses of the additive, 2,2'-
ethylidenebis(4,6-di-tert-butylphenyl)fluorophosphonite will result in 
exposure to the additive of no greater than 0.70 parts per million in 
the daily diet (3 kilograms) which corresponds to an estimated daily 
intake of no greater than 2.1 milligrams per person per day (mg/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 studies. Based on its review of these studies 
and the low level of exposure to the additive, the agency concludes 
that there is an adequate margin of safety for the proposed use of the 
additive.
    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 lifetime human risk 
presented by the carcinogenic chemical, methylene chloride, that may be 
present as an impurity in the additive. This risk evaluation of 
methylene chloride has two aspects: (1) Assessment of the worst-case 
exposure to this impurity from the proposed use of the additive, and 
(2) extrapolation of the risk observed in the animal bioassays to the 
condition of worst-case exposure to humans.

A. Methylene Chloride

    FDA has estimated the hypothetical worst-case exposure to methylene 
chloride from the petitioned uses of the additive to be no greater than 
0.9 microgram (g)/person/day (Ref. 3). The agency used data 
from the National Toxicology Program report (Ref. 4) of an inhalation 
bioassay on methylene chloride to estimate the upper-bound limit of 
lifetime human risk from exposure to this chemical resulting from the 
proposed use of the petitioned additive. The results of the bioassay 
demonstrated that methylene chloride was carcinogenic for mice under 
the conditions of the study. The test material induced benign and 
malignant neoplasms in both the liver and lung of both sexes.
    The agency also evaluated data from a second study in mice of the 
same strain as used in the inhalation study. In this study, in which 
methylene chloride was administered in the drinking water of the mice 
(Ref. 5), there was no significant increase in the incidence of 
neoplasms at any site examined. However, assuming that methylene 
chloride would induce neoplasia at a dose just above the highest level 
tested in the drinking water study, a maximum potency can be estimated. 
This estimate is approximately the same as the potency calculated from 
the data of the inhalation study, providing confidence that using the 
inhalation study for upper-bound risk assessment is not likely to 
underestimate any potential risk due to ingested methylene chloride 
(Ref. 6).
    Based on the estimated worst-case exposure of 0.9 g/
person/day, FDA estimates that the upper-bound limit of lifetime human 
risk from the uses of this additive is 6.6 x 10-9, or 6.6 in 1 
billion (Ref. 7). Because of numerous conservative assumptions used in 
calculating the exposure estimate, the actual lifetime-averaged 
individual exposure to methylene chloride is likely to be substantially 
less than the worse-case exposure, and therefore even the upper-bound 
limit of lifetime human risk would be less. Thus, the agency concludes 
that there is a reasonable certainty that no harm from exposure to 
methylene chloride would result from the proposed use of the additive.

B. Need for Specifications

    The agency has also considered whether specifications are necessary 
to control the amount of methylene chloride present as an impurity in 
the additive. The agency finds that specifications are not necessary 
for the following reasons: (1) Because of the low levels at which 
methylene chloride may be expected to remain as an impurity, the agency 
would not expect this 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 methylene chloride, even under worst-case 
assumptions, is very low (less than 7 in 1 billion).

III. Conclusion

    FDA has evaluated data in the petition and other relevant material. 
Based on this information, the agency concludes that the proposed use 
of the additive as an antioxidant used in adhesives and in the 
preparation of polymers intended for contact with food is safe, and 
that the additive will achieve its intended technical effect.

[[Page 2013]]

Therefore, the agency concludes that the regulations in Secs. 175.105 
and 178.2010 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 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 February 14, 1997, 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.

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 R. M. Jenkins, Chemistry Review Branch, to D. 
Harrison, Indirect Additives Branch, dated July 23, 1992.
    2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in 
Chemical Safety Regulation and Compliance, edited by F. Hombuger, J. 
K. Marquis, and S. Karger, New York, NY, pp. 24-33, 1985.
    3. Memorandum from R. M. Jenkins, Chemistry Review Branch, to D. 
Harrison, Indirect Additives Branch, dated March 22, 1993.
    4. ``Toxicology and Carcinogenesis Studies of Dichloromethane 
(Methylene Chloride) (CAS Reg. No. 75-09-2) in F344/N Rats and 
B6C3F1 Mice (Inhalation Studies),'' NTP Technical Report 306, 
National Institutes of Health, Publication No. 86-2562, 1986.
    5. Memorandum from C. S. Lin, Food Additives Evaluation Branch, 
to R. Lorentzen, Executive Secretary, Cancer Assessment Committee, 
dated August 21, 1985.
    6. Memorandum from the Quantitative Risk Assessment Committee to 
W. G. Hamm, Director, Office of Toxicology, dated November 15, 1985.
    7. Memorandum from D. N. Harrison, Indirect Additives Branch, to 
S. H. Henry, Quantitative Risk Assessment Committee, dated November 
8, 1993.

List of Subjects

21 CFR Part 175

    Adhesives, Food additives, Food packaging.

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 parts 
175 and 178 are amended as follows:

PART 175--INDIRECT FOOD ADDITIVES: ADHESIVES AND COMPONENTS OF 
COATINGS

    1. The authority citation for 21 CFR part 175 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. Section 175.105 is amended in the table in paragraph (c)(5) by 
alphabetically adding a new entry under the headings ``Substances'' and 
``Limitations'' to read as follows:

Sec. 175.105  Adhesives.

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    (c) * * *
    (5) * * *

                                                                        
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                Substances                           Limitations        
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2,2'-Ethylidenebis(4,6-di-tert-             For use as an antioxidant   
 butylphenyl)fluorophosphonite (CAS Reg.     and/or stabilizer only.    
 No. 118337-09-0).                                                      
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                   *                    *                    *          
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PART 178--INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND 
SANITIZERS

    3. 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).

    4. Section 178.2010 is amended in the table in paragraph (b) by 
alphabetically adding a new entry under the headings ``Substances'' and 
``Limitations'' to read as follows:

Sec. 178.2010  Antioxidants and/or stabilizers for polymers.

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[[Page 2014]]



                                                                        
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          Substances                          Limitations               
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2,2'-Ethylidenebis(4,6-di-     For use only:                            
 tert-                         1. As provided in Sec.  175.105 of this  
 butylphenyl)fluorophosphonit   chapter.                                
 e (CAS Reg. No. 118337-09-    2. In all polymers used in contact with  
 0).                            food of types I, II, IV-B, VI-A, VI-B,  
                                VII-B, and VIII, under conditions of use
                                B through H described in Tables 1 and 2 
                                of Sec.  176.170(c) of this chapter at  
                                levels not to exceed 0.25 percent by    
                                weight of polymers.                     
                               3. In polypropylene complying with Sec.  
                                177.1520(c) of this chapter, item 1.1,  
                                in contact with food of types III, IV-A,
                                V, VII-A, and IX, under:                
                               (a) Conditions of use B through H        
                                described in Tables 1 and 2 of Sec.     
                                176.170(c) of this chapter at levels not
                                to exceed 0.25 percent by weight of the 
                                polymer; or                             
                               (b) Condition of use A, limited to levels
                                not to exceed 0.1 percent by weight of  
                                the polymer; provided that the food-    
                                contact surface has an average thickness
                                not exceeding 375 micrometers (0.015    
                                inch).                                  
                               4. In olefin copolymers complying with   
                                Sec.  177.1520(c) of this chapter, items
                                3.1a or 3.2a, and containing not less   
                                than 85 percent by weight of polymer    
                                units derived from propylene, in contact
                                with food of types III, IV-A, V, VII-A, 
                                and IX, and under:                      
                               (a) Conditions of use C through G,       
                                described in Tables 1 and 2 of Sec.     
                                176.170(c) of this chapter, limited to  
                                levels no greater than 0.2 percent by   
                                weight of the copolymers; or            
                               (b) Conditions of use A, B, and H,       
                                limited to levels no greater than 0.1   
                                percent by weight of the olefin         
                                copolymers; provided that the food-     
                                contact surface has an average thickness
                                not exceeding 375 micrometers (0.015    
                                inch).                                  
                               5. In olefin polymers complying with Sec.
                                 177.1520(c) of this chapter, items 1.2 
                                or 1.3 in contact with food of types    
                                III, IV-A, V, VII-A, and IX, under      
                                conditions of use A through H, described
                                in Tables 1 and 2 of Sec.  176.170(c) of
                                this chapter at levels not to exceed 0.1
                                percent by weight of the polymers;      
                                provided that the food-contact surface  
                                has an average thickness not exceeding  
                                375 micrometers (0.015 inch).           
                               6. In polyethylene complying with Sec.   
                                177.1520(c) of this chapter, items 2.1  
                                or 2.2, having a density of not less    
                                than 0.94, in contact with food of types
                                III, IV-A, V, VII-A, and IX, and under: 
                               (a) Conditions of use B through H,       
                                described in Tables 1 and 2 of Sec.     
                                176.170(c) of this chapter limited to   
                                levels not to exceed 0.2 percent by     
                                weight of the polymers; or              
                               (b) Condition of use A, described in     
                                Tables 1 and 2 of Sec.  176.170(c) of   
                                this chapter, limited to levels not to  
                                exceed 0.1 percent by weight of the     
                                polymer; provided that the food-contact 
                                surface has an average thickness not    
                                exceeding 125 micrometers (0.005 inch). 
                               7. In olefin copolymers complying with   
                                Sec.  177.1520(c) of this chapter, items
                                3.1a, 3.1b, 3.2a, or 3.2b, containing   
                                not less than 85 percent by weight of   
                                polymer units derived from ethylene and 
                                having a density of not less than 0.94, 
                                in contact with food of types III, IV-A,
                                V, VII-A, and IX, and under:            
                               (a) Conditions of use C through G,       
                                described in Tables 1 and 2 of Sec.     
                                176.170(c) of this chapter limited to   
                                levels not to exceed 0.2 percent by     
                                weight of the copolymers; or            
                               (b) Conditions of use A, B, and H,       
                                limited to levels not to exceed 0.1     
                                percent by weight of the copolymers;    
                                provided that the food-contact surface  
                                has an average thickness not exceeding  
                                125 micrometers (0.005 inch).           
                               8. In olefin polymers complying with Sec.
                                 177.1520(c) of this chapter, items     
                                3.1a, 3.1b, 3.2a, or 3.2b containing not
                                less than 85 percent by weight of       
                                polymer units derived from ethylene, in 
                                contact with food of types III, IV-A, V,
                                VII-A, and IX, under conditions of use A
                                through H, as described in Tables 1 and 
                                2 of Sec.  176.170(c) of this chapter at
                                levels not to exceed 0.1 percent by     
                                weight of the copolymer; provided that  
                                the food-contact surface has an average 
                                thickness not exceeding 75 micrometers  
                                (0.003 inch).                           
                               9. In polyethylene phthalate polymers    
                                complying with Sec.  177.1630 of this   
                                chapter in contact with food of types   
                                III, IV-A, V, VI-C, VII-A, and IX, and  
                                under:                                  
                               (a) Conditions of use B through H,       
                                described in Tables 1 and 2 of Sec.     
                                176.170(c) of this chapter, limited to  
                                levels not to exceed 0.3 percent by     
                                weight of the polymers; or              
                               (b) Condition of use A with food of types
                                III, IV-A, V, VII-A, and IX, and limited
                                to levels not to exceed 0.1 percent by  
                                weight of the polymers; provided that   
                                the film thickness does not exceed 875  
                                micrometers (0.035 inch).               
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    Dated: January 6, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-1021 Filed 1-14-97; 8:45 am]
BILLING CODE 4160-01-F