[Federal Register Volume 60, Number 54 (Tuesday, March 21, 1995)]
[Proposed Rules]
[Pages 14918-14919]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-6919]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

 21 CFR Parts 101, 111, 170, and 310

[Docket Nos. 91P-0186 and 93P-0306]


Acute Toxicity of Elemental (Reduced, Metallic Powder) Forms of 
Iron Relative to That of Iron Salts; Notice of a Public Workshop

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a public 
workshop on the acute toxicity of elemental (reduced, metallic powder) 
forms of iron. The purpose of this workshop is to solicit scientific 
data and information from interested persons about the acute toxicity 
of elemental forms of iron with regard to whether such forms are 
sufficiently safe in dietary supplement and drug products to warrant 
exemption from the special packaging and labeling requirements that FDA 
has proposed for products containing iron salts.

DATES: The public workshop will be held on April 20, 1995, 8:30 a.m. to 
5 p.m. Submit written comments by April 20, 1995.

ADDRESSES: The public workshop will be held at the Parklawn Bldg., 
conference room G, 5600 Fishers Lane, Rockville, MD 20857. Written 
comments regarding the workshop may be submitted to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, rm. 1-23, 
12420 Parklawn Dr., Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: John N. Hathcock, Center for Food 
Safety and Applied Nutrition (HFS-465), Food and Drug Administration, 
8301 Muirkirk Rd., Laurel, MD 20708, 301-594-6006.

SUPPLEMENTARY INFORMATION: In the Federal Register of October 6, 1994 
(59 FR 51030), FDA issued a proposal (the initial proposal) on actions 
that it tentatively concluded were necessary to stem the recent 
epidemic of pediatric poisonings from over-consuming iron-containing 
products. In the Federal Register of February 16, 1995 (60 FR 8989), 
the agency issued a supplementary proposal to clarify changes in its 
legal authority with the passage of the Dietary Supplement Health and 
Education Act (Pub. L. 103-417).
    In the initial proposal, FDA briefly described the three basic 
types of elemental iron powders that are marketed for use in foods. The 
three types are reduced iron, electrolytic iron, and carbonyl iron. The 
term ``carbonyl'' refers to the production process, not the composition 
of the product. The bioavailability of these various elemental iron 
sources is dependent primarily on their physical characteristics, which 
in turn depend on the manufacturing method. For example, higher 
relative bioavailabilities of elemental iron are obtained with smaller 
particle sizes.
    Some evidence suggests that carbonyl iron may be a useful 
substitute for the more commonly used chemical compounds of iron in 
reducing the risk of accidental iron poisonings. Data from studies in 
animals suggest that carbonyl iron may be only 1/100th as toxic as 
ferrous sulfate in single doses, i.e., the LD50 (lethal dose for 
50 percent of the test group) of ferrous sulfate is approximately 0.30 
gram ferrous per kilogram (g Fe/kg) (The Merck Index, 11th ed., p. 635 
(1989)), and the LD50 for carbonyl iron is approximately 30.0 g 
Fe/kg body weight. At the same time, data from human subjects indicate 
that the overall bioavailability of carbonyl iron in supporting the 
nutritional functions of iron is about 70 percent that of ferrous 
sulfate. Thus, carbonyl iron, in comparison with ferrous sulfate, 
appears to have a much larger margin of safety between the level that 
would provide adequate iron nutrition and the level that causes acute 
toxicity. Consequently, carbonyl iron may be inherently safer to use, 
and its use may help to reduce the risk of iron poisoning in children, 
than ferrous sulfate.
    In the initial proposal, FDA expressed interest in receiving data 
on the potential of elemental iron to have acute toxicity in humans, 
and particularly in children, and stated that the agency would 
carefully consider any information that it received on this subject. 
FDA stated that, if the information it received was persuasive in 
establishing that the use of elemental iron would substantially 
decrease the risk of pediatric poisoning while allowing for effective 
dietary iron supplementation, FDA would consider exempting iron-
containing products that incorporate elemental iron from any 
regulations that result from this rulemaking.
    In response to this request for information, FDA received several 
comments that supplied information on this topic. Some of the comments 
included citations to scientific literature or copies of scientific 
articles. The comments argued that the information supports an 
exemption of products formulated with elemental iron from the labeling 
and packaging requirements applied to products containing iron salts. 
These comments have convinced FDA that the issues and data that they 
have presented should be discussed in a public workshop.
    The purpose of the workshop on the acute toxicity of elemental iron 
is to:
    1. Identify data that objectively describe the acute toxicity of 
elemental iron.
    2. Identify the market uses of elemental iron and any adverse 
reaction reporting systems or processes used by manufacturers and 
vendors.
    3. Identify any data on acute, accidental exposure of children or 
adults to products containing elemental iron.
    4. Discuss a possible conceptual framework for evaluation of the 
effects of elemental forms of iron upon acute exposure.
    5. Discuss the validity, and limitations, of acute toxicity data in 
experimental animals in predicting the risk in young children.
    Specific topics that may be relevant and on which discussion is 
invited include:
    1. Physiological factors that influence acute toxicity of elemental 
forms of iron, in comparison with those for iron salts.
    2. The quality, results, and relevance of animal studies on acute 
toxicity of elemental iron and iron salts.
    3. The quality and results of human studies for evaluating the 
effects of elemental iron.
    4. Factors influencing the validity of extrapolation of 
experimental animal data on acute toxicity of various forms of iron for 
predicting the risk in young children.
    5. Current uses of elemental iron in dietary supplements and drugs 
and the data available on potential adverse effects.
     Discussion of these topics will be considered by FDA in the 
development of any final rule on the packaging and labeling of products 
containing iron salts. In conjunction with the workshop, FDA 
specifically requests comments on the appropriateness of elemental iron 
as a source of iron in drugs and dietary supplements. The comments 
should focus on whether the use of elemental [[Page 14919]] iron in 
iron-containing products will decrease the risk of pediatric 
poisonings, while providing desirable iron nutrition to those who need 
iron supplementation, and on whether an exemption for products that 
contain elemental iron from any packaging and labeling requirements 
that result from the underlying rulemaking is appropriate.
    Interested persons may on or before April 20, 1995, submit to the 
Dockets Management Branch (address above) comments on the workshop. 
Additional written comments may be submitted for 30 days after the date 
of this workshop. Two copies of any comments are to be submitted, 
except that individuals may submit one copy. Written comments and 
submitted documents are to be identified with the docket numbers found 
in brackets in the heading of this document. Received comments and the 
transcript of the discussion identified with the same docket numbers 
may be seen in the office above between 9 a.m. and 4 p.m., Monday 
through Friday.

    Dated: March 16, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 95-6919 Filed 3-20-95; 8:45 am]
BILLING CODE 4160-01-F