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12560 Federal Register / Vol. 72, No.

51 / Friday, March 16, 2007 / Rules and Regulations

Issued in Kansas City, Missouri, on March FDA published a notice of filing of growth, eggshell formation, as well as
6, 2007. this petition in the Federal Register of other endocrine system functions (Ref.
Kim Smith, October 24, 1995 (60 FR 54505), and 2).
Manager, Small Airplane Directorate, Aircraft gave interested parties an opportunity to Animals, including poultry, do not
Certification Service. submit comments to the agency. FDA have a dietary requirement for vitamin
[FR Doc. E7–4729 Filed 3–15–07; 8:45 am] did not receive any comments in D when sufficient ultraviolet (UV) light
BILLING CODE 4910–13–P response to that notice. Subsequent to is available, because vitamin D is
the filing of the petition, sponsorship produced through action of UV light on
was changed to IsoGen L.L.C., Monsanto a provitamin present in the skin. This
DEPARTMENT OF HEALTH AND Co., Roche Vitamins, Inc., and lastly, to provitamin is synthesized in the body
HUMAN SERVICES DSM Nutritional Products, Inc., 45 and present in large amounts in skin,
Waterview Blvd., Parsippany, NJ, intestinal wall, and other tissues (Ref.
Food and Drug Administration 07054–1298. 2). Vitamin D becomes a nutritionally
important factor in the absence of
21 CFR Part 584 II. Standards for GRAS Affirmation sufficient UV light either from the sun
Under § 570.30 (21 CFR 570.30), or from an artificial source. Under
[Docket No. 1995G–0321] (formerly 95G–
0321) general recognition of safety of food modern farming conditions, many
ingredients may be based only on the animals are raised in total confinement
Food Substances Affirmed as views of experts qualified by scientific with limited exposure to UV light thus
Generally Recognized as Safe in Feed training and experience to evaluate the creating the need for a dietary supply of
and Drinking Water of Animals: 25- safety of food substances directly or vitamin D.
Hydroxyvitamin D3 indirectly added to food. The basis of There are two predominant forms of
such views may be either of the vitamin D for poultry. Vitamin D2 comes
AGENCY: Food and Drug Administration, following: (1) Scientific procedures, or mainly from plants. Vitamin D3 is
HHS. (2) in the case of a substance used in produced in a bird’s body when
ACTION: Final rule. food prior to January 1, 1958, through sunlight reacts with vitamin D
experience based on common use in precursors obtained from the bird’s diet.
SUMMARY: The Food and Drug
food. General recognition of safety based Since vitamin D3 is 30 to 40 times more
Administration (FDA) is amending its potent than D2, plants are considered
regulations to affirm that the use of 25- upon scientific procedures requires the
same quantity and quality of scientific insignificant sources of vitamin D for
hydroxyvitamin D3 is generally birds.
recognized as safe (GRAS) as a source of evidence as is required to obtain
approval of a food additive regulation Commonly, broiler chickens are
vitamin D3 activity in broiler chicken grown within the confines of buildings
feeds and drinking water when used in for the ingredient and ordinarily is to be
based upon published studies, which with large numbers of birds per building
accordance with certain limitations. and are supplied with bulk feed and
This action is in response to a petition may be corroborated by unpublished
studies and other data and information water for ad libitum consumption.
filed by Amoco BioProducts Corp. Various strains of chicken have been
Subsequently, the sponsorship for this (§ 570.30(b)). General recognition of
safety through experience based on developed for broiler production. They
petition was changed to IsoGen L.L.C., have been bred primarily for rapid
Monsanto Co., Roche Vitamins, Inc., common use of a substance in food prior
weight gain and efficient feed
and lastly, to DSM Nutritional Products, to January 1, 1958, may be determined
utilization. Typically, broilers are
Inc. without the quantity or quality of
slaughtered at 6 to 7 weeks of age if size
DATES: This rule is effective March 16, scientific evidence required for approval
and weight requirements are attained.
2007. of a food additive regulation. Ordinarily
Crumbled starter feed is supplied during
it is to be based upon generally available
weeks 1 to 3, pelletized grower feed
Michaela Alewynse, Center for data and information (§ 570.30(c)).
during weeks 4 to 6, and finisher feed
Veterinary Medicine (HFV–228), Food The subject petition relies on
until slaughter. The major differences
and Drug Administration, 7519 Standish scientific procedures evidence to
among these types of feed are the levels
Pl., Rockville, MD 20855, 240–453– support the GRAS affirmation of 25-OH
and sources of nutrients provided in the
6866, e-mail: D3 as a source of vitamin D3 activity in
feed, such as amino acids, minerals, and
mika.alewynse@fda.hhs.gov. broiler chicken feeds and drinking
vitamins. The level of vitamin
SUPPLEMENTARY INFORMATION: supplementation provided in the broiler
III. Safety Evaluation industry is based on type of diets fed,
I. Background species, age of the bird, dietary
A. Introduction antagonists, form of vitamin product,
In accordance with the procedures
described in 21 CFR 570.35, Amoco 25-OH D3, also called 25- requirement status (optimum or
BioProducts Corp., P.O. Box 3011, hydroxycholecalciferol, is a normal minimum requirements), disease status,
Naperville, IL, 60566, submitted a metabolite of vitamin D3 in mammals complexity of the ration, and
petition (GRASP 2449) requesting that and birds. Chemically, the substance is environmental factors, primarily
25-hydroxyvitamin D3 (25-OH D3) be 9,10-secocholesta-5,7,10(19)-triene-3b, ambient temperature. Only after all
affirmed as GRAS for use as a source of 25-diol. 25-OH D3 is the principal these factors are considered can the
vitamin D3 activity in broiler chicken circulating form of vitamin D3, which is optimal vitamin requirements for
feeds. In the original petition, 25-OH D3 the primary source of vitamin D activity poultry be estimated (Ref. 2).
was proposed for use in feed only. The for livestock animals. The metabolism of The National Research Council’s
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proposed use was amended in a vitamin D in animals is well understood (NRC) recommendation for dietary
submission dated January 7, 1998, to and is documented in biochemistry vitamin D3 requirement of broiler
include administration through drinking textbooks (for example, Ref. 1). In chickens is 200 International Units (IU)
water. Furthermore, all data for feed are poultry, vitamin D regulates calcium of vitamin D3 per kilogram (/kg) of feed
applicable to water. and phosphorus homeostasis, bone (Ref. 3). One unit of vitamin D3 is

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Federal Register / Vol. 72, No. 51 / Friday, March 16, 2007 / Rules and Regulations 12561

defined as the activity of 0.025 safe use of 25-OH D3, the label and 1. Target Animal Safety
microgram (µg) of vitamin D3. Thus, a labeling shall bear adequate mixing The NRC reported that the existing
supplement of 200 IU/kg of feed is directions to ensure that the product data for broiler chickens do not allow
equivalent to 5 µg of vitamin D3/kg of (and its premixes) is uniformly blended precise estimates to be made for
feed. This requirement is based on diets throughout the feed or drinking water. maximum vitamin D (and vitamin D
containing the required amounts of In addition, since there are no animal metabolites such as 25-OH D3) tolerance
calcium and available phosphorus and consumption data to support the levels; however, it indicated that under
is considered by NRC to be the concurrent use of 25-OH D3 in feed and short-term feeding conditions (less than
minimum amount required to prevent water, there must be a statement on all 60 days), most species including
deficiency signs. premix labeling (feed and drinking chickens, can tolerate as much as 100
B. Manufacturing and Specifications water forms) that 25-OH D3 should not times (100 X) their apparent vitamin D
According to the petition, the be used concurrently in both feed and dietary requirements, i.e., 500 µg/kg of
production of 25-OH D3 uses a water. feed (Ref. 6).
bioengineered strain of the yeast Estimates of the tolerance of 25-OH D3
D. General Recognition of Safety by broiler chickens were assessed by the
Saccharomyces cerevisiae. The 25-OH
D3 final product is a white to slightly The petition provides information to expert panel (Ref. 7) primarily from two
pink, odorless, crystalline substance. support a determination that the use of field trials conducted for Amoco
The petition lists the specifications for 25-OH D3 in broiler chicken diets or BioProducts Corp. The aim of these
25-OH D3 as: not less than 94.0 percent studies was to determine the utility of
drinking water is GRAS based upon the
25-OH D3; not more than 1 percent of 25-OH D3 as a source of vitamin D3
existence of an expert consensus, based
any individual sterol; not more than 5 activity and/or to evaluate whether 25-
on scientific procedures, that 25-OH D3
percent water; not more than 20 parts OH D3 exhibited toxic effects when
has been shown to be safe. Foremost in
per million (ppm) lead; not more than added to broiler diets. One of the
the support of the determination is the studies (Ref. 8) was compromised due to
20 ppm aluminum; not more than 1.0 same kind and quality of safety data as
percent solvents; and non-detectable the high mortality rate (up to 16
would be required to obtain FDA percent) that occurred in all groups
levels of 2’, 4’, 5’, 7’-tetraiodofluorescin. approval of 25-OH D3 for use as a food
In order to ensure vitamin potency so including controls. The other study (Ref.
additive. In particular, the majority of 9) was requested by the expert panel
that the 25-OH D3 ‘‘performs an
the data is published, and there is a and is discussed below.
appropriate function in the food,’’ an
consensus among qualified experts, In addition to the field trials
expiration date should be included on
feed and water premixes (§ 570.30(f)(2)). based on the data, that this use of the conducted for Amoco BioProducts
substance is safe. Corp., the expert panel evaluated
C. Use in Feed and Drinking Water Information in the petition shows that information from separate published
The petitioner claims that the NRC the safety of 25-OH D3 has been sources, including the results of several
recommendation of 5 µg of vitamin D3/ evaluated by an expert panel. The animal feeding studies. Based on its
kg of feed is virtually never used in the expert panel was convened by the Life comprehensive review of the literature,
broiler industry because commercial Sciences Research Office, Federation of the expert panel concluded that dietary
broiler strains currently grow much American Societies for Experimental levels up to 10 µg of 25-OH D3/kg of
faster, utilize feed more efficiently, and Biology. The expert panel obtained feed are safe for broiler chickens for
are reared in confinement with less background information, identified and prolonged feeding. It was noted that
exposure to UV light than when the analyzed pertinent literature and broiler chickens fed 100 µg of 25-OH D3/
NRC made its recommendation. As a experimental studies, and reached an kg of feed exhibited toxicity signs
result, petitioner claims characterized by epithelial necrosis and
opinion as to whether the available
supplementation of broiler feed with mineralization in the distal convoluted
information and data on the health
vitamin D3 is typically at a considerably tubules of the kidney (Ref. 10).
effects of 25-OH D3 were sufficient to
higher level. A survey of commercial However, a detailed evaluation of the
meet the regulatory requirements of
practices in regard to vitamin study revealed significant inadequacies
safety as a GRAS substance for the
supplementation of poultry feed in its design and experimental
intended use. The expert panel procedures. Thus, the expert panel did
supported this argument, i.e., it revealed
that the amounts of vitamin D3 concluded that the available not place great weight on this study in
commonly added by the broiler chicken information supports a GRAS its evaluation of safety. Additionally, a
feed companies range from 50.0 to 62.5 classification of 25-OH D3 when number of studies were performed in
parts per billion (ppb) (µg/kg) of supplied as a source of vitamin D other poultry species. No signs of
finished feed (Ref. 4). activity in broiler feed at the intended toxicity were reported in laying hens
The petitioner proposes that 25-OH level of use of about 69 µg/kg of feed. when 25-OH D3 was fed at levels up to
D3is GRAS when added to broiler Corroborating evidence has shown that 50 µg/kg of feed for periods up to 448
chicken feed at levels not to exceed 69 25-OH D3 is a normal metabolite of days (Ref. 11). Laying Japanese quail
ppb (µg/kg) of finished feed. Based on vitamin D3 and the principal circulating and growing turkeys were fed diets
the manufacturing and composition of a form of vitamin D3 in mammals and containing up to 16.6 µg of 25-OH D3/
liquid product and its liquid release and birds (Ref. 2). In addition, the petitioner kg of feed for periods up to 42 days with
stability data, the petitioner also provided testimony of a world- no adverse effects recorded (Refs. 12
proposes that 25-OH D3 is GRAS when renowned expert on vitamin D who and 13).
added to broiler chickens’ drinking concluded that 25-OH D3 would be a Because the concentration of 25-OH
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water at levels not to exceed 34.5 ppb. safer dietary ingredient than vitamin D, D3 in broiler feed that may elicit toxic
This is because it is generally assumed since it does not accumulate in the body effects was not known, the expert panel
that birds drink approximately twice as and thus, would not cause toxicity requested that Amoco BioProducts
much water as the amount of feed because of accumulation to toxic levels Corp. conduct an additional target
consumed on a weight basis. To assure (Ref. 5). animal safety study (Ref. 9). 25-OH D3

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12562 Federal Register / Vol. 72, No. 51 / Friday, March 16, 2007 / Rules and Regulations

was tested at multiple levels at and 2. Consumer Exposure vitamin D compounds. However, the
above (0, 1, 10, 50, 100, and 200X) the The safety of 25-OH D3 has been agency does not have sufficient
maximum proposed use level. No evaluated to assess its potential toxicity information to disqualify the rabbit
significant differences in body weight, in humans who consume edible tissues model in toxicity testing. While not
mortality rate, or treatment-related derived from broiler chickens fed 25-OH disregarding the rabbit study, FDA took
lesions were observed in the 25-OH D3 D3—supplemented feed. The evaluation into account the high sensitivity of the
group at the maximum proposed level of was based on FDA’s review of published rabbit model and used a 100-fold safety
69 µg/kg of feed. However, 35 percent of and unpublished information provided factor rather than the usual 1000-fold
the birds in the 690 µg 25-OH D3/kg in the petition, including the safety safety factor in calculating an acceptable
group (10X) developed renal evaluation performed by the expert daily intake (ADI) for 25-OH D3.
calcification. In addition, by the end of panel (Ref. 7). Based on the available Consequently, FDA set the ADI based on
the study, the body weights of the birds current information at 0.05 µg/kg BW/
information and evaluation of the
from the 690 µg/kg group fell 12 percent day. The safe concentrations of 25-OH
biological effects of 25-OH D3, the
when compared with the birds from the D3 in chicken tissues based on an ADI
expert panel concluded that ‘‘The
69 µg/kg group. Data were not collected of 0.05 µg/kg BW/day is 10 ppb in
available information supports a
to determine the level between 69 and muscle, 30 ppb in liver, and 60 ppb in
Generally Recognized as Safe (GRAS)
690 µg 25-OH D3/kg of feed at which skin/fat. These values are well within
classification of 25-hydroxyvitamin D3
toxic effects were seen. High mortality the estimated safe concentrations for
when supplied as a source of vitamin D
was observed in birds exposed to high consumers (Ref. 17). Although liver
activity in broiler feed at the intended
levels of 25-OH D3 (50, 100, and 200X) concentrations of 25-OH D3 were not
level of use of about 68.8 µg (63.8 to
thus, these treatments were terminated measured, it is anticipated that these
before the end of the study. Based on its 73.7 µg) per kilogram of feed.’’ values similarly would be within the
Having evaluated the data and
review of the available information, calculated acceptable levels. FDA
information contained in the petition,
including the results of this additional concludes that the available data
FDA preliminarily found that this use of
study, the expert panel concluded that indicate that residue levels of 25-OH D3
25-OH D3 in broiler feed was safe;
the proposed maximum level (69 µg 25- will not result in any unsafe residues of
OH D3/kg of feed) is within the range however, some concerns regarding the 25-OH D3 in edible chicken tissues.
that growing broilers can tolerate. teratogenicity of 25-OH D3 in the rabbit In its evaluation of 25-OH D3, FDA
After evaluating the results of the (the most sensitive species) remained. has reviewed not only the safety of the
latter study (Ref. 9), FDA found that, Specifically, Dutch Belted rabbits dosed product itself, but also the safety of the
although no toxic effects were observed at 25 and 50 µg/kg bodyweight (BW)/ chemical impurities that may be present
at the maximum proposed use level (69 day by oral intubation from gestation in the product from the manufacturing
µg/kg of feed), significant treatment- day 6 to day 18 produced pups with process. Residual amounts of reactants
related lesions occurred when birds skeletal and vascular anomalies. These and manufacturing aids are commonly
were exposed to 10 times (690 µg/kg of dose-related effects included domed found as contaminants in chemical
feed) that level. In the absence of key skulls, enlarged cardiac atria, and products, including products added to
data to determine the level between 69 dilated pulmonary arteries. None of animal feeds.
and 690 µg/kg at which toxicity effects these abnormalities were noted in the The biological stain, 2’, 4’, 5’, 7’-
were seen, there was no assurance that negative controls or the 5 µg/kg BW/day tetraiodofluorescin (also known as
toxicity would not occur at levels just group. This and other toxicity studies FD&C Red No. 3 or erythrosin), is used
above 69 µg/kg. Thus, to identify the were previously reviewed by FDA in as a photosensitizer in the production of
margin of safety for the intended use, support of the use of 25-OH D3 as the 25-OH D3. This use of 2’, 4’, 5’, 7’-
FDA requested another target animal therapeutic drug for humans, calcifediol tetraiodofluorescin may result in
safety study. (Ref. 15). unintended residue levels of 50 ppm
The study (Ref. 14) was designed to The petitioner argued that the rabbit’s maximum in the finished 25-OH D3
show safety to broiler chickens by unique calcium metabolism and product (Ref. 18). At a 50 ppm
testing 25-OH D3 at varying levels unusual sensitivity to the effects of concentration in the 25-OH D3 final
between 69 and 690 µg/kg of feed which vitamin D compounds rendered it too product, when the 25-OH D3 is diluted
represented 0 (control), 1, 3, 5, and 10 sensitive a model for assessing the in feed to a concentration of 69 ppb (69
times the maximum proposed use level. teratogenic potential of vitamin D in µg/kg), 2’, 4’, 5’, 7’-tetraiodofluorescin
The results of the study corroborated humans (Ref. 16). In addition, the would be present at 3.45 parts per
previous findings that 25-OH D3 petitioner provided the testimony of Dr. trillion (ppt) in finished broiler chicken
supplementation at levels up to the Hector De Luca, a world-renowned feed.
maximum proposed use rate resulted in expert (Ref. 5) on vitamin D, who noted FDA used risk assessment procedures
no toxic effect, and at levels 10 times that rabbits are extraordinarily sensitive to estimate the upper-bound of risk
the proposed use level resulted in renal to vitamin D and that they rapidly go presented by 2’, 4’, 5’, 7’-
calcification. The study also found that into hyperglycemia at low doses of any tetraiodofluorescin, a carcinogenic
no treatment-related lesions occurred form of vitamin D. Dr. De Luca stated chemical (21 CFR 81.10(u)), that may be
when broilers were fed at levels up to that in the rabbit, hyperglycemia likely present in the 25-OH D3 product. Using
five times the highest proposed use causes the observed teratogenic effects. a worst case estimate, taking into
level. In the expert’s view, the rabbit should account a bird feed efficiency of
FDA has determined that the not be used as a toxicology model for approximately 1.9 and 80 percent
published studies, as corroborated by man for studies of vitamin D uptake, the worst case concentration of
this unpublished study, provide an compounds, because they almost stand 2’, 4’, 5’, 7’-tetraiodofluorescin in edible
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adequate basis upon which to conclude alone in their sensitivity among species tissue would be 5.2 ppt (3.45 ppt x 1.9
that 25-OH D3 is a safe source of vitamin used for the safety studies. x 0.8 = 5.2 ppt). Therefore, the agency
D3 activity for broiler chickens when fed Based on information provided in the would not expect this impurity to
at nutritional levels not to exceed 69 µg/ petition, FDA concurs that the rabbit is become a component of food at other
kg of finished feed. unusually sensitive to the effects of than minute levels. However, because

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Federal Register / Vol. 72, No. 51 / Friday, March 16, 2007 / Rules and Regulations 12563

2’, 4’, 5’, 7’-tetraiodofluorescin is a who stated that 25-OH D3 would be a 6. National Research Council,
carcinogenic chemical, FDA advised safer dietary supplement than vitamin ‘‘Vitamin D,’’ in Vitamin Tolerance of
that the sponsor should either find a D, since it does not accumulate in the Animals, 1st ed., National Academy
replacement for 2’, 4’, 5’, 7’- body and thus, would not cause toxicity Press, Washington, DC, pp. 11–22, 1987.
tetraiodofluorescin or remove 2’, 4’, 5’, because of accumulation to toxic levels. 7. GRASP 2449, Appendix E: Expert
7’-tetraiodofluorescin from the final Therefore, the agency is issuing this Panel Report, Life Sciences Research
product in a consistent manner. final rule affirming that 25-OH D3 is Office, Federation of American Societies
Subsequently, the petitioner developed GRAS as a source of vitamin D3 activity for Experimental Biology, Bethesda,
a purification process for complete in broiler feeds and drinking water MD, 1994.
removal of 2’, 4’, 5’, 7’- when given to broiler chickens at 8. Quarles, C. L., Safety study using
tetraiodofluorescin from the final 25-OH nutritional levels not to exceed 69 ppb 25-OH D3 in broiler chickens, Colorado
D3 product. The petitioner provided in feed or 34.5 ppb in drinking water AM–1–93, Colorado Quality Research
details on the experimental conditions and when used in accordance with Inc., Fort Collins, CO, 1993, (available
and the supporting analytical data for additional limitations. in the petition: vol. 11, pp. 02005–
the analytical method used to quantitate 02493).
residual 2’, 4’, 5’, 7’-tetraiodofluorescin V. Environmental Impact
9. Quarles, C. L., Safety study using
in the 25-OH D3 product. FDA found the FDA has determined under 21 CFR 25-OH D3 and vitamin D3 in broiler
purification process to be effective 25.32(r) that this action is of the type chickens, Colorado AM–2–94, Colorado
based on the analytical work submitted. that does not individually or Quality Research, Inc., Fort Collins, CO,
The analytical method for the detection cumulatively have a significant effect on 1994, (available in the petition: vol. 12,
of the 2’, 4’, 5’, 7’-tetraiodofluorescin the human environment. Therefore, pp. 2494–2862).
has been appropriately validated by the neither an environmental assessment 10. Morrissey, J. L., et al., Journal of
petitioner and FDA found it to be nor an environmental impact statement Nutrition, vol. 107, pp. 1027–10324,
accurate, precise, and acceptable for its is required. 1977 (available in the petition: vol. 19,
purpose. pp. 5220–5227).
VI. Effective Date
IV. Conclusion 11. Janssen, W. M. M. A., H. A. J.
As this rule recognizes an exemption Versteegh, P. J. W. Van Schagen, Archiv
FDA has determined that the petition from the food additive definition in the fur Geflugelkunde, vol. 45, pp. 194–200,
provides information to support a Federal Food, Drug, and Cosmetic Act, 1981 (available in the petition: vol. 18,
determination that the use of 25-OH D3 and from the approval requirements pp. 5018–5024).
is GRAS as a source of vitamin D3 applicable to food additives, no delay in 12. Kaetzel, D. M., Jr. and J. H. Soares,
activity for broiler chicken feeds and effective date is required by the Jr., Journal of Nutrition, vol. 109, pp.
drinking water based upon the existence Administrative Procedure Act (5 U.S.C.
of an expert consensus that 25-OH D3 1601–1608, 1979 (available in the
553(d)). The rule therefore will be petition: vol. 18, pp. 5033–5040).
has been shown to be safe based on effective immediately (5 U.S.C.
scientific procedures. The 13. Stevens, V. L. and R. Blair,
553(d)(1)). Nutrition Reports International, vol. 35,
determination was based upon
published scientific data, corroborating VII. References pp. 755–764, 1987 (available in the
unpublished studies, and other data and The following references have been petition: vol. 19, pp. 5465–5474).
information. The agency has reached the placed on display in the Division of 14. GRASP 2449, Amendment C–
following conclusions: (1) 25-OH D3 is Dockets Management (HFA–305), 5630 0027: Safety Study Using 25-OH D3 in
a suitable source of vitamin D3 activity Fishers Lane, rm. 1061, Rockville, MD Broiler Chickens (Project No. ISG–98–2).
for broiler chickens; (2) 25-OH D3 at 20852 and may be seen by interested September 1998 (available in the
levels up to 69 ppb in feed, or 34.5 ppb persons between 9 a.m. and 4 p.m., petition: vol. 31–34).
in drinking water, is safe to broiler Monday through Friday. 15. Dutta, S. N., Clinical review and
chickens and to the people consuming 1. Garret, R. H. and C. M. Grisham, evaluation of NDA 018312 (Organon
the broiler chickens’ edible meat ‘‘The Vitamin D Group,’’ in USA, Inc.’s CALDEROL brand of 25-OH
products; and (3) an expert panel also Biochemistry, 2d ed., Saunders College D3), 1979.
concluded that the available Publishing, New York, NY, pp. 604–605, 16. GRASP 2449, Amendment C–
information supports a GRAS 1999. 0028: Human Food Safety of the Use of
classification for 25-OH D3 when 2. Ameenuddin, S., M. L. Sunde, E. 25-OH D3 in Broiler Feed, February
supplied as a source of vitamin D M. Cook, World’s Poultry Science 1999.
activity in broiler feed at the intended Journal, vol. 41, pp. 52–63, 1985 17. FDA Center for Veterinary
level of use of 69 µg/kg of feed. (available in the petition: vol. 17, pp. Medicine, Guideline for Industry #3:
The evaluation was based on the same 4463–4474). ‘‘General Principles for Evaluating the
type and quality of data as would be 3. National Research Council, Safety of Compounds Used in Food-
required to obtain FDA approval of 25- ‘‘Vitamins,’’ p. 15, and ‘‘Nutrient Producing Animals,’’ Part 4: ‘‘Guideline
OH D3 for use as a food additive. In Requirements of Chickens,’’ pp. 19–34, for Establishing a Safe Concentration,’’
addition, the majority of the data is in Nutrient Requirements of Poultry, 9th 1994.
published, and there is a consensus ed., National Academy Press, 18. GRASP 2449, Amendment C–
among qualified experts, based on the Washington, DC, 1994. 0029: Safety of the Use of Erythrosin in
data, that this intended use of the 4. Ward, N. E., Journal of Applied the 25-OH D3 Final Product, May 1999.
substance is safe. Corroborating Poultry Research, vol. 2, pp. 286–296, List of Subjects in 21 CFR Part 584
evidence has shown that 25-OH D3 is a 1993 (available in the petition: vol. 19,
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normal metabolite of vitamin D3 and the pp. 5619–5629). Animal feeds, Food additives.
principal circulating form of vitamin D3 5. GRASP 2449, Amendment C–0032: ■ Therefore, under the Federal Food,
in mammals and birds. In addition, the ‘‘Safety of 25-OH D3 to Consumers,’’ Drug, and Cosmetic Act and under
petitioner provided testimony of a (testimony of Dr. Hector De Luca), authority delegated to the Commissioner
world-renowned expert on vitamin D November 1999. of Food and Drugs, and redelegated to

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12564 Federal Register / Vol. 72, No. 51 / Friday, March 16, 2007 / Rules and Regulations

the Center for Veterinary Medicine, 21 DEPARTMENT OF VETERANS authority that has been provided to the
CFR part 584 is amended as follows: AFFAIRS Veterans Health Administration and the
Veterans Benefits Administration. The
PART 584-FOOD SUBSTANCES 38 CFR Part 2 Under Secretary for Memorial Affairs
AFFIRMED AS GENERALLY will notify the Secretary when making
RIN 2900–AM18
RECOGNIZED AS SAFE IN FEED AND decisions to accept or decline gifts and
DRINKING WATER OF ANIMALS Delegations of Authority—National donations of offers that are unique,
■ 1. The authority citation for 21 CFR Cemetery Administration unusual or substantial in nature, or that
part 584 continues to read as follows: may be of public interest because of the
AGENCY: Department of Veterans Affairs. subject of the offer or identity of the
Authority: 21 U.S.C. 321, 342, 348, 371. ACTION: Final rule. donor. The authority to accept land will
■ 2. Section 584.725 is added to subpart remain with the Secretary. The Under
SUMMARY: This final rule amends the Secretary for Memorial Affairs will
B to read as follows:
Department of Veterans Affairs (VA) continue to refer all offers of land to the
§ 584.725 25–Hydroxyvitamin D3. regulation, ‘‘Secretary’s delegations of Secretary, with supporting information
(a) Product. 25–Hydroxyvitamin D3 authority to certain officials.’’ The and a recommendation for action.
(9,10-secocholesta-5,7,10(19)-triene-3b, amendment updates the regulation This rule revises paragraph (f)(3) to 38
25-diol). governing certain delegations of CFR 2.6 by removing the reference ‘‘[t]o
(b) Conditions of use. This substance authority exercised by the Under accept donations of a minor nature,
is generally recognized as safe as a Secretary for Memorial Affairs. This such as, individual trees for planting in
source of vitamin D3 activity in feed or minor technical amendment provides burial areas and privately purchased
drinking water of broiler chickens when delegation of authority from the grave markers’’ and adding ‘‘[t]o accept
used in accordance with the limitations Secretary of Veterans Affairs to the all donations, except offers of land,
in paragraph (c) of this section. Under Secretary for Memorial Affairs to made in any manner, for the
accept monetary and/or non-monetary beautification or benefit of national
(c) Limitations. (1) Not to exceed 69
gifts and donations, made in any cemeteries.’’
parts per billion (ppb) in feed or 34.5
manner, which are made for the purpose
ppb in drinking water. It shall be used Administrative Procedure Act
of beautifying or benefiting national
in accordance with good manufacturing
cemeteries. The authority to accept This final rule states rules of agency
and feeding practices.
offers of land will remain with the procedure or practice and is therefore
(2) The product must comply with the
Secretary of Veterans Affairs. exempt from the notice and public
following specifications:
(i) Not less than 94.0 percent 25- DATES: Effective Date: March 16, 2007. comment procedures of 5 U.S.C. 553(b).
hydroxyvitamin D3. FOR FURTHER INFORMATION CONTACT: Further, this final rule is not a
(ii) Not more than 1 percent of any Patrick Hallinan, Deputy Director, substantive rule and, consequently, the
individual sterol. Office of Field Programs (41A), National delayed effective date provisions of 5
Cemetery Administration, Department U.S.C. 553(d) are not applicable.
(iii) Not more than 5 percent water.
(iv) Not more than 20 parts per of Veterans Affairs, 810 Vermont Unfunded Mandates
million (ppm) lead. Avenue, NW., Washington, DC 20420;
The Unfunded Mandates Reform Act
(v) Not more than 20 ppm aluminum. telephone: (202) 273–5229 (this is not a
of 1995 requires, at 2 U.S.C. 1532, that
(vi) Not more than 1.0 percent toll-free number).
agencies prepare an assessment of
solvents and non-detectable levels of 2’, SUPPLEMENTARY INFORMATION: The anticipated costs and benefits before
4’, 5’, 7’-tetraiodofluorescin. provisions of 38 U.S.C. 2407 authorize issuing any rule that may result in an
(3) Product labeling shall bear the the Secretary to ‘‘accept gifts, devises, or expenditure by State, local, or tribal
following: bequests from legitimate societies and governments, in the aggregate, or by the
organizations or reputable individuals, private sector, of $100 million or more
(i) A statement to indicate that the made in any manner, which are made (adjusted annually for inflation) in any
maximum use level of 25- for the purpose of beautifying national given year. This rule would have no
hydroxyvitamin D3 must not exceed 69 cemeteries, or are determined to be such effect on State, local, or tribal
ppb in feed or 34.5 ppb in drinking beneficial to such cemetery.’’ Currently, governments, or the private sector.
water. under 38 CFR 2.6(f)(3), the Secretary has
delegated authority to the Under Paperwork Reduction Act
(ii) Adequate use directions to ensure Secretary for Memorial Affairs ‘‘[t]o This document contains no provisions
that 25-hydroxyvitamin D3 (and all accept donations of a minor nature, constituting a collection of information
premixes) is uniformly blended such as, individual trees for planting in under the Paperwork Reduction Act (44
throughout the feed or drinking water. burial areas and privately purchased U.S.C. 3501–3521).
(iii) An expiration date on all premix grave markers.’’ (Emphasis added) The
current regulatory language no longer Executive Order 12866
(iv) A statement on all premix reflects the needs of the agency since Executive Order 12866 directs
labeling (feed and drinking water forms) the National Cemetery Administration agencies to assess all costs and benefits
that 25-hydroxyvitamin D3 should not frequently receives offers for donations of available regulatory alternatives and,
be used simultaneously in both feed and that may be perceived as more than when regulation is necessary, to select
water. ‘‘minor in nature.’’ Such offers have regulatory approaches that maximize
included heavy equipment, rose net benefits (including potential
Dated: March 1, 2007.
sroberts on PROD1PC70 with RULES

gardens, cash, and electric vehicles. economic, environmental, public health

Stephen F. Sundlof, Providing authority to the National and safety, and other advantages;
Director, Center for Veterinary Medicine. Cemetery Administration to accept distributive impacts; and equity). The
[FR Doc. E7–4796 Filed 3–15–07; 8:45 am] donations, regardless of monetary value, Executive Order classifies a ‘‘significant
BILLING CODE 4160–01–S would be commensurate with the regulatory action,’’ requiring review by

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