12560 Federal Register / Vol. 72, No. 51 / Friday, March 16, 2007 / Rules and Regulations 

Issued in Kansas City, Missouri, on March 

6, 2007. 

Kim Smith, 

Manager, Small Airplane Directorate, Aircraft 

Certification Service. 

[FR Doc. E7–4729 Filed 3–15–07; 8:45 am] 

BILLING CODE 4910–13–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 584 

[Docket No. 1995G–0321] (formerly 95G–

0321) 

Food Substances Affirmed as 

Generally Recognized as Safe in Feed 

and Drinking Water of Animals: 25- 

Hydroxyvitamin D3

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is amending its 

regulations to affirm that the use of 25- 

hydroxyvitamin D3 is generally 

recognized as safe (GRAS) as a source of 

vitamin D3 activity in broiler chicken 

feeds and drinking water when used in 

accordance with certain limitations. 

This action is in response to a petition 

filed by Amoco BioProducts Corp. 

Subsequently, the sponsorship for this 

petition was changed to IsoGen L.L.C., 

Monsanto Co., Roche Vitamins, Inc., 

and lastly, to DSM Nutritional Products, 

Inc. 

DATES: This rule is effective March 16, 

2007. 

FOR FURTHER INFORMATION CONTACT: 

Michaela Alewynse, Center for 

Veterinary Medicine (HFV–228), Food 

and Drug Administration, 7519 Standish 

Pl., Rockville, MD 20855, 240–453–

6866, e-mail: 

mika.alewynse@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In accordance with the procedures 

described in 21 CFR 570.35, Amoco 

BioProducts Corp., P.O. Box 3011, 

Naperville, IL, 60566, submitted a 

petition (GRASP 2449) requesting that 

25-hydroxyvitamin D3 (25-OH D3) be 

affirmed as GRAS for use as a source of 

vitamin D3 activity in broiler chicken 

feeds. In the original petition, 25-OH D3

was proposed for use in feed only. The 

proposed use was amended in a 

submission dated January 7, 1998, to 

include administration through drinking 

water. Furthermore, all data for feed are 

applicable to water. 

FDA published a notice of filing of 

this petition in the Federal Register of 

October 24, 1995 (60 FR 54505), and 

gave interested parties an opportunity to 

submit comments to the agency. FDA 

did not receive any comments in 

response to that notice. Subsequent to 

the filing of the petition, sponsorship 

was changed to IsoGen L.L.C., Monsanto 

Co., Roche Vitamins, Inc., and lastly, to 

DSM Nutritional Products, Inc., 45 

Waterview Blvd., Parsippany, NJ, 

07054–1298. 

II. Standards for GRAS Affirmation 

Under § 570.30 (21 CFR 570.30), 

general recognition of safety of food 

ingredients may be based only on the 

views of experts qualified by scientific 

training and experience to evaluate the 

safety of food substances directly or 

indirectly added to food. The basis of 

such views may be either of the 

following: (1) Scientific procedures, or 

(2) in the case of a substance used in 

food prior to January 1, 1958, through 

experience based on common use in 

food. General recognition of safety based 

upon scientific procedures requires the 

same quantity and quality of scientific 

evidence as is required to obtain 

approval of a food additive regulation 

for the ingredient and ordinarily is to be 

based upon published studies, which 

may be corroborated by unpublished 

studies and other data and information 

(§ 570.30(b)). General recognition of 

safety through experience based on 

common use of a substance in food prior 

to January 1, 1958, may be determined 

without the quantity or quality of 

scientific evidence required for approval 

of a food additive regulation. Ordinarily 

it is to be based upon generally available 

data and information (§ 570.30(c)). 

The subject petition relies on 

scientific procedures evidence to 

support the GRAS affirmation of 25-OH 

D3 as a source of vitamin D3 activity in 

broiler chicken feeds and drinking 

water. 

III. Safety Evaluation 

A. Introduction 

25-OH D3, also called 25- 

hydroxycholecalciferol, is a normal 

metabolite of vitamin D3 in mammals 

and birds. Chemically, the substance is 

9,10-secocholesta-5,7,10(19)-triene-3b, 

25-diol. 25-OH D3 is the principal 

circulating form of vitamin D3, which is 

the primary source of vitamin D activity 

for livestock animals. The metabolism of 

vitamin D in animals is well understood 

and is documented in biochemistry 

textbooks (for example, Ref. 1). In 

poultry, vitamin D regulates calcium 

and phosphorus homeostasis, bone 

growth, eggshell formation, as well as 

other endocrine system functions (Ref. 

2). 

Animals, including poultry, do not 

have a dietary requirement for vitamin 

D when sufficient ultraviolet (UV) light 

is available, because vitamin D is 

produced through action of UV light on 

a provitamin present in the skin. This 

provitamin is synthesized in the body 

and present in large amounts in skin, 

intestinal wall, and other tissues (Ref. 

2). Vitamin D becomes a nutritionally 

important factor in the absence of 

sufficient UV light either from the sun 

or from an artificial source. Under 

modern farming conditions, many 

animals are raised in total confinement 

with limited exposure to UV light thus 

creating the need for a dietary supply of 

vitamin D. 

There are two predominant forms of 

vitamin D for poultry. Vitamin D2 comes 

mainly from plants. Vitamin D3 is 

produced in a bird’s body when 

sunlight reacts with vitamin D 

precursors obtained from the bird’s diet. 

Since vitamin D3 is 30 to 40 times more 

potent than D2, plants are considered 

insignificant sources of vitamin D for 

birds. 

Commonly, broiler chickens are 

grown within the confines of buildings 

with large numbers of birds per building 

and are supplied with bulk feed and 

water for ad libitum consumption. 

Various strains of chicken have been 

developed for broiler production. They 

have been bred primarily for rapid 

weight gain and efficient feed 

utilization. Typically, broilers are 

slaughtered at 6 to 7 weeks of age if size 

and weight requirements are attained. 

Crumbled starter feed is supplied during 

weeks 1 to 3, pelletized grower feed 

during weeks 4 to 6, and finisher feed 

until slaughter. The major differences 

among these types of feed are the levels 

and sources of nutrients provided in the 

feed, such as amino acids, minerals, and 

vitamins. The level of vitamin 

supplementation provided in the broiler 

industry is based on type of diets fed, 

species, age of the bird, dietary 

antagonists, form of vitamin product, 

requirement status (optimum or 

minimum requirements), disease status, 

complexity of the ration, and 

environmental factors, primarily 

ambient temperature. Only after all 

these factors are considered can the 

optimal vitamin requirements for 

poultry be estimated (Ref. 2). 

The National Research Council’s 

(NRC) recommendation for dietary 

vitamin D3 requirement of broiler 

chickens is 200 International Units (IU) 

of vitamin D3 per kilogram (/kg) of feed 

(Ref. 3). One unit of vitamin D3 is 


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defined as the activity of 0.025 

microgram (μg) of vitamin D3. Thus, a 

supplement of 200 IU/kg of feed is 

equivalent to 5 μg of vitamin D3/kg of 

feed. This requirement is based on diets 

containing the required amounts of 

calcium and available phosphorus and 

is considered by NRC to be the 

minimum amount required to prevent 

deficiency signs. 

B. Manufacturing and Specifications 

According to the petition, the 

production of 25-OH D3 uses a 

bioengineered strain of the yeast 

Saccharomyces cerevisiae. The 25-OH 

D3 final product is a white to slightly 

pink, odorless, crystalline substance. 

The petition lists the specifications for 

25-OH D3 as: not less than 94.0 percent 

25-OH D3; not more than 1 percent of 

any individual sterol; not more than 5 

percent water; not more than 20 parts 

per million (ppm) lead; not more than 

20 ppm aluminum; not more than 1.0 

percent solvents; and non-detectable 

levels of 2’, 4’, 5’, 7’-tetraiodofluorescin. 

In order to ensure vitamin potency so 

that the 25-OH D3 ‘‘performs an 

appropriate function in the food,’’ an 

expiration date should be included on 

feed and water premixes (§ 570.30(f)(2)). 

C. Use in Feed and Drinking Water 

The petitioner claims that the NRC 

recommendation of 5 μg of vitamin D3/ 

kg of feed is virtually never used in the 

broiler industry because commercial 

broiler strains currently grow much 

faster, utilize feed more efficiently, and 

are reared in confinement with less 

exposure to UV light than when the 

NRC made its recommendation. As a 

result, petitioner claims 

supplementation of broiler feed with 

vitamin D3 is typically at a considerably 

higher level. A survey of commercial 

practices in regard to vitamin 

supplementation of poultry feed 

supported this argument, i.e., it revealed 

that the amounts of vitamin D3

commonly added by the broiler chicken 

feed companies range from 50.0 to 62.5 

parts per billion (ppb) (μg/kg) of 

finished feed (Ref. 4). 

The petitioner proposes that 25-OH 

D3is GRAS when added to broiler 

chicken feed at levels not to exceed 69 

ppb (μg/kg) of finished feed. Based on 

the manufacturing and composition of a 

liquid product and its liquid release and 

stability data, the petitioner also 

proposes that 25-OH D3 is GRAS when 

added to broiler chickens’ drinking 

water at levels not to exceed 34.5 ppb. 

This is because it is generally assumed 

that birds drink approximately twice as 

much water as the amount of feed 

consumed on a weight basis. To assure 

safe use of 25-OH D3, the label and 

labeling shall bear adequate mixing 

directions to ensure that the product 

(and its premixes) is uniformly blended 

throughout the feed or drinking water. 

In addition, since there are no animal 

consumption data to support the 

concurrent use of 25-OH D3 in feed and 

water, there must be a statement on all 

premix labeling (feed and drinking 

water forms) that 25-OH D3 should not 

be used concurrently in both feed and 

water. 

D. General Recognition of Safety 

The petition provides information to 

support a determination that the use of 

25-OH D3 in broiler chicken diets or 

drinking water is GRAS based upon the 

existence of an expert consensus, based 

on scientific procedures, that 25-OH D3

has been shown to be safe. Foremost in 

the support of the determination is the 

same kind and quality of safety data as 

would be required to obtain FDA 

approval of 25-OH D3 for use as a food 

additive. In particular, the majority of 

the data is published, and there is a 

consensus among qualified experts, 

based on the data, that this use of the 

substance is safe. 

Information in the petition shows that 

the safety of 25-OH D3 has been 

evaluated by an expert panel. The 

expert panel was convened by the Life 

Sciences Research Office, Federation of 

American Societies for Experimental 

Biology. The expert panel obtained 

background information, identified and 

analyzed pertinent literature and 

experimental studies, and reached an 

opinion as to whether the available 

information and data on the health 

effects of 25-OH D3 were sufficient to 

meet the regulatory requirements of 

safety as a GRAS substance for the 

intended use. The expert panel 

concluded that the available 

information supports a GRAS 

classification of 25-OH D3 when 

supplied as a source of vitamin D 

activity in broiler feed at the intended 

level of use of about 69 μg/kg of feed. 

Corroborating evidence has shown that 

25-OH D3 is a normal metabolite of 

vitamin D3 and the principal circulating 

form of vitamin D3 in mammals and 

birds (Ref. 2). In addition, the petitioner 

provided testimony of a worldrenowned expert on vitamin D who 

concluded that 25-OH D3 would be a 

safer dietary ingredient than vitamin D, 

since it does not accumulate in the body 

and thus, would not cause toxicity 

because of accumulation to toxic levels 

(Ref. 5). 

1. Target Animal Safety 

The NRC reported that the existing 

data for broiler chickens do not allow 

precise estimates to be made for 

maximum vitamin D (and vitamin D 

metabolites such as 25-OH D3) tolerance 

levels; however, it indicated that under 

short-term feeding conditions (less than 

60 days), most species including 

chickens, can tolerate as much as 100 

times (100 X) their apparent vitamin D 

dietary requirements, i.e., 500 μg/kg of 

feed (Ref. 6). 

Estimates of the tolerance of 25-OH D3

by broiler chickens were assessed by the 

expert panel (Ref. 7) primarily from two 

field trials conducted for Amoco 

BioProducts Corp. The aim of these 

studies was to determine the utility of 

25-OH D3 as a source of vitamin D3

activity and/or to evaluate whether 25- 

OH D3 exhibited toxic effects when 

added to broiler diets. One of the 

studies (Ref. 8) was compromised due to 

the high mortality rate (up to 16 

percent) that occurred in all groups 

including controls. The other study (Ref. 

9) was requested by the expert panel 

and is discussed below. 

In addition to the field trials 

conducted for Amoco BioProducts 

Corp., the expert panel evaluated 

information from separate published 

sources, including the results of several 

animal feeding studies. Based on its 

comprehensive review of the literature, 

the expert panel concluded that dietary 

levels up to 10 μg of 25-OH D3/kg of 

feed are safe for broiler chickens for 

prolonged feeding. It was noted that 

broiler chickens fed 100 μg of 25-OH D3/ 

kg of feed exhibited toxicity signs 

characterized by epithelial necrosis and 

mineralization in the distal convoluted 

tubules of the kidney (Ref. 10). 

However, a detailed evaluation of the 

study revealed significant inadequacies 

in its design and experimental 

procedures. Thus, the expert panel did 

not place great weight on this study in 

its evaluation of safety. Additionally, a 

number of studies were performed in 

other poultry species. No signs of 

toxicity were reported in laying hens 

when 25-OH D3 was fed at levels up to 

50 μg/kg of feed for periods up to 448 

days (Ref. 11). Laying Japanese quail 

and growing turkeys were fed diets 

containing up to 16.6 μg of 25-OH D3/ 

kg of feed for periods up to 42 days with 

no adverse effects recorded (Refs. 12 

and 13). 

Because the concentration of 25-OH 

D3 in broiler feed that may elicit toxic 

effects was not known, the expert panel 

requested that Amoco BioProducts 

Corp. conduct an additional target 

animal safety study (Ref. 9). 25-OH D3


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was tested at multiple levels at and 

above (0, 1, 10, 50, 100, and 200X) the 

maximum proposed use level. No 

significant differences in body weight, 

mortality rate, or treatment-related 

lesions were observed in the 25-OH D3

group at the maximum proposed level of 

69 μg/kg of feed. However, 35 percent of 

the birds in the 690 μg 25-OH D3/kg 

group (10X) developed renal 

calcification. In addition, by the end of 

the study, the body weights of the birds 

from the 690 μg/kg group fell 12 percent 

when compared with the birds from the 

69 μg/kg group. Data were not collected 

to determine the level between 69 and 

690 μg 25-OH D3/kg of feed at which 

toxic effects were seen. High mortality 

was observed in birds exposed to high 

levels of 25-OH D3 (50, 100, and 200X) 

thus, these treatments were terminated 

before the end of the study. Based on its 

review of the available information, 

including the results of this additional 

study, the expert panel concluded that 

the proposed maximum level (69 μg 25- 

OH D3/kg of feed) is within the range 

that growing broilers can tolerate. 

After evaluating the results of the 

latter study (Ref. 9), FDA found that, 

although no toxic effects were observed 

at the maximum proposed use level (69 

μg/kg of feed), significant treatmentrelated lesions occurred when birds 

were exposed to 10 times (690 μg/kg of 

feed) that level. In the absence of key 

data to determine the level between 69 

and 690 μg/kg at which toxicity effects 

were seen, there was no assurance that 

toxicity would not occur at levels just 

above 69 μg/kg. Thus, to identify the 

margin of safety for the intended use, 

FDA requested another target animal 

safety study. 

The study (Ref. 14) was designed to 

show safety to broiler chickens by 

testing 25-OH D3 at varying levels 

between 69 and 690 μg/kg of feed which 

represented 0 (control), 1, 3, 5, and 10 

times the maximum proposed use level. 

The results of the study corroborated 

previous findings that 25-OH D3

supplementation at levels up to the 

maximum proposed use rate resulted in 

no toxic effect, and at levels 10 times 

the proposed use level resulted in renal 

calcification. The study also found that 

no treatment-related lesions occurred 

when broilers were fed at levels up to 

five times the highest proposed use 

level. 

FDA has determined that the 

published studies, as corroborated by 

this unpublished study, provide an 

adequate basis upon which to conclude 

that 25-OH D3 is a safe source of vitamin 

D3 activity for broiler chickens when fed 

at nutritional levels not to exceed 69 μg/ 

kg of finished feed. 

2. Consumer Exposure 

The safety of 25-OH D3 has been 

evaluated to assess its potential toxicity 

in humans who consume edible tissues 

derived from broiler chickens fed 25-OH 

D3—supplemented feed. The evaluation 

was based on FDA’s review of published 

and unpublished information provided 

in the petition, including the safety 

evaluation performed by the expert 

panel (Ref. 7). Based on the available 

information and evaluation of the 

biological effects of 25-OH D3, the 

expert panel concluded that ‘‘The 

available information supports a 

Generally Recognized as Safe (GRAS) 

classification of 25-hydroxyvitamin D3

when supplied as a source of vitamin D 

activity in broiler feed at the intended 

level of use of about 68.8 μg (63.8 to 

73.7 μg) per kilogram of feed.’’

Having evaluated the data and 

information contained in the petition, 

FDA preliminarily found that this use of 

25-OH D3 in broiler feed was safe; 

however, some concerns regarding the 

teratogenicity of 25-OH D3 in the rabbit 

(the most sensitive species) remained. 

Specifically, Dutch Belted rabbits dosed 

at 25 and 50 μg/kg bodyweight (BW)/ 

day by oral intubation from gestation 

day 6 to day 18 produced pups with 

skeletal and vascular anomalies. These 

dose-related effects included domed 

skulls, enlarged cardiac atria, and 

dilated pulmonary arteries. None of 

these abnormalities were noted in the 

negative controls or the 5 μg/kg BW/day 

group. This and other toxicity studies 

were previously reviewed by FDA in 

support of the use of 25-OH D3 as the 

therapeutic drug for humans, calcifediol 

(Ref. 15). 

The petitioner argued that the rabbit’s 

unique calcium metabolism and 

unusual sensitivity to the effects of 

vitamin D compounds rendered it too 

sensitive a model for assessing the 

teratogenic potential of vitamin D in 

humans (Ref. 16). In addition, the 

petitioner provided the testimony of Dr. 

Hector De Luca, a world-renowned 

expert (Ref. 5) on vitamin D, who noted 

that rabbits are extraordinarily sensitive 

to vitamin D and that they rapidly go 

into hyperglycemia at low doses of any 

form of vitamin D. Dr. De Luca stated 

that in the rabbit, hyperglycemia likely 

causes the observed teratogenic effects. 

In the expert’s view, the rabbit should 

not be used as a toxicology model for 

man for studies of vitamin D 

compounds, because they almost stand 

alone in their sensitivity among species 

used for the safety studies. 

Based on information provided in the 

petition, FDA concurs that the rabbit is 

unusually sensitive to the effects of 

vitamin D compounds. However, the 

agency does not have sufficient 

information to disqualify the rabbit 

model in toxicity testing. While not 

disregarding the rabbit study, FDA took 

into account the high sensitivity of the 

rabbit model and used a 100-fold safety 

factor rather than the usual 1000-fold 

safety factor in calculating an acceptable 

daily intake (ADI) for 25-OH D3. 

Consequently, FDA set the ADI based on 

current information at 0.05 μg/kg BW/ 

day. The safe concentrations of 25-OH 

D3 in chicken tissues based on an ADI 

of 0.05 μg/kg BW/day is 10 ppb in 

muscle, 30 ppb in liver, and 60 ppb in 

skin/fat. These values are well within 

the estimated safe concentrations for 

consumers (Ref. 17). Although liver 

concentrations of 25-OH D3 were not 

measured, it is anticipated that these 

values similarly would be within the 

calculated acceptable levels. FDA 

concludes that the available data 

indicate that residue levels of 25-OH D3

will not result in any unsafe residues of 

25-OH D3 in edible chicken tissues. 

In its evaluation of 25-OH D3, FDA 

has reviewed not only the safety of the 

product itself, but also the safety of the 

chemical impurities that may be present 

in the product from the manufacturing 

process. Residual amounts of reactants 

and manufacturing aids are commonly 

found as contaminants in chemical 

products, including products added to 

animal feeds. 

The biological stain, 2’, 4’, 5’, 7’- 

tetraiodofluorescin (also known as 

FD&C Red No. 3 or erythrosin), is used 

as a photosensitizer in the production of 

25-OH D3. This use of 2’, 4’, 5’, 7’- 

tetraiodofluorescin may result in 

unintended residue levels of 50 ppm 

maximum in the finished 25-OH D3

product (Ref. 18). At a 50 ppm 

concentration in the 25-OH D3 final 

product, when the 25-OH D3 is diluted 

in feed to a concentration of 69 ppb (69 

μg/kg), 2’, 4’, 5’, 7’-tetraiodofluorescin 

would be present at 3.45 parts per 

trillion (ppt) in finished broiler chicken 

feed. 

FDA used risk assessment procedures 

to estimate the upper-bound of risk 

presented by 2’, 4’, 5’, 7’- 

tetraiodofluorescin, a carcinogenic 

chemical (21 CFR 81.10(u)), that may be 

present in the 25-OH D3 product. Using 

a worst case estimate, taking into 

account a bird feed efficiency of 

approximately 1.9 and 80 percent 

uptake, the worst case concentration of 

2’, 4’, 5’, 7’-tetraiodofluorescin in edible 

tissue would be 5.2 ppt (3.45 ppt x 1.9 

x 0.8 = 5.2 ppt). Therefore, the agency 

would not expect this impurity to 

become a component of food at other 

than minute levels. However, because 


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2’, 4’, 5’, 7’-tetraiodofluorescin is a 

carcinogenic chemical, FDA advised 

that the sponsor should either find a 

replacement for 2’, 4’, 5’, 7’- 

tetraiodofluorescin or remove 2’, 4’, 5’, 

7’-tetraiodofluorescin from the final 

product in a consistent manner. 

Subsequently, the petitioner developed 

a purification process for complete 

removal of 2’, 4’, 5’, 7’- 

tetraiodofluorescin from the final 25-OH 

D3 product. The petitioner provided 

details on the experimental conditions 

and the supporting analytical data for 

the analytical method used to quantitate 

residual 2’, 4’, 5’, 7’-tetraiodofluorescin 

in the 25-OH D3 product. FDA found the 

purification process to be effective 

based on the analytical work submitted. 

The analytical method for the detection 

of the 2’, 4’, 5’, 7’-tetraiodofluorescin 

has been appropriately validated by the 

petitioner and FDA found it to be 

accurate, precise, and acceptable for its 

purpose. 

IV. Conclusion 

FDA has determined that the petition 

provides information to support a 

determination that the use of 25-OH D3

is GRAS as a source of vitamin D3

activity for broiler chicken feeds and 

drinking water based upon the existence 

of an expert consensus that 25-OH D3

has been shown to be safe based on 

scientific procedures. The 

determination was based upon 

published scientific data, corroborating 

unpublished studies, and other data and 

information. The agency has reached the 

following conclusions: (1) 25-OH D3 is 

a suitable source of vitamin D3 activity 

for broiler chickens; (2) 25-OH D3 at 

levels up to 69 ppb in feed, or 34.5 ppb 

in drinking water, is safe to broiler 

chickens and to the people consuming 

the broiler chickens’ edible meat 

products; and (3) an expert panel also 

concluded that the available 

information supports a GRAS 

classification for 25-OH D3 when 

supplied as a source of vitamin D 

activity in broiler feed at the intended 

level of use of 69 μg/kg of feed. 

The evaluation was based on the same 

type and quality of data as would be 

required to obtain FDA approval of 25- 

OH D3 for use as a food additive. In 

addition, the majority of the data is 

published, and there is a consensus 

among qualified experts, based on the 

data, that this intended use of the 

substance is safe. Corroborating 

evidence has shown that 25-OH D3 is a 

normal metabolite of vitamin D3 and the 

principal circulating form of vitamin D3

in mammals and birds. In addition, the 

petitioner provided testimony of a 

world-renowned expert on vitamin D 

who stated that 25-OH D3 would be a 

safer dietary supplement than vitamin 

D, since it does not accumulate in the 

body and thus, would not cause toxicity 

because of accumulation to toxic levels. 

Therefore, the agency is issuing this 

final rule affirming that 25-OH D3 is 

GRAS as a source of vitamin D3 activity 

in broiler feeds and drinking water 

when given to broiler chickens at 

nutritional levels not to exceed 69 ppb 

in feed or 34.5 ppb in drinking water 

and when used in accordance with 

additional limitations. 

V. Environmental Impact 

FDA has determined under 21 CFR 

25.32(r) that this action is of the type 

that does not individually or 

cumulatively have a significant effect on 

the human environment. Therefore, 

neither an environmental assessment 

nor an environmental impact statement 

is required. 

VI. Effective Date 

As this rule recognizes an exemption 

from the food additive definition in the 

Federal Food, Drug, and Cosmetic Act, 

and from the approval requirements 

applicable to food additives, no delay in 

effective date is required by the 

Administrative Procedure Act (5 U.S.C. 

553(d)). The rule therefore will be 

effective immediately (5 U.S.C. 

553(d)(1)). 

VII. References 

The following references have been 

placed on display in the Division of 

Dockets Management (HFA–305), 5630 

Fishers Lane, rm. 1061, Rockville, MD 

20852 and may be seen by interested 

persons between 9 a.m. and 4 p.m., 

Monday through Friday. 

1. Garret, R. H. and C. M. Grisham, 

‘‘The Vitamin D Group,’’ in 

Biochemistry, 2d ed., Saunders College 

Publishing, New York, NY, pp. 604–605, 

1999. 

2. Ameenuddin, S., M. L. Sunde, E. 

M. Cook, World’s Poultry Science 

Journal, vol. 41, pp. 52–63, 1985 

(available in the petition: vol. 17, pp. 

4463–4474). 

3. National Research Council, 

‘‘Vitamins,’’ p. 15, and ‘‘Nutrient 

Requirements of Chickens,’’ pp. 19–34, 

in Nutrient Requirements of Poultry, 9th 

ed., National Academy Press, 

Washington, DC, 1994. 

4. Ward, N. E., Journal of Applied 

Poultry Research, vol. 2, pp. 286–296, 

1993 (available in the petition: vol. 19, 

pp. 5619–5629). 

5. GRASP 2449, Amendment C–0032: 

‘‘Safety of 25-OH D3 to Consumers,’’

(testimony of Dr. Hector De Luca), 

November 1999. 

6. National Research Council, 

‘‘Vitamin D,’’ in Vitamin Tolerance of 

Animals, 1st ed., National Academy 

Press, Washington, DC, pp. 11–22, 1987. 

7. GRASP 2449, Appendix E: Expert 

Panel Report, Life Sciences Research 

Office, Federation of American Societies 

for Experimental Biology, Bethesda, 

MD, 1994. 

8. Quarles, C. L., Safety study using 

25-OH D3 in broiler chickens, Colorado 

AM–1–93, Colorado Quality Research 

Inc., Fort Collins, CO, 1993, (available 

in the petition: vol. 11, pp. 02005–

02493). 

9. Quarles, C. L., Safety study using 

25-OH D3 and vitamin D3 in broiler 

chickens, Colorado AM–2–94, Colorado 

Quality Research, Inc., Fort Collins, CO, 

1994, (available in the petition: vol. 12, 

pp. 2494–2862). 

10. Morrissey, J. L., et al., Journal of 

Nutrition, vol. 107, pp. 1027–10324, 

1977 (available in the petition: vol. 19, 

pp. 5220–5227). 

11. Janssen, W. M. M. A., H. A. J. 

Versteegh, P. J. W. Van Schagen, Archiv 

fur Geflugelkunde, vol. 45, pp. 194–200, 

1981 (available in the petition: vol. 18, 

pp. 5018–5024). 

12. Kaetzel, D. M., Jr. and J. H. Soares, 

Jr., Journal of Nutrition, vol. 109, pp. 

1601–1608, 1979 (available in the 

petition: vol. 18, pp. 5033–5040). 

13. Stevens, V. L. and R. Blair, 

Nutrition Reports International, vol. 35, 

pp. 755–764, 1987 (available in the 

petition: vol. 19, pp. 5465–5474). 

14. GRASP 2449, Amendment C–

0027: Safety Study Using 25-OH D3 in 

Broiler Chickens (Project No. ISG–98–2). 

September 1998 (available in the 

petition: vol. 31–34). 

15. Dutta, S. N., Clinical review and 

evaluation of NDA 018312 (Organon 

USA, Inc.’s CALDEROL brand of 25-OH 

D3), 1979. 

16. GRASP 2449, Amendment C–

0028: Human Food Safety of the Use of 

25-OH D3 in Broiler Feed, February 

1999. 

17. FDA Center for Veterinary 

Medicine, Guideline for Industry #3: 

‘‘General Principles for Evaluating the 

Safety of Compounds Used in FoodProducing Animals,’’ Part 4: ‘‘Guideline 

for Establishing a Safe Concentration,’’

1994. 

18. GRASP 2449, Amendment C–

0029: Safety of the Use of Erythrosin in 

the 25-OH D3 Final Product, May 1999. 

List of Subjects in 21 CFR Part 584 

Animal feeds, Food additives. 

■ Therefore, under the Federal Food, 

Drug, and Cosmetic Act and under 

authority delegated to the Commissioner 

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 

CFR part 584 is amended as follows: 

PART 584-FOOD SUBSTANCES 

AFFIRMED AS GENERALLY 

RECOGNIZED AS SAFE IN FEED AND 

DRINKING WATER OF ANIMALS 

■ 1. The authority citation for 21 CFR 

part 584 continues to read as follows: 

Authority: 21 U.S.C. 321, 342, 348, 371. 

■ 2. Section 584.725 is added to subpart 

B to read as follows: 

§ 584.725 25–Hydroxyvitamin D3. 

(a) Product. 25–Hydroxyvitamin D3

(9,10-secocholesta-5,7,10(19)-triene-3b, 

25-diol). 

(b) Conditions of use. This substance 

is generally recognized as safe as a 

source of vitamin D3 activity in feed or 

drinking water of broiler chickens when 

used in accordance with the limitations 

in paragraph (c) of this section. 

(c) Limitations. (1) Not to exceed 69 

parts per billion (ppb) in feed or 34.5 

ppb in drinking water. It shall be used 

in accordance with good manufacturing 

and feeding practices. 

(2) The product must comply with the 

following specifications: 

(i) Not less than 94.0 percent 25- 

hydroxyvitamin D3. 

(ii) Not more than 1 percent of any 

individual sterol. 

(iii) Not more than 5 percent water. 

(iv) Not more than 20 parts per 

million (ppm) lead. 

(v) Not more than 20 ppm aluminum. 

(vi) Not more than 1.0 percent 

solvents and non-detectable levels of 2’, 

4’, 5’, 7’-tetraiodofluorescin. 

(3) Product labeling shall bear the 

following: 

(i) A statement to indicate that the 

maximum use level of 25- 

hydroxyvitamin D3 must not exceed 69 

ppb in feed or 34.5 ppb in drinking 

water. 

(ii) Adequate use directions to ensure 

that 25-hydroxyvitamin D3 (and all 

premixes) is uniformly blended 

throughout the feed or drinking water. 

(iii) An expiration date on all premix 

labeling. 

(iv) A statement on all premix 

labeling (feed and drinking water forms) 

that 25-hydroxyvitamin D3 should not 

be used simultaneously in both feed and 

water. 

Dated: March 1, 2007. 

Stephen F. Sundlof, 

Director, Center for Veterinary Medicine. 

[FR Doc. E7–4796 Filed 3–15–07; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF VETERANS 

AFFAIRS 

38 CFR Part 2 

RIN 2900–AM18 

Delegations of Authority—National 

Cemetery Administration 

AGENCY: Department of Veterans Affairs. 

ACTION: Final rule. 

SUMMARY: This final rule amends the 

Department of Veterans Affairs (VA) 

regulation, ‘‘Secretary’s delegations of 

authority to certain officials.’’ The 

amendment updates the regulation 

governing certain delegations of 

authority exercised by the Under 

Secretary for Memorial Affairs. This 

minor technical amendment provides 

delegation of authority from the 

Secretary of Veterans Affairs to the 

Under Secretary for Memorial Affairs to 

accept monetary and/or non-monetary 

gifts and donations, made in any 

manner, which are made for the purpose 

of beautifying or benefiting national 

cemeteries. The authority to accept 

offers of land will remain with the 

Secretary of Veterans Affairs. 

DATES: Effective Date: March 16, 2007. 

FOR FURTHER INFORMATION CONTACT: 

Patrick Hallinan, Deputy Director, 

Office of Field Programs (41A), National 

Cemetery Administration, Department 

of Veterans Affairs, 810 Vermont 

Avenue, NW., Washington, DC 20420; 

telephone: (202) 273–5229 (this is not a 

toll-free number). 

SUPPLEMENTARY INFORMATION: The 

provisions of 38 U.S.C. 2407 authorize 

the Secretary to ‘‘accept gifts, devises, or 

bequests from legitimate societies and 

organizations or reputable individuals, 

made in any manner, which are made 

for the purpose of beautifying national 

cemeteries, or are determined to be 

beneficial to such cemetery.’’ Currently, 

under 38 CFR 2.6(f)(3), the Secretary has 

delegated authority to the Under 

Secretary for Memorial Affairs ‘‘[t]o 

accept donations of a minor nature, 

such as, individual trees for planting in 

burial areas and privately purchased 

grave markers.’’ (Emphasis added) The 

current regulatory language no longer 

reflects the needs of the agency since 

the National Cemetery Administration 

frequently receives offers for donations 

that may be perceived as more than 

‘‘minor in nature.’’ Such offers have 

included heavy equipment, rose 

gardens, cash, and electric vehicles. 

Providing authority to the National 

Cemetery Administration to accept 

donations, regardless of monetary value, 

would be commensurate with the 

authority that has been provided to the 

Veterans Health Administration and the 

Veterans Benefits Administration. The 

Under Secretary for Memorial Affairs 

will notify the Secretary when making 

decisions to accept or decline gifts and 

donations of offers that are unique, 

unusual or substantial in nature, or that 

may be of public interest because of the 

subject of the offer or identity of the 

donor. The authority to accept land will 

remain with the Secretary. The Under 

Secretary for Memorial Affairs will 

continue to refer all offers of land to the 

Secretary, with supporting information 

and a recommendation for action. 

This rule revises paragraph (f)(3) to 38 

CFR 2.6 by removing the reference ‘‘[t]o 

accept donations of a minor nature, 

such as, individual trees for planting in 

burial areas and privately purchased 

grave markers’’ and adding ‘‘[t]o accept 

all donations, except offers of land, 

made in any manner, for the 

beautification or benefit of national 

cemeteries.’’

Administrative Procedure Act 

This final rule states rules of agency 

procedure or practice and is therefore 

exempt from the notice and public 

comment procedures of 5 U.S.C. 553(b). 

Further, this final rule is not a 

substantive rule and, consequently, the 

delayed effective date provisions of 5 

U.S.C. 553(d) are not applicable. 

Unfunded Mandates 

The Unfunded Mandates Reform Act 

of 1995 requires, at 2 U.S.C. 1532, that 

agencies prepare an assessment of 

anticipated costs and benefits before 

issuing any rule that may result in an 

expenditure by State, local, or tribal 

governments, in the aggregate, or by the 

private sector, of $100 million or more 

(adjusted annually for inflation) in any 

given year. This rule would have no 

such effect on State, local, or tribal 

governments, or the private sector. 

Paperwork Reduction Act 

This document contains no provisions 

constituting a collection of information 

under the Paperwork Reduction Act (44 

U.S.C. 3501–3521). 

Executive Order 12866 

Executive Order 12866 directs 

agencies to assess all costs and benefits 

of available regulatory alternatives and, 

when regulation is necessary, to select 

regulatory approaches that maximize 

net benefits (including potential 

economic, environmental, public health 

and safety, and other advantages; 

distributive impacts; and equity). The 

Executive Order classifies a ‘‘significant 

regulatory action,’’ requiring review by 


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