Substances Prohibited From Use in Animal Food or Feed; Specified Offal From Adult Sheep and Goats Prohibited in Ruminant Feed; Scrapie

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 589

[Docket No. 93N-0467]

Substances Prohibited From Use in Animal Food or Feed; Specified

Offal From Adult Sheep and Goats Prohibited in Ruminant Feed; Scrapie

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) proposes to declare

that specified offal from adult (more than 12 months of age) sheep and

goats is not generally recognized as safe (GRAS) for use in ruminant

feed and is an unapproved food additive when added to ruminant feed.

Accordingly, in the absence of an approved food additive regulation or

investigational exemption, the use in ruminant feed of ingredients

containing specified offal from adult sheep or goats will cause the

feeds to be considered adulterated within the meaning of the Federal

Food, Drug, and Cosmetic Act (the act). FDA is proposing this action

because the specified offal may contain the agent that causes scrapie,

a transmissible spongiform encephalopathy (TSE) of sheep and goats. In

the United Kingdom scrapie has been epidemiologically associated with

the occurrence of bovine spongiform encephalopathy (BSE), another TSE.

Because FDA cannot positively rule out a direct association between

scrapie, BSE and human TSE's, FDA is proposing this action to protect

the health of animals and humans.

DATES: Written comments by November 14, 1994. FDA is proposing that any

final rule that may issue based upon this proposal become effective 30

days after its publication in the Federal Register).

ADDRESSES: Submit written comments 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 P. Honstead, Center For

Veterinary Medicine (HFV-222), Food and Drug Administration, 7500

Standish Pl., Rockville, MD 20855, 301-594-1728.

SUPPLEMENTARY INFORMATION:

I. Background

Processed tissues from sheep and goats are used as ingredients in

animal feeds. These products are derived from slaughter byproducts

(slaughter inedibles) and dead, dying, diseased, and disabled (4-D)

animals. The slaughter inedibles include certain offal (brain, spinal

cord, spleen, thymus, tonsil, lymph nodes, or intestines) that is

subject of this proposed rule. Four-D animals also contain these

designated materials. Such materials are designated ``specified

offals'' in this proposed rule.

The Association of American Feed Control Officials (AAFCO) has

recognized and defined several animal products as feed ingredients in

its official publication (Ref. 1). Products which are likely to contain

specified offal include, dried meat solubles, glandular meal, meat

meal, meat and bone meal, animal byproduct meal, meat meal tankage,

animal digest, bone ash, bone charcoal, spent bone charcoal, cooked

bone meal, and bone phosphate.

A. Processing Animal Tissues for Feed Ingredients

Generally, feed ingredients from slaughter byproducts and 4-D

animals are processed by rendering. Rendering involves cooking the

slaughter byproducts or the whole carcasses of 4-D animals at 240 to

290 deg.F for 20 minutes to 3 hours to separate oils, fats, and

protein (Ref. 2). These rendered products are used as ingredients to

provide essential nutrients in animal feed. However, there are

processes other than rendering, such as drying, in which slaughter

byproducts are manufactured into feed ingredients.

Because of the prolonged application of heat and the associated

transformation of the tissues, rendering is generally regarded by FDA

as a process that ensures that the ingredients pose no threat of

disease to animals or to the health of humans who consume animal

products such as meat, milk, and eggs. In its role as regulator of

rendering practices, FDA has focused on the efficacy of a facility's

rendering process in the prevention of disease transmission and the

prevention of contamination of the finished products (Ref. 3). FDA has

no previous evidence of a human or animal health TSE hazard or any

other health hazard associated with the feeding of adequately rendered

ingredients to animals. Processed animal byproducts have a long history

of safe use in the United States as a source of nutrients for animals.

However, the agent responsible for the transmission of BSE and

related TSE diseases is not well characterized. It is believed to be a

cattle variant of the sheep scrapie agent (Refs. 4 and 5). As explained

more fully below, epidemiological evidence from the United Kingdom

suggests that a disease agent contained in sheep may have survived the

rendering process to cause BSE in cattle. This is the first reported

instance in which it is suspected that a disease agent survived

rendering.

The occurrence of BSE in cattle has not been shown to cause a TSE

disease in humans (Ref. 6). On the other hand, the possibility of a

causal relationship has not been disproved. BSE has not been diagnosed

in cattle in the United States (Ref. 7). However, sheep scrapie is

present in the United States. Accordingly, the agency believes that the

potential implications for humans as well as animal health require

regulatory action to minimize the possibility for the introduction of

the disease into U.S. cattle. For reasons described more fully below,

FDA is proposing that any feed ingredient that contains specified offal

from adult sheep or goats is a food additive when added to the feed of

ruminants.

B. Transmissible Spongiform Encephalopathies (TSE's)

TSE's are progressively degenerative central nervous system (CNS)

diseases of man and animals that are characterized by a long incubation

period, a relatively short clinical course of neurological signs, and a

100-percent mortality (Ref. 8). TSE's are believed to be caused by

abnormal isoform neuronal membrane proteins which contain no detectable

nucleic acids, are resistant to most methods of sterilization, and

survive severe environmental conditions such as 360 deg.C dry heat

(Refs. 6 and 9). The agent, however, is not generally believed to be a

virus, but rather a protein devoid of nucleic acid components. Nucleic

acid components are characteristic of other living microorganisms.

These proteins have been termed prions, and are abnormal forms of

proteins already present in all animals (Refs. 10 and 11). In most

cases the natural route of exposure to the TSE agent is suspected to be

oral, although genetic disposition is known to play a role in some

cases of sheep scrapie and human TSE diseases including Creutzfeldt-

Jakob disease, and Gerstmann-Straussler Syndrome (Ref. 12).

Antemortem diagnostic tests for the detection of TSE do not exist.

Postmortem tests are required to confirm suspected TSE cases. The

observation of histopathological changes in the brain, such as

vacuolization of the brainstem, are positive indicators (Ref. 13).

Other diagnostic tests available are immunohistochemical staining and

immunoblotting the abnormal protein (Ref. 14). Detection and titration

of the TSE agent can also be accomplished by intracerebral inoculation

in mice or hamsters with a brain homogenate from a suspected animal.

After an appropriate incubation period, the brain of the laboratory

animal is examined for histopathological changes characteristic of TSE

(Ref. 15).

1. Sheep Scrapie

Scrapie is a slowly progressive, transmissible disease of the CNS

in sheep and goats. Scrapie is characterized by a prolonged incubation

period averaging 2 years, followed by a clinical course of 2 to 6

months when the animal exhibits sensory and motor malfunction,

depression, and death. The agent presumably moves from infected to

susceptible animals by direct or indirect contact and enters through

the gastrointestinal tract. Consequently, its spread is both vertical

(mother to offspring in utero) (Ref. 16) and horizontal (direct

contact) between sheep (Ref. 15). Early signs of scrapie include subtle

changes in behavior or temperament which may be followed by scratching

and rubbing against fixed objects. Other signs include loss of

coordination, weight loss despite a good appetite, biting of feet and

limbs, tremor around head and neck, and unusual walking habits (Ref.

17). Since there is no detectable immune response to scrapie, diagnosis

of scrapie in live sheep is possible only when clinical signs are

evident and must be confirmed by histopathology at postmortem (Ref.

14).

The scrapie agent may be identified in lymphatic tissue (spleen,

thymus, tonsil, and lymph nodes) in sheep with preclinical infections;

however, in clinically affected adult sheep, the agent is identified in

the intestines, nervous tissues (brain and spinal cord), and lymphatic

tissues (Ref. 15). The brain has been shown to contain by far the

highest scrapie infectivity of any body tissue.

Scrapie is known to have existed in Britain, Ireland, France, and

Germany for over 200 years. It has been observed in the United States

and Canada for about 50 years. The first case of scrapie in the United

States was diagnosed in Michigan in 1947. From 1947 through January

1993, approximately 653 flocks have been diagnosed with scrapie (Ref.

18).

In 1993, there were estimated to be a total of 11 million sheep in

112,000 flocks in the United States. At the present time, there are 108

known scrapie-infected flocks (flocks with sheep diagnosed with

scrapie) containing a total of 7,430 sheep, and there are 13 known

scrapie-source flocks (flocks to which scrapie-infected sheep were

traced) containing a total of 3,418 sheep (Ref. 19).

In the absence of an antemortem diagnostic test, it is not possible

to establish with absolute certainty that a flock is free of scrapie

infection. Moreover, lack of reporting, the long incubation period, and

open range husbandry practices in the western United States make it

difficult to detect classical clinical signs and accurately monitor

scrapie in the United States.

2. Bovine Spongiform Encephalopathy (BSE)

BSE was first recognized as a new cattle disease by researchers at

the Central Veterinary Laboratory of the British Ministry of

Agriculture, Fisheries, and Foods at Weybridge, England in November

1986. In retrospect, the literature indicates that the first clinical

case of BSE may have been observed as early as April 1985 (Ref. 20). As

of September 1993, there have been more than 100,000 confirmed cases of

BSE in England, Scotland, and Wales. In the United Kingdom, 44 percent

of the dairy herds and 9 percent of the beef herds are infected (Ref.

21). BSE has also been reported in Northern Ireland, the Republic of

Ireland, Switzerland, France, Oman, and the Falkland Islands (Ref. 22).

BSE is a transmissible, slowly progressive, degenerative disease of

the CNS of adult cattle. This disease has a prolonged incubation period

in cattle following oral exposure (2 to 8 years) and is always fatal.

BSE is characterized by abnormalities of behavior, sensation, posture,

and gait. These signs are similar to those seen in sheep that are

infected with scrapie. BSE is associated with spongiform lesions in the

gray matter neuropil of the brainstem and neuronal vacuolization (Ref.

21). The clinical signs usually begin with changes in animal behavior

that are suggestive of apprehension, anxiety, and fear. There is

increased reaction to sound and touch. A swaying gait is sometimes

coupled with high stepping of the feet and is most evident in the hind

limbs. Changes in the normal behavior of the individual cow may also

include separation from the rest of the herd while at pasture,

disorientation, or excessive licking of the nose or flanks (Ref. 23).

The most common history given by the herdsman was nervousness or

altered behavior or temperament, weakness associated with pelvic limb

ataxia, paresis, and loss of body weight (Ref. 24).

In some animals there are few gross pathological changes at

necropsy associated with BSE other than the loss of body weight.

However, postmortem histopathology of BSE distinguish it from other

neurological disorders (Refs. 25 and 26).

3. Other Animal TSE's

Transmissible mink encephalopathy (TME) is a mink disease with

clinical signs and brain lesions similar to those of sheep infected

with scrapie. The development of TME on a mink farm that reportedly fed

only cattle byproducts has led some to believe that BSE exists at a low

level in the United States (Ref. 27). TME is a rare disease in the

United States, with only 5 outbreaks (involving 11 mink farms) reported

in the last 50 years. Based on available evidence, the U.S. Department

of Agriculture (USDA) has concluded that the byproducts from United

States cattle are unlikely to have caused the TME outbreak on the mink

farm (Ref. 28).

Other animals have TSE's with typical characteristics of long

incubation, neurological degeneration, and a 100-percent death rate.

These include elk and deer (Refs. 29 and 30), zoo ruminants (Refs. 31,

32, and 33), and domestic cats (Refs. 34 and 35).

C. The Association Between Scrapie and BSE

Epidemiological studies of the outbreak of BSE in the United

Kingdom, including a computer simulation of the BSE epidemic, have

characterized it as an extended common-source epidemic. Each case has

been considered a primary case resulting from exposure to a single

common source of infection. It is believed that rendered feed

ingredients contaminated with sheep scrapie and BSE agents served as

the common source of infection. One study demonstrated that meat and

bone meal could be incorporated into the cattle feed in sufficient

quantity to initiate clinical BSE in some of the animals that consumed

the feed (Ref. 36). Thus far, other research has not confirmed that the

feeding of scrapie-infected feed ingredients to cattle produces BSE.

Therefore, the theory that BSE evolved naturally in cattle has not been

ruled out (Ref. 37). Furthermore, the United Kingdom studies suggest

that the spread of BSE appeared to have been exacerbated by the

practice of feeding ingredients from rendered BSE-infected cattle to

calves, a practice that was subsequently banned. Incomplete immediate

compliance with the feeding ban may account for the fact that some

calves born after the ban continue to be infected with BSE has

complicated any theory of vertical transmission of the disease.

Maternal transmission has been documented, but at a rate insufficient

to maintain the epidemic (Ref. 38).

Investigators have identified major risk factors that apparently

contributed to the emergence of BSE epidemic in the United Kingdom

(Refs. 39 to 42). These include:

(1) A large sheep population, relative to cattle population;

(2) A high scrapie incidence rate;

(3) The practice of feeding rendered products from BSE-infected

cattle to young cattle at high amounts (up to 4 percent of the diet);

(4) The feeding of greaves. In the United Kingdom, whole dead

animals were processed as a source of tallow. The remaining unextracted

bone and protein solids, termed ``greaves,'' were used as dairy calf

feed. The greaves may have contained the BSE agent. This practice is

not followed in the United States and has stopped in the United

Kingdom; and

(5) Changes in the rendering process. In 1981-1982, the rendering

industry in the United Kingdom reduced the use of hydrocarbon solvent

extraction in the rendering process (Ref. 43). The United States

rendering industry had taken this step in the 1970's. The appearance of

BSE in the United Kingdom approximately 3 years after the change in the

rendering process is consistent with the 2- to 8-year incubation period

of BSE. The epidemiological evidence has suggested that changes in the

solvent extraction process was the major factor responsible for

initiating a BSE epidemic in the United Kingdom. Furthermore,

laboratory tests based on intracerebral injection studies in rodents

indicated that the hydrocarbon extraction method inactivated the

causative agent while the heat method did not inactivate the scrapie-

like agent present in rendered animal byproducts (Refs. 13 and 40). The

heat extraction method is the most common rendering process currently

in use world wide.

D. Historical Efforts To Control BSE

1. United Kingdom Regulatory Actions

Regulatory controls taken to manage the BSE epidemic in the United

Kingdom and to address public health concern include: (1) An action in

June 1988 to make the disease reportable; (2) a ban in July 1988 on the

feeding of ruminant-derived protein supplements to other ruminants; (3)

an order in August 1988 for the compulsory slaughter and incineration

of BSE suspect cattle; (4) a ban in November 1988 on the human

consumption of specified offals (including brain, spinal cord, thymus,

spleen, tonsils, and intestines) of ruminants; and (5) a ban in

September 1990 of feeding any ingredient containing specified offals to

all pet and farm animals.

The Office Internationale Epizootics (OIE) has supported the U.K.

ban on the use of specified offals and has recommended that the same

action be taken in other countries with a high incidence of the disease

(Ref. 44). OIE has recommended that British manufacturers of human and

animal drugs and biologics not use source material from BSE-positive

countries.

2. United States Regulatory Actions

The USDA Animal and Plant Health Inspection Service (APHIS) has had

a scrapie control program in effect since 1952. This program has been

responsible for the relatively low incidence of the disease in the

United States. In December 1991, APHIS placed a ban on importation of

certain products of ruminant origin from countries known to have BSE

(56 FR 63865, December 6, 1991). These products include meat-and-bone

meal, bone meal, blood meal, offal, fat, and glands. In addition to

prohibiting the materials listed above, the regulation requires that

imported meat for human or animal consumption from the ruminants in the

Bovidae family (e.g., cattle) be deboned, with visible lymphatic and

nervous tissue removed; that it be obtained from animals which have

undergone a veterinary examination prior to slaughter; and that it be

obtained from ruminants which have not been in any country in which BSE

has been reported during a period of time when that country permitted

the use of ruminant protein in ruminant feed.

In addition to these import restrictions, APHIS has increased its

surveillance efforts to verify that the United States is free of BSE

and to detect the disease should it be introduced into the United

States. APHIS is tracing the movement and current health status of 459

cattle that were imported from United Kingdom between 1981 and 1989.

Due to concerns about BSE in the United States, USDA has

implemented several programs to monitor United States cattle.

Pathologists at Iowa State University and the National Veterinary

Service Laboratories (NVSL) of APHIS, USDA, are examining bovine brains

submitted to NVSL from the following sources: (1) Foreign animal

disease investigations where suspected encephalitic conditions in

cattle are reported; (2) Centers for Disease Control laboratories

(specimens that were found negative for rabies); (3) the USDA Food

Safety and Inspection Service (specimens from nonambulatory, commonly

called downer cows); and (4) veterinary diagnostic laboratories in the

United States. Between 1989 and October 1993, a total of 1,153 bovine

brains have been examined and none of these specimens contained lesions

with the characteristics and distribution typical for BSE (Ref. 45).

This program is ongoing. Data on the incidence of cattle in the United

States showing clinical symptoms of CNS disease that are similar to

clinical symptoms of BSE have shown no increase during the past 5 years

(Ref. 46).

To decrease further the incidence of scrapie and the threat of BSE

in the United States, APHIS, in 1992, initiated a voluntary

certification program for sheep (57 FR 58132, December 9, 1992). Flocks

that have not had a diagnosed case of scrapie within 5 years, or a case

traced back to the flock in that period, may apply for APHIS

certification and be officially identified as such. This new control

effort provides a mechanism to recognize flocks as scrapie-free in the

absence of a live animal diagnostic test.

3. Voluntary Ban by Renderers

In 1989, the National Renderers Association (NRA) and the Animal

Protein Producers Industry (APPI) recommended to its members that they

stop rendering adult sheep or sheep offal for sale as meat and bone

meal for inclusion in cattle feed (Ref. 47). Following adoption of the

voluntary ban, the FDA carried out a survey of current practices in the

United States for rendering or otherwise disposing of adult sheep

carcasses and parts, specifically head, brain, and spinal cord. Limited

inspections of rendering plants were conducted to: (1) Assess

compliance by United States renderers with the industry imposed

voluntary ban on rendering adult sheep for cattle feed; (2) identify

rendering plant practices concerning adult sheep; and (3) determine if

rendered adult sheep protein byproducts were being sold or labeled for

use as feed or feed components for cattle. Of the 19 plants surveyed,

15 rendered carcasses or offal of adult sheep. These 15 plants

processed more than 85 percent of the adult sheep rendered in the

United States. Eleven of the 15 rendered carcasses of adult sheep with

heads, 7 of the 15 rendered sheep carcasses separately from other

species, 6 of the 15 maintained meat and bone meal from adult sheep

separate from meat and bone meal from other species, and 4 of the 15

rendered sheep that had died of causes other than slaughter. Six of the

11 renderers processing adult sheep with heads had sold meat and bone

meal to manufacturers of cattle feed; thus, the rendering industry's

voluntary ban was not fully implemented at the time of the survey (Ref.

48).

II. The Regulatory Issues

The term ``food'' as defined in the act includes animal feed.

Section 201(f) of the act (21 U.S.C. 321(f)) defines food as ``articles

used for food or drink for man or other animals'' and ``articles used

for components of any such article.'' Furthermore, any substance whose

intended use results or may reasonably be expected to result in its

becoming a component of food is a food additive unless, among other

things, it is GRAS or is the subject of a prior sanction. Section

402(a)(2)(C) of the act (21 U.S.C. 342(a)(2)(C)) deems food adulterated

``if it is, or it bears or contains, any food additive which is unsafe

within the meaning of section 409 * * * .'' Under section 409(a)(2) of

the act (21 U.S.C. 348(a)(2)), a food additive is unsafe unless a food

additive regulation or an exemption is in effect with respect to its

use or its intended use.

A food additive regulation is established by the submission and

approval of a food additive petition, as provided in 21 CFR 571.1, or

on FDA's initiative as provided in Sec. 570.38 (21 CFR 570.38). The

Commissioner of Food and Drugs (the Commissioner), on his own

initiative or at the request of an interested party, may propose to

determine that a substance intended for use in animal feed is not GRAS

and is a food additive subject to section 409 of the act and

Sec. 570.38. Subsequent to the publication of such a proposal and after

consideration of public comments, the Commissioner may issue a final

rule declaring the substance to be a food additive and require

discontinuation of its use except when used in compliance with a food

additive regulation.

A. GRAS Determination

A determination that a substance added directly or indirectly to a

food is GRAS is generally based on specific information regarding the

composition of the substance, its use, method of preparation, methods

for detecting its presence in food, and information about its

functionality in food (21 CFR 570.35) as determined by experts

qualified by scientific training and experience to evaluate the safety

of such a substance. A substance added to food becomes GRAS as the

result of a common understanding about the substance throughout the

scientific community familiar with safety of such substances. The basis

of expert views may be either scientific procedures, or, in the case of

a substance used in food prior to January 1, 1958, experience based on

common use in food (Sec. 570.30(a) (21 CFR 570.30(a))).

General recognition of safety through experience based on common

use in food prior to January 1, 1958, may be determined without the

quantity or quality of scientific studies required for the approval of

a food additive regulation. However, substances that are GRAS based on

such use must be currently recognized as safe based on their pre-1958

use. (See United States v. Naremco, 553 F.2d 1138 (8th Cir. 1977);

compare United States v. Western Serum, 666 F.2d 335 (9th Cir. 1982).)

A recognition of safety through common use is ordinarily to be based on

generally available data and information (Sec. 570.30(c)). An

ingredient that was not in common use in food prior to January 1, 1958,

may achieve general recognition of safety only through scientific

procedures.

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 (Sec. 570.30(b); United States v. Naremco, supra, 553 F.2d

at 1143). A substance is not GRAS if there is a genuine dispute among

experts as to its recognition (An Article of Drug * * * Furestrol

Vaginal Suppositories, 251 F. Supp. 1307 (N.D. Ga. 1968), aff'd 415

F.2d 390 (5th Cir. 1969)). Further, general recognition of safety

through scientific procedures must be based upon published studies

(United States v. Articles of Food and Drug Colitrol 80 Medicated, 372

F. Supp. 915 (N.D. Ga. 1974), aff'd, 518 F.2d 743, 747 (5th Cir.

1975)), so that the results are generally available to experts. It is

not enough, in attempting to establish that a substance is GRAS, to

establish that there is an absence of scientific studies that

demonstrate the substance to be unsafe; there must be studies that show

the substance to be safe (United States v. An Article of Food, 752 F.2d

11, 15 (1st Cir. 1985)).

Conversely, a substance may be ineligible for GRAS status if

studies show that the substance is, or may be, unsafe. This is true

whether the studies are published or unpublished (50 FR 27294 at 27296,

July 2, 1985). If there are studies that tend to support a finding that

a particular substance is GRAS, but also studies that tend to support a

contrary position, the conflict in the studies, just as a conflict in

expert opinion, may prevent the general recognition of the safe use of

the substance.

B. Food Additive Status of Specified Offal From Adult Sheep and Goats

The agency recognizes that the processed slaughter byproducts and

4-D adult sheep and goats have a long history of use in animal feeds

without known adverse effects. However, the evidence for the

development of a new pattern of disease transmission now indicates that

these ingredients can no longer be categorically regarded as safe. The

agency believes that the epidemiological evidence linking the

occurrence of BSE in ruminants with the feed ingredients containing

specified offal from adult sheep and goats precludes any claim of

reliance upon a general recognition of safety as a sufficient basis for

the continued use of these specified offals in food.

The agency reached this conclusion in light of the findings

regarding a possible mechanism for the transmission of BSE to ruminants

as a result of feed ingredients containing specified offal from

scrapie-infected adult sheep and goats, as discussed in section I.B. of

this document. FDA cannot determine what level of feed ingredients from

processed adult sheep and goat products, if any, is safe in ruminant

feed.

A search of the scientific literature did not reveal information

that would provide a basis for the GRAS status of feed ingredients

derived from processed adult sheep or goat slaughter byproducts. Nor is

the agency aware of a prior sanction for any feed products that contain

these products.

In view of the above, FDA has preliminarily concluded that the

addition of specified offal to ruminant feed constitutes, in light of

the epidemiological evidence about BSE, the use of an unapproved food

additive. A regulation for the use of processed adult sheep- and goat-

specified offal in ruminant feed is not in effect. Therefore, it is

FDA's preliminary conclusion that any ruminant feed that contains such

an ingredient is adulterated. Accordingly, FDA is proposing to list

specified offal from sheep or goat over 12 months of age in 21 CFR Part

589--Substances Prohibited From Use in Animal Food or Feed.

III. Description of the Proposed Rule

The proposed rule would prohibit use of any feed ingredient

containing specified offal from sheep and goats over 12 months of age

in ruminant feed. Specified offal is defined as any tissue from the

brain, spinal cord, spleen, thymus, tonsil, lymph nodes, or intestines

(duodenum to anus, inclusive) of sheep or goats, or any processed

product that is reasonably expected to contain specified offal.

A. Exclusion of Sheep and Goats Under 12 Months

The exclusion of animal tissues from young animals is based on the

observation that sheep less than 12 months old rarely exhibit clinical

symptoms of scrapie, although a few cases have been reported in sheep

as young as 7 months (Ref. 49). Historically, APHIS scrapie regulations

and indemnity programs have used a 12-month cutoff for eligible adult

sheep. The NRA and APPI voluntary ban on rendering sheep for cattle

feed also used a 12-month cutoff for high-risk sheep. The median age of

onset of clinical scrapie is 3 1/2 years, and 82 percent of sheep died

of scrapie between the ages of 2 and 5 years (Ref. 14). Based on all of

the available data, the agency has tentatively concluded that any

ruminant feed ingredients derived from sheep and goats under 12 months

of age represent a minimal risk of exposure to the scrapie agent. The

agency invites comment on the exclusion of sheep and goats less than 12

months old from the proposed ban.

B. Inclusion of Goats

Scrapie is a disease which may affect both sheep and goats.

However, in the United States only four cases have been diagnosed in

goats (Ref. 18). All four goats were raised with sheep flocks in which

sheep scrapie was present. Even though the number of reported cases in

goats is low, there may be a substantial number of cases undiagnosed

and unreported. Because of the possibility of unreported scrapies in

goats, FDA is proposing to include adult goats in this regulation. The

agency invites comment on the inclusion of adult goats in the proposed

rule.

C. Exemption of APHIS-Certified Flocks

FDA has considered exempting adult sheep and goats from one or more

categories of APHIS-certified flocks from this prohibition. This would

provide added incentive for producers to enroll in the certification

program. On the other hand, such exclusion could cause enforcement

difficulties, because of the need for separate identification of sheep

and goats from certified flocks. The agency has tentatively decided not

to exempt specified offal from certified flocks. However, the agency

invites comment on this issue, and will consider adding the exclusion

to the final rule.

D. Summary of the Basis for FDA Regulation

Epidemiological studies in the United Kingdom indicate that feeding

calves products containing feed ingredients processed from sheep

infected with scrapie initiated BSE in cattle. Scrapie-infected sheep

flocks are present in the United States, and the scrapie agent is known

to survive the rendering procedures currently in use. A 1992 FDA survey

showed that renderers have not complied fully with their voluntary ban

on selling rendered adult sheep products for use in cattle feed. Thus,

to help prevent a BSE outbreak in the United States, regulation and

enforcement are needed to ensure that feed ingredients made from

specified offal derived from processed slaughter inedibles and

carcasses of adult sheep and goats are not used in ruminant feed.

The agency has considered whether to impose a broader ruminant-to-

ruminant ban, i.e., a restriction on feeding to cattle and other

ruminants the specified offal from all ruminants rather than just from

sheep and goats. The purpose of a ruminant-to-ruminant ban would be to

prevent the spread of BSE between cows. Since no case of BSE has been

documented in the United States under the extensive monitoring

described in section I.D.2. of this document, the agency has determined

that a broader ruminant-to-ruminant ban is not warranted at this time.

If, and when, BSE is documented in the United States, the agency will

reevaluate this determination.

While controlled scientific studies have not established a

definitive association between scrapie and BSE, epidemiologic studies

have linked the feeding of scrapie infected feedstuffs to cattle with

the occurrence of BSE. Therefore, the agency believes the action set

forth in this proposal is warranted to minimize the potential risk that

scrapie from sheep and goats may result in the introduction of BSE to

cattle in the United States in light of the impact that BSE may have on

animal and human health. The agency's proposal is consistent with

action taken by APHIS, USDA to reduce the risk that BSE will occur in

the United States by eliminating scrapie from U.S. sheep.

IV. Environmental Impact

FDA has carefully considered the potential environmental effects of

this proposed rule and has concluded that the proposed rule will not

have a significant impact on the human environment and that an

environmental impact statement is not required. FDA's finding of no

significant impact (FONSI) and the evidence supporting that finding,

contained in an environmental assessment (EA) prepared under 21 CFR

25.31, may be seen in the Dockets Management Branch (address above)

between 9 a.m. and 4 p.m., Monday through Friday. FDA invites comments

and submission of data concerning the EA and FONSI.

V. Analysis of Impacts

FDA has examined the impacts of the proposed rule under Executive

Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354).

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 agency believes that

this proposed rule is consistent with the regulatory philosophy and

principles identified in the Executive Order. In addition, the proposed

rule is not a significant regulatory action as defined by the Executive

Order and so is not subject to review under the Executive Order.

The Regulatory Flexibility Act requires agencies to analyze

regulatory options that would minimize any significant impact of a rule

on small entities. Based on a study conducted for the agency by the

Eastern Research Group (ERG), a private consulting firm, FDA has

determined the annual costs of the proposed regulation to the affected

industries. FDA estimated the annual loss of revenues to the sheep

ranching and goat ranching industries to be $2,400,000 and $1,500,000,

respectively. FDA further estimated the decrease in profits to the

slaughtering and rendering industries due to the decline in

slaughtering and rendering activities to be $356,000 per year.

Additional disposal costs to slaughterers are estimated to range from

$111,000 to $166,000 per year. The effects of the proposed regulation

on feed manufacturers are believed to be negligible. Therefore, the

agency certifies that the proposed rule will not have a significant

economic impact on a substantial number of small entities, and, under

the Regulatory Flexibility Act, no further analysis is required.

A copy of the ERG report supporting these determinations is on file

with the Dockets Management Branch (address above).

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. AAFCO, ``Official Publication 1993 Association of American

Feed Control Officials,'' pp. 128-137, 1993.

2. John, R. E., ``National Renderers Association Feed Safety

Assurance Efforts,'' in a symposium, ``Feed Quality Assurance, A

System-Wide Approach,'' p. 67, 1990.

3. FDA, Compliance Policy Guide 7126.24, ``Rendered Animal Feed

Ingredients,'' 1980.

4. Hope, J. et al., ``Fibrils From Brains of Cows With New

Cattle Disease Contain Scrapie-Associated Protein,'' Nature,

336:390, 1988.

5. Kimberlin, R. H., ``Transmissible Encephalopathies in

Animals,'' Canadian Journal of Veterinary Research, 54:30-37, 1990.

6. Taylor, D. M., ``Inactivation of BSE Agent,'' in ``Symposium

on Virological Aspects of the Safety of Biological Products,'' 1990.

7. USDA, ``Bovine Spongiform Encephalopathy Surveillance in the

United States,'' 1993.

8. McCaskey, P. C., ``Spongiform Encephalopathy in Other

Species,'' Toxicology Forum, 185-195, 1991.

9. Brown, P., P. P. Liberski, A. Wolff, and D. C. Gajdusek,

``Resistance of Scrapie Infectivity to Steam Autoclaving After

Formaldehyde Fixation and Limited Survival After Ashing at 360

deg.C: Practical and Theoretical Implications,'' Journal of

Infectious Diseases, 161:467-472, 1989.

10. Prusiner, S. B. et al., ``Immunologic and Molecular Biologic

Studies of Prion Proteins in Bovine Spongiform Encephalopathy,''

Journal of Infections Diseases, 167:602-613, 1993.

11. Stahl, N. and S. B. Prusiner, ``Prions and Prion Proteins,''

FASEB Journal, 5:2799-2807, 1991.

12. Hsiao, K., ``Mutation of the Prion Protein in Libyan Jews

With Creutzfeldt-Jakob Disease,'' New England Journal of Medicine,

324:1091-1097, 1991.

13. Kimberlin, R. H., ``Bovine Spongiform Encephalopathy,''

Scientific and Technical Review, 11(2):347-390, 1992.

14. Detweiler, L. A., ``Scrapie,'' Revue Scientifique et

Technique, Office Internationale Epizootics, 11(2):491-537, 1992.

15. Hadlow, W. J., R. C. Kennedy, and R. E. Race, ``Natural

Infection of Suffolk Sheep With Scrapie Virus,'' Journal of

Infectious Diseases, 146:657, 1982.

16. Foster, J. D. et al., ``Studies on Maternal Transmission of

Scrapie in Sheep,'' Veterinary Record, 130:341-343, 1992.

17. Kimberling, C. V., ``Jensen and Swift's Diseases of Sheep,''

Lea and Febiger, pp. 336-340, Philadelphia, 1988.

18. USDA, APHIS, Veterinary Services, ``Fact Sheet: Scrapie,''

June 1993.

19. Lang, J., ``Scrapie Progress Report,'' 1(1):1-4, March 15,

1993.

20. Wells, G. A. H., A. C. Scott, and C. T. Johnson, et al., ``A

Novel Progressive Spongiform Encephalopathy in Cattle,'' Veterinary

Record, 121:419-420, 1987.

21. Bradley, R., ``Editorial: Bovine Spongiform Encephalopathy:

The Need for Knowledge, Balance, Patience, and Action,'' Journal of

Pathology, 160:283-285, 1990.

22. Denny, O, A. Doherty, B. Hornlimann, and J. Wilesmith,

``Bovine Spongiform Encephalopathy,'' in ``DxMonitor,'' Summer 1993.

23. Hueston, W., ``Clinical Signs of BSE,'' in ``Animal Health

Insight,'' Summer:4, 1991.

24. Wilesmith, J. W., G. A. H. Wells, M. P. Cranwell, and J. B.

M. Ryan, ``Bovine Spongiform Encephalopathy: Epidemiological

Studies,'' Veterinary Record, 123:638-644, 1988.

25. Wells, G. A. H. et al., ``Bovine Spongiform Encephalopathy:

Diagnostic Significance of Vacuolar Changes in Selected Nuclei of

the Medulla Oblongata,'' Veterinary Record, 125:521-524, 1989.

26. Davis, A. J., A. L. Jenny, and L. D. Miller, ``Diagnostic

Characteristics of Bovine Spongiform Encephalopathy,'' Journal of

Veterinary Diagnostic Investigations, 3:266-271, 1991.

27. Marsh, R. F. and R. A. Bessen, ``Epidemiologic and

Experimental Studies on Transmissible Mink Encephalopathy,'' in

``Transmissible Spongiform Encephalopathy--Impact on Animal and

Human Health,'' 80:105-112, 1993.

28. Bridges, V., A. Bleem, and K. Walker, ``Risk of

Transmissible Mink Encephalopathy in the United States,'' in

``Animal Health Insight,'' pp. 7-14, USDA Veterinary Services, Fall

1991.

29. Williams, E. S. and S. Young, ``Neuropathology of Chronic

Wasting Disease of Mule Deer and Elk,'' Veterinary Pathology, 30:36-

45, 1993.

30. Williams, E. S. and S. Young, ``Chronic Wasting Disease of

Captive Mule Deer: A Spongiform Encephalopathy,'' Journal of

Wildlife Diseases, 16-1:89-98, 1980.

31. Fleetwood, A. J. and C. W. Furley, ``Spongiform

Encephalopathy in an Eland,'' Veterinary Record, April 21, 1990.

32. Jeffrey, M. and G. A. H. Wells, ``Spongiform Encephalopathy

in a Nyala,'' Veterinary Pathology, 25:398-399, 1988.

33. Kirkwood, J. K. et al, ``Spongiform Encephalopathy in an

Arabian Oryx and a Greater Kudu,'' Veterinary Record, 127,17:418-

420, 1990.

34. Wyatt, J. M. et al., ``Naturally Occurring Scrapie-like

Spongiform Encephalopathy in Five Domestic Cats,'' Veterinary

Record, 129:233-236, 1991.

35. Leggett, M. M., J. Dukes, and H. M. Pirie, ``A Spongiform

Encephalopathy in a Cat,'' Veterinary Record, 1990.

36. Collee, J. G., ``Food Borne Illness--Bovine Spongiform

Encephalopathy,'' Lancet, 336:1300-1303, 1990.

37. Fraser, H. et al., ``Transmission of Bovine Spongiform

Encephalopathy and Scrapie to Mice,'' Journal of General Virology,

73:1891-1897, 1992.

38. Robinson, M. M., ``Bovine Spongiform Encephalopathy,''

Foreign Animal Disease, pp. 134-138, 1992.

39. USDA, APHIS, ``Qualitative Analysis of BSE Risk Factors in

the United States,'' 1991.

40. USDA, APHIS, ``Quantitative Risk Assessment of BSE in United

States,'' 1991.

41. Walker, K. D. et al, ``Comparison of Bovine Spongiform

Encephalopathy Risk Factors in the United States and Great

Britain,'' Journal of the American Veterinary Medical Association,

199:11, 1554-1561, 1991.

42. USDA, ``A Review of Bovine Spongiform Encephalopathy in

Great Britain and an Update on Risk Factors for BSE in the United

States,'' 1993.

43. Wilesmith, J. W., ``The Epidemiology of Bovine Spongiform

Encephalopathy,'' Seminars in Virology, 2:239-245, 1991.

44. Office Internationale Epizootics, International Animal

Health Code, chapter 3.2.13 on BSE, pp. 231-235, July 1993.

45. USDA, Animal and Plant Health Inspection Service, Emergency

Programs Activities, ``Bovine Spongiform Encephalopathy (BSE)

Surveillance Program,'' in ``Foreign Animal Disease Report,'' No.

20-3/4, pp. 1-2, 1992, and poster display at U.S. Animal Health

Association annual meeting, October 30, 1993.

46. Fancy, B., W. Hueston, A. Davis, A. Jenny, and L. Miller,

``Retrospective Surveillance for Bovine Spongiform Encephalopathy

(BSE) in the United States,'' in ``Animal Health Insight,'' pp. 11-

16, Winter 1991.

47. Bisplinghoff, F. D., National Renderers Association letter

to Animal Protein Producers, 1989.

48. FDA, ``Report of Findings of Directed Inspections of Sheep

Rendering Facilities,'' January 1993.

49. Lamming, E., ``Bovine Spongiform Encephalopathy and Other

Spongiform Encephalopathies,'' in ``The Report of the Expert Group

on Animal Feedingstuffs to the Minister of Agriculture, Fisheries,

and Food, the Secretary of State for Health and the Secretaries of

State for Wales, Scotland, and Northern Ireland,'' 1992.

VII. Comments

Interested persons may, on or before November 14, 1994, submit

comments to the Dockets Management Branch (address above) written

comments regarding this proposal. Two copies of any comments are to be

submitted, except that individuals may submit one copy. Comments are to

be identified with the docket number found in brackets in the heading

of this document. Received comments may be seen in the office above

between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects in 21 CFR Part 589

Animal feeds, Animal foods, Food additives.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under

authority delegated to the Commissioner of Food and Drugs, it is

proposed that 21 CFR part 589 be amended as follows:

PART 589--SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED

1. The authority citation for 21 CFR part 589 continues to read as

follows:

Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug,

and Cosmetic Act (21 U.S.C. 321, 342, 348, 371).

2. New Sec. 589.2000 is added to subpart B to read as follows:

Sec. 589.2000 Specified offal from sheep and goats over 12 months old.

(a) The Food and Drug Administration has determined that specified

offal from sheep and goats over 12 months old is not generally

recognized as safe for use in ruminant feed and is a food additive

subject to section 409 of the Federal Food, Drug, and Cosmetic Act (the

act). The Food and Drug Administration has determined that specified

offal from sheep and goats over 12 months old is not prior sanctioned

for use in ruminant feed. In the absence of a regulation providing for

its safe use as a food additive under section 409 of the act, the use

in ruminant feed of ingredients containing specified offal from sheep

and goats over 12 months old causes the feed to be adulterated and in

violation of the act, unless it is subject to an effective notice of

claimed exemption for a food additive under Sec. 570.17 of this

chapter.

(b) For purposes of this part, the term ``specified offal'' means

any tissue from the brain, spinal cord, spleen, thymus, tonsil, lymph

nodes, or intestines (duodenum to anus, inclusive) of sheep or goats or

any processed product that is reasonably expected to contain specified

offal. Processed products that may contain specified offal include, but

are not limited to, meat meal, meat and bone meal, animal byproduct

meal, meat byproducts, glandular meal, and cooked bone meal.

Dated: August 16, 1994.

Linda A. Suydam,

Interim Deputy Commissioner for Operations.

[FR Doc. 94-21278 Filed 8-26-94; 8:45 am]

BILLING CODE 4160-01-F