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From: TSS (216-119-143-91.ipset23.wt.net)
Subject: 2004N-0081: BSE RISK MATERIALS IN FOODS AND COSMETICS
Date: January 18, 2005 at 2:35 pm PST

GREETINGS,

thought some might be interested in this comment and others...TSS

-------- Original Message --------
Subject: 2004N-0081: BSE RISK MATERIALS IN FOODS AND COSMETICS
Date: Tue, 18 Jan 2005 13:06:38 -0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE


##################### Bovine Spongiform Encephalopathy #####################

FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
August 13, 2004
Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane
Room 1061
Rockville, MD 20852
Re: Docket No: 2004N-0081
Dear Sir or Madame:
As scientists and recognized experts who have worked in the field of
TSEs for decades,
we are deeply concerned by the recent discoveries of indigenous BSE
infected cattle in
North America and appreciate the opportunity to submit comments to this
very important
Advance Notice of Proposed Rulemaking (ANPRM). 69 Fed. Reg. 42288 (July 14,
2004).
We hope that the discovery of these indigenous cases will at last
provide the necessary
impetus to implement, monitor and enforce a comprehensive and protective
feed ban that
is more congruent with the measures that have been proven to be
effective in the United
Kingdom. The currently implemented ban in the UK evolved in response to
repeated
disappointments in predicted downturns in the epidemic course. The feed
ban was
implemented in 1988 followed by a specified bovine offals (SBO) ban two
years later.
The epidemic peaked two years after that but lingered much longer than
anticipated. To
bring it fully under control required increasingly inclusive bans and
much more stringent
enforcement. Inspired and justified by the appearance of the first human
cases and the
looming threat of a vCJD epidemic, beginning in 1996 there was an
extension of the SBO
ban to specified risk materials, SRMs; implementation of the OTM
scheme in which
cattle over thirty months of age are placed in a higher risk category;
and gradual
extensions of the feed ban to all mammals and then all vertebrates and
finally all feed
uses. The change in enforcement in 1996 is readily evident in the
epidemic record giving
rise to the term BARBs, Born After the Real Ban in UK scientific
circles. We in
North America could do this experiment all over again, waiting for each
new warning
before adding more stringency to our control measures, or we can benefit
from the British
experience and take decisive measures now to arrest any further
development of the
underlying epidemic that is implicit in the two BSE cases discovered to
date.
Hopefully, the cases that have currently come to light in North America
represent the
peak of whatever epidemic was incubating at the time that our own feed
bans were
implemented in 1998. If the bans (US and Canada) were effective, and the
epidemic
progressed similarly to that in the UK, we would expect a peak in 2004.
However, if the
bans have not been effective, either due to its exclusions, limited
scope, or inadequate
enforcement, the epidemic could still be growing.
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
There is no way to distinguish these two possibilities from the
currently available data.
The only way to obtain this data is through a much more comprehensive
testing program
than that proposed by the USDA, one designed specifically to establish
the current
prevalence of infected animals. (We recognize that a comprehensive
program of this sort
would also have ancillary benefits as a screening test for food.) Since
we hope that the
prevalence rates are low and stay low, we do not see how this can be
accomplished
credibly without universal testing. Without sound data on the actual
prevalence of the
infection it will not be possible to track the effectiveness of any
control measures that are
implemented. If the control measures are not effective it will
eventually become apparent
in the appearance of increasing numbers of new cases. However, the UK
epidemic has
taught us that by the time a BSE epidemic becomes readily apparent there
are already a
large cohort of infected individuals, large numbers of humans have
already been put at
risk, and it becomes increasingly difficult to control.
To guarantee our safety, it is essential that the North American bans
provide absolute
controls for specified risk materials (SRMs) by eliminating existing
exemptions; by
eliminating dead ruminant livestock as a source of animal feed; and by
providing for
greater control over cross contamination of ruminant feed by ruminant
protein.
With SRM exemptions providing a source of infectivity to the animal feed
system, the
current US feed ban, still allows the possibility for cattle to be
exposed to BSE through:
1. Feeding of ruminant protein back to ruminants per legal exemptions
(e.g., poultry
litter, plate waste)
2. Cross feeding (the feeding of non-ruminant rations to ruminants) on farms
3. Cross contamination of ruminant and non-ruminant feed
In addition, there are other species which are susceptible to BSE and
the regulations
allow for SRMs to still be included in feed for these animals.
Hence we believe that FDA must assure that all possible sources of
contaminated
materials are fully removed from all animal feeds and that legal
exemptions which allow
ruminant protein to be fed back to ruminants (with the exception of
milk) should be
discontinued.1
SRMs
Because infectivity studies are logistically challenging and expensive
not every tissue on
the SRM list has been bioassayed. The SRMs included in the USDA
regulation, are
tissues known to contain infectivity or to be closely associated with
tissues known to
contain infectivity. For example, the skull and vertebral column which
encase the brain
1 Milk has not been a significant source of transmission of BSE in cattle.
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
and spinal cord, respectively, can be assumed to have gross
contamination. The tissue
distribution of infectivity in BSE infected cattle has primarily been
determined by 3
studies conducted in the United Kingdom all of which had serious
limitations.
In two of the studies bioassays were done in mice which are at least
1000 fold less
sensitive to BSE than cattle themselves. Only the high titers of
infectivity can be
detected by this method. These investigations found infectivity in the
brain and central
nervous system as expected but also in the distal ileum of
experimentally infected calves
beginning only six months after challenge and continuing throughout
life. (Wells et. al.,
1994; 1998). Positive immunostaining for PrPres was identified along the
length of the
intestine providing evidence that the entire intestine should be
considered as SRM
consistent with EU regulations (personal communication Danny Matthews,
UK, VLA).
We also note that the International Advisory Committee appointed by
Secretary
Veneman also recommended that the SRM ban in the US be amended to
include the
entire intestine from duodenum to rectum. Studies bioassayed in calves
where sensitivity
of the assay should be high has produced similar results and in addition
found infectivity
in tonsil and bone marrow and the lymphoid tissue of third eyelid (Dr.
Danny Matthews,
UK DEFRA, personal communication).
While bioassay in cattle is far preferable to mice in terms of
sensitivity, cattle
nevertheless present their own limitations in terms of the long
incubation time (four to six
years for high titer inoculum, and >10 to 12 years for low titer
inoculations) and the
limited number of animals that can be used for assay compared to
rodents. As a
consequence the significance of the negative finding for many tissues is
questionable.
For example, while muscle produced no infections, only 0.5g of muscle
was bioassayed
from a total of 1500 kg (Gerald Wells, UK DEFRA personal communication). In
contrast, three recent reports have found either TSE infectivity or PrP
amyloid in the
muscles of sheep and rodents. In contrast with humans, sheep, monkeys,
mice and
hamsters, no infectivity was found in the blood of BSE infected cattle.
We consider it
very unlikely that cattle are the sole outlier to what has been a
consistent finding in all
other TSE diseases where the measurement has been made with sufficient
sensitivity to
detect the low levels of infectivity that are present in blood. Rather
this failure is more
likely a measure of the lack of sensitivity of the experimental methods
of measurement.
If blood is infected then all vascularized tissues can be expected to
contain some
infectivity in proportion to the content of residual blood. Certainly,
blood and blood
proteins should not be used as feed without conclusive evidence that
they are safe.
Specific Exemptions to the feed ban that should be eliminated
Poultry Litter
There are two sources of risk from poultry litter. Poultry litter not
only consists of
digested feed but also of feed which spills from the cages. As a
consequence, the
practice of feeding litter back to cattle is by its nature non-compliant
with the current feed
ban if the poultry themselves are being fed ruminant protein. Poultry
traditionally
consumed a large proportion of the MBM produced in the US. Given that
ruminant
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
protein can no longer be fed to ruminants in the US and that most if not
all countries will
no longer import our ruminant MBM, an even larger part of poultry diets
is now ruminant
MBM. Spillage provides a direct link to back to cattle.
There is also no reason to expect that TSE infectivity would be
inactivated by passage
through the poultry gut, and only a dim possibility that it would be
inactivated by
composting. Thus the poultry feces are another potential route of
transmission back to
cattle. Evidence for this comes from rodent experiments where
infectivity was
demonstrated in the feces after being fed: Laboratory experiments
(Dickinson et al)
show that mice orally challenged with scrapie have detectable
infectivity that passes
through the gut. Gut contents and fecal matter may therefore contain
infectivity, and it is
noted that in experimental oral challenges in cattle conducted in the
UK, feces must be
treated as medical waste for one month following the challenge. It is
concluded that
digestive contents and fecal material from livestock or poultry
currently being fed with
MBM potentially contaminated with BSE should not be used as a feed
ingredient for
animal feed. [Proceedings: Joint WHO/FAO/OIE/ Technical Consultation on
BSE:
public health, animal health and trade. Paris, 10-14 June 2001.
It may be possible to remove the risk from poultry litter by
sterilization. However, unless
or until a method can be developed and validated, poultry litter should
be banned from
ruminant feed.
Plate Waste
Plate waste is not limited to meat (muscle tissue). For example, cuts
that include a
portion of the spinal cord or that are contaminated by cord or ganglia
during preparation
could contain high levels of infectivity if derived from a TSE infected
animal late in the
preclinical stage of infection. At best this material would only be
exposed to normal
cooking temperatures. USDA, APHIS experience with the Swine Health
Protection Act
has revealed that plate waste also includes uncooked trimmings and
bones. Although the
current FDA regulation requires the plate waste be treated again, there
are no
specifications which would render a TSE agent inactive. Of greatest risk
would be bovine
sources of infectivity but sheep scrapie, although not known to be a
risk for human
consumption, is one of the possible origins of BSE. The sheep scrapie
agent is known to
be widely dispersed including relatively high titers in lymphoid as well
as nervous tissue.
We support the USDAs opposition to the exemption of plate waste as
stated in written
comments since 1997.
Ruminant Blood
As discussed above, we consider likely that the blood of BSE infected
cattle contains low levels
of infectivity similar to those found in humans, monkeys, sheep, mice
and hamsters including
sheep and mice infected with BSE. However, there is another, perhaps
even more dangerous
source of blood-borne infectivity in slaughtered cattle carrying the
infection. This is because
stunning releases micro emboli of brain tissue into the circulatory
system where they become
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
widely distributed in the few moments before the exsanguination and
death. (Anil et al, 1999;
Anil, et al, 2001a & b; Anil et al, 2002; Love, et al, 2000; Mackey and
Derrick, 1979)
The risks from this source of infection extend really to all tissues in
the body including those that
end up as food and plate waste and as a consequence this issue has
profound implications for
public health as well as bovine health. It also impacts the significance
and rational for SRM and
clearly needs to be understood far better than it is at present to be
fully accounted for in a science
based policy. This may be a special problem where sprayed dried blood is
being used as a milk
replacer for calves. The infection might never be seen in veal calves
where this practice is most
common, but could nevertheless amplify the spread the disease through
other loop holes in the
ban like plate waste. It is thought that young animals are especially
susceptible to infection.
Unfiltered Tallow
Ruminant tallow is exempted from the current feed ban. Tallow contains
protein
impurities (i.e. MBM) that could be a source of TSE infectivity. There
are no FDA
impurity level requirements for this tallow. It has been reported that
it is standard
practice to produce tallow which has an impurity level of .15% or below.
However, it is
not clear that this is adequate to remove the risk of transmission and
there is no
requirement to meet even this standard.
Risk from Deadstock
The levels of total infectivity in a TSE infected animal increase as the
animal approaches
and progresses to clinical disease and infected individuals only exhibit
recognizable
clinical symptoms once infectivity titers have reached high levels in
the brain.
Surveillance data collected throughout Europe indicates there is a much
greater
likelihood for BSE to be detected in dead or down cattle than from
healthy normal
animals. An animal which dies of BSE would be at the peak of
infectivity, that is they
would carry the greatest amount of agent at this point in the disease.
In the 2001 Harvard risk assessment model it was shown that eliminating
dead and
downer, 4D cattle, from the feed stream was a disproportionately
effective means of
reducing the risk of reinfection. We endorse this approach and strongly
recommend
provisions to eliminate this source of exposure from ruminant feed.
(Harvard Risk
Assessment, 2001 Executive Summary)
Exposure: Cross Feeding and Cross Contmaination
The UK epidemiology has clearly shown that BSE contaminated feed is the
primary if
not sole vehicle for the transmission of BSE between cattle. Moreover,
results from the
United Kingdoms attack rate study indicate that it does not take much
exposure to
transmit BSE to cattle. Recent results from the attack rate study which
is still in progress
has found that .1 gr of brain transmitted BSE to 3 cows out of 15 thus
far, and .01 and
.001gr of brain has transmitted BSE (1 cow out of 15). (Danny Matthews,
DEFRA
presentation at TAFS meeting, Washington, DC April 2004).
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
Rendering may reduce infectivity but it does not eliminate it. (Taylor
et al, 1995; Taylor
et al, 1997; Schreuder et al, 1998). Given that BSE can be transmitted
to cattle via an
oral route with just .001 gram of infected tissue, it does not take much
infectivity to
contaminate feed and keep the disease recycling. This is especially true
in the US and
other countries which do not have dedicated lines and equipment to
manufacture and
process feed for ruminants and non ruminants.
In addition, epidemiological investigations in European countries have
shown that cross
feeding and cross contamination on farm can be a significant vehicle for
continued BSE
transmission even after feed bans are well established. Cross feeding is
the inadvertent
practice of feeding meal for poultry or pigs (which has a likelihood of
being ruminant
MBM) to cattle on the same farm. This is usually due to simple human
error. (Hoinville,
1994; Hoinville et al, 1995; Doherr et al, 2002a; Stevenson et al, 2000)
FDA, CVM reports that compliance with the feed ban is over 90%. For the
most part this
does not include the compliance level on the farm. There are hundreds of
thousands of
farms in the US. Many of these have multiple species. That is they have
cattle, pigs,
chickens etc. The sheer numbers of farms make it very difficult to
assure compliance on
farm and to adequately cover all farms by inspection. The rendering
industry and feed
industry can maintain 100% compliance at there facilities but if a
producer inadvertently
feeds chicken feed to cattle the compliance rate higher in the chain is
negated.
The May 2003 Canadian BSE case illustrates the possibility of these
mistakes. The
positive cow was rendered and then MBM distributed to various locations.
Two of these
locations included poultry farms which mixed their own feed. The farms
also had cattle.
The investigation could not eliminate the possibility that the cattle
were fed the same feed
as the poultry. The cattle on these farms were completely depopulated.
Human error is extremely difficult to prevent especially when
enforcement has extreme
logistical challenges. By eliminating all material (SRMs and deadstock)
which may
introduce infectivity into the system before any processing, the
resulting MBM becomes
inherently safer. If mistakes are then made on farm, they become much
less relevant in
regards to the recycling of BSE.
Exposure: Susceptibility of other Species
Felines
A transmissible spongiform encephalopathy has been diagnosed in eight
species of captive wild
ruminants as well as exotic (cheetahs, pumas, a tiger and an ocelot) and
domestic cats. There
have been over 80 domestic cat cases of Feline Spongiform Encephalopathy
(FSE) in Great
Britain, and cats in Norway, Northern Ireland, Lichtenstein and
Switzerland. The agent isolated
from several of these cases is indistinguishable from BSE in cattle
using strain typing in mice,
suggesting that FSE is actually BSE in exotic and domestic cats. This
also appears to be true for
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
the other ruminants. Epidemiological evidence suggests BSE contaminated
feed to be the
primary source of infection in these species. (MAFF Progress Report,
June 1997), thus providing
additional supporting evidence for the dangers of BSE contaminated feed
the necessity of
removing all sources of potential contamination from the feed stream.
Other species
Studies conducted at the National Institutes of Health Rocky Mountain
Laboratory
caution against assuming that animals which do not become clinically ill
are not infected.
It is unknown if certain animals may become carriers, i.e., become
infected, shed agent
but do not progress to develop clinical disease. Infection of certain
rodent species with
different TSE strains suggests the possibility of a carrier state
(Collis and Kimberlin
1985; Race and Chesebro, 1998; Race et. al, 2001). In the most recent
study, mice were
inoculated with 263K hamster scrapie. There was a prolonged period
(approximately one
year) where there was no evidence of replication of infectivity.
Furthermore, there was no
evidence of PrPSc during this phase of inactive persistence. This study
found that this
phase was followed by a period of active replication of infectivity and
agent adaptation.
In most cases, PrPSc was not detected in the active phase as well (Race
et. al., 2001). It is
important to determine if this persistence and adaptation occurs in
other species exposed
to TSEs as it may have significance in feeding programs which
continually expose
certain species to BSE infectivity. For example, if BSE infected brain
and spinal cord
are continually fed to certain species, it may be possible for the agent
to persist and adapt
in these new species. Over time, the resistant species may become a
source of agent.
Considering the results of the study by Race and colleagues, if there
were an inactive
persistence phase in certain species, PrP Sc would not be detectable,
yet there would be
infectivity (Race et. al., 2001).
Pigs displayed evidence of a TSE after exposure to BSE by 3 parenteral
routes(Dawson
et. al., 1990). In this transmission there was evidence of infectivity
in the CNS, stomach,
intestine and pancreas of the pigs. Oral transmission has been attempted
in swine. The
inoculated swine were euthanized after 84 months of age and had not
exhibited any signs
of a TSE. Parenteral and oral transmission has also been attempted in
chickens with no
evidence of disease. Tissues from the BSE-challenged pigs and chickens
were inoculated
into susceptible mice to look for residual infectivity, to date none has
been found. The
criticism of this study is the use of mice instead of cattle as the
assay model due to the
decrease of sensitivity.
If any of these scenarios became established in commercial species they
could become
reservoirs for reinfection of cattle and perpetuation or reintroduction
of the epidemic. We
offer these possibilities to reinforce the need to eliminate all
possible sources of
contamination from the feed stream.
The need to remove high risk material from all animal feed is also
supported by other
bodies with expertise in the field of TSEs:
Recommendations of the World Health Organization (WHO)
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
The World Health Organization (WHO) has issued the following
recommendations for
countries with BSE or those where a known exposure exists:
" No part or product of any animal which has shown signs of a TSE should
enter any
food chain (human or animal). In particular:
o All countries must ensure the killing and safe disposal of all parts
or products
of such animals so that TSE infectivity cannot enter any food chain.
o Countries should not permit tissues that are likely to contain the BSE
agent to
enter any food chain (human or animal).
From the report of a WHO Consultation on Public Health Issues related
to Human and
Animal Transmissible Spongiform Encephalopathies WHO/EMC/DIS 96.147, Geneva,
2-3 April 1996.
Recommendations of the Harvard/Tuskegee BSE Risk Assessment
Executive Summary of the 2001 release:
Specific pathways or practices that would contribute the most to the
spread of BSE if it
were introduced into the U.S. relate to compliance with the FDA feed ban
and include
misfeeding on the farm and the mislabeling of feed and feed products
prohibited for
consumption by cattle. The disposition of cattle that die on the farm
would also have a
substantial influence on the spread of BSE if this disease were
introduced into the U.S.
Our evaluation of potential risk mitigation actions highlights
potential measures to
further reduce the already low likelihood that BSE could spread to
cattle or contaminate
human food if it were to arise. Prohibiting the rendering of animals
that die on the farm,
possibly of BSE, removes a great deal of potential contamination in the
animal feed chain
and reduces average predicted cases of BSE following introduction of ten
infected cattle
by 77%. Implementation of a UK-style ban on specified risk material
(e.g., spinal cords,
brains, vertebral columns) from both human food and animal feed reduces
the predicted
number of BSE cases in cattle by 80% and the potential human exposure by
95%.
The disposition of cattle that die on the farm would also have a
substantial influence on
the spread of BSE if the disease were introduced. The base case
scenario showed that
the mean total number of ID50s (i.e., dosage sufficient to infect 50
percent of exposed
cattle) from healthy animals at slaughter presented to the food/feed
system was 1500.
The mean total number of ID50s from adult cattle deadstock presented to
the feed system
was 37,000. This illustrates the risk of 4D cattle (i.e., deadstock).
From the Harvard
Risk Assessment, 2001, Appendix 3A Base Case.
Recommendations of the Subcommittee to the USDAs Foreign Animal and Poultry
Disease Advisory Committee
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
An international panel of transmissible spongiform encephalopathy (TSE)
experts
appointed by Secretary of Agriculture Ann M. Veneman as a subcommittee
to the
Foreign Animal and Poultry Disease Advisory Committee issued a report in
February
2004 which stated:
& given the epidemiological evidence indicating that BSE agent was already
circulating in ruminant feed prior to the feed ban in 1997, and the
integration of the
North American cattle and feed industries, strong consideration should
be given to
excluding all SRM from both the human food and animal feed supplies.
Considering the BSE situation in North America, the subcommittee
believes the partial
(ruminant to ruminant) feed ban that is currently in place is
insufficient to prevent
exposure of cattle to the BSE agent.
From the Secretarys Advisory Committee on Foreign Animal and Poultry
Diseases
Subcommittee on the United States Response to the Detection of a Case
of Bovine
Spongiform Encephalopathy, Report on Measures Relating to Bovine Spongiform
Encephalopathy (BSE) in the United States, 2 February 2004, p. 8.
Conclusion
In conclusion we urge the FDA to implement, monitor and enforce a
comprehensive and
protective feed ban that is more congruent with the measures that have
been proven to be
effective in the United Kingdom. We do not feel that we can overstate
the dangers from
the insidious threat from these diseases and the need to control and
arrest them before the
spread widely.
However we also wish to emphasize that as scientists that have dedicated
substantive
portions of our careers to defining the risks from TSEs as well as
developing strategies
for managing those risks, we are confident that there will eventually be
technical
solutions to many of the challenges that we currently confront from
these diseases. Thus,
we urge the FDA to frame its regulations in terms that allow for the use
of any banned
material if it can be proven safe for a given application.
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FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
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hyperbaric rendering procedures in inactivating bovine spongiform
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scrapie agents. Veterinary Record 142, 474-480
Stevenson, M. A., Wilesmith, J. W., Ryan, J. B. M., Morris, R.S.,
Lockhart, J. W., Lin,
D. & Jackson, R. (2000) Temporal aspects of bovine spongiform
encepalopathy in Great
Britain: individual animal-associated risk factors for the disease. Vet.
Rec. 147, 349-354.
Stevenson, M. A., Wilesmith, J. W., Ryan, J. B. M., Morris, R. S.,
Lawson, A.B.,
Pfeiffer, D. U. & Lin, D. (2000) Descriptive spatial analysis of the
epidemic of bovine
spongiform encephalopathy in Great Britain to June 1997. Vet. Rec. 147,
379-384.
Taylor, D.M., Woodgate, S.L., Atkinson, M.J., 1995. Inactivation of the
bovine spongiform
encephalopathy agent by rendering procedures. Veterinary Record,
Vol.137: pp.605-610.
Taylor, D.M., Woodgate, S.L., Fleetwood, A.J., Cawthorne, R.J.G., 1997.
The effect of rendering
procedures on scrapie agent. Veterinary Record, Vol.141, pp 643-649.
Wilesmith, J.W., Ryan, J. B. M., Hueston, W. D., & Hoinville, L. J.
(1992) Bovine
spongiform encephalopathy: epidemiological features 1985 to 1990. Vet.
Rec., 130, 90-
94.
Wilesmith, J. W., Wells, G. A. H., Ryan, J. B. M., Gavier-Widen, D., &
Simmons, M. M.
(1997) A cohort study to examine maternally associated risk factors for
bovine
spongiform encephalopathy. Vet. Rec., 141, 239-243.
Wells G.A.H., Dawson M., Hawkins, S.A.C., Green R. B., Dexter I.,
Francis M. E.,
Simmons M. M., Austin A. R., & Horigan M. W. (1994) Infectivity in the
ileum of
cattle challenged orally with bovine spongiform encephalopathy. Vet.
Rec., 135, 40-41.
Wells G.A.H., Hawkins, S.A.C., Green R. B., Austin A. R., Dexter I.,
Spencer, Y. I.,
Chaplin, M. J., Stack, M. J., & Dawson, M. (1998) Preliminary
observations on the
pathogenesis of experimental bovine spongiform encephalopathy (BSE): an
update. Vet.
Rec., 142, 103-106.
Wyatt. J. M. et al. 1991. Naturally occurring scrapie-like spongiform
encephalopathy in
five domestic cats. Veterinary Record. 129. 233.
Signatories:
Linda Detwiler, DVM
Consultant, TSE Risk Management
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47
Robert G. Rohwer, Ph.D.
Director, Molecular Neurovirology Laboratory
Veterans Affairs Medical Center
Medical Research Service 151
and
Assoc. Professor of Neurology
School of Medicine
University of Maryland at Baltimore
address:
10 N. Greene St.
Baltimore, MD 21201
ph. 410-605-7000 x6462
secretary x6466
Fax 410-605-7959
email: rrohwer@umaryland.edu
Paul W. Brown, M.D.
Consultant, TSE Risk Management
FDA CVM Docket No. 2004N-0081 RIN-0910-AF47

http://www.fda.gov/ohrms/dockets/dockets/04n0081/04N-0081_emc-000005-01.pdf

2004N-0081: BSE RISK MATERIALS IN FOODS AND COSMETICS
------------------------------------------------------------------------

Document #
Received Date
Filed Date
Submitter Code
Submitter
FR Date
FR Page
Comment
Date
Files
Remarks

C1
02/03/2004
02/03/2004
Association
Cosmetic, Toiletry, and Fragrance Assn (CTFA)

pdf

Signature:
Gerald N. McEwen, Jr., Ph.D., J.D.


C2
03/15/2004
03/15/2004
Association
The Soap and Detergent Assn (SDA)

pdf

Signature:
Ernie Rosenberg


BKG1
07/14/2004
07/09/2004
Federal Government

Background Information Refs 1-63

Tab-1
,
Tab-2
,
Tab-3
,
Tab-4,
Tab-5
,
Tab-6
,
Tab-7
,
Tab-8
,
Tab-9
,
Tab-10
,
Tab-11
,
Tab-12

,
Tab-13
,
Tab-14
,
Tab-15
,
Tab-16
,
Tab-17
,
Tab-18
,
Tab-19
,
Tab-20
,
Tab-21
,
Tab-22
,
Tab-23
,
Tab-24
,
Tab-25
,
Tab-26
,
Tab-27
,
Tab-28
,
Tab-29(1)
,
Tab 29(2)
,
Tab-30
,
Tab-31
,
Tab-32

, Tab-33
,
Tab-34
,
Tab-35
,
Tab-36
,
Tab-37
,
Tab-38
,
Tab-39
,
Tab-40
,

Tab-41
,

Tab-42
,

Tab-43
,

Tab-44

,
Tab-45
,
Tab-46
,

Tab-47
,

Tab-48
,

Tab-49
,

Tab-50(1)
,
Tab-50(2)

,
Tab-51(1)
,
Tab-51(2)
,
Tab-51(3)
,
Tab-52
,

Tab-53
,

Tab-54
,

Tab-55
,

Tab-56
,

Tab-57
,

Tab-58
,

Tab-59
,

Tab-60
,
Tab-61
,
Tab-62(mdb)
,
Tabl62 (doc)
,
Tab-63 (1)
,
Tab-63(2)
,
TOCvol2

TOCvol3

TOCvol4

TOCvol5


Signature:
Background Information Refs 1-63


EA1
07/09/2004
07/09/2004
Federal Government

Environmental Assessment

pdf


Signature:
Environmental Assessment


FONS1
07/09/2004
07/09/2004
Federal Government

Finding of No Significant Impact

pdf


Signature:
Finding of No Significant Impact


NIR1

07/09/2004
FDA
FDA
07/14/2004
42256-42274
10/12/2004
pdf

Signature:
LESTER M/ CRAWFORD


EMC1
07/13/2004
07/13/2004
Individual Consumer
T. Singeltary, Sr.


Signature:
Terry S. Singeltary, Sr.


REF1
07/16/2004
07/16/2004
Federal Government

OMB Review for July 14, 2004

pdf
,
Tabs: A
,
B
,
C


Signature:
OMB Review for July 14, 2004


EMC2
07/24/2004
07/24/2004
Individual Consumer
B. Sachau


Signature:
B. Sachau


SUP1
07/29/2004
07/29/2004
Federal Government

BSE Stakeholders Conference Calls

doc


Signature:
BSE Stakeholders Conference Calls


C3
07/30/2004
07/29/2004
International Industry

S Foods, Inc.

pdf


Signature:
Hayao Morishima


EMC3
08/09/2004
08/09/2004
Food Industry
Golden State Foods (GSF)

txt
,
Attachment

Signature:
David Gilbert


EMC4
08/12/2004
08/12/2004
Private Industry
Lafarge North America, Inc. (Lafarge)

txt
,
Attachments: png1
,
png2


Signature:
Richard G. Stoll

EMC5
08/13/2004
08/13/2004
Private Industry
Rohwer Technical Consulting, LLC

txt
,
Attachment pdf
,
doc


Signature:
Robert G. Rohwer, PhD


C4
08/13/2004
08/12/2004
Private Industry
Lafarage North America, Inc. (Lafarge)

pdf1
,
pdf2

Signature:
Richard G. Stoll


C5
08/17/2004
08/17/2004
International Government

Embassy of Australia

pdf1, pdf2


Signature:
Andrew Cupit


EMC6
08/12/2004
08/12/2004
International Government

Australian Government

txt
,
Attachment pdf
,
doc


Signature:
Andrew Cupit


EMC7
08/13/2004
08/13/2004
International Government

Australian Government

txt
,
Attachment pdf
,
doc


Signature:
Andrew Cupit


C6
09/13/2004
09/08/2004
Private Industry
Hymed Group Corporation

pdf

Signature:
Dr. George D. Petito

http://www.fda.gov/ohrms/dockets/dockets/04n0081/04n0081.htm

Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW
BSE SAFEGUARDS (comment submission)

https://web01.aphis.usda.gov/regpublic.nsf/0/eff9eff1f7c5cf2b87256ecf000df08d?OpenDocument

Docket No. 03-080-1 -- USDA ISSUES PROPOSED RULE TO ALLOW LIVE ANIMAL
IMPORTS FROM CANADA


https://web01.aphis.usda.gov/BSEcom.nsf/0/b78ba677e2b0c12185256dd300649f9d?OpenDocument&AutoFramed


Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION]

http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt

Docket Management Docket: 02N-0273 - Substances Prohibited From Use in

Animal Food or Feed; Animal Proteins Prohibited in Ruminant Feed

Comment Number: EC -10

Accepted - Volume 2


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be07.html

PART 2


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be09.html

PDF]Freas, William TSS SUBMISSION

File Format: PDF/Adobe Acrobat -

Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary

Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf

Asante/Collinge et al, that BSE transmission to the 129-methionine

genotype can lead to an alternate phenotype that is indistinguishable

from type 2 PrPSc, the commonest _sporadic_ CJD;

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm

Docket Management Docket: 96N-0417 - Current Good Manufacturing Practice
in Manufacturing, Packing, or Holding Dietary Ingredients a
Comment Number: EC -2
Accepted - Volume 7

http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm


[PDF] Appendices to PL107-9 Inter-agency Working Group Final Report 1-1
File Format: PDF/Adobe Acrobat - View as HTML
Agent, Weapons of Mass Destruction Operations Unit Federal Bureau of
those who provided comments in response to Docket No. ...
Meager 8/18/01 Terry S. Singeltary Sr ...


www.aphis.usda.gov/lpa/pubs/pubs/PL107-9_Appen.pdf

Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION
TO DOCKET 2003N-0312]

http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt

# Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of
2002; [TSS SUBMISSION ON POTENTIAL FOR BSE/TSE & FMD 'SUITCASE BOMBS'] -
TSS 1/27/03 (0)

Docket Management

Docket: 02N-0276 - Bioterrorism Preparedness; Registration of Food Facilities, Section 305
Comment Number: EC-254 [TSS SUBMISSION]

http://www.fda.gov/ohrms/dockets/dockets/02n0276/02N-0276-EC-254.htm


Dockets Entered On October 2, 2003 Table of Contents, Docket #,
Title, 1978N-0301,

OTC External Analgesic Drug Products, ... EMC 7, Terry S. Singeltary Sr.
Vol #: 1, ...

www.fda.gov/ohrms/dockets/dailys/03/oct03/100203/100203.htm


Daily Dockets Entered on 02/05/03

DOCKETS ENTERED on 2/5/03. ... EMC 4 Terry S. Singeltary Sr. Vol#: 2.
... Vol#: 1.

03N-0009 Federal Preemption of State & Local Medical Device Requireme. ...


www.fda.gov/ohrms/dockets/dailys/03/Feb03/020503/020503.htm


Docket Management

Docket: 02N-0370 - Neurological Devices; Classification of Human Dura Mater

Comment Number: EC -1

Accepted - Volume 1


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be11.html


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfe.html


http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004bdfc.html


Daily Dockets - 04/10/03

... 00D-1662 Use of Xenotransplantation Products in Humans.
EMC 98 Terry S. Singeltary Sr. Vol#: 3. 01F ...
www.fda.gov/ohrms/dockets/dailys/03/Apr03/041003/041003.htm - 05-20-2003
- Cached


2003D-0186
Guidance for Industry: Use of Material From Deer and Elk In Animal Feed


EMC 1
Terry S. Singeltary Sr.
Vol #:
1

http://www.fda.gov/ohrms/dockets/dailys/03/Jun03/060903/060903.htm


2003D-0186
Guidance for Industry: Use of Material From Deer and Elk In Animal Feed


EMC 7
Terry S. Singeltary Sr.
Vol #:
1

2003D-0186
Guidance for Industry: Use of Material From Deer and Elk In Animal Feed


EMC 7
Terry S. Singeltary Sr.
Vol #:
1


http://www.fda.gov/ohrms/dockets/dailys/03/oct03/100203/100203.htm

01N-0423 Substances Prohibited from use in animal food/Feed Ruminant

APE 5 National Renderers Association, Inc. Vol#: 2

APE 6 Animal Protein Producers Industry Vol#: 2

APE 7 Darling International Inc. Vol#: 2

EMC 1 Terry S. Singeltary Sr. Vol#: 3

http://www.fda.gov/ohrms/dockets/dailys/01/Oct01/101501/101501.htm

TSS

######### https://listserv.kaliv.uni-karlsruhe.de/warc/bse-l.html ##########


PLEASE FOLLOW THREAD ON ;

Neuroinvasion by Scrapie following Inoculation via the
SKIN IS Independent of Migratory Langerhans Cells ;

http://www.vegsource.com/talk/madcow/messages/93822.html

TSS






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